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31.
Rosmarinus species are aromatic plants that mainly grow in the Mediterranean region. They are widely used in folk medicine, food, and flavor industries and represent a valuable source of biologically active compounds (e.g., terpenoids, flavonoids, and phenolic acids). The extraction of rosemary essential oil is being done using three main methods: carbon dioxide supercritical extraction, steam distillation, and hydrodistillation. Furthermore, interesting antioxidant, antibacterial, antifungal, antileishmanial, anthelmintic, anticancer, anti‐inflammatory, antidepressant, and antiamnesic effects have also been broadly recognized for rosemary plant extracts. Thus the present review summarized data on economically important Rosmarinus officinalis species, including isolation, extraction techniques, chemical composition, pharmaceutical, and food applications.  相似文献   
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Objectives

Anti–programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) immunotherapy has demonstrated success in the treatment of advanced NSCLC. Recently, PD-1/PD-L1 blockade also has demonstrated interesting results in small trials of neoadjuvant treatment in stage IB to IIIA NSCLC. In addition, several clinical trials using anti–PD-1/PD-L1 immunotherapy as an adjuvant or neoadjuvant treatment in patients with resectable stage NSCLC are ongoing. However, few analyses of anti–PD-1/PD-L1 immunotherapy–related biomarkers in early-stage squamous cell lung carcinoma (SqCLC) have been reported. In this study, we evaluated PD-L1 protein expression, tumor mutation burden, and expression of an immune gene signature in early-stage SqCLC, providing data for identifying the potential role for patients with anti–PD-1/PD-L1 treatment in early-stage SqCLC.

Methods

A total of 255 specimens from patients with early-stage SqCLC were identified within participating centers of the Strategic Partnering to Evaluate Cancer Signatures program. PD-L1 protein expression by immunohistochemistry was evaluated by using the Dako PD-L1 22C3 pharmDx kit on the Dako Link 48 auto-stainer (Dako, Carpinteria, CA). Tumor mutation burden (TMB) was calculated on the basis of data from targeted genome sequencing. The T-effector and interferon gamma (IFN-γ) gene signature was determined from Affymetrix gene chip data (Affymetrix, Santa Clara, CA) from frozen specimens.

Results

The prevalence of PD-L1 expression was 9.8% at a tumor proportion score cutoff of at least 50%. PD-L1 mRNA and programmed cell death 1 ligand 2 mRNA positively correlated with PD-L1 protein expression on tumor cells (TCs) and tumor-infiltrating immune cells. PD-L1 protein expression on tumor-infiltrating immune cells was correlated with the T-effector and IFN-γ gene signature (p < 0.001), but not with TMB. For TCs, all of these biomarkers were independent of each other and neither PD-L1 protein expression, TMB, or T-effector and IFN-γ gene signatures were independently prognostic for patient outcomes.

Conclusions

Evaluation of PD-L1 expression, TMB, and T-effector and IFN-γ gene signatures in the cohort with early-stage SqCLC found them to be independent of each other, and none was associated with overall survival. Our results also support the hypothesis that PD-L1 expression is regulated by an intrinsic mechanism on TCs and an adaptive mechanism on immune cells.  相似文献   
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Bulletin of Environmental Contamination and Toxicology - This work describes the development of an analytical protocol combining cleanup by liquid–solid extraction and GC–MS for the...  相似文献   
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38.

Aims

The 2014 British Thyroid Association thyroid cancer guidelines recommend lifelong follow-up of thyroid cancer patients. This is probably unnecessary, can cause patient anxiety, is time consuming and places significant demand on National Health Service resources. It has been suggested that low-risk differentiated thyroid cancer (DTC) patients could be discharged to primary care once they are 5 years from diagnosis and treatment. The aim of this study was to investigate the potential safety of this practice.

Materials and methods

In total, 756 patients with dynamically risk-stratified (DRS) low-risk/excellent response to treatment DTC treated over 2001–2013 in the Leeds region were followed after diagnostic surgery and the recurrence rate calculated.

Results

The median follow-up time was nearly 10 years (5–17 years). Radiological recurrence occurred in 13/756 (1.7%) patients and was always preceded by raised thyroglobulin/ thyroglobulin antibody levels. In all 13 patients elevation of thyroglobulin occurred within 5 years of diagnosis. Two additional patients were found to have rising thyroglobulin at almost 9 and 10.5 years from diagnosis, although to date radiological recurrence has not been detected. Assuming these two patients developed recurrence with longer duration of follow-up, then 0.26% (2/756) of patients would not have their recurrence discovered within 5 years of diagnosis. To detect 100% of patients with a putative recurrence in our cohort would require 10.5 years of follow-up. Four patients had transiently raised thyroglobulin, which became undetectable within 2 years (in three patients), without any treatment and radiological recurrence was not discovered.

Conclusion

Discharge of DRS low-risk DTC patients to primary care after 5 years of secondary care follow-up is reasonable, accepting that late recurrence may occur in a very small minority of individuals (0.26%, ~1:400). A more cautious approach would be to continue monitoring for 10 years, although the frequency of assessments could be reduced with increasing duration of follow-up.  相似文献   
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Objective

This paper constitutes the first attempt to draw lessons from the recent uptake of health economic evaluation of innovative drugs in the French regulatory framework.

Study Design

Taking the example of new direct-acting antivirals against hepatitis C virus, the paper asks whether and how the cost-effectiveness (CE) opinions issued by the French National Health Authority improve the information available to support the pricing decisions.

Methods

The analysis compares the assessment of these drugs based on three different sources: CE opinions, clinical opinions, and the published cost-utility analyses (CUA) available in the literature and identified through a systematic review.

Results

The results show that CE opinions bring to the fore three issues prone to impact the incremental cost utility ratio and those were not available to the decision maker through clinical opinions or published CUA: the stage of treatment initiation, the modeling of the disease progression, and the uncertainty around the efficacy rates.

Conclusions

France has introduced the criterion of the cost per QALY gained in the pricing and regulation of innovative pharmaceuticals since 2013. Our analysis shows that the use of CUA does enhance the information available to the decision makers on the value of the treatments.  相似文献   
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