The Advanced REACH Tool (ART) is the most sophisticated tool used for evaluating exposure levels under the European Union's Registration, Evaluation, Authorisation and restriction of CHemicals (REACH) regulations. ART provides estimates at different percentiles of exposure and within different confidence intervals (CIs). However, its performance has only been tested on a limited number of exposure data. The present study compares ART's estimates with exposure measurements collected over many years in Switzerland. Measurements from 584 cases of exposure to vapours, mists, powders, and abrasive dusts (wood/stone and metal) were extracted from a Swiss database. The corresponding exposures at the 50th and 90th percentiles were calculated in ART. To characterize the model's performance, the 90% CI of the estimates was considered. ART's performance at the 50th percentile was only found to be insufficiently conservative with regard to exposure to wood/stone dusts, whereas the 90th percentile showed sufficient conservatism for all the types of exposure processed. However, a trend was observed with the residuals, where ART overestimated lower exposures and underestimated higher ones. The median was more precise, however, and the majority (≥60%) of real-world measurements were within a factor of 10 from ART's estimates. We provide recommendations based on the results and suggest further, more comprehensive, investigations.
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http://dx.doi.org/10.1093/annweh/wxx069 | DOI Listing |
Front Pharmacol
December 2024
Syreon Research Institute, Budapest, Hungary.
Background: Non-adherence to medication remains a persistent and significant challenge, with profound implications for patient outcomes and the long-term sustainability of healthcare systems. Two decades ago, the World Health Organization (WHO) dedicated its seminal report to adherence to long-term therapies, catalysing notable changes that advanced both research and practice in medication adherence. The aim of this paper was to identify the most important progress made over the last 2 decades in medication adherence management and to initiate a discussion on future objectives, suggesting priority targets for the next 20 years.
View Article and Find Full Text PDFJ Clin Transl Endocrinol
December 2024
Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138 Bologna, Italy.
Thanks to the identification of crucial molecular pathways, the therapeutic landscape for advanced differentiated thyroid tumors (DTCs) has significantly improved during the last ten years. The therapeutic scenario has been greatly impacted by the discovery of mutually exclusive gene changes in the MAPK and PI3K/AKT pathways, such as or fusions and pathogenic mutations of the and genes. Indeed, multi-kinase inhibitors and selective inhibitors have demonstrated outstanding efficacy for radioactive iodine-refractory (RAI-R) drug treatment, with overall response rates reaching up to 86%.
View Article and Find Full Text PDFApplications of genetic code expansion in live cells are widespread and continually emerging, yet they have been limited by their reliance on the supplementation of non-standard amino acids (nsAAs) to cell culturing media. While advances in cell-free biocatalysis are improving nsAA synthesis cost and sustainability, such processes remain reliant on multi-step processes of product isolation followed by supplementation to engineered cells. Here, we report the design of a modular and genetically encoded system that combines the steps of biosynthesis of diverse phenylalanine derivatives, which are the most frequently used family of nsAAs for genetic code expansion, and their site-specific incorporation within target proteins using a single engineered bacterial host.
View Article and Find Full Text PDFFront Immunol
December 2024
Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
Background: Transarterial therapy (TAT), bevacizumab (Bev), and immune checkpoint inhibitors (ICIs) have individually exhibited efficacy in treating advanced-stage hepatocellular carcinoma (HCC). This study aimed to assess the efficacy and safety of the combination of these three treatments as a neoadjuvant modality in patients with locally advanced HCC.
Methods: The primary endpoint is overall survival (OS).
EClinicalMedicine
November 2024
China-Australia Joint Research Centre for Infectious Diseases, School of Public Health, Xi'an Jiaotong University Health Science Centre, Xi'an, Shaanxi, China.
Background: In the context of the World Health Organization's (WHO) 90-70-90 targets for accelerating cervical cancer elimination, we aimed to assess the impact of achieving these targets and altering intervention factors on cervical cancer elimination in China and their potential benefits from preventing other human papillomavirus (HPV)-related cancers.
Methods: We developed a sexual contact network-Markov model to simulate HPV transmission and the progression of HPV-related cancers (cervical, vaginal, vulvar, penile, anal, and oropharyngeal cancers). We projected the population impact of achieving 90-70-90 targets by 2030 on the overall HPV-related cancer burden in China during 2024-2100.
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