Correction: Gender differences in time use across age groups: A study of ten industrialized countries, 2005-2015.

[This corrects the article DOI: 10.1371/journal.pone.0264411.].

Genomic deletions explain the generation of alternative BRAF isoforms conferring resistance to MAPK inhibitors in melanoma.

Resistance to MAPK inhibitors (MAPKi), the main cause of relapse in BRAF-mutant melanoma, is associated with the production of alternative BRAF mRNA isoforms (altBRAFs) in up to 30% of patients receiving BRAF inhibitor monotherapy. These altBRAFs have been described as being generated by alternative pre-mRNA splicing, and splicing modulation has been proposed as a therapeutic strategy to overcome resistance. In contrast, we report that altBRAFs are generated through genomic deletions. Using different in vitro models of altBRAF-mediated melanoma resistance, we demonstrate the production of altBRAFs exclusively from the BRAF V600E allele, correlating with corresponding genomic deletions. Genomic deletions are also detected in tumor samples from melanoma and breast cancer patients expressing altBRAFs. Along with the identification of altBRAFs in BRAF wild-type and in MAPKi-naive melanoma samples, our results represent a major shift in our understanding of mechanisms leading to the generation of BRAF transcripts variants associated with resistance in melanoma.

Fourier tools for the evaluation of refractive multifocal designs.

This paper presents innovative tools and methodologies for the theoretical assessment of optical properties in refractive multifocal designs. Utilizing lens segmentation techniques and classical Fourier optics, these tools can be of help evaluating multifocal contact lenses, intraocular lenses, small aperture designs, and corneal inlays. As an example of their utility, this study presents the through-focus Visual Strehl ratios in the frequency domain of 12 multifocal contact lenses from four companies, derived from the sagittal power profiles obtained with a NIMO equipment (LAMBDA-X) for three base prescriptions (- 6.00 D, - 3.00 D, and + 1.00 D). The contact lenses are also assessed alongside higher-order aberrations obtained from 65 eyes, measured using a Wavefront Sciences Complete Ophthalmic Analysis System (AMO). Diameter variations, corresponding to individual pupil sizes (2.45-6.27 mm), were considered in the evaluation. These novel tools enable the theoretical evaluation of multifocal solutions without the need for prototypes. In the case examples presented, they differentiate between lenses tailored for different presbyopic age groups, offer guidance on optimizing hyperfocal distance in contact lens design, and underscore the relevance of the effective aperture effect. Notably, this paper introduces the pioneering conversion of sagittal powers of multifocal solutions into an equivalent wavefront and optical quality metric, with potential applications in myopia control assessments. The author hopes that readers recognize and utilize these tools to advance the field of refractive multifocality.