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Background: Effective follow-up of brain metastasis (BM) patients post-treatment is crucial for adapting therapies and detecting new lesions. Current guidelines (Response Assessment in Neuro-Oncology-BM) have limitations, such as patient-level assessments and arbitrary lesion selection, which may not reflect outcomes in high tumor burden cases. Accurate, reproducible, and automated response assessments can improve follow-up decisions, including (1) optimizing re-treatment timing to avoid treating responding lesions or delaying treatment of progressive ones, and (2) enhancing precision in evaluating responses during clinical trials., Methods: We compared manual and automatic (deep learning-based) lesion contouring using unidimensional and volumetric criteria. Analysis focused on (1) agreement in size and RANO-BM categories, (2) stability of measurements under scanner rotations and over time, and (3) predictability of 1-year outcomes. The study included 49 BM patients, with 184 MRI studies and 448 lesions, retrospectively assessed by radiologists., Results: Automatic contouring and volumetric criteria demonstrated superior stability ( P  < .001 for rotation; P  < .05 over time) and better outcome predictability compared to manual methods. These approaches reduced observer variability, offering reliable and efficient response assessments. The best outcome predictability, defined as 1-year response, was achieved using automatic contours and volumetric measurements. These findings highlight the potential of automated tools to streamline clinical workflows and provide consistency across evaluators, regardless of expertise., Conclusion: Automatic BM contouring and volumetric measurements provide promising tools to improve follow-up and treatment decisions in BM management. By enhancing precision and reproducibility, these methods can streamline clinical workflows and improve the evaluation of response in trials and practice., Competing Interests: None declared., (© The Author(s) 2025. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Manual segmentation of lesions, required for radiotherapy planning and follow-up, is time-consuming and error-prone. Automatic detection and segmentation can assist radiologists in these tasks. This work explores the automated detection and segmentation of brain metastases (BMs) in longitudinal MRIs. It focuses on several important aspects: identifying and segmenting new lesions for screening and treatment planning, re-segmenting lesions in successive images using prior lesion locations as an additional input channel, and performing multi-component segmentation to distinguish between enhancing tissue, edema, and necrosis. The key component of the proposed approach is to propagate the lesion mask from the previous time point to improve the detection performance, which we refer to as "re-segmentation". The retrospective data includes 518 metastases in 184 contrast-enhanced T1-weighted MRIs originating from 49 patients (63% male, 37% female). 131 time-points (36 patients, 418 BMs) are used for cross-validation, the remaining 53 time-points (13 patients, 100 BMs) are used for testing. The lesions were manually delineated with label 1: enhancing lesion, label 2: edema, and label 3: necrosis. One-tailed t-tests are used to compare model performance including multiple segmentation and detection metrics. Significance is considered as p < 0.05. A Dice Similarity Coefficient (DSC) of 0.79 and F 1 -score of 0.80 are obtained for the segmentation of new lesions. On follow-up scans, the re-segmentation model significantly outperforms the segmentation model (DSC and F 1 0.78 and 0.88 vs 0.56 and 0.60). The re-segmentation model also significantly outperforms the simple segmentation model on the enhancing lesion (DSC 0.76 vs 0.53) and edema (0.52 vs 0.47) components, while similar scores are obtained on the necrosis component (0.62 vs 0.63). Additionally, we analyze the correlation between lesion size and segmentation performance, as demonstrated in various studies that highlight the challenges in segmenting small lesions. Our findings indicate that this correlation disappears when utilizing the re-segmentation approach and evaluating with the unbiased normalized DSC. In conclusion, the automated segmentation of new lesions and subsequent re-segmentation in follow-up images was achievable, with high level of performance obtained for single- and multiple-component segmentation tasks., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Competing Interests: Nous tenons à remercier notre tutrice, Nathalie Koch, ainsi que toutes les personnes interviewées dans le cadre de cette recherche.

Mammalian transcription factors (TFs) differ broadly in their nuclear mobility and sequence-specific/non-specific DNA binding. How these properties affect their ability to occupy specific genomic sites and modify the epigenetic landscape is unclear. The association of TFs with mitotic chromosomes observed by fluorescence microscopy is largely mediated by non-specific DNA interactions and differs broadly between TFs. Here we combine quantitative measurements of mitotic chromosome binding (MCB) of 501 TFs, TF mobility measurements by fluorescence recovery after photobleaching, single molecule imaging of DNA binding, and mapping of TF binding and chromatin accessibility. TFs associating to mitotic chromosomes are enriched in DNA-rich compartments in interphase and display slower mobility in interphase and mitosis. Remarkably, MCB correlates with relative TF on-rates and genome-wide specific site occupancy, but not with TF residence times. This suggests that non-specific DNA binding properties of TFs regulate their search efficiency and occupancy of specific genomic sites.

During mitosis, gene transcription stops, and the bulk of DNA-binding proteins are excluded from condensed chromosomes. While most gene-specific transcription factors are largely evicted from mitotic chromosomes, a subset remains bound to specific and non-specific DNA sites. Here, we review the current knowledge on the mechanisms leading to the retention of a subset of transcription factors on mitotic chromosomes and discuss the implications in gene expression regulation and their potential as an epigenetic mechanism controlling stem cell self-renewal and differentiation., (© 2017 Federation of European Biochemical Societies.)

Mitotic bookmarking transcription factors remain bound to chromosomes during mitosis and were proposed to regulate phenotypic maintenance of stem and progenitor cells at the mitosis-to-G1 (M-G1) transition. However, mitotic bookmarking remains largely unexplored in most stem cell types, and its functional relevance for cell fate decisions remains unclear. Here we screened for mitotic chromosome binding within the pluripotency network of embryonic stem (ES) cells and show that SOX2 and OCT4 remain bound to mitotic chromatin through their respective DNA-binding domains. Dynamic characterization using photobleaching-based methods and single-molecule imaging revealed quantitatively similar specific DNA interactions, but different nonspecific DNA interactions, of SOX2 and OCT4 with mitotic chromatin. Using ChIP-seq (chromatin immunoprecipitation [ChIP] combined with high-throughput sequencing) to assess the genome-wide distribution of SOX2 on mitotic chromatin, we demonstrate the bookmarking activity of SOX2 on a small set of genes. Finally, we investigated the function of SOX2 mitotic bookmarking in cell fate decisions and show that its absence at the M-G1 transition impairs pluripotency maintenance and abrogates its ability to induce neuroectodermal differentiation but does not affect reprogramming efficiency toward induced pluripotent stem cells. Our study demonstrates the mitotic bookmarking property of SOX2 and reveals its functional importance in pluripotency maintenance and ES cell differentiation., (© 2016 Deluz et al.; Published by Cold Spring Harbor Laboratory Press.)

Unlabelled: Mycobacterium tuberculosis possesses a thick and highly hydrophobic cell wall principally composed of a mycolyl-arabinogalactan-peptidoglycan complex, which is critical for survival and virulence. DprE1 is a well-characterized component of decaprenyl-phospho-ribose epimerase, which produces decaprenyl-phospho-arabinose (DPA) for the biosynthesis of mycobacterial arabinans. Upstream of dprE1 lies rv3789, which encodes a short transmembrane protein of the GtrA family, whose members are often involved in the synthesis of cell surface polysaccharides. We demonstrate that rv3789 and dprE1 are cotranscribed from a common transcription start site situated 64 bp upstream of rv3789. Topology mapping revealed four transmembrane domains in Rv3789 and a cytoplasmic C terminus consistent with structural models built using analysis of sequence coevolution. To investigate its role, we generated an unmarked rv3789 deletion mutant in M. tuberculosis. The mutant was characterized by impaired growth and abnormal cell morphology, since the cells were shorter and more swollen than wild-type cells. This phenotype likely stems from the decreased incorporation of arabinan into arabinogalactan and was accompanied by an accumulation of DPA. A role for Rv3789 in arabinan biosynthesis was further supported by its interaction with the priming arabinosyltransferase AftA, as demonstrated by a two-hybrid approach. Taken together, the data suggest that Rv3789 does not act as a DPA flippase but, rather, recruits AftA for arabinogalactan biosynthesis., Importance: Upstream of the essential dprE1 gene, encoding a key enzyme of the decaprenyl phospho-arabinose (DPA) pathway, lies rv3789, coding for a short transmembrane protein of unknown function. In this study, we demonstrated that rv3789 and dprE1 are cotranscribed from a common transcription start site located 64 bp upstream of rv3789 in M. tuberculosis. Furthermore, the deletion of rv3789 led to a reduction in arabinan content and to an accumulation of DPA, confirming that Rv3789 plays a role in arabinan biosynthesis. Topology mapping, structural modeling, and protein interaction studies suggest that Rv3789 acts as an anchor protein recruiting AftA, the first arabinosyl transferase. This investigation provides deeper insight into the mechanism of arabinan biosynthesis in mycobacteria., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)