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Guevara, D.

Publications and source records attributed to Guevara, D..

2 recordsLinked to original sources

{micro}CT Scanning Effects on DNA and a Multi-Step Workflow for Archaeological Petrous Bones

The petrous portion of the temporal bone is a key element in human evolutionary studies due to its exceptional preservation of biomolecules and morphological information. However, intensive and often redundant sampling has raised concerns about sustainability and long-term conservation. Here we present the first systematic evaluation of whether micro-Computed Tomography ({micro}CT)--a widely used tool for digital preservation--affects ancient DNA (aDNA) integrity in human petrous bones. We analyzed 93 archaeological samples from Argentina, of which 50 had been scanned using {micro}CT and 43 had not. We compared six molecular parameters, including endogenous content, read length, cytosine deamination patterns and contamination estimates. No statistically significant differences were observed between scanned and unscanned samples across any parameter (Mann-Whitney/Wilcoxon tests, p <0.05). Although mitochondrial contamination was marginally higher in scanned samples (p = 0.051), this was not driven by contamination estimates above the widely accepted 5% threshold for genomic analysis, Moreover, this pattern was not observed when considering nuclear contamination. These results indicate that, under appropriate scanning conditions, {micro}CT imaging does not compromise DNA preservation. Building on this evidence, we propose a sustainable, multi-step workflow that integrates biological profiling, osteobiography, imaging, and compositional pre-screening prior to molecular sampling. This interdisciplinary approach maximizes the scientific information obtained from skeletal collections while minimizing destructive practices, thereby promoting ethical and sustainable research on irreplaceable anthropological remains, and fosters collaboration across research fields.

paleontology↗

Pan-Cancer PDOs Preserve Tumor Heterogeneity and Uncover Therapeutic Vulnerabilities

We developed a tumor-matched, pan-cancer patient-derived organoid (PDO) platform comprising 220 PDOs from 190 patients across 15 cancer types to advance functional precision oncology. Our comprehensively characterized PDOs showed 93% histopathology concordance, 80% median genomic concordance for driver mutations, and a 0.85 median gene expression correlation with parent tumors. Gene expression in PDOs remained stable across [&ge;] 10 passages, supporting reproducibility for long-term drug screening. Even PDOs with low genomic concordance retained oncogenic drivers, supporting their use as disease models. Clonality analysis revealed that 85% of PDOs preserved dominant tumor clones. Higher genomic concordance was associated with greater clonal similarity, while lower genomic concordance was associated with clonal divergence. Functional assays showed that 58% of PDOs from a subset of patients ineligible for FDA-approved PARP inhibitors responded to Talazoparib, with sensitivity linked to alterations in DNA damage repair. Combination screens revealed drugs that effectively overcame resistance, especially in TP53-mutant PDOs. In summary, our platform supports investigation of targeted therapies, identification of molecular features linked to drug sensitivity, and translational discovery, offering insights into personalized cancer treatment beyond current biomarker guidelines.

cancer biology↗