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Lehmbecker, A.

Publications and source records attributed to Lehmbecker, A..

2 recordsLinked to original sources

Computer-Assisted Mitotic Count Using a Deep Learning-based Algorithm Improves Inter-Observer Reproducibility and Accuracy in canine cutaneous mast cell tumors

The mitotic count (MC) is an important histological parameter for prognostication of malignant neoplasms. However, it has inter- and intra-observer discrepancies due to difficulties in selecting the region of interest (MC-ROI) and in identifying/classifying mitotic figures (MFs). Recent progress in the field of artificial intelligence has allowed the development of high-performance algorithms that may improve standardization of the MC. As algorithmic predictions are not flawless, the computer-assisted review by pathologists may ensure reliability. In the present study we have compared partial (MC-ROI preselection) and full (additional visualization of MF candidate proposal and display of algorithmic confidence values) computer-assisted MC analysis to the routine (unaided) MC analysis by 23 pathologists for whole slide images of 50 canine cutaneous mast cell tumors (ccMCTs). Algorithmic predictions aimed to assist pathologists in detecting mitotic hotspot locations, reducing omission of MF and improving classification against imposters. The inter-observer consistency for the MC significantly increased with computer assistance (interobserver correlation coefficient, ICC = 0.92) compared to the unaided approach (ICC = 0.70). Classification into prognostic stratifications had a higher accuracy with computer assistance. The algorithmically preselected MC-ROIs had a consistently higher MCs than the manually selected MC-ROIs. Compared to a ground truth (developed with immunohistochemistry for phosphohistone H3), pathologist performance in detecting individual MF was augmented when using computer assistance (F1-score of 0.68 increased to 0.79) with a reduction in false negatives by 38%. The results of this study prove that computer assistance may lead to a more reproducible and accurate MCs in ccMCTs.

pathology↗

De-novo variants in XIRP1 associated with polydactyly and polysyndactyly in Holstein cattle

Congenital polydactylous cattle are sporadically observed. Impairment of the limb patterning process due to altered control of the zone of polarizing activity (ZPA) was associated in several species with preaxial polydactyly and syndactyly. In cattle, the role of ZPA and other genes involved in limb patterning for polydactyly was not yet elucidated. Herein, we report on a preaxial type II polydactyly and a praeaxial type II+V polysyndactyly in two Holstein calves and screen whole genome sequencing data for associated variants. Using whole genome sequencing data of both affected calves did not show mutations in the candidate regions of ZRS and pZRS or in candidate genes associated with polydactyly, syndactyly and polysyndactyly in other species. Two indels, which are located in XIRP1 within a common haplotype, were highly associated with the two phenotypes. Bioinformatic analyses retrieved an interaction between XIRP1 and FGFR1, CTNNB1 and CTNND1 supporting a link between the XIRP1 variants and embryonic limb patterning. The heterozygous haplotype was highly associated with the present polydactylous phenotypes due to dominant mode of inheritance with an incomplete penetrance in Holstein cattle.

genetics↗