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Second premolar agenesis is associated with mandibular form： a geometric morphometric analysis of mandibular cross-sections

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International Journal of Oral Science 2016年第4期8卷 254-260页

作者： michael h bertl Kristina bertl Manuel Wagner Andre Gahleitner Andreas Stavropoulos Christian Ulm Philipp Mitteroecker Division of Orthodontics School of Dentistry Medical University of Vienna Vienna Austria Department of Periodontology Faculty of Odontology University of Malmo MalmoSweden Division of Oral Surgery School of Dentistry Medical University of Vienna Vienna Austria Department of Diagnostic Radiology Division of Osteoradiology General Hospital Medical University of Vienna Vienna Austria Department of Theoretical Biology University of Vienna Vienna Austria

The aim of this study was to compare mandibular form （i.e., size and shape） between patients with agenesis of the lower second premolar （P2） and a control group with no agenesis. Three hypotheses were tested：（h1） agenesis causes a change in mandibular morphology because of inadequate alveolar ridge development in the area of the missing tooth （mandibular plasticity）; （h2） agenesis is caused by spatial limitations within the mandible （dental plasticity）; and （h3） common genetic/ epigenetic factors cause agenesis and affect mandibular form （pleiotropy）. A geometric morphometric analysis was applied to cross-sectional images of computed tomography （CT） scans of three matched groups （n= 50 each）：（1） regularly erupted P2; （2） agenesis of P2 and the primary second molar in situ; and （3） agenesis of P2 and the primary second molar missing for 〉3 months. Cross-sections of the three areas of interest （first premolar, P2, first molar） were digitized with 23 landmarks and superimposed by a generalized Procrustes analysis. On average, the mandibular cross-sections were narrower and shorter in patients with P2 agenesis compared with that in the control group. Both agenesis groups featured a pronounced submandibular fossa. These differences extended at least one tooth beyond the agenesis-affected region. Taken together with the large interindividual variation that resulted in massively overlapping group distributions, these findings support genetic and/or epigenetic pleiotropy （h3） as the most likely origin of the observed covariation between mandibular form and odontogenesis. Clinically, reduced dimensions and greater variability of mandibular form, as well as a pronounced submandibular fossa, should be expected during the treatment planning of patients with P2 agenesis.

关键词： agenesis cross-sections geometric morphometrics mandibular form

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Tumour mutational burden is overestimated by target cancer gene panels

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Journal of the National Cancer Center 2023年第1期3卷 56-64页

作者： hu Fang Johanna bertl Xiaoqiang Zhu Tai Chung Lam Song Wu David J.h.Shih Jason W.h.Wong School of Biomedical Sciences Li Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina South China hospital Health Science CenterShenzhen UniversityShenzhenChina Department of Mathematics Aarhus UniversityAarhusDenmark Department of Clinical Oncology Li Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina

Background:Tumour mutational burden(TMB)has emerged as a predictive marker for responsiveness to immune checkpoint inhibitors(ICI)in multiple tumour *** can be calculated from somatic mutations detected from whole exome or targeted panel sequencing *** mutations are unevenly distributed across the cancer genome,the clinical implications from TMB calculated using different genomic regions are not ***:Pan-cancer data of 10,179 samples were collected from The Cancer Genome Atlas cohort and 6,831 cancer patients with either ICI or non-ICI treatment outcomes were derived from published *** was calculated as the count of non-synonymous mutations and normalised by the size of genomic *** method,linear regression and Poisson calibration models are used to unify TMB from different gene ***:We found that panels based on cancer genes usually overestimate TMB compared to whole exome,potentially leading to misclassification of patients to receive *** overestimation is caused by positive selection for mutations in cancer genes and cannot be completely addressed by the removal of mutational *** compared different approaches to address this discrepancy and developed a generalised statistical model capable of interconverting TMB derived from whole exome and different panel sequencing data,enabling TMB correction for patient stratification for ICI *** show that in a cohort of lung cancer patients treated with ICI,when using a TMB cutoffof 10 mut/Mb,our corrected TMB outperforms the original panel-based ***:Cancer gene-based panels usually overestimate TMB,and these findings will be valuable for unifying TMB calculations across cancer gene panels in clinical practice.

关键词： Tumour mutational burden Immune checkpoint inhibitor Immune response Biomarker

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焦炉加热系统的新发展

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国外炼焦化学 1990年第3期9卷 44-49页

作者： bertl.,h 王杰

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