Herzog August Library

An der Herzog August Bibliothek Wolfenbüttel werden seit gut 20 Jahren digitale Editionen von historischen Quellen aus Mittelalter und Früher Neuzeit erarbeitet und publiziert. Dieses runde Jubiläum nehmen wir zum Anlass, einen explorativen Rückblick auf die Editionen in der Wolfenbütteler Digitalen Bibliothek zu werfen. Mithilfe von quantitativen Analysen ausgewählter Metadaten sowie der Volltexte unternehmen wir ein korpusbasiertes Distant Reading, um übergreifende Themen und Charakteristiken der edierten Quellen und ihrer digitalen Repräsentationen herauszuarbeiten. Die Grundfrage ist dabei, inwieweit digitale Editionen einen Beitrag zur Profilierung von Mittelalter und Früher Neuzeit als historiografische Großepochen leisten können. Mithin steht damit auch ihr Erkenntnispotenzial für (digitale) Geschichtswissenschaften auf dem Prüfstand.

No abstract available.

IntroductionAn emerging challenge in early breast cancer (eBC) is improving risk assessment through the use of biomarkers. Clinical guidelines have recommended urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 for risk evaluation. This study aimed to validate the prognostic and predictive impact of uPA/PAI-1.Patients and methodsFrom a prospective cohort of 1270 patients (PiA-study, Prognostic assessment in routine Application, NCT01592825), concentrations of uPA and PAI-1 were determined in fresh tumour tissue (n = 813) by ELISA (FEMTELLE®; LOXO Diagnostics). The uPA/PAI-1 status was defined as low if both uPA and PAI-1 levels were low and as high if one or both were elevated. Primary objectives were the distribution of the uPA/PAI-1 status and its association with clinical/histopathological parameters. Secondary objectives were the association of the uPA/PAI-1 status with recurrence-free interval (RFI), overall survival (OS), and benefit from adjuvant chemotherapy.ResultsA low uPA/PAI-1 status was observed in 37.6% (306 of 813) of the entire cohort and in 47.9% (181 of 378) of those classified as intermediate-risk patients (≥ 35yrs, ≤ pN1, G2, sHR positive/HER2 negative). A low uPA/PAI-1 status was associated with parameters that predict a favourable prognosis. Overall, 96.7% (95% CI 94.5–98.9) of patients with a low uPA/PAI-1-status remained recurrence-free at five years and 87.2% (95% CI 84.1–90.3) with a high uPA/PAI-1 status even after adjustment to tumour size, nodal status, grading, steroid hormone receptor (sHR) status and HER2 status (adjusted HR 2.6, 95% CI 1.29–5.23). Among intermediate-risk patients without chemotherapy (n = 197), the prognostic value was even more pronounced (HR 10.10, 95% CI 1.13–16.12). Similar results were observed for OS. Only patients with a high uPA/PAI-1 status appeared to benefit from chemotherapy (adjusted HR 0.28, 95% CI 0.07-1.12, p = 0.07).ConclusionThis prospective analysis confirms the uPA/PAI-1 status as an independent prognostic factor and suggests a predictive impact considering benefit from chemotherapy.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10549-025-07850-z.