Specific detection of OCT3/4 isoform A/B/B1 expression in solid (germ cell) tumours and cell lines: Confirmation of OCT3/4 specificity for germ cell tumours

Background: OCT3/4 (POU5F1) is an established diagnostic immunohistochemical marker for specific histological variants of human malignant germ cell tumours (GCTs), including the seminomatous types and the stem cell component of non-seminomas, known as embryonal carcinoma. OCT3/4 is crucial for the regulation of pluripotency and the self-renewal of normal embryonic stem-and germ cells. Detection of expression of this transcription factor is complicated by the existence of multiple pseudogenes and isoforms. Various claims have been made about OCT3/4 expression in non-GCTs, possibly related to using nonspecific detection methods. False-positive findings undermine the applicability of OCT3/4 as a specific diagnostic tool in a clinical setting. In addition, false-positive findings could result in misinterpretation of pluripotency regulation in solid somatic cancers and their stem cells. Of the three identified isoforms-OCT4A, OCT4B and OCT4B1-only OCT4A proved to regulate pluripotency. Up until now, no convincing nuclear OCT4A protein expression has been shown in somatic cancers or tissues. Methods: This study investigates expression of the various OCT3/4 isoforms in GCTs (both differentiated and undifferentiated) and somatic (non-germ cell) cancers, including representative cell lines and xenografts. Results: Using specific methods, OCT4A and OCT4B1 are shown to be preferentially expressed in undifferentiated GCTs. The OCT4B variant shows no difference in expression between GCTs (either differentiated or undifferentiated) and somatic cancers. In spite of the presence of OCT4A mRNA in somatic cancer-derived cell lines, no OCT3/4

Hospital reforms in 11 Central and Eastern European countries between 2008 and 2019 : a comparative analysis

This paper aims to: (1) provide a brief overview of hospital sector characteristics in 11 Central and East-ern European countries (Bulgaria, Czech Republic, Estonia, Croatia, Latvia, Lithuania, Hungary, Poland,Romania, Slovakia, Slovenia); (2) compare recent (2008 – 2019) hospital reforms in these countries; and(3) identify common trends, success factors and challenges for reforms. Methods applied involved fivestages: (1) a theoretical framework of hospital sector reforms was developed; (2) basic quantitative datacharacterizing hospital sectors were compared; (3) a scoping review was performed to identify an initiallist of reforms per country; (4) the list was sent to national researchers who described the top threereforms based on a standardized questionnaire; (5) received questionnaires were analysed and vali-dated with available literature. Results indicate that the scope of conducted reforms is very broad. Yet,reforms related to hospital sector governance and changes in purchasing and payment systems are muchmore frequent than reforms concerning relations with other providers. Most governance reforms aimedat transforming hospital infrastructure, improving financial management and/or improving quality ofcare, while purchasing and payment reforms focused on limiting hospital activities and/or on incen-tivising a shift to ambulatory/day care. Three common challenges included the lack of a comprehensiveapproach; unclear outcomes; and political influence. Given similar reform areas across countries, thereis considerable potential for shared learning