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Anja Almn Jnína Gujnsdttir Nils Heimland Britta Hjgaard Hanne Waltenburg Anders Widmark 《The British journal of radiology》2022,95(1130)
Objective:The purpose of this study was to explore the feasibility to determine regional diagnostic reference levels (RDRLs) for paediatric conventional and CT examinations using the European guidelines and to compare RDRLs derived from weight and age groups, respectively.Methods:Data were collected from 31 hospitals in 4 countries, for 7 examination types for a total of 2978 patients. RDRLs were derived for each weight and age group, respectively, when the total number of patients exceeded 15.Results:It was possible to derive RDRLs for most, but not all, weight-based and age-based groups for the seven examinations. The result using weight-based and age-based groups differed substantially. The RDRLs were lower than or equal to the European and recently published national DRLs.Conclusion:It is feasible to derive RDRLs. However, a thorough review of the clinical indications and methodologies has to be performed previous to data collection. This study does not support the notion that DRLs derived using age and weight groups are exchangeable.Advances in knowledge:Paediatric DRLs should be derived using weight-based groups with access to the actual weight of the patients. DRLs developed using weight differ markedly from those developed with the use of age. There is still a need to harmonize the method to derive solid DRLs for paediatric radiological examinations. 相似文献
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Anne M. Schultheis Ino de Bruijn Pier Selenica Gabriel S. Macedo Edaise M. da Silva Salvatore Piscuoglio Achim A. Jungbluth Kay J. Park David S. Klimstra Eva Wardelmann Wolfgang Hartmann Claus Dieter Gerharz Mareike von Petersdorff Reinhard Buettner Jorge S. ReisFilho Britta Weigelt 《Molecular oncology》2022,16(4):833
Small cell carcinoma (SCC) of the uterine cervix is a rare and aggressive form of neuroendocrine carcinoma, which resembles small cell lung cancer (SCLC) in its histology and poor survival rate. Here, we sought to define the genetic underpinning of SCCs of the uterine cervix and compare their mutational profiles with those of human papillomavirus (HPV)‐positive head and neck squamous cell carcinomas, HPV‐positive cervical carcinomas, and SCLCs using publicly available data. Using a combination of whole‐exome and targeted massively parallel sequencing, we found that the nine uterine cervix SCCs, which were HPV18‐positive (n = 8) or HPV16‐positive (n = 1), harbored a low mutation burden, few copy number alterations, and other than TP53 in two cases no recurrently mutated genes. The majority of mutations were likely passenger missense mutations, and only few affected previously described cancer‐related genes. Using RNA‐sequencing, we identified putative viral integration sites on 18q12.3 and on 8p22 in two SCCs of the uterine cervix. The overall nonsilent mutation rate of uterine cervix SCCs was significantly lower than that of SCLCs, HPV‐driven cervical adeno‐ and squamous cell carcinomas, or HPV‐positive head and neck squamous cell carcinomas. Unlike SCLCs, which are reported to harbor almost universal TP53 and RB1 mutations and a dominant tobacco smoke‐related signature 4, uterine cervix SCCs rarely harbored mutations affecting these genes (2/9, 22% TP53; 0% RB1) and displayed a dominant aging (67%) or APOBEC mutational signature (17%), akin to HPV‐driven cancers, including cervical adeno‐ and squamous cell carcinomas and head and neck squamous cell carcinomas. Taken together, in contrast to SCLCs, which are characterized by highly recurrent TP53 and RB1 alterations, uterine cervix SCCs were positive for HPV leading to inactivation of the suppressors p53 and RB, suggesting that these SCCs are convergent phenotypes. 相似文献
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Raquel Blazquez Eva Rietkötter Britta Wenske Darius Wlochowitz Daniela Sparrer Elena Vollmer Gunnar Müller Julia Seegerer Xueni Sun Katja Dettmer Alonso Barrantes-Freer Lena Stange Kirsten Utpatel Annalen Bleckmann Hannes Treiber Hanibal Bohnenberger Christof Lenz Matthias Schulz Christian Reimelt Christina Hackl Marian Grade Deram Büyüktas Laila Siam Marko Balkenhol Christine Stadelmann Dieter Kube Michael P. Krahn Martin A. Proescholdt Markus J. Riemenschneider Matthias Evert Peter J. Oefner Chistoph A. Klein Uwe K. Hanisch Claudia Binder Tobias Pukrop 《International journal of cancer. Journal international du cancer》2020,146(11):3170-3183
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Thais Basili Higinio Dopeso Sarah H. Kim Lorenzo Ferrando Fresia Pareja Arnaud Da Cruz Paula Edaise M. da Silva Anthe Stylianou Ana Maroldi Caterina Marchiò Brian P. Rubin Mauro Papotti Britta Weigelt Carlos Gil Moreira Ferreira José Roberto Lapa e Silva Jorge S. Reis-Filho 《International journal of cancer. Journal international du cancer》2020,147(8):2253-2264
Hyalinizing trabecular tumors of the thyroid are rare and mostly benign epithelial neoplasms of follicular cell origin, which have recently been shown to be underpinned by the PAX8-GLIS3 fusion gene. In our study, we sought to investigate the potential oncogenic mechanisms of the PAX8-GLIS3 fusion gene. Forced expression of PAX8-GLIS3 was found to increase proliferation, clonogenic potential and migration of human nonmalignant thyroid (Nthy-ori 3-1) and embryonic kidney (HEK-293) cells. Moreover, in xenografts, Nthy-ori 3-1 PAX8-GLIS3 expressing cells generated significantly larger and more proliferative tumors compared to controls. These oncogenic effects were found to be mediated through activation of the Sonic Hedgehog (SHH) pathway. Targeting of smoothened (SMO), a key protein in the SHH pathway, using the small molecule inhibitor Cyclopamine partially reversed the increased proliferation, colony formation and migration in PAX8-GLIS3 expressing cells. Our data demonstrate that the oncogenic effects of the PAX8-GLIS3 fusion gene are, at least in part, due to an increased activation of the SHH pathway. 相似文献
107.
Massimo Palatini Simon Franz Müller Michael Kirstgen Silke Leiting Felix Lehmann Lena Soppa Nora Goldmann Christin Müller Kira Alessandra Alicia Theresa Lowjaga Jrg Alber Giuliano Ciarimboli John Ziebuhr Dieter Glebe Joachim Geyer 《Viruses》2022,14(4)
The Na+/taurocholate co-transporting polypeptide (NTCP, gene symbol SLC10A1) is both a physiological bile acid transporter and the high-affinity hepatic receptor for the hepatitis B and D viruses (HBV/HDV). Virus entry via endocytosis of the virus/NTCP complex involves co-factors, but this process is not fully understood. As part of the innate immunity, interferon-induced transmembrane proteins (IFITM) 1–3 have been characterized as virus entry-restricting factors for many viruses. The present study identified IFITM3 as a novel protein–protein interaction (PPI) partner of NTCP based on membrane yeast-two hybrid and co-immunoprecipitation experiments. Surprisingly, IFITM3 knockdown significantly reduced in vitro HBV infection rates of NTCP-expressing HuH7 cells and primary human hepatocytes (PHHs). In addition, HuH7-NTCP cells showed significantly lower HDV infection rates, whereas infection with influenza A virus was increased. HBV-derived myr-preS1 peptide binding to HuH7-NTCP cells was intact even under IFITM3 knockdown, suggesting that IFITM3-mediated HBV/HDV infection enhancement occurs in a step subsequent to the viral attachment to NTCP. In conclusion, IFITM3 was identified as a novel NTCP co-factor that significantly affects in vitro infection with HBV and HDV in NTCP-expressing hepatoma cells and PHHs. While there is clear evidence for a direct PPI between IFITM3 and NTCP, the specific mechanism by which this PPI facilitates the infection process remains to be identified in future studies. 相似文献
108.
Rebecca E. Schultze‐Florey Sabine Tischer‐Zimmermann Hans‐Gert Heuft Christoph Priesner Britta Lamottke Albert Heim Martin Sauer Karl‐Walter Sykora Rainer Blasczyk Britta Eiz‐Vesper Britta Maecker‐Kolhoff 《Transplant infectious disease》2020,22(1)
Adenovirus (HAdV) infections confer a high risk of morbidity and mortality for immunocompromised patients after stem cell transplantation (SCT). Treatment with standard antiviral drugs is of limited efficacy and associated with a high rate of adverse effects. HAdV‐specific T cells are crucial for sustained viral elimination and the efficacy of adoptive T‐cell therapy with donor‐derived HAdV‐specific T cells has been reported by several investigators. Here, we report our experience with the transfer of HAdV‐specific T cells specific for penton, which was recently identified as an immunodominant target of T cells, and hexon in a 14‐year‐old boy after T‐cell‐depleted haploidentical SCT for myelodysplastic syndrome (MDS). He developed severe HAdV‐associated enteritis complicated by acute graft‐versus‐host disease (GvHD). The patient received ten infusions of allogeneic HAdV‐specific T cells manufactured from the haploidentical stem cell donor using the CliniMacs Interferon‐γ (IFN‐γ) cytokine capture and immunomagnetic selection. Initially, T cells were generated against the immunodominant target hexon and in subsequent transfers dual antigen‐specific T cells against hexon and penton were applied. T‐cell transfers were scheduled individually tailored to current immunosuppressive treatment. Each transfer was followed by reduction of HAdV load in peripheral blood and clinical improvement. Importantly, T‐cell responses to both penton and hexon pools emerged in patient blood after repetitive transfers. Unfortunately, the patient experienced bacterial sepsis, and in this context, severe GvHD requiring intensive immunosuppression followed by secondary progression of HAdV infection. The patient succumbed to multiorgan failure 283 days after SCT. This case demonstrates the feasibility of HAdV‐specific T‐cell transfer even in the presence of immunosuppressive treatment. Targeting of multiple immunodominant viral proteins may prove valuable in patients with complicated HAdV infections. 相似文献
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