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A growing number of clinical risk scores have been proposed to predict allograft failure after liver transplantation. However, validation of currently available scores in the Eurotransplant region is still lacking. We aimed to analyze all clinically relevant donor and recipient risk scores on a large German liver transplantation data set and performed a retrospective cohort analysis of liver transplantations performed at the Charité-Universitätsmedizin Berlin from January 2007 until December 2021 with organs from donation after brain death. We analyzed 9 previously published scores in 906 liver transplantations [Eurotransplant donor risk index (ET-DRI/DRI), donor age and model for end-stage liver disease (D-MELD), balance of risk (BAR), early allograft dysfunction (EAD), model for early allograft function (MEAF), liver graft assessment following transplantation (L-GrAFT7), early allograft failure simplified estimation (EASE), and a score by Rhu and colleagues). The EASE score had the best predictive value for 3-month, 6-month, and 12-month graft survival with a c-statistic of 0.8, 0.77, and 0.78, respectively. In subgroup analyses, the EASE score was suited best for male recipients with a high-MELD (>25) and an EAD organ. Scores only based on pretransplant data performed worse compared to scores including postoperative data (eg, ET-DRI vs. EAD, p

Additional file 1: Table S1 Standardized mean differences (SMD) prior and after propensity score matching.

Cities, which have been one of the most important settlements of people throughout history; In the process until the Industrial Revolution, it had a structure dominated by agricultural production, producing small workshops, and having a more homogeneous structure compared to today, although not as much as the rural area in terms of population. With the industrial revolution, urban structuring has completely changed. This change has manifested itself in economy, politics, social structure and daily life. The changing mode of production, the establishment of factories, has caused people to migrate to cities. Social structure and cultural structure were also affected by this situation. The urbanization process in Turkey started to increase with the 1950s. Because the modernization movements in the agricultural field have reduced the job opportunities in the rural areas and the families who cannot find a job have started to migrate to the big cities. In addition to this situation, the increase in the attractive factors of the cities has also been an important factor that accelerated the migration process. The urbanization process in Turkey has become visible in all areas of life. With this study, how the increasing migration to cities in Turkey in the 1950s reflected on Turkish Cinema was examined and an urbanization map of Turkey was tried to be drawn with the movie "Bitmeyen Yol"., Tarih boyunca insanların en önemli yerleşim alanlarından biri olan kentler; Sanayi Devrimine kadar olan süreçte tarımsal üretimin hakim olduğu, küçük atölye üretimi yapan ve nüfus açısından kırsal alan kadar olmasa da günümüze oranla daha homojen olan bir yapılanmaya sahip olmuştu. Sanayi devrimi ile birlikte kent yapılanmaları tamamen değişime uğramıştır. Bu değişim ekonomide, siyasette, toplumsal yapıda ve günlük hayatta kendini göstermiştir. Değişen üretim biçimi yani fabrikaların kurulması insanların kentlere göç etmesine sebebiyet vermiştir. Toplumsal yapı ve kültürel yapı da bu durumdan oldukça etkilenmiştir. Türkiye’de kentleşme süreci 1950’li yıllarla birlikte artış göstermeye başlamıştır. Çünkü tarımsal alanda yapılan modernleşme hareketleri kırsal alanda iş imkânını azaltmış ve iş bulamayan aileler büyük kentlere göç etmeye başlamıştır. Bu durumun yanında kentlerin çekici etmenlerinin artması da göç sürecini hızlandıran önemli bir etken olmuştur. Türkiye’de kentleşme süreci hayatın her alanında görünür hale gelmiştir. Bu çalışma ile birlikte Türkiye’de 1950’li yıllarda kentlere artan göçün Türk Sineması’na nasıl yansıdığı incelenmiş ve “Bitmeyen Yol” filmi eşliğinde Türkiye’nin kentleşme haritası çıkarılmaya çalışılmıştır.

Severe COVID-19 is linked to both dysfunctional immune response and unrestrained immunopathology, and it remains unclear whether T cells contribute to disease pathology. Here, we combined single-cell transcriptomics and single-cell proteomics with mechanistic studies to assess pathogenic T cell functions and inducing signals. We identified highly activated, CD16+ T cells with increased cytotoxic functions in severe COVID-19. CD16 expression enabled immune complex-mediated, T cell receptor-independent degranulation and cytotoxicity not found in other diseases. CD16+ T cells from COVID-19 patients promoted microvascular endothelial cell injury and release of neutrophil and monocyte chemoattractants. CD16+ T cell clones persisted beyond acute disease maintaining their cytotoxic phenotype. Increased generation of C3a in severe COVID-19 induced activated CD16+ cytotoxic T cells. Proportions of activated CD16+ T cells and plasma levels of complement proteins upstream of C3a were associated with fatal outcome of COVID-19, supporting a pathological role of exacerbated cytotoxicity and complement activation in COVID-19., Generation of the C3a complement protein fragment by SARS-CoV-2 infection drives differentiation of a CD16-expressing T cell population that associates with severe COVID-19 disease outcomes.

YÖK Tez No: 686137 İnsanları kendilerine çeken kentler en genel tanımıyla tarımsal faaliyetin olmadığı tarım dışı etkinliğin fazla olduğu mekânlar olarak tanımlanmaktadır. Bu mekânlar tarih boyunca pek çok değişim ve dönüşüm yaşamıştır. Ancak hiç biri kentleri sanayi devrimi kadar etkilememiştir. Sanayi devrimi kentleri ekonomik, sosyal, siyasi ve hatta kültürel açıdan bir değişim ve dönüşüme zorlamıştır. Bu değişim ve dönüşümün kent için en büyük etkisi ise kentleşme süreci olmuştur. Türkiye'de kentleşeme süreci 1950'li yıllarda tarımsal alanda yapılan modernleşme hareketiyle başlamıştır. Bu modernleşme hareketi kırsal alanda iş imkânı bulamayan aileleri büyük kentlere göç etmeye zorlayarak kentleşeme sürecinin yaşanmasına neden olmuştur. Bu tarihten itibaren hızlı bir kentleşme süreci yaşayan Türkiye, kentleşmenin etkisiyle pek çok sorunla karşı karşıya kalmıştır. Bu sorunların tespiti ve çözümlenmesinde yazılı kaynaklar kadar görsel kaynaklarda büyük önem taşımaktadır. Bu önem göz önüne alınarak Türkiye'de yaşanan kentleşme süreci sinema eşliğinde dönemlere ayrılarak Türkiye'nin kentleşme haritası çıkarılmaya çalışılacaktır. Cities that attract people to them are defined as places where there is a high number of non-agricultural activities without agricultural activities in the most general definition.These venues have undergone many changes and transformations throughout history. However, none affected cities as much as the industrial revolution. The industrial revolution forced cities to change and transform economically, socially, politically and even culturally. The biggest impact of this change and transformation for the city has been the urbanization process. The urbanization process in Turkey began in the 1950s with the modernization movement in the agricultural field. This modernization movement forced families who could not find employment in the countryside to migrate to large cities, causing urbanization to occur. Having experienced a rapid urbanization process since this date, Turkey has faced many problems with the effect of urbanization. Visual sources are as important as written sources in identifying and resolving these problems. Considering this importance, the urbanization process in Turkey will be divided into periods with cinema and an urbanization map of Turkey will be tried to be drawn.

Journal of Clinical Medicine 10(15), 3392 (2021). doi:10.3390/jcm10153392 special issue: "Special Issue "Clinical Research in Hepatology" / Special Issue Editor: Prof. Dr. Yulia A. Nevzorova, Guest Editor", Published by MDPI, Basel

The implementation of immune checkpoint inhibitors (ICI) into the clinical management of different malignancies has largely changed our understanding of cancer treatment. After having proven efficacy in different tumor entities such as malignant melanoma and lung cancer, ICI were intensively tested in the setting of hepatocellular carcinoma (HCC). Here they could achieve higher and more durable response rates compared to tyrosine-kinase inhibitors (TKI), that were sole standard of care for the last decade. Most recently, ICI treatment was approved in a first line setting of HCC, for cases not suitable for curative strategies. However, only a subset of patients benefits from ICI therapy, while others experience rapid tumor progression, worsening of liver function and poor prognosis. Efforts are being made to find immune characteristics that predict tumor responsiveness to ICI, but no reliable biomarker could be identified so far. Nevertheless, data convincingly demonstrate that combination therapies (such as dual inhibition of PD-L1 and VEGF) are more effective than the application of single agents. In this review, we will briefly recapitulate the current algorithms for systemic treatment, discuss available results from checkpoint inhibitor trials and give an outlook on future directions of immunotherapy in HCC.

Liver affection of Alpha1-antitrypsin deficiency (AATD) can lead to cirrhosis and hepatocellular carcinoma (HCC). A noninvasive severity assessment of liver disease in AATD is urgently needed since laboratory parameters may not accurately reflect the extent of liver involvement. Preliminary data exist on two-dimensional shear wave elastography (2D-SWE) being a suitable method for liver fibrosis measurement in AATD. AATD patients without HCC were examined using 2D-SWE, shear wave dispersion imaging (SWD) and transient elastography (TE). Furthermore, liver steatosis was assessed using the controlled attenuation parameter (CAP) and compared to the new method of attenuation imaging (ATI). 29 AATD patients were enrolled, of which 18 had the PiZZ genotype, eight had PiMZ, two had PiSZ and one had a PiZP-Lowell genotype. 2D-SWE (median 1.42 m/S, range 1.14–1.83 m/S) and TE (median 4.8 kPa, range 2.8–24.6 kPa) values displayed a significant correlation (R = 0.475, p &lt, 0.05). 2D-SWE, ATI (median 0.56 dB/cm/MHz, range 0.43–0.96 dB/cm/MHz) and CAP (median 249.5 dB/m, range 156–347 dB/m) values were higher in PiZZ when compared to other AATD genotypes. This study provides evidence that 2D-SWE is a suitable method for the assessment of liver disease in AATD. The newer methods of SWD and ATI require further evaluation in the context of AATD.

Cholangiocarcinoma (CCA) comprises a heterogeneous group of primary liver tumors. They emerge from different hepatic (progenitor) cell populations, typically via sporadic mutations. Chronic biliary inflammation, as seen in primary sclerosing cholangitis (PSC), may trigger CCA development. Although several efforts were made in the last decade to better understand the complex processes of biliary carcinogenesis, it was only recently that new therapeutic advances have been achieved. Animal models are a crucial bridge between in vitro findings on molecular or genetic alterations, pathophysiological understanding, and new therapeutic strategies for the clinic. Nevertheless, it is inherently difficult to recapitulate simultaneously the stromal microenvironment (e.g., immune-competent cells, cholestasis, inflammation, PSC-like changes, fibrosis) and the tumor biology (e.g., mutational burden, local growth, and metastatic spread) in an animal model, so that it would reflect the full clinical reality of CCA. In this review, we highlight available data on animal models for CCA. We discuss if and how these models reflect human disease and whether they can serve as a tool for understanding the pathogenesis, or for predicting a treatment response in patients. In addition, open issues for future developments will be discussed.

Background and aimsMicroRNAs (miRNAs) are profoundly involved into the pathophysiology of manifold cancers. Recent data suggested a pivotal role of miRNAs as biomarkers in different biological processes including carcinogenesis. However, their role in neuroendocrine tumors (NETs) is only poorly understood.MethodsWe determined circulating levels of miR-21 and miR-223 in 45 samples from patients with NET treated between 2010 and 2019 at our department and compared them to healthy controls. Results were correlated with clinical records.ResultsIn the total cohort of Patients with NET, miR-223 presented significantly lower levels compared to healthy control samples. In contrast, levels of miR-21 indicated no significant changes between the two groups. Interestingly, despite being significantly downregulated in all NET patients, concentrations of miR-223 were independent of clinical or histopathological factors such as proliferation activity according to Ki-67 index, tumor grading, TNM stage, somatostatin receptor expression, presence of functional/ non-functional disease or tumor relapse. Moreover, in contrast to data from recent publications analyzing other tumor entities, levels of miR-223 serum levels did not reflect prognosis of patients with NET.ConclusionLower concentrations of circulating miR-223 rather reflect the presence of NET itself than certain tumor characteristics. The value of miR-223 as a biomarker in NET might be limited to diagnostic, but not prognostic purposes.

While tumor resection and liver transplantation (LT) represent potentially curative therapeutic options for patients with early-stage hepatocellular carcinoma (HCC), the identification of the ideal surgical candidates has remained challenging. Just recently, miRNA-193a-5p was described as a tumor suppressor in murine and human HCC but only little is known about circulating miRNA-193a-5p in HCC patients. Here, we evaluated serum levels of miR-193a-5p by qPCR in 41 HCC patients undergoing tumor resection (n = 33) or LT (n = 8) and 20 controls. Circulating relative miR-193a-5p levels were significantly elevated in HCC patients compared to healthy controls. While relative miR-193a-5p levels were comparable between patients of different underlying disease etiology and tumor size, high relative miR-193a-5p levels were predictive for the patients’ postoperative outcome, which was confirmed in uni- and multivariate Cox-regression analysis. As such, HCC patients with a preoperative relative miR-193a-5p level above the ideal cut-off value (3.57) had a median overall survival (OS) of only 451 days compared to 1158 days in patients with a relative miR-193a-5p level below this cut-off value. Our data support a novel function of miR-193a-5p as a biomarker in early-stage HCC patients that might help to identify the best surgical candidates in terms of postoperative outcome.