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We aimed to evaluate the factors associated with hemorrhage (HA) of melanoma brain metastases (MBM) after Cyberknife stereotactic radiosurgery (SRS) in the modern era of systemic therapy. A total of 55 patients with 279 MBM were treated in 93 fractions. The median age, SRS dose, radiological follow-up, and time to HA were 60.4 years, 20 Gy, 17.7 months, and 10.7 months, respectively. Radiologically evident HA was documented in 47 (16.8%) metastases. Of the 55 patients, 25 (45.4%) suffered an HA. Among those, HA caused grade 3 toxicity in 10 patients (40%) and grade 1 symptoms in 5 patients (20%). Ten patients (40%) with HA experienced no toxicity. Logistic regression revealed the use of anticoagulants and the administration of systemic therapy within 7/15 days from SRS to be predictive for HA. When considering the HA causing grade 3 symptomatology, only the use of anticoagulants was significant, with the delivery of whole brain radiation therapy (WBRT) before the HA narrowly missing statistical significance. Our retrospective analysis showed that the administration of modern systemic therapy within 7/15 days from SRS may contribute to HA of MBM, though it appears safe, at least concerning grade 3 toxicity. The use of anticoagulants by the time of SRS significantly increased the risk of HA.
Cutaneous T cell lymphomas (CTCLs) represent a heterogeneous group of T cell lymphomas that primarily affect the skin. The most frequent forms of CTCL are mycosis fungoides and Sézary syndrome. Both are characterized by frequent recurrence, developing chronic conditions and high mortality with a lack of a curative treatment. In this study, we evaluated the effect of short-chain, cell-permeable C6 Ceramide (C6Cer) on CTCL cell lines and keratinocytes. C6Cer significantly reduced cell viability of CTCL cell lines and induced cell death via apoptosis and necrosis. In contrast, primary human keratinocytes and HaCaT keratinocytes were less affected by C6Cer. Both keratinocyte cell lines showed higher expressions of ceramide catabolizing enzymes and HaCaT keratinocytes were able to metabolize C6Cer faster and more efficiently than CTCL cell lines, which might explain the observed protective effects. Along with other existing skin-directed therapies, C6Cer could be a novel well-tolerated drug for the topical treatment of CTCL.
hallmark of ageing is the redistribution of body fat. Particularly, subcutaneous fat decreases paralleled by a decrease of skin collagen I are typical for age-related skin atrophy. In this paper, we hypothesize that collagen I may be a relevant molecule stimulating the differentiation of adipose-derived stem cells (ASCs) into adipocytes augmenting subcutaneous fat. In this context lipogenesis, adiponectin, and collagen I receptor expression were determined. Freshly isolated ASCs were characterized by stemness-associated surface markers by FACS analysis and then transdifferentiated into adipocytes by specific medium supplements. Lipogenesis was evaluated using Nile Red staining and documented by fluorescence microscopy or quantitatively measured by using a multiwell spectrofluorometer. Expression of adiponectin was measured by real-time RT-PCR and in cell-free supernatants by ELISA, and expression of collagen I receptors was observed by western blot analysis. It was found that supports coated with collagen I promote cell adhesion and lipogenesis of ASCs. Interestingly, a reverse correlation to adiponectin expression was observed. Moreover, we found upregulation of the collagen receptor, discoidin domain-containing receptor 2; receptors of the integrin family were absent or downregulated. These findings indicate that collagen I is able to modulate lipogenesis and adiponectin expression and therefore may contribute to metabolic dysfunctions associated with ageing.
The presented work inside this thesis aims to raise the degree of automation in analog circuit design. Therefore, a framework was developed to provide the necessary mechanisms in order to carry out a fully automated analog circuit synthesis, i.e., the construction of an analog circuit fulfilling all previously defined (electrical) specifications. Nowadays, analog circuit design in general is a very time consuming process compared to a digital design flow. Due to its discrete nature, the digital design process is highly automated and thus very efficient compared to analog circuit design. In modern Very-Large-Scale integration (VLSI) circuits the analog parts are mostly just a small portion of the overall chip area. Although this small portion is known to consume a major part of the needed workforce. Paired with product cycles which constantly get shorter, the time needed to develop the analog parts of an integrated circuit (IC) becomes a determinant factor. Apart from this, the ongoing progress in semiconductor processing technologies promises more speed with less power consumption on smaller areas, forcing the IC developers to keep track with the technology nodes in order to maintain competitiveness. Analog circuitry exhibits the inherent property of being hard to reuse, as porting from one technology node to another imposes critical changes for operating conditions (e.g., supply voltage) - mostly leading to a full redesign for most of the analog modules. This productivity gap between digital and analog design resembles the primary motivation for this thesis. Due to the availability of commercial sizing tools, this work deliberately focuses on the construction of circuit topologies in distinction to parameter synthesis, which can be obtained with a dedicated sizing tool. The focus on circuit construction allows the development of a framework which allows a full design space exploration. This thesis describes the needed concepts and methods to realize a deterministic, explorative analog synthesis framework. Despite this, a reference implementation is presented, which demonstrates the applicability in current analog design flows.
Background: SARS-CoV-2 has massively changed the care situation in hospitals worldwide. Although tumour care should not be affected, initial reports from European countries were suggestive for a decrease in skin cancer during the first pandemic wave and only limited data are available thereafter.
Objectives: The aim of this study was to investigate skin cancer cases and surgeries in a nationwide inpatient dataset in Germany.
Methods: Comparative analyses were performed in a prepandemic (18 March 2019 until 17 March 2020) and a pandemic cohort (18 March 2020 until 17 March 2021). Cases were identified and analysed using the WHO international classification of diseases codes (ICDs) and process key codes (OPSs).
Results: Comparing the first year of the pandemic with the same period 1 year before, a persistent decrease of 14% in skin cancer cases (n = 19 063) was observed. The largest decrease of 24% was seen in non-invasive in situ tumours (n = 1665), followed by non-melanoma skin cancer (NMSC) with a decrease of 16% (n = 15 310) and malignant melanoma (MM) with a reduction of 7% (n = 2088). Subgroup analysis showed significant differences in the distribution of sex, age, hospital carrier type and hospital volume. There was a decrease of 17% in surgical procedures (n = 22 548), which was more pronounced in minor surgical procedures with a decrease of 24.6% compared to extended skin surgery including micrographic surgery with a decrease of 15.9%.
Conclusions: Hospital admissions and surgical procedures decreased persistently since the beginning of the pandemic in Germany for skin cancer patients. The higher decrease in NMSC cases compared to MM might reflect a prioritization effect. Further evidence from tumour registries is needed to investigate the consequences of the therapy delay and identify the upcoming challenges in skin cancer care.
The results from the STAR Collaboration on directed flow (v1), elliptic flow (v2), and the fourth harmonic (v4) in the anisotropic azimuthal distribution of particles from Au+Au collisions at sqrt[sNN]=200GeV are summarized and compared with results from other experiments and theoretical models. Results for identified particles are presented and fit with a blast-wave model. Different anisotropic flow analysis methods are compared and nonflow effects are extracted from the data. For v2, scaling with the number of constituent quarks and parton coalescence are discussed. For v4, scaling with v22 and quark coalescence are discussed.
Evaluation of 2‑methoxyestradiol serum levels as a potential prognostic marker in malignant melanoma
(2021)
Experimental findings indicated that 2‑methoxyestradiol (2‑ME), an endogenous metabolite of 17β‑estradiol, may exhibit anti‑tumorigenic properties in various types of tumour, such as melanoma and endometrial carcinoma. In patients with endometrial cancer, the serum levels of 2‑ME are decreased compared with those in healthy controls, and this finding has been associated with a poor outcome. The aim of the present study was to examine whether the serum levels of 2‑ME are decreased in patients with melanoma, and whether this decrease may be correlated with disease stage and, therefore, serve as a prognostic indicator. ELISA was used to detect serum levels of 2‑ME in patients with stage I‑IV malignant melanoma (MM). A cohort of 78 patients with MM was analysed, along with 25 healthy controls, among whom 15 were women in the second trimester of pregnancy (positive control). As expected, significantly elevated levels of serum 2‑ME were observed in pregnant control patients compared with those in patients with MM and healthy controls. There was no observed correlation between 2‑ME serum levels in patients with MM and disease stage, tumour thickness, lactate dehydrogenase or S100 calcium‑binding protein B levels. In addition, the 2‑ME levels of patients with MM did not differ significantly from those of normal healthy controls. Overall, the findings of the present study indicated that the 2‑ME serum levels in patients with MM were not decreased, and there was no correlation with early‑ or advanced‑stage disease. Therefore, in contrast to published results on endometrial cancer, endogenous serum 2‑ME levels in MM were not found to be correlated with tumour stage and did not appear to be a suitable prognostic factor in MM.