Since recent studies revealed the feasibility to detect blood-based microRNAs (miRNAs, miRs) in breast cancer (BC) patients a new field has been opened for circulating miRNAs as potential biomarkers ...in BC. In this pilot study, we evaluated to our knowledge for the first time whether distinct pattern of urinary miRNAs might be also applicable as innovative biomarkers for BC detection.
Urinary miRNA expression levels of nine BC-related miRNAs (miR-21, miR-34a, miR-125b, miR-155, miR-195, miR-200b, miR-200c, miR-375, miR-451) from 24 untreated, primary BC patients and 24 healthy controls were quantified by realtime-PCR. The receiver operating characteristic analyses (ROC) and logistic regression were calculated to assess discriminatory accuracy.
Significant differences were found in the expression of four BC-associated miRNAs quantified as median miRNA expression levels. Urinary miR-155 levels were significantly higher in BC patients compared to healthy controls (1.49vs.0.25; p < 0.001). In contrast, compared to healthy controls, BC patients exhibited significantly lower urinary expression levels of miR-21 (2.27vs.5.07; p < 0.001), miR-125b (0.71vs.1.62; p < 0.001), and miR-451 (0.02vs.0.59 p = 0.004), respectively. The ROC including all miRNAs as well as the group of the four significant deregulated miRNAs separated BC patients from healthy controls with a very high (area under the receiver operating characteristic curve AUC = 0.932) and high accuracy (AUC = 0.887), respectively.
We were able to demonstrate for the first time the feasibility to detect distinct BC-dependent urinary miRNA profiles. The expression levels of four urinary miRNAs were specifically altered in our cohort of BC patients compared to healthy controls. This distinct pattern offers the possibility for a specific discrimination between healthy women and primary BC patients. This sustains the potential role of urinary miRNAs as non-invasive innovative urine-based biomarkers for BC detection.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Markus Jaeger explores the coalescence of Joan Baez's work as a singer and songwriter with her endeavors as a political activist throughout the last sixty years. He illustrates an American popular ...singer's significance as a political activist—for her audiences and for her opponents as well as for those victims of politically organized violence who have profited from her work. Mingling popular culture with political activism can be a helpful means to achieve non-violent societal progress: Joan Baez’s work offers an excellent example for this hypothesis. Revised and updated edition, with an additional chapter on Joan Baez’s artistic and political endeavours in the 2010s.
Due to the nonlinear material behavior and contradicting application requirements, the selection of a specific electrical steel grade for a highly efficient electrical machine during its design stage ...is challenging. With sufficient knowledge of the correlations between material and magnetic properties and capable material models, a material design for specific requirements can be enabled. In this work, the correlations between magnetization behavior, iron loss and the most relevant material parameters for non-oriented electrical steels, i.e., alloying, sheet thickness and grain size, are studied on laboratory-produced iron-based electrical steels of 2.4 and 3.2 wt % silicon. Different final thicknesses and grain sizes for both alloys are obtained by different production parameters to produce a total of 21 final material states, which are characterized by state-of-the-art material characterization methods. The magnetic properties are measured on a single sheet tester, quantified up to 5 kHz and used to parametrize the semi-physical IEM loss model. From the loss parameters, a tailor-made material, marked by its thickness and grain size is deduced. The influence of different steel grades and the chance of tailor-made material design is discussed in the context of an exemplary e-mobility application by performing finite-element electrical machine simulations and post-processing on four of the twenty-one materials and the tailor-made material. It is shown that thicker materials can lead to fewer iron losses if the alloying and grain size are adapted and that the three studied parameters are in fact levers for material design where resources can be saved by a targeted optimization.
Cancer-testis antigens (CTA) comprise a family of proteins, which are physiologically expressed in adult human tissues solely in testicular germ cells and occasionally placenta. However, CTA ...expression has been reported in various malignancies. CTAs have been identified by their ability to elicit autologous cellular and or serological immune responses, and are considered potential targets for cancer immunotherapy. The breast differentiation antigen NY-BR-1, expressed specifically in normal and malignant breast tissue, has also immunogenic properties. Here we evaluated the expression patterns of CTAs and NY-BR-1 in breast cancer in correlation to clinico-pathological parameters in order to determine their possible impact as prognostic factors.
The reactivity pattern of various mAbs (6C1, MA454, M3H67, 57B, E978, GAGE #26 and NY-BR-1 #5) were assessed by immunohistochemistry in a tissue micro array series of 210 randomly selected primary invasive breast cancers in order to study the diversity of different CTAs (e.g. MAGE-A, NY-ESO-1, GAGE) and NY-BR-1. These expression data were correlated to clinico-pathological parameters and outcome data including disease-free and overall survival.
Expression of at least one CTA was detectable in the cytoplasm of tumor cells in 37.2% of the cases. NY-BR-1 expression was found in 46.6% of tumors, respectively. Overall, CTA expression seemed to be linked to adverse prognosis and M3H67 immunoreactivity specifically was significantly correlated to shorter overall and disease-free survival (p=0.000 and 0.024, respectively).
Our findings suggest that M3H67 immunoreactivity could serve as potential prognostic marker in primary breast cancer patients. The exclusive expression of CTAs in tumor tissues as well as the frequent expression of NY-BR-1 could define new targets for specific breast cancer therapies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Production deviations have a remarkable effect on the radiated sound of electrical machines, introducing additional signal components besides the fundamental field waves which significantly change ...and enrich the subjectively perceived sound characteristic. In literature these harmonics are mainly traced back to dynamic eccentricity, which modulates the fundamental fieldwaves. In this paper a thorough mechanic and electromagnetic analysis of a modern, well-constructed traction drive (permanent magnet synchronous machine) is performed to showthat for this typical rotor configuration dynamic eccentricity is negligible. Instead, deviations in the rotor magnetization are shown to be the dominant cause for vibration harmonics.
Breast cancer (BC) represents the most common type of cancer in females worldwide. Endocrine therapy evolved as one of the main concepts in treatment of hormone-receptor positive BC. Current research ...focuses on the elucidation of tumour resistance mechanisms against endocrine therapy. In a translational in vitro approach, potential regulatory effects of clinically implemented BC anti-oestrogens on ERα, its coactivators DDX5, DDX17 and other DEADbox proteins as well as on the proliferation markers cyclin D1 and Ki67 were investigated on both the RNA and protein level. BC in vitro models for hormone-receptor positive (MCF-7, T-47D) and hormone-receptor negative cells (BT-20) were subjected to endocrine therapy. Anti-oestrogen-dependent expression regulation of target genes on the transcriptional and translational level was quantified and statistically assessed. Endocrine therapy decreases the expression levels of Ki67, cyclin D1 and ERα in hormone-receptor positive cells. In the hormone-receptor negative cells, the three parameters remained stable after endocrine therapy. Endoxifen triggers a downregulation of DDX5 and DDX23 in MCF-7 cells. Fulvestrant treatment downregulates the expression levels of all investigated DEADbox proteins in MCF-7 cells. In T-47D cells, endoxifen and fulvestrant lead to a decrease of all target gene expression levels. Interestingly, endocrine therapy affects DEADbox RNA expression levels in BT-20 cells, too. However, this result could only be confirmed for DDX1, immunocytologically. The investigated DEADbox proteins appear to correlate with the oestrogen-dependent tumourigenesis in hormone-receptor positive BC and show expression alterations after endocrine treatment.
We provide an empirical survey of the current practice on involuntary psychiatric hospital admission.
Bases on clinical case records, we performed a retrospective analysis of 346 cases with an ...involuntary hospital admission according to public law in 2020 (21.0% of all inpatient admissions in this period).
Announcement of suicide was the most frequent cause for involuntary hospital admission (45.1%). Most common diagnoses were substance-related disorders (30.1%), stress-related disorders (19.9%), and schizophrenic psychoses (18.8%). Only 12.7% of the involuntary admissions resulted in a further involuntary hospitalization, whereas 44.5% of all episodes were followed by a discharge within 24 hours.
In many cases, involuntary hospital admissions are reactions to suicidal crises. It will be interesting to see, if the introduction of alternative low-threshold services can help to reduce the frequency of such admissions.
Historically, the Wernicke-Kleist-Leonhard School represents a countermovement to psychopathology as described by Karl Jaspers and Kurt Schneider. The School aimed to interlink psychopathological and ...neurobiological aspects. Starting from the model of different functional neuronal systems, each of which can be disturbed in the sense of a hypofunction, hyperfunction, or parafunction, it developed a comprehensive phenomenology of psychopathological symptoms and syndromes that finally culminated in Karl Leonhard's course descriptions. This school of thought can provide important impulses even today. Thus, on the one hand, the neurobiological models can serve as the basis for additional research projects and on the other hand, the psychopathological descriptions of disorders can perhaps also be interpreted in the sense of typological constructs that can contribute to pragmatic clinical decisionmaking.
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