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  • 1
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    Online Resource
    Prevalence of Pruritus and Association with Anxiety and Depression in Patients with Nonalcoholic Fatty Liver Disease
    MDPI AG ; 2022
    In:  Biomedicines Vol. 10, No. 2 ( 2022-02-15), p. 451-
    Details
    In: Biomedicines, MDPI AG, Vol. 10, No. 2 ( 2022-02-15), p. 451-
    Abstract: Patient-reported outcomes are important in nonalcoholic fatty liver disease (NAFLD). Pruritus is of special interest for evolving therapies with farnesoid X receptor (FXR) agonists. The aim of this study was to investigate the prevalence of pruritus in a real-life NAFLD cohort and analyze associations with anxiety and depression. Pruritus was assessed using a visual analogue- (VAS) and 5-D itch-scale (5-D). Anxiety and depression were evaluated by Beck’s-Depression-Inventory (BDI) and the Hospital Anxiety and Depression Scale (HADS-A, HADS-D). An optimal logistic regression model was found with a stepwise procedure to investigate variables associated with pruritus. In total, 123 NAFLD patients were recruited. VAS and 5-D were highly correlated (Spearman’s correlation coefficient 0.89). Moderate/severe pruritus was reported in 19% (VAS) and 21% (5-D) of patients. Anxiety and depression were present in 12% and 4% (HADS-A and HADS-D, respectively) and 12% (BDI) of cases. There was a significant association between VAS and BDI (p = 0.019). The final multivariate model for 5-D included diabetes mellitus (OR 4.51; p = 0.01), BDI (OR 5.98; p = 0.024), and HADS-A (OR 7.75; p = 0.011). One-fifth of NAFLD patients reported moderate or severe pruritus. 5-D was significantly associated with diabetes mellitus, depression, and anxiety. These findings should be tested in larger populations and considered in candidates for treatment with FXR agonists.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    URL: Article
    DOI: 10.3390/biomedicines10020451
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2720867-9
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  • 2
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    Disseminating Metaproteomic Informatics Capabilities and Knowledge Using the Galaxy-P Framework
    MDPI AG ; 2018
    In:  Proteomes Vol. 6, No. 1 ( 2018-01-31), p. 7-
    Details
    In: Proteomes, MDPI AG, Vol. 6, No. 1 ( 2018-01-31), p. 7-
    Type of Medium: Online Resource
    ISSN: 2227-7382
    URL: Article
    DOI: 10.3390/proteomes6010007
    Language: English
    Publisher: MDPI AG
    Publication Date: 2018
    detail.hit.zdb_id: 2720995-7
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  • 3
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    Flux States of Active Galactic Nuclei
    MDPI AG ; 2019
    In:  Galaxies Vol. 7, No. 2 ( 2019-05-21), p. 57-
    Details
    In: Galaxies, MDPI AG, Vol. 7, No. 2 ( 2019-05-21), p. 57-
    Abstract: Blazars are known to show variability on time scales from minutes to years covering a wide range of flux states. Studying the flux distribution of a source allows for various insights. The shape of the flux distribution can provide information on the nature of the underlying variability processes. The level of a possible quiescent state can be derived from the main part of the distribution that can be described by a Gaussian distribution. Dividing the flux states into quiescent and active, the duty cycle of a source can be calculated. Finally, this allows alerting the multi-wavelength and multi-messenger community in case a source is in an active state. To get consistent and conclusive results from flux distributions, unbiased long-term observations are crucial. Only like this is a complete picture of the variability and flux states, e.g., an all-time quiescent state, possible. In seven years of monitoring of bright TeV blazars, the first G-APD Cherenkov telescope (FACT) has collected a total of more than 11,700 hours of physics data with 1500 hours to 3000 hours per source for Mrk 421, Mrk 501, 1ES 1959+650, and 1ES 2344+51.
    Type of Medium: Online Resource
    ISSN: 2075-4434
    URL: Article
    DOI: 10.3390/galaxies7020057
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2691049-4
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  • 4
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    New Electro-Thermal Battery Pack Model of an Electric Vehicle
    MDPI AG ; 2016
    In:  Energies Vol. 9, No. 7 ( 2016-07-20), p. 563-
    Details
    In: Energies, MDPI AG, Vol. 9, No. 7 ( 2016-07-20), p. 563-
    Type of Medium: Online Resource
    ISSN: 1996-1073
    URL: Article
    DOI: 10.3390/en9070563
    Language: English
    Publisher: MDPI AG
    Publication Date: 2016
    detail.hit.zdb_id: 2437446-5
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  • 5
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    Implementing an Extended Kalman Filter for SoC Estimation of a Li-Ion Battery with Hysteresis: A Step-by-Step Guide
    MDPI AG ; 2021
    In:  Energies Vol. 14, No. 13 ( 2021-06-22), p. 3733-
    Details
    In: Energies, MDPI AG, Vol. 14, No. 13 ( 2021-06-22), p. 3733-
    Abstract: The growing share of renewable energies in power production and the rise of the market share of battery electric vehicles increase the demand for battery technologies. In both fields, a predictable operation requires knowledge of the internal battery state, especially its state of charge (SoC). Since a direct measurement of the SoC is not possible, Kalman filter-based estimation methods are widely used. In this work, a step-by-step guide for the implementation and tuning of an extended Kalman filter (EKF) is presented. The structured approach of this paper reduces efforts compared with empirical filter tuning and can be adapted to various battery models, systems, and cell types. This work can act as a tutorial describing all steps to get a working SoC estimator based on an extended Kalman filter.
    Type of Medium: Online Resource
    ISSN: 1996-1073
    URL: Article
    DOI: 10.3390/en14133733
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
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  • 6
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    CCR2 of Tumor Microenvironmental Cells Is a Relevant Modulator of Glioma Biology
    MDPI AG ; 2020
    In:  Cancers Vol. 12, No. 7 ( 2020-07-13), p. 1882-
    Details
    In: Cancers, MDPI AG, Vol. 12, No. 7 ( 2020-07-13), p. 1882-
    Abstract: Glioblastoma multiforme (GBM) shows a high influx of tumor-associated macrophages (TAMs). The CCR2/CCL2 pathway is considered a relevant signal for the recruitment of TAMs and has been suggested as a therapeutic target in malignant gliomas. We found that TAMs of human GBM specimens and of a syngeneic glioma model express CCR2 to varying extents. Using a Ccr2-deficient strain for glioma inoculation revealed a 30% reduction of TAMs intratumorally. This diminished immune cell infiltration occurred with augmented tumor volumes likely based on increased cell proliferation. Remaining TAMs in Ccr2-/- mice showed comparable surface marker expression patterns in comparison to wildtype mice, but expression levels of inflammatory transcription factors (Stat3, Irf7, Cox2) and cytokines (Ifnβ, Il1β, Il12α) were considerably affected. Furthermore, we demonstrated an impact on blood vessel integrity, while vascularization of tumors appeared similar between mouse strains. The higher stability and attenuated leakiness of the tumor vasculature imply improved sustenance of glioma tissue in Ccr2-/- mice. Additionally, despite TAMs residing in the perivascular niche in Ccr2-/- mice, their pro-angiogenic activity was reduced by the downregulation of Vegf. In conclusion, lacking CCR2 solely on tumor microenvironmental cells leads to enhanced tumor progression, whereby high numbers of TAMs infiltrate gliomas independently of the CCR2/CCL2 signal.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers12071882
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527080-1
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  • 7
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    CUX1—Transcriptional Master Regulator of Tumor Progression in Pancreatic Neuroendocrine Tumors
    MDPI AG ; 2020
    In:  Cancers Vol. 12, No. 7 ( 2020-07-19), p. 1957-
    Details
    In: Cancers, MDPI AG, Vol. 12, No. 7 ( 2020-07-19), p. 1957-
    Abstract: Recently, we identified the homeodomain transcription factor Cut homeobox 1 (CUX1) as mediator of tumour de-differentiation and metastatic behaviour in human insulinoma patients. In insulinomas, CUX1 enhanced tumour progression by stimulating proliferation and angiogenesis in vitro and in vivo. In patients with non-functional pancreatic neuroendocrine tumours (PanNET), however, the impact of CUX1 remains to be elucidated. Here, we analysed CUX1 expression in two large independent cohorts (n = 43 and n = 141 tissues) of non-functional treatment-naïve and pre-treated PanNET patients, as well as in the RIP1Tag2 mouse model of pancreatic neuroendocrine tumours. To further assess the functional role of CUX1, expression profiling of DNA damage-, proliferation- and apoptosis-associated genes was performed in CUX1-overexpressing Bon-1 cells. Validation of differentially regulated genes was performed in Bon-1 and QGP1 cells with knock-down and overexpression strategies. CUX1 expression assessed by a predefined immunoreactivity score (IRS) was significantly associated with shorter progression-free survival (PFS) of pre-treated PanNET patients (23 vs. 8 months; p = 0.005). In treatment-naïve patients, CUX1 was negatively correlated with grading and recurrence-free survival (mRFS of 39 versus 8 months; p = 0.022). In both groups, high CUX1 levels indicated a metastatic phenotype. Functionally, CUX1 upregulated expression of caspases and death associated protein kinase 1 (DAPK1), known as mediators of tumour progression and resistance to cytotoxic drugs. This was also confirmed in both cell lines and human tissues. In the RIP1Tag2 mouse model, CUX1 expression was associated with advanced tumour stage and resistance to apoptosis. In summary, we identified the transcription factor CUX1 as mediator of tumour progression in non-functional PanNET in vitro and in vivo, indicating that the CUX1-dependent signalling network is a promising target for future therapeutic intervention.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers12071957
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527080-1
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  • 8
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    Long-Term Clinical Outcome and Prognostic Factors of Children and Adolescents with Localized Rhabdomyosarcoma Treated on the CWS-2002P Protocol
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 4 ( 2022-02-11), p. 899-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 4 ( 2022-02-11), p. 899-
    Abstract: We report here the results of the prospective, non-randomized, historically controlled CWS-2002P study in patients ≤ 21 years with localized RMS developed with the aim to improve the long-term outcome by adapting the burden of therapy to risk profile and to investigate the feasibility and relation to the outcome of maintenance therapy (MT) in the high-risk groups. Patients were allocated into low-risk (LR), standard-risk (SR), high-risk (HR), and very high-risk (VHR) groups. Chemotherapy consisted of vincristine (VCR) and dactinomycin (ACTO-D) for all patients with the addition of ifosfamide (IFO) in the SR, HR, and VHR and doxorubicin (DOX) in the HR and VHR groups. Low-dose cyclophosphamide and vinblastine maintenance therapy (MT) over 6 months was recommended in the HR and VHR groups. A total of 444 patients have been included in this analysis. With a median follow-up of 9·6 years (IQR 7·6–10·9) for patients alive, the 5-year EFS and OS for the whole group was 73% (95% CI 69–77) and 80% (95% CI 76–84), respectively. The 5-year EFS by risk group was 100% in the LR, 79% (95% CI 72–84) in the SR, 69% (95% CI 63–75) in the HR, and 42% (95% CI 23–61) in the VHR (log-rank p = 0.000). The 5-year EFS was 77% (95% CI 70–84) for 155 patients in the HR group who received MT as compared to 63% (95% CI 50–76) for 49 patients who did not (log-rank p = 0.015). Neither the reduction in the IFO dose in the SR nor the increased dose intensity of DOX in HR groups influenced the outcome when compared to the previous CWS and other European studies. MT was feasible, seemed to have an impact on prognosis, and should be studied in a well-controlled prospective trial in this patient population. The weighting of risk factors used for therapy stratification needs to be reevaluated.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14040899
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
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  • 9
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    Cerebrospinal Fluid Findings of 36 Adult Patients with Autism Spectrum Disorder
    MDPI AG ; 2020
    In:  Brain Sciences Vol. 10, No. 6 ( 2020-06-08), p. 355-
    Details
    In: Brain Sciences, MDPI AG, Vol. 10, No. 6 ( 2020-06-08), p. 355-
    Abstract: Autism spectrum disorder (ASD) is a common neurodevelopmental disorder characterized by difficulties with social interaction, repetitive behavior, and additional features, such as special interests. Its precise etiology is unclear. Recently, immunological mechanisms, such as maternal autoantibodies/infections, have increasingly been the subject of discussion. Cerebrospinal fluid (CSF) investigations play a decisive role in the detection of immunological processes in the brain. This study therefore retrospectively analyzed the CSF findings of adult patients with ASD. CSF basic measures (white blood cell count, total protein, albumin quotient, immunoglobulin G (IgG) index, and oligoclonal bands) and various antineuronal antibody findings of 36 adult patients with ASD, who had received lumbar puncture, were compared with an earlier described mentally healthy control group of 39 patients with idiopathic intracranial hypertension. CSF protein concentrations and albumin quotients of patients with ASD were significantly higher as compared to controls (age corrected: p = 0.003 and p = 0.004, respectively); 17% of the patients with ASD showed increased albumin quotients. After correction for age and gender, the group effect for total protein remained significant (p = 0.041) and showed a tendency for albumin quotient (p = 0.079). In the CSF of two ASD patients, an intrathecal synthesis of anti-glutamate decarboxylase 65 (GAD65) antibodies was found. In total, more of the ASD patients (44%) presented abnormal findings in CSF basic diagnostics compared to controls (18%; p = 0.013). A subgroup of the patients with adult ASD showed indication of a blood–brain barrier dysfunction, and two patients displayed an intrathecal synthesis of anti-GAD65 antibodies; thus, the role of these antibodies in patients with ASD should be further investigated. The results of the study are limited by its retrospective and open design. The group differences in blood–brain barrier markers could be influenced by a different gender distribution between ASD patients and controls.
    Type of Medium: Online Resource
    ISSN: 2076-3425
    URL: Article
    DOI: 10.3390/brainsci10060355
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2651993-8
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  • 10
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    Managing Size of Public Schools and School Boards: A Multi-Level Cost Approach Applied to Dutch Primary Education
    MDPI AG ; 2019
    In:  Sustainability Vol. 11, No. 23 ( 2019-11-25), p. 6662-
    Details
    In: Sustainability, MDPI AG, Vol. 11, No. 23 ( 2019-11-25), p. 6662-
    Abstract: In many countries, the provision of primary education is among the core responsibilities of local governments. One of the main questions local governments face concerns the optimal configuration of school boards and size of schools. In this paper we analyse the relation between cost and scale in school boards and in schools. The influence of both the governing layer (board) and the operational layer (school) on average cost are jointly modelled. Board cost is modelled as an aggregation of individual school cost functions so that individual school cost data are not required in order to estimate the model. The results indicate that small schools ( 〈 60) pupils are operating under sizable economies of scale. The optimum school size is estimated at roughly 450 pupils, but average cost remains roughly constant with regard to size. In contrast to school size, the effect of board size (in terms of the number of schools governed) on average cost is limited. The policy recommendation is that municipalities should create at least three schoolboards within their jurisdiction and take measures in case individual school size declines below 60 pupils.
    Type of Medium: Online Resource
    ISSN: 2071-1050
    URL: Article
    DOI: 10.3390/su11236662
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2518383-7
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