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  • 1
    In: Diagnostics, MDPI AG, Vol. 13, No. 4 ( 2023-02-05), p. 586-
    Kurzfassung: Bite force measuring devices that are generally suitable for edentulous patients or patients undergoing mandibular reconstruction are missing. This study assesses the validity of a new bite force measuring device (prototype of loadpad®, novel GmbH) and evaluates its feasibility in patients after segmental mandibular resection. Accuracy and reproducibility were analyzed with two different protocols using a universal testing machine (Z010 AllroundLine, Zwick/Roell, Ulm, Germany). Four groups were tested to evaluate the impact of silicone layers around the sensor: no silicone (“pure”), 2.0 mm soft silicone (“2-soft”), 7.0 mm soft silicone (“7-soft”) and 2.0 mm hard silicone (“2-hard”). Thereafter, the device was tested in 10 patients prospectively who underwent mandibular reconstruction using a fibula free flap. Average relative deviations of the measured force in relation to the applied load reached 0.77% (“7-soft”) to 5.28% (“2-hard”). Repeated measurements in “2-soft” revealed a mean relative deviation of 2.5% until an applied load of 600 N. Maximum bite force decreased postoperatively by 51.8% to a maximum mean bite force of 131.5 N. The novel device guarantees a high accuracy and degree of reproducibility. Furthermore, it offers new opportunities to quantify perioperative oral function after reconstructive surgery of the mandible also in edentulous patients.
    Materialart: Online-Ressource
    ISSN: 2075-4418
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2023
    ZDB Id: 2662336-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    In: Cancers, MDPI AG, Vol. 13, No. 22 ( 2021-11-17), p. 5763-
    Kurzfassung: Introduction: Several studies suggest an estrogen receptor alpha (ERα)-mediated influence on the pathogenesis of oral squamous cell carcinoma (OSCC), as described for other malignancies that are not considered to be primarily hormone-dependent. Recently, an association between ERα expression and improved survival in oropharyngeal squamous cell carcinoma (OPSCC) has been found. However, the prognostic relevance of ERα in OSCC has not been proven to date. Therefore, the aim of this study was to evaluate ERα expression in OSCC in a large patient cohort and analyze its influence on survival and recurrence. Material and Methods: A total of 316 patients with primary OSCC who received initial surgical therapy were included in this analysis. The expression of ERα was evaluated on tissue microarrays by immunohistochemistry in the primary tumor and/or primary lymph node metastases. The expression level was quantified by light microscopy using the immunoreactive score (IRS) for estrogen receptor detection. An IRS equal to or greater than 2 was considered positive. The 5-year overall survival (OS) and relapse-free survival (RFS) were examined by the Kaplan–Meier method and log-rank test. Results: A total of 316 patients (111 females; 205 males) with a mean age of 61.3 years (range 27–96 years) were included in this study. In 16 patients (5.1%; 6 females and 10 males), positive ERα expression was found in the primary tumor (n = 11; 11/302) or lymph node metastases (n = 5; 5/52). Patients with positive ERα expression in primary tumors/primary lymph node metastases had a significantly lower OS and RFS (p = 0.012; p = 0.0053) compared to ERα-negative patients. Sub-group analysis in relation to gender revealed a highly significant influence of ERα expression on OS and RFS in males but not in females, both for the ERα-positive primary tumor cohort (males: p = 0.0013; p 〈 0.0001; females: p = 0.56; p = 0.89) and the ERα-positive primary tumor/primary lymph node metastasis cohort (males: p 〈 0.0001; p 〈 0.0001; females: p = 0.95; p = 0.96). In multivariate cox regression analysis, the ERα IRS of primary tumors (dichotomized; ERα+ vs. ERα−) was an independent risk factor for OS (HR = 4.230; 95%CI 1.616–11.076; p = 0.003) and RFS (HR = 12.390; 95%CI 4.073–37.693; p 〈 0.001) in the male cohort. There was a significant difference (p = 0.006) of ERα positivity with regard to the localization of the primary tumor. ERα positivity in the primary tumor was significantly associated (p = 0.026) with UICC stage, with most of the cases being diagnosed in stage IV. Furthermore, there was a significantly (p = 0.049) higher rate of bone infiltration in ERα-positive patients. Conclusion: Expression of ERα is rare in OSCC; however, it is associated with a dramatic decrease in OS in male patients. Further studies are necessary to confirm our results and to evaluate the exact mechanism underlying this observation. Hence, ERα-positive OSCC patients might benefit from an ER-based therapeutic (adjuvant) approach in the future.
    Materialart: Online-Ressource
    ISSN: 2072-6694
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2021
    ZDB Id: 2527080-1
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
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    MDPI AG ; 2013
    In:  Journal of Personalized Medicine Vol. 3, No. 1 ( 2013-01-17), p. 14-22
    In: Journal of Personalized Medicine, MDPI AG, Vol. 3, No. 1 ( 2013-01-17), p. 14-22
    Materialart: Online-Ressource
    ISSN: 2075-4426
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2013
    ZDB Id: 2662248-8
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
    In: Cancers, MDPI AG, Vol. 15, No. 4 ( 2023-02-08), p. 1088-
    Kurzfassung: Introduction: In lateralized oral squamous cell carcinoma (OSCC) with ipsilateral cervical lymph node metastasis (CLNM), the surgical management of the unsuspicious contralateral neck remains a matter of debate. The aim of this study was to analyze this cohort and to compare the outcomes of patients with and without contralateral elective neck dissection (END). Material and Methods: A retrospective analysis of patients with lateralized OSCC, ipsilateral CLNM (pN+) and contralateral cN0-stage was performed. Patients were divided into two groups according to the surgical management of the contralateral neck: I: END; and II: no END performed. Adjuvant radiotherapy was applied bilaterally in both groups according to individual risk. Results: A total of 65 patients (group I: 16 (24.6%); group II: 49 (75.4%)) with a median follow-up of 28 months were included. Initially, there was no case of contralateral CLNM after surgery. During follow-up, 6 (9.2%) patients presented with recurrent CLNM. In 5 of these cases (7.7%), the contralateral neck (group I: 3/16 (18.8%); group II: 2/49 (4.1%)) was affected. Increased ipsilateral lymph node ratio was associated with contralateral CLNM (p = 0.07). END of the contralateral side showed no significant benefit regarding OS (p = 0.59) and RFS (p = 0.19). Conclusions: Overall, the risk for occult contralateral CLNM in patients with lateralized OSCC ipsilateral CLNM is low. Our data suggest that END should not be performed routinely in this cohort. Risk-adapted radiotherapy of the contralateral neck alone seems to be sufficient from the oncological point of view.
    Materialart: Online-Ressource
    ISSN: 2072-6694
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2023
    ZDB Id: 2527080-1
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
    In: Cancers, MDPI AG, Vol. 13, No. 9 ( 2021-04-26), p. 2095-
    Kurzfassung: Acute myeloid leukemia (AML) is characterized by recurrent genetic events. The BCL6 corepressor (BCOR) and its homolog, the BCL6 corepressor-like 1 (BCORL1), have been reported to be rare but recurrent mutations in AML. Previously, smaller studies have reported conflicting results regarding impacts on outcomes. Here, we retrospectively analyzed a large cohort of 1529 patients with newly diagnosed and intensively treated AML. BCOR and BCORL1 mutations were found in 71 (4.6%) and 53 patients (3.5%), respectively. Frequently co-mutated genes were DNTM3A, TET2 and RUNX1. Mutated BCORL1 and loss-of-function mutations of BCOR were significantly more common in the ELN2017 intermediate-risk group. Patients harboring loss-of-function mutations of BCOR had a significantly reduced median event-free survival (HR = 1.464 (95%-Confidence Interval (CI): 1.005–2.134), p = 0.047), relapse-free survival (HR = 1.904 (95%-CI: 1.163–3.117), p = 0.01), and trend for reduced overall survival (HR = 1.495 (95%-CI: 0.990–2.258), p = 0.056) in multivariable analysis. Our study establishes a novel role for loss-of-function mutations of BCOR regarding risk stratification in AML, which may influence treatment allocation.
    Materialart: Online-Ressource
    ISSN: 2072-6694
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2021
    ZDB Id: 2527080-1
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
    In: Nutrients, MDPI AG, Vol. 9, No. 5 ( 2017-05-15), p. 499-
    Materialart: Online-Ressource
    ISSN: 2072-6643
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2017
    ZDB Id: 2518386-2
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
    In: Cells, MDPI AG, Vol. 9, No. 3 ( 2020-03-04), p. 613-
    Kurzfassung: ATP-binding cassette (ABC) transporters, such as breast cancer resistance protein (BCRP), are key players in resistance to multiple anti-cancer drugs, leading to cancer treatment failure and cancer-related death. Currently, there are no clinically approved drugs for reversal of cancer drug resistance caused by ABC transporters. This study investigated if a novel drug candidate, SCO-201, could inhibit BCRP and reverse BCRP-mediated drug resistance. We applied in vitro cell viability assays in SN-38 (7-Ethyl-10-hydroxycamptothecin)-resistant colon cancer cells and in non-cancer cells with ectopic expression of BCRP. SCO-201 reversed resistance to SN-38 (active metabolite of irinotecan) in both model systems. Dye efflux assays, bidirectional transport assays, and ATPase assays demonstrated that SCO-201 inhibits BCRP. In silico interaction analyses supported the ATPase assay data and suggest that SCO-201 competes with SN-38 for the BCRP drug-binding site. To analyze for inhibition of other transporters or cytochrome P450 (CYP) enzymes, we performed enzyme and transporter assays by in vitro drug metabolism and pharmacokinetics studies, which demonstrated that SCO-201 selectively inhibited BCRP and neither inhibited nor induced CYPs. We conclude that SCO-201 is a specific, potent, and potentially non-toxic drug candidate for the reversal of BCRP-mediated resistance in cancer cells.
    Materialart: Online-Ressource
    ISSN: 2073-4409
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2020
    ZDB Id: 2661518-6
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
    In: Cells, MDPI AG, Vol. 9, No. 9 ( 2020-08-29), p. 1989-
    Kurzfassung: The ongoing threat of viral infections and the emergence of antiviral drug resistance warrants a ceaseless search for new antiviral compounds. Broadly-inhibiting compounds that act on elements shared by many viruses are promising antiviral candidates. Here, we identify a peptide derived from the cowpox virus protein CPXV012 as a broad-spectrum antiviral peptide. We found that CPXV012 peptide hampers infection by a multitude of clinically and economically important enveloped viruses, including poxviruses, herpes simplex virus-1, hepatitis B virus, HIV-1, and Rift Valley fever virus. Infections with non-enveloped viruses such as Coxsackie B3 virus and adenovirus are not affected. The results furthermore suggest that viral particles are neutralized by direct interactions with CPXV012 peptide and that this cationic peptide may specifically bind to and disrupt membranes composed of the anionic phospholipid phosphatidylserine, an important component of many viral membranes. The combined results strongly suggest that CPXV012 peptide inhibits virus infections by direct interactions with phosphatidylserine in the viral envelope. These results reiterate the potential of cationic peptides as broadly-acting virus inhibitors.
    Materialart: Online-Ressource
    ISSN: 2073-4409
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2020
    ZDB Id: 2661518-6
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
    In: Metabolites, MDPI AG, Vol. 9, No. 10 ( 2019-09-23), p. 200-
    Kurzfassung: Metabolomics aims to measure and characterise the complex composition of metabolites in a biological system. Metabolomics studies involve sophisticated analytical techniques such as mass spectrometry and nuclear magnetic resonance spectroscopy, and generate large amounts of high-dimensional and complex experimental data. Open source processing and analysis tools are of major interest in light of innovative, open and reproducible science. The scientific community has developed a wide range of open source software, providing freely available advanced processing and analysis approaches. The programming and statistics environment R has emerged as one of the most popular environments to process and analyse Metabolomics datasets. A major benefit of such an environment is the possibility of connecting different tools into more complex workflows. Combining reusable data processing R scripts with the experimental data thus allows for open, reproducible research. This review provides an extensive overview of existing packages in R for different steps in a typical computational metabolomics workflow, including data processing, biostatistics, metabolite annotation and identification, and biochemical network and pathway analysis. Multifunctional workflows, possible user interfaces and integration into workflow management systems are also reviewed. In total, this review summarises more than two hundred metabolomics specific packages primarily available on CRAN, Bioconductor and GitHub.
    Materialart: Online-Ressource
    ISSN: 2218-1989
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2019
    ZDB Id: 2662251-8
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
    In: Cells, MDPI AG, Vol. 12, No. 1 ( 2023-01-03), p. 193-
    Kurzfassung: Critically ill COVID-19 patients suffer from thromboembolic as well as bleeding events. Endothelial dysfunction, spiking of von Willebrand factor (vWF), and excessive cytokine signaling result in coagulopathy associated with substantial activation of plasmatic clotting factors. Thrombocytopenia secondary to extensive platelet activation is a frequent finding, but abnormal platelet dysfunction may also exist in patients with normal platelet counts. In this study, we performed analyses of platelet function and of von Willebrand factor in critically ill COVID-19 patients (n = 13). Platelet aggregometry was performed using ADP, collagen, epinephrin, and ristocetin. VWF and fibrinogen binding of platelets and CD62 and CD63 expression after thrombin stimulation were analyzed via flow cytometry. In addition, VWF antigen (VWF:Ag), collagen binding capacity (VWF:CB), and multimer analysis were performed next to routine coagulation parameters. All patients exhibited reduced platelet aggregation and decreased CD62 and CD63 expression. VWF binding of platelets was reduced in 12/13 patients. VWF:CB/VWF:Ag ratios were pathologically decreased in 2/13 patients and elevated in 2/13 patients. Critically ill COVID-19 patients exhibit platelet secretion defects independent of thrombocytopenia. Platelet exhaustion and VWF dysfunction may result in impaired primary hemostasis and should be considered when treating coagulopathy in these patients.
    Materialart: Online-Ressource
    ISSN: 2073-4409
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2023
    ZDB Id: 2661518-6
    Standort Signatur Einschränkungen Verfügbarkeit
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