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  • 1
    In: Cancers, MDPI AG, Vol. 15, No. 17 ( 2023-09-04), p. 4415-
    Abstract: Purpose: In meningiomas, TERT promotor mutations are rare but qualify the diagnosis of anaplasia, directly impacting adjuvant therapy. Effective screening for patients at risk for promotor mutations could enable more targeted molecular analyses and improve diagnosis and treatment. Methods: Semiautomatic segmentation of intracranial grade 2/3 meningiomas was performed on preoperative magnetic resonance imaging. Discriminatory power to predict TERT promoter mutations was analyzed using a random forest algorithm with an increasing number of radiomic features. Two final models with five and eight features with both fixed and differing radiomics features were developed and adjusted to eliminate random effects and to avoid overfitting. Results: A total of 117 image sets including training (N = 94) and test data (N = 23) were analyzed. To eliminate random effects and demonstrate the robustness of our approach, data partitioning and subsequent model development and testing were repeated a total of 100 times (each time with repartitioned training and independent test data). The established five- and eight-feature models with both fixed and different radiomics features enabled the prediction of TERT with similar but excellent performance. The five-feature (different/fixed) model predicted TERT promotor mutation status with a mean AUC of 91.8%/94.3%, mean accuracy of 85.5%/88.9%, mean sensitivity of 88.6%/91.4%, mean specificity of 83.2%/87.0%, and a mean Cohen’s Kappa of 71.0%/77.7%. The eight-feature (different/fixed) model predicted TERT promotor mutation status with a mean AUC of 92.7%/94.6%, mean accuracy of 87.3%/88.9%, mean sensitivity of 89.6%/90.6%, mean specificity of 85.5%/87.5%, and a mean Cohen’s Kappa of 74.4%/77.6%. Of note, the addition of further features of up to N = 8 only slightly increased the performance. Conclusions: Radiomics-based machine learning enables prediction of TERT promotor mutation status in meningiomas with excellent discriminatory performance. Future analyses in larger cohorts should include grade 1 lesions as well as additional molecular alterations.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527080-1
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  • 2
    Online Resource
    Online Resource
    MDPI AG ; 2020
    In:  International Journal of Environmental Research and Public Health Vol. 17, No. 8 ( 2020-04-14), p. 2694-
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 17, No. 8 ( 2020-04-14), p. 2694-
    Abstract: In recent years, built environmental characteristics have been linked to childhood overweight, but the results remain inconsistent across studies. The present study examines associations between several built environmental features and body weight status (BMI) z-score among a large sample of preschool children in the city of Hannover, Germany. Walkability (Index), green space availability, and playground availability related to preschool children’s home environments were measured using data from OpenStreetMap (OSM). These built environment characteristics were linked to the data from the 2010–2014 school entry examinations in the Hannover city (n = 22,678), and analysed using multilevel linear regression models to examine associations between the built environment features and the BMI z-score of these children (4–8 years old). No significant associations of built environmental factors on children’s BMI were detected, but the effect between green space availability and BMI was modified by the parental educational level. In children with lower compared to higher educated parents, a higher spatial availability of greenspace was significantly associated with reduced body weight. Future research should continue to monitor the disparities in diverse built environment features and how these are related to children’s health.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2175195-X
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  • 3
    Online Resource
    Online Resource
    MDPI AG ; 2012
    In:  Nutrients Vol. 4, No. 10 ( 2012-10-16), p. 1490-1503
    In: Nutrients, MDPI AG, Vol. 4, No. 10 ( 2012-10-16), p. 1490-1503
    Type of Medium: Online Resource
    ISSN: 2072-6643
    Language: English
    Publisher: MDPI AG
    Publication Date: 2012
    detail.hit.zdb_id: 2518386-2
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  • 4
    In: Minerals, MDPI AG, Vol. 10, No. 11 ( 2020-10-29), p. 969-
    Abstract: Hydrothermal venting is an important transfer process of energy and elements between the Earth’s solid material and the oceans. Compared to mid-ocean-ridge hydrothermal vent fields, those at intra-oceanic island arcs are typically in shallower water depth and have a more variable geochemical fluid composition. Biologically essential trace elements (such as Fe and Mn) are generally elevated in fluids of both deep and shallow hydrothermal vent fields, while vents at shallower water depth influence the photic zone more directly and thus are potentially more relevant for marine primary productivity. However, fluid flux estimations of island arc hydrothermal systems into the surrounding water column are scarce. This study (I) presents a method based on short-lived radium isotopes to estimate submarine hydrothermal discharge (SHD), (II) applies this method at Brothers volcano in the southern Kermadec arc, located northeast of New Zealand, and (III) gives dissolved Fe, Mn and He isotope flux estimates for the Earth´s longest intra-oceanic island arc, the Kermadec arc. The comparison between measured inert He isotope concentrations in the plume with calculated concentrations based on Ra isotopes matched reasonably well, which supports the use of a Ra-based discharge model. Overall, this study represents a novel approach to assess fluid and thus trace element fluxes from one hydrothermal vent field, which can be applied in future studies on various hydrothermal systems to improve geochemical models of element cycling in the ocean.
    Type of Medium: Online Resource
    ISSN: 2075-163X
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2655947-X
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  • 5
    In: Pathogens, MDPI AG, Vol. 9, No. 1 ( 2019-12-30), p. 33-
    Abstract: Streptococcus (S.) suis is a major cause of economic losses in the pig industry worldwide and is an emerging zoonotic pathogen. One important virulence-associated factor is suilysin (SLY), a toxin that belongs to the family of cholesterol-dependent pore-forming cytolysins (CDC). However, the precise role of SLY in host–pathogen interactions is still unclear. Here, we investigated the susceptibility of different respiratory epithelial cells to SLY, including immortalized cell lines (HEp-2 and NPTr cells), which are frequently used in in vitro studies on S. suis virulence mechanisms, as well as primary porcine respiratory cells, which represent the first line of barrier during S. suis infections. SLY-induced cell damage was determined by measuring the release of lactate dehydrogenase after infection with a virulent S. suis serotype 2 strain, its isogenic SLY-deficient mutant strain, or treatment with the recombinant protein. HEp-2 cells were most susceptible, whereas primary epithelial cells were hardly affected by the toxin. This prompted us to study possible explanations for these differences. We first investigated the binding capacity of SLY using flow cytometry analysis. Since binding and pore-formation of CDC is dependent on the membrane composition, we also determined the cellular cholesterol content of the different cell types using TLC and HPLC. Finally, we examined the ability of those cells to reseal SLY-induced pores using flow cytometry analysis. Our results indicated that the amount of membrane-bound SLY, the cholesterol content of the cells, as well as their resealing capacity all affect the susceptibility of the different cells regarding the effects of SLY. These findings underline the differences of in vitro pathogenicity models and may further help to dissect the biological role of SLY during S. suis infections.
    Type of Medium: Online Resource
    ISSN: 2076-0817
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2695572-6
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  • 6
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 18, No. 6 ( 2021-03-18), p. 3116-
    Abstract: There is an urgent need to assess European citizens’ perspective regarding their plastic consumption and to evaluate their awareness of the direct and indirect effect of plastics on human health in order to influence current behavior trends. In this study, the evaluation has been cross-related with scientific facts, with the final aim of detecting the most recommendable paths in increasing human awareness, reducing plastic consumption, and consequently impacting human health. A statistical analysis of quantitative data, gathered from 1000 European citizens via an online survey in the period from May to June 2020, showed that a general awareness about the direct impact of plastic consumption and contamination (waste) on human health is high in Europe. However, only a few participants (from a higher educational group) were aware of the indirect negative effects that oil extraction and industrial production of plastic can have on human health. This finding calls for improved availability of this information to general public. Despite the participants’ positive attitude toward active plastic reduction (61%), plastic consumption on a daily basis is still very high (86%). The most common current actions toward plastic reduction are plastic bag usage, reusage, or replacement with sustainable alternatives (e.g., textile bags) and selecting products with less plastic packaging. The participants showed important criticism toward the information available to the general public about plastics and health. This awareness is important since significant relation has been found between the available information and the participants’ decisions on the actions they might undertake to reduce plastic consumption. The study clearly showed the willingness of the participants to take action, but they also requested to be strongly supported with joint efforts from government, policies, and marketing, defining it as the most successful way toward implementing these changes.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2175195-X
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  • 7
    In: Cancers, MDPI AG, Vol. 15, No. 13 ( 2023-07-04), p. 3491-
    Abstract: WT1 is a true chameleon, both acting as an oncogene and tumor suppressor. As its exact role in leukemogenesis is still ambiguous, research with model systems representing natural conditions surrounding the genetic alterations in WT1 is necessary. In a cohort of 59 leukemia/lymphoma cell lines, we showed aberrant expression for WT1 mRNA, which does not always translate into protein levels. We also analyzed the expression pattern of the four major WT1 protein isoforms in the cell lines and primary AML blasts with/without WT1 mutations and demonstrated that the presence of mutations does not influence these patterns. By introduction of key intronic and exonic sequences of WT1 into a lentiviral expression vector, we developed a unique tool that can stably overexpress the four WT1 isoforms at their naturally occurring tissue-dependent ratio. To develop better cellular model systems for WT1, we sequenced large parts of its gene locus and also other important myeloid risk factor genes and revealed previously unknown alterations. Functionally, inhibition of the nonsense-mediated mRNA decay machinery revealed that under natural conditions, the mutated WT1 alleles go through a robust degradation. These results offer new insights and model systems regarding the characteristics of WT1 in leukemia and lymphoma.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527080-1
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  • 8
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 20, No. 13 ( 2023-07-03), p. 6286-
    Abstract: Bullying often results in negative coping in victims, including an increased consumption of alcohol. Recently, however, an increase in alcohol use has also been reported among perpetrators of bullying. The factors triggering this pattern are still unclear. We investigated the role of empathy in the interaction between bullying and alcohol use in an adolescent sample (IMAGEN) at age 13.97 (±0.53) years (baseline (BL), N = 2165, 50.9% female) and age 16.51 (±0.61) years (follow-up 1 (FU1), N = 1185, 54.9% female). General empathic distress served as a significant moderator of alcohol use in perpetrators (F9, 493 = 17.978, p 〈 0.01), which was specific for males and FU1. Male perpetrators, who are generally less sensitive to distress, might thus be more vulnerable to alcohol abuse.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2175195-X
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  • 9
    In: Sensors, MDPI AG, Vol. 21, No. 17 ( 2021-08-30), p. 5833-
    Abstract: Healthy adults and neurological patients show unique mobility patterns over the course of their lifespan and disease. Quantifying these mobility patterns could support diagnosing, tracking disease progression and measuring response to treatment. This quantification can be done with wearable technology, such as inertial measurement units (IMUs). Before IMUs can be used to quantify mobility, algorithms need to be developed and validated with age and disease-specific datasets. This study proposes a protocol for a dataset that can be used to develop and validate IMU-based mobility algorithms for healthy adults (18–60 years), healthy older adults ( 〉 60 years), and patients with Parkinson’s disease, multiple sclerosis, a symptomatic stroke and chronic low back pain. All participants will be measured simultaneously with IMUs and a 3D optical motion capture system while performing standardized mobility tasks and non-standardized activities of daily living. Specific clinical scales and questionnaires will be collected. This study aims at building the largest dataset for the development and validation of IMU-based mobility algorithms for healthy adults and neurological patients. It is anticipated to provide this dataset for further research use and collaboration, with the ultimate goal to bring IMU-based mobility algorithms as quickly as possible into clinical trials and clinical routine.
    Type of Medium: Online Resource
    ISSN: 1424-8220
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2052857-7
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