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  • 1
    Online Resource
    Online Resource
    Targeted Plasma Metabolic Profiles and Risk of Recurrence in Stage II and III Colorectal Cancer Patients: Results from an International Cohort Consortium
    MDPI AG ; 2021
    In:  Metabolites Vol. 11, No. 3 ( 2021-02-24), p. 129-
    Details
    In: Metabolites, MDPI AG, Vol. 11, No. 3 ( 2021-02-24), p. 129-
    Abstract: The identification of patients at high-risk for colorectal cancer (CRC) recurrence remains an unmet clinical need. The aim of this study was to investigate associations of metabolites with risk of recurrence in stage II/III CRC patients. A targeted metabolomics assay (128 metabolites measured) was performed on pre-surgery collected EDTA plasma samples from n = 440 newly diagnosed stage II/III CRC patients. Patients have been recruited from four prospective cohort studies as part of an international consortium: Metabolomic profiles throughout the continuum of CRC (MetaboCCC). Cox proportional hazard models were computed to investigate associations of metabolites with recurrence, adjusted for age, sex, tumor stage, tumor site, body mass index, and cohort; false discovery rate (FDR) was used to account for multiple testing. Sixty-nine patients (15%) had a recurrence after a median follow-up time of 20 months. We identified 13 metabolites that were nominally associated with a reduced risk of recurrence. None of the associations were statistically significant after controlling for multiple testing. Pathway topology analyses did not reveal statistically significant associations between recurrence and alterations in metabolic pathways (e.g., sphingolipid metabolism p = 0.04; pFDR = 1.00). To conclude, we did not observe statistically significant associations between metabolites and CRC recurrence using a well-established metabolomics assay. The observed results require follow-up in larger studies.
    Type of Medium: Online Resource
    ISSN: 2218-1989
    URL: Article
    DOI: 10.3390/metabo11030129
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662251-8
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  • 2
    Online Resource
    Online Resource
    The Austrian Semantic EO Data Cube Infrastructure
    MDPI AG ; 2021
    In:  Remote Sensing Vol. 13, No. 23 ( 2021-11-26), p. 4807-
    Details
    In: Remote Sensing, MDPI AG, Vol. 13, No. 23 ( 2021-11-26), p. 4807-
    Abstract: Big optical Earth observation (EO) data analytics usually start from numerical, sub-symbolic reflectance values that lack inherent semantic information (meaning) and require interpretation. However, interpretation is an ill-posed problem that is difficult for many users to solve. Our semantic EO data cube architecture aims to implement computer vision in EO data cubes as an explainable artificial intelligence approach. Automatic semantic enrichment provides semi-symbolic spectral categories for all observations as an initial interpretation of color information. Users graphically create knowledge-based semantic models in a convergence-of-evidence approach, where color information is modelled a-priori as one property of semantic concepts, such as land cover entities. This differs from other approaches that do not use a-priori knowledge and assume a direct 1:1 relationship between reflectance values and land cover. The semantic models are explainable, transferable, reusable, and users can share them in a knowledgebase. We provide insights into our web-based architecture, called Sen2Cube.at, including semantic enrichment, data models, knowledge engineering, semantic querying, and the graphical user interface. Our implemented prototype uses all Sentinel-2 MSI images covering Austria; however, the approach is transferable to other geographical regions and sensors. We demonstrate that explainable, knowledge-based big EO data analysis is possible via graphical semantic querying in EO data cubes.
    Type of Medium: Online Resource
    ISSN: 2072-4292
    URL: Article
    DOI: 10.3390/rs13234807
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2513863-7
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  • 3
    Online Resource
    Online Resource
    The Essential Role of IL-17 as the Pathogenetic Link between Psoriasis and Metabolic-Associated Fatty Liver Disease
    MDPI AG ; 2023
    In:  Life Vol. 13, No. 2 ( 2023-02-02), p. 419-
    Details
    In: Life, MDPI AG, Vol. 13, No. 2 ( 2023-02-02), p. 419-
    Abstract: Interleukin 17 (IL-17) is an effector cytokine that plays a key role in the pathogenesis of both psoriasis and metabolic-associated fatty liver disease (MAFLD), a condition that is more prevalent and severe in patients with psoriasis. In liver inflammation, IL-17 is mainly produced by CD4+ T (TH17) and CD8+ T cells (Tc17), although numerous other cells (macrophages, natural killer cells, neutrophils and Tγδ cells) also contribute to the production of IL-17. In hepatocytes, IL-17 mediates systemic inflammation and the recruitment of inflammatory cells to the liver, and it is also implicated in the development of fibrosis and insulin resistance. IL-17 levels have been correlated with progression from MAFLD to steatohepatitis, cirrhosis, and even hepatocellular carcinoma. Clinical trials have shown that inhibiting IL-17A in patients with psoriasis could potentially contribute to the improvement of metabolic and liver parameters. A better understanding of the key factors involved in the pathogenesis of these chronic inflammatory processes could potentially lead to more efficient treatment for both psoriasis and MAFLD, and help to develop holistic strategies to improve the management of these patients.
    Type of Medium: Online Resource
    ISSN: 2075-1729
    URL: Article
    DOI: 10.3390/life13020419
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662250-6
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  • 4
    Online Resource
    Online Resource
    Adjuvant Docetaxel in Node-Negative Breast Cancer Patients: A Randomized Trial of AGO-Breast Study Group, German Breast Group, and EORTC-Pathobiology Group
    MDPI AG ; 2023
    In:  Cancers Vol. 15, No. 5 ( 2023-03-03), p. 1580-
    Details
    In: Cancers, MDPI AG, Vol. 15, No. 5 ( 2023-03-03), p. 1580-
    Abstract: Background: In node-negative breast cancer (NNBC), a high risk of recurrence is determined by clinico-pathological or tumor-biological assessment. Taxanes may improve adjuvant chemotherapy. Methods: NNBC 3-Europe, the first randomized phase-3 trial in node-negative breast cancer (BC) with tumor-biological risk assessment, recruited 4146 node-negative breast cancer patients from 2002 to 2009 in 153 centers. Risk assessment was performed by clinico-pathological factors (43%) or biomarkers (uPA/PAI-1, urokinase-type plasminogen activator/its inhibitor PAI-1). High-risk patients received six courses 5-fluorouracil (500 mg/m2), epirubicin (100 mg/m2), cyclophosphamide (500 mg/m2) (FEC), or three courses FEC followed by three courses docetaxel 100 mg/m2 (FEC-Doc). Primary endpoint was disease-free survival (DFS). Results: In the intent-to-treat population, 1286 patients had received FEC-Doc, and 1255 received FEC. Median follow-up was 45 months. Tumor characteristics were equally distributed; 90.6% of tested tumors had high uPA/PAI-1-concentrations. Planned courses were given in 84.4% (FEC-Doc) and 91.5% (FEC). Five-year-DFS was 93.2% (95% C.I. 91.1–94.8) with FEC-Doc and 93.7% (91.7–95.3) with FEC. Five-year-overall survival was 97.0% (95.4–98.0) for FEC-Doc and 96.6% % (94.9–97.8) for FEC. Conclusions: With adequate adjuvant chemotherapy, even high-risk node-negative breast cancer patients have an excellent prognosis. Docetaxel did not further reduce the rate of early recurrences and led to significantly more treatment discontinuations.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers15051580
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527080-1
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  • 5
    Online Resource
    Online Resource
    Seasonal Variations in the Diagnosis of Testicular Germ Cell Tumors: A National Cancer Registry Study in Austria
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 21 ( 2021-10-27), p. 5377-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 21 ( 2021-10-27), p. 5377-
    Abstract: We conducted a retrospective National Cancer Registry study in Austria to assess a possible seasonal variation in the clinical diagnosis of testicular germ cell tumors (TGCT). In total, 3615 testicular cancer diagnoses were identified during an 11-year period from 2008 to 2018. Rate ratios for the monthly number of TGCT diagnoses, as well as of seasons and half-years, were assessed using a quasi-Poisson model. We identified, for the first time, a statistically significant seasonal trend (p 〈 0.001) in the frequency of monthly newly diagnosed cases of TGCT. In detail, clear seasonal variations with a reduction in the tumor incidence during the summer months (Apr–Sep) and an increase during the winter months (Oct–Mar) were observed (p 〈 0.001). Focusing on seasonality, the incidence during the months of Oct–Dec (p = 0.008) and Jan–Mar (p 〈 0.001) was significantly higher compared to the months of Jul–Sep, respectively. Regarding histopathological features, there is a predominating incidence in the winter months compared to summer months, mainly concerning pure seminomas (p 〈 0.001), but not the non-seminoma or mixed TGCT groups. In conclusion, the incidence of TGCT diagnoses in Austria has a strong seasonal pattern, with the highest rate during the winter months. These findings may be explained by a delay of self-referral during the summer months. However, the hypothetical influence of vitamin D3 in testicular carcinogenesis underlying seasonal changes in TGCT diagnosis should be the focus of further research.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13215377
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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  • 6
    Online Resource
    Online Resource
    Exploring Castellaniella defragrans Linalool (De)hydratase-Isomerase for Enzymatic Hydration of Alkenes
    MDPI AG ; 2019
    In:  Molecules Vol. 24, No. 11 ( 2019-06-01), p. 2092-
    Details
    In: Molecules, MDPI AG, Vol. 24, No. 11 ( 2019-06-01), p. 2092-
    Abstract: Acyclic monoterpenes constitute a large and highly abundant class of secondary plant metabolites and are, therefore, attractive low-cost raw materials for the chemical industry. To date, numerous biocatalysts for their transformation are known, giving access to highly sought-after monoterpenoids. In view of the high selectivity associated with many of these reactions, the demand for enzymes generating commercially important target molecules is unabated. Here, linalool (de)hydratase-isomerase (Ldi, EC 4.2.1.127) from Castellaniella defragrans was examined for the regio- and stereoselective hydration of the acyclic monoterpene β-myrcene to (S)-(+)-linalool. Expression of the native enzyme in Escherichia coli allowed for identification of bottlenecks limiting enzyme activity, which were investigated by mutating selected residues implied in enzyme assembly and function. Combining these analyses with the recently published 3D structures of Ldi highlighted the precisely coordinated reduction–oxidation state of two cysteine pairs in correct oligomeric assembly and the catalytic mechanism, respectively. Subcellular targeting studies upon fusion of Ldi to different signal sequences revealed the significance of periplasmic localization of the mature enzyme in the heterologous expression host. This study provides biochemical and mechanistic insight into the hydration of β-myrcene, a nonfunctionalized terpene, and emphasizes its potential for access to scarcely available but commercially interesting tertiary alcohols.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules24112092
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2008644-1
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  • 7
    Online Resource
    Online Resource
    Perceived Serviceability of Outplacement Programs as a Part of Sustainable Human Resource Management
    MDPI AG ; 2019
    In:  Sustainability Vol. 11, No. 17 ( 2019-08-30), p. 4748-
    Details
    In: Sustainability, MDPI AG, Vol. 11, No. 17 ( 2019-08-30), p. 4748-
    Abstract: Work and employment are important elements of every working person’s life. If an employee loses his or her job, he or she loses an important and determining part of his or her life. To reduce the negative effects that affect the quality of an employee’s life, outplacement programs were established as a part of sustainable human resource management. Sustainable human resource management emphasises the importance of employee care. Outplacement, for its part, includes support for employees at their last stage in the organization. The main aims of the paper are to present the research results focused on the perceived usefulness of outplacement programs for dismissed employees, to analyse the relationships between the emotions felt by redundancies and other employees as well as the comparison of differences in emotions felt by different generations of dismissed employees. A valid collection tool (research questionnaire) was developed for research purposes and distributed to employees of industrial enterprises in the Slovak Republic. Overall, the research set was composed of n = 692 employees from different generational groups. The research results proved the existence of a relationships between the emotions felt by redundancies and other employees and differences in emotions felt by employees from different generational groups.
    Type of Medium: Online Resource
    ISSN: 2071-1050
    URL: Article
    DOI: 10.3390/su11174748
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2518383-7
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  • 8
    Online Resource
    Online Resource
    Novel Polyomaviruses in Mammals from Multiple Orders and Reassessment of Polyomavirus Evolution and Taxonomy
    MDPI AG ; 2019
    In:  Viruses Vol. 11, No. 10 ( 2019-10-10), p. 930-
    Details
    In: Viruses, MDPI AG, Vol. 11, No. 10 ( 2019-10-10), p. 930-
    Abstract: As the phylogenetic organization of mammalian polyomaviruses is complex and currently incompletely resolved, we aimed at a deeper insight into their evolution by identifying polyomaviruses in host orders and families that have either rarely or not been studied. Sixteen unknown and two known polyomaviruses were identified in animals that belong to 5 orders, 16 genera, and 16 species. From 11 novel polyomaviruses, full genomes could be determined. Splice sites were predicted for large and small T antigen (LTAg, STAg) coding sequences (CDS) and examined experimentally in transfected cell culture. In addition, splice sites of seven published polyomaviruses were analyzed. Based on these data, LTAg and STAg annotations were corrected for 10/86 and 74/86 published polyomaviruses, respectively. For 25 polyomaviruses, a spliced middle T CDS was observed or predicted. Splice sites that likely indicate expression of additional, alternative T antigens, were experimentally detected for six polyomaviruses. In contrast to all other mammalian polyomaviruses, three closely related cetartiodactyl polyomaviruses display two introns within their LTAg CDS. In addition, the VP2 of Glis glis (edible dormouse) polyomavirus 1 was observed to be encoded by a spliced transcript, a unique experimental finding within the Polyomaviridae family. Co-phylogenetic analyses based on LTAg CDS revealed a measurable signal of codivergence when considering all mammalian polyomaviruses, most likely driven by relatively recent codivergence events. Lineage duplication was the only other process whose influence on polyomavirus evolution was unambiguous. Finally, our analyses suggest that an update of the taxonomy of the family is required, including the creation of novel genera of mammalian and non-mammalian polyomaviruses.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    URL: Article
    DOI: 10.3390/v11100930
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2516098-9
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  • 9
    Online Resource
    Online Resource
    Semantic Earth Observation Data Cubes
    MDPI AG ; 2019
    In:  Data Vol. 4, No. 3 ( 2019-07-17), p. 102-
    Details
    In: Data, MDPI AG, Vol. 4, No. 3 ( 2019-07-17), p. 102-
    Abstract: There is an increasing amount of free and open Earth observation (EO) data, yet more information is not necessarily being generated from them at the same rate despite high information potential. The main challenge in the big EO analysis domain is producing information from EO data, because numerical, sensory data have no semantic meaning; they lack semantics. We are introducing the concept of a semantic EO data cube as an advancement of state-of-the-art EO data cubes. We define a semantic EO data cube as a spatio-temporal data cube containing EO data, where for each observation at least one nominal (i.e., categorical) interpretation is available and can be queried in the same instance. Here we clarify and share our definition of semantic EO data cubes, demonstrating how they enable different possibilities for data retrieval, semantic queries based on EO data content and semantically enabled analysis. Semantic EO data cubes are the foundation for EO data expert systems, where new information can be inferred automatically in a machine-based way using semantic queries that humans understand. We argue that semantic EO data cubes are better positioned to handle current and upcoming big EO data challenges than non-semantic EO data cubes, while facilitating an ever-diversifying user-base to produce their own information and harness the immense potential of big EO data.
    Type of Medium: Online Resource
    ISSN: 2306-5729
    URL: Article
    DOI: 10.3390/data4030102
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2856531-9
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