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  • 1
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    Online Resource
    Prognostic Value of Perineural Invasion on Survival and Recurrence in Oral Squamous Cell Carcinoma
    MDPI AG ; 2022
    In:  Diagnostics Vol. 12, No. 5 ( 2022-04-24), p. 1062-
    Details
    In: Diagnostics, MDPI AG, Vol. 12, No. 5 ( 2022-04-24), p. 1062-
    Abstract: A diagnosis of perineural invasion (PNI) is widely accepted as an unfavorable prognostic factor in various solid malignancies. Although PNI has been described as a high-risk parameter in oral squamous cell carcinoma (OSCC), its role in the current staging manuals of the American Joint Committee on Cancer (AJCC) is rather subordinate. We analysed the prognostic value of PNI on survival and recurrence in a large, multicenter OSCC cohort and a population-based approach. A total of 493 OSCC patients with primary tumor resection to negative margins and concomitant neck dissection between 2010 and 2017 were enrolled. PNI was evaluated in relation to overall survival (OAS) and recurrence-free survival (RFS) using uni- and multi-variable Cox regression. The median follow-up time was 5.0 years and PNI was diagnosed in 48 patients (9.7%). A pathohistological verification of PNI correlated significantly with a deteriorated OAS in uni- (HR 2.312; 95% CI 2.312–3.493, p = 0.001) and multivariable Cox regression (HR 1.820; 95% CI 1.164–2.847, p = 0.009). Additionally, a diagnosis of PNI correlated with increased cumulative, as well as distant, metastasis 5-year-recurrence rates (p = 0.027 and p = 0.011, respectively). The application of adjuvant radiotherapy (RT) or radiochemotherapy (RCT) in patients with PNI did not alter OAS or RFS in survival analysis when compared to patients without PNI. The results underline the adverse impact of PNI on the survival and recurrence of surgically treated OSCC patients. Based on our findings, we highly recommend an emphasis on PNI in the TNM staging concept.
    Type of Medium: Online Resource
    ISSN: 2075-4418
    URL: Article
    DOI: 10.3390/diagnostics12051062
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662336-5
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  • 2
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    Spatio-Temporal Distribution of Deep Convection Observed along the Trans-Mexican Volcanic Belt
    MDPI AG ; 2021
    In:  Remote Sensing Vol. 13, No. 6 ( 2021-03-23), p. 1215-
    Details
    In: Remote Sensing, MDPI AG, Vol. 13, No. 6 ( 2021-03-23), p. 1215-
    Abstract: Complex terrain features—in particular, environmental conditions, high population density and potential socio-economic damage—make the Trans-Mexican Volcanic Belt (TMVB) of particular interest regarding the study of deep convection and related severe weather. In this research, 10 years of Moderate-Resolution Imaging Spectroradiometer (MODIS) cloud observations are combined with Climate Hazards Group Infrared Precipitation with Station (CHIRPS) rainfall data to characterize the spatio-temporal distribution of deep convective clouds (DCCs) and their relationship to extreme precipitation. From monthly distributions, wet and dry phases are identified for cloud fraction, deep convective cloud frequency and convective precipitation. For both DCC and extreme precipitation events, the highest frequencies align just over the higher elevations of the TMVB. A clear relationship between DCCs and terrain features, indicating the important role of orography in the development of convective systems, is noticed. For three sub-regions, the observed distributions of deep convective cloud and extreme precipitation events are assessed in more detail. Each sub-region exhibits different local conditions, including terrain features, and are known to be influenced differently by emerging moisture fluxes from the Gulf of Mexico and the Pacific Ocean. The observed distinct spatio-temporal variabilities provide the first insights into the physical processes that control the convective development in the study area. A signal of the midsummer drought in Mexico (i.e., “canícula”) is recognized using MODIS monthly mean cloud observations.
    Type of Medium: Online Resource
    ISSN: 2072-4292
    URL: Article
    DOI: 10.3390/rs13061215
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2513863-7
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  • 3
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    Estimation of Aerosol Layer Height from OLCI Measurements in the O2A-Absorption Band over Oceans
    MDPI AG ; 2023
    In:  Remote Sensing Vol. 15, No. 16 ( 2023-08-18), p. 4080-
    Details
    In: Remote Sensing, MDPI AG, Vol. 15, No. 16 ( 2023-08-18), p. 4080-
    Abstract: The aerosol layer height (ALH) is an important parameter that characterizes aerosol interaction with the environment. An estimation of the vertical distribution of aerosol is necessary for studies of those interactions, their effect on radiance and for aerosol transport models. ALH can be retrieved from satellite-based radiance measurements within the oxygen absorption band between 760 and 770 nm (O2A band). The oxygen absorption is reduced when light is scattered by an elevated aerosol layer. The Ocean and Land Colour Imager (OLCI) has three bands within the oxygen absorption band. We show a congruent sensitivity study with respect to ALH for dust and smoke cases over oceans. Furthermore, we developed a retrieval of the ALH for those cases and an uncertainty estimation by applying linear uncertainty propagation and a bootstrap method. The sensitivity study and the uncertainty estimation are based on radiative transfer simulations. The impact of ALH, aerosol optical thickness (AOT), the surface roughness (wind speed) and the central wavelength on the top of atmosphere (TOA) radiance is discussed. The OLCI bands are sufficiently sensitive to ALH for cases with AOTs larger than 0.5 under the assumption of a known aerosol type. With an accurate spectral characterization of the OLCI O2A bands better than 0.1 nm, ALH can be retrieved with an uncertainty of a few hundred meters. The retrieval of ALH was applied successfully on an OLCI dust and smoke scene. The found ALH is similar to parallel measurements by the Tropospheric Monitoring Instrument (TROPOMI). OLCI’s high spatial resolution and coverage allow a detailed overview of the vertical aerosol distribution over oceans.
    Type of Medium: Online Resource
    ISSN: 2072-4292
    URL: Article
    DOI: 10.3390/rs15164080
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2513863-7
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  • 4
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    Marginal Adaptation and Microbial Leakage at Conometric Prosthetic Connections for Implant-Supported Single Crowns: An In Vitro Investigation
    MDPI AG ; 2021
    In:  International Journal of Molecular Sciences Vol. 22, No. 2 ( 2021-01-17), p. 881-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 2 ( 2021-01-17), p. 881-
    Abstract: Encouraging clinical results were reported on a novel cone-in-cone coupling for the fixation of dental implant-supported crowns (Acuris, Dentsply Sirona Implants, Mölndal, Sweden). However, the presence or absence of a microgap and a potential bacterial leakage at the conometric joint has not yet been investigated. A misfit and a resulting gap between the conometric components could potentially serve as a bacterial reservoir that promotes plaque formation, which in turn may lead to inflammation of the peri-implant tissues. Thus, a two-fold study set-up was designed in order to evaluate the bidirectional translocation of bacteria along conometrically seated single crowns. On conometric abutments filled with a culture suspension of anaerobic bacteria, the corresponding titanium nitride-coated (TiN) caps were fixed by friction. Each system was sterilized and immersed in culture medium to provide an optimal environment for microbial growth. Positive and negative controls were prepared. Specimens were stored in an anaerobic workstation, and total and viable bacterial counts were determined. Every 48 h, samples were taken from the reaction tubes to inoculate blood agar plates and to isolate bacterial DNA for quantification using qrt-PCR. In addition, one Acuris test system was subjected to scanning electron microscopy (SEM) to evaluate the precision of fit of the conometric coupling and marginal crown opening. Throughout the observational period of one week, blood agar plates of the specimens showed no viable bacterial growth. qrt-PCR, likewise, yielded a result approaching zero with an amount of about 0.53 × 10−4 µg/mL DNA. While the luting gap/marginal opening between the TiN-cap and the ceramic crown was within the clinically acceptable range, the SEM analysis failed to identify a measurable microgap at the cone-in-cone junction. Within the limits of the in-vitro study it can be concluded that the Acuris conometric interface does not allow for bacterial translocation under non-dynamic loading conditions.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms22020881
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 5
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    Unexpected Pro-Fibrotic Effect of MIF in Non-Alcoholic Steatohepatitis Is Linked to a Shift in NKT Cell Populations
    MDPI AG ; 2021
    In:  Cells Vol. 10, No. 2 ( 2021-01-28), p. 252-
    Details
    In: Cells, MDPI AG, Vol. 10, No. 2 ( 2021-01-28), p. 252-
    Abstract: Macrophage migration inhibitory factor (MIF) is a pleiotropic inflammatory cytokine with anti-fibrotic properties in toxic liver injury models and anti-steatotic functions in non-alcoholic fatty liver disease (NAFLD) attributed to the CD74/AMPK signaling pathway. As NAFLD progression is associated with fibrosis, we studied MIF function during NAFLD-associated liver fibrogenesis in mice and men by molecular, histological and immunological methods in vitro and in vivo. After NASH diet feeding, hepatic Mif expression was strongly induced, an effect which was absent in Mif∆hep mice. In contrast to hepatotoxic fibrosis models, NASH diet-induced fibrogenesis was significantly abrogated in Mif−/− and Mif∆hep mice associated with a reduced accumulation of the pro-fibrotic type-I NKT cell subpopulation. In vitro, MIF skewed the differentiation of NKT cells towards the type-I subtype. In line with the murine results, expression of fibrosis markers strongly correlated with MIF, its receptors, and markers of NKT type-I cells in NASH patients. We conclude that MIF expression is induced during chronic metabolic injury in mice and men with hepatocytes representing the major source. In NAFLD progression, MIF contributes to liver fibrogenesis skewing NKT cell polarization toward a pro-fibrotic phenotype highlighting the complex, context-dependent role of MIF during chronic liver injury.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells10020252
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2661518-6
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  • 6
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    Immunogenetic Predisposition to SARS-CoV-2 Infection
    MDPI AG ; 2022
    In:  Biology Vol. 12, No. 1 ( 2022-12-25), p. 37-
    Details
    In: Biology, MDPI AG, Vol. 12, No. 1 ( 2022-12-25), p. 37-
    Abstract: Herein, we included 527 individuals from two Hospitals, Chemnitz and University-Hospital Leipzig. In total, 199 were negative for PCR and 328 were positive upon first admission. We used next generation sequencing for HLA-A, B, C, DRB1, DRB345, DQA1, DQB1, DPA1, and DPB1, and in some cases, HLA-E, F, G, and H. Furthermore, we molecularly defined 22 blood group systems comprising 26 genes and 5 platelet antigen genes. We observed a significant enrichment of homozygosity for DQA/DQB in the positive group. Within the negative subjects, HLA-B*57:01, HLA-B*55:01, DRB1*13:01, and DRB1*01:01 were enriched, and in the positive group, homozygosity for DQA/DQB, DRB1*09:01, and DRB1*15:01 was observed. DQA1*01:01, DQA1*02:01, and DQA1*01:03 were enriched in the negative group. HLA-DQB1*06:02 was enriched in the positive group, and HLA-DQB1*05:01 and HLA-DQB1*06:03 were enriched in the negative group. For the blood group systems MNS, RH, LE, FY, JK, YT, DO, and KN, enrichment was seen in both groups, depending on the antigen under observation. Homozygosity for D-positive RHD alleles, as well as the phenotypes M-N+ of the MNS blood group system and Yk(a-) of the KN system, were enriched in the positive group. All of these significances disappeared upon correction. Subjects who carried homozygous HPA-1a were more frequent in the negative group, contrasting with the finding that HPA-1ab was enriched in the positive group.
    Type of Medium: Online Resource
    ISSN: 2079-7737
    URL: Article
    DOI: 10.3390/biology12010037
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2661517-4
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  • 7
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    Statin Use Ameliorates Survival in Oral Squamous Cell Carcinoma—Data from a Population-Based Cohort Study Applying Propensity Score Matching
    MDPI AG ; 2023
    In:  Biomedicines Vol. 11, No. 2 ( 2023-01-27), p. 369-
    Details
    In: Biomedicines, MDPI AG, Vol. 11, No. 2 ( 2023-01-27), p. 369-
    Abstract: The anti-cancer properties of statins have attracted much attention recently, but little is known about the prognostic role of statins in oral squamous cell carcinoma (OSCC). In a retrospective approach, we analyzed a population-based cohort of 602 OSCC patients with primary curative tumor resection to negative margins and concomitant neck dissection between 2005–2017. Long-term medication with statins was correlated with overall survival (OAS) as well as recurrence-free survival (RFS) using uni- and multivariable Cox regression. Additionally, propensity score matching was applied to adjust for confounders. Statin use was present in 96 patients (15.9%) at a median age of 65.7 years. Statin treatment correlated with ameliorated survival in multivariable Cox regression in the complete cohort (OAS: HR 0.664; 95% CI 0.467–0.945, p = 0.023; RFS: HR 0.662; 95% CI 0.476–0.920, p = 0.014) as well as matched-pair cohort of OSCC patients (OAS: HR 0.691; 95% CI 0.479–0.997, p = 0.048; RFS: HR 0.694; 95% CI 0.493–0.976, p = 0.036) when compared to patients not taking statins at time of diagnosis. These findings were even more pronounced by sub-group analysis in the matched-pair cohort (age 〈 70 years). These data indicate that statin use might ameliorate the oncological outcome in primarily resected OSCC patients, but prospective clinical trials are highly recommended.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    URL: Article
    DOI: 10.3390/biomedicines11020369
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2720867-9
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  • 8
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    Marfan Syndrome Caused by Disruption of the FBN1 Gene due to A Reciprocal Chromosome Translocation
    MDPI AG ; 2021
    In:  Genes Vol. 12, No. 11 ( 2021-11-21), p. 1836-
    Details
    In: Genes, MDPI AG, Vol. 12, No. 11 ( 2021-11-21), p. 1836-
    Abstract: Marfan syndrome (MFS) is a hereditary connective tissue disease caused by heterozygous mutations in the fibrillin-1 gene (FBN1) located on chromosome 15q21.1. A complex chromosomal rearrangement leading to MFS has only been reported in one case so far. We report on a mother and daughter with marfanoid habitus and no pathogenic variant in the FBN1 gene after next generation sequencing (NGS) analysis, both showing a cytogenetically reciprocal balanced translocation between chromosomes 2 and 15. By means of fluorescence in situ hybridization of Bacterial artificial chromosome (BAC) clones from the breakpoint area on chromosome 15 the breakpoint was narrowed down to a region of approximately 110 kb in FBN1. With the help of optical genome mapping (OGM), the translocation breakpoints were further refined on chromosomes 2 and 15. Sequencing of the regions affected by the translocation identified the breakpoint of chromosome 2 as well as the breakpoint of chromosome 15 in the FBN1 gene leading to its disruption. To our knowledge, this is the first report of patients with typical clinical features of MFS showing a cytogenetically reciprocal translocation involving the FBN1 gene. Our case highlights the importance of structural genome variants as an underlying cause of monogenic diseases and the useful clinical application of OGM in the elucidation of structural variants.
    Type of Medium: Online Resource
    ISSN: 2073-4425
    URL: Article
    DOI: 10.3390/genes12111836
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527218-4
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  • 9
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    Screening of Klebsiella pneumoniae Isolates for Carbapenemase and Hypervirulence-Associated Genes by Combining the Eazyplex® Superbug CRE and hvKp Assays
    MDPI AG ; 2023
    In:  Antibiotics Vol. 12, No. 6 ( 2023-05-25), p. 959-
    Details
    In: Antibiotics, MDPI AG, Vol. 12, No. 6 ( 2023-05-25), p. 959-
    Abstract: The acquisition of hypervirulence-associated genes by carbapenemase-producing Klebsiella pneumoniae is being increasingly observed, and easy-to-use diagnostic tests are needed for the surveillance of the hypervirulent K. pneumoniae (hvKp). In this pilot study, 87 K. pneumoniae isolates from invasive infections collected in 2022 and 2023 were analysed using the LAMP-based eazyplex® Superbug CRE and hvKp assays for the simultaneous identification of carbapenemases and virulence genes (rmpA/A2, iuC, iroC, ybt, clb). Nine isolates showed a Kleborate virulence score of 4 or 5 (10.3%). The time for the results of the eazyplex® assays ranged from 6.5 to 13 min, and the total turnaround time, including sample preparation, was less than 30 min. Five isolates, three of which produced New Delhi metallo-beta lactamase (NDM), were subjected to whole-genome sequencing (WGS) analysis for further characterisation. The eazyplex® test results for beta-lactamase and virulence genes were confirmed. The eazyplex® hvKp, currently only available as a Research Use Only assay, may be a useful tool for the rapid identification of hvKp without significant additional workload when combined with the eazyplex® Superbug CRE assay for the detection of carbapenemases.
    Type of Medium: Online Resource
    ISSN: 2079-6382
    URL: Article
    DOI: 10.3390/antibiotics12060959
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2681345-2
    SSG: 15,3
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  • 10
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    Familial Multiple Coagulation Factor Deficiencies (FMCFDs) in a Large Cohort of Patients—A Single-Center Experience in Genetic Diagnosis
    MDPI AG ; 2021
    In:  Journal of Clinical Medicine Vol. 10, No. 2 ( 2021-01-18), p. 347-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 10, No. 2 ( 2021-01-18), p. 347-
    Abstract: Background: Familial multiple coagulation factor deficiencies (FMCFDs) are a group of inherited hemostatic disorders with the simultaneous reduction of plasma activity of at least two coagulation factors. As consequence, the type and severity of symptoms and the management of bleeding/thrombotic episodes vary among patients. The aim of this study was to identify the underlying genetic defect in patients with FMCFDs. Methods: Activity levels were collected from the largest cohort of laboratory-diagnosed FMCFD patients described so far. Genetic analysis was performed using next-generation sequencing. Results: In total, 52 FMCFDs resulted from coincidental co-inheritance of single-factor deficiencies. All coagulation factors (except factor XII (FXII)) were involved in different combinations. Factor VII (FVII) deficiency showed the highest prevalence. The second group summarized 21 patients with FMCFDs due to a single-gene defect resulting in combined FV/FVIII deficiency or vitamin K–dependent coagulation factor deficiency. In the third group, nine patients with a combined deficiency of FVII and FX caused by the partial deletion of chromosome 13 were identified. The majority of patients exhibited bleeding symptoms while thrombotic events were uncommon. Conclusions: FMCFDs are heritable abnormalities of hemostasis with a very low population frequency rendering them orphan diseases. A combination of comprehensive screening of residual activities and molecular genetic analysis could avoid under- and misdiagnosis.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm10020347
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662592-1
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