GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    Instrumental Activities of Daily Living Tools in Very-Low Vision: Ready for Use in Trials?
    MDPI AG ; 2022
    In:  Pharmaceutics Vol. 14, No. 11 ( 2022-11-10), p. 2435-
    Details
    In: Pharmaceutics, MDPI AG, Vol. 14, No. 11 ( 2022-11-10), p. 2435-
    Abstract: Traditional endpoints assessing visual function are limited by their responsiveness to interventions restoring or maintaining vision. An alternative concept is assessing instrumental activities of daily living (IADL). Herein, we review all available vision-specific IADL instruments relevant for vision restoration trials and report data for the most promising instrument. Six relevant instruments exist: The Low Vision Functional Status Evaluation (LVFSE), Timed IADL (TIADL), Melbourne Low-Vision Activities of Daily Living Index (MLVAI), Assessment of Disability Related to Vision (ADREV), Functional Low-Vision Observer Rated Assessment (FLORA), and Very Low Vision IADL (IADL-VLV). Both internal consistency and test-retest data were available for the LVFSE, MLVAI, and IADL-VLV. In a sample from a low-vision clinic (n = 51; age 57 ± 16 years), we report additional validation data on the IVI-VLV including test–retest reliability (intraclass correlation coefficient 0.981 [0.961; 0.991]). The LVSFE was noticeably less reliable than the MLVAI and the IADL-VLV. Content and construct validity data were available for the LVFSE, TIADL, MLVAI, ADREV, and IADL-VLV, but only the MLVAI and IADL-VLV were developed for an ultra-low vision context. Ceiling effects were present across instruments. Thus, of all appropriate IADL instruments related to vision, the IADL-VLV and MLVAI best meet existing requirements for use in vision restoration trials, e.g., in gene therapies or visual prostheses in inherited retinal diseases, but require further validation.
    Type of Medium: Online Resource
    ISSN: 1999-4923
    URL: Article
    DOI: 10.3390/pharmaceutics14112435
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527217-2
    SSG: 15,3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    PPAR-Responsive Elements Enriched with Alu Repeats May Contribute to Distinctive PPARγ–DNMT1 Interactions in the Genome
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 16 ( 2021-08-07), p. 3993-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 16 ( 2021-08-07), p. 3993-
    Abstract: Background: PPARγ (peroxisome proliferator-activated receptor gamma) is involved in the pathology of numerous diseases, including UM and other types of cancer. Emerging evidence suggests that an interaction between PPARγ and DNMTs (DNA methyltransferase) plays a role in cancer that is yet to be defined. Methods: The configuration of the repeating elements was performed with CAP3 and MAFFT, and the structural modelling was conducted with HDOCK. An evolutionary action scores algorithm was used to identify oncogenic variants. A systematic bioinformatic appraisal of PPARγ and DNMT1 was performed across 29 tumor types and UM available in The Cancer Genome Atlas (TCGA). Results: PPAR-responsive elements (PPREs) enriched with Alu repeats are associated with different genomic regions, particularly the promotor region of DNMT1. PPARγ–DNMT1 co-expression is significantly associated with several cancers. C-terminals of PPARγ and DNMT1 appear to be the potential protein–protein interaction sites where disease-specific mutations may directly impair the respective protein functions. Furthermore, PPARγ expression could be identified as an additional prognostic marker for UM. Conclusions: We hypothesize that the function of PPARγ requires an additional contribution of Alu repeats which may directly influence the DNMT1 network. Regarding UM, PPARγ appears to be an additional discriminatory prognostic marker, in particular in disomy 3 tumors.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13163993
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Prediction of Function in ABCA4-Related Retinopathy Using Ensemble Machine Learning
    MDPI AG ; 2020
    In:  Journal of Clinical Medicine Vol. 9, No. 8 ( 2020-07-29), p. 2428-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 9, No. 8 ( 2020-07-29), p. 2428-
    Abstract: Full-field electroretinogram (ERG) and best corrected visual acuity (BCVA) measures have been shown to have prognostic value for recessive Stargardt disease (also called “ABCA4-related retinopathy”). These functional tests may serve as a performance-outcome-measure (PerfO) in emerging interventional clinical trials, but utility is limited by variability and patient burden. To address these limitations, an ensemble machine-learning-based approach was evaluated to differentiate patients from controls, and predict disease categories depending on ERG (‘inferred ERG’) and visual impairment (‘inferred visual impairment’) as well as BCVA values (‘inferred BCVA’) based on microstructural imaging (utilizing spectral-domain optical coherence tomography) and patient data. The accuracy for ‘inferred ERG’ and ‘inferred visual impairment’ was up to 99.53 ± 1.02%. Prediction of BCVA values (‘inferred BCVA’) achieved a precision of ±0.3LogMAR in up to 85.31% of eyes. Analysis of the permutation importance revealed that foveal status was the most important feature for BCVA prediction, while the thickness of outer nuclear layer and photoreceptor inner and outer segments as well as age of onset highly ranked for all predictions. ‘Inferred ERG’, ‘inferred visual impairment’, and ‘inferred BCVA’, herein, represent accurate estimates of differential functional effects of retinal microstructure, and offer quasi-functional parameters with the potential for a refined patient assessment, and investigation of potential future treatment effects or disease progression.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm9082428
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2662592-1
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Reliability of Retinal Layer Annotation with a Novel, High-Resolution Optical Coherence Tomography Device: A Comparative Study
    MDPI AG ; 2023
    In:  Bioengineering Vol. 10, No. 4 ( 2023-03-31), p. 438-
    Details
    In: Bioengineering, MDPI AG, Vol. 10, No. 4 ( 2023-03-31), p. 438-
    Abstract: Optical coherence tomography (OCT) enables in vivo diagnostics of individual retinal layers in the living human eye. However, improved imaging resolution could aid diagnosis and monitoring of retinal diseases and identify potential new imaging biomarkers. The investigational high-resolution OCT platform (High-Res OCT; 853 nm central wavelength, 3 µm axial-resolution) has an improved axial resolution by shifting the central wavelength and increasing the light source bandwidth compared to a conventional OCT device (880 nm central wavelength, 7 µm axial-resolution). To assess the possible benefit of a higher resolution, we compared the retest reliability of retinal layer annotation from conventional and High-Res OCT, evaluated the use of High-Res OCT in patients with age-related macular degeneration (AMD), and assessed differences of both devices on subjective image quality. Thirty eyes of 30 patients with early/intermediate AMD (iAMD; mean age 75 ± 8 years) and 30 eyes of 30 age-similar subjects without macular changes (62 ± 17 years) underwent identical OCT imaging on both devices. Inter- and intra-reader reliability were analyzed for manual retinal layer annotation using EyeLab. Central OCT B-scans were graded for image quality by two graders and a mean-opinion-score (MOS) was formed and evaluated. Inter- and intra-reader reliability were higher for High-Res OCT (greatest benefit for inter-reader reliability: ganglion cell layer; for intra-reader reliability: retinal nerve fiber layer). High-Res OCT was significantly associated with an improved MOS (MOS 9/8, Z-value = 5.4, p 〈 0.01) mainly due to improved subjective resolution (9/7, Z-Value 6.2, p 〈 0.01). The retinal pigment epithelium drusen complex showed a trend towards improved retest reliability in High-Res OCT in iAMD eyes but without statistical significance. Improved axial resolution of the High-Res OCT benefits retest reliability of retinal layer annotation and improves perceived image quality and resolution. Automated image analysis algorithms could also benefit from the increased image resolution.
    Type of Medium: Online Resource
    ISSN: 2306-5354
    URL: Article
    DOI: 10.3390/bioengineering10040438
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2746191-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Comprehensive Geno- and Phenotyping in a Complex Pedigree Including Four Different Inherited Retinal Dystrophies
    MDPI AG ; 2020
    In:  Genes Vol. 11, No. 2 ( 2020-01-28), p. 137-
    Details
    In: Genes, MDPI AG, Vol. 11, No. 2 ( 2020-01-28), p. 137-
    Abstract: Inherited retinal dystrophies (IRDs) are characterized by high clinical and genetic heterogeneity. A precise characterization is desirable for diagnosis and has impact on prognosis, patient counseling, and potential therapeutic options. Here, we demonstrate the effectiveness of the combination of in-depth retinal phenotyping and molecular genetic testing in complex pedigrees with different IRDs. Four affected Caucasians and two unaffected relatives were characterized including multimodal retinal imaging, functional testing, and targeted next-generation sequencing. A considerable intrafamilial phenotypic and genotypic heterogeneity was identified. While the parents of the index family presented with rod-cone dystrophy and ABCA4-related retinopathy, their two sons revealed characteristics in the spectrum of incomplete congenital stationary night blindness and ocular albinism, respectively. Molecular testing revealed previously described variants in RHO, ABCA4, and MITF as well as a novel variant in CACNA1F. Identified variants were verified by intrafamilial co-segregation, bioinformatic annotations, and in silico analysis. The coexistence of four independent IRDs caused by distinct mutations and inheritance modes in one pedigree is demonstrated. These findings highlight the complexity of IRDs and underscore the need for the combination of extensive molecular genetic testing and clinical characterization. In addition, a novel variant in the CACNA1F gene is reported associated with incomplete congenital stationary night blindness.
    Type of Medium: Online Resource
    ISSN: 2073-4425
    URL: Article
    DOI: 10.3390/genes11020137
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527218-4
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Mutational Landscape of the BAP1 Locus Reveals an Intrinsic Control to Regulate the miRNA Network and the Binding of Protein Complexes in Uveal Melanoma
    MDPI AG ; 2019
    In:  Cancers Vol. 11, No. 10 ( 2019-10-19), p. 1600-
    Details
    In: Cancers, MDPI AG, Vol. 11, No. 10 ( 2019-10-19), p. 1600-
    Abstract: The BAP1 (BRCA1-associated protein 1) gene is associated with a variety of human cancers. With its gene product being a nuclear ubiquitin carboxy-terminal hydrolase with deubiquitinase activity, BAP1 acts as a tumor suppressor gene with potential pleiotropic effects in multiple tumor types. Herein, we focused specifically on uveal melanoma (UM) in which BAP1 mutations are associated with a metastasizing phenotype and decreased survival rates. We identified the ubiquitin carboxyl hydrolase (UCH) domain as a major hotspot region for the pathogenic mutations with a high evolutionary action (EA) score. This also includes the mutations at conserved catalytic sites and the ones overlapping with the phosphorylation residues. Computational protein interaction studies revealed that distant BAP1-associated protein complexes (FOXK2, ASXL1, BARD1, BRCA1) could be directly impacted by this mutation paradigm. We also described the conformational transition related to BAP1-BRCA-BARD1 complex, which may pose critical implications for mutations, especially at the docking interfaces of these three proteins. The mutations affect - independent of being somatic or germline - the binding affinity of miRNAs embedded within the BAP1 locus, thereby altering the unique regulatory network. Apart from UM, BAP1 gene expression and survival associations were found to be predictive for the prognosis in several (n = 29) other cancer types. Herein, we suggest that although BAP1 is conceptually a driver gene in UM, it might contribute through its interaction partners and its regulatory miRNA network to various aspects of cancer. Taken together, these findings will pave the way to evaluate BAP1 in a variety of other human cancers with a shared mutational spectrum.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers11101600
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2527080-1
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    Fundus Autofluorescence Imaging in Patients with Choroidal Melanoma
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 7 ( 2022-04-02), p. 1809-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 7 ( 2022-04-02), p. 1809-
    Abstract: Choroidal melanocytic lesions require reliable and precise clinical examination and diagnosis to differentiate benign choroidal nevi from choroidal melanoma, as the latter may become life-threatening through metastatic disease. To come to an accurate diagnosis, as well as for monitoring, and to assess the efficacy of therapy, various imaging modalities may be used, one of which is non-invasive fundus autofluorescence (FAF) imaging using novel high-resolution digital imaging technology. FAF imaging is based on the visualization of intrinsic fluorophores in the ocular fundus. Lipofuscin and melanolipofuscin within the postmitotic retinal pigment epithelium (RPE) cells represent the major fluorophores that contribute to the FAF signal. In addition, the presence or loss of absorbing molecular constituents may have an impact on the FAF signal. A choroidal melanoma can cause secondary retinal and RPE alterations that affect the FAF signal (e.g., occurrence of orange pigment). Therefore, FAF imaging supports multimodal imaging and gives additional information over and above conventional imaging modalities regarding retinal metabolism and RPE health status. This article summarises the features of FAF imaging and the role of FAF imaging in the context of choroidal melanoma, both before and following therapeutic intervention.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14071809
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 8
    Online Resource
    Online Resource
    Clinical Outcomes of XEN45®-Stent Implantation after Failed Trabeculectomy: A Retrospective Single-Center Study
    MDPI AG ; 2023
    In:  Journal of Clinical Medicine Vol. 12, No. 4 ( 2023-02-06), p. 1296-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 12, No. 4 ( 2023-02-06), p. 1296-
    Abstract: Background: The implantation of a collagen gel micro-stent (XEN45®) as a minimally invasive form of glaucoma surgery (MIGS) after a failed trabeculectomy (TE) may be an effective option with few risks. This study investigated the clinical outcome of XEN45® implantation after a failed TE, with follow-up data of up to 30 months. Materials and Methods: In this paper, we present a retrospective review of patients undergoing XEN45® implantation after a failed TE at the University Eye Hospital Bonn, Germany, from 2012 to 2020. Results: In total, 14 eyes from 14 patients were included. The mean follow-up time was 20.4 months. The mean time duration between the failed TE and XEN45® implantation was 110 months. The mean intraocular pressure (IOP) decreased from 17.93 mmHg to 12.08 mmHg after one year. This value increased again to 17.63 mmHg at 24 months and 16.00 mmHg at 30 months. The number of glaucoma medications decreased from 3.2 to 0.71, 2.0, and 2.71 at 12, 24, and 30 months, respectively. Conclusions: XEN45® stent implantation after a failed TE did not lead to an effective long-term decrease in IOP and glaucoma medications in many patients in our cohort. Nevertheless, there were cases without the development of a failure event and complications, and others in whom further, more invasive surgery was delayed. XEN45® implantation in some failed trabeculectomy cases may, therefore, be a good option, especially in older patients with multiple comorbidities.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm12041296
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662592-1
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 9
    Online Resource
    Online Resource
    Early Vitrectomy with Silicone Oil Tamponade in the Management of Postoperative Endophthalmitis
    MDPI AG ; 2023
    In:  Journal of Clinical Medicine Vol. 12, No. 15 ( 2023-08-03), p. 5097-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 12, No. 15 ( 2023-08-03), p. 5097-
    Abstract: Background: Early vitrectomy for postsurgical endophthalmitis may improve visual acuity outcomes. Silicone oil as a tamponade has some potential benefits in the management of endophthalmitis. This study aims to evaluate the use of a silicone oil tamponade in the surgical management of endophthalmitis. Material and Methods: All patients with a pars plana vitrectomy with silicone oil tamponade for postsurgical endophthalmitis at the Department of Ophthalmology, University of Bonn, Germany, between 2017 and 2021 were retrospectively reviewed. We included all preoperative data, including BCVA at diagnosis, clinical findings, and symptoms. For every follow-up visit, we looked at BCVA and complications. Results: In total, 82 patients were included in this study. The mean follow-up was 13.1 months (range 1–58 months). An intravitreal injection was the cause in 42 patients (51.2%) and cataract surgery in 29 patients (35.4%). The mean interval between the causing event and the date of onset was 8.8 days (range, 1–59 days). The most prevalent pathogen was Staphylococcus epidermidis in 16 patients (19.5%). In 47 patients (57.3%), no pathogen was found. The initial best-corrected visual acuity was 2.1 logMAR and improved significantly to 1.0 logMAR after six months (p 〈 0.001) and 1.1 logMAR after 1 year (p 〈 0.001). In a multivariate analysis, a low BCVA at diagnosis (p = 0.041) was a significant predictor for poor visual acuity outcomes. A total of 17 patients (20.1%) developed postoperative complications. Five patients (6.1%) needed an anterior chamber washout with repeated injections of antibiotics. Two patients (2.4%) had persistent fibrin and were treated with YAG-laser treatment. Three patients (6.7%) developed a retinal detachment. Two patients (2.4%) had persistent corneal decompensation with endothelial cell loss and received perforating keratoplasty. We performed a matched-pair analysis (n = 30, each group n = 15) to compare a silicone oil tamponade with BSS at the end of surgery. The visual acuity outcome showed no significant differences (BCVA after one year: 1.17 logMAR in eyes with silicone oil and 0.90 logMAR in eyes with BSS; p = 0.684). Conclusions: In our study, a vitrectomy with silicone oil tamponade in the surgical management of postoperative endophthalmitis led to a significant improvement in visual acuity and had a low complication rate. Low BCVA at diagnosis was significantly associated with poor visual acuity outcomes. A comparison of silicone oil and BSS at the end of surgery showed similar results.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm12155097
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662592-1
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 10
    Online Resource
    Online Resource
    Ubiquitin Carboxyl-Terminal Hydrolases (UCHs): Potential Mediators for Cancer and Neurodegeneration
    MDPI AG ; 2020
    In:  International Journal of Molecular Sciences Vol. 21, No. 11 ( 2020-05-30), p. 3910-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 21, No. 11 ( 2020-05-30), p. 3910-
    Abstract: Emerging evidence suggests an inverse association between cancer and neurodegenerative diseases (NDD). Although phenotypically different, both diseases display a significant imbalance in the ubiquitination/deubiquitination processes. Therefore, we particularly investigated the expression of ubiquitin C-terminal hydrolases (UCHs: UCH-L1, UCH-L3, UCH-L5 and BAP1), a subfamily of deubiquitinating enzymes (DUBs), using publically available datasets (GTEx, TCGA) and observed altered expression of UCH-L1, UCH-L3, UCH-L5 in 17 cancer types. Interestingly, UCH-L1 (known to be enriched in neurons and interacting with the Parkinson’s disease-associated protein α-synuclein) appeared to be a prognostic indicator of unfavorable outcome in endometrial and urothelial cancer, while increased expression of UCH-L3 and UCH-L5 was associated with poor survival in liver and thyroid cancer, respectively. In normal tissues, UCH-L1 was found to be strongly expressed in the cerebral cortex and hypothalamus, while UCH-L3 expression was somewhat higher in the testis. The occurrence of mutation rates in UCHs also suggests that BAP1 and UCH-L5 may play a more dominant role in cancers than UCH-L1 and UCH-L3. We also characterized the functional context and configuration of the repeat elements in the promoter of DUBs genes and found that UCHs are highly discriminatory for catabolic function and are mainly enriched with LINE/CR1 repeats. Regarding the thesis of an inverse association between cancer and NDD, we observed that among all DUBs, UCHs are the one most involved in both entities. Considering a putative therapeutic potential based on presumed common mechanisms, it will be useful to determine whether other DUBs can compensate for the loss of UCH activity under physiological conditions. However, experimental evidence is required to substantiate this argument.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms21113910
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2019364-6
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...