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  • 1
    Publication Date: 2018-01-25
    Description: Recent advances in wearable electronics combined with wireless communications are essential to the realization of medical applications through health monitoring technologies. For example, a smart contact lens, which is capable of monitoring the physiological information of the eye and tear fluid, could provide real-time, noninvasive medical diagnostics. However, previous reports concerning the smart contact lens have indicated that opaque and brittle components have been used to enable the operation of the electronic device, and this could block the user’s vision and potentially damage the eye. In addition, the use of expensive and bulky equipment to measure signals from the contact lens sensors could interfere with the user’s external activities. Thus, we report an unconventional approach for the fabrication of a soft, smart contact lens in which glucose sensors, wireless power transfer circuits, and display pixels to visualize sensing signals in real time are fully integrated using transparent and stretchable nanostructures. The integration of this display into the smart lens eliminates the need for additional, bulky measurement equipment. This soft, smart contact lens can be transparent, providing a clear view by matching the refractive indices of its locally patterned areas. The resulting soft, smart contact lens provides real-time, wireless operation, and there are in vivo tests to monitor the glucose concentration in tears (suitable for determining the fasting glucose level in the tears of diabetic patients) and, simultaneously, to provide sensing results through the contact lens display.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 2
    Publication Date: 2018-01-09
    Description: Superantigens (SAgs) produced by Staphylococcus aureus at high concentrations induce proliferation of T cells bearing specific TCR Vβ sequences and massive cytokinemia that cause toxic shock syndrome. However, the biological relevance of SAgs produced at very low concentrations during asymptomatic colonization or chronic infections is not understood. In this study, we demonstrate that suboptimal stimulation of human PBMCs with a low concentration (1 ng/ml) of staphylococcal enterotoxin C1, at which half-maximal T cell proliferation was observed, induced CD8 + CD25 + T cells expressing markers related to regulatory T cells (Tregs), such as IFN-, IL-10, TGF-β, FOXP3, CD28, CTLA4, TNFR2, CD45RO, and HLA-DR. Importantly, these CD8 + CD25 + T cells suppressed responder cell proliferation mediated in contact-dependent and soluble factor–dependent manners, involving galectin-1 and granzymes, respectively. In contrast, optimal stimulation of human PBMCs with a high concentration (1 μg/ml) of staphylococcal enterotoxin C1, at which maximal T cell proliferation was observed, also induced similar expression of markers related to Tregs, including FOXP3 in CD8 + CD25 + cells, but these T cells were not functionally immunosuppressive. We further demonstrated that SAg-induced TCR Vβ–restricted and MHC class II–restricted expansion of immunosuppressive CD8 + CD25 + T cells is independent of CD4 + T cells. Our results suggest that the concentration of SAg strongly affects the functional characteristics of activated T cells, and low concentrations of SAg produced during asymptomatic colonization or chronic S. aureus infection induce immunosuppressive CD8 + Tregs, potentially promoting colonization, propagation, and invasion of S. aureus in the host.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
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  • 3
    Publication Date: 2018-11-06
    Description: Background/Aim: Patients with advanced non-small cell lung cancer (NSCLC) frequently face a dismal prognosis because of lack of curative therapies. We, therefore, conducted a preclinical investigation of the therapeutic efficacy of microRNA-107 (miR-107). Materials and Methods: The effects of miR-107 on cell proliferation and target gene expression were studied. Combinatorial effects of miR-107 and parthenolide were evaluated. Results: Cell proliferation was repressed in A549 NSCLC cells transfected with miR-107. Inhibitor of nuclear factor kappa B kinase subunit gamma was directly targeted by miR-107. Overexpression of miR-107 in A549 cells sensitized them to parthenolide along with a marked reduction of cyclin-dependent kinase 2. Conclusion: Our findings unveil an important biological function of miR-107 in regulating lung cancer cell proliferation and elevating an antiproliferative effect of parthenolide on lung cancer cells, suggesting that miR-107 could be beneficial benefit treatment for advanced NSCLC.
    Print ISSN: 0250-7005
    Electronic ISSN: 1791-7530
    Topics: Medicine
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  • 4
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    The American Association for Clinical Chemistry (AACC)
    Publication Date: 2018-11-29
    Description: BACKGROUND: Genetic information is unique among all laboratory data because it not only informs the current health of the specific person tested but may also be predictive of the future health of the individual and, to varying degrees, all biological relatives. CONTENT: As DNA sequencing has become ubiquitous with decreasing cost, large repositories of genomic data have emerged from the domains of research, healthcare, law enforcement, international security, and recreational consumer interest (i.e., genealogy). Broadly shared genomic data are believed to be a key element for future discoveries in human disease. For example, the National Cancer Institute's Genomic Data Commons is designed to promote cancer research discoveries by providing free access to the genome data sets of 12000 cancer patients. However, in parallel with the promise of curing diseases, genomic data also have the potential for harm. Genomic data that are deidentified by standard healthcare practices (e.g., removal of name, date of birth) can be reidentified by methods that combine genomic software with publicly available demographic databases (e.g., phone book). Recent law enforcement cases (i.e., Bear Brook Murders, Golden State Killer) in the US have demonstrated the power of combining DNA profiles with genealogy databases. SUMMARY: We examine the current environment of genomic privacy and confidentiality in the US and describe current and future risks to genomic privacy. Reidentification and inference of genetic information of biological relatives will become more important as larger databases of clinical, criminal, and recreational genomic information are developed over the next decade.
    Keywords: Molecular Diagnostics and Genetics
    Print ISSN: 0009-9147
    Electronic ISSN: 1530-8561
    Topics: Medicine
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  • 5
    Publication Date: 2018-11-23
    Description: The WHO Classification of Tumours of Haematopoietic and Lymphoid Tissue notes instances of Burkitt lymphoma/leukemia (BL) with IG- MYC rearrangement displaying a B-cell precursor immunophenotype (termed herein "preBLL"). To characterize the molecular pathogenesis of preBLL, we investigated 13 preBLL cases (including 1 cell line), of which 12 were analyzable using genome, exome, and targeted sequencing, imbalance mapping, and DNA methylation profiling. In 5 patients with reads across the IG- MYC breakpoint junctions, we found evidence that the translocation derived from an aberrant VDJ recombination, as is typical for IG translocations arising in B-cell precursors. Genomic changes like biallelic IGH translocations or VDJ rearrangements combined with translocation into the VDJ region on the second allele, potentially preventing expression of a productive immunoglobulin, were detected in 6 of 13 cases. We did not detect mutations in genes frequently altered in BL, but instead found activating NRAS and/or KRAS mutations in 7 of 12 preBLLs. Gains on 1q, recurrent in BL and preB lymphoblastic leukemia/lymphoma (pB-ALL/LBL), were detected in 7 of 12 preBLLs. DNA methylation profiling showed preBLL to cluster with precursor B cells and pB-ALL/LBL, but apart from BL. We conclude that preBLL genetically and epigenetically resembles pB-ALL/LBL rather than BL. Therefore, we propose that preBLL be considered as a pB-ALL/LBL with recurrent genetic abnormalities.
    Keywords: Lymphoid Neoplasia, Brief Reports
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 6
    Publication Date: 2018-05-25
    Description: Objectives To validate the performances of two prediction models (Brock and Lee models) for the differentiation of minimally invasive adenocarcinoma (MIA) and invasive pulmonary adenocarcinoma (IPA) from preinvasive lesions among subsolid nodules (SSNs). Design A retrospective cohort study. Setting A tertiary university hospital in South Korea. Participants 410 patients with 410 incidentally detected SSNs who underwent surgical resection for the pulmonary adenocarcinoma spectrum between 2011 and 2015. Primary and secondary outcome measures Using clinical and radiological variables, the predicted probability of MIA/IPA was calculated from pre-existing logistic models (Brock and Lee models). Areas under the receiver operating characteristic curve (AUCs) were calculated and compared between models. Performance metrics including sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were also obtained. Results For pure ground-glass nodules (n=101), the AUC of the Brock model in differentiating MIA/IPA (59/101) from preinvasive lesions (42/101) was 0.671. Sensitivity, specificity, accuracy, PPV and NPV based on the optimal cut-off value were 64.4%, 64.3%, 64.4%, 71.7% and 56.3%, respectively. Sensitivity, specificity, accuracy, PPV and NPV according to the Lee criteria were 76.3%, 42.9%, 62.4%, 65.2% and 56.3%, respectively. AUC was not obtained for the Lee model as a single cut-off of nodule size (≥10 mm) was suggested by this model for the assessment of pure ground-glass nodules. For part-solid nodules (n=309; 26 preinvasive lesions and 283 MIA/IPAs), the AUC was 0.746 for the Brock model and 0.771 for the Lee model (p=0.574). Sensitivity, specificity, accuracy, PPV and NPV were 82.3%, 53.8%, 79.9%, 95.1% and 21.9%, respectively, for the Brock model and 77.0%, 69.2%, 76.4%, 96.5% and 21.7%, respectively, for the Lee model. Conclusions The performance of prediction models for the incidentally detected SSNs in differentiating MIA/IPA from preinvasive lesions might be suboptimal. Thus, an alternative risk calculation model is required for the incidentally detected SSNs.
    Keywords: Open access, Oncology
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
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  • 7
    Publication Date: 2018-12-01
    Description: Background/Aim: This study aimed to determine the effect of different BRCA1 exonal mutations on the clinical course of epithelial ovarian cancer (EOC). Patients and Methods: Clinicopathological variables and survival outcomes were compared among 53 primary EOC patients with pathogenic BRCA1 mutations in exons 1-11 (5’ mutations) and in exons 12-24 (3’ mutations). Results: BRCA1 5’ exonal mutations were found in 35 (66.0%) patients. The median follow-up period was 40 months. Clinicopathological variables remained unchanged between the two groups. Patients with 5’ mutations had a significantly longer progression-free survival than those with C-terminal mutations (p=0.034), better predicting progression-free survival [2.923 (1.402-6.093), p=0.004], but not overall survival in cases of multiple relapses (p=0.497). Conclusion: N-terminal BRCA1 mutations in EOC patients are associated with favourable primary progression-free survival, a trend observed only in primary progression-free survival, not in overall survival.
    Print ISSN: 0250-7005
    Electronic ISSN: 1791-7530
    Topics: Medicine
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  • 8
    Publication Date: 2018-12-14
    Description: Despite progress in defining genetic risk for psychiatric disorders, their molecular mechanisms remain elusive. Addressing this, the PsychENCODE Consortium has generated a comprehensive online resource for the adult brain across 1866 individuals. The PsychENCODE resource contains ~79,000 brain-active enhancers, sets of Hi-C linkages, and topologically associating domains; single-cell expression profiles for many cell types; expression quantitative-trait loci (QTLs); and further QTLs associated with chromatin, splicing, and cell-type proportions. Integration shows that varying cell-type proportions largely account for the cross-population variation in expression (with 〉88% reconstruction accuracy). It also allows building of a gene regulatory network, linking genome-wide association study variants to genes (e.g., 321 for schizophrenia). We embed this network into an interpretable deep-learning model, which improves disease prediction by ~6-fold versus polygenic risk scores and identifies key genes and pathways in psychiatric disorders.
    Keywords: Genetics, Neuroscience, Online Only
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2018-03-06
    Description: A semiquantitative 123 I-metaiodobenzylguanidine ( 123 I-MIBG) scoring method (the Curie score, or CS) was previously examined in the Children’s Oncology Group (COG) high-risk neuroblastoma trial, COG A3973, with a postinduction CS of more than 2 being associated with poor event-free survival (EFS). The validation of the CS in an independent dataset, International Society of Paediatric Oncology European Neuroblastoma/High-Risk Neuroblastoma 1 (SIOPEN/HR-NBL1), is now reported. Methods: A retrospective analysis of 123 I-MIBG scans obtained from patients who had been prospectively enrolled in SIOPEN/HR-NBL1 was performed. All patients exhibited 123 I-MIBG–avid, International Neuroblastoma Staging System stage 4 neuroblastoma. 123 I-MIBG scans were evaluated at 2 time points, diagnosis ( n = 345) and postinduction ( n = 330), before consolidation myeloablative therapy. Scans of 10 anatomic regions were evaluated, with each region being scored 0–3 on the basis of disease extent and a cumulative CS generated. Cut points for outcome analysis were identified by Youden methodology. CSs from patients enrolled in COG A3973 were used for comparison. Results: The optimal cut point for CS at diagnosis was 12 in SIOPEN/HR-NBL1, with a significant outcome difference by CS noted (5-y EFS, 43.0% ± 5.7% [CS ≤ 12] vs. 21.4% ± 3.6% [CS 〉 12], P 〈 0.0001). The optimal CS cut point after induction was 2 in SIOPEN/HR-NBL1, with a postinduction CS of more than 2 being associated with an inferior outcome (5-y EFS, 39.2% ± 4.7% [CS ≤ 2] vs. 16.4% ± 4.2% [CS 〉 2], P 〈 0.0001). The postinduction CS maintained independent statistical significance in Cox models when adjusted for the covariates of age and MYCN gene copy number. Conclusion: The prognostic significance of postinduction CSs has now been validated in an independent cohort of patients (SIOPEN/HR-NBL1), with a postinduction CS of more than 2 being associated with an inferior outcome in 2 independent large, cooperative group trials.
    Print ISSN: 0022-3123
    Topics: Medicine
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  • 10
    Publication Date: 2018-02-10
    Description: Resolution of inflammation is an active process that leads to tissue homeostasis and involves multiple cellular and molecular mechanisms. Myeloid-derived suppressor cells (MDSCs) have recently emerged as important cellular components in the resolution of inflammation because of their activities to suppress T cell activation. In this article, we show that HLA-DR – CD11b + CD33 + CD14 + human MDSCs and CD11b + Ly6G – Ly6C + mouse MDSCs markedly increased in patients and mice during and before the resolution phase of autoimmune uveoretinitis. CD11b + Ly6C + monocytes isolated from autoimmune uveoretinitis mice were able to suppress T cell proliferation in culture, and adoptive transfer of the cells accelerated the remission of autoimmune uveoretinitis in mice. Alternatively, depletion of CD11b + Ly6C + monocytes at the resolution phase, but not CD11b + Ly6G + granulocytes, exacerbated the disease. These findings collectively indicate that monocytic MDSCs serve as regulatory cells mediating the resolution of autoimmune uveoretinitis.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
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