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  • 1
    Online Resource
    Online Resource
    Mitigation of SARS-CoV-2 transmission at a large public university
    Springer Science and Business Media LLC ; 2022
    In:  Nature Communications Vol. 13, No. 1 ( 2022-06-09)
    Details
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2022-06-09)
    Abstract: In Fall 2020, universities saw extensive transmission of SARS-CoV-2 among their populations, threatening health of the university and surrounding communities, and viability of in-person instruction. Here we report a case study at the University of Illinois at Urbana-Champaign, where a multimodal “SHIELD: Target, Test, and Tell” program, with other non-pharmaceutical interventions, was employed to keep classrooms and laboratories open. The program included epidemiological modeling and surveillance, fast/frequent testing using a novel low-cost and scalable saliva-based RT-qPCR assay for SARS-CoV-2 that bypasses RNA extraction, called covidSHIELD, and digital tools for communication and compliance. In Fall 2020, we performed 〉 1,000,000 covidSHIELD tests, positivity rates remained low, we had zero COVID-19-related hospitalizations or deaths amongst our university community, and mortality in the surrounding Champaign County was reduced more than 4-fold relative to expected. This case study shows that fast/frequent testing and other interventions mitigated transmission of SARS-CoV-2 at a large public university.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    URL: Article
    DOI: 10.1038/s41467-022-30833-3
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2553671-0
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  • 2
    Online Resource
    Online Resource
    Single CAR-T cell treatment controls disseminated ovarian cancer in a syngeneic mouse model
    BMJ ; 2023
    In:  Journal for ImmunoTherapy of Cancer Vol. 11, No. 5 ( 2023-05), p. e006509-
    Details
    In: Journal for ImmunoTherapy of Cancer, BMJ, Vol. 11, No. 5 ( 2023-05), p. e006509-
    Abstract: Treatment of some blood cancers with T cells that express a chimeric antigen receptor (CAR) against CD19 have shown remarkable results. In contrast, CAR-T cell efficacy against solid tumors has been difficult to achieve. Methods To examine the potential of CAR-T cell treatments against ovarian cancers, we used the mouse ovarian cancer cell line ID8 in an intraperitoneal model that exhibits disseminated solid tumors in female C57BL/6J mice. The CAR contained a single-chain Fv from antibody 237 which recognizes a Tn-glycopeptide-antigen expressed by ID8 due to aberrant O-linked glycosylation in the absence of the transferase-dependent chaperone Cosmc . The efficacy of four Tn-dependent CARs with varying affinity to Tn antigen, and each containing CD28/CD3ζ cytoplasmic domains, were compared in vitro and in vivo in this study. Results In line with many observations about the impact of aberrant O-linked glycosylation, the ID8 Cosmc knock-out (ID8 Cosmc -KO) exhibited more rapid tumor progression compared with wild-type ID8. Despite the enhanced tumor growth in vivo, 237 CAR and a mutant with 30-fold higher affinity, but not CARs with lower affinity, controlled advanced ID8 Cosmc -KO tumors. Tumor regression could be achieved with a single intravenous dose of the CARs, but intraperitoneal administration was even more effective. The CAR-T cells persisted over a period of months, allowing CAR-treated mice to delay tumor growth in a re-challenge setting. The most effective CARs exhibited the highest affinity for antigen. Antitumor effects observed in vivo were associated with increased numbers of T cells and macrophages, and higher levels of cleaved caspase-3, in the tumor microenvironment. Notably, the least therapeutically effective CAR mediated tonic signaling leading to antigen-independent cytokine expression and it had higher levels of the immunosuppressive cytokine interleukin10. Conclusion The findings support the development of affinity-optimized CAR-T cells as a potential treatment for established ovarian cancer, with the most effective CARs mediating a distinct pattern of inflammatory cytokine release in vitro. Importantly, the most potent Tn-dependent CAR-T cells showed no evidence of toxicity in tumor-bearing mice in a syngeneic, immunocompetent system.
    Type of Medium: Online Resource
    ISSN: 2051-1426
    URL: Article
    DOI: 10.1136/jitc-2022-006509
    Language: English
    Publisher: BMJ
    Publication Date: 2023
    detail.hit.zdb_id: 2719863-7
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  • 3
    Online Resource
    Online Resource
    Direct Saliva versus Conventional Nasopharyngeal Swab qRT-PCR to Diagnose SARS – CoV2: Validity Study
    Sciencedomain International ; 2021
    In:  Asian Journal of Research in Infectious Diseases ( 2021-03-05), p. 37-46
    Details
    In: Asian Journal of Research in Infectious Diseases, Sciencedomain International, ( 2021-03-05), p. 37-46
    Abstract: Background: Saliva has been demonstrated as a feasible alternative specimen to nasopharyngeal swab for the detection of SARS-CoV-2 using real-time or quantitative reverse transcription polymerase chain reaction (qRT-PCR) method that bypasses the need for explicit viral ribonucleic acid (RNA) extraction. Aim: To assess the diagnostic validity of direct saliva-to-qRT-PCR in the detection of SARS-CoV-2 compared to conventional nasopharyngeal swab qRT-PCR. Methodology: Self-collected saliva samples were processed by heating at 95oC for 30 minutes followed by addition of buffer and detergent while viral RNA from nasopharyngeal swabs were extracted using the Sansure Biotech sample release reagent.  Paired samples were used as templates for qRT-PCR using the Sansure Novel Coronavirus (COVID-19) Nucleic Acid Diagnostic Kit and Sansure Biotech MA6000 Real-Time Quantitative PCR System. Direct saliva-to-qRT-PCR was compared to nasopharyngeal swab qRT-PCR in terms of diagnostic validity and agreement parameters, and both platforms were compared separately in terms of similar parameters with a composite reference standard (CRS) wherein the criteria for a positive result is SARS-CoV-2 detection in at least either nasopharyngeal swab or saliva. Results:  Of the 238 nasopharyngeal swab-saliva pairs tested, 20 (8.4%) nasopharyngeal swab and 24 (10.1%) saliva specimens tested positive. We documented a sensitivity of 85.0% (95% CI: 62.1%, 96.8%), specificity of 96.8% (95% CI: 93.5%, 98.7%), accuracy of 95.8% (95% CI: 92.4%, 98.0%) and Cohen Kappa of 0.75 (95% CI: 0.60, 0.90) when direct saliva-to-qRT-PCR was compared to the conventional platform. When the two platforms were individually compared to the CRS, numerically higher but not statistically significant sensitivity and accuracy were noted for direct saliva-to-qRT-PCR than for nasopharyngeal swab qRT-PCR. Conclusion: Direct saliva-to-qRT-PCR is non-inferior to nasopharyngeal swab qRT-PCR for detecting SARS-CoV-2 using the Sansure Novel Coronavirus Nucleic Acid Diagnostic Kit.
    Type of Medium: Online Resource
    ISSN: 2582-3221
    URL: Article
    DOI: 10.9734/ajrid/2021/v6i230193
    Language: Unknown
    Publisher: Sciencedomain International
    Publication Date: 2021
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  • 4
    Online Resource
    Online Resource
    RIG-I–Like Receptor LGP2 Is Required for Tumor Control by Radiotherapy
    American Association for Cancer Research (AACR) ; 2020
    In:  Cancer Research Vol. 80, No. 24 ( 2020-12-15), p. 5633-5641
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 24 ( 2020-12-15), p. 5633-5641
    Abstract: Dendritic cells (DC) play an essential role in innate immunity and radiation-elicited immune responses. LGP2 is a RIG-I–like receptor involved in cytoplasmic RNA recognition and antiviral responses. Although LGP2 has also been linked to cell survival of both tumor cells and T cells, the role of LGP2 in mediating DC function and antitumor immunity elicited by radiotherapy remains unclear. Here, we report that tumor DCs are linked to the clinical outcome of patients with breast cancer who received radiotherapy, and the presence of DC correlates with gene expression of LGP2 in the tumor microenvironment. In preclinical models, host LGP2 was essential for optimal antitumor control by ionizing radiation (IR). The absence of LGP2 in DC dampened type I IFN production and the priming capacity of DC. In the absence of LGP2, MDA5-mediated activation of type I IFN signaling was abrogated. The MDA5/LGP2 agonist high molecular weight poly I:C improved the antitumor effect of IR. This study reveals a previously undefined role of LGP2 in host immunity and provides a new strategy to improve the efficacy of radiotherapy. Significance: These findings reveal an essential role of LGP2 in promoting antitumor immunity after radiotherapy and provide a new strategy to enhance radiotherapy.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-20-2324
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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