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- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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- Huang, DL, et al.
(författare)
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Vaccine elicitation of HIV broadly neutralizing antibodies from engineered B cells
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 5850-
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Tidskriftsartikel (refereegranskat)abstract
- HIV broadly neutralizing antibodies (bnAbs) can suppress viremia and protect against HIV infection. However, their elicitation is made difficult by low frequencies of appropriate precursor B cell receptors and the complex maturation pathways required to generate bnAbs from these precursors. Antibody genes can be engineered into B cells for expression as both a functional antigen receptor on cell surfaces and as secreted antibody. Here, we show that HIV bnAb-engineered primary mouse B cells can be adoptively transferred and vaccinated in immunocompetent mice resulting in the expansion of durable bnAb memory and long-lived plasma cells. Somatic hypermutation after immunization indicates that engineered cells have the capacity to respond to an evolving pathogen. These results encourage further exploration of engineered B cell vaccines as a strategy for durable elicitation of HIV bnAbs to protect against infection and as a contributor to a functional HIV cure.
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- Sahin, O, et al.
(författare)
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International Multi-Specialty Expert Physician Preoperative Identification of Extranodal Extension n Oropharyngeal Cancer Patients using Computed Tomography: Prospective Blinded Human Inter-Observer Performance Evaluation
- 2024
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Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory.
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundExtranodal extension (ENE) is an important adverse prognostic factor in oropharyngeal cancer (OPC) and is often employed in therapeutic decision making. Clinician-based determination of ENE from radiological imaging is a difficult task with high inter-observer variability. However, the role of clinical specialty on the determination of ENE has been unexplored.MethodsPre-therapy computed tomography (CT) images for 24 human papillomavirus-positive (HPV+) OPC patients were selected for the analysis; 6 scans were randomly chosen to be duplicated, resulting in a total of 30 scans of which 21 had pathologically-confirmed ENE. 34 expert clinician annotators, comprised of 11 radiologists, 12 surgeons, and 11 radiation oncologists separately evaluated the 30 CT scans for ENE and noted the presence or absence of specific radiographic criteria and confidence in their prediction. Discriminative performance was measured using accuracy, sensitivity, specificity, area under the receiver operating characteristic curve (AUC), and Brier score for each physician. Statistical comparisons of discriminative performance were calculated using Mann Whitney U tests. Significant radiographic factors in correct discrimination of ENE status were determined through a logistic regression analysis. Interobserver agreement was measured using Fleiss’ kappa.ResultsThe median accuracy for ENE discrimination across all specialties was 0.57. There were significant differences between radiologists and surgeons for Brier score (0.33 vs. 0.26), radiation oncologists and surgeons for sensitivity (0.48 vs. 0.69), and radiation oncologists and radiologists/surgeons for specificity (0.89 vs. 0.56). There were no significant differences between specialties for accuracy or AUC. Indistinct capsular contour, nodal necrosis, and nodal matting were significant factors in regression analysis. Fleiss’ kappa was less than 0.6 for all the radiographic criteria, regardless of specialty.ConclusionsDetection of ENE in HPV+OPC patients on CT imaging remains a difficult task with high variability, regardless of clinician specialty. Although some differences do exist between the specialists, they are often minimal. Further research in automated analysis of ENE from radiographic images is likely needed.
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