| 1. |
- Hermsen, Meyke, et al.
(författare)
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Quantitative assessment of inflammatory infiltrates in kidney transplant biopsies using multiplex tyramide signal amplification and deep learning
- 2021
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Ingår i: Laboratory Investigation. - : Springer Nature. - 0023-6837 .- 1530-0307. ; 101:8, s. 970-982
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Tidskriftsartikel (refereegranskat)abstract
- Delayed graft function (DGF) is a strong risk factor for development of interstitial fibrosis and tubular atrophy (IFTA) in kidney transplants. Quantitative assessment of inflammatory infiltrates in kidney biopsies of DGF patients can reveal predictive markers for IFTA development. In this study, we combined multiplex tyramide signal amplification (mTSA) and convolutional neural networks (CNNs) to assess the inflammatory microenvironment in kidney biopsies of DGF patients (n = 22) taken at 6 weeks post-transplantation. Patients were stratified for IFTA development (<10% versus >= 10%) from 6 weeks to 6 months post-transplantation, based on histopathological assessment by three kidney pathologists. One mTSA panel was developed for visualization of capillaries, T- and B-lymphocytes and macrophages and a second mTSA panel for T-helper cell and macrophage subsets. The slides were multi spectrally imaged and custom-made python scripts enabled conversion to artificial brightfield whole-slide images (WSI). We used an existing CNN for the detection of lymphocytes with cytoplasmatic staining patterns in immunohistochemistry and developed two new CNNs for the detection of macrophages and nuclear-stained lymphocytes. F1-scores were 0.77 (nuclear-stained lymphocytes), 0.81 (cytoplasmatic-stained lymphocytes), and 0.82 (macrophages) on a test set of artificial brightfield WSI. The CNNs were used to detect inflammatory cells, after which we assessed the peritubular capillary extent, cell density, cell ratios, and cell distance in the two patient groups. In this cohort, distance of macrophages to other immune cells and peritubular capillary extent did not vary significantly at 6 weeks post-transplantation between patient groups. CD163(+) cell density was higher in patients with >= 10% IFTA development 6 months post-transplantation (p < 0.05). CD3(+)CD8(-)/CD3(+)CD8(+) ratios were higher in patients with <10% IFTA development (p < 0.05). We observed a high correlation between CD163(+) and CD4(+)GATA3(+) cell density (R = 0.74, p < 0.001). Our study demonstrates that CNNs can be used to leverage reliable, quantitative results from mTSA-stained, multi spectrally imaged slides of kidney transplant biopsies. This study describes a methodology to assess the microenvironment in sparse tissue samples. Deep learning, multiplex immunohistochemistry, and mathematical image processing techniques were incorporated to quantify lymphocytes, macrophages, and capillaries in kidney transplant biopsies of delayed graft function patients. The quantitative results were used to assess correlations with development of interstitial fibrosis and tubular atrophy.
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| 2. |
- Papitto, A., et al.
(författare)
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The INTEGRAL view of the pulsating hard X-ray sky : from accreting and transitional millisecond pulsars to rotation-powered pulsars and magnetars
- 2020
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Ingår i: New astronomy reviews (Print). - : Elsevier BV. - 1387-6473 .- 1872-9630. ; 91
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Tidskriftsartikel (refereegranskat)abstract
- In the last 25 years a new generation of X-ray satellites imparted a significant leap forward in our knowledge of X-ray pulsars. The discovery of accreting and transitional millisecond pulsars proved that disk accretion can spin up a neutron star to a very high rotation speed. The detection of MeV-GeV pulsed emission from a few hundreds of rotation-powered pulsars probed particle acceleration in the outer magnetosphere, or even beyond. Also, a population of two dozens of magnetars has emerged. INTEGRAL played a central role to achieve these results by providing instruments with high temporal resolution up to the hard X-ray/soft, gamma-ray band and a large field of view imager with good angular resolution to spot hard X-ray transients. In this article we review the main contributions by INTEGRAL to our understanding of the pulsating hard X-ray sky, such as the discovery and characterization of several accreting and transitional millisecond pulsars, the generation of the first catalog of hard X-ray/soft gamma-ray rotation-powered pulsars, the detection of polarization in the hard X-ray emission from the Crab pulsar, and the discovery of persistent hard X-ray emission from several magnetars.
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