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Article: [No title information]

Bellini, Nicolas / Lodge, Robert / Cohen, Éric A

2022 Volume 26, Issue 1, Page(s) 41–53

Abstract: Résumé La thérapie antirétrovirale (TAR) inhibe la réplication du VIH-1 mais n'est pas curative. Pendant la TAR, le génome intégré du VIH-1 persiste principalement dans les lymphocytes T mémoires CD4+ ainsi que dans d'autres cellules immunitaires, ... ...

Title translation	Des petits ARN qui voient grand : les microARN et la persistance du VIH-1.
Abstract	Résumé La thérapie antirétrovirale (TAR) inhibe la réplication du VIH-1 mais n'est pas curative. Pendant la TAR, le génome intégré du VIH-1 persiste principalement dans les lymphocytes T mémoires CD4+ ainsi que dans d'autres cellules immunitaires, notamment les cellules myéloïdes comme les macrophages. La majorité de ces cellules ne produisent pas de particules virales infectieuses et constituent le réservoir latent. D'importants progrès ont été réalisés dans l'identification des facteurs qui contribuent à l'établissement et au maintien du réservoir latent qui demeure le principal obstacle à l'éradication du VIH-1. Dans cette revue, nous mettrons en relief le rôle des microARN dans le développement des réservoirs viraux vu que ceux-ci sont d'importants modulateurs de l'expression génique, ciblant des facteurs de transcription ainsi que d'autres effecteurs nécessaires à l'infection productive du VIH-1. Certains microARN ciblent même directement les transcrits viraux. Nous soulignerons les grandes questions en suspens sur la participation active des microARN de l'hôte aux mécanismes de persistance virale et notamment ceux régissant la latence virale. Finalement, compte tenu des stratégies actuelles qui ne permettent toujours pas de réduire efficacement les réservoirs viraux, les perspectives quant à l'utilisation des microARN comme approche pour contrer la persistance des réservoirs latents seront discutées.
MeSH term(s)	HIV-1 ; Humans ; MicroRNAs
Chemical Substances	MicroRNAs
Language	French
Publishing date	2022-06-28
Publishing country	France
Document type	Journal Article
ZDB-ID	2118387-9
ISSN	1950-6961 ; 1267-8694
ISSN (online)	1950-6961
ISSN	1267-8694
DOI	10.1684/vir.2022.0928
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Article ; Online: Non-Isocentric Geometry for Next-Generation Tomosynthesis With Super-Resolution.

Acciavatti, Raymond J / Choi, Chloe J / Vent, Trevor L / Barufaldi, Bruno / Cohen, Eric A / Wileyto, E Paul / Maidment, Andrew D A

IEEE transactions on medical imaging

2024 Volume 43, Issue 1, Page(s) 377–391

Abstract: Our lab at the University of Pennsylvania (UPenn) is investigating novel designs for digital breast tomosynthesis. We built a next-generation tomosynthesis system with a non-isocentric geometry (superior-to-inferior detector motion). This paper examines ... ...

Abstract	Our lab at the University of Pennsylvania (UPenn) is investigating novel designs for digital breast tomosynthesis. We built a next-generation tomosynthesis system with a non-isocentric geometry (superior-to-inferior detector motion). This paper examines four metrics of image quality affected by this design. First, aliasing was analyzed in reconstructions prepared with smaller pixelation than the detector. Aliasing was assessed with a theoretical model of r -factor, a metric calculating amplitudes of alias signal relative to input signal in the Fourier transform of the reconstruction of a sinusoidal object. Aliasing was also assessed experimentally with a bar pattern (illustrating spatial variations in aliasing) and 360°-star pattern (illustrating directional anisotropies in aliasing). Second, the point spread function (PSF) was modeled in the direction perpendicular to the detector to assess out-of-plane blurring. Third, power spectra were analyzed in an anthropomorphic phantom developed by UPenn and manufactured by Computerized Imaging Reference Systems (CIRS), Inc. (Norfolk, VA). Finally, calcifications were analyzed in the CIRS Model 020 BR3D Breast Imaging Phantom in terms of signal-to-noise ratio (SNR); i.e., mean calcification signal relative to background-tissue noise. Image quality was generally superior in the non-isocentric geometry: Aliasing artifacts were suppressed in both theoretical and experimental reconstructions prepared with smaller pixelation than the detector. PSF width was also reduced at most positions. Anatomic noise was reduced. Finally, SNR in calcification detection was improved. (A potential trade-off of smaller-pixel reconstructions was reduced SNR; however, SNR was still improved by the detector-motion acquisition.) In conclusion, the non-isocentric geometry improved image quality in several ways.
MeSH term(s)	Humans ; Image Processing, Computer-Assisted/methods ; Breast/diagnostic imaging ; Mammography/methods ; Computer Simulation ; Models, Theoretical ; Calcinosis ; Phantoms, Imaging ; Algorithms
Language	English
Publishing date	2024-01-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	622531-7
ISSN	1558-254X ; 0278-0062
ISSN (online)	1558-254X
ISSN	0278-0062
DOI	10.1109/TMI.2023.3307004
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Article ; Online: Is the Central Nervous System Reservoir a Hurdle for an HIV Cure?

Mohammadzadeh, Nazanin / Chomont, Nicolas / Estaquier, Jerome / Cohen, Eric A / Power, Christopher

Viruses

2023 Volume 15, Issue 12

Abstract: There is currently no cure for HIV infection although adherence to effective antiretroviral therapy (ART) suppresses replication of the virus in blood, increases ... ...

Abstract	There is currently no cure for HIV infection although adherence to effective antiretroviral therapy (ART) suppresses replication of the virus in blood, increases CD4
MeSH term(s)	Humans ; HIV Infections/drug therapy ; Central Nervous System ; Anti-Retroviral Agents/therapeutic use ; Anti-Retroviral Agents/pharmacology ; Macrophages ; Virus Replication ; Viral Load ; CD4-Positive T-Lymphocytes
Chemical Substances	Anti-Retroviral Agents
Language	English
Publishing date	2023-12-05
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v15122385
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Article ; Online: From arrest to escape: HIV-1 Vpr cuts a deal.

Cohen, Eric A

Cell host & microbe

2014 Volume 15, Issue 2, Page(s) 125–127

Abstract: HIV Vpr induces a cell-cycle arrest at the G2-to-M transition through a poorly understood mechanism. In a recent issue of Cell, Laguette et al. (2014) demonstrate that untimely activation of the structure-specific endonuclease regulator SLX4 complex by ... ...

Abstract	HIV Vpr induces a cell-cycle arrest at the G2-to-M transition through a poorly understood mechanism. In a recent issue of Cell, Laguette et al. (2014) demonstrate that untimely activation of the structure-specific endonuclease regulator SLX4 complex by Vpr promotes G2/M arrest and escape from innate immune sensing.
MeSH term(s)	G2 Phase Cell Cycle Checkpoints ; HIV Infections/pathology ; HIV-1/metabolism ; Humans ; Immunity, Innate ; Multiprotein Complexes/metabolism ; Recombinases/metabolism ; vpr Gene Products, Human Immunodeficiency Virus/metabolism
Chemical Substances	Multiprotein Complexes ; Recombinases ; vpr Gene Products, Human Immunodeficiency Virus
Language	English
Publishing date	2014-02-14
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2278004-X
ISSN	1934-6069 ; 1931-3128
ISSN (online)	1934-6069
ISSN	1931-3128
DOI	10.1016/j.chom.2014.01.012
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Article ; Online: The Ongoing Saga of the Evolution of Percutaneous Coronary Intervention: From Balloon Angioplasty to Recent Innovations to Future Prospects.

Picard, Fabien / Pighi, Michele / Marquis-Gravel, Guillaume / Labinaz, Marino / Cohen, Eric A / Tanguay, Jean-François

The Canadian journal of cardiology

2022 Volume 38, Issue 10S1, Page(s) S30–S41

Abstract: The advances in percutaneous coronary intervention (PCI) have been, above all, dependent on the work of pioneers in surgery, radiology, and interventional cardiology. From Grüntzig's first balloon angioplasty, PCI has expanded through technology ... ...

Abstract	The advances in percutaneous coronary intervention (PCI) have been, above all, dependent on the work of pioneers in surgery, radiology, and interventional cardiology. From Grüntzig's first balloon angioplasty, PCI has expanded through technology development, improved protocols, and dissemination of best-practice techniques. We can nowadays treat more complex lesions in higher-risk patients with favourable results. Guide wires, balloon types and profiles, debulking techniques such as atherectomy or lithotripsy, stents, and scaffolds all represent evolutions that have allowed us to tackle complex lesions such as an unprotected left main coronary artery, complex bifurcations, or chronic total occlusions. Best-practice PCI, including physiology assessment, imaging, and optimal lesion preparation are now the gold standard when performing PCI for sound indications, and new technologies such as intravascular lithotripsy for lesion preparation, or artificial intelligence, are innovations in the steps of 4 decades of pioneers to improve patient care in interventional cardiology. In the present review, major innovations in PCI since the first balloon angioplasty and also uncertainties and obstacles inherent to such medical advances are described.
MeSH term(s)	Angioplasty, Balloon ; Angioplasty, Balloon, Coronary/methods ; Artificial Intelligence ; Coronary Angiography/methods ; Coronary Artery Disease/etiology ; Coronary Artery Disease/surgery ; Humans ; Percutaneous Coronary Intervention/adverse effects ; Stents ; Treatment Outcome
Language	English
Publishing date	2022-06-28
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	632813-1
ISSN	1916-7075 ; 0828-282X
ISSN (online)	1916-7075
ISSN	0828-282X
DOI	10.1016/j.cjca.2022.06.019
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Article ; Online: Conserved residues within the HIV-1 Vpu transmembrane-proximal hinge region modulate BST2 binding and antagonism.

Lukhele, Sabelo / Cohen, Éric A

Retrovirology

2017 Volume 14, Issue 1, Page(s) 18

Abstract: Background: BST2 inhibits HIV-1 release by tethering nascent virions to the surface of infected cells. HIV-1 Vpu overcomes this restriction by removing BST2 from viral budding sites via BST2 intracellular trapping and sequestration, surface ... ...

Abstract	Background: BST2 inhibits HIV-1 release by tethering nascent virions to the surface of infected cells. HIV-1 Vpu overcomes this restriction by removing BST2 from viral budding sites via BST2 intracellular trapping and sequestration, surface downregulation and/or displacement mechanisms. Vpu is composed of a short luminal tail, a transmembrane domain (TMD) and a cytoplasmic hinge region that is followed by two helices. BST2 counteraction relies on the ability of Vpu to physically bind BST2 through TMD interactions and recruit the clathrin-dependent trafficking machinery via a canonical acidic di-leucine signalling motif within the helix-2 of Vpu. The highly conserved Vpu transmembrane-proximal hinge region encompasses residues that resemble an acidic leucine-based trafficking motif, whose functional roles are currently ill-defined. In this study, we investigated the contribution of these residues towards Vpu-mediated BST2 antagonism. Results: We show that while these conserved residues have no intrinsic activity on the cellular distribution of Vpu in the absence of BST2, they regulate the ability of Vpu to bind to BST2 and, consequently, govern both BST2-dependent trafficking properties of the protein as well as its co-localization with BST2. Moreover, these residues, particularly a glutamic acid residue positioned immediately following the TMD, are a determinant not only for efficient targeting of BST2, but also binding and degradation of CD4, another host membrane protein targeted by Vpu. Mechanistically, our data are consistent with a role of these residues in the maintenance of the Vpu TMD conformational configuration such that interactions with membrane-associated host targets are favoured. Conclusions: Altogether, this work demonstrates an important regulatory role of the transmembrane-proximal Vpu hinge region residues towards enabling the protein to efficiently engage its target host proteins. Thus, this highly conserved, cytosolic Vpu hinge region may represent an attractive target for the development of anti-Vpu inhibitors.
MeSH term(s)	Antigens, CD/metabolism ; DNA Mutational Analysis ; GPI-Linked Proteins/antagonists & inhibitors ; GPI-Linked Proteins/metabolism ; HIV-1/genetics ; HIV-1/physiology ; Host-Pathogen Interactions ; Human Immunodeficiency Virus Proteins/genetics ; Human Immunodeficiency Virus Proteins/metabolism ; Humans ; Protein Binding ; Viral Regulatory and Accessory Proteins/genetics ; Viral Regulatory and Accessory Proteins/metabolism
Chemical Substances	Antigens, CD ; BST2 protein, human ; GPI-Linked Proteins ; Human Immunodeficiency Virus Proteins ; Viral Regulatory and Accessory Proteins ; vpu protein, Human immunodeficiency virus 1
Language	English
Publishing date	2017-03-14
Publishing country	England
Document type	Journal Article
ISSN	1742-4690
ISSN (online)	1742-4690
DOI	10.1186/s12977-017-0345-6
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Article ; Online: MicroRNA-25/93 induction by Vpu as a mechanism for counteracting MARCH1-restriction on HIV-1 infectivity in macrophages.

Lodge, Robert / Xu, Zaikun / Eklund, Mckenna / Stürzel, Christina / Kirchhoff, Frank / Tremblay, Michel J / Hobman, Tom C / Cohen, Éric A

mBio

2023 Volume 14, Issue 5, Page(s) e0195023

Abstract: Importance: In order to efficiently produce infectious viral particles, HIV must counter several restrictions exerted by host cell antiviral proteins. MARCH1 is a member of the MARCH protein family that restricts HIV infection by limiting the ... ...

Abstract	Importance: In order to efficiently produce infectious viral particles, HIV must counter several restrictions exerted by host cell antiviral proteins. MARCH1 is a member of the MARCH protein family that restricts HIV infection by limiting the incorporation of viral envelope glycoproteins into nascent virions. Here, we identified two regulatory RNAs, microRNAs-25 and -93, induced by the HIV-1 accessory protein Vpu, that downregulate
MeSH term(s)	Humans ; HIV Infections/metabolism ; HIV-1/physiology ; Viral Regulatory and Accessory Proteins/genetics ; Viral Regulatory and Accessory Proteins/metabolism ; Human Immunodeficiency Virus Proteins/genetics ; HIV Seropositivity ; Antiviral Agents/metabolism ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Macrophages/metabolism ; GPI-Linked Proteins/metabolism
Chemical Substances	Viral Regulatory and Accessory Proteins ; Human Immunodeficiency Virus Proteins ; Antiviral Agents ; MicroRNAs ; GPI-Linked Proteins ; MIRN25 microRNA, human
Language	English
Publishing date	2023-09-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mbio.01950-23
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Article ; Online: Caspase cleavage of gasdermin E causes neuronal pyroptosis in HIV-associated neurocognitive disorder.

Fernandes, Jason P / Branton, William G / Cohen, Eric A / Koopman, Gerrit / Kondova, Ivanela / Gelman, Benjamin B / Power, Christopher

Brain : a journal of neurology

2023 Volume 147, Issue 2, Page(s) 717–734

Abstract: Despite effective antiretroviral therapies, 20-30% of persons with treated HIV infection develop a neurodegenerative syndrome termed HIV-associated neurocognitive disorder (HAND). HAND is driven by HIV expression coupled with inflammation in the brain ... ...

Abstract	Despite effective antiretroviral therapies, 20-30% of persons with treated HIV infection develop a neurodegenerative syndrome termed HIV-associated neurocognitive disorder (HAND). HAND is driven by HIV expression coupled with inflammation in the brain but the mechanisms underlying neuronal damage and death are uncertain. The inflammasome-pyroptosis axis coordinates an inflammatory type of regulated lytic cell death that is underpinned by the caspase-activated pore-forming gasdermin proteins. The mechanisms driving neuronal pyroptosis were investigated herein in models of HAND, using multi-platform molecular and morphological approaches that included brain tissues from persons with HAND and simian immunodeficiency virus (SIV)-infected non-human primates as well as cultured human neurons. Neurons in the frontal cortices from persons with HAND showed increased cleaved gasdermin E (GSDME), which was associated with β-III tubulin degradation and increased HIV levels. Exposure of cultured human neurons to the HIV-encoded viral protein R (Vpr) elicited time-dependent cleavage of GSDME and Ninjurin-1 (NINJ1) induction with associated cell lysis that was inhibited by siRNA suppression of both proteins. Upstream of GSDME cleavage, Vpr exposure resulted in activation of caspases-1 and 3. Pretreatment of Vpr-exposed neurons with the caspase-1 inhibitor, VX-765, reduced cleavage of both caspase-3 and GSDME, resulting in diminished cell death. To validate these findings, we examined frontal cortical tissues from SIV-infected macaques, disclosing increased expression of GSDME and NINJ1 in cortical neurons, which was co-localized with caspase-3 detection in animals with neurological disease. Thus, HIV infection of the brain triggers the convergent activation of caspases-1 and -3, which results in GSDME-mediated neuronal pyroptosis in persons with HAND. These findings demonstrate a novel mechanism by which a viral infection causes pyroptotic death in neurons while also offering new diagnostic and therapeutic strategies for HAND and other neurodegenerative disorders.
MeSH term(s)	Animals ; Humans ; Pyroptosis ; Caspases/metabolism ; Caspases/pharmacology ; Caspase 3/metabolism ; Caspase 3/pharmacology ; Gasdermins ; HIV/metabolism ; HIV Infections/complications ; Neurons/metabolism ; Neurocognitive Disorders/etiology ; Nerve Growth Factors/metabolism ; Cell Adhesion Molecules, Neuronal/metabolism
Chemical Substances	Caspases (EC 3.4.22.-) ; Caspase 3 (EC 3.4.22.-) ; Gasdermins ; NINJ1 protein, human ; Nerve Growth Factors ; Cell Adhesion Molecules, Neuronal
Language	English
Publishing date	2023-11-06
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80072-7
ISSN	1460-2156 ; 0006-8950
ISSN (online)	1460-2156
ISSN	0006-8950
DOI	10.1093/brain/awad375
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Article ; Online: Human Immunodeficiency Virus Type 1 Vpr Mediates Degradation of APC1, a Scaffolding Component of the Anaphase-Promoting Complex/Cyclosome.

Barbosa, Jérémy A Ferreira / Sparapani, Samantha / Boulais, Jonathan / Lodge, Robert / Cohen, Éric A

Journal of virology

2021 Volume 95, Issue 15, Page(s) e0097120

Abstract: HIV-1 encodes several accessory proteins-Nef, Vif, Vpr, and Vpu-whose functions are to modulate the cellular environment to favor immune evasion and viral replication. While Vpr was shown to mediate a ... ...

Abstract	HIV-1 encodes several accessory proteins-Nef, Vif, Vpr, and Vpu-whose functions are to modulate the cellular environment to favor immune evasion and viral replication. While Vpr was shown to mediate a G
MeSH term(s)	Apc1 Subunit, Anaphase-Promoting Complex-Cyclosome/metabolism ; CD4-Positive T-Lymphocytes/virology ; Cell Line, Tumor ; G2 Phase Cell Cycle Checkpoints/genetics ; HEK293 Cells ; HIV Infections/pathology ; HIV-1/growth & development ; HIV-1/metabolism ; HeLa Cells ; Humans ; Macrophages/virology ; Protein Serine-Threonine Kinases/genetics ; RNA Interference ; RNA, Small Interfering/genetics ; Tandem Mass Spectrometry ; Ubiquitin-Protein Ligases/genetics ; Virus Replication/genetics ; vpr Gene Products, Human Immunodeficiency Virus/genetics ; vpr Gene Products, Human Immunodeficiency Virus/metabolism
Chemical Substances	ANAPC1 protein, human ; Apc1 Subunit, Anaphase-Promoting Complex-Cyclosome ; RNA, Small Interfering ; vpr Gene Products, Human Immunodeficiency Virus ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; DCAF1 protein, human (EC 2.7.11.1) ; Protein Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2021-07-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.00971-20
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Article ; Online: Generalized ComBat harmonization methods for radiomic features with multi-modal distributions and multiple batch effects.

Horng, Hannah / Singh, Apurva / Yousefi, Bardia / Cohen, Eric A / Haghighi, Babak / Katz, Sharyn / Noël, Peter B / Shinohara, Russell T / Kontos, Despina

Scientific reports

2022 Volume 12, Issue 1, Page(s) 4493

Abstract: Radiomic features have a wide range of clinical applications, but variability due to image acquisition factors can affect their performance. The harmonization tool ComBat is a promising solution but is limited by inability to harmonize multimodal ... ...

Abstract	Radiomic features have a wide range of clinical applications, but variability due to image acquisition factors can affect their performance. The harmonization tool ComBat is a promising solution but is limited by inability to harmonize multimodal distributions, unknown imaging parameters, and multiple imaging parameters. In this study, we propose two methods for addressing these limitations. We propose a sequential method that allows for harmonization of radiomic features by multiple imaging parameters (Nested ComBat). We also employ a Gaussian Mixture Model (GMM)-based method (GMM ComBat) where scans are split into groupings based on the shape of the distribution used for harmonization as a batch effect and subsequent harmonization by a known imaging parameter. These two methods were evaluated on features extracted with CapTK and PyRadiomics from two public lung computed tomography datasets. We found that Nested ComBat exhibited similar performance to standard ComBat in reducing the percentage of features with statistically significant differences in distribution attributable to imaging parameters. GMM ComBat improved harmonization performance over standard ComBat (- 11%, - 10% for Lung3/CAPTK, Lung3/PyRadiomics harmonizing by kernel resolution). Features harmonized with a variant of the Nested method and the GMM split method demonstrated similar c-statistics and Kaplan-Meier curves when used in survival analyses.
MeSH term(s)	Tomography, X-Ray Computed
Language	English
Publishing date	2022-03-16
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-08412-9
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