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1.
Artigo em Inglês | MEDLINE | ID: mdl-34519889

RESUMO

PURPOSE: Without a standard test for pancreatic carcinomas, this highly lethal disease is normally diagnosed at its advanced stage, leading to a low survival rate of patients. Trophoblast cell-surface antigen 2 (Trop-2), a transmembrane glycoprotein, is associated with cell proliferation and highly expressed in most of solid epithelial tumors, including pancreatic cancer. A non-invasive method of imaging Trop-2 would greatly benefit clinical diagnosis and monitoring of pancreatic cancer. In the current study, 89Zr-labeled anti-Trop-2 antibody (AF650) was recruited for the systemic evaluation of Trop-2 as an immunoPET target for pancreatic cancer imaging. METHODS: AF650 was conjugated with desferrioxamine (DFO) and then radiolabeled with 89Zr. Trop-2 expression levels were determined in three pancreatic cancer cell lines (BxPC-3, MIA PaCa-2, and AsPC-1) via western blot, flow cytometry, saturation binding assay, and immunofluorescence staining. The targeting capacity of 89Zr-DFO-AF650 was evaluated in mouse models with subcutaneous xenograft of pancreatic cancers via PET imaging and bio-distribution studies. In addition, a Trop-2-positive orthotopic cancer model was recruited for further validating the targeting specificity of 89Zr-DFO-AF650. RESULTS: BxPC-3 cells expressed high levels of Trop-2, while AsPC-1 and MIA PaCa-2 cells expressed low levels of Trop-2. Additionally, 89Zr-DFO-AF650 exhibited high specificity to Trop-2 in BxPC-3 cells (Kd = 22.34 ± 2.509 nM). In subcutaneous xenograft models, about 28.8 ± 7.63%ID/g tracer accumulated in the BxPC-3 tumors at 120 h post injection, which was much higher than those reaching MIA PaCa-2 (6.76 ± 2.08%ID/g) and AsPC-1 (3.51 ± 0.69%ID/g) tumors (n = 4). More importantly, 89Zr-DFO-AF650 could efficiently distinguish primary tumors in the orthotopic BxPC-3 cancer model, showing high correlation between PET imaging and bio-distribution and sensitivity. CONCLUSIONS: 89Zr-DFO-AF650 can be effectively used to detect pancreatic cancer via Trop-2-mediated immunoPET in vivo, clearly revealing the great potential of Trop-2-based non-invasive imaging in pancreatic cancer detection and treatment monitoring.

2.
Am J Nucl Med Mol Imaging ; 11(4): 327-331, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513286

RESUMO

This perspective briefly reviewed the applications of 18F-FDG PET/CT in the clinical management of lymphoma and the need for lesion segmentation in those applications. It discussed the limitations of existing segmentation technologies and the great potential of using deep learning convolutional neural network (DLCNN) to accomplish automatic lymphoma segmentation and characterizations. Finally, the authors shared perspectives on the technical challenges that need to be addressed to fully unleash the potential of DLCNN and 18F-FDG PET/CT in the diagnosis, prognosis, and treatment of lymphoma.

3.
Am J Nucl Med Mol Imaging ; 11(4): 332-336, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513287

RESUMO

The COVID-19 pandemic continues to influence every aspect of human life across the globe. It was reported that vascular angiogenesis of COVID-19 was elevated in patients with equally severe influenza virus infection. In this issue of AJNMMI, Farolfi et al. reported that there was lung uptake not related to prostate cancer in almost all COVID-19 patients who performed 68Ga-PSMA-11 PET/CT scans and most of the lung uptake lesions were matched with typical CT patterns of COVID-19. With the advantages of having various tracers for whole-body imaging, PET provides opportunities to study the mechanism of COVID-19 from different aspects and obtain patterns of extrapulmonary lesions in COVID-19, which helps explore more effective treatments for the patients. This case series opened the door to many future studies. Furthermore, such a multi-national/multi-institutional collaboration in the pandemic truly encouraged us that science is indeed without borders.

4.
Theranostics ; 11(18): 9177-9179, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34522233

RESUMO

Ideal nuclear imaging tracers should exhibit high target uptake and low background signal. Traditional renal scintigraphy and SPECT scans examine kidney function via static or dynamic tracing of radioactive probes in the kidneys. The lack of tracer affinity to specific biological processes and high background uptake from urinary excretion have added many difficulties to precision renal diagnosis. In this issue of Theranostics, Jin and colleagues innovatively devised a recombinant probe for preferential kidney imaging through targeting of tubular neonatal Fc receptor and proximal tubular basement membrane for sustained tubular reabsorption and accumulation. This work has broad implications regarding how an in depth understanding of physiology and pathology may be of service for tracer development, renal diagnosis, and disease theranostics.

6.
Science ; 373(6552): 337-342, 2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34437153

RESUMO

Piezoelectric biomaterials are intrinsically suitable for coupling mechanical and electrical energy in biological systems to achieve in vivo real-time sensing, actuation, and electricity generation. However, the inability to synthesize and align the piezoelectric phase at a large scale remains a roadblock toward practical applications. We present a wafer-scale approach to creating piezoelectric biomaterial thin films based on γ-glycine crystals. The thin film has a sandwich structure, where a crystalline glycine layer self-assembles and automatically aligns between two polyvinyl alcohol (PVA) thin films. The heterostructured glycine-PVA films exhibit piezoelectric coefficients of 5.3 picocoulombs per newton or 157.5 × 10-3 volt meters per newton and nearly an order of magnitude enhancement of the mechanical flexibility compared with pure glycine crystals. With its natural compatibility and degradability in physiological environments, glycine-PVA films may enable the development of transient implantable electromechanical devices.


Assuntos
Materiais Biocompatíveis/química , Eletricidade , Glicina/química , Álcool de Polivinil/química , Animais , Sobrevivência Celular , Células Cultivadas , Cristalização , Teoria da Densidade Funcional , Elasticidade , Humanos , Ligação de Hidrogênio , Próteses e Implantes , Ratos , Ratos Sprague-Dawley , Estresse Mecânico
7.
Cancers (Basel) ; 13(13)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34202358

RESUMO

An essential aspect of thyroid cancer (TC) management is personalized and precision medicine. Functional imaging of TC with radioiodine and [18F]FDG has been frequently used in disease evaluation for several decades now. Recently, advances in molecular imaging have led to the development of novel tracers based on aptamer, peptide, antibody, nanobody, antibody fragment, and nanoparticle platforms. The emerging targets-including HER2, CD54, SHP2, CD33, and more-are promising targets for clinical translation soon. The significance of these tracers may be realized by outlining the way they support the management of TC. The provided examples focus on where preclinical investigations can be translated. Furthermore, advances in the molecular imaging of TC may inspire the development of novel therapeutic or theranostic tracers. In this review, we summarize TC-targeting probes which include transporter-based and immuno-based imaging moieties. We summarize the most recent evidence in this field and outline how these emerging strategies may potentially optimize clinical practice.

8.
Adv Nanobiomed Res ; 1(1)2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34212160

RESUMO

A method is developed for membrane labeling of erythrocytes with porphyrin-phospholipid (PoP). To generate a concentrated PoP solution for labeling human red blood cells (RBCs), various surfactants and solvents are screened to identify conditions that avoid hemolysis, while minimizing non-specific PoP co-precipitation with RBCs in the pellet during centrifugation washes. Cholate, Tween 80 and Tween 40 are identified as useful surfactants for this purpose. When labeled RBCs are mixed with unlabeled ones, substantial non-specific PoP exchange is observed. Egg-yolk lecithin is included in a washing buffer to remove loosely bound PoP and reduce PoP exchange with unlabeled erythrocytes, based on flow cytometry and photodynamic hemolysis assays. Murine RBCs that are labeled with 64Cu-chelated PoP displayed altered biodistribution with longer blood circulation relative to directly administered 64Cu-chelated PoP.

9.
Cancers (Basel) ; 13(14)2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34298651

RESUMO

We explored the clinical value of 18F-FDG PET/MR in a head-to-head comparison with PET/CT in loco-regional recurrent and metastatic cervical lymph nodes of differentiated thyroid carcinoma (DTC) patients after comprehensive treatment. 18F-FDG PET/CT and neck PET/MR scans that were performed in DTC patients with suspected recurrence or cervical lymph node metastasis after comprehensive treatment were retrospectively analyzed. Detection rates, diagnostic efficacy, image conspicuity, and measured parameters were compared between 18F-FDG PET/CT and PET/MR. The gold standard was histopathological diagnosis or clinical and imaging follow-up results for more than 6 months. Among the 37 patients enrolled, no suspicious signs of tumor were found in 10 patients, 24 patients had lymph node metastasis, and 3 patients had both recurrence and lymph node metastases. A total of 130 lesions were analyzed, including 3 malignant and 6 benign thyroid nodules, as well as 74 malignant and 47 benign cervical lymph nodes. Compared with PET/CT, PET/MR presented better detection rates (91.5% vs. 80.8%), image conspicuity (2.74 ± 0.60 vs. 1.9 ± 0.50, p < 0.001, especially in complex level II), and sensitivity (80.5% vs. 61.0%). SUVmax differed in benign and malignant lymph nodes in both imaging modalities (p < 0.05). For the same lesion, the SUVmax, SUVmean, and diameters measured by PET/MR and PET/CT were consistent and had significant correlation. In conclusion, compared with 18F-FDG PET/CT, PET/MR was more accurate in determining recurrent and metastatic lesions, both from a patient-based and from a lesion-based perspective. Adding local PET/MR after whole-body PET/CT may be recommended to provide more precise diagnostic information and scope of surgical resection without additional ionizing radiation. Further scaling-up prospective studies and economic benefit analysis are expected.

10.
Front Cell Dev Biol ; 9: 680301, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34277621

RESUMO

Astrocytes are the key component of the central nervous system (CNS), serving as pivotal regulators of neuronal synapse formation and maturation through their ability to dynamically and bidirectionally communicate with synapses throughout life. In the past 20 years, numerous astrocyte-derived molecules promoting synaptogenesis have been discovered. However, our understanding of the cell biological basis underlying intra-neuron processes and astrocyte-mediated synaptogenesis is still in its infancy. Here, we provide a comprehensive overview of the various ways astrocytes talk to neurons, and highlight astrocytes' heterogeneity that allow them to displays regional-specific capabilities in boosting synaptogenesis. Finally, we conclude with promises and future directions on how organoids generated from human induced pluripotent stem cells (hiPSCs) effectively address the signaling pathways astrocytes employ in synaptic development.

11.
Natl Sci Rev ; 8(6)2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34262791

RESUMO

Photothermal nanotheranostics, especially in the near infrared II (NIR-II) region, exhibits a great potential in precision and personalized medicine, owing to high tissue penetration of NIR-II light. The NIR-II-photothermal nanoplatforms with high biocompatibility as well as high photothermal effect are urgently needed but rarely reported so far. Te nanomaterials possess high absorbance to NIR-II light but also exhibit high cytotoxicity, impeding their biomedical applications. In this work, the controllable incorporation of biocompatible Se into the lattice of Te nanostructures is proposed to intrinsically tune their inherent cytotoxicity and enhance their biocompatibility, developing TeSex nano-alloys as a new kind of theranostic nanoplatforms. We have uncovered that the cytotoxicity of Te nanomaterials primarily derives from irreversible oxidation stress and intracellular imbalance of organization and energy, and can be eliminated by incorporating a moderate proportion of Se (x=0.43). We have also discovered that the as-prepared TeSex nano-alloys have extraordinarily high NIR-II-photothermal conversion efficiency (77.2%), 64Cu coordination and computed tomography (CT) contrast capabilities, enabling high-efficacy multimodal photothermal/photoacoustic/positron emission tomography (PET)/CT imaging-guided NIR-II-photothermal therapy of cancer. The proposed nano-alloying strategy provides a new route to improve the biocompatibility of biomedical nanoplatforms and endow them with versatile theranostic functions.

12.
Proc Natl Acad Sci U S A ; 118(28)2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34260393

RESUMO

Electrostimulation has been recognized as a promising nonpharmacological treatment in orthopedics to promote bone fracture healing. However, clinical applications have been largely limited by the complexity of equipment operation and stimulation implementation. Here, we present a self-powered implantable and bioresorbable bone fracture electrostimulation device, which consists of a triboelectric nanogenerator for electricity generation and a pair of dressing electrodes for applying electrostimulations directly toward the fracture. The device can be attached to irregular tissue surfaces and provide biphasic electric pulses in response to nearby body movements. We demonstrated the operation of this device on rats and achieved effective bone fracture healing in as short as 6 wk versus the controls for more than 10 wk to reach the same healing result. The optimized electrical field could activate relevant growth factors to regulate bone microenvironment for promoting bone formation and bone remodeling to accelerate bone regeneration and maturation, with statistically significant 27% and 83% improvement over the control groups in mineral density and flexural strength, respectively. This work provided an effective implantable fracture therapy device that is self-responsive, battery free, and requires no surgical removal after fulfilling the biomedical intervention.

13.
Adv Sci (Weinh) ; 8(10): 2001879, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34026426

RESUMO

Lymphoma is a heterogeneous disease with varying clinical manifestations and outcomes. Many subtypes of lymphoma, such as Burkitt's lymphoma and diffuse large B cell lymphoma, are highly aggressive with dismal prognosis even after conventional chemotherapy and radiotherapy. As such, exploring specific biomarkers for lymphoma is of high clinical significance. Herein, a potential marker, CD38, is investigated for differentiating lymphoma. A CD38-targeting monoclonal antibody (mAb, daratumumab) is then radiolabeled with Zr-89 and Lu-177 for theranostic applications. As the diagnostic component, the Zr-89-labeled mAb is highly specific in delineating CD38-positive lymphoma via positron emission tomography (PET) imaging, while the Lu-177-labeled mAb serves well as the therapeutic component to suppress tumor growth after a one-time administration. These results strongly suggest that CD38 is a lymphoma-specific marker and prove that 89Zr/177Lu-labeled daratumumab facilitates immunoPET imaging and radioimmunotherapy of lymphoma in preclinical models. Further clinical evaluation and translation of this CD38-targeted theranostics may be of significant help in lymphoma patient stratification and management.

14.
Int J Mol Sci ; 22(9)2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33946583

RESUMO

Molecular imaging of pathologic lesions can improve efficient detection of cancer and cardiovascular diseases. A shared pathophysiological feature is angiogenesis, the formation of new blood vessels. Endoglin (CD105) is a coreceptor for ligands of the Transforming Growth Factor-ß (TGF-ß) family and is highly expressed on angiogenic endothelial cells. Therefore, endoglin-based imaging has been explored to visualize lesions of the aforementioned diseases. This systematic review highlights the progress in endoglin-based imaging of cancer, atherosclerosis, myocardial infarction, and aortic aneurysm, focusing on positron emission tomography (PET), single-photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), near-infrared fluorescence (NIRF) imaging, and ultrasound imaging. PubMed was searched combining the following subjects and their respective synonyms or relevant subterms: "Endoglin", "Imaging/Image-guided surgery". In total, 59 papers were found eligible to be included: 58 reporting about preclinical animal or in vitro models and one ex vivo study in human organs. In addition to exact data extraction of imaging modality type, tumor or cardiovascular disease model, and tracer (class), outcomes were described via a narrative synthesis. Collectively, the data identify endoglin as a suitable target for intraoperative and diagnostic imaging of the neovasculature in tumors, whereas for cardiovascular diseases, the evidence remains scarce but promising.


Assuntos
Doenças Cardiovasculares/diagnóstico por imagem , Endoglina/análise , Neoplasias/diagnóstico por imagem , Animais , Doenças Cardiovasculares/cirurgia , Humanos , Imageamento por Ressonância Magnética/métodos , Neoplasias/cirurgia , Imagem Óptica/métodos , Tomografia por Emissão de Pósitrons/métodos , Cirurgia Assistida por Computador/métodos , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Ultrassonografia/métodos
15.
Am J Cancer Res ; 11(4): 1586-1599, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33948375

RESUMO

With advancement in antibody engineering, the development and characterization of new cancer-specific molecular targets are in the forefront of this PET-antibody combination "revolution". Overexpression of CD146 in different types of tumors, including breast tumor, has been associated with tumor progression and poor prognosis. Non-invasive detection of CD146 with a monoclonal antibody may provide a noninvasive diagnostic tool with high specificity and accountability. METHODS: Herein, we have developed a CD146-specific monoclonal antibody (YY146), radiolabeled it with 52Mn and 89Zr and identified its capability in acting as a non-invasive imaging agent that specific targets CD146 in different murine breast cancer models. CD146 expression was first screened in different breast tumor cell lines through Western Blot and confirmed its binding ability to YY146 using Flow Cytometry. Serial immunoPET images were carried out after intravenous administration of 52Mn or 89Zr labeled YY146. In addition, we also performed in vivo fluorescence imaging in animals injected with YY146 conjugated with Cy5.5. RESULTS: Western Blot results show that MDA-MB-435 cell line had greater levels of CD146 expression when compared to the other cell lines investigated. Flow cytometry confirmed binding ability of YY146. PET images revealed well correlated uptake between tumor uptake and CD146 expression levels, confirmed by biodistribution studies and fluorescence imaging. CONCLUSION: PET imaging, for up to 7 days, of mice bearing three different breast tumors were carried out and revealed radiotracer uptake in tumors that strongly (r2 = 0.98, P < 0.01), correlated with CD146 expression levels, as confirmed by in vitro and ex vivo studies.

17.
Nano Lett ; 21(11): 4692-4699, 2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-34029471

RESUMO

Theranostic nanoparticles hold the potential to greatly improve cancer management by providing personalized medicine. Although many theranostic nanoconstructs have been successful in preclinical studies, clinical translation is still hampered by their limited targeting capability and lack of successful therapeutic efficacy. We report the use of novel ultrasmall porous silica nanoparticles (UPSN) with enhanced in vivo pharmacokinetics such as high target tissue accumulation (12% ID/g in the tumor) and evasion from the reticuloendothelial system (RES) organs. Herein, UPSN is conjugated with the isotopic pair 90/86Y, enabling both noninvasive imaging as well as internal radiotherapy. In vivo PET imaging demonstrates prolonged blood circulation and excellent tumor contrast with 86Y-DOTA-UPSN. Tumor-to-muscle and tumor-to-liver uptake values were significantly high (12.4 ± 1.7 and 1.5 ± 0.5, respectively), unprecedented for inorganic nanomaterials. 90Y-DOTA-UPSN significantly inhibits tumor growth and increases overall survival, indicating the promise of UPSN for future clinical translation as a cancer theranostic agent.


Assuntos
Nanopartículas , Neoplasias , Linhagem Celular Tumoral , Humanos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Porosidade , Medicina de Precisão , Dióxido de Silício
18.
J Nanobiotechnology ; 19(1): 107, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33858424

RESUMO

BACKGROUND: Nonspecific liver uptake of nanomaterials after intravenous injection has hindered nanomedicine for clinical translation. However, nanomaterials' propensity for liver distribution might enable their use in hepatic ischemia-reperfusion injury (IRI) repair. During hepatic IRI, reactive oxygen species (ROS) are generated and the fifth component of complement (C5a) is activated. In addition, C5a is confirmed to exacerbate the vicious cycle of oxidative stress and inflammatory damage. For these reasons, we have investigated the development of nanomaterials with liver uptake to scavenge ROS and block C5a for hepatic IRI repair. RESULTS: To achieve this goal, a traditional nanoantioxidant of nanoceria was surface conjugated with the anti-C5a aptamers (Ceria@Apt) to scavenge the ROS and reduce C5a-mediated inflammation. High uptake of Ceria@Apt in the liver was confirmed by preclinical positron emission tomography (PET) imaging. The clinical symptoms of hepatic IRI were effectively alleviated by Ceria@Apt with ROS scavenging and C5a blocking in mice model. The released pro-inflammatory cytokines were significantly reduced, and subsequent inflammatory reaction involved in the liver was inhibited. CONCLUSIONS: The synthesized Ceria@Apt has great potential of medical application in hepatic IRI repair, which could also be applied for other ischemic-related diseases.


Assuntos
Antioxidantes/metabolismo , Antioxidantes/farmacologia , Complemento C5a/metabolismo , Fígado/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Animais , Cério , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Inflamação , Mediadores da Inflamação/metabolismo , Mediadores da Inflamação/farmacologia , Isquemia , Fígado/patologia , Camundongos , Nanomedicina , Estresse Oxidativo/efeitos dos fármacos , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/patologia
19.
Eur J Nucl Med Mol Imaging ; 48(9): 2737-2748, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33537836

RESUMO

PURPOSE: We dual-labeled an intercellular adhesion molecule-1 (ICAM-1) monoclonal antibody (mAb) and evaluated its effectiveness for lesion detection and surgical navigation in pancreatic ductal adenocarcinoma (PDAC) via multiple noninvasive imaging approaches, including positron emission tomography (PET), near-infrared fluorescence (NIRF), and Cerenkov luminescence imaging (CLI). METHODS: ICAM-1 expression in PDAC cell lines (BxPC-3 and AsPC-1) was assessed via flow cytometry and immunofluorescent staining. An ICAM-1 mAb labeled by IRDye 800CW and radionuclide zirconium-89 (denoted as [89Zr]Zr-DFO-ICAM-1-IR800) was synthesized. Its performance was validated via in vivo comparative PET/NIRF/CLI and biodistribution (Bio-D) studies in nude mice bearing subcutaneous BxPC-3/AsPC-1 tumors or orthotopic BxPC-3 tumor models using nonspecific IgG as an isotype control tracer. RESULTS: ICAM-1 expression was strong in the BxPC-3 and minimal in the AsPC-1 cell line. Both multimodality imaging and Bio-D data exhibited more prominent uptake of [89Zr]Zr-DFO-ICAM-1-IR800 in BxPC-3 tumors than in AsPC-1 tumors. The uptake of [89Zr]Zr-DFO-IgG-IR800 in BxPC-3 tumors was similar to that of [89Zr]Zr-DFO-ICAM-1-IR800 in AsPC-1 tumors. These results demonstrate the desirable affinity and specificity of [89Zr]Zr-DFO-ICAM-1-IR800 compared to [89Zr]Zr-DFO-IgG-IR800. Orthotopic BxPC-3 tumor foci could also be clearly delineated by [89Zr]Zr-DFO-ICAM-1-IR800. An intermodal match was achieved in the ICAM-1-targeted immunoPET/NIRF/CLI. The positive expression levels of ICAM-1 in BxPC-3 tumor tissue were further confirmed by immunohistopathology. CONCLUSION: We successfully developed a dual-labeled ICAM-1-targeted tracer for PET/NIRF/CLI of PDAC that can facilitate better diagnosis and intervention of PDAC upon clinical translation.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Animais , Carcinoma Ductal Pancreático/diagnóstico por imagem , Linhagem Celular Tumoral , Molécula 1 de Adesão Intercelular , Camundongos , Camundongos Nus , Neoplasias Pancreáticas/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Distribuição Tecidual , Zircônio
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