Resultados totales (Incluyendo duplicados): 45302
Encontrada(s) 4531 página(s)
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351949
Dataset. 2023

SUPPLEMENTARY MATERIAL: MONITORING OF KINETICS AND EXHAUSTION MARKERS OF CIRCULATING CAR-T CELLS AS EARLY PREDICTIVE FACTORS IN PATIENTS WITH B-CELL MALIGNANCIES

  • García-Calderón, Clara B.
  • Sierro-Martínez, Belén
  • García-Guerrero, Estefanía
  • Sanoja-Flores, Luzalba
  • Muñoz García, Raquel
  • Ruiz-Maldonado, Victoria
  • Jiménez-León, María Reyes
  • Delgado-Serrano, Javier
  • Molinos-Quintana, A.
  • Guijarro-Albaladejo, Beatriz
  • Carrasco-Brocal, Inmaculada
  • Lucena-Soto, José Manuel
  • García-Lozano, José Raúl
  • Blázquez-Goñi, Cristina
  • Reguera-Ortega, Juan Luis
  • González-Escribano, María Francisca
  • Reinoso-Segura, Marta
  • Briones, Javier
  • Pérez-Simón, José A.
  • Caballero-Velázquez, Teresa
Supplementary Figures: Supplementary Figure 1. Evaluation of the specificity of the detection reagents for the identification of academic CAR-T cells by flow cytometry.-- Supplementary figure 2. Evaluation of the specificity of the detection reagents for the identification of commercial CAR-T cells by flow cytometry.-- Supplementary Figure 3. Commercial CD19 CAR-T cell expansion in the blood of patients with lymphoma.-- Supplementary Figure 4. Comparison of the expansion dynamics of different commercial CD19 CAR-T cell products.-- Supplementary Figure 5. Immunophenotype characterization of non-modified T cells and CAR-T cells at the time of peak expansion in blood of patients with lymphoma.-- Supplementary Figure 6. Immunophenotype characterization of non-modified T cells and CAR-T cells at the time of peak expansion in blood of patients infused with Tisa-cel vs Axi-cel.-- Supplementary Figure 7. Comparison of T cell subsets between leukapheresis and non-modified T and CAR-T cells at the time of peak expansion.-- Supplementary Figure 8. Quantitative determination of the TCR Vβ repertoire of human T lymphocytes by flow cytometry.-- Supplementary Figure 9. Correlation between CAR-T cell expansion in blood of patients with lymphoma and toxicity or response.-- Supplementary Figure 10. Comparison of the toxicity and efficacy of Tisa-cel and Axi-cel products. // Supplementary Table 1. Flow cytometry reagents for the validation of the detection and immune-phenotype characterization of academic and commercial CD19 CAR-T cells, Purpose: CAR-T cell therapy has proven to be a disruptive treatment in the hematology field, however, less than 50% of patients maintain long-term response and early predictors of outcome are still inconsistently defined. Here, we aimed to optimize the detection of CD19 CAR-T cells in blood and to identify phenotypic features as early biomarkers associated with toxicity and outcomes., Experimental design: In this study, monitoring by flow cytometry and digital PCR (dPCR), and immunophenotypic characterization of circulating CAR-T cells from 48 patients treated with Tisa-cel or Axi-cel was performed., Results: Validation of the flow cytometry reagent for the detection of CAR-T cells in blood revealed CD19 protein conjugated with streptavidin as the optimal detection method. Kinetics of CAR-T cell expansion in blood confirmed median day of peak expansion at seven days post-infusion by both flow cytometry and digital PCR. Circulating CAR-T cells showed an activated, proliferative, and exhausted phenotype at the time of peak expansion. Patients with increased expansion showed more severe CRS and ICANs. Immunophenotypic characterization of CAR-T cells at the peak expansion identified the increased expression of co-inhibitory molecules PD1 and LAG3 and reduced levels of the cytotoxicity marker CD107a as predictors of a better long-term disease control., Conclusions: These data show the importance of CAR-T cells in vivo monitoring and identify the expression of PD1LAG3 and CD107a as early biomarkers of long-term disease control after CAR-T cell therapy., This work has been supported by the Instituto de Salud Carlos III (ISCIII), Project RD21/0017/0021, Red Española de Terapias Avanzadas TERAV funded by European Union-NextGenerationEU. “Plan de Recuperación Transformación y Resiliencia” and Consejería de Salud y Familia, Junta de Andalucía PECART-0185-2020-7, PECART-0185-2020 CSYF 2021 – Proyectos Fondos FEDER. Proyectos estratégicos en Investigación en CAR-T. “Monitorización inmune tras tratamiento con células CAR-T: búsqueda de biomarcadores y medición de la actividadmetabólica como predictores de respuesta”., Peer reviewed

Proyecto: //
DOI: http://hdl.handle.net/10261/351949
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351949
HANDLE: http://hdl.handle.net/10261/351949
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351949
PMID: http://hdl.handle.net/10261/351949
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351949
Ver en: http://hdl.handle.net/10261/351949
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351949

Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351951
Dataset. 2023

SUPPLEMENTARY FILES OF THE ARTICLE TISSUE-SPECIFIC CHROMATIN-BINDING PATTERNS OF CAENORHABDITIS ELEGANS HETEROCHROMATIN PROTEINS HPL-1 AND HPL-2 REVEAL DIFFERENTIAL ROLES IN THE REGULATION OF GENE EXPRESIÓN (DATASET)

  • Cruz, Patricia de la
  • Rodríguez-Palero, María Jesús
  • Askjaer, Peter
  • Artal-Sanz, Marta
Supplementary_File_1_HP1_peaks Supplementary_File_2_HP1_gene_tissues Supplementary_File_3_Overlapping between HP1 bound genes with tissue-specific genes Supplementary_File_4_Overlapping between tissue-specific genes bound by HP1 proteins Supplemental Figures and Tables, Peer reviewed

Proyecto: //
DOI: http://hdl.handle.net/10261/351951
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351951
HANDLE: http://hdl.handle.net/10261/351951
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351951
PMID: http://hdl.handle.net/10261/351951
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351951
Ver en: http://hdl.handle.net/10261/351951
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351951

Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351957
Dataset. 2023

PBIO.3002315.T002 - LINEAGE TRACING IDENTIFIES HETEROGENEOUS HEPATOBLAST CONTRIBUTION TO CELL LINEAGES AND POSTEMBRYONIC ORGAN GROWTH DYNAMICS [DATASET]

  • Unterweger, Iris. A.
  • Klepstad, Julie
  • Hannezo, Edouard
  • Lundegaard, Pia R.
  • Trusina, Ala
  • Ober, Elke A.
pbio.3002315.t002 - Lineage tracing identifies heterogeneous hepatoblast contribution to cell lineages and postembryonic organ growth dynamics, Peer reviewed

Proyecto: //
DOI: http://hdl.handle.net/10261/351957
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351957
HANDLE: http://hdl.handle.net/10261/351957
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351957
PMID: http://hdl.handle.net/10261/351957
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351957
Ver en: http://hdl.handle.net/10261/351957
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351957

Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351958
Dataset. 2023

PBIO.3002315.T001 - LINEAGE TRACING IDENTIFIES HETEROGENEOUS HEPATOBLAST CONTRIBUTION TO CELL LINEAGES AND POSTEMBRYONIC ORGAN GROWTH DYNAMICS [DATASET]

  • Thomas, Laura
  • Taleb Ismail, Basma
  • Askjaer, Peter
  • Seydoux, Geraldine
pbio.3002315.t001 - Lineage tracing identifies heterogeneous hepatoblast contribution to cell lineages and postembryonic organ growth dynamics, Peer reviewed

Proyecto: //
DOI: http://hdl.handle.net/10261/351958
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351958
HANDLE: http://hdl.handle.net/10261/351958
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351958
PMID: http://hdl.handle.net/10261/351958
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351958
Ver en: http://hdl.handle.net/10261/351958
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351958

Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351959
Dataset. 2023

WORKING MODEL OF HEPATOBLAST CONTRIBUTION TO LINEAGE DECISION AND POSTEMBRYONIC GROWTH [DATASET]

  • Thomas, Laura
  • Taleb Ismail, Basma
  • Askjaer, Peter
  • Seydoux, Geraldine
Schematics showing the current working models: (A) uni- and bipotent hepatoblast contributions to hepatocytes and BECs following heterogeneous lineage decisions. (B) Hepatoblasts contribute with heterogeneous proliferation behaviours to postembryonic liver growth. Cells from the embryonic left lobe contribute to the ventral lobe, including the formation of giant clusters (magenta). (C) The liver morphology changes dramatically simultaneous to the intestinal bending occurring during postembryonic growth (green). BEC, biliary epithelial cell; dpf, day postfertilization; SL, standard length., Peer reviewed

Proyecto: //
DOI: http://hdl.handle.net/10261/351959
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351959
HANDLE: http://hdl.handle.net/10261/351959
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351959
PMID: http://hdl.handle.net/10261/351959
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351959
Ver en: http://hdl.handle.net/10261/351959
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351959

Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351960
Dataset. 2023

VENTRAL LIVER LOBE FORMATION DURING POSTEMBRYONIC GROWTH [DATASET]

  • Thomas, Laura
  • Taleb Ismail, Basma
  • Askjaer, Peter
  • Seydoux, Geraldi
(A) The 6 steps of ventral liver lobe formation correlate with fish standard length (SL). The numerical values that were used to generate the graph can be found in S1 Data. (B) Stage I: A small tissue extension at the tip of the left lobe is visible (n = 12 livers). (C) Stage II: a thin ventral lobe originates in the lower half of the left lobe (n = 6 livers). (D) Stage III: the thin ventral lobe shifts position towards the more anterior part of the left lobe (n = 4 livers). (E) Stage IV: the tip of the ventral lobe starts to expand (n = 7 livers). (F) Stage V: lateral-oriented expansion of the ventral lobe (n = 28 livers). (G) Stage VI: enlargement of all lobes in width (n = 6 livers). The blue areas in the schematics mark the region characteristic for the respective stage. (H) Schematic depicting the morphology of the liver in relation to the folding of the intestine in stages I-VI. A, anterior; P, posterior; R, right; L, left; RL, right lobe; LL, left lobe; VL, ventral lobe., Peer reviewed

Proyecto: //
DOI: http://hdl.handle.net/10261/351960
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351960
HANDLE: http://hdl.handle.net/10261/351960
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351960
PMID: http://hdl.handle.net/10261/351960
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351960
Ver en: http://hdl.handle.net/10261/351960
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351960

Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351961
Dataset. 2023

POLYPLOID CELLS APPEAR TRANSIENTLY IN HEPATIC POSTEMBRYONIC GROWTH IN ZEBRAFISH [DATASET]

  • Thomas, Laura
  • Taleb Ismail, Basma
  • Askjaer, Peter
  • Seydoux, Geraldine
(A) Whole-mount of a 14-dpf zebrafish liver, displaying sparse multinucleated hepatocytes (N = 1, n = 2 livers; yellow arrowheads indicate binucleated cells). (B) Approximately 5 μm projection of a region of a juvenile liver. Fish SL = 11.16 mm (N = 3, n = 6 livers). (C) Segmentation shows variable nuclear volumes, which correlate with the sum intensity of DAPI, indicating that bigger nuclei have a higher amount of DNA (D). (E) Approximately 5 μm projection of an adult liver region (N = 3, n = 3 livers). (F) Segmented nuclei show only sparse variability in volume, with few bigger nuclei. Nuclear volume correlates with sum intensity of DAPI (G). (H) Schematics representing the transient appearance of polyploid cells over time; blue trajectory is manually approximated based on qualitative analysis. The numerical values that were used to generate the graphs in (D, G, H) can be found in S1 Data. DAPI, 4′,6-diamidino-2-phenylindole; dpf, day postfertilization; SL, standard length., Peer reviewed

Proyecto: //
DOI: http://hdl.handle.net/10261/351961
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351961
HANDLE: http://hdl.handle.net/10261/351961
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351961
PMID: http://hdl.handle.net/10261/351961
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351961
Ver en: http://hdl.handle.net/10261/351961
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351961

Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351962
Dataset. 2023

ADDITIONAL FILE FOR: MONOCYTE-DERIVED CELLS INVADE BRAIN PARENCHYMA AND AMYLOID PLAQUES IN HUMAN ALZHEIMER’S DISEASE HIPPOCAMPUS

  • Muñoz-Castro, Clara
  • Mejías-Ortega, Marina
  • Sánchez-Mejias, Elisabeth
  • Navarro, Victoria
  • Trujillo-Estrada, Laura
  • Jiménez, Sebastián
  • García-León, Juan Antonio
  • Fernández-Valenzuela, Juan J.
  • Sánchez-Mico, María V.
  • Romero-Molina, Carmen
  • Moreno-González, Inés
  • Baglietto-Vargas, David
  • Vizuete, Marisa
  • Gutiérrez, Antonia
  • Vitorica, Javier
© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data., Additional figures (S1-S7) and tables (S1-S2)., Microglia are brain-resident myeloid cells and play a major role in the innate immune responses of the CNS and the pathogenesis of Alzheimer's disease (AD). However, the contribution of nonparenchymal or brain-infiltrated myeloid cells to disease progression remains to be demonstrated. Here, we show that monocyte-derived cells (MDC) invade brain parenchyma in advanced stages of AD continuum using transcriptional analysis and immunohistochemical characterization in post-mortem human hippocampus. Our findings demonstrated that a high proportion (60%) of demented Braak V–VI individuals was associated with up-regulation of genes rarely expressed by microglial cells and abundant in monocytes, among which stands the membrane-bound scavenger receptor for haptoglobin/hemoglobin complexes or Cd163. These Cd163-positive MDC invaded the hippocampal parenchyma, acquired a microglial-like morphology, and were located in close proximity to blood vessels. Moreover, and most interesting, these invading monocytes infiltrated the nearby amyloid plaques contributing to plaque-associated myeloid cell heterogeneity. However, in aged-matched control individuals with hippocampal amyloid pathology, no signs of MDC brain infiltration or plaque invasion were found. The previously reported microglial degeneration/dysfunction in AD hippocampus could be a key pathological factor inducing MDC recruitment. Our data suggest a clear association between MDC infiltration and endothelial activation which in turn may contribute to damage of the blood brain barrier integrity. The recruitment of monocytes could be a consequence rather than the cause of the severity of the disease. Whether monocyte infiltration is beneficial or detrimental to AD pathology remains to be fully elucidated. These findings open the opportunity to design targeted therapies, not only for microglia but also for the peripheral immune cell population to modulate amyloid pathology and provide a better understanding of the immunological mechanisms underlying the progression of AD., This study was supported by Instituto de Salud Carlos III (ISCiii) of Spain, co-financed by FEDER funds from European Union, through grants PI18/01556 and PI21/00914 (to JV) and PI18/01557 and PI21/00915 (to AG); by Junta de Andalucia Consejería de Economía y Conocimiento through grants US-1262734 and P20-00843 (to JV), UMA18-FEDERJA-211 (to AG) and PI18-RT-2233 (to AG) co-financed by Programa Operativo FEDER 2014-2020; by Spanish Minister of Science and Innovation grant PID2019-108911RA-100 (to DBV), Beatriz Galindo Program BAGAL18/00052 (to DBV), grant PID2019-107090RA-I00 (to IMG) and Ramon y Cajal Program RYC-2017-21879 (to IMG); and by Malaga University grant B-2019_06 (to ESM)., Peer reviewed

DOI: http://hdl.handle.net/10261/351962
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351962
HANDLE: http://hdl.handle.net/10261/351962
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351962
PMID: http://hdl.handle.net/10261/351962
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351962
Ver en: http://hdl.handle.net/10261/351962
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351962

Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351963
Dataset. 2023

ASSESSMENT OF POST-INFARCT VENTRICULAR SEPTAL DEFECTS THROUGH 3D PRINTING AND STATISTICAL SHAPE ANALYSIS: SUPPLEMENTARY TABLE

  • Asif, Ashar
  • Shearn, Andrew I. U.
  • Turner, Mark S.
  • Ordoñez, María V.
  • Sophocleous, Froso
  • Méndez-Santos, Ana
  • Valverde, Israel
  • Angelini, Gianni D.
  • Caputo, Massimo
  • Hamilton, Mark C. K.
  • Biglino, Giovanni
Table 1: Examples of feedback from clinicians in relation to dominant themes from analysis of model evaluation., Background: Post-infarct ventricular septal defect (PIVSD) is a serious complication of myocardial infarction. We evaluated 3D-printing models in PIVSD clinical assessment and the feasibility of statistical shape modeling for morphological analysis of the defects. Methods: Models (n = 15) reconstructed from computed tomography data were evaluated by clinicians (n = 8). Statistical shape modeling was performed on 3D meshes to calculate the mean morphological configuration of the defects. Results: Clinicians’ evaluation highlighted the models’ utility in displaying defects for interventional/surgical planning, education/training and device development. However, models lack dynamic representation. Morphological analysis was feasible and revealed oval-shaped (n = 12) and complex channel-like (n = 3) defects. Conclusion: 3D-PIVSD models can complement imaging data for teaching and procedural planning. Statistical shape modeling is feasible in this scenario., The authors gratefully acknowledge the support of the British Heart Foundation (CH/17/1/32804), the Bristol BHF Accelerator Award (AA/18/1/34219), The Grand Appeal (Bristol Children’s Hospital Charity), and the Bristol National Institute for Health Research (NIHR) Biomedical Research Centre (BRC). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed., Peer reviewed

Proyecto: //
DOI: http://hdl.handle.net/10261/351963
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351963
HANDLE: http://hdl.handle.net/10261/351963
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351963
PMID: http://hdl.handle.net/10261/351963
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351963
Ver en: http://hdl.handle.net/10261/351963
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351963

Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351973
Dataset. 2023

LINEAGE TRACING REVEALS HETEROGENEOUS CLUSTER TOPOLOGIES DURING POSTEMBRYONIC GROWTH [DATASET]

  • Unterweger, Iris. A.
  • Klepstad, Julie
  • Hannezo, Edouard
  • Lundegaard, Pia R.
  • Trusina, Ala
  • Ober, Elke A.
(A) Schematic depicting key stages in postembryonic zebrafish liver development. (B) Experimental schematics of long-term lineage tracing experiments using fraeppli-nls embryos, inducing recombination by heat shock at 26 hpf to label hepatoblasts. At 120 hpf, embryos were screened by live imaging at the confocal microscope, and only sparsely labelled embryos were raised and fixed in either juvenile or adult stages. (C-H) Recombined livers showed different cluster topologies: clusters along central veins (C-C’) (n = 9 livers), proximal–distal stripes (D) (n = 23 livers) or giant clusters in the ventral lobe in adult (F-G’) (n = 3 livers). Large clusters in the ventral lobe can originate from one single-labelled cell at 5 dpf (n = 1 liver) (E). (F) Stereomicroscope image showing the spatial location of the giant clone originating from a single recombined cell (H). Recombined livers show a range of cluster sizes from small (H’) to medium (H”). (I) Schematics of characteristic cluster topologies in recombined livers. Red lines indicate the blood vessel orientation in the liver. (C-H) Total numbers are (N = 9, n = 79 livers). A, anterior; P, posterior; R, right; L, left; RL, right lobe; LL, left lobe; VL, ventral lobe., Peer reviewed

Proyecto: //
DOI: http://hdl.handle.net/10261/351973
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351973
HANDLE: http://hdl.handle.net/10261/351973
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351973
PMID: http://hdl.handle.net/10261/351973
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351973
Ver en: http://hdl.handle.net/10261/351973
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/351973

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