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Posts Taged drug-delivery

1st Forum of CIBER-BBN/NANBIOSIS and CSIC Nanomed Conection researchers

The Nanomed Conection of the Spanish Research Council (CSIC) and the Networking Biomedical Research Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), together with its singular infrastructure NANBIOSIS, have organised a Forum on Nanomedicine Research during the days 30 of June and 1st of July to be held at the Institute of Advanced Chemistry of Catalonia (IQAC-CSIC) in Barcelona. The event will be also transmitted on-line previous registration.

This is the first meeting gathering together scientists from CIBER-BBN and its ICTS NANBIOSIS and from the CSIC’ Nanomed Conection with a shared interest in Nanomedicine.

This two days meeting will allow researchers to present their works in progress, share their scientific concerns and needs and discuss the impact of nanomedicine in the emerging fields of drug delivery, diagnosis and therapy.

The programe, available in the web of the forum includes these sessions:

  • Nanobiotechnological solutions for diagnosis and therapy
  • Drug delivery nanosystems
  • Applications for oncology (I and II)
  • Nanomedicine & other frontier applications

Attendance to the Forum (in person / or online) is free prior registration in the web of the forum (following this link):

Registration will remain open until June 26.
We hope to see you there!

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Women in the fight against breast cancer: Ibane Ibasolo

The International Day of Women and Girls in Science on February 11 honor women’s significant achievements in science and place a much-needed focus on girls entering Science, Technology, Engineering, and Mathematics (STEM) careers.

We want to take this day to congratulate all the women scientists, especially our scientists at NANBIOSIS ICTS. Some of them take an active role in the dissemination of research results and reseach contribution to the society, as Dr. Ibane Abasolo who last week participated in different events to explain her team work in the figth against breast cancer.

Ibane Abasolo is the Scientific Coordinator of NANBIOSIS U20 and also the leader of the Drug Delivery & Targeting group of the CIBER-BBN at the Vall d’Hebron Research Institute (VHIR) which coordinates the unit 20 of NANBIOSIS, a team composed mainly by women.

The group cooworks to improve cancer treatment through the development of nanoparticles specially directed towards breast cancer stem cells. These cells are the ones that, despite dividing slowly, give rise to the differentiation of the rest of the tumor cells and are also the most resistant to conventional antitumor treatments.

That is why the group seeks to attack these cells in three ways:

i) selected drugs that induce the differentiation of tumor stem cells into more differentiated cells (and easier to treat),

2) using mechanisms to evade the efflux pumps of drugs and

3) targeting the nanoparticles specifically towards tumor stem cells by using targeting agents (ie antibodies) against antigens on the surface of tumor stem cells.

Dr. Abasolo has illustrated these three approaches by citing papers published in her group during 2021, in which the ICTS Nanbiosis U20 has also directly participated:

Gustavo Carreño, Alfredo Pereira, Fabián Ávila-Salas, Adolfo Marican, Fernanda Andrade, Maria Mercé Roca-Melendres, Oscar Valdés, Sekar Vijayakumar, Simó Schwartz, Ibane Abasolo, Diana Rafael, Esteban F. Durán-Lara, Development of “on-demand” thermo-responsive hydrogels for anti-cancer drugs sustained release: Rational design, in silico prediction and in vitro validation in colon cancer models, Materials Science and Engineering: C, Volume 131, 2021, 112483, ISSN 0928-4931, https://doi.org/10.1016/j.msec.2021.112483.

Yolanda Fernández, Julie Movellan,Laia Foradada, Vanessa Giménez, Natalia García-Aranda, Sandra Mancilla, Ana Armiñán, Sven Even Borgos, Astrid Hyldbakk, Anna Bogdanska, Oliviero L. Gobbo, Adriele Prina-Mello, Jessica Ponti, Luigi Calzolai, Oleksandr Zagorodko, Elena Gallon, Amaya Niño-Pariente, Alison Paul, Simó Schwartz Jr, Ibane Abasolo, María J. Vicent In Vivo Antitumor and Antimetastatic Efficacy of a Polyacetal-Based Paclitaxel Conjugate for Prostate Cancer Therapy. Adv Healthc Mater. 2021 Oct 27;e2101544. doi: 10.1002/adhm.202101544.

Diana Rafael, Maria Mercè Roca Melendres, Fernanda Andrade, Sara Montero, Francesc Martinez-Trucharte, Mireia Vilar-Hernandez, Esteban Francisco Durán-Lara, Simó Schwartz Jr, Ibane Abasolo,
Thermo-responsive hydrogels for cancer local therapy: Challenges and state-of-art, International Journal of Pharmaceutics, Volume 606, 2021,
120954, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2021.120954.

Marwa M Abu-Serie , Fernanda Andrade, Patricia Cámara-Sánchez, Joaquin Seras-Franzoso, Diana Rafael, Zamira V Díaz-Riascos, Petra Gener, Ibane Abasolo, Simó Schwartz Jr Pluronic F127 micelles improve the stability and enhance the anticancer stem cell efficacy of citral in breast cancer. Nanomedicine VOL. 16, NO. 17. 2021 Jul;16(17):1471-1485. doi: 10.2217/nnm-2021-0013.

Eva Espinosa-Cano, Miguel Huerta-Madroñal, Patricia Cámara-Sánchez, Joaquin Seras-Franzoso, Simo Schwartz, Ibane Abasolo, Julio San Román, Maria Rosa Aguilar, Hyaluronic acid (HA)-coated naproxen-nanoparticles selectively target breast cancer stem cells through COX-independent pathways, Materials Science and Engineering: C, Volume 124, 2021, 112024, ISSN 0928-4931, https://doi.org/10.1016/j.msec.2021.112024.

Fernanda Andrade, Diana Rafael, Mireia Vilar-Hernández, Sara Montero, Francesc Martínez-Trucharte, Joaquin Seras-Franzoso, Zamira V. Díaz-Riascos, Ana Boullosa, Natalia García-Aranda, Patricia Cámara-Sánchez, Diego Arango, Marika Nestor, Ibane Abasolo, Bruno Sarmento, Simó Schwartz, Polymeric micelles targeted against CD44v6 receptor increase niclosamide efficacy against colorectal cancer stem cells and reduce circulating tumor cells in vivo, Journal of Controlled Release, Volume 331, 2021, 198-212, ISSN 0168-3659, https://doi.org/10.1016/j.jconrel.2021.01.022.

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Best Emergeging Researcher Award in the Biomedical Area to Edorta Santos

Edorta Santos Vizcaíno has been awarded as Best Emerging Researcher in the biomedical area by the Bioaraba Health Research Institute in the XXII edition of the Research and Innovation Conference.

This award aims to recognize the work of researchers under the age of 40 who carry out their research activity in any public center of the Araba Health Network (OSI ARABA UNIVERSITY HOSPITAL / BIOARABA). The main award´’s criteria are the quality of the research carried out, active participation in public and private research projects, fidelity to the line of biomedical research and the usefulness and interest of the research developed for the environment are valued. The award also carries a financial endowment destined to continue promoting the research career of the awarded person.

Edorta Santos Vizcaíno (NANBIOSIS Unit 10 “Drug Formulation”) has a degree in Biochemistry and a doctorate in Pharmacy, with an international mention and an extraordinary award, from the UPV / EHU. He has been part of the research group NanoBioCel of the UPV / EHU, Consolidated Group of Excellence of the Basque university system, since 2006. In the same way, he is a member of the Center for Biomedical Research in Network for Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), a consortium dependent on the Carlos III Health Institute through the Ministry of Science and Innovation, and the Bioaraba Health Research Institute. Edorta has extensive experience in cell therapy and drug delivery systems. During the last years, his research has focused on the biomedical application of different biomaterials (for example, alginate, gelatin, collagen), mesenchymal stem cells (MSC) and their secretome (extracellular vesicles and soluble factors), in order to exert a immunomodulatory and regenerative effect in the treatment of immune-mediated inflammatory diseases (for example, inflammatory bowel disease, IBD) and the regeneration of chronic wounds, among other applications.

Bioaraba‘s mission is to develop research and innovation of excellence and quality that allows the translation of its results aimed at solving the health problems of the population, also promoting scientific research and for this, it annually carries out the Research and Innovation Conference.

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Study of new liposomes for the delivery of enzymes through biological membranes

Judit Tomsen, researcher at Nanomol Group – NANBIOSIS U6 (ICMAB-CSIC and CIBER-BBN)  will defend her PhD thesis on Thursday, 15 July 2021, at 11 am in an hybrid session, from the ICMAB Seminar Room “Carles Miravitlles”. 

Further information and Registration to attend the PhD Thesis defense via Zoom  at ICMAB-website.

Supervisors:

Nora Ventosa (Scientific Director of NANBIOSIS U6 Biomaterial Processing and Nanostructuring Unit and leader of Nanomol Group of CIBER-BBN- ICMAB-CSIC

Elisabet González, Nanomol Group of CIBER-BBN – ICMAB-CSIC

Abstract: Liposomes are lipid-based nanovesicles widely explored as nanocarriers for the transport of biomolecules or drugs of interest to the place of action, and for the development of new nanomedicines. This Thesis is devoted to the study of liposomal systems functionalized with targeting-ligands, with the final goal to be used as nanocarriers of therapeutically active enzymes. The new liposomal formulations have been specifically investigated and developed for the effective transportation of α-galactosidase A enzyme through cellular and blood-brain membranes, and for the achievement of a new liposomal intravenous pharmaceutical product candidate (nanoGLA) for the treatment of Fabry disease. The achieved results support the strong potential of targeted liposomal systems for drug delivery application. The successful development and optimization of the nanoGLA product for improving the current enzymatic replacement therapy in Fabry disease especially contributes as an example of translational and interdisciplinary research.

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Identification of a novel nanotherapy active in cancer cells resistant to chemotherapy

Researchers of the Nanotoxicology Unit (u18-nanotoxicology-unit) led by Ramon Mangues and Isolda Casanova at the Research Institute of the Hospital de Sant Pau and the Protein Production Platform (u1-protein-production-platform-ppp), led by Antonio Villaverde and Neus Ferrer Miralles of the Institute of Biotechnology and Biomedicine at the Autonomous University of Barcelona, both belonging to the ICTS NANBIOSIS (nanbiosis.es) of the CIBER-BBN, have participated in the production of a novel Nanotoxin capable of selectively killing cancer cells which became resistant to chemotherapy. Development of cancer resistance frequently associates with the overexpression of the CXCR4 receptor.

It is known that chemotherapy kills cancer cells, mainly, by induction of apoptosis, after damaging the cell DNA; therefore, to survive resistant cancer cells develop anti-apoptotic mechanisms. In contrast, a Nanotoxin that has incorporated the exotoxin of Corynebacterium diphtheriae and a targeted ligand that selectively internalizes in CXCR4+ cancer cells, exploits a mechanism of cell death alternative to apoptosis, thus, effectively killing resistant cancer cells in a colorectal cancer model.  The new mechanism is the induction of a blockade of protein translation, by inhibition of the elongation factor 2, which renders sensitive to therapy cancer cells resistant to chemotherapy.

The described work opens a new avenue for the exploration of antitumor activity in cancer that relapses after current therapy, an unmet medical need in oncology, and therefore, it could have an important impact in cancer patient well being.

Reference:

Naroa Serna, Patricia Álamo, Prashanthi Ramesh, Daria Vinokurova, Laura Sánchez-García, Ugutz Unzueta, Alberto Gallardo, María Virtudes Céspedes, Esther Vázquez, Antonio Villaverde, Ramón Mangues, Jan Paul Medema. Nanostructured toxins for the selective destruction of drug-resistant human CXCR4 + colorectal cancer stem cells. doi: 10.1016/j.jconrel.2020.01.019.

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New patented peptide to allows the faster internalization of drugs within cells and the design of more effective therapeutic nanoconjugates

Researchers of NANBIOSIS Unit 20 In vivo Experimental Platform of CIBER-BBN and Vall d’Hebron Research Institute (VHIR) have patented a peptide that, in comparison to the current standard treatment, is much faster, internalizes much more, and does not cause any toxicity.

The membrane of a cell is an effective barrier that hinders the targeted delivery of molecules, such as therapeutic compounds. During the last years, several strategies have been developed to get the molecules into the cell interior but, in general, the methods developed still show a low efficacy and / or toxicity. “The use of therapeutic nanoconjugates such as nanomedicines facilitates the transport and delivery of drugs in target cells, but often with less efficiency than we would like,” says Dr Simó Schwart Jr, head of the Scientific Director of NANBIOSIS Unit 20 and the CIBBIM-Nanomedicine group: Direction i Alliberament Farmacològic del Vall d’Hebron Research Institute (VHIR)/CIBER-BBN.

Given the need to get more drugs or proteins into cells, one of the alternatives to be able to increase the amount that enters their interior more quickly is what is known as Cell penetrating peptides or cellular internalizing peptides, small sequences of amino acids that have the ability to interact with the plasma membranes of cells and, as a result of this interaction, make it easier to internalize the cargo they carry. An example of application would be when an internalizing peptide binds to a therapeutic nanoconjugate, achieving a greater capacity for the nanoconjugate to enter the cell interior and, therefore, to release the drugs it carries into the cells.

Until now, one of the most important internalizing peptides used has been known as TAT. Now, a team of researchers led by Dr. Schwartz Jr, has discovered a sequence common to a family of peptides that significantly outperforms the TAT results and facilitates the cellular internalization of nanoconjugates in a very significant way. These peptides are derived from a membrane protein called CD300 which has a very high capacity to interact with sphingomyelin, a lipid found in all plasma membranes and also in intracellular organelles. “The peptides in our patent”, explains Dr. Simó Schwartz Jr, “are derived from an extracellular part of CD300, which has a high capacity to bind sphingomyelin. Compared to the current standard treatment, TAT, CD300f7 is much faster, internalizes much more, and does not cause any toxicity. The use of these peptides in nanomedicine therefore facilitates and increases the internalization process of all the cargo they carry. This means that we are able to introduce drugs into cells in less time and in greater quantities ”. The results of this discovery not only allow for faster internalization within the cell, but also open the door to designing much more effective therapeutic nanoconjugates.

Souce of information: VHIR news

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New nanocarrier for bio-imaging and drug-delivery applications

Researchers of CIBER-BBN and NANBIOSIS-ICTS (U6 Biomaterial Processing and Nanostructuring Unit at ICMAB-CSIC and U18 Nanotoxicology Unit at  Hospital de la Santa Creu i Sant Pau have developed a new nanocarrier for bio-imaging and drug-delivery applications

The new nanovesicle formulation is based on the quatsome architecture – which stands out due to the high colloidal stability and homogeneity in size – and has now been shown to be suitable for in vivo dosing.

Quatsomes are new non-liposomal lipid-based nanovesicles that have been developed by Nanomol group in recent years, and have been shown to be highly homogeneous and stable in different media for years. This colloidal stability involves important advantages for the development of pharmaceutical formulations and for guaranteeing the final product quality. Quatsomes are a promising nanocarrier for bio-imaging and drug-delivery applications, suitable for the encapsulation of both hydrophilic and hydrophobic molecules, easily functionalized with elements that favor the directionality towards therapeutic targets.

To facilitate their use in in vivo applications, Nanomol group has now developed a new Quatsome formulation, composed of cholesterol and myristalkonium chloride (MKC), the C14 homolog of benzalkonium chloride (BAK), the latter being extensively used as antimicrobial preservative in many ophthalmic and parenteral formulations on the EU and USA market. These novel MKC-Quatsomes have been synthesized in different media that are suitable for parenteral administration, in which they showed to be stable for at least 18 months. Moreover, vesicles remained stable in human serum for at least 24 hours.

In collaboration with the Oncogenesis and Antitumour Drug group of the Biomedical Research Institute of the Hospital de la Santa Creu i Sant Pau, these MKC-Quatsomes were tested in live mice bearing xenografted colorectal tumors. After intravenous injection of fluorescently labelled MKC-Quatsomes, biodistribution assays showed nanovesicle accumulation in tumors, liver, spleen, and kidneys, but not in any other organ. Importantly, MKC-Quatsomes were well-tolerated at the administered doses, and no histological alterations or toxicity was found in any of these organs. These new results suggest the applicability of quatsomes in therapeutic approaches that require systemic delivery.

NANOMOL group, Coordinator of NANBIOSIS U6 at ICMAB-CSIC and the Oncogenesis and Antitumor Drug group, coordinator NANBIOSIS U18 at Biomedical Research Institute (Hospital de la Santa Creu i Sant Pau) are members of Biomedical Research Networking center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) and have a wide expertise and recognized excellence in the synthesis, processing and study of molecular and polymeric materials and the study of their biomedical properties. NANOMOL is also a member of the technology transfer network TECNIO. ‘

Article of reference:

MKC-Quatsomes. A stable nanovesicle platform for bio-imaging and drug-delivery applications co-authored by Guillem Vargas-Nadal et al., Nanomedicine: Nanotechnology, Biology and Medicine, 24 (2020) 102136. https://doi.org/10.1016/j.nano.2019.102136

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Nano-carrier to release drugs into damaged cells

Senescent cells are damaged cells that do not perform their normal roles anymore but that are not dead –hence they are commonly known as zombi cells. These cells interfere with the functioning of the tissue in which they accumulate. Senescence is a cell program that is triggered by many types of damage and senescent cells are present in many diseases. They accumulate in diverse types of tissues during aging, thus contributing to the progressive deterioration associated to aging. Eliminating these zombi cells is one of the challenges facing science today.

In the Cellular Plasticity and Disease lab headed by the ICREA researcher Manuel Serrano at the Institute for Research in Biomedicine (IRB Barcelona) and supported by “la Caixa” Banking Foundation, the researchers devise strategies to eliminate senescent cells. In a study published in EMBO Molecular Medicine, they present a proof of principle of a drug delivery system with selectivity for tissues that harbour senescent cells.

In collaboration with a team headed by Ramón Martínez-Máñez, Scientific Diirector of NANBIOSIS Unit 26 NMR: Biomedical Applications II ,  the IRB Barcelona scientists have exploited a particular hallmark of senescent cells in order to design a delivery system that specifically targets them. They have demonstrated its efficacy in cells in vitro and in two experimental mouse models, namely pulmonary fibrosis and cancer. These diseases are characterized by the presence of damaged cells, and in the case of cancer this is particularly true after treatment with chemotherapy.

In these models, the senescent cells take up the carrier more efficiently than other cells and once inside the cell the casing of the carrier degrades to release the drug cargo. When the nano-vehicles contained cytotoxic compounds, the senescent cells were killed and this resulted in therapeutic improvements in mice with pulmonary fibrosis or with cancer.

“This nano-carrier may pave the way for new therapeutic approaches for serious conditions, such as pulmonary fibrosis or to eliminate chemotherapy-induced senescent cells,” explains Manuel Serrano. Another outcome of this study is that these nano-carriers could be used for diagnostic tests of senescence as they can transport a fluorescent compound or marker.

This study, performed by IRB Barcelona in collaboration with the Universidad Politécnica de Valencia, CNIO, the University of Cambridge, CIBER-BBN, and the company Pfizer in the US, is a step towards achieving the capacity to eliminate senescent cells. Developing tools to specifically eliminate senescent cells is currently a central goal for many pharmaceutical companies, among them the one set up by Manuel Serrano himself together with Ramón Martínez-Máñez and José Ramón Murguia, Senolytic Therapeutics, which is located at the Barcelona Science Park and in Boston.

The study has been funded by “la Caixa” Banking Foundation, the Botín Foundation, the European Research Council, CRUK Cambridge Centre Early Detection Programme, the Ministry of Economy and Competitiveness/ERDFs and the Catalan Governmen

Daniel Muñoz‐Espín, Miguel Rovira, Irene Galiana, Cristina Giménez, Beatriz Lozano‐Torres, Marta Paez‐Ribes, Susana Llanos, Selim Chaib, Maribel Muñoz‐Martín, Alvaro C Ucero, Guillermo Garaulet, Francisca Mulero, Stephen G Dann, Todd VanArsdale, David J Shields, Andrea Bernardos, José Ramón Murguía, Ramón Martínez‐Máñez, Manuel Serrano A versatile drug delivery system targeting senescent cells EMBO Molecular Medicine (2018) DOI 10.15252/emmm.201809355

Image: The figure shows two views, frontal and lateral, of the image obtained by CT of the lungs of a mouse with fibrosis (grey areas) before and after receiving nano-therapy directed at senescent cells. (Guillem Garaulet and Francisca Mulero, CNIO)

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Switching cell penetrating and CXCR4-binding activities of nanoscale-organized arginine-rich peptides

Scientists of Units 1 and 18 of NANBIOSIS are coathors of the article  “Switching cell penetrating and CXCR4-binding activities of nanoscale-organized arginine-rich peptides” published by Nanomedicine: Nanotechnology, Biology and Medicine

Arginine-rich protein motifs have been described as potent cell-penetrating peptides (CPPs) but also as rather specific ligands of the cell surface chemokine receptor CXCR4, involved in the infection by the human immunodeficiency virus (HIV).

Polyarginines are commonly used to functionalize nanoscale vehicles for gene therapy and drug delivery, aimed to enhance cell penetrability of the therapeutic cargo. However, under which conditions these peptides do act as either unspecific or specific ligands is unknown. The authors have here explored the cell penetrability of differently charged polyarginines in two alternative presentations, namely as unassembled fusion proteins or assembled in multimeric protein nanoparticles. By this, they have observed that arginine-rich peptides switch between receptor-mediated and receptor-independent mechanisms of cell penetration. The relative weight of these activities is determined by the electrostatic charge of the construct and the oligomerizationstatus of the nanoscale material, both regulatable by conventional protein engineering approaches

Protein production has been partially performed by the ICTS “NANBIOSIS”, more specifically by the U1. Protein Production Platform (PPP), whereas the in vivo biodistribution assays were performed in the NANBIOSIS U18. Nanotoxicology Unit,

Article of reference:

Marianna Teixeira de Pinho FavaroNaroa SernaLaura Sánchez-GarcíaRafael Cubarsi, Mónica Roldán, Alejandro Sánchez-Chardi, Ugutz Unzueta, Ramón ManguesNeus Ferrer-MirallesAdriano Rodrigues Azzoni, Esther Vázquez, Antonio VillaverdeSwitching cell penetrating and CXCR4-binding activities of nanoscale-organized arginine-rich peptides Nanomedicine: Nanotechnology, Biology and Medicine Volume 14, Issue 6, August 2018, Pages 1777-1786 

 

 

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NANOMEDICINE APPLICATIONS IN DRUG DELIVERY AND TARGETING: NANBIOSIS – NANOMED Industrial Forum

Yesterday took place in Barcelona, at Barcelona School of Management, Universitat Pompeu Fabra, a meeting of resarch groups and units of NANBIOSIS and CIBER-BBN and companies in the third B2B Forum organized by NANBIOSIS, in this case together with NANOMED SPAIN.

Thirteen companies and twelve groups from CIBER-BBN and CCMIJU (ten of them coordinating NANBIOSIS units) got together to explain, through short presentations of ten minutes, those lines of their work aimed at finding synergies and potential collaborations in the area of Nanomedicine apllications in drug delivery and targeting. There was also a talk by a  representative of CDTI (Spanish National Center for Industrial and Technological Development) to explain the financing opportunities for the companies as well as a presentation by the NANBIOSIS Coordinator, Jesús Izco, to show the new Cutting Edge Biomedical Solutions offered by the ICTS-NANBIOSIS

After lunch, the groups and companies had the opportunity to discuss in more detail, during bilateral interviews coordinated by NANBIOSIS a, those aspects that had attracted their attention, as well as, in some cases, to draw potential collaborations. The event was successfully developed with 45 attendees and more than 50 individual B2B mettings.

 

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