Images and their Time

La reflexión acerca de la multiplicidad de tiempos existentes en un mismo momento histórico que conforman una heterocronía, así como la capacidad de las obras de arte e imágenes visuales de crear un tiempo anacrónico o estético, en el momento de su recepción por el espectador de cualquier época, lleva a repensar los modos de abordaje de la Historia del Arte y los alcances del lenguaje para la interpretación.The reflection on the multiplicity of existent times in the same historic moment forming an heterochrony, as well as the ability of the works of art and visual images to create an anachronistic or aesthetic time, in the moment it is received by an audience in any period in time leads to a reconsideration in the ways of approaching the History of Art and the scope of the language used to its interpretation.Facultad de Bellas Arte

In Vitro Modeling of Non-Solid Tumors: How Far Can Tissue Engineering Go?

[EN] In hematological malignancies, leukemias or myelomas, malignant cells present bone marrow (BM) homing, in which the niche contributes to tumor development and drug resistance. BM architecture, cellular and molecular composition and interactions define differential microenvironments that govern cell fate under physiological and pathological conditions and serve as a reference for the native biological landscape to be replicated in engineered platforms attempting to reproduce blood cancer behavior. This review summarizes the different models used to efficiently reproduce certain aspects of BM in vitro; however, they still lack the complexity of this tissue, which is relevant for fundamental aspects such as drug resistance development in multiple myeloma. Extracellular matrix composition, material topography, vascularization, cellular composition or stemness vs. differentiation balance are discussed as variables that could be rationally defined in tissue engineering approaches for achieving more relevant in vitro models. Fully humanized platforms closely resembling natural interactions still remain challenging and the question of to what extent accurate tissue complexity reproduction is essential to reliably predict drug responses is controversial. However, the contributions of these approaches to the fundamental knowledge of non-solid tumor biology, its regulation by niches, and the advance of personalized medicine are unquestionable.PROMETEO/2016/063 project is acknowledged. The CIBER-BBN initiative is funded by the VI National R&D&I Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program. CIBER actions are financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. This work was also supported by the Spanish Ministry of Science, Innovation and Universities through Grant FPU17/05810 awarded to Sandra Clara-Trujillo.Clara-Trujillo, S.; Gallego Ferrer, G.; Gómez Ribelles, JL. (2020). In Vitro Modeling of Non-Solid Tumors: How Far Can Tissue Engineering Go?. International Journal of Molecular Sciences. 21(16):1-31. https://doi.org/10.3390/ijms21165747S1312116Langer, R., & Vacanti, J. P. (1993). Tissue Engineering. Science, 260(5110), 920-926. doi:10.1126/science.8493529Kelm, J. M., Lal-Nag, M., Sittampalam, G. S., & Ferrer, M. (2019). Translational in vitro research: integrating 3D drug discovery and development processes into the drug development pipeline. Drug Discovery Today, 24(1), 26-30. doi:10.1016/j.drudis.2018.07.007Pradhan, S., Hassani, I., Clary, J. M., & Lipke, E. A. (2016). Polymeric Biomaterials for In Vitro Cancer Tissue Engineering and Drug Testing Applications. Tissue Engineering Part B: Reviews, 22(6), 470-484. doi:10.1089/ten.teb.2015.0567Khetani, S. R., & Bhatia, S. N. (2006). Engineering tissues for in vitro applications. Current Opinion in Biotechnology, 17(5), 524-531. doi:10.1016/j.copbio.2006.08.009Gomes, M. E., Rodrigues, M. T., Domingues, R. M. A., & Reis, R. L. (2017). Tissue Engineering and Regenerative Medicine: New Trends and Directions—A Year in Review. Tissue Engineering Part B: Reviews, 23(3), 211-224. doi:10.1089/ten.teb.2017.0081Wang, Z., Lee, S. J., Cheng, H.-J., Yoo, J. J., & Atala, A. (2018). 3D bioprinted functional and contractile cardiac tissue constructs. Acta Biomaterialia, 70, 48-56. doi:10.1016/j.actbio.2018.02.007Tsukamoto, Y., Akagi, T., & Akashi, M. (2020). Vascularized cardiac tissue construction with orientation by layer-by-layer method and 3D printer. Scientific Reports, 10(1). doi:10.1038/s41598-020-59371-yVan Grunsven, L. A. (2017). 3D in vitro models of liver fibrosis. Advanced Drug Delivery Reviews, 121, 133-146. doi:10.1016/j.addr.2017.07.004Griffith, L. G., & Swartz, M. A. (2006). Capturing complex 3D tissue physiology in vitro. Nature Reviews Molecular Cell Biology, 7(3), 211-224. doi:10.1038/nrm1858Schenke-Layland, K., & Nerem, R. M. (2011). In vitro human tissue models — moving towards personalized regenerative medicine. Advanced Drug Delivery Reviews, 63(4-5), 195-196. doi:10.1016/j.addr.2011.05.001Dagogo-Jack, I., & Shaw, A. T. (2017). Tumour heterogeneity and resistance to cancer therapies. Nature Reviews Clinical Oncology, 15(2), 81-94. doi:10.1038/nrclinonc.2017.166Wright, W. E., & Shay, J. W. (2000). Telomere dynamics in cancer progression and prevention: fundamental differences in human and mouse telomere biology. Nature Medicine, 6(8), 849-851. doi:10.1038/78592Brancato, V., Oliveira, J. M., Correlo, V. M., Reis, R. L., & Kundu, S. C. (2020). Could 3D models of cancer enhance drug screening? Biomaterials, 232, 119744. doi:10.1016/j.biomaterials.2019.119744Riedl, A., Schlederer, M., Pudelko, K., Stadler, M., Walter, S., Unterleuthner, D., … Dolznig, H. (2016). Comparison of cancer cells cultured in 2D vs 3D reveals differences in AKT/mTOR/S6-kinase signaling and drug response. Journal of Cell Science. doi:10.1242/jcs.188102Wu, T., & Dai, Y. (2017). Tumor microenvironment and therapeutic response. Cancer Letters, 387, 61-68. doi:10.1016/j.canlet.2016.01.043Håkanson, M., Cukierman, E., & Charnley, M. (2014). Miniaturized pre-clinical cancer models as research and diagnostic tools. Advanced Drug Delivery Reviews, 69-70, 52-66. doi:10.1016/j.addr.2013.11.010Radhakrishnan, J., Varadaraj, S., Dash, S. K., Sharma, A., & Verma, R. S. (2020). Organotypic cancer tissue models for drug screening: 3D constructs, bioprinting and microfluidic chips. Drug Discovery Today, 25(5), 879-890. doi:10.1016/j.drudis.2020.03.002Broutier, L., Mastrogiovanni, G., Verstegen, M. M., Francies, H. E., Gavarró, L. M., Bradshaw, C. R., … Huch, M. (2017). Human primary liver cancer–derived organoid cultures for disease modeling and drug screening. Nature Medicine, 23(12), 1424-1435. doi:10.1038/nm.4438Drost, J., & Clevers, H. (2018). Organoids in cancer research. Nature Reviews Cancer, 18(7), 407-418. doi:10.1038/s41568-018-0007-6Angeloni, V., Contessi, N., De Marco, C., Bertoldi, S., Tanzi, M. C., Daidone, M. G., & Farè, S. (2017). Polyurethane foam scaffold as in vitro model for breast cancer bone metastasis. Acta Biomaterialia, 63, 306-316. doi:10.1016/j.actbio.2017.09.017Kim, M. J., Chi, B. H., Yoo, J. J., Ju, Y. M., Whang, Y. M., & Chang, I. H. (2019). Structure establishment of three-dimensional (3D) cell culture printing model for bladder cancer. PLOS ONE, 14(10), e0223689. doi:10.1371/journal.pone.0223689Carvalho, M. R., Barata, D., Teixeira, L. M., Giselbrecht, S., Reis, R. L., Oliveira, J. M., … Habibovic, P. (2019). Colorectal tumor-on-a-chip system: A 3D tool for precision onco-nanomedicine. Science Advances, 5(5). doi:10.1126/sciadv.aaw1317Paolillo, Colombo, Serra, Belvisi, Papetti, Ciusani, … Schinelli. (2019). Stem-like Cancer Cells in a Dynamic 3D Culture System: A Model to Study Metastatic Cell Adhesion and Anti-cancer Drugs. Cells, 8(11), 1434. doi:10.3390/cells8111434Lichtman, M. A. (2008). Battling the Hematological Malignancies: The 200 Years’ War. The Oncologist, 13(2), 126-138. doi:10.1634/theoncologist.2007-0228Jagannathan-Bogdan, M., & Zon, L. I. (2013). Hematopoiesis. Development, 140(12), 2463-2467. doi:10.1242/dev.083147Rieger, M. A., & Schroeder, T. (2012). Hematopoiesis. Cold Spring Harbor Perspectives in Biology, 4(12), a008250-a008250. doi:10.1101/cshperspect.a008250Harris, N. L., Jaffe, E. S., Diebold, J., Flandrin, G., Muller-Hermelink, H. K., Vardiman, J., … Bloomfield, C. D. (2000). The World Health Organization Classification of Neoplasms of the Hematopoietic and Lymphoid Tissues: Report of the Clinical Advisory Committee Meeting – Airlie House, Virginia, November, 1997. The Hematology Journal, 1(1), 53-66. doi:10.1038/sj.thj.6200013Arber, D. A., Orazi, A., Hasserjian, R., Thiele, J., Borowitz, M. J., Le Beau, M. M., … Vardiman, J. W. (2016). The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood, 127(20), 2391-2405. doi:10.1182/blood-2016-03-643544Palumbo, A., & Anderson, K. (2011). Multiple Myeloma. New England Journal of Medicine, 364(11), 1046-1060. doi:10.1056/nejmra1011442Méndez-Ferrer, S., Bonnet, D., Steensma, D. P., Hasserjian, R. P., Ghobrial, I. M., Gribben, J. G., … Krause, D. S. (2020). Bone marrow niches in haematological malignancies. Nature Reviews Cancer, 20(5), 285-298. doi:10.1038/s41568-020-0245-2Kumar, R., Godavarthy, P. S., & Krause, D. S. (2018). The bone marrow microenvironment in health and disease at a glance. Journal of Cell Science, 131(4). doi:10.1242/jcs.201707Galán-Díez, M., Cuesta-Domínguez, Á., & Kousteni, S. (2017). The Bone Marrow Microenvironment in Health and Myeloid Malignancy. Cold Spring Harbor Perspectives in Medicine, 8(7), a031328. doi:10.1101/cshperspect.a031328Itkin, T., Gur-Cohen, S., Spencer, J. A., Schajnovitz, A., Ramasamy, S. K., Kusumbe, A. P., … Lapidot, T. (2016). Distinct bone marrow blood vessels differentially regulate haematopoiesis. Nature, 532(7599), 323-328. doi:10.1038/nature17624Morikawa, T., & Takubo, K. (2017). Use of Imaging Techniques to Illuminate Dynamics of Hematopoietic Stem Cells and Their Niches. Frontiers in Cell and Developmental Biology, 5. doi:10.3389/fcell.2017.00062Galán-Díez, M., & Kousteni, S. (2017). The Osteoblastic Niche in Hematopoiesis and Hematological Myeloid Malignancies. Current Molecular Biology Reports, 3(2), 53-62. doi:10.1007/s40610-017-0055-9Klamer, S., & Voermans, C. (2014). The role of novel and known extracellular matrix and adhesion molecules in the homeostatic and regenerative bone marrow microenvironment. Cell Adhesion & Migration, 8(6), 563-577. doi:10.4161/19336918.2014.968501Walkley, C. R., Shea, J. M., Sims, N. A., Purton, L. E., & Orkin, S. H. (2007). Rb Regulates Interactions between Hematopoietic Stem Cells and Their Bone Marrow Microenvironment. Cell, 129(6), 1081-1095. doi:10.1016/j.cell.2007.03.055Walkley, C. R., Olsen, G. H., Dworkin, S., Fabb, S. A., Swann, J., McArthur, G. A., … Purton, L. E. (2007). A Microenvironment-Induced Myeloproliferative Syndrome Caused by Retinoic Acid Receptor γ Deficiency. Cell, 129(6), 1097-1110. doi:10.1016/j.cell.2007.05.014Xie, M., Lu, C., Wang, J., McLellan, M. D., Johnson, K. J., Wendl, M. C., … Ding, L. (2014). Age-related mutations associated with clonal hematopoietic expansion and malignancies. Nature Medicine, 20(12), 1472-1478. doi:10.1038/nm.3733Jaiswal, S., Fontanillas, P., Flannick, J., Manning, A., Grauman, P. V., Mar, B. G., … Ebert, B. L. (2014). Age-Related Clonal Hematopoiesis Associated with Adverse Outcomes. New England Journal of Medicine, 371(26), 2488-2498. doi:10.1056/nejmoa1408617Genovese, G., Kähler, A. K., Handsaker, R. E., Lindberg, J., Rose, S. A., Bakhoum, S. F., … McCarroll, S. A. (2014). Clonal Hematopoiesis and Blood-Cancer Risk Inferred from Blood DNA Sequence. New England Journal of Medicine, 371(26), 2477-2487. doi:10.1056/nejmoa1409405Sala-Torra, O., Hanna, C., Loken, M. R., Flowers, M. E. D., Maris, M., Ladne, P. A., … Radich, J. P. (2006). Evidence of Donor-Derived Hematologic Malignancies after Hematopoietic Stem Cell Transplantation. Biology of Blood and Marrow Transplantation, 12(5), 511-517. doi:10.1016/j.bbmt.2006.01.006Ghosh, A. K., Secreto, C. R., Knox, T. R., Ding, W., Mukhopadhyay, D., & Kay, N. E. (2010). Circulating microvesicles in B-cell chronic lymphocytic leukemia can stimulate marrow stromal cells: implications for disease progression. Blood, 115(9), 1755-1764. doi:10.1182/blood-2009-09-242719Zhang, B., Chu, S., Agarwal, P., Campbell, V. L., Hopcroft, L., Jørgensen, H. G., … Bhatia, R. (2016). Inhibition of interleukin-1 signaling enhances elimination of tyrosine kinase inhibitor–treated CML stem cells. Blood, 128(23), 2671-2682. doi:10.1182/blood-2015-11-679928Schepers, K., Pietras, E. M., Reynaud, D., Flach, J., Binnewies, M., Garg, T., … Passegué, E. (2013). Myeloproliferative Neoplasia Remodels the Endosteal Bone Marrow Niche into a Self-Reinforcing Leukemic Niche. Cell Stem Cell, 13(3), 285-299. doi:10.1016/j.stem.2013.06.009Hawkins, E. D., Duarte, D., Akinduro, O., Khorshed, R. A., Passaro, D., Nowicka, M., … Lo Celso, C. (2016). T-cell acute leukaemia exhibits dynamic interactions with bone marrow microenvironments. Nature, 538(7626), 518-522. doi:10.1038/nature19801Paggetti, J., Haderk, F., Seiffert, M., Janji, B., Distler, U., Ammerlaan, W., … Moussay, E. (2015). Exosomes released by chronic lymphocytic leukemia cells induce the transition of stromal cells into cancer-associated fibroblasts. Blood, 126(9), 1106-1117. doi:10.1182/blood-2014-12-618025Arranz, L., Sánchez-Aguilera, A., Martín-Pérez, D., Isern, J., Langa, X., Tzankov, A., … Méndez-Ferrer, S. (2014). Neuropathy of haematopoietic stem cell niche is essential for myeloproliferative neoplasms. Nature, 512(7512), 78-81. doi:10.1038/nature13383Dias, S., Hattori, K., Zhu, Z., Heissig, B., Choy, M., Lane, W., … Rafii, S. (2000). Autocrine stimulation of VEGFR-2 activates human leukemic cell growth and migration. Journal of Clinical Investigation, 106(4), 511-521. doi:10.1172/jci8978Warburg, O. (1956). On the Origin of Cancer Cells. Science, 123(3191), 309-314. doi:10.1126/science.123.3191.309Kreitz, J., Schönfeld, C., Seibert, M., Stolp, V., Alshamleh, I., Oellerich, T., … Serve, H. (2019). Metabolic Plasticity of Acute Myeloid Leukemia. Cells, 8(8), 805. doi:10.3390/cells8080805Lagadinou, E. D., Sach, A., Callahan, K. P., Rossi, R. M., Neering, S., Pei, S., … Jordan, C. T. (2012). Bcl-2 Inhibitor ABT-263 Targets Oxidative Phosphorylation and Selectively Eradicates Quiescent Human Leukemia Stem Cells. Blood, 120(21), 206-206. doi:10.1182/blood.v120.21.206.206Lutzny, G., Kocher, T., Schmidt-Supprian, M., Rudelius, M., Klein-Hitpass, L., Finch, A. J., … Ringshausen, I. (2013). Protein Kinase C-β-Dependent Activation of NF-κB in Stromal Cells Is Indispensable for the Survival of Chronic Lymphocytic Leukemia B Cells In Vivo. Cancer Cell, 23(1), 77-92. doi:10.1016/j.ccr.2012.12.003Yao, J.-C., & Link, D. C. (2016). Concise Review: The Malignant Hematopoietic Stem Cell Niche. STEM CELLS, 35(1), 3-8. doi:10.1002/stem.2487Spaggiari, G. M., Capobianco, A., Abdelrazik, H., Becchetti, F., Mingari, M. C., & Moretta, L. (2008). Mesenchymal stem cells inhibit natural killer–cell proliferation, cytotoxicity, and cytokine production: role of indoleamine 2,3-dioxygenase and prostaglandin E2. Blood, 111(3), 1327-1333. doi:10.1182/blood-2007-02-074997Jin, L., Hope, K. J., Zhai, Q., Smadja-Joffe, F., & Dick, J. E. (2006). Targeting of CD44 eradicates human acute myeloid leukemic stem cells. Nature Medicine, 12(10), 1167-1174. doi:10.1038/nm1483Krause, D. S., Lazarides, K., von Andrian, U. H., & Van Etten, R. A. (2006). Requirement for CD44 in homing and engraftment of BCR-ABL–expressing leukemic stem cells. Nature Medicine, 12(10), 1175-1180. doi:10.1038/nm1489Azab, A. K., Runnels, J. M., Pitsillides, C., Moreau, A.-S., Azab, F., Leleu, X., … Ghobrial, I. M. (2009). CXCR4 inhibitor AMD3100 disrupts the interaction of multiple myeloma cells with the bone marrow microenvironment and enhances their sensitivity to therapy. Blood, 113(18), 4341-4351. doi:10.1182/blood-2008-10-186668Jacamo, R., Chen, Y., Wang, Z., Ma, W., Zhang, M., Spaeth, E. L., … Andreeff, M. (2014). Reciprocal leukemia-stroma VCAM-1/VLA-4-dependent activation of NF-κB mediates chemoresistance. Blood, 123(17), 2691-2702. doi:10.1182/blood-2013-06-511527Hatano, K., Kikuchi, J., Takatoku, M., Shimizu, R., Wada, T., Ueda, M., … Ozawa, K. (2008). Bortezomib overcomes cell adhesion-mediated drug resistance through downregulation of VLA-4 expression in multiple myeloma. Oncogene, 28(2), 231-242. doi:10.1038/onc.2008.385Bourgine, P. E., Martin, I., & Schroeder, T. (2018). Engineering Human Bone Marrow Proxies. Cell Stem Cell, 22(3), 298-301. doi:10.1016/j.stem.2018.01.002Chramiec, A., & Vunjak-Novakovic, G. (2019). Tissue engineered models of healthy and malignant human bone marrow. Advanced Drug Delivery Reviews, 140, 78-92. doi:10.1016/j.addr.2019.04.003Tavakol, D. N., Tratwal, J., Bonini, F., Genta, M., Campos, V., Burch, P., … Braschler, T. (2020). Injectable, scalable 3D tissue-engineered model of marrow hematopoiesis. Biomaterials, 232, 119665. doi:10.1016/j.biomaterials.2019.119665Isern, J., Martín-Antonio, B., Ghazanfari, R., Martín, A. M., López, J. A., del Toro, R., … Méndez-Ferrer, S. (2013). Self-Renewing Human Bone Marrow Mesenspheres Promote Hematopoietic Stem Cell Expansion. Cell Reports, 3(5), 1714-1724. doi:10.1016/j.celrep.2013.03.041Jing, D., Fonseca, A. V., Alakel, N., Fierro, F. A., Muller, K., Bornhauser, M., … Ordemann, R. (2010). Hematopoietic stem cells in co-culture with mesenchymal stromal cells - modeling the niche compartments in vitro. Haematologica, 95(4), 542-550. doi:10.3324/haematol.2009.010736Butler, J. M., Gars, E. J., James, D. J., Nolan, D. J., Scandura, J. M., & Rafii, S. (2012). Development of a vascular niche platform for expansion of repopulating human cord blood stem and progenitor cells. Blood, 120(6), 1344-1347. doi:10.1182/blood-2011-12-398115Leisten, I., Kramann, R., Ventura Ferreira, M. S., Bovi, M., Neuss, S., Ziegler, P., … Schneider, R. K. (2012). 3D co-culture of hematopoietic stem and progenitor cells and mesenchymal stem cells in collagen scaffolds as a model of the hematopoietic niche. Biomaterials, 33(6), 1736-1747. doi:10.1016/j.biomaterials.2011.11.034Raic, A., Rödling, L., Kalbacher, H., & Lee-Thedieck, C. (2014). Biomimetic macroporous PEG hydrogels as 3D scaffolds for the multiplication of human hematopoietic stem and progenitor cells. Biomaterials, 35(3), 929-940. doi:10.1016/j.biomaterials.2013.10.038Severn, C. E., Macedo, H., Eagle, M. J., Rooney, P., Mantalaris, A., & Toye, A. M. (2016). Polyurethane scaffolds seeded with CD34+ cells maintain early stem cells whilst also facilitating prolonged egress of haematopoietic progenitors. Scientific Reports, 6(1). doi:10.1038/srep32149Mahadik, B. P., Bharadwaj, N. A. K., Ewoldt, R. H., & Harley, B. A. C. (2017). Regulating dynamic signaling between hematopoietic stem cells and niche cells via a hydrogel matrix. Biomaterials, 125, 54-64. doi:10.1016/j.biomaterials.2017.02.013Wilkinson, A. C., Ishida, R., Kikuchi, M., Sudo, K., Morita, M., Crisostomo, R. V., … Yamazaki, S. (2019). Long-term ex vivo haematopoietic-stem-cell expansion allows nonconditioned transplantation. Nature, 571(7763), 117-121. doi:10.1038/s41586-019-1244-xSieber, S., Wirth, L., Cavak, N., Koenigsmark, M., Marx, U., Lauster, R., & Rosowski, M. (2017). Bone marrow‐on‐a‐chip: Long‐term culture of human haematopoietic stem cells in a three‐dimensional microfluidic environment. Journal of Tissue Engineering and Regenerative Medicine, 12(2), 479-489. doi:10.1002/term.2507Bourgine, P. E., Klein, T., Paczulla, A. M., Shimizu, T., Kunz, L., Kokkaliaris, K. D., … Martin, I. (2018). In vitro biomimetic engineering of a human hematopoietic niche with functional properties. Proceedings of the National Academy of Sciences, 115(25), E5688-E5695. doi:10.1073/pnas.1805440115De la Puente, P., Muz, B., Gilson, R. C., Azab, F., Luderer, M., King, J., … Azab, A. K. (2015). 3D tissue-engineered bone marrow as a novel model to study pathophysiology and drug resistance in multiple myeloma. Biomaterials, 73, 70-84. doi:10.1016/j.biomaterials.2015.09.017Torisawa, Y., Spina, C. S., Mammoto, T., Mammoto, A., Weaver, J. C., Tat, T., … Ingber, D. E. (2014). Bone marrow–on–a–chip replicates hematopoietic niche physiology in vitro. Nature Methods, 11(6), 663-669. doi:10.1038/nmeth.2938Reinisch, A., Hernandez, D. C., Schallmoser, K., & Majeti, R. (2017). Generation and use of a humanized bone-marrow-ossicle niche for hematopoietic xenotransplantation into mice. Nature Protocols, 12(10), 2169-2188. doi:10.1038/nprot.2017.088Theocharides, A. P. A., Rongvaux, A., Fritsch, K., Flavell, R. A., & Manz, M. G. (2015). Humanized hemato-lymphoid system mice. Haematologica, 101(1), 5-19. doi:10.3324/haematol.2014.115212Abarrategi, A., Mian, S. A., Passaro, D., Rouault-Pierre, K., Grey, W., & Bonnet, D. (2018). Modeling the human bone marrow niche in mice: From host bone marrow engraftment to bioengineering approaches. Journal of Experimental Medicine, 215(3), 729-743. doi:10.1084/jem.20172139Rose-Zerilli, M. J. J., Gibson, J., Wang, J., Tapper, W., Davis, Z., Parker, H., … Strefford, J. C. (2016). Longitudinal copy number, whole exome and targeted deep sequencing of «good risk» IGHV-mutated CLL patients with progressive disease. Leukemia, 30(6), 1301-1310. doi:10.1038/leu.2016.10Reinisch, A., Thomas, D., Corces, M. R., Zhang, X., Gratzinger, D., Hong, W.-J., … Majeti, R. (2016). A humanized bone marrow ossicle xenotransplantation model enables improved engraftment of healthy and leukemic human hematopoietic cells. Nature Medicine, 22(7), 812-821. doi:10.1038/nm.4103Vaiselbuh, S. R., Edelman, M., Lipton, J. M., & Liu, J. M. (2010). Ectopic Human Mesenchymal Stem Cell-Coated Scaffolds in NOD/SCID Mice: An In Vivo Model of the Leukemia Niche. Tissue Engineering Part C: Methods, 16(6), 1523-1531. doi:10.1089/ten.tec.2010.0179Groen, R. W. J., Noort, W. A., Raymakers, R. A., Prins, H.-J., Aalders, L., Hofhuis, F. M., … Martens, A. C. M. (2012). Reconstructing the human hematopoietic niche in immunodeficient mice: opportunities for studying primary multiple myeloma. Blood, 120(3), e9-e16. doi:10.1182/blood-2012-03-414920Chen, Y., Jacamo, R., Shi, Y., Wang, R., Battula, V. L., Konoplev, S., … Andreeff, M. (2012). Human extramedullary bone marrow in mice: a novel in vivo model of genetically controlled hematopoietic microenvironment. Blood, 119(21), 4971-4980. doi:10.1182/blood-2011-11-389957Holzapfel, B. M., Hutmacher, D. W., Nowlan, B., Barbier, V., Thibaudeau, L., Theodoropoulos, C., … Levesque, J.-P. (2015). Tissue enginee

La preparación física del músico. Revisión sistemática

During the last years, the interest for the health of the musicians is increasing. The 76% of the musicians suffer or have suffered physical problems preventing them from performing at their usual level and 84% of the musicians have had injuries during the practice. A systematic review of the last 10 years has been carried out on intervention studies with physical activity in musicians in primary sources (MPPA journal) and secondary sources (Music Thesis in Spain, PubMed, WOS, and SciElo), to identify and assess the applications physical activity has in musicians. 2 doctoral theses and 9 research articles have been systematically analyzed, and subsequently classified according to the sample, the group or instrument, the methodology of the exercise program, and the duration. Physical activity interventions have positive effects on pain, body posture, musical performance and fitness. In addition, it promotes awareness of the benefits of exercise for prevention. Improving body awareness, incorporating new habits of physical activity, introducing breaks, and making a correct physical and musical programming is decisive for the prevention of musculoskeletal injuries common in this group.En los últimos años, está creciendo el interés por la salud de los músicos, ya que cada vez el nivel de exigencia es mayor. Las investigaciones muestran que alrededor del 76% sufren o han sufrido problemas físicos que les impide realizar su actividad con normalidad, y el 84% ha tenido lesiones que habían interferido en su práctica. Se ha realizado una búsqueda bibliográfica sistemática de los últimos 10 años sobre estudios de intervención con actividad física en músicos en fuentes primarias (revista MPPA) y secundarias (Tesis de música en España, PubMed, WOS, y SciElo), para conocer, identificar y reflexionar las aplicaciones que tiene la actividad física en los músicos. Un total de 2 tesis doctorales y 9 artículos de investigación han sido analizados sistemáticamente, y clasificados posteriormente en función de la muestra, el colectivo o instrumento, la metodología del programa de ejercicios, y la duración.  Las intervenciones con actividad física tienen efectos positivos sobre el dolor, la postura corporal, el rendimiento musical y la condición física. Además, favorece la conciencia sobre los beneficios del ejercicio para la prevención. Mejorar el conocimiento del cuerpo, incorporar nuevos hábitos de actividad física, introducir descansos, y hacer una correcta programación tanto física como musical será determinante para la prevención de lesiones músculo-esqueléticas comunes en este colectivo

Comparative life cycle assessment of seawater desalination technologies enhanced by graphene membranes

Graphene oxide (GO)-enhanced membranes are being developed to solve major limitations in both reverse osmosis (RO) and membrane distillation (MD) technologies, which include high electricity and thermal energy consumption. This study performed, for the first time, a life cycle assessment to determine the effects of using GO-enhanced membranes on the environmental impacts of seawater desalination via RO and MD. Four scenarios were evaluated and eighteen environmental impacts were quantified according to the ReCiPe impact assessment method. The average impacts for the RO-GO scenarios were lower than those of RO by 3–7 %. The reduction in the climate change impact was 3–8 %, which could avoid the release of 380–850 kt CO2 eq. per year globally if these membranes were used in current seawater RO systems. The MD-GO scenarios had, on average, 27–34 % lower impacts than the MD scenarios. Overall, the RO-GO systems were the most favourable, with lower impacts than MD-GO for most categories. However, using solar-thermal energy instead of natural gas in MD desalination would lead to 43–93 % lower impacts in nine categories than RO powered predominantly by fossil fuels. This includes climate change, which would be 64 % lower; however, freshwater ecotoxicity would be more than four-times higher. The results of this work indicate the potential environmental benefits of GO-enhanced membranes and discuss the future developments needed to improve the performance of RO and MD

Reseña I Jornada Multidisciplinar para las Artes Escénicas

El 6 de Octubre del 2018, tuvo lugar en el Hospital La Fe de Valencia, la I Jornada multidisciplinar para las artes escénicas organizada por la Asociación Multidisciplinar Para las Artes Escénicas (AMPAE), en colaboración con el Hospital Universitario y Politécnico La Fe de Valencia y la Asociación Española de Psicología de la Música y la Interpretación musical (AEPMIM

Intervención educativa del menor en centro de día como medida de preservación familiar

Durante los últimos años el trabajo con menores en situación de desprotección ha me­jorado, pero la realidad es que en la actualidad son numerosos los casos en los que es necesario un trabajo de calidad con las familias, situación que se ha visto agravada en gran medida con la crisis económica producida por la pandemia. Tras esta evidencia, se ha llevado a cabo una intervención individualizada dirigida a un menor que asiste a un centro de acogimiento residencial en la modalidad de centro de día como medida de intervención educativa de preservación familiar, donde cobra especial importancia la competencia monoparental femenina, velando por la promoción de sus competencias y realizaJ1do un trabajo coordinado entre la institución y la familia, para asegurar la per­manencia del menor en el núcleo familiar mediante una disminución de los factores de rjesgo y fortalecer los factores protectores, evitando así su posible separación familiar

First data on the prevalence and distribution of pathogens in bumblebees (Bombus terrestris and Bombus pascuorum) from Spain

Bumblebees provide pollination services not only to wildflowers but also to economically important crops. In the context of the global decline of pollinators, there is an increasing interest in determining the pathogen diversity of bumblebee species. In this work, wild bumblebees of the species Bombus terrestris and Bombus pascuorum from northern and southern Spain were molecularly screened to detect and estimate prevalence of pathogens. One third of bumblebees were infected: while viruses only infected B. pascuorum, B. terrestris was infected by Apicystis bombi, Crithidia bombi and Nosema bombi. Ecological differences between host species might affect the success of the pathogens biological cycle and consequently infection prevalence. Furthermore, sex of the bumblebees (workers or males), sampling area (north or south) and altitude were important predictors of pathogen prevalence. Understanding how these factors affect pathogens distribution is essential for future conservation of bumblebee wild populations

Novel microgel culture system as semi-solid three-dimensional in vitro model for the study of multiple myeloma proliferation and drug resistance

[EN] Multiple myeloma (MM) is a hematological malignancy in which the patient's drug resistance is one of the main clinical problems. As 2D cultures do not recapitulate the cellular microenvironment, which has a key role in drug resistance, there is an urgent need for better biomimetic models. Here, a novel 3D platform is used to model MM. The semi-solid culture consists of a dynamic suspension of microspheres and MM cells, termed as microgel. Microspheres are synthesized with acrylic polymers of different sizes, compositions, and functionalities (fibronectin or hyaluronic acid). Optimal conditions for the platform in terms of agitation speed and microsphere size have been determined. With these parameters the system allows good proliferation of the MM cell lines RPMI8226, U226, and MM1.S. Interestingly, when used for drug resistance studies, culture of the three MM cell lines in microgels showed close agreement in revealing the role of acrylic acid in resistance to anti-MM drugs such as dexamethasone and bortezomib. This work presents a unique platform for the in vitro modeling of non-solid tumors since it allows keeping non-adherent cells in suspension conditions but in a 3D context that can be easily tuned with different functionalizations.This work was funded by the Spanish State Research Agency (AEI) through the PID2019-106099RB-C41/AEI/10.13039/501100011033 Project. CIBER-BBN is an initiative funded by the VI National R&D&I Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program. CIBER Actions were financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. This work was also supported by the Spanish Ministry of Science, Innovation and Universities through Grant NO FPU17/05810 awarded to Sandra Clara-Trujillo. The Microscopy Service of the UPV (UniversitatPolitecnica de València) is gratefully acknowledged for helping with FESEM characterization.Clara-Trujillo, S.; Tolosa, L.; Cordón, L.; Sempere, A.; Gallego Ferrer, G.; Gómez Ribelles, JL. (2022). Novel microgel culture system as semi-solid three-dimensional in vitro model for the study of multiple myeloma proliferation and drug resistance. Biomaterials Advances. 135:1-13. https://doi.org/10.1016/j.bioadv.2022.21274911313

Plan de mejoramiento integral en la empresa Uva Arquitectura para el año 2020

Esta investigación descriptiva contiene la elaboración de plan de mejoramiento integral, diseñado para una empresa dedicada a la prestación de servicios arquitectónicos llamada, UVA- Unidad Vectorial de Arquitectura; este plan de mejoramiento hace parte de una técnica gerencial llamada Mejora Continua; cuyo objetivo es mitigar los daños a causa de las debilidades de la empresa, además de identificar y potencializar sus fortalezas. UVA- Unidad Vectorial de Arquitectura es una empresa concebida empíricamente en el año 2017 gracias a la visión de un joven recién graduado de Arquitectura y actual director; quien genero el concepto de una arquitectura sensitiva, inspirada en una conexión entre lo tangible de la estructura con lo sensorial de las emociones, generando con ello que las personas vibren mediante el diseño y generen así una conexión fuerte con la obra arquitectónica. Este concepto ha buenos resultados en términos comerciales y de satisfacción del cliente; por ende, ha permitido que la empresa haya generado utilidades manteniéndose activa en el mercado. Sin embargo, no ha sido ajena la problemática que presentan las empresas de carácter empírico y cuyos creadores tienen una formación académica inclinada a los procesos operacionales más que a los procesos administrativos o modelos gerenciales. Durante la investigación descriptiva se realizó una actividad de diagnóstico con el estudio de las situaciones, prácticas y actitudes predominantes en la dinámica empresarial de UVA- Unidad Vectorial de Arquitectura; sus procesos, estructura jerárquica y perfiles de los colaboradores, entre otros. Como era de esperarse, luego de realizar la actividad investigativa con la empresa UVA- Unidad Vectorial de Arquitectura se evidencio que su mayor oportunidad de mejora se encuentra centrada en la estructura administrativa; es por ello que el plan de mejoramiento integral mostrara como con la ejecución de unas sencillas actividades, la empresa podrá lograr definir y comunicar de forma asertiva a colaboradores y clientes del servicio su oferta de valor, políticas y valores corporativos, además de poder adoptar una metodología pilar de la administración como lo es medir, controlar y así mejorar las actividades que hacen parte del día a día.This descriptive research contains the development of the comprehensive improvement plan, designed for a company dedicated to the provision of architectural services called, UVA- Unidad Vectorial de Arquitectura; This improvement plan is part of a management technique called Continuous Improvement; whose objective is to mitigate the damage due to the weaknesses of the company, in addition to identifying and strengthening its strengths. UVA- Unidad Vectorial de Arquitectura, It is a company empirically conceived in 2017, thanks to the vision of a young architecture graduate and current director; who generated the concept of “sensitive architecture”, inspired by a connection between the tangible structure, with the sensory emotions, thereby generating people to vibrate through design and thus generate a strong connection with the architectural work. Concept that has given good results in commercial terms and customer satisfaction; therefore, it has allowed the company to generate profits by staying active in the market. However, the problem presented by companies of an empirical nature and whose creators have an academic training inclined to operational processes rather than administrative processes or management models has not been alien. During the descriptive investigation, a diagnostic activity was carried out with the study of the predominant situations, practices and attitudes in the business dynamics of UVA- Vector Architecture Unit; its processes, hierarchical structure and employee profiles, among others. As expected, after carrying out the research activity with the UVA-Vector Architecture Unit, it was evidenced that its greatest opportunity for improvement is centered on the administrative structure; That is why the comprehensive improvement plan will show how with the execution of simple activities, the company will be able to define and communicate assertively to collaborators and customers of the service, its offer of value, policies and corporate values, in addition to being able to adopt a pillar methodology of the administration such as measuring, controlling and thus improving the activities that are part of the day to day