Small Lesions Evaluation Based on Unsupervised Cluster Analysis of Signal-Intensity Time Courses in Dynamic Breast MRI

An application of an unsupervised neural network-based computer-aided diagnosis (CAD) system is reported for the detection and characterization of small indeterminate breast lesions, average size 1.1 mm, in dynamic contrast-enhanced MRI. This system enables the extraction of spatial and temporal features of dynamic MRI data and additionally provides a segmentation with regard to identification and regional subclassification of pathological breast tissue lesions. Lesions with an initial contrast enhancement ≥50% were selected with semiautomatic segmentation. This conventional segmentation analysis is based on the mean initial signal increase and postinitial course of all voxels included in the lesion. In this paper, we compare the conventional segmentation analysis with unsupervised classification for the evaluation of signal intensity time courses for the differential diagnosis of enhancing lesions in breast MRI. The results suggest that the computerized analysis system based on unsupervised clustering has the potential to increase the diagnostic accuracy of MRI mammography for small lesions and can be used as a basis for computer-aided diagnosis of breast cancer with MR mammography

A novel system for glycosylation engineering by natural and artificial micrornas

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A broken heart in a broken car

Takotsubo syndrome (TTS) is still a relatively understudied and often undetected disease. It is usually preceded by emotional or physical triggers. We here report a case of TTS following a car accident. Typical apical ballooning with moderate reduction of left ventricular ejection fraction (LVEF) and increased level of pro-B-type natriuretic peptide (BNP) as well as slightly increased creatine kinase and troponin T values were found in this 76-year-old female patient, 6 h after a car accident. At 10 weeks follow-up, we observed a normalization of regional wall motion, LVEF, electrocardiogram and pro-BNP. TTS is an acute heart failure syndrome and an important differential diagnosis of acute coronary syndrome

All-inorganic core-shell silica-titania mesoporous colloidal nanoparticles showing orthogonal functionality

Colloidal mesoporous silica (CMS) nanoparticles with a thin titania-enriched outer shell showing a spatially resolved functionality were synthesized by a delayed co-condensation approach. The titaniashell can serve as a selective nucleation site for the growth of nanocrystalline anatase clusters. These fully inorganic pure silica-core titania-enriched shell mesoporous nanoparticles show orthogonal functionality, demonstrated through the selective adsorption of a carboxylate-containing ruthenium N3-dye. UV-Vis and fluorescence spectroscopy indicate the strong interaction of the N3-dye with the titania-phase at the outer shell of the CMS nanoparticles. In particular, this interaction and thus the selective functionalization are greatly enhanced when anatase nanocrystallites are nucleated at the titania-enriched shell surface

Dual enzyme-triggered controlled release on capped nanometric silica mesoporous supports

We thank the Spanish Government (project MAT2009-14564-C04 and CTQ2007-64735-AR07) the Generalitat Valencia (project PROMETEO/2009/016) for support. A.A. and L.M. thank the Generalitat Valenciana for their Santiago Grisolia Fellowship and VALI+D postdoctoral contract, respectively. We thank the confocal microscopy service from CIPF for technical support.Agostini, A.; Mondragón Martínez, L.; Coll Merino, MC.; Aznar Gimeno, E.; Marcos Martínez, MD.; Martínez Mañez, R.; Sancenón Galarza, F.... (2012). Dual enzyme-triggered controlled release on capped nanometric silica mesoporous supports. ChemistryOpen. 1:17-20. https://doi.org/10.1002/open.201200003S17201Saha, S., Leung, K. C.-F., Nguyen, T. D., Stoddart, J. F., & Zink, J. I. (2007). Nanovalves. Advanced Functional Materials, 17(5), 685-693. doi:10.1002/adfm.200600989Trewyn, B. G., Slowing, I. I., Giri, S., Chen, H.-T., & Lin, V. S.-Y. (2007). Synthesis and Functionalization of a Mesoporous Silica Nanoparticle Based on the Sol–Gel Process and Applications in Controlled Release. Accounts of Chemical Research, 40(9), 846-853. doi:10.1021/ar600032uAznar, E., Martínez-Máñez, R., & Sancenón, F. (2009). Controlled release using mesoporous materials containing gate-like scaffoldings. Expert Opinion on Drug Delivery, 6(6), 643-655. doi:10.1517/17425240902895980Beck, J. S., Vartuli, J. C., Roth, W. J., Leonowicz, M. E., Kresge, C. T., Schmitt, K. D., … Schlenker, J. L. (1992). A new family of mesoporous molecular sieves prepared with liquid crystal templates. Journal of the American Chemical Society, 114(27), 10834-10843. doi:10.1021/ja00053a020Wight, A. P., & Davis, M. E. (2002). Design and Preparation of Organic−Inorganic Hybrid Catalysts. Chemical Reviews, 102(10), 3589-3614. doi:10.1021/cr010334mKickelbick, G. (2004). Mesoporöse anorganisch-organische Hybridmaterialien. Angewandte Chemie, 116(24), 3164-3166. doi:10.1002/ange.200301751Kickelbick, G. (2004). Hybrid Inorganic–Organic Mesoporous Materials. Angewandte Chemie International Edition, 43(24), 3102-3104. doi:10.1002/anie.200301751Mal, N. K., Fujiwara, M., & Tanaka, Y. (2003). Photocontrolled reversible release of guest molecules from coumarin-modified mesoporous silica. Nature, 421(6921), 350-353. doi:10.1038/nature01362Mal, N. K., Fujiwara, M., Tanaka, Y., Taguchi, T., & Matsukata, M. (2003). Photo-Switched Storage and Release of Guest Molecules in the Pore Void of Coumarin-Modified MCM-41. Chemistry of Materials, 15(17), 3385-3394. doi:10.1021/cm0343296Zhu, Y., & Fujiwara, M. (2007). Installing Dynamic Molecular Photomechanics in Mesopores: A Multifunctional Controlled-Release Nanosystem. Angewandte Chemie, 119(13), 2291-2294. doi:10.1002/ange.200604850Zhu, Y., & Fujiwara, M. (2007). Installing Dynamic Molecular Photomechanics in Mesopores: A Multifunctional Controlled-Release Nanosystem. Angewandte Chemie International Edition, 46(13), 2241-2244. doi:10.1002/anie.200604850Liu, N., Chen, Z., Dunphy, D. R., Jiang, Y.-B., Assink, R. A., & Brinker, C. J. (2003). Angewandte Chemie, 115(15), 1773-1776. doi:10.1002/ange.200250189Liu, N., Chen, Z., Dunphy, D. R., Jiang, Y.-B., Assink, R. A., & Brinker, C. J. (2003). Photoresponsive Nanocomposite Formed by Self-Assembly of an Azobenzene-Modified Silane. Angewandte Chemie International Edition, 42(15), 1731-1734. doi:10.1002/anie.200250189Aznar, E., Casasús, R., García-Acosta, B., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., … Amorós, P. (2007). Photochemical and Chemical Two-Channel Control of Functional Nanogated Hybrid Architectures. Advanced Materials, 19(17), 2228-2231. doi:10.1002/adma.200601958Park, C., Lee, K., & Kim, C. (2009). Photoresponsive Cyclodextrin-Covered Nanocontainers and Their Sol-Gel Transition Induced by Molecular Recognition. Angewandte Chemie International Edition, 48(7), 1275-1278. doi:10.1002/anie.200803880Ferris, D. P., Zhao, Y.-L., Khashab, N. M., Khatib, H. A., Stoddart, J. F., & Zink, J. I. (2009). Light-Operated Mechanized Nanoparticles. Journal of the American Chemical Society, 131(5), 1686-1688. doi:10.1021/ja807798gLin, Q., Huang, Q., Li, C., Bao, C., Liu, Z., Li, F., & Zhu, L. (2010). Anticancer Drug Release from a Mesoporous Silica Based Nanophotocage Regulated by Either a One- or Two-Photon Process. Journal of the American Chemical Society, 132(31), 10645-10647. doi:10.1021/ja103415tKnežević, N. Ž., Trewyn, B. G., & Lin, V. S.-Y. (2011). Light- and pH-Responsive Release of Doxorubicin from a Mesoporous Silica-Based Nanocarrier. Chemistry - A European Journal, 17(12), 3338-3342. doi:10.1002/chem.201002960Knežević, N. Ž., Trewyn, B. G., & Lin, V. S.-Y. (2011). Functionalized mesoporous silica nanoparticle-based visible light responsive controlled release delivery system. Chemical Communications, 47(10), 2817. doi:10.1039/c0cc04424eTrewyn, B. G., Giri, S., Slowing, I. I., & Lin, V. S.-Y. (2007). Mesoporous silica nanoparticle based controlled release, drug delivery, and biosensor systems. Chemical Communications, (31), 3236. doi:10.1039/b701744hTorney, F., Trewyn, B. G., Lin, V. S.-Y., & Wang, K. (2007). Mesoporous silica nanoparticles deliver DNA and chemicals into plants. Nature Nanotechnology, 2(5), 295-300. doi:10.1038/nnano.2007.108Radu, D. R., Lai, C.-Y., Jeftinija, K., Rowe, E. W., Jeftinija, S., & Lin, V. S.-Y. (2004). A Polyamidoamine Dendrimer-Capped Mesoporous Silica Nanosphere-Based Gene Transfection Reagent. Journal of the American Chemical Society, 126(41), 13216-13217. doi:10.1021/ja046275mGiri, S., Trewyn, B. G., Stellmaker, M. P., & Lin, V. S.-Y. (2005). Stimuli-Responsive Controlled-Release Delivery System Based on Mesoporous Silica Nanorods Capped with Magnetic Nanoparticles. Angewandte Chemie, 117(32), 5166-5172. doi:10.1002/ange.200501819Giri, S., Trewyn, B. G., Stellmaker, M. P., & Lin, V. S.-Y. (2005). Stimuli-Responsive Controlled-Release Delivery System Based on Mesoporous Silica Nanorods Capped with Magnetic Nanoparticles. Angewandte Chemie International Edition, 44(32), 5038-5044. doi:10.1002/anie.200501819Fujiwara, M., Terashima, S., Endo, Y., Shiokawa, K., & Ohue, H. (2006). Switching catalytic reaction conducted in pore void of mesoporous material by redox gate control. Chemical Communications, (44), 4635. doi:10.1039/b610444dLiu, R., Zhao, X., Wu, T., & Feng, P. (2008). Tunable Redox-Responsive Hybrid Nanogated Ensembles. Journal of the American Chemical Society, 130(44), 14418-14419. doi:10.1021/ja8060886Nguyen, T. D., Liu, Y., Saha, S., Leung, K. C.-F., Stoddart, J. F., & Zink, J. I. (2007). Design and Optimization of Molecular Nanovalves Based on Redox-Switchable Bistable Rotaxanes. Journal of the American Chemical Society, 129(3), 626-634. doi:10.1021/ja065485rCasasús, R., Marcos, M. D., Martínez-Máñez, R., Ros-Lis, J. V., Soto, J., Villaescusa, L. A., … Latorre, J. (2004). Toward the Development of Ionically Controlled Nanoscopic Molecular Gates. Journal of the American Chemical Society, 126(28), 8612-8613. doi:10.1021/ja048095iCasasús, R., Climent, E., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., Soto, J., … Ruiz, E. (2008). Dual Aperture Control on pH- and Anion-Driven Supramolecular Nanoscopic Hybrid Gate-like Ensembles. Journal of the American Chemical Society, 130(6), 1903-1917. doi:10.1021/ja0756772Aznar, E., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., Soto, J., Amorós, P., & Guillem, C. (2009). pH- and Photo-Switched Release of Guest Molecules from Mesoporous Silica Supports. Journal of the American Chemical Society, 131(19), 6833-6843. doi:10.1021/ja810011pAngelos, S., Yang, Y.-W., Khashab, N. M., Stoddart, J. F., & Zink, J. I. (2009). Dual-Controlled Nanoparticles Exhibiting AND Logic. Journal of the American Chemical Society, 131(32), 11344-11346. doi:10.1021/ja9042752Angelos, S., Yang, Y.-W., Patel, K., Stoddart, J. F., & Zink, J. I. (2008). pH-Responsive Supramolecular Nanovalves Based on Cucurbit[6]uril Pseudorotaxanes. Angewandte Chemie, 120(12), 2254-2258. doi:10.1002/ange.200705211Angelos, S., Yang, Y.-W., Patel, K., Stoddart, J. F., & Zink, J. I. (2008). pH-Responsive Supramolecular Nanovalves Based on Cucurbit[6]uril Pseudorotaxanes. Angewandte Chemie International Edition, 47(12), 2222-2226. doi:10.1002/anie.200705211Angelos, S., Khashab, N. M., Yang, Y.-W., Trabolsi, A., Khatib, H. A., Stoddart, J. F., & Zink, J. I. (2009). pH Clock-Operated Mechanized Nanoparticles. Journal of the American Chemical Society, 131(36), 12912-12914. doi:10.1021/ja9010157Du, L., Liao, S., Khatib, H. A., Stoddart, J. F., & Zink, J. I. (2009). Controlled-Access Hollow Mechanized Silica Nanocontainers. Journal of the American Chemical Society, 131(42), 15136-15142. doi:10.1021/ja904982jYang, Q., Wang, S., Fan, P., Wang, L., Di, Y., Lin, K., & Xiao, F.-S. (2005). pH-Responsive Carrier System Based on Carboxylic Acid Modified Mesoporous Silica and Polyelectrolyte for Drug Delivery. Chemistry of Materials, 17(24), 5999-6003. doi:10.1021/cm051198vPark, C., Oh, K., Lee, S. C., & Kim, C. (2007). Controlled Release of Guest Molecules from Mesoporous Silica Particles Based on a pH-Responsive Polypseudorotaxane Motif. Angewandte Chemie, 119(9), 1477-1479. doi:10.1002/ange.200603404Park, C., Oh, K., Lee, S. C., & Kim, C. (2007). Controlled Release of Guest Molecules from Mesoporous Silica Particles Based on a pH-Responsive Polypseudorotaxane Motif. Angewandte Chemie International Edition, 46(9), 1455-1457. doi:10.1002/anie.200603404Chen, L., Di, J., Cao, C., Zhao, Y., Ma, Y., Luo, J., … Jiang, L. (2011). A pH-driven DNA nanoswitch for responsive controlled release. Chemical Communications, 47(10), 2850. doi:10.1039/c0cc04765aCliment, E., Bernardos, A., Martínez-Máñez, R., Maquieira, A., Marcos, M. D., Pastor-Navarro, N., … Amorós, P. (2009). Controlled Delivery Systems Using Antibody-Capped Mesoporous Nanocontainers. Journal of the American Chemical Society, 131(39), 14075-14080. doi:10.1021/ja904456dCliment, E., Martínez-Máñez, R., Sancenón, F., Marcos, M. D., Soto, J., Maquieira, A., & Amorós, P. (2010). Controlled Delivery Using Oligonucleotide-Capped Mesoporous Silica Nanoparticles. Angewandte Chemie, 122(40), 7439-7441. doi:10.1002/ange.201001847Climent, E., Martínez-Máñez, R., Sancenón, F., Marcos, M. D., Soto, J., Maquieira, A., & Amorós, P. (2010). Controlled Delivery Using Oligonucleotide-Capped Mesoporous Silica Nanoparticles. Angewandte Chemie International Edition, 49(40), 7281-7283. doi:10.1002/anie.201001847Patel, K., Angelos, S., Dichtel, W. R., Coskun, A., Yang, Y.-W., Zink, J. I., & Stoddart, J. F. (2008). Enzyme-Responsive Snap-Top Covered Silica Nanocontainers. Journal of the American Chemical Society, 130(8), 2382-2383. doi:10.1021/ja0772086Schlossbauer, A., Kecht, J., & Bein, T. (2009). Biotin-Avidin as a Protease-Responsive Cap System for Controlled Guest Release from Colloidal Mesoporous Silica. Angewandte Chemie, 121(17), 3138-3141. doi:10.1002/ange.200805818Schlossbauer, A., Kecht, J., & Bein, T. (2009). Biotin-Avidin as a Protease-Responsive Cap System for Controlled Guest Release from Colloidal Mesoporous Silica. Angewandte Chemie International Edition, 48(17), 3092-3095. doi:10.1002/anie.200805818Bernardos, A., Aznar, E., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., Soto, J., … Amorós, P. (2009). Enzyme-Responsive Controlled Release Using Mesoporous Silica Supports Capped with Lactose. Angewandte Chemie, 121(32), 5998-6001. doi:10.1002/ange.200900880Bernardos, A., Aznar, E., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., Soto, J., … Amorós, P. (2009). Enzyme-Responsive Controlled Release Using Mesoporous Silica Supports Capped with Lactose. Angewandte Chemie International Edition, 48(32), 5884-5887. doi:10.1002/anie.200900880Bernardos, A., Mondragón, L., Aznar, E., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., … Amorós, P. (2010). Enzyme-Responsive Intracellular Controlled Release Using Nanometric Silica Mesoporous Supports Capped with «Saccharides». ACS Nano, 4(11), 6353-6368. doi:10.1021/nn101499dPark, C., Kim, H., Kim, S., & Kim, C. (2009). Enzyme Responsive Nanocontainers with Cyclodextrin Gatekeepers and Synergistic Effects in Release of Guests. Journal of the American Chemical Society, 131(46), 16614-16615. doi:10.1021/ja9061085Thornton, P. D., & Heise, A. (2010). Highly Specific Dual Enzyme-Mediated Payload Release from Peptide-Coated Silica Particles. Journal of the American Chemical Society, 132(6), 2024-2028. doi:10.1021/ja9094439Coll, C., Mondragón, L., Martínez-Máñez, R., Sancenón, F., Marcos, M. D., Soto, J., … Pérez-Payá, E. (2011). Enzyme-Mediated Controlled Release Systems by Anchoring Peptide Sequences on Mesoporous Silica Supports. Angewandte Chemie, 123(9), 2186-2188. doi:10.1002/ange.201004133Coll, C., Mondragón, L., Martínez-Máñez, R., Sancenón, F., Marcos, M. D., Soto, J., … Pérez-Payá, E. (2011). Enzyme-Mediated Controlled Release Systems by Anchoring Peptide Sequences on Mesoporous Silica Supports. Angewandte Chemie International Edition, 50(9), 2138-2140. doi:10.1002/anie.201004133Cabrera, S., El Haskouri, J., Guillem, C., Latorre, J., Beltrán-Porter, A., Beltrán-Porter, D., … Amorós *, P. (2000). Generalised syntheses of ordered mesoporous oxides: the atrane route. Solid State Sciences, 2(4), 405-420. doi:10.1016/s1293-2558(00)00152-7Goldcamp, M. J., Rosa, D. T., Landers, N. A., Mandel, S. M., Krause Bauer, J. A., & Baldwin, M. J. (2000). Facile and Versatile Synthesis of Polydentate Metal Chelators with Both Amide and Oxime Donor Groups. Synthesis, 2000(14), 2033-2038. doi:10.1055/s-2000-8724Felix, F., Ferguson, J., Guedel, H. U., & Ludi, A. (1980). The electronic spectrum of tris(2,2’-bipyridine)ruthenium(2+). Journal of the American Chemical Society, 102(12), 4096-4102. doi:10.1021/ja00532a019Lytle, F. E., & Hercules, D. M. (1969). Luminescence of tris(2,2’-bipyridine)ruthenium(II) dichloride. Journal of the American Chemical Society, 91(2), 253-257. doi:10.1021/ja01030a00

The intrusive nature of epicardial adipose tissue as revealed by cardiac magnetic resonance

The epicardial adipose tissue (EAT) refers to the deposition of adipose tissue fully enclosed by the pericardial sac. EAT has a complex mixture of adipocytes, nervous tissue, as well as inflammatory, stromal and immune cells secreting bioactive molecules. This heterogeneous composition reveals that it is not a simply fat storage depot, but rather a biologically active organ that appears playing a “dichotomous” role, either protective or proinflammatory and proatherogenic. The cardiac magnetic resonance (CMR) allows a clear visualization of EAT using a specific pulse sequence called steady-state free precession. When abundant, the EAT assumes a pervasive presence not only covering the entire epicardial surface but also invading spaces that usually are almost virtual and separating walls that usually are so close each other to resemble a single wall. To the best of our knowledge, this aspect of cardiac anatomy has never been described before. In this pictorial review, we therefore focus our attention on certain cardiac areas in which EAT, when abundant, is particularly intrusive. In particular, we describe the presence of EAT into: (a) the interatrial groove, the atrioventricular septum, and the inferior pyramidal space, (b) the left lateral ridge, (c) the atrioventricular grooves, and (d) the transverse pericardial sinus. To confirm the reliability in depicting the EAT distribution, we present CMR images side-by-side with corresponding anatomic specimens

Finely tuned temperature-controlled cargo release using paraffin-capped mesoporous silica nanoparticles

Trapped: Mesoporous silica nanoparticles were loaded with a fluorescent guest and functionalized with octadecyltrimethoxysilane. The alkyl chains interact with paraffins, which build a hydrophobic layer around the particle (see picture). Upon melting of the paraffin, the guest molecule is released, as demonstrated in cells for the guest doxorubicin. The release temperature can be tuned by choosing an appropriate paraffin. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Financial support from the Spanish Government (projects MAT2009-14564-C04-01 and SAF2010-15512) and the Generalitat Valenciana (projects PROMETEO/2009/016 and PROMETEO/2010/005) is gratefully acknowledged. L. M. thanks the Generalitat Valenciana for a VALi + d postdoctoral contract. We thank UPV electron microscopy and CIPF confocal microscopy services for technical support.Aznar Gimeno, E.; Mondragón Martínez, L.; Ros-Lis, JV.; Sancenón Galarza, F.; Marcos Martínez, MD.; Martínez Mañez, R.; Soto Camino, J.... (2011). Finely tuned temperature-controlled cargo release using paraffin-capped mesoporous silica nanoparticles. Angewandte Chemie International Edition. (50):11172-11175. https://doi.org/10.1002/anie.20110275611172111755

Exocytosis of mesoporous silica nanoparticles from mammalian cells: from asymmetric cell-to-cell transfer to protein harvesting

The exocytosis of mesoporous silica nanoparticles (MSNs) from mammalian cells is demonstrated for the first time. The differences in the degree of exocytosis of MSNs between healthy and cancer cells are shown to be responsible for the asymmetric transfer of the particles between both cell types. The exo­cytosis of highly adsorbent magnetic MSNs proves to be useful as a means for harvesting biomolecules from living cells