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2. Integration of transcription regulation and functional genomic data reveals lncRNA SNHG6’s role in hematopoietic differentiation and leukemia

Author

Joshua M. Hazan, Raziel Amador, Tahleel Ali-Nasser, Tamar Lahav, Stav Roni Shotan, Miryam Steinberg, Ziv Cohen, Dvir Aran, David Meiri, Yehuda G. Assaraf, Roderic Guigó, and Assaf C. Bester

Subjects
lncRNA, CRISPR screening, Machine learning, Gene regulation, Hematopoiesis., Medicine
Abstract

Abstract Background Long non-coding RNAs (lncRNAs) are pivotal players in cellular processes, and their unique cell-type specific expression patterns render them attractive biomarkers and therapeutic targets. Yet, the functional roles of most lncRNAs remain enigmatic. To address the need to identify new druggable lncRNAs, we developed a comprehensive approach integrating transcription factor binding data with other genetic features to generate a machine learning model, which we have called INFLAMeR (Identifying Novel Functional LncRNAs with Advanced Machine Learning Resources). Methods INFLAMeR was trained on high-throughput CRISPR interference (CRISPRi) screens across seven cell lines, and the algorithm was based on 71 genetic features. To validate the predictions, we selected candidate lncRNAs in the human K562 leukemia cell line and determined the impact of their knockdown (KD) on cell proliferation and chemotherapeutic drug response. We further performed transcriptomic analysis for candidate genes. Based on these findings, we assessed the lncRNA small nucleolar RNA host gene 6 (SNHG6) for its role in myeloid differentiation. Finally, we established a mouse K562 leukemia xenograft model to determine whether SNHG6 KD attenuates tumor growth in vivo. Results The INFLAMeR model successfully reconstituted CRISPRi screening data and predicted functional lncRNAs that were previously overlooked. Intensive cell-based and transcriptomic validation of nearly fifty genes in K562 revealed cell type-specific functionality for 85% of the predicted lncRNAs. In this respect, our cell-based and transcriptomic analyses predicted a role for SNHG6 in hematopoiesis and leukemia. Consistent with its predicted role in hematopoietic differentiation, SNHG6 transcription is regulated by hematopoiesis-associated transcription factors. SNHG6 KD reduced the proliferation of leukemia cells and sensitized them to differentiation. Treatment of K562 leukemic cells with hemin and PMA, respectively, demonstrated that SNHG6 inhibits red blood cell differentiation but strongly promotes megakaryocyte differentiation. Using a xenograft mouse model, we demonstrate that SNHG6 KD attenuated tumor growth in vivo. Conclusions Our approach not only improved the identification and characterization of functional lncRNAs through genomic approaches in a cell type-specific manner, but also identified new lncRNAs with roles in hematopoiesis and leukemia. Such approaches can be readily applied to identify novel targets for precision medicine.

Published
2024
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6. Congenital heart disease in the ESC EORP Registry of Pregnancy and Cardiac disease (ROPAC)

Author

Hall, Roger, Roos-Hesselink, Jolien, Stein, Joerg, Parsonage, William Anthony, Budts, Werner, De Backer, Julie, Grewal, Jasmin, Marelli, Ariane, Kaemmerer, Harald, Jondeau, Guillaume, Johnson, Mark, Maggioni, Aldo P., Tavazzi, Luigi, Thilen, Ulf, Elkayam, Uri, Otto, Catherine, Sliwa, Karen, Aquieri, A., Saad, A., Vega, H. Ruda, Hojman, J., Caparros, J.M., Blanco, M. Vazquez, Arstall, M., Chung, C.M., Mahadavan, G., Aldridge, E., Wittwer, M., Chow, Y.Y., Parsonage, W.A., Lust, K., Collins, N., Warner, G., Hatton, R., Gordon, A., Nyman, E., Stein, J., Donhauser, E., Gabriel, H., Bahshaliyev, A., Guliyev, F., Hasanova, I., Jahangirov, T., Gasimov, Z., Salim, A., Ahmed, C.M., Begum, F., Hoque, M.H., Mahmood, M., Islam, M.N., Haque, P.P., Banerjee, S.K., Parveen, T., Morissens, M., De Backer, J., Demulier, L., de Hosson, M., Budts, W., Beckx, M., Kozic, M., Lovric, M., Kovacevic-Preradovic, T., Chilingirova, N., Kratunkov, P., Wahab, N., McLean, S., Gordon, E., Walter, L., Marelli, A., Montesclaros, A.R., Monsalve, G., Rodriguez, C., Balthazar, F., Quintero, V., Palacio, W., Cadavid, L.A. Mejía, Ortiz, E. Munoz, Hoyos, F. Fortich, Guerrero, E. Arevalo, Ricardo, J. Gandara, Penagos, J. Velasquez, Vavera, Z., Prague, Popelova, J., Vejlstrup, N., Grønbeck, L., Johansen, M., Ersboll, A., Elrakshy, Y., Eltamawy, K., Abd-El Aziz, M. Gamal, El Nagar, A., Ebaid, H., Elenin, H. Abo, Saed, M., Farag, S., Makled, W., Sorour, K., Ashour, Z., El-Sayed, G., Meguid Mahdy, M. Abdel, Taha, N., Dardeer, A., Shabaan, M., Ali, M., Moceri, P., Duthoit, G., Gouton, M., Nizard, J., Baris, L., Cohen, S., Ladouceur, M., Khimoud, D., Iung, B., Berger, F., Olsson, A., Gembruch, U., Merz, W.M., Reinert, E., Clade, S., Kliesch, Y., Wald, C., Sinning, C., Kozlik-Feldmann, R., Blankenberg, S., Zengin-Sahm, E., Mueller, G., Hillebrand, M., Hauck, P., von Kodolitsch, Y., Zarniko, N., Baumgartner, Muenster H., Schmidt, R., Hellige, A., Tutarel, O., Kaemmerer, H., Kuschel, B., Nagdyman, N., Motz, R., Maisuradze, D., Frogoudaki, A., Iliodromitis, E., Anastasiou-Nana, M., Marousi, Triantafyllis, D., Bekiaris, G., Karvounis, H., Giannakoulas, G., Ntiloudi, D., Mouratoglou, S.A., Temesvari, A., Balint, H., Kohalmi, D., Merkely, B., Liptai, C., Nemes, A., Forster, T., Kalapos, A., Berek, K., Havasi, K., Ambrus, N., Shelke, A., Kawade, R., Patil, S., Martanto, E., Aprami, T.M., Purnomowati, A., Cool, C.J., Hasan, M., Akbar, R., Hidayat, S., Dewi, T.I., Permadi, W., Soedarsono, D.A., Ansari-Ramandi, M.M., Samiei, N., Tabib, A., Kashfi, F., Ansari-Ramandi, S., Rezaei, S., Farhan, H. Ali, Al-Hussein, A., Al-Saedi, G., Mahmood, G., Yaseen, I.F., Al-Yousuf, L., AlBayati, M., Mahmood, S., Raheem, S., AlHaidari, T., Dakhil, Z., Thornton, P., Donnelly, J., Bowen, M., Blatt, A., Elbaz-Greener, G., Shotan, A., Yalonetsky, S., Goland, S., Biener, M., Assenza, G. Egidy, Bonvicini, M., Donti, A., Bulgarelli, A., Prandstraller, D., Romeo, C., Crepaz, R., Sciatti, E., Metra, M., Orabona, R., Ali, L. Ait, Festa, P., Fesslova, V., Bonanomi, C., Calcagnino, M., Lombardi, F., Colli, A.M., Ossola, M.W., Gobbi, C., Gherbesi, E., Tondi, L., Schiavone, M., Squillace, M., Carmina, M.G., Maina, A., Macchi, C., Gollo, E., Comoglio, F.M., Montali, N., Re, P., Bordese, R., Todros, T., Donvito, V., Marra, W. Grosso, Sinagra, G., D'Agata Mottolese, B., Bobbo, M., Gesuete, V., Rakar, S., Ramani, F., Niwa, K., Mekebekova, D., Mussagaliyeva, A., Lee, T., Mirrakhimov, E., Abilova, S., Bektasheva, E., Neronova, K., Lunegova, O., Žaliūnas, R., Jonkaitienė, R., Petrauskaitė, J., Laucevicius, A., Jancauskaite, D., Lauciuviene, L., Gumbiene, L., Lankutiene, L., Glaveckaite, S., Laukyte, M., Solovjova, S., Rudiene, V., Chee, K.H., Yim, C.C.-W., Ang, H.L., Kuppusamy, R., Watson, T., Caruana, M., Estensen, M.-E., Kayani, M.G.A. Mahmood, Munir, R., Tomaszuk-Kazberuk, A., Sobkowicz, B., Przepiesc, J., Lesniak-Sobelga, A., Tomkiewicz-Pajak, L., Komar, M., Olszowska, M., Podolec, P., Wisniowska-Smialek, S., Lelonek, M., Faflik, U., Cichocka-Radwan, A., Plaskota, K., Trojnarska, O., Guerra, N., de Sousa, L., Cruz, C., Ribeiro, V., Jovanova, S., Petrescu, V., Jurcut, R., Ginghina, C., Coman, I. Mircea, Musteata, M., Osipova, O., Golivets, T., Khamnagadaev, I., Golovchenko, O., Nagibina, A., Ropatko, I., Gaisin, I.R., Shilina, L. Valeryevna, Sharashkina, N., Shlyakhto, E., Irtyuga, O., Moiseeva, O., Karelkina, E., Zazerskaya, I., Kozlenok, A., Sukhova, I., Jovovic, L., Prokšelj, K., Koželj, M., Askar, A.O., Abdilaahi, A.A., Mohamed, M.H., Dirir, A.M., Sliwa, K., Manga, P., Pijuan-Domenech, A., Galian-Gay, L., Tornos, P., Subirana, M.T., T, M., Subirana, Oliver, J.M., Garcia-Aranda Dominguez, B., Gonzalez, I. Hernandez, Jimenez, J.F. Delgado, Subias, P. Escribano, Murga, N., Elbushi, A., Suliman, A., Jazzar, K., Murtada, M., Ahamed, N., Dellborg, M., Furenas, E., Jinesjo, M., Skoglund, K., Eriksson, P., Gilljam, T., Thilen, U., Tobler, D., Wustmann, K., Schwitz, F., Schwerzmann, M., Rutz, T., Bouchardy, J., Greutmann, M., Lopes, B.M. Santos, Meier, L., Arrigo, M., de Boer, K., Konings, T., Wajon, E., Wagenaar, L.J., Polak, P., Pieper, E.P.G., Roos-Hesselink, J., van Hagen, I., Duvekot, H., Cornette, J.M.J., De Groot, C., van Oppen, C., Sarac, L., Esen, O. Batukan, Enar, S. Catirli, Mondo, C., Ingabire, P., Nalwanga, B., Semu, T., Salih, B.T., Almahmeed, W.A.R., Wani, S., Farook, F.S. Mohamed, Ain, Al, Gerges, F., Komaranchath, A.M., Al bakshi, F., Al Mulla, A., Yusufali, A.H., Al Hatou, E.I., Bazargani, N., Hussain, F., Hudsmith, L., Thompson, P., Thorne, S., Bowater, S., Money-Kyrle, A., Clifford, P., Ramrakha, P., Firoozan, S., Chaplin, J., Bowers, N., Adamson, D., Schroeder, F., Wendler, R., Hammond, S., Nihoyannopoulos, P., Norfolk, Norwich, Hall, R., Freeman, L., Veldtman, G., Kerr, J., Tellett, L., Scott, N., Bhatt, A.B., DeFaria Yeh, D., Youniss, M.A., Wood, M., Sarma, A.A., Tsiaras, S., Stefanescu, A., Duran, J.M., Stone, L., Majdalany, D.S., Chapa, J., Chintala, K., Gupta, P., Botti, J., Ting, J., Davidson, W.R., Wells, G., Sparks, D., Paruchuri, V., Marzo, K., Patel, D., Wagner, W., Ahanya, S.N., Colicchia, L., Jentink, T., Han, K., Loichinger, M., Parker, M., Longtin, C., Yetman, A., Erickson, K., Cramer, J., Tsai, S., Fletcher, B., Warta, S., Cohen, C., Lindblade, C., Puntel, R., Nagaran, K., Croft, N., Gurvitz, M., Otto, C., Talluto, C., Murphy, D., Perlroth, M.G., Ramlakhan, Karishma P., Johnson, Mark R., Lelonek, Malgorzata, Saad, Aly, Gasimov, Zaur, Sharashkina, Natalia V., Thornton, Patrick, Arstall, Margaret, and Roos-Hesselink, Jolien W.

Published
2021
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9. Congenital heart disease in the ESC EORP Registry of Pregnancy and Cardiac disease (ROPAC)

Author

Karishma P. Ramlakhan, Mark R. Johnson, Malgorzata Lelonek, Aly Saad, Zaur Gasimov, Natalia V. Sharashkina, Patrick Thornton, Margaret Arstall, Roger Hall, Jolien W. Roos-Hesselink, Jolien Roos-Hesselink, Joerg Stein, William Anthony Parsonage, Werner Budts, Julie De Backer, Jasmin Grewal, Ariane Marelli, Harald Kaemmerer, Guillaume Jondeau, Mark Johnson, Aldo P. Maggioni, Luigi Tavazzi, Ulf Thilen, Uri Elkayam, Catherine Otto, Karen Sliwa, A. Aquieri, A. Saad, H. Ruda Vega, J. Hojman, J.M. Caparros, M. Vazquez Blanco, M. Arstall, C.M. Chung, G. Mahadavan, E. Aldridge, M. Wittwer, Y.Y. Chow, W.A. Parsonage, K. Lust, N. Collins, G. Warner, R. Hatton, A. Gordon, E. Nyman, J. Stein, E. Donhauser, H. Gabriel, A. Bahshaliyev, F. Guliyev, I. Hasanova, T. Jahangirov, Z. Gasimov, A. Salim, C.M. Ahmed, F. Begum, M.H. Hoque, M. Mahmood, M.N. Islam, P.P. Haque, S.K. Banerjee, T. Parveen, M. Morissens, J. De Backer, L. Demulier, M. de Hosson, W. Budts, M. Beckx, M. Kozic, M. Lovric, T. Kovacevic-Preradovic, N. Chilingirova, P. Kratunkov, N. Wahab, S. McLean, E. Gordon, L. Walter, A. Marelli, A.R. Montesclaros, G. Monsalve, C. Rodriguez, F. Balthazar, V. Quintero, W. Palacio, L.A. Mejía Cadavid, E. Munoz Ortiz, F. Fortich Hoyos, E. Arevalo Guerrero, J. Gandara Ricardo, J. Velasquez Penagos, Z. Vavera, Prague, J. Popelova, N. Vejlstrup, L. Grønbeck, M. Johansen, A. Ersboll, Y. Elrakshy, K. Eltamawy, M. Gamal Abd-El Aziz, A. El Nagar, H. Ebaid, H. Abo Elenin, M. Saed, S. Farag, W. Makled, K. Sorour, Z. Ashour, G. El-Sayed, M. Abdel Meguid Mahdy, N. Taha, A. Dardeer, M. Shabaan, M. Ali, P. Moceri, G. Duthoit, M. Gouton, J. Nizard, L. Baris, S. Cohen, M. Ladouceur, D. Khimoud, B. Iung, F. Berger, A. Olsson, U. Gembruch, W.M. Merz, E. Reinert, S. Clade, Y. Kliesch, C. Wald, C. Sinning, R. Kozlik-Feldmann, S. Blankenberg, E. Zengin-Sahm, G. Mueller, M. Hillebrand, P. Hauck, Y. von Kodolitsch, N. Zarniko, Muenster H. Baumgartner, R. Schmidt, A. Hellige, O. Tutarel, H. Kaemmerer, B. Kuschel, N. Nagdyman, R. Motz, D. Maisuradze, A. Frogoudaki, E. Iliodromitis, M. Anastasiou-Nana, Marousi, D. Triantafyllis, G. Bekiaris, H. Karvounis, G. Giannakoulas, D. Ntiloudi, S.A. Mouratoglou, A. Temesvari, H. Balint, D. Kohalmi, B. Merkely, C. Liptai, A. Nemes, T. Forster, A. Kalapos, K. Berek, K. Havasi, N. Ambrus, A. Shelke, R. Kawade, S. Patil, E. Martanto, T.M. Aprami, A. Purnomowati, C.J. Cool, M. Hasan, R. Akbar, S. Hidayat, T.I. Dewi, W. Permadi, D.A. Soedarsono, M.M. Ansari-Ramandi, N. Samiei, A. Tabib, F. Kashfi, S. Ansari-Ramandi, S. Rezaei, H. Ali Farhan, A. Al-Hussein, G. Al-Saedi, G. Mahmood, I.F. Yaseen, L. Al-Yousuf, M. AlBayati, S. Mahmood, S. Raheem, T. AlHaidari, Z. Dakhil, P. Thornton, J. Donnelly, M. Bowen, A. Blatt, G. Elbaz-Greener, A. Shotan, S. Yalonetsky, S. Goland, M. Biener, G. Egidy Assenza, M. Bonvicini, A. Donti, A. Bulgarelli, D. Prandstraller, C. Romeo, R. Crepaz, E. Sciatti, M. Metra, R. Orabona, L. Ait Ali, P. Festa, V. Fesslova, C. Bonanomi, M. Calcagnino, F. Lombardi, A.M. Colli, M.W. Ossola, C. Gobbi, E. Gherbesi, L. Tondi, M. Schiavone, M. Squillace, M.G. Carmina, A. Maina, C. Macchi, E. Gollo, F.M. Comoglio, N. Montali, P. Re, R. Bordese, T. Todros, V. Donvito, W. Grosso Marra, G. Sinagra, B. D'Agata Mottolese, M. Bobbo, V. Gesuete, S. Rakar, F. Ramani, K. Niwa, D. Mekebekova, A. Mussagaliyeva, T. Lee, E. Mirrakhimov, S. Abilova, E. Bektasheva, K. Neronova, O. Lunegova, R. Žaliūnas, R. Jonkaitienė, J. Petrauskaitė, A. Laucevicius, D. Jancauskaite, L. Lauciuviene, L. Gumbiene, L. Lankutiene, S. Glaveckaite, M. Laukyte, S. Solovjova, V. Rudiene, K.H. Chee, C.C.-W. Yim, H.L. Ang, R. Kuppusamy, T. Watson, M. Caruana, M.-E. Estensen, M.G.A. Mahmood Kayani, R. Munir, A. Tomaszuk-Kazberuk, B. Sobkowicz, J. Przepiesc, A. Lesniak-Sobelga, L. Tomkiewicz-Pajak, M. Komar, M. Olszowska, P. Podolec, S. Wisniowska-Smialek, M. Lelonek, U. Faflik, A. Cichocka-Radwan, K. Plaskota, O. Trojnarska, N. Guerra, L. de Sousa, C. Cruz, V. Ribeiro, S. Jovanova, V. Petrescu, R. Jurcut, C. Ginghina, I. Mircea Coman, M. Musteata, O. Osipova, T. Golivets, I. Khamnagadaev, O. Golovchenko, A. Nagibina, I. Ropatko, I.R. Gaisin, L. Valeryevna Shilina, N. Sharashkina, E. Shlyakhto, O. Irtyuga, O. Moiseeva, E. Karelkina, I. Zazerskaya, A. Kozlenok, I. Sukhova, L. Jovovic, K. Prokšelj, M. Koželj, A.O. Askar, A.A. Abdilaahi, M.H. Mohamed, A.M. Dirir, K. Sliwa, P. Manga, A. Pijuan-Domenech, L. Galian-Gay, P. Tornos, M.T. Subirana, M. T, Subirana, J.M. Oliver, B. Garcia-Aranda Dominguez, I. Hernandez Gonzalez, J.F. Delgado Jimenez, P. Escribano Subias, N. Murga, A. Elbushi, A. Suliman, K. Jazzar, M. Murtada, N. Ahamed, M. Dellborg, E. Furenas, M. Jinesjo, K. Skoglund, P. Eriksson, T. Gilljam, U. Thilen, D. Tobler, K. Wustmann, F. Schwitz, M. Schwerzmann, T. Rutz, J. Bouchardy, M. Greutmann, B.M. Santos Lopes, L. Meier, M. Arrigo, K. de Boer, T. Konings, E. Wajon, L.J. Wagenaar, P. Polak, E.P.G. Pieper, J. Roos-Hesselink, I. van Hagen, H. Duvekot, J.M.J. Cornette, C. De Groot, C. van Oppen, L. Sarac, O. Batukan Esen, S. Catirli Enar, C. Mondo, P. Ingabire, B. Nalwanga, T. Semu, B.T. Salih, W.A.R. Almahmeed, S. Wani, F.S. Mohamed Farook, Al Ain, F. Gerges, A.M. Komaranchath, F. Al bakshi, A. Al Mulla, A.H. Yusufali, E.I. Al Hatou, N. Bazargani, F. Hussain, L. Hudsmith, P. Thompson, S. Thorne, S. Bowater, A. Money-Kyrle, P. Clifford, P. Ramrakha, S. Firoozan, J. Chaplin, N. Bowers, D. Adamson, F. Schroeder, R. Wendler, S. Hammond, P. Nihoyannopoulos, Norwich Norfolk, R. Hall, L. Freeman, G. Veldtman, J. Kerr, L. Tellett, N. Scott, A.B. Bhatt, D. DeFaria Yeh, M.A. Youniss, M. Wood, A.A. Sarma, S. Tsiaras, A. Stefanescu, J.M. Duran, L. Stone, D.S. Majdalany, J. Chapa, K. Chintala, P. Gupta, J. Botti, J. Ting, W.R. Davidson, G. Wells, D. Sparks, V. Paruchuri, K. Marzo, D. Patel, W. Wagner, S.N. Ahanya, L. Colicchia, T. Jentink, K. Han, M. Loichinger, M. Parker, C. Longtin, A. Yetman, K. Erickson, J. Cramer, S. Tsai, B. Fletcher, S. Warta, C. Cohen, C. Lindblade, R. Puntel, K. Nagaran, N. Croft, M. Gurvitz, C. Otto, C. Talluto, D. Murphy, and M.G. Perlroth

Subjects
Congenital heart disease, Pregnancy, Maternal health, Observational registry, Diseases of the circulatory (Cardiovascular) system, RC666-701
Published
2021
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11. Performance of Prognostic Risk Scores in Chronic Heart Failure Patients Enrolled in the European Society of Cardiology Heart Failure Long-Term Registry

Author

Crespo-Leiro, M., Anker, S., Mebazaa, A., Coats, A., Filippatos, G., Ferrari, R., Maggioni, A.P., Piepoli, M.F., Amir, O., Chioncel, O., Dahlström, U., Delgado Jimenez, J.F., Drozdz, J., Erglis, A., Fazlibegovic, E., Fonseca, C., Fruhwald, F., Gatzov, P., Goncalvesova, E., Hassanein, M., Hradec, J., Kavoliuniene, A., Lainscak, M., Logeart, D., Merkely, B., Metra, M., Otljanska, M., Seferovic, P.M., Srbinovska Kostovska, E., Temizhan, A., Tousoulis, D., Ferreira, T., Andarala, M., Fiorucci, E., Folkesson Lefrancq, E., Glémot, M., Gracia, G., Konte, M., Laroche, C., McNeill, P.A., Missiamenou, V., Taylor, C., Auer, J., Ablasser, K., Dolze, T., Brandner, K., Gstrein, S., Poelzl, G., Moertl, D., Reiter, S., Podczeck-Schweighofer, A., Muslibegovic, A., Vasilj, M., Cesko, M., Zelenika, D., Palic, B., Pravdic, D., Cuk, D., Vitlianova, K., Katova, T., Velikov, T., Kurteva, T., Kamenova, D., Antova, M., Sirakova, V., Krejci, J., Mikolaskova, M., Spinar, J., Krupicka, J., Malek, F., Hegarova, M., Lazarova, M., Monhart, Z., Sobhy, M., El Messiry, F., El Shazly, A.H., Elrakshy, Y., Youssef, A., Moneim, A.A., Noamany, M., Reda, A., Abdel Dayem, T.K., Farag, N., Ibrahim Halawa, S., Abdel Hamid, M., Said, K., Saleh, A., Ebeid, H., Hanna, R., Aziz, R., Louis, O., Enen, M.A., Ibrahim, B.S., Nasr, G., Elbahry, A., Sobhy, H., Ashmawy, M., Gouda, M., Aboleineen, W., Bernard, Y., Luporsi, P., Meneveau, N., Pillot, M., Morel, M., Seronde, M.-F., Schiele, F., Briand, F., Delahaye, F., Damy, T., Eicher, J.-C., de Groote, P., Fertin, M., Lamblin, N., Isnard, R., Lefol, C., Thevenin, S., Hagege, A., Jondeau, G., Le Marcis, V., Ly, J.-F., Coisne, D., Lequeux, B., Le Moal, V., Mascle, S., Lotton, P., Behar, N., Donal, E., Thebault, C., Ridard, C., Reynaud, A., Basquin, A., Bauer, F., Codjia, R., Galinier, M., Tourikis, P., Stavroula, M., Stefanadis, C., Chrysohoou, C., Kotrogiannis, I., Matzaraki, V., Dimitroula, T., Karavidas, A., Tsitsinakis, G., Kapelios, C., Nanas, J., Kampouri, H., Nana, E., Kaldara, E., Eugenidou, A., Vardas, P., Saloustros, I., Patrianakos, A., Tsaknakis, T., Evangelou, S., Nikoloulis, N., Tziourganou, H., Tsaroucha, A., Papadopoulou, A., Douras, A., Polgar, L., Kosztin, A., Nyolczas, N., Csaba Nagy, A., Halmosi, R., Elber, J., Alony, I., Shotan, A., Vazan Fuhrmann, A., Romano, S., Marcon, S., Penco, M., Di Mauro, M., Lemme, E., Carubelli, V., Rovetta, R., Bulgari, M., Quinzani, F., Lombardi, C., Bosi, S., Schiavina, G., Squeri, A., Barbieri, A., Di Tano, G., Pirelli, S., Fucili, A., Passero, T., Musio, S., Di Biase, M., Correale, M., Salvemini, G., Brognoli, S., Zanelli, E., Giordano, A., Agostoni, P., Italiano, G., Salvioni, E., Copelli, S., Modena, M.G., Reggianini, L., Valenti, C., Olaru, A., Bandino, S., Deidda, M., Mercuro, G., Cadeddu Dessalvi, C., Marino, P.N., Di Ruocco, M.V., Sartori, C., Piccinino, C., Parrinello, G., Licata, G., Torres, D., Giambanco, S., Busalacchi, S., Arrotti, S., Novo, S., Inciardi, R.M., Pieri, P., Chirco, P.R., Ausilia Galifi, M., Teresi, G., Buccheri, D., Minacapelli, A., Veniani, M., Frisinghelli, A., Priori, S.G., Cattaneo, S., Opasich, C., Gualco, A., Pagliaro, M., Mancone, M., Fedele, F., Cinque, A., Vellini, M., Scarfo, I., Romeo, F., Ferraiuolo, F., Sergi, D., Anselmi, M., Melandri, F., Leci, E., Iori, E., Bovolo, V., Pidello, S., Frea, S., Bergerone, S., Botta, M., Canavosio, F.G., Gaita, F., Merlo, M., Cinquetti, M., Sinagra, G., Ramani, F., Fabris, E., Stolfo, D., Artico, J., Miani, D., Fresco, C., Daneluzzi, C., Proclemer, A., Cicoira, M., Zanolla, L., Marchese, G., Torelli, F., Vassanelli, C., Voronina, N., Tamakauskas, V., Smalinskas, V., Karaliute, R., Petraskiene, I., Kazakauskaite, E., Rumbinaite, E., Vysniauskas, V., Brazyte-Ramanauskiene, R., Petraskiene, D., Stankala, S., Switala, P., Juszczyk, Z., Sinkiewicz, W., Gilewski, W., Pietrzak, J., Orzel, T., Kasztelowicz, P., Kardaszewicz, P., Lazorko-Piega, M., Gabryel, J., Mosakowska, K., Bellwon, J., Rynkiewicz, A., Raczak, G., Lewicka, E., Dabrowska-Kugacka, A., Bartkowiak, R., Sosnowska-Pasiarska, B., Wozakowska-Kaplon, B., Krzeminski, A., Zabojszcz, M., Mirek-Bryniarska, E., Grzegorzko, A., Bury, K., Nessler, J., Zalewski, J., Furman, A., Broncel, M., Poliwczak, A., Bala, A., Zycinski, P., Rudzinska, M., Jankowski, L., Kasprzak, J.D., Michalak, L., Wojtczak Soska, K., Huziuk, I., Retwinski, A., Flis, P., Weglarz, J., Bodys, A., Grajek, S., Kaluzna-Oleksy, M., Straburzynska-Migaj, E., Dankowski, R., Szymanowska, K., Grabia, J., Szyszka, A., Nowicka, A., Samcik, M., Wolniewicz, L., Baczynska, K., Komorowska, K., Poprawa, I., Komorowska, E., Sajnaga, D., Zolbach, A., Dudzik-Plocica, A., Abdulkarim, A.-F., Lauko-Rachocka, A., Kaminski, L., Kostka, A., Cichy, A., Ruszkowski, P., Splawski, M., Fitas, G., Szymczyk, A., Serwicka, A., Fiega, A., Zysko, D., Krysiak, W., Szabowski, S., Skorek, E., Pruszczyk, P., Bienias, P., Ciurzynski, M., Welnicki, M., Mamcarz, A., Folga, A., Zielinski, T., Rywik, T., Leszek, P., Sobieszczanska-Malek, M., Piotrowska, M., Kozar-Kaminska, K., Komuda, K., Wisniewska, J., Tarnowska, A., Balsam, P., Marchel, M., Opolski, G., Kaplon-Cieslicka, A., Gil, R.J., Mozenska, O., Byczkowska, K., Gil, K., Pawlak, A., Michalek, A., Krzesinski, P., Piotrowicz, K., Uzieblo-Zyczkowska, B., Stanczyk, A., Skrobowski, A., Ponikowski, P., Jankowska, E., Rozentryt, P., Polonski, L., Gadula-Gacek, E., Nowalany-Kozielska, E., Kuczaj, A., Kalarus, Z., Szulik, M., Przybylska, K., Klys, J., Prokop-Lewicka, G., Kleinrok, A., Tavares Aguiar, C., Ventosa, A., Pereira, S., Faria, R., Chin, J., De Jesus, I., Santos, R., Silva, P., Moreno, N., Queirós, C., Lourenço, C., Pereira, A., Castro, A., Andrade, A., Oliveira Guimaraes, T., Martins, S., Placido, R., Lima, G., Brito, D., Francisco, A.R., Cardiga, R., Proenca, M., Araujo, I., Marques, F., Moura, B., Leite, S., Campelo, M., Silva-Cardoso, J., Rodrigues, J., Rangel, I., Martins, E., Sofia Correia, A., Peres, M., Marta, L., Ferreira da Silva, G., Severino, D., Durao, D., Leao, S., Magalhaes, P., Moreira, I., Filipa Cordeiro, A., Ferreira, C., Araujo, C., Ferreira, A., Baptista, A., Radoi, M., Bicescu, G., Vinereanu, D., Sinescu, C.-J., Macarie, C., Popescu, R., Daha, I., Dan, G.-A., Stanescu, C., Dan, A., Craiu, E., Nechita, E., Aursulesei, V., Christodorescu, R., Otasevic, P., Simeunovic, D., Ristic, A.D., Celic, V., Pavlovic-Kleut, M., Suzic Lazic, J., Stojcevski, B., Pencic, B., Stevanovic, A., Andric, A., Iric-Cupic, V., Jovic, M., Davidovic, G., Milanov, S., Mitic, V., Atanaskovic, V., Antic, S., Pavlovic, M., Stanojevic, D., Stoickov, V., Ilic, S., Deljanin Ilic, M., Petrovic, D., Stojsic, S., Kecojevic, S., Dodic, S., Cemerlic Adic, N., Cankovic, M., Stojiljkovic, J., Mihajlovic, B., Radin, A., Radovanovic, S., Krotin, M., Klabnik, A., Pernicky, M., Murin, J., Kovar, F., Kmec, J., Semjanova, H., Strasek, M., Savnik Iskra, M., Ravnikar, T., Cernic Suligoj, N., Komel, J., Fras, Z., Jug, B., Glavic, T., Losic, R., Bombek, M., Krajnc, I., Krunic, B., Horvat, S., Kovac, D., Rajtman, D., Cencic, V., Letonja, M., Winkler, R., Valentincic, M., Melihen-Bartolic, C., Bartolic, A., Pusnik Vrckovnik, M., Kladnik, M., Slemenik Pusnik, C., Marolt, A., Klen, J., Drnovsek, B., Leskovar, B., Fernandez Anguita, M.J., Gallego Page, J.C., Salmeron Martinez, F.M., Andres, J., Genis, A.B., Mirabet, S., Mendez, A., Garcia-Cosio, L., Roig, E., Leon, V., Gonzalez-Costello, J., Muntane, G., Garay, A., Alcade-Martinez, V., Lopez Fernandez, S., Rivera-Lopez, R., Puga-Martinez, M., Fernandez-Alvarez, M., Serrano-Martinez, J.L., Grille-Cancela, Z., Marzoa-Rivas, R., Blanco-Canosa, P., Paniagua-Martin, M.J., Barge-Caballero, E., Laynez Cerdena, I., Famara Hernandez Baldomero, I., Lara Padron, A., Ofelia Rosillo, S., Dalmau Gonzalez-Gallarza, R., Salvador Montanes, O., Iniesta Manjavacas, A.M., Castro Conde, A., Araujo, A., Soria, T., Garcia-Pavia, P., Gomez-Bueno, M., Cobo-Marcos, M., Alonso-Pulpon, L., Segovia Cubero, J., Sayago, I., Gonzalez-Segovia, A., Briceno, A., Escribano Subias, P., Vicente Hernandez, M., Ruiz Cano, M.J., Gomez Sanchez, M.A., Barrios Garrido-Lestache, E., Garcia Pinilla, J.M., Garcia de la Villa, B., Sahuquillo, A., Bravo Marques, R., Torres Calvo, F., Perez-Martinez, M.T., Gracia-Rodenas, M.R., Garrido-Bravo, I.P., Pastor-Perez, F., Pascual-Figal, D.A., Diaz Molina, B., Orus, J., Epelde Gonzalo, F., Bertomeu, V., Valero, R., Martinez-Abellan, R., Quiles, J., Rodrigez-Ortega, J.A., Mateo, I., ElAmrani, A., Fernandez-Vivancos, C., Bierge Valero, D., Almenar-Bonet, L., Sanchez-Lazaro, I.J., Marques-Sule, E., Facila-Rubio, L., Perez-Silvestre, J., Garcia-Gonzalez, P., Ridocci-Soriano, F., Garcia-Escriva, D., Pellicer-Cabo, A., de la Fuente Galan, L., Lopez Diaz, J., Recio Platero, A., Arias, J.C., Blasco-Peiro, T., Sanz Julve, M., Sanchez-Insa, E., Aured-Guallar, C., Portoles-Ocampo, A., Melin, M., Hägglund, E., Stenberg, A., Lindahl, I.-M., Asserlund, B., Olsson, L., Afzelius, M., Karlström, P., Tengvall, L., Wiklund, P.-A., Olsson, B., Kalayci, S., Cavusoglu, Y., Gencer, E., Yilmaz, M.B., Gunes, H., Canepa, Marco, Fonseca, Candida, Chioncel, Ovidiu, Laroche, Cécile, Crespo-Leiro, Maria G., Coats, Andrew J.S., Mebazaa, Alexandre, Piepoli, Massimo F., Tavazzi, Luigi, and Maggioni, Aldo P.

Published
2018
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12. Differentiation between myopericarditis and acute myocardial infarction on presentation in the emergency department using the admission C-reactive protein to troponin ratio.

Author

Simcha R Meisel, Hamuda Nashed, Randa Natour, Rami Abu Fanne, Majdi Saada, Naama Amsalem, Carmel Levin, Ofer Kobo, Aaron Frimerman, Yaniv Levi, Jameel Mohsen, Avraham Shotan, Ariel Roguin, and Michael Kleiner-Shochat

Subjects
Medicine, Science
Abstract

BackgroundThe treatment of myopericarditis is different than that of acute myocardial infarction (AMI). However, since their clinical presentation is frequently similar it may be difficult to distinguish between these entities despite a disparate underlying pathogenesis. Myopericarditis is primarily an inflammatory disease associated with high C-reactive protein (CRP) and relatively low elevated troponin concentrations, while AMI is characterized by the opposite. We hypothesized that evaluation of the CRP/troponin ratio on presentation to the emergency department could improve the differentiation between these two related clinical entities whose therapy is different. Such differentiation should facilitate triage to appropriate and expeditious therapy.MethodsWe evaluated the CRP/troponin ratio on presentation among patients consecutively included in a large single center registry that included 1898 consecutive patients comprising 1025 ST-elevation myocardial infarction (STEMI) patients, 518 Non-STEMI (NSTEMI) patients, and 355 patients diagnosed on discharge as myopericarditis. CRP and troponin were sampled on admission in all patients and their ratio was assessed against discharge diagnosis. ROC analysis of the CRP/troponin ratios evaluated the diagnostic accuracy of myopericarditis against all AMI, STEMI, and NSTEMI patients.ResultsMedian admission CRP/troponin ratios were 84, 65, and 436 mg×ml/liter×ng in STEMI, NSTEMI and myopericarditis groups, respectively (p500 resulted in specificity exceeding 85%, and for a ratio>1000, specificity>92%.ConclusionThe CRP/troponin ratio can serve as an effective tool to differentiate between myopericarditis and AMI. In the appropriate clinical context, the CRP/troponin ratio may preclude further evaluation.

Published
2021
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13. Direct Admission of Patients With ST‐Segment–Elevation Myocardial Infarction to the Catheterization Laboratory Shortens Pain‐to‐Balloon and Door‐to‐Balloon Time Intervals but Only the Pain‐to‐Balloon Interval Impacts Short‐ and Long‐Term Mortality

Author

Simcha R. Meisel, Michael Kleiner‐Shochat, Rami Abu‐Fanne, Aaron Frimerman, Asaf Danon, Sa’ar Minha, Yaniv Levi, Alex Blatt, Jameel Mohsen, Avraham Shotan, and Ariel Roguin

Subjects
admission pathway, long‐term mortality, ST‐segment–elevation myocardial infarction, primary percutaneous coronary intervention, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background Shortening the pain‐to‐balloon (P2B) and door‐to‐balloon (D2B) intervals in patients with ST‐segment–elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PPCI) is essential in order to limit myocardial damage. We investigated whether direct admission of PPCI‐treated patients with STEMI to the catheterization laboratory, bypassing the emergency department, expedites reperfusion and improves prognosis. Methods and Results Consecutive PPCI‐treated patients with STEMI included in the ACSIS (Acute Coronary Syndrome in Israel Survey), a prospective nationwide multicenter registry, were divided into patients admitted directly or via the emergency department. The impact of the P2B and D2B intervals on mortality was compared between groups by logistic regression and propensity score matching. Of the 4839 PPCI‐treated patients with STEMI, 1174 were admitted directly and 3665 via the emergency department. Respective median P2B and D2B were shorter among the directly admitted patients with STEMI (160 and 35 minutes) compared with those admitted via the emergency department (210 and 75 minutes, P

Published
2021
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14. The Level of Methionine Residues in Storage Proteins Is the Main Limiting Factor of Protein-Bound-Methionine Accumulation in Arabidopsis Seeds

Author

Aiswarya Girija, David Shotan, Yael Hacham, and Rachel Amir

Subjects
2S sunflower albumin, cystathionine-γ-synthase, metabolic profiling, metabolism, methionine, seed storage proteins, Plant culture, SB1-1110
Abstract

The low level of methionine, an essential sulfur-containing amino acid, limits the nutritional quality of seeds. Two main factors can control the level of protein-bound methionine: the level of free methionine that limits protein accumulation and the methionine residues inside the storage proteins. To reveal the main limiting factor, we generated transgenic Arabidopsis thaliana seed-specific plants expressing the methionine-rich sunflower seed storage (SSA) protein (A1/A2). The contents of protein-bound methionine in the water-soluble protein fraction that includes the SSA in A1/A2 were 5.3- and 10.5-fold, respectively, compared to control, an empty vector (EV). This suggests that free methionine can support this accumulation. To elucidate if the level of free methionine could be increased further in the protein-bound methionine, these lines were crossed with previously characterized plants having higher levels of free methionine in seeds (called SSE). The progenies of the crosses (A1S, A2S) exhibited the highest level of protein-bound methionine, but this level did not differ significantly from A2, suggesting that all the methionine residues of A2 were filled with methionine. It also suggests that the content of methionine residues in the storage proteins is the main limiting factor. The results also proposed that the storage proteins can change their content in response to high levels of free methionine or SSA. This was assumed since the water-soluble protein fraction was highest in A1S/A2S as well as in SSE compared to EV and A1/A2. By using these seeds, we also aimed at gaining more knowledge about the link between high free methionine and the levels of metabolites that usually accumulate during abiotic stresses. This putative connection was derived from a previous analysis of SSE. The results of metabolic profiling showed that the levels of 29 and 20 out of the 56 metabolites were significantly higher in SSE and A1, respectively, that had higher level of free methionine, compared A1S/A2S, which had lower free methionine levels. This suggests a strong link between high free methionine and the accumulation of stress-associated metabolites.

Published
2020
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18. HT-KZ detector system: R&D considerations and prototype performance

Author

Uakhitov Tileubek, Batyrkhanov Ayan, Beznosko Dmitriy, Iakovlev Alexander, Jakupov Shotan, Kaipiyev Amir, Konysbayeva Arailym, Yeltokov Alikhan, Yessimbet Kamilya, and Zhukov Valeriy

Subjects
Physics, QC1-999
Abstract

Following the experience with the Horizon-10T detector systems, a completely new detector of Extensive Air Showers (EAS) has been designed to be built at Nazarbayev University, Astana, Kazakhstan. The motivation of building HorizonT-Kazakhstan is to study in detail the phenomenon of the multi-modal EAS events that were initially explored by Horizon-8T and 10T detector systems. This detector will have a ns-level resolution of charged particle arrival times and pulse shape resolution. Each detection point is designed to have a total scintillation area approximately equal to 7.7 m2 and consists of three 1.6×1.6 m detectors located in a triangular arrangement for the local determination of the EAS disk arrival direction, and to have ns precision in timing between points. Local arrival direction is important following evidence of large angle differences in the multimodal events seen previously.

Published
2019
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28. Baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF)

Author

McMurray, John J.V., Anand, Inder S., Diaz, Rafael, Maggioni, Aldo P., OʼConnor, Christopher, Pfeffer, Marc A., Solomon, Scott D., Tendera, Michal, van Veldhuisen, Dirk J., Albizem, Moetaz, Cheng, Sunfa, Scarlata, Debra, Swedberg, Karl, Young, James B., Amuchastegui, M., Belziti, C., Bluguermann, J., Caccavo, M., Cartasegna, L., Colque, R., Cuneo, C., Fernandez, A., Gabito, A., Goicochea, R., Gonzalez, M., Gorosito, V., Grinfeld, L., Hominal, M., Kevorkian, R., Litvak Bruno, M., Llanos, J., Mackinnon, I., Manuale, O., Marzetti, E., Nul, D., Perna, E., Riccitelli, M., Sanchez, A., Santos, D., Schygiel, P., Toblli, J., Vogel, D., Aggarwal, A., Amerena, J., De Looze, F., Fletcher, P., Hare, D., Ireland, M., Krum, H., Lattimore, J., Marwick, T., Sindone, A., Thompson, P., Waites, J., Altenberger, J., Ebner, C., Lenz, K., Pacher, R., Poelzl, G., Charlier, F., de Ceuninck, M., De Keulenaer, G., Dendale, P., Maréchal, P., Mullens, W., Thoeng, J., Vanderheyden, M., Vanhaecke, J., Weytjens, C., Wollaert, B., Albuquerque, D., Almeida, D., Aspe y Rosas, J., Bocchi, E., Bordignon, S., Clausell, N., Kaiser, S., Leaes, P., Martins Alves, S., Montera, M., Moura, L., Pereira de Castro, R., Rassi, S., Reis, A., Saraiva, J., Simões, M., Souza Neto, J., Teixeira, M., Benov, H., Chompalova, B., Donova, T., Georgiev, P., Gotchev, D., Goudev, A., Grigorov, M., Guenova, D., Hergeldjieva, V., Ivanov, D., Kostova, E., Manolova, A., Marchev, S., Nikolov, F., Popov, A., Raev, D., Tzekova, M., Czarnecki, W., Giannetti, N., Haddad, H., Heath, J., Huynh, T., Lepage, S., Liu, P., Lonn, E., Ma, P., Manyari, D., Moe, G., Parker, J., Pesant, Y., Rajda, M., Ricci, J., Roth, S., Sestier, F., Sluzar, V., Sussex, B., Vizel, S., Antezana, G., Bugueno, C., Castro, P., Conejeros, C., Manriquez, L., Martinez, D., Potthoff, S., Stockins, B., Vukasovic, J., Gregor, P., Herold, M., Jerabek, O., Jirmar, R., Kuchar, R., Linhart, A., Podzemska, B., Soucek, M., Spac, J., Spacek, R., Vodnansky, P., Bronnum-Schou, J., Clemmensen, K., Egstrup, K., Jensen, G., Kjoller-Hansen, L., Kober, L., Markenvard, J., Rokkedal, J., Skagen, K., Torp-Pedersen, C., Tuxen, C., Videbak, L., Laks, T., Vahula, V., Harjola, V., Kettunen, R., Kotila, M., Bauer, F., Cohen Solal, A., Coisne, D., Davy, J., De Groote, P., Dos Santos, P., Funck, F., Galinier, M., Gibelin, P., Isnard, R., Neuder, Y., Roul, G., Sabatier, R., Trochu, J., Anker, S., Denny, S., Dreykluft, T., Flesch, M., Genth-Zotz, S., Hambrecht, R., Hein, J., Jeserich, M., John, M., Kreider-Stempfle, H., Laufs, U., Muellerleile, K., Natour, M., Sandri, M., Schäufele, T., von Hodenberg, E., Weyland, K., Winkelmann, B., Tse, H., Yan, B., Barsi, B., Csikasz, J., Dezsi, C., Edes, I., Forster, T., Karpati, P., Kerekes, C., Kis, E., Kosa, I., Lupkovics, G., Nagy, A., Preda, I., Ronaszeki, A., Tomcsanyi, J., Zamolyi, K., Agarwal, D., Bahl, V., Bordoloi, A., Chockalingam, K., Chopda, M., Chopra, V., Dugal, J., Ghaisas, N., Ghosh, S., Grant, P., Hiremath, S., Iyengar, S., Jagadeesa Subramania, B., Jain, P., Joshi, A., Khan, A., Mullasari, A., Naik, S., Oomman, A., Pai, V., Pareppally Gopal, R., Parikh, K., Patel, T., Prakash, V., Sastry, B., Sathe, S., Sinha, N., Srikanthan, V., Subburamakrishnan, P., Thacker, H., Wander, G., Admon, D., Katz, A., Klainman, E., Lewis, B., Marmor, A., Moriel, M., Mosseri, M., Shotan, A., Weinstein, J., Zimlichman, R., Agostoni, P., Albanese, M., Alunni, G., Bini, R., Boccanelli, A., Bolognese, L., Campana, C., Carbonieri, E., Carpino, C., Checco, L., Cosmi, F., DʼAngelo, G., De Cristofaro, M., Floresta, A., Fucili, A., Galvani, M., Ivleva, A., Marra, S., Musca, G., Peccerillo, N., Perrone Filardi, P., Picchio, E., Russo, T., Scelsi, L., Senni, M., Tavazzi, L., Erglis, A., Jasinkevica, I., Kakurina, N., Veze, I., Volans, E., Bagdonas, A., Berukstis, E., Celutkiene, J., Dambrauskaite, A., Jarasuniene, D., Luksiene, D., Rudys, A., Sakalyte, G., Sliaziene, S., Aguilar-Romero, R., Cardona-Muñoz, E., Castro-Jimenez, J., Chavez-Herrera, J., Chuquiure Valenzuela, E., De la Pena, G., Herrera, E., Leiva-Pons, J., Lopez Alvarado, A., Mendez Machado, G., Ramos-Lopez, G., Basart, D., Buijs, E., Cornel, J., de Leeuw, M., Dijkgraaf, R., Dunselman, P., Freericks, M., Hamraoui, K., Lenderlink, T., Linssen, G., Lodewick, P., Lodewijks, C., Lok, D., Nierop, P., Ronner, E., Somsen, A., van Dantzig, J., van der Burgh, P., van Kempen, L., van Vlies, B., Voors, A., Wardeh, A., Willems, F., Dickstein, K., Gundersen, T., Hole, T., Thalamus, J., Westheim, A., Dabrowski, M., Gorski, J., Korewicki, J., Kuc, K., Miekus, P., Musial, W., Niegowska, J., Piotrowski, W., Podolec, P., Polonski, L., Ponikowski, P., Rynkiewicz, A., Szelemej, R., Trusz-Gluza, M., Ujda, M., Wojciechowski, D, Wysokinski, A., Camacho, A., Fonseca, C., Monteiro, P., Apetrei, E., Bruckner, I., Carasca, E., Coman, I., Datcu, M., Dragulescu, S., Ionescu, P., Iordachescu-Petica, D., Manitiu, I., Popa, V., Pop-Moldovan, A., Radoi, M., Stamate, S., Tomescu, M., Vita, I., Aroutiounov, G., Ballyuzek, M., Bart, B., Churina, S., Glezer, M., Goloshchekin, B., Ivleva, A., Kobalava, Z., Kostenko, V., Lopatin, Y., Martynov, A., Orlov, V., Semernin, E., Shogenov, Z., Sidorenko, B., Skvortsov, A., Storzhakov, G., Sulimov, V., Talibov, O., Tereshenko, S., Tsyrline, V., Zadionchenko, V., Zateyshchikov, D., Dzupina, A., Hranai, M., Kmec, J., Micko, K., Murin, J., Pella, D., Sojka, G., Spisak, V., Vahala, P., Vinanska, D., Badat, A., Bayat, J., Dawood, S., Delport, E., Ellis, G., Garda, R., Klug, E., Mabin, T., Naidoo, D., Pretorius, M., Ranjith, N., Van Zyl, L., Weich, H., Anguita, M., Berrazueta, J., Bruguera i Cortada, J., de Teresa, E., Gómez Sánchez, M., González Juanatey, J., Gonzalez-Maqueda, I., Jordana, R., Lupon, J., Manzano, L., Pascual Figal, D., Pulpón, L., Recio, J., Ridocci Soriano, F., Rodríguez Lambert, J., Roig Minguell, E., Roig Minguell, E., Romero, J., Valdovinos, P., Klintberg, L., Kronvall, T., Lycksell, M., Morner, S., Rydberg, E., Swedberg, K., Timberg, I., Wikstrom, G., Moccetti, T.4, Ashok, J., Banerjee, P., Carr-White, G., Cleland, J., Connolly, E., Francis, M., Greenbaum, R., Kadr, H., Lindsay, S., McMurray, J., Megarry, S., Memon, A., Murdoch, D., Senior, R., Squire, I., Tan, L., Witte, K., Adams, K., Adamson, P., Adler, A., Altschul, L., Altschuller, A., Amirani, H., Anand, I., Andreou, C., Ansari, M., Antonishen, M., Banchs, H., Banerjee, S., Banish, D., Bank, A., Barbagelata, A., Barnard, D., Bellinger, R., Benn, A., Berk, M., Berry, B., Bethala, V., Bilazarian, S., Bisognano, J., Bleyer, F., Blum, M., Boehmer, J., Bouchard, A., Boyle, A., Bozkurt, B., Brown, C., Burlew, B., Burnham, K., Butler, J., Call, J., Cambier, P., Cappola, T., Carlson, R., Chandler, B., Chandra, R., Chandraratna, P., Chernick, R., Colan, D., Colfer, H., Colucci, W., Connelly, T., Costantini, O., Dadkhah, S., Dauber, I., Davis, J., Davis, S., Denning, S., Drazner, M., Dunlap, S., Egbujiobi, L., Elkayam, U., Elliott, J., El-Shahawy, M., Essandoh, L., Ewald, G., Fang, J., Farhoud, H., Felker, G., Fernandez, J., Festin, R., Fishbein, G., Florea, V., Flores, E., Floro, J., Gabris, M., Garg, M., Gatewood, R., Geller, M., Ghali, J., Ghumman, W., Gibbs, G., Gillespie, E., Gilmore, R., Gogia, H., Goldberg, L., Gradus-Pizlo, I., Grainger, T., Gudmundsson, G., Gunawardena, D., Gupta, D., Hack, T., Hall, S., Hamroff, G., Hankins, S., Hanna, M., Hargrove, J., Haught, W., Hauptman, P., Hazelrigg, M., Herzog, C., Heywood, J., Hill, T., Hilton, T., Hirsch, H., Hunter, J., Ibrahim, H., Imburgia, M., Iteld, B., Jackson, B., Jaffrani, N., Jain, D., Jain, A., James, M., Jimenez, J., Johnson, E., Kale, P., Kaneshige, A., Kapadia, S., Karia, D., Karlsberg, R., Katholi, R., Kerut, E., Khoury, W., Kipperman, R., Klapholz, M., Kosinski, E., Kozinn, M., Kraus, D., Krueger, S., Krum, H., Kumar, S., Lader, E., Lee, C., Levy, W., Lewis, E., Light-McGroary, K., Loh, I., Lombardi, W., Machado, C., Maislos, F., Mancini, D., Markus, T., Mather, P., McCants, K., McGrew, F., McLaurin, B., McMillan, E., McNamara, D., Meyer, T., Meymandi, S., Miller, A., Minami, E., Modi, M., Mody, F., Mohanty, P., Moscoso, R., Moskowitz, R., Moustafa, M., Mullen, M., Naz, T., Noonan, T., OʼBrien, T., Oellerich, W., Oren, R., Pamboukian, S., Pereira, N., Pitt, W., Porter, C., Prabhu, S., Promisloff, S., Ratkovec, R., Richardson, R., Ross, A., Saleh, N., Saltzberg, M., Sarkar, S., Schmedtje, J., Schneider, R., Schuyler, G., Shanes, J., Sharma, A., Siegel, C., Siegel, R., Silber, D., Singh, V., Singh, N., Singh, J., Sklar, J., Small, R., Smith, A., Smith, E., Smith, E., Smull, D., Sotolongo, R., Staniloae, C., Stapleton, D., Steele, P., Stehlik, J., Stein, M., Tang, W., Thadani, U., Torre-Amoine, G., Trichon, B., Tsai, C., Tummala, R., Van Bakel, A., Vicari, R., Vijay, N., Vijayaraghavan, K., Vittorio, T., Vossler, M., Wagoner, L., Wallis, D., Ward, N., Widmer, M., Wight, J., Wilkins, C., Williams, C., Williams, G., Winchester, M., Winkel, E., Wittmer, B., Wood, D., Wormer, D., Wright, R., Xu, Z., Yasin, M., and Zolty, R.

Published
2013
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30. Maternal and fetal outcomes of subsequent pregnancies in women with peripartum cardiomyopathy

Author

Elkayam, Uri, Tummala, Padmini P., Rao, Kalpana, Akhter, Mohammed W., Karaalp, Ilyas S., Wani, Omar R., Hameed, Afshan, Gviazda, Israel, and Shotan, Avraham

Subjects
Cardiomyopathy -- Prognosis, Pregnancy, Complications of -- Prognosis, Pregnant women -- Diseases
Abstract

Women with a history of peripartum cardiomyopathy who become pregnant have a high risk of heart failure and death. Peripartum cardiomyopathy is a heart disease that occurs during pregnancy or in the postpartum period. Most women recover partially or completely.

Published
2001

32. ESC Guidelines on the management of cardiovascular diseases during pregnancy: The Task Force on the Management of Cardiovascular Diseases during Pregnancy of the European Society of Cardiology (ESC)

Author

Regitz-Zagrosek, Vera, Blomstrom Lundqvist, Carina, Borghi, Claudio, Cifkova, Renata, Ferreira, Rafael, Foidart, Jean-Michel, Gibbs, J. Simon R., Gohlke-Baerwolf, Christa, Gorenek, Bulent, Iung, Bernard, Kirby, Mike, Maas, Angela H. E. M., Morais, Joao, Nihoyannopoulos, Petros, Pieper, Petronella G., Presbitero, Patrizia, Roos-Hesselink, Jolien W., Schaufelberger, Maria, Seeland, Ute, Torracca, Lucia, Bax, Jeroen, Auricchio, Angelo, Baumgartner, Helmut, Ceconi, Claudio, Dean, Veronica, Deaton, Christi, Fagard, Robert, Funck-Brentano, Christian, Hasdai, David, Hoes, Arno, Knuuti, Juhani, Kolh, Philippe, McDonagh, Theresa, Moulin, Cyril, Poldermans, Don, Popescu, Bogdan A., Reiner, Zeljko, Sechtem, Udo, Sirnes, Per Anton, Torbicki, Adam, Vahanian, Alec, Windecker, Stephan, Baumgartner, Helmut, Deaton, Christi, Aguiar, Carlos, Al-Attar, Nawwar, Garcia, Angeles Alonso, Antoniou, Anna, Coman, Ioan, Elkayam, Uri, Gomez-Sanchez, Miguel Angel, Gotcheva, Nina, Hilfiker-Kleiner, Denise, Kiss, Robert Gabor, Kitsiou, Anastasia, Konings, Karen T. S., Lip, Gregory Y. H., Manolis, Athanasios, Mebaaza, Alexandre, Mintale, Iveta, Morice, Marie-Claude, Mulder, Barbara J., Pasquet, Agnès, Price, Susanna, Priori, Silvia G., Salvador, Maria J., Shotan, Avraham, Silversides, Candice K., Skouby, Sven O., Stein, Jörg-Ingolf, Tornos, Pilar, Vejlstrup, Niels, Walker, Fiona, and Warnes, Carole

Published
2011
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43. Differentiation between myopericarditis and acute myocardial infarction on presentation in the emergency department using the admission C-reactive protein to troponin ratio.

Author

Meisel, Simcha R., Nashed, Hamuda, Natour, Randa, Abu Fanne, Rami, Saada, Majdi, Amsalem, Naama, Levin, Carmel, Kobo, Ofer, Frimerman, Aaron, Levi, Yaniv, Mohsen, Jameel, Shotan, Avraham, Roguin, Ariel, and Kleiner-Shochat, Michael

Subjects
MYOCARDIAL infarction, TROPONIN, COPEPTINS, HOSPITAL emergency services, YIELD curve (Finance), HOSPITAL admission & discharge
Abstract

Background: The treatment of myopericarditis is different than that of acute myocardial infarction (AMI). However, since their clinical presentation is frequently similar it may be difficult to distinguish between these entities despite a disparate underlying pathogenesis. Myopericarditis is primarily an inflammatory disease associated with high C-reactive protein (CRP) and relatively low elevated troponin concentrations, while AMI is characterized by the opposite. We hypothesized that evaluation of the CRP/troponin ratio on presentation to the emergency department could improve the differentiation between these two related clinical entities whose therapy is different. Such differentiation should facilitate triage to appropriate and expeditious therapy. Methods: We evaluated the CRP/troponin ratio on presentation among patients consecutively included in a large single center registry that included 1898 consecutive patients comprising 1025 ST-elevation myocardial infarction (STEMI) patients, 518 Non-STEMI (NSTEMI) patients, and 355 patients diagnosed on discharge as myopericarditis. CRP and troponin were sampled on admission in all patients and their ratio was assessed against discharge diagnosis. ROC analysis of the CRP/troponin ratios evaluated the diagnostic accuracy of myopericarditis against all AMI, STEMI, and NSTEMI patients. Results: Median admission CRP/troponin ratios were 84, 65, and 436 mg×ml/liter×ng in STEMI, NSTEMI and myopericarditis groups, respectively (p<0.001) demonstrating good differentiating capability. The Receiver-operator-curve of admission CRP/troponin ratio for diagnosis of myopericarditis against all AMI, STEMI, and NSTEMI patients yielded an area-under-the curve of 0.74, 0.73, and 0.765, respectively. CRP/troponin ratio>500 resulted in specificity exceeding 85%, and for a ratio>1000, specificity>92%. Conclusion: The CRP/troponin ratio can serve as an effective tool to differentiate between myopericarditis and AMI. In the appropriate clinical context, the CRP/troponin ratio may preclude further evaluation. [ABSTRACT FROM AUTHOR]

Published
2021
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47. Microcavity-coupled emitters in hexagonal boron nitride.

Author

Proscia, Nicholas V., Jayakumar, Harishankar, Ge, Xiaochen, Lopez-Morales, Gabriel, Shotan, Zav, Zhou, Weidong, Meriles, Carlos A., and Menon, Vinod M.

Subjects
BORON nitride, WHISPERING gallery modes, OPTICAL resonators
Abstract

Integration of quantum emitters in photonic structures is an important step in the broader quest to generate and manipulate on-demand single photons via compact solid-state devices. Unfortunately, implementations relying on material platforms that also serve as the emitter host often suffer from a tradeoff between the desired emitter properties and the photonic system practicality and performance. Here, we demonstrate "pick and place" integration of a Si3N4 microdisk optical resonator with a bright emitter host in the form of ∼20-nm-thick hexagonal boron nitride (hBN). The film folds around the microdisk maximizing contact to ultimately form a hybrid hBN/Si3N4 structure. The local strain that develops in the hBN film at the resonator circumference deterministically activates a low density of defect emitters within the whispering gallery mode volume of the microdisk. These conditions allow us to demonstrate cavity-mediated out-coupling of emission from defect states in hBN through the microdisk cavity modes. Our results pave the route toward the development of chip-scale quantum photonic circuits with independent emitter/resonator optimization for active and passive functionalities. [ABSTRACT FROM AUTHOR]

Published
2020
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48. The Level of Methionine Residues in Storage Proteins Is the Main Limiting Factor of Protein-Bound-Methionine Accumulation in Arabidopsis Seeds.

Author

Girija, Aiswarya, Shotan, David, Hacham, Yael, and Amir, Rachel

Subjects
METHIONINE, ESSENTIAL amino acids, SUNFLOWER seeds, PROTEINS, ARABIDOPSIS, ARABIDOPSIS thaliana, SEED storage
Abstract

The low level of methionine, an essential sulfur-containing amino acid, limits the nutritional quality of seeds. Two main factors can control the level of protein-bound methionine: the level of free methionine that limits protein accumulation and the methionine residues inside the storage proteins. To reveal the main limiting factor, we generated transgenic Arabidopsis thaliana seed-specific plants expressing the methionine-rich sunflower seed storage (SSA) protein (A1/A2). The contents of protein-bound methionine in the water-soluble protein fraction that includes the SSA in A1/A2 were 5.3- and 10.5-fold, respectively, compared to control, an empty vector (EV). This suggests that free methionine can support this accumulation. To elucidate if the level of free methionine could be increased further in the protein-bound methionine, these lines were crossed with previously characterized plants having higher levels of free methionine in seeds (called SSE). The progenies of the crosses (A1S, A2S) exhibited the highest level of protein-bound methionine, but this level did not differ significantly from A2, suggesting that all the methionine residues of A2 were filled with methionine. It also suggests that the content of methionine residues in the storage proteins is the main limiting factor. The results also proposed that the storage proteins can change their content in response to high levels of free methionine or SSA. This was assumed since the water-soluble protein fraction was highest in A1S/A2S as well as in SSE compared to EV and A1/A2. By using these seeds, we also aimed at gaining more knowledge about the link between high free methionine and the levels of metabolites that usually accumulate during abiotic stresses. This putative connection was derived from a previous analysis of SSE. The results of metabolic profiling showed that the levels of 29 and 20 out of the 56 metabolites were significantly higher in SSE and A1, respectively, that had higher level of free methionine, compared A1S/A2S, which had lower free methionine levels. This suggests a strong link between high free methionine and the accumulation of stress-associated metabolites. [ABSTRACT FROM AUTHOR]

Published
2020
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