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1. Rare HCV subtypes and retreatment outcomes in a cohort of European DAA-experienced patients

Author

Antoni, C., Teufel, A., Vogelmann, R., Ebert, M., Balavoine, J., Giostra, E., Berning, M., Hampe, J., Boettler, T., Neumann-Haefelin, C., Thimme, R., De Gottardi, A., Rauch, A., Semmo, N., Ellenrieder, V., Gress, M., Herrmann, A., Stallmach, A., Hoffmann, D., Protzer, U., Kodal, A., Löbermann, M., Götze, T., Keitel-Anselmino, V., Lange, C.M., Zachoval, R., Mayerle, J., Maieron, A., Michl, P., Merle, U., Moradpour, D., Chave, J.-P., Muche, M., Epple, H.-J., Müller-Schilling, M., Kocheise, F., Müller, T., Tacke, F., Roeb, E., Rissland, J., Krawczyk, M., Schulze, P., Semela, D., Spengler, U., Rockstroh, J., Strassburg, C.P., Siebler, J., Schulze zur Wiesch, J., Piecha, F., von Felden, J., Jordan, S., Lohse, A., Sprinzl, M., Galle, P., Stauber, R., Strey, B., Steckstor, W., Schmiegel, W., Brockmeyer, N.H., Canbay, A., Trautwein, C., Uschner, F., Trebicka, J., Weber, T., Wedemeyer, H., Cornberg, M., Manns, M., Wietzke-Braun, P., Günther, R., Willuweit, K., Hilgard, G., Schmidt, H., Zizer, E., Backhus, J., Seufferlein, T., Al-Taie, O., Angeli, W., Beckebaum, S., Erhardt, A., Garrido-Lüneburg, A., Gattringer, H., Genné, D., Gschwantler, M., Gundling, F., Hametner, S., Schöfl, R., Haag, S., Heinzow, H., Heyer, T., Hirschi, C., Jussios, A., Kanzler, S., Kordecki, N., Kraus, M., Kullig, U., Wollschläger, S., Magenta, L., Beretta-Piccoli, B. Terziroli, Menges, M., Mohr, L., Muehlenberg, K., Niederau, C., Paulweber, B., Petrides, A., Pinkernell, M., Piso, R., Rambach, W., Reinhardt, L., Reiser, M., Riecken, B., Rieke, A., Roth, J., Schelling, M., Schlee, P., Schneider, A., Scholz, D., Schott, E., Schuchmann, M., Schulten-Baumer, U., Seelhoff, A., Stich, A., Stickel, F., Ungemach, J., Walter, E., Weber, A., Wege, H., Winzer, T., Abels, W., Adler, M., Audebert, F., Baermann, C., Bästlein, E., Barth, R., Barthel, K., Becker, W., Behrends, J., Benninger, J., Berger, F., Berzow, D., Beyer, T., Bierbaum, M., Blaukat, O., Bodtländer, A., Böhm, G., Börner, N., Bohr, U., Bokemeyer, B., Bruch, H.R., Bucholz, D., Buggisch, P., Matschenz, K., Petersen, J., Burkhard, O., Busch, N., Chirca, C., Delker, R., Diedrich, J., Frank, M., Diehl, M., Tal, A.O., Schneider, M., Dienethal, A., Dietel, P., Dikopoulos, N., Dreck, M., Dreher, F., Drude, L., Ende, K., Ehrle, U., Baumgartl, K., Emke, F., Glosemeyer, R., Felten, G., Hüppe, D., Fischer, J., Fischer, U., Frederking, D., Frick, B., Friese, G., Gantke, B., Geyer, P., Schwind, H.R., Glas, M., Glaunsinger, T., Goebel, F., Göbel, U., Görlitz, B., Graf, R., Gruber, H., Hartmann, C., Klag, C., Härter, G., Herder, M., Heuchel, T., Heuer, S., Hinrichsen, H., Seegers, B., Höffl, K.-H., Hörster, H., Sonne, J.-U., Hofmann, W.P., Holst, F., Hunstiger, M., Hurst, A., Jägel-Guedes, E., John, C., Jung, M., Kallinowski, B., Kapzan, B., Kerzel, W., Khaykin, P., Klarhof, M., Klüppelberg, U., Wolfratshausen, Klugewitz, K., Knapp, B., Knevels, U., Kochsiek, T., Körfer, A., Köster, A., Kuhn, M., Langekamp, A., Künzig, B., Link, R., Littman, M., Löhr, H., Lutz, T., Gute, P., Knecht, G., Lutz, U., Mainz, D., Mahle, I., Maurer, P., Mauss, S., Mayer, C., Möller, H., Heyne, R., Moritzen, D., Mroß, M., Mundlos, M., Naumann, U., Nehls, O., K, Ningel, R., Oelmann, A., Olejnik, H., Gadow, K., Pascher, E., Philipp, A., Pichler, M., Polzien, F., Raddant, R., Riedel, M., Rietzler, S., Rössle, M., Rufle, W., Rump, A., Schewe, C., Hoffmann, C., Schleehauf, D., Schmidt, W., Schmidt-Heinevetter, G., Fabris, J. Schmidtler-von, Schneider, L., Schober, A., Niehaus-Hahn, S., Schwenzer, J., Seidel, T., Seitel, G., Sick, C., Simon, K., Stähler, D., Stenschke, F., Steffens, H., Stein, K., Steinmüller, M., Sternfeld, T., Svensson, K., Tacke, W., Teuber, G., Teubner, K., Thieringer, J., Tomesch, A., Trappe, U., Ullrich, J., Urban, G., Usadel, S., von Lucadou, A., Weinberger, F., Werheid-Dobers, M., Werner, P., Winter, T., Zehnter, E., Zipf, A., Dietz, Julia, Graf, Christiana, Berg, Christoph P., Port, Kerstin, Deterding, Katja, Buggisch, Peter, Peiffer, Kai-Henrik, Vermehren, Johannes, Dultz, Georg, Geier, Andreas, Reiter, Florian P., Bruns, Tony, Schattenberg, Jörn M., Durmashkina, Elena, Gustot, Thierry, Moreno, Christophe, Trauth, Janina, Discher, Thomas, Fischer, Janett, Berg, Thomas, Kremer, Andreas E., Müllhaupt, Beat, Zeuzem, Stefan, and Sarrazin, Christoph

Published
2024
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2. Long-term persistence of HCV resistance-associated substitutions after DAA treatment failure

Author

Balavoine, J., Giostra, E., Berning, M., Hampe, J., Canbay, A., Steckstor, W., Schmiegel, W., Brockmeyer, N.H., De Gottardi, A., Rauch, A., Semmo, N., Fischer, J., Gress, M., Heinzow, H., Hilgard, G., Schmidt, H., Herrmann, A., Stallmach, A., Hoffmann, D., Protzer, U., Klinker, H., Schulze, P., Kodal, A., Kremer, A., Siebler, J., Löbermann, M., Götze, T., Weigt, J., Lohse, A., Von Felden, J., Jordan, S., Lange, C.M., Zachoval, R., Mayerle, J., Maieron, A., Moradpour, D., Chave, J.-P., Moreno, C., Muche, M., Epple, H.-J., Müller-Schilling, M., Kocheise, F., Müllhaupt, B., Port, K., Deterding, K., Wedemeyer, H., Cornberg, M., Manns, M., Reinhardt, L., Ellenrieder, V., Rissland, J., Semela, D., Spengler, U., Rockstroh, J., Roeb, E., Sprinzl, M., Galle, P., Stauber, R., Stremmel, W., Strey, B., Thimme, R., Boettler, T., Tacke, F., Teufel, A., Vogelmann, R., Ebert, M., Tomasiewicz, K., Trautwein, C., Koenen, T., Weber, T., Wietzke-Braun, P., Günther, R., Zizer, E., Backhus, J., Seufferlein, T., Angeli, W., Beckebaum, S., Doberauer, C., Durmashkina, E., Hackelsberger, A., Erhardt, A., Garrido-Lüneburg, A., Gattringer, H., Genné, D., Gschwantler, M., Gundling, F., Hametner, S., Schöfl, R., Hartmann, C., Heyer, T., Hirschi, C., Jussios, A., Kanzler, S., Kordecki, N., Kraus, M., Kullig, U., Wollschläger, S., Magenta, L., Terziroli Beretta-Piccoli, B., Menges, M., Mohr, L., Muehlenberg, K., Niederau, C., Paulweber, B., Petrides, A., Pinkernell, M., Piso, R., Rambach, W., Reiser, M., Riecken, B., Rieke, A., Roth, J., Schelling, M., Schlee, P., Schneider, A., Scholz, D., Schott, E., Schuchmann, M., Schulten-Baumer, U., Seelhoff, A., Stich, A., Stickel, F., Ungemach, J., Walter, E., Weber, A., Winzer, T., Abels, W., Adler, M., Audebert, F., Baermann, C., Bästlein, E., Barth, R., Barthel, K., Becker, W., Behrends, J., Benninger, J., Berger, F., Berzow, D., Beyer, T., Bierbaum, M., Blaukat, O., Bodtländer, A., Böhm, G., Börner, N., Bohr, U., Bokemeyer, B., Bruch, H.R., Bucholz, D., Burkhard, O., Busch, N., Chirca, C., Delker, R., Diedrich, J., Frank, M., Diehl, M., Dienethal, A., Dietel, P., Dikopoulos, N., Dreck, M., Dreher, F., Drude, L., Ende, K., Ehrle, U., Baumgartl, K., Emke, F., Glosemeyer, R., Felten, G., Hüppe, D., Fischer, U., Frederking, D., Frick, B., Friese, G., Gantke, B., Geyer, P., Schwind, H.R., Glas, M., Glaunsinger, T., Goebel, F., Göbel, U., Görlitz, B., Graf, R., Gruber, H., Härter, G., Herder, M., Heuchel, T., Heuer, S., Höffl, K.-H., Hörster, H., Sonne, J.-U., Hofmann, W.P., Holst, F., Hunstiger, M., Hurst, A., Jägel-Guedes, E., John, C., Jung, M., Kallinowski, B., Kapzan, B., Kerzel, W., Khaykin, P., Klarhof, M., Klüppelberg, U., Wolfratshausen, Klugewitz, K., Knapp, B., Knevels, U., Kochsiek, T., Körfer, A., Köster, A., Kuhn, M., Langekamp, A., Künzig, B., Link, R., Littman, M., Löhr, H., Lutz, T., Knecht, G., Lutz, U., Mainz, D., Mahle, I., Maurer, P., Mayer, C., Meister, V., Möller, H., Heyne, R., Moritzen, D., Mroß, M., Mundlos, M., Naumann, U., Nehls, O., Ningel, K.R., Oelmann, A., Olejnik, H., Gadow, K., Pascher, E., Petersen, J., Philipp, A., Pichler, M., Polzien, F., Raddant, R., Riedel, M., Rietzler, S., Rössle, M., Rufle, W., Rump, A., Schewe, C., Hoffmann, C., Schleehauf, D., Schmidt, W., Schmidt-Heinevetter, G., Schmidtler-von Fabris, J., Schneider, L., Schober, A., Niehaus-Hahn, S., Schwenzer, J., Seegers, B., Seidel, T., Seitel, G., Sick, C., Simon, K., Stähler, D., Stenschke, F., Steffens, H., Stein, K., Steinmüller, M., Sternfeld, T., Svensson, K., Tacke, W., Teuber, G., Teubner, K., Thieringer, J., Tomesch, A., Trappe, U., Ullrich, J., Urban, G., Usadel, S., Von Lucadou, A., Weinberger, F., Werheid-Dobers, M., Werner, P., Winter, T., Zehnter, E., Zipf, A., Dietz, Julia, Müllhaupt, Beat, Buggisch, Peter, Graf, Christiana, Peiffer, Kai-Henrik, Matschenz, Katrin, Schattenberg, Jörn M., Antoni, Christoph, Mauss, Stefan, Niederau, Claus, Discher, Thomas, Trauth, Janina, Dultz, Georg, Schulze zur Wiesch, Julian, Piecha, Felix, Klinker, Hartwig, Müller, Tobias, Berg, Thomas, Neumann-Haefelin, Christoph, Berg, Christoph P., Zeuzem, Stefan, and Sarrazin, Christoph

Published
2023
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3. Efficacy of Retreatment After Failed Direct-acting Antiviral Therapy in Patients With HCV Genotype 1–3 Infections

Author

Balavoine, J., Giostra, E., Berning, M., Hampe, J., De Gottardi, A., Rauch, A., Semmo, N., Discher, T., Trauth, J., Fischer, J., Gress, M., Günther, R., Heinzow, H., Schmidt, J., Herrmann, A., Stallmach, A., Hilgard, G., Deterding, K., Lange, C.M., Ciesek, S., Wedemeyer, H., Hoffmann, D., Klinker, H., Schulze, P., Kocheise, F., Müller-Schilling, M., Kodal, A., Kremer, A., Ganslmayer, M., Siebler, J., Lammert, F., Rissland, J., Löbermann, M., Götze, T., Canbay, A., Lohse, A., von Felden, J., Jordan, S., Maieron, A., Moradpour, D., Chave, J.-P., Moreno, C., Müller, T., Muche, M., Epple, H.-J., Port, K., von Hahn, T., Cornberg, M., Manns, M., Reinhardt, L., Ellenrieder, V., Rockstroh, J., Schattenberg, J., Sprinzl, M., Galle, P., Roeb, E., Steckstor, M., Schmiegel, W., Brockmeyer, N.H., Seufferlein, T., Stremmel, W., Strey, B., Thimme, R., Teufel, A., Vogelmann, R., Ebert, M., Tomasiewicz, K., Trautwein, C., Tacke, F., Koenen, T., Weber, T., Zachoval, R., Mayerle, J., Raziorrouh, B., Angeli, W., Beckebaum, S., Doberauer, C., Durmashkina, E., Hackelsberger, A., Erhardt, A., Garrido-Lüneburg, A., Gattringer, H., Genné, D., Gschwantler, M., Gundling, F., Hametner, S., Schöfl, R., Hartmann, C., Heyer, T., Hirschi, C., Jussios, A., Kanzler, S., Kordecki, N., Kraus, M., Kullig, U., Wollschläger, S., Magenta, L., Beretta-Piccoli, B. Terziroli, Menges, M., Mohr, L., Muehlenberg, K., Niederau, C., Paulweber, B., Petrides, A., Pinkernell, M., Piso, R., Rambach, W., Reiser, M., Riecken, B., Rieke, A., Roth, J., Schelling, M., Schlee, P., Schneider, A., Scholz, D., Schott, E., Schuchmann, M., Schulten-Baumer, U., Seelhoff, A., Stich, A., Stickel, F., Ungemach, J., Walter, E., Weber, A., Winzer, T., Abels, W., Adler, M., Audebert, F., Baermann, C., Bästlein, E., Barth, R., Barthel, K., Becker, W., Behrends, J., Benninger, J., Berger, F., Berzow, D., Beyer, T., Bierbaum, M., Blaukat, O., Bodtländer, A., Böhm, G., Börner, N., Bohr, U., Bokemeyer, B., Bruch, H.R., Bucholz, D., Burkhard, O., Busch, N., Chirca, C., Delker, R., Diedrich, J., Frank, M., Diehl, M., Dienethal, A., Dietel, P., Dikopoulos, N., Dreck, M., Dreher, F., Drude, L., Ende, K., Ehrle, U., Baumgartl, K., Emke, F., Glosemeyer, R., Felten, G., Hüppe, D., Fischer, U., Frederking, D., Frick, B., Friese, G., Gantke, B., Geyer, P., Schwind, H.R., Glas, M., Glaunsinger, T., Goebel, F., Göbel, U., Görlitz, B., Graf, R., Gruber, H., Härter, G., Herder, M., Heuchel, T., Heuer, S., Höffl, K.-H., Hörster, H., Sonne, J.-U., Hofmann, W.P., Holst, F., Hunstiger, M., Hurst, A., Jägel-Guedes, E., John, C., Jung, M., Kallinowski, B., Kapzan, B., Kerzel, W., Khaykin, P., Klarhof, M., Klüppelberg, U., Klugewitz, K., Knapp, B., Knevels, U., Kochsiek, T., Körfer, A., Köster, A., Kuhn, M., Langekamp, A., Künzig, B., Link, R., Littman, M., Löhr, H., Lutz, T., Knecht, G., Lutz, U., Mainz, D., Mahle, I., Maurer, P., Mayer, C., Meister, V., Möller, H., Heyne, R., Moritzen, D., Mroß, M., Mundlos, M., Naumann, U., Nehls, O., Ningel, K.&R., Oelmann, A., Olejnik, H., Gadow, K., Pascher, E., Petersen, J., Philipp, A., Pichler, M., Polzien, F., Raddant, R., Riedel, M., Rietzler, S., Rössle, M., Rufle, W., Rump, A., Schewe, C., Hoffmann, C., Schleehauf, D., Schmidt, K.J., Schmidt, W., Schmidt-Heinevetter, G., Schmidtler-von Fabris, J., Schnaitmann, E., Schneider, L., Schober, A., Niehaus-Hahn, S., Schwenzer, J., Seidel, T., Seitel, G., Sick, C., Simon, K.G., Stähler, D., Stenschke, F., Steffens, H., Stein, K., Steinmüller, M., Sternfeld, T., Svensson, K., Tacke, W., Teuber, G., Teubner, K., Thieringer, J., Tomesch, A., Trappe, U., Ullrich, J., Urban, G., Usadel, S., von Lucadou, A., Weinberger, F., Werheid-Dobers, M., Werner, P., Winter, T., Zehnter, E., Zipf, A., Dietz, Julia, Spengler, Ulrich, Müllhaupt, Beat, Schulze zur Wiesch, Julian, Piecha, Felix, Mauss, Stefan, Seegers, Barbara, Hinrichsen, Holger, Antoni, Christoph, Wietzke-Braun, Perdita, Peiffer, Kai-Henrik, Berger, Annemarie, Matschenz, Katrin, Buggisch, Peter, Backhus, Johanna, Zizer, Eugen, Boettler, Tobias, Neumann-Haefelin, Christoph, Semela, David, Stauber, Rudolf, Berg, Thomas, Berg, Christoph, Zeuzem, Stefan, Vermehren, Johannes, and Sarrazin, Christoph

Published
2021
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4. Patterns of Resistance-Associated Substitutions in Patients With Chronic HCV Infection Following Treatment With Direct-Acting Antivirals

Author

Antoni, C., Vogelmann, R., Ebert, M., Backhus, J., Seufferlein, T., Balavoine, J., Giostra, E., Berg, C., Cornberg, M., Wedemeyer, H., Manns, M., De Gottardi, A., Esteban, R., Discher, T., Roeb, E., Gress, M., Günther, R., Wietzke-Braun, P., Herrmann, A., Stallmach, A., Hoffmann, D., Klinker, H., Kodal, A., Lammert, F., Löbermann, M., Schulze zur Wiesch, J., von Felden, J., Piecha, F., Lohse, A., Götze, T., Malfertheiner, P., Mayerle, J., Moradpour, D., Moreno, C., Neumann-Haefelin, C., Thimme, R., Reinhardt, L., Ellenrieder, V., Schattenberg, J., Sprinzl, M., Galle, P., Schmidt, J., Schott, E., Epple, H.-J., Siebler, J., Stauber, R., Steckstor, M., Schmiegel, W., Stremmel, W., Strey, B., Tomasiewicz, K., Trautwein, C., Zachoval, R., Angeli, W., Beckebaum, S., Doberauer, C., Ende, K., Erhardt, A., Garrido-Lüneburg, A., Gattringer, H., Genné, D., Gschwantler, M., Gundling, F., Hartmann, C., Heyer, T., Hirschi, C., Kanzler, S., Kordecki, N., Kraus, M., Kullig, U., Magenta, L., Terziroli Beretta-Piccoli, B., Menges, M., Mohr, L., Muehlenberg, K., Niederau, C., Paulweber, B., Petrides, A., Piso, R., Rambach, W., Reiser, M., Riecken, B., Roth, J., Schöfl, R., Maieron, A., Schneider, A., Schuchmann, M., Schulten-Baumer, U., Seelhoff, A., Semela, D., Stich, A., Vollmer, C., Brückner, J., Ungemach, J., Walter, E., Weber, A., Winzer, T., Abels, W., Adler, M., Audebert, F., Baermann, C., Bästlein, E., Barth, R., Barthel, K., Baumgartl, K., Becker, W., Benninger, J., Beyer, T., Bodtländer, A., Böhm, G., Bohr, U., Moll, A., Naumann, U., Börner, N., Bruch, H.R., Busch, N., Burkhard, O., Chirca, C., Dienethal, A., Dietel, P., Dreher, F., Efken, P., Ehrle, U., Emke, F., Fischer, J., Fischer, U., Frederking, D., Frick, B., Gantke B, B., Geyer, P., Glaunsinger, T., Goebel, F., Göbel, U., Graf, R., Herder, M., Heuchel, T., Heuer, S., Heyne, R., Höffl, K.H., Hofmann, W.P., Holst, F., Hörster, H., John, C., Jung, M.C., Kallinowski, B., Kerzel, W., Khaykin, P., Klarhof, M., Knapp, B., Knevels, U., Körfer, A., Köster, A., Künzig, B., Langenkamp, A., Kuhn, M., Littman, M., Löhr, H., Ludwig, L., Lutz, U., Maurer, P., Mayer, C., Meister, V., Moritzen, D., Mroß, M., Mundlos, M., Nehls, O., Ningel, K., Oelmann, A., Olejnik, H., Pascher, E., Philipp, A., Pichler, M., Polzien, F., Raddant, R., Riedel, M., Rietzler, S., Rump, A., Schmidt, W., Schmidtler-von Fabris, J., Schneider, L., Schober, A., Schwenzer, J., Seidel, T., Seitel, G., Sick, C., Simon, K., Stähler, D., Steffens, H., Svensson, K., Tacke, W., Teubner, K., Thieringer, J., Trappe, U., Ullrich, J., Usadel, S., von Lucadou, A., Werheid-Dobers, M., Zehnter, E., Zipf, A., Dietz, Julia, Susser, Simone, Vermehren, Johannes, Peiffer, Kai-Henrik, Grammatikos, Georgios, Berger, Annemarie, Ferenci, Peter, Buti, Maria, Müllhaupt, Beat, Hunyady, Bela, Hinrichsen, Holger, Mauss, Stefan, Petersen, Jörg, Buggisch, Peter, Felten, Gisela, Hüppe, Dietrich, Knecht, Gaby, Lutz, Thomas, Schott, Eckart, Berg, Christoph, Spengler, Ulrich, von Hahn, Thomas, Berg, Thomas, Zeuzem, Stefan, and Sarrazin, Christoph

Published
2018
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10. A framework for validating AI in precision medicine: considerations from the European ITFoC consortium

Author

Tsopra, R, Fernandez, X, Luchinat, C, Alberghina, L, Lehrach, H, Vanoni, M, Dreher, F, Sezerman, O, Cuggia, M, de Tayrac, M, Miklasevics, E, Itu, L, Geanta, M, Ogilvie, L, Godey, F, Boldisor, C, Campillo-Gimenez, B, Cioroboiu, C, Ciusdel, C, Coman, S, Hijano Cubelos, O, Itu, A, Lange, B, Le Gallo, M, Lespagnol, A, Mauri, G, Soykam, H, Rance, B, Turano, P, Tenori, L, Vignoli, A, Wierling, C, Benhabiles, N, Burgun, A, Tsopra R., Fernandez X., Luchinat C., Alberghina L., Lehrach H., Vanoni M., Dreher F., Sezerman O. U., Cuggia M., de Tayrac M., Miklasevics E., Itu L. M., Geanta M., Ogilvie L., Godey F., Boldisor C. N., Campillo-Gimenez B., Cioroboiu C., Ciusdel C. F., Coman S., Hijano Cubelos O., Itu A., Lange B., Le Gallo M., Lespagnol A., Mauri G., Soykam H. O., Rance B., Turano P., Tenori L., Vignoli A., Wierling C., Benhabiles N., Burgun A., Tsopra, R, Fernandez, X, Luchinat, C, Alberghina, L, Lehrach, H, Vanoni, M, Dreher, F, Sezerman, O, Cuggia, M, de Tayrac, M, Miklasevics, E, Itu, L, Geanta, M, Ogilvie, L, Godey, F, Boldisor, C, Campillo-Gimenez, B, Cioroboiu, C, Ciusdel, C, Coman, S, Hijano Cubelos, O, Itu, A, Lange, B, Le Gallo, M, Lespagnol, A, Mauri, G, Soykam, H, Rance, B, Turano, P, Tenori, L, Vignoli, A, Wierling, C, Benhabiles, N, Burgun, A, Tsopra R., Fernandez X., Luchinat C., Alberghina L., Lehrach H., Vanoni M., Dreher F., Sezerman O. U., Cuggia M., de Tayrac M., Miklasevics E., Itu L. M., Geanta M., Ogilvie L., Godey F., Boldisor C. N., Campillo-Gimenez B., Cioroboiu C., Ciusdel C. F., Coman S., Hijano Cubelos O., Itu A., Lange B., Le Gallo M., Lespagnol A., Mauri G., Soykam H. O., Rance B., Turano P., Tenori L., Vignoli A., Wierling C., Benhabiles N., and Burgun A.

Abstract

Background: Artificial intelligence (AI) has the potential to transform our healthcare systems significantly. New AI technologies based on machine learning approaches should play a key role in clinical decision-making in the future. However, their implementation in health care settings remains limited, mostly due to a lack of robust validation procedures. There is a need to develop reliable assessment frameworks for the clinical validation of AI. We present here an approach for assessing AI for predicting treatment response in triple-negative breast cancer (TNBC), using real-world data and molecular -omics data from clinical data warehouses and biobanks. Methods: The European “ITFoC (Information Technology for the Future Of Cancer)” consortium designed a framework for the clinical validation of AI technologies for predicting treatment response in oncology. Results: This framework is based on seven key steps specifying: (1) the intended use of AI, (2) the target population, (3) the timing of AI evaluation, (4) the datasets used for evaluation, (5) the procedures used for ensuring data safety (including data quality, privacy and security), (6) the metrics used for measuring performance, and (7) the procedures used to ensure that the AI is explainable. This framework forms the basis of a validation platform that we are building for the “ITFoC Challenge”. This community-wide competition will make it possible to assess and compare AI algorithms for predicting the response to TNBC treatments with external real-world datasets. Conclusions: The predictive performance and safety of AI technologies must be assessed in a robust, unbiased and transparent manner before their implementation in healthcare settings. We believe that the consideration of the ITFoC consortium will contribute to the safe transfer and implementation of AI in clinical settings, in the context of precision oncology and personalized care.

Published
2021

11. Modulation der CNV-Aktivität durch systemische Faktoren: Erste Ergebnisse der BIOMAC-Studie

Author

Zeitz, O, Flesch, LTM, Knecht, VA, Frentzel, DP, Rau, S, Rübsam, A, Künzel, SE, Wolf, S, Dreher, F, Schuette, M, Lange, B, Yaspo, ML, Lehrach, H, and Joussen, AM

Subjects
ddc: 610, Medicine and health
Abstract

Hintergrund: Der IVOM-Bedarf von Patienten mit neovaskulärer AMD (nAMD) ist hoch individuell und variabel. Das Ziel der BIOMAC-Studie ist es, systemische Faktoren zu identifizieren, die den Grad der CNV-Aktivität modulieren und damit den IVOM-Bedarf beeinflussen. Methoden: Die BIOMAC-Studie [zum vollständigen Text gelangen Sie über die oben angegebene URL]

Published
2022
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12. Efficacy of Retreatment After Failed Direct-acting Antiviral Therapy in Patients With HCV Genotype 1-3 Infections

Author

Dietz, Julia, Spengler, Ulrich, Mullhaupt, Beat, zur Wiesch, Julian Schulze, Piecha, Felix, Mauss, Stefan, Seegers, Barbara, Hinrichsen, Holger, Antoni, Christoph, Wietzke-Braun, Perdita, Peiffer, Kai-Henrik, Berger, Annemarie, Matschenz, Katrin, Buggisch, Peter, Backhus, Johanna, Zizer, Eugen, Boettler, Tobias, Neumann-Haefelin, Christoph, Semela, David, Stauber, Rudolf, Berg, Thomas, Berg, Christoph, Zeuzem, Stefan, Vermehren, Johannes, Sarrazin, Christoph, Balavoine, J., Giostra, E., Berning, M., Hampe, J., De Gottardi, A., Rauch, A., Semmo, N., Discher, T., Trauth, J., Fischer, J., Gress, M., Guenther, R., Heinzow, H., Schmidt, J., Herrmann, A., Stallmach, A., Hilgard, G., Deterding, K., Lange, C. M., Ciesek, S., Wedemeyer, H., Hoffmann, D., Klinker, H., Schulze, P., Kocheise, F., Mueller-Schilling, M., Kodal, A., Kremer, A., Ganslmayer, M., Siebler, J., Lammert, F., Rissland, J., Loebermann, M., Goetze, T., Canbay, A., Lohse, A., von Felden, J., Jordan, S., Maieron, A., Moradpour, D., Chave, J. -P., Moreno, C., Mueller, T., Muche, M., Epple, H. -J., Port, K., von Hahn, T., Cornberg, M., Manns, M., Reinhardt, L., Ellenrieder, V., Rockstroh, J., Schattenberg, J., Sprinzl, M., Galle, P., Roeb, E., Steckstor, M., Schmiegel, W., Brockmeyer, N. H., Seufferlein, T., Stremmel, W., Strey, B., Thimme, R., Teufel, A., Vogelmann, R., Ebert, M., Tomasiewicz, K., Trautwein, C., Tacke, F., Koenen, T., Weber, T., Zachoval, R., Mayerle, J., Raziorrouh, B., Angeli, W., Beckebaum, S., Doberauer, C., Durmashkina, E., Hackelsberger, A., Erhardt, A., Garrido-Luneburg, A., Gattringer, H., Genne, D., Gschwantler, M., Gundling, F., Hametner, S., Schofl, R., Hartmann, C., Heyer, T., Hirschi, C., Jussios, A., Kanzler, S., Kordecki, N., Kraus, M., Kullig, U., Wollschlager, S., Magenta, L., Beretta-Piccoli, B. Terziroli, Menges, M., Mohr, L., Muehlenberg, K., Niederau, C., Paulweber, B., Petrides, A., Pinkernell, M., Piso, R., Rambach, W., Reiser, M., Riecken, B., Rieke, A., Roth, J., Schelling, M., Schlee, P., Schneider, A., Scholz, D., Schott, E., Schuchmann, M., Schulten-Baumer, U., Seelhoff, A., Stich, A., Stickel, F., Ungemach, J., Walter, E., Weber, A., Winzer, T., Abels, W., Adler, M., Baermann, C., Bastlein, E., Barth, R., Barthel, K., Becker, W., Behrends, J., Benninger, J., Berger, F., Berzow, D., Beyer, T., Bierbaum, M., Blaukat, O., Bodtlander, A., Bohm, G., Borner, N., Bohr, U., Bokemeyer, B., Bruch, H. R., Bucholz, D., Burkhard, O., Busch, N., Chirca, C., Delker, R., Diedrich, J., Frank, M., Diehl, M., Dienethal, A., Dietel, P., Dikopoulos, N., Dreck, M., Dreher, F., Drude, L., Ende, K., Ehrle, U., Baumgartl, K., Emke, F., Glosemeyer, R., Felten, G., Huppe, D., Fischer, U., Frederking, D., Frick, B., Friese, G., Gantke, B., Geyer, P., Schwind, H. R., Glas, M., Glaunsinger, T., Goebel, F., Gobel, U., Gorlitz, B., Graf, R., Gruber, H., Harter, G., Herder, M., Heuchel, T., Heuer, S., Hoffl, K. -H., Horster, H., Sonne, J. -U., Hofmann, W. P., Holst, F., Hunstiger, M., Hurst, A., Jagel-Guedes, E., John, C., Jung, M., Kallinowski, B., Kapzan, B., Kerzel, W., Khaykin, P., Klarhof, M., Kluppelberg, U., Klugewitz, K., Knapp, B., Knevels, U., Kochsiek, T., Korfer, A., Koster, A., Kuhn, M., Langekamp, A., Kunzig, B., Link, R., Littman, M., Lohr, H., Lutz, T., Knecht, G., Lutz, U., Mainz, D., Mahle, I., Maurer, P., Mayer, C., Meister, V., Moller, H., Heyne, R., Moritzen, D., Mross, M., Mundlos, M., Naumann, U., Nehls, O., Ningel, R., Oelmann, A., Olejnik, H., Gadow, K., Pascher, E., Petersen, J., Philipp, A., Pichler, M., Polzien, F., Raddant, R., Riedel, M., Rietzler, S., Rossle, M., Rufle, W., Rump, A., Schewe, C., Hoffmann, C., Schleehauf, D., Schmidt, K. J., Schmidt, W., Schmidt-Heinevetter, G., Schmidtler-von Fabris, J., Schnaitmann, E., Schneider, L., Schober, A., Niehaus-Hahn, S., Schwenzer, J., Seidel, T., Seitel, G., Sick, C., Simon, K. G., Stahler, D., Stenschke, F., Steffens, H., Stein, K., Steinmuller, M., Sternfeld, T., Svensson, K., Tacke, W., Teuber, G., Teubner, K., Thieringer, J., Tomesch, A., Trappe, U., Ullrich, J., Urban, G., Usadel, S., von Lucadou, A., Weinberger, F., Werheid-Dobers, M., Werner, P., Winter, T., Zehnter, E., Zipf, A., Dietz, Julia, Spengler, Ulrich, Mullhaupt, Beat, zur Wiesch, Julian Schulze, Piecha, Felix, Mauss, Stefan, Seegers, Barbara, Hinrichsen, Holger, Antoni, Christoph, Wietzke-Braun, Perdita, Peiffer, Kai-Henrik, Berger, Annemarie, Matschenz, Katrin, Buggisch, Peter, Backhus, Johanna, Zizer, Eugen, Boettler, Tobias, Neumann-Haefelin, Christoph, Semela, David, Stauber, Rudolf, Berg, Thomas, Berg, Christoph, Zeuzem, Stefan, Vermehren, Johannes, Sarrazin, Christoph, Balavoine, J., Giostra, E., Berning, M., Hampe, J., De Gottardi, A., Rauch, A., Semmo, N., Discher, T., Trauth, J., Fischer, J., Gress, M., Guenther, R., Heinzow, H., Schmidt, J., Herrmann, A., Stallmach, A., Hilgard, G., Deterding, K., Lange, C. M., Ciesek, S., Wedemeyer, H., Hoffmann, D., Klinker, H., Schulze, P., Kocheise, F., Mueller-Schilling, M., Kodal, A., Kremer, A., Ganslmayer, M., Siebler, J., Lammert, F., Rissland, J., Loebermann, M., Goetze, T., Canbay, A., Lohse, A., von Felden, J., Jordan, S., Maieron, A., Moradpour, D., Chave, J. -P., Moreno, C., Mueller, T., Muche, M., Epple, H. -J., Port, K., von Hahn, T., Cornberg, M., Manns, M., Reinhardt, L., Ellenrieder, V., Rockstroh, J., Schattenberg, J., Sprinzl, M., Galle, P., Roeb, E., Steckstor, M., Schmiegel, W., Brockmeyer, N. H., Seufferlein, T., Stremmel, W., Strey, B., Thimme, R., Teufel, A., Vogelmann, R., Ebert, M., Tomasiewicz, K., Trautwein, C., Tacke, F., Koenen, T., Weber, T., Zachoval, R., Mayerle, J., Raziorrouh, B., Angeli, W., Beckebaum, S., Doberauer, C., Durmashkina, E., Hackelsberger, A., Erhardt, A., Garrido-Luneburg, A., Gattringer, H., Genne, D., Gschwantler, M., Gundling, F., Hametner, S., Schofl, R., Hartmann, C., Heyer, T., Hirschi, C., Jussios, A., Kanzler, S., Kordecki, N., Kraus, M., Kullig, U., Wollschlager, S., Magenta, L., Beretta-Piccoli, B. Terziroli, Menges, M., Mohr, L., Muehlenberg, K., Niederau, C., Paulweber, B., Petrides, A., Pinkernell, M., Piso, R., Rambach, W., Reiser, M., Riecken, B., Rieke, A., Roth, J., Schelling, M., Schlee, P., Schneider, A., Scholz, D., Schott, E., Schuchmann, M., Schulten-Baumer, U., Seelhoff, A., Stich, A., Stickel, F., Ungemach, J., Walter, E., Weber, A., Winzer, T., Abels, W., Adler, M., Baermann, C., Bastlein, E., Barth, R., Barthel, K., Becker, W., Behrends, J., Benninger, J., Berger, F., Berzow, D., Beyer, T., Bierbaum, M., Blaukat, O., Bodtlander, A., Bohm, G., Borner, N., Bohr, U., Bokemeyer, B., Bruch, H. R., Bucholz, D., Burkhard, O., Busch, N., Chirca, C., Delker, R., Diedrich, J., Frank, M., Diehl, M., Dienethal, A., Dietel, P., Dikopoulos, N., Dreck, M., Dreher, F., Drude, L., Ende, K., Ehrle, U., Baumgartl, K., Emke, F., Glosemeyer, R., Felten, G., Huppe, D., Fischer, U., Frederking, D., Frick, B., Friese, G., Gantke, B., Geyer, P., Schwind, H. R., Glas, M., Glaunsinger, T., Goebel, F., Gobel, U., Gorlitz, B., Graf, R., Gruber, H., Harter, G., Herder, M., Heuchel, T., Heuer, S., Hoffl, K. -H., Horster, H., Sonne, J. -U., Hofmann, W. P., Holst, F., Hunstiger, M., Hurst, A., Jagel-Guedes, E., John, C., Jung, M., Kallinowski, B., Kapzan, B., Kerzel, W., Khaykin, P., Klarhof, M., Kluppelberg, U., Klugewitz, K., Knapp, B., Knevels, U., Kochsiek, T., Korfer, A., Koster, A., Kuhn, M., Langekamp, A., Kunzig, B., Link, R., Littman, M., Lohr, H., Lutz, T., Knecht, G., Lutz, U., Mainz, D., Mahle, I., Maurer, P., Mayer, C., Meister, V., Moller, H., Heyne, R., Moritzen, D., Mross, M., Mundlos, M., Naumann, U., Nehls, O., Ningel, R., Oelmann, A., Olejnik, H., Gadow, K., Pascher, E., Petersen, J., Philipp, A., Pichler, M., Polzien, F., Raddant, R., Riedel, M., Rietzler, S., Rossle, M., Rufle, W., Rump, A., Schewe, C., Hoffmann, C., Schleehauf, D., Schmidt, K. J., Schmidt, W., Schmidt-Heinevetter, G., Schmidtler-von Fabris, J., Schnaitmann, E., Schneider, L., Schober, A., Niehaus-Hahn, S., Schwenzer, J., Seidel, T., Seitel, G., Sick, C., Simon, K. G., Stahler, D., Stenschke, F., Steffens, H., Stein, K., Steinmuller, M., Sternfeld, T., Svensson, K., Tacke, W., Teuber, G., Teubner, K., Thieringer, J., Tomesch, A., Trappe, U., Ullrich, J., Urban, G., Usadel, S., von Lucadou, A., Weinberger, F., Werheid-Dobers, M., Werner, P., Winter, T., Zehnter, E., and Zipf, A.

Published
2021

13. Classification of Molecular Subtypes of High-Grade Serous Ovarian Cancer by MALDI-Imaging

Author

Kassuhn, W, Klein, O, Darb-Esfahani, S, Lammert, H, Handzik, S, Taube, ET, Schmitt, WD, Keunecke, C, Horst, D, Dreher, F, George, J, Bowtell, DD, Dorigo, O, Hummel, M, Sehouli, J, Bluthgen, N, Kulbe, H, Braicu, EI, Kassuhn, W, Klein, O, Darb-Esfahani, S, Lammert, H, Handzik, S, Taube, ET, Schmitt, WD, Keunecke, C, Horst, D, Dreher, F, George, J, Bowtell, DD, Dorigo, O, Hummel, M, Sehouli, J, Bluthgen, N, Kulbe, H, and Braicu, EI

Abstract

Despite the correlation of clinical outcome and molecular subtypes of high-grade serous ovarian cancer (HGSOC), contemporary gene expression signatures have not been implemented in clinical practice to stratify patients for targeted therapy. Hence, we aimed to examine the potential of unsupervised matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) to stratify patients who might benefit from targeted therapeutic strategies. Molecular subtyping of paraffin-embedded tissue samples from 279 HGSOC patients was performed by NanoString analysis (ground truth labeling). Next, we applied MALDI-IMS paired with machine-learning algorithms to identify distinct mass profiles on the same paraffin-embedded tissue sections and distinguish HGSOC subtypes by proteomic signature. Finally, we devised a novel approach to annotate spectra of stromal origin. We elucidated a MALDI-derived proteomic signature (135 peptides) able to classify HGSOC subtypes. Random forest classifiers achieved an area under the curve (AUC) of 0.983. Furthermore, we demonstrated that the exclusion of stroma-associated spectra provides tangible improvements to classification quality (AUC = 0.988). Moreover, novel MALDI-based stroma annotation achieved near-perfect classifications (AUC = 0.999). Here, we present a concept integrating MALDI-IMS with machine-learning algorithms to classify patients according to distinct molecular subtypes of HGSOC. This has great potential to assign patients for personalized treatment.

Published
2021

14. Efficacy of Retreatment After Failed Direct-acting Antiviral Therapy in Patients With HCV Genotype 1–3 Infections

Author

Dietz, Julia, primary, Spengler, Ulrich, additional, Müllhaupt, Beat, additional, Schulze zur Wiesch, Julian, additional, Piecha, Felix, additional, Mauss, Stefan, additional, Seegers, Barbara, additional, Hinrichsen, Holger, additional, Antoni, Christoph, additional, Wietzke-Braun, Perdita, additional, Peiffer, Kai-Henrik, additional, Berger, Annemarie, additional, Matschenz, Katrin, additional, Buggisch, Peter, additional, Backhus, Johanna, additional, Zizer, Eugen, additional, Boettler, Tobias, additional, Neumann-Haefelin, Christoph, additional, Semela, David, additional, Stauber, Rudolf, additional, Berg, Thomas, additional, Berg, Christoph, additional, Zeuzem, Stefan, additional, Vermehren, Johannes, additional, Sarrazin, Christoph, additional, Balavoine, J., additional, Giostra, E., additional, Berning, M., additional, Hampe, J., additional, De Gottardi, A., additional, Rauch, A., additional, Semmo, N., additional, Discher, T., additional, Trauth, J., additional, Fischer, J., additional, Gress, M., additional, Günther, R., additional, Heinzow, H., additional, Schmidt, J., additional, Herrmann, A., additional, Stallmach, A., additional, Hilgard, G., additional, Deterding, K., additional, Lange, C.M., additional, Ciesek, S., additional, Wedemeyer, H., additional, Hoffmann, D., additional, Klinker, H., additional, Schulze, P., additional, Kocheise, F., additional, Müller-Schilling, M., additional, Kodal, A., additional, Kremer, A., additional, Ganslmayer, M., additional, Siebler, J., additional, Lammert, F., additional, Rissland, J., additional, Löbermann, M., additional, Götze, T., additional, Canbay, A., additional, Lohse, A., additional, von Felden, J., additional, Jordan, S., additional, Maieron, A., additional, Moradpour, D., additional, Chave, J.-P., additional, Moreno, C., additional, Müller, T., additional, Muche, M., additional, Epple, H.-J., additional, Port, K., additional, von Hahn, T., additional, Cornberg, M., additional, Manns, M., additional, Reinhardt, L., additional, Ellenrieder, V., additional, Rockstroh, J., additional, Schattenberg, J., additional, Sprinzl, M., additional, Galle, P., additional, Roeb, E., additional, Steckstor, M., additional, Schmiegel, W., additional, Brockmeyer, N.H., additional, Seufferlein, T., additional, Stremmel, W., additional, Strey, B., additional, Thimme, R., additional, Teufel, A., additional, Vogelmann, R., additional, Ebert, M., additional, Tomasiewicz, K., additional, Trautwein, C., additional, Tacke, F., additional, Koenen, T., additional, Weber, T., additional, Zachoval, R., additional, Mayerle, J., additional, Raziorrouh, B., additional, Angeli, W., additional, Beckebaum, S., additional, Doberauer, C., additional, Durmashkina, E., additional, Hackelsberger, A., additional, Erhardt, A., additional, Garrido-Lüneburg, A., additional, Gattringer, H., additional, Genné, D., additional, Gschwantler, M., additional, Gundling, F., additional, Hametner, S., additional, Schöfl, R., additional, Hartmann, C., additional, Heyer, T., additional, Hirschi, C., additional, Jussios, A., additional, Kanzler, S., additional, Kordecki, N., additional, Kraus, M., additional, Kullig, U., additional, Wollschläger, S., additional, Magenta, L., additional, Beretta-Piccoli, B. Terziroli, additional, Menges, M., additional, Mohr, L., additional, Muehlenberg, K., additional, Niederau, C., additional, Paulweber, B., additional, Petrides, A., additional, Pinkernell, M., additional, Piso, R., additional, Rambach, W., additional, Reiser, M., additional, Riecken, B., additional, Rieke, A., additional, Roth, J., additional, Schelling, M., additional, Schlee, P., additional, Schneider, A., additional, Scholz, D., additional, Schott, E., additional, Schuchmann, M., additional, Schulten-Baumer, U., additional, Seelhoff, A., additional, Stich, A., additional, Stickel, F., additional, Ungemach, J., additional, Walter, E., additional, Weber, A., additional, Winzer, T., additional, Abels, W., additional, Adler, M., additional, Audebert, F., additional, Baermann, C., additional, Bästlein, E., additional, Barth, R., additional, Barthel, K., additional, Becker, W., additional, Behrends, J., additional, Benninger, J., additional, Berger, F., additional, Berzow, D., additional, Beyer, T., additional, Bierbaum, M., additional, Blaukat, O., additional, Bodtländer, A., additional, Böhm, G., additional, Börner, N., additional, Bohr, U., additional, Bokemeyer, B., additional, Bruch, H.R., additional, Bucholz, D., additional, Burkhard, O., additional, Busch, N., additional, Chirca, C., additional, Delker, R., additional, Diedrich, J., additional, Frank, M., additional, Diehl, M., additional, Dienethal, A., additional, Dietel, P., additional, Dikopoulos, N., additional, Dreck, M., additional, Dreher, F., additional, Drude, L., additional, Ende, K., additional, Ehrle, U., additional, Baumgartl, K., additional, Emke, F., additional, Glosemeyer, R., additional, Felten, G., additional, Hüppe, D., additional, Fischer, U., additional, Frederking, D., additional, Frick, B., additional, Friese, G., additional, Gantke, B., additional, Geyer, P., additional, Schwind, H.R., additional, Glas, M., additional, Glaunsinger, T., additional, Goebel, F., additional, Göbel, U., additional, Görlitz, B., additional, Graf, R., additional, Gruber, H., additional, Härter, G., additional, Herder, M., additional, Heuchel, T., additional, Heuer, S., additional, Höffl, K.-H., additional, Hörster, H., additional, Sonne, J.-U., additional, Hofmann, W.P., additional, Holst, F., additional, Hunstiger, M., additional, Hurst, A., additional, Jägel-Guedes, E., additional, John, C., additional, Jung, M., additional, Kallinowski, B., additional, Kapzan, B., additional, Kerzel, W., additional, Khaykin, P., additional, Klarhof, M., additional, Klüppelberg, U., additional, Klugewitz, K., additional, Knapp, B., additional, Knevels, U., additional, Kochsiek, T., additional, Körfer, A., additional, Köster, A., additional, Kuhn, M., additional, Langekamp, A., additional, Künzig, B., additional, Link, R., additional, Littman, M., additional, Löhr, H., additional, Lutz, T., additional, Knecht, G., additional, Lutz, U., additional, Mainz, D., additional, Mahle, I., additional, Maurer, P., additional, Mayer, C., additional, Meister, V., additional, Möller, H., additional, Heyne, R., additional, Moritzen, D., additional, Mroß, M., additional, Mundlos, M., additional, Naumann, U., additional, Nehls, O., additional, Ningel, K.&R., additional, Oelmann, A., additional, Olejnik, H., additional, Gadow, K., additional, Pascher, E., additional, Petersen, J., additional, Philipp, A., additional, Pichler, M., additional, Polzien, F., additional, Raddant, R., additional, Riedel, M., additional, Rietzler, S., additional, Rössle, M., additional, Rufle, W., additional, Rump, A., additional, Schewe, C., additional, Hoffmann, C., additional, Schleehauf, D., additional, Schmidt, K.J., additional, Schmidt, W., additional, Schmidt-Heinevetter, G., additional, Schmidtler-von Fabris, J., additional, Schnaitmann, E., additional, Schneider, L., additional, Schober, A., additional, Niehaus-Hahn, S., additional, Schwenzer, J., additional, Seidel, T., additional, Seitel, G., additional, Sick, C., additional, Simon, K.G., additional, Stähler, D., additional, Stenschke, F., additional, Steffens, H., additional, Stein, K., additional, Steinmüller, M., additional, Sternfeld, T., additional, Svensson, K., additional, Tacke, W., additional, Teuber, G., additional, Teubner, K., additional, Thieringer, J., additional, Tomesch, A., additional, Trappe, U., additional, Ullrich, J., additional, Urban, G., additional, Usadel, S., additional, von Lucadou, A., additional, Weinberger, F., additional, Werheid-Dobers, M., additional, Werner, P., additional, Winter, T., additional, Zehnter, E., additional, and Zipf, A., additional

Published
2021
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15. A late Eemian aridity pulse in central Europe during the last glacial inception

Author

Sirocko, F., Seelos, K., Schaber, K., Rein, B., Dreher, F., Diehl, M., Lehne, R., Jager, K., Krbetschek, M., and Degering, D.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): F. Sirocko (corresponding author) [1]; K. Seelos [1]; K. Schaber [1]; B. Rein [1]; F. Dreher [1]; M. Diehl [1]; R. Lehne [1]; K. Jäger [1]; M. Krbetschek [2]; [...]

Published
2005
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22. Patterns of Resistance-Associated Substitutions in Patients With Chronic HCV Infection Following Treatment With Direct-Acting Antivirals

Author

Dietz, Julia, primary, Susser, Simone, additional, Vermehren, Johannes, additional, Peiffer, Kai-Henrik, additional, Grammatikos, Georgios, additional, Berger, Annemarie, additional, Ferenci, Peter, additional, Buti, Maria, additional, Müllhaupt, Beat, additional, Hunyady, Bela, additional, Hinrichsen, Holger, additional, Mauss, Stefan, additional, Petersen, Jörg, additional, Buggisch, Peter, additional, Felten, Gisela, additional, Hüppe, Dietrich, additional, Knecht, Gaby, additional, Lutz, Thomas, additional, Schott, Eckart, additional, Berg, Christoph, additional, Spengler, Ulrich, additional, von Hahn, Thomas, additional, Berg, Thomas, additional, Zeuzem, Stefan, additional, Sarrazin, Christoph, additional, Antoni, C., additional, Vogelmann, R., additional, Ebert, M., additional, Backhus, J., additional, Seufferlein, T., additional, Balavoine, J., additional, Giostra, E., additional, Berg, C., additional, Cornberg, M., additional, Wedemeyer, H., additional, Manns, M., additional, De Gottardi, A., additional, Esteban, R., additional, Discher, T., additional, Roeb, E., additional, Gress, M., additional, Günther, R., additional, Wietzke-Braun, P., additional, Herrmann, A., additional, Stallmach, A., additional, Hoffmann, D., additional, Klinker, H., additional, Kodal, A., additional, Lammert, F., additional, Löbermann, M., additional, Schulze zur Wiesch, J., additional, von Felden, J., additional, Piecha, F., additional, Lohse, A., additional, Götze, T., additional, Malfertheiner, P., additional, Mayerle, J., additional, Moradpour, D., additional, Moreno, C., additional, Neumann-Haefelin, C., additional, Thimme, R., additional, Reinhardt, L., additional, Ellenrieder, V., additional, Schattenberg, J., additional, Sprinzl, M., additional, Galle, P., additional, Schmidt, J., additional, Schott, E., additional, Epple, H.-J., additional, Siebler, J., additional, Stauber, R., additional, Steckstor, M., additional, Schmiegel, W., additional, Stremmel, W., additional, Strey, B., additional, Tomasiewicz, K., additional, Trautwein, C., additional, Zachoval, R., additional, Angeli, W., additional, Beckebaum, S., additional, Doberauer, C., additional, Ende, K., additional, Erhardt, A., additional, Garrido-Lüneburg, A., additional, Gattringer, H., additional, Genné, D., additional, Gschwantler, M., additional, Gundling, F., additional, Hartmann, C., additional, Heyer, T., additional, Hirschi, C., additional, Kanzler, S., additional, Kordecki, N., additional, Kraus, M., additional, Kullig, U., additional, Magenta, L., additional, Terziroli Beretta-Piccoli, B., additional, Menges, M., additional, Mohr, L., additional, Muehlenberg, K., additional, Niederau, C., additional, Paulweber, B., additional, Petrides, A., additional, Piso, R., additional, Rambach, W., additional, Reiser, M., additional, Riecken, B., additional, Roth, J., additional, Schöfl, R., additional, Maieron, A., additional, Schneider, A., additional, Schuchmann, M., additional, Schulten-Baumer, U., additional, Seelhoff, A., additional, Semela, D., additional, Stich, A., additional, Vollmer, C., additional, Brückner, J., additional, Ungemach, J., additional, Walter, E., additional, Weber, A., additional, Winzer, T., additional, Abels, W., additional, Adler, M., additional, Audebert, F., additional, Baermann, C., additional, Bästlein, E., additional, Barth, R., additional, Barthel, K., additional, Baumgartl, K., additional, Becker, W., additional, Benninger, J., additional, Beyer, T., additional, Bodtländer, A., additional, Böhm, G., additional, Bohr, U., additional, Moll, A., additional, Naumann, U., additional, Börner, N., additional, Bruch, H.R., additional, Busch, N., additional, Burkhard, O., additional, Chirca, C., additional, Dienethal, A., additional, Dietel, P., additional, Dreher, F., additional, Efken, P., additional, Ehrle, U., additional, Emke, F., additional, Fischer, J., additional, Fischer, U., additional, Frederking, D., additional, Frick, B., additional, Gantke B, B., additional, Geyer, P., additional, Glaunsinger, T., additional, Goebel, F., additional, Göbel, U., additional, Graf, R., additional, Herder, M., additional, Heuchel, T., additional, Heuer, S., additional, Heyne, R., additional, Höffl, K.H., additional, Hofmann, W.P., additional, Holst, F., additional, Hörster, H., additional, John, C., additional, Jung, M.C., additional, Kallinowski, B., additional, Kerzel, W., additional, Khaykin, P., additional, Klarhof, M., additional, Knapp, B., additional, Knevels, U., additional, Körfer, A., additional, Köster, A., additional, Künzig, B., additional, Langenkamp, A., additional, Kuhn, M., additional, Littman, M., additional, Löhr, H., additional, Ludwig, L., additional, Lutz, U., additional, Maurer, P., additional, Mayer, C., additional, Meister, V., additional, Moritzen, D., additional, Mroß, M., additional, Mundlos, M., additional, Nehls, O., additional, Ningel, K., additional, Oelmann, A., additional, Olejnik, H., additional, Pascher, E., additional, Philipp, A., additional, Pichler, M., additional, Polzien, F., additional, Raddant, R., additional, Riedel, M., additional, Rietzler, S., additional, Rump, A., additional, Schmidt, W., additional, Schmidtler-von Fabris, J., additional, Schneider, L., additional, Schober, A., additional, Schwenzer, J., additional, Seidel, T., additional, Seitel, G., additional, Sick, C., additional, Simon, K., additional, Stähler, D., additional, Steffens, H., additional, Svensson, K., additional, Tacke, W., additional, Teubner, K., additional, Thieringer, J., additional, Trappe, U., additional, Ullrich, J., additional, Usadel, S., additional, von Lucadou, A., additional, Werheid-Dobers, M., additional, Zehnter, E., additional, and Zipf, A., additional

Published
2018
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35. Continuous Images of Cantor's Ternary Set.

Author

Dreher, F. and Samuel, T.

Subjects
*MATHEMATICS theorems, *SET theory, *MATHEMATICS, *ALGEBRAIC spaces, *ALGEBRAIC geometry
Abstract

The article reports that the Hausdorff-Alexandroff Theorem states that any compact metric space is the continuous image of Cantor's ternary set C. Restricting the cardinality leads to a sufficient condition. the cardinality of a space, which is the continuous image of C. The restriction on cardinality is a necessary and there are compact Hausdorff spaces with cardinality.

Published
2014
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39. Impact of Ultraviolet Radiation and Ozone on the Transepidermal Water Loss as a Function of Skin Temperature in Hairless Mice.

Author

Thiele, J. J., Dreher, F., Maibach, H. I., and Packer, L.

Subjects
*ULTRAVIOLET radiation, *OXIDATIVE stress, *SKIN, *OZONE, *XENOBIOTICS
Abstract

Exposure to ultraviolet radiation or ozone leads to skin damage including oxidation of skin biomolecules, as well as to depletion of constitutive antioxidants. The highly organized stratum corneum forming the main barrier against most xenobiotics is particularly susceptible to such damage and possible barrier perturbation may be the consequence. Whereas ample evidence exists for an increased permeability for different solutes including water after exposure to ultraviolet radiation, such an effect has not yet been reported for ozone. This study reports on the effect of such oxidative stressors using the hairless mouse as the skin model and measuring temperature-controlled transepidermal water loss (TEWL) as an indicator for skin barrier integrity. First, a strong dependency of the TEWL on skin temperature was observed, an effect that was clearly more pronounced than that found in man. Given this temperature dependency in untreated animals, we proceeded to determine the effects of both ultraviolet radiation and ozone on TEWL over a relevant physiological skin temperature range. Solar-simulated ultraviolet radiation (0.75-3 minimal erythemal dose) resulted in a delayed and dose-dependent skin barrier disruption over the entire temperature range investigated. Conversely, daily ozone exposure at 2 ppm for 1 week, however, did not significantly alter TEWL up to 72 h after the last exposure. The results demonstrate a differential response of the epidermis to two environmental stressors associated with oxidative damage; they suggest that chronic ozone exposure at relevant environmental levels does not lead to a detectable skin barrier defect, while solar UV exposure was demonstrated to increase epidermal water loss. Furthermore, experimental evidence clearly suggests that future studies applying TEWL measurements in animal models should be performed under carefully controlled skin temperature conditions. [ABSTRACT FROM AUTHOR]

Published
2003
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42. Colorimetric Method for Quantifying Human Stratum Corneum Removed by Adhesive-Tape-Stripping.

Author

Dreher, F., Arens, A., Hostýnek, J. J., Mudumba, S., Ademola, J., and Maibach, H. I.

Subjects
*ADHESIVE tape, *EPIDERMIS, *COLORIMETRIC analysis
Abstract

Tape-stripping of the skin is a useful method for removing the stratum corneum and obtaining more information about the function of this skin layer as the main barrier for skin penetration. The amount of stratum corneum removed is of relevance in establishing the concentration profile of chemicals within the stratum corneum after topical application. Weighing is the preferred method for measuring the amount stripped, but because it is often subject to artifacts, alternative methods are sought. We present a simple, colorimetric method for determining the amount stratum corneum removed by sequential adhesive-tape-stripping of human skin in vivo. The method is based on quantification of the sodium hydroxide soluble protein fraction using a commercially available protein assay similar to the Lowry assay. The method is shown to be an accurate and reproducible alternative to weighing, also demonstrating uniform removal of stratum corneum layers following the very initial strips. [ABSTRACT FROM AUTHOR]

Published
1998
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44. DIPSBC - data integration platform for systems biology collaborations

Author

Dreher Felix, Kreitler Thomas, Hardt Christopher, Kamburov Atanas, Yildirimman Reha, Schellander Karl, Lehrach Hans, Lange Bodo MH, and Herwig Ralf

Subjects
Data integration, XML, Data visualization, Computer applications to medicine. Medical informatics, R858-859.7, Biology (General), QH301-705.5
Abstract

Abstract Background Modern biomedical research is often organized in collaborations involving labs worldwide. In particular in systems biology, complex molecular systems are analyzed that require the generation and interpretation of heterogeneous data for their explanation, for example ranging from gene expression studies and mass spectrometry measurements to experimental techniques for detecting molecular interactions and functional assays. XML has become the most prominent format for representing and exchanging these data. However, besides the development of standards there is still a fundamental lack of data integration systems that are able to utilize these exchange formats, organize the data in an integrative way and link it with applications for data interpretation and analysis. Results We have developed DIPSBC, an interactive data integration platform supporting collaborative research projects, based on Foswiki, Solr/Lucene, and specific helper applications. We describe the main features of the implementation and highlight the performance of the system with several use cases. All components of the system are platform independent and open-source developments and thus can be easily adopted by researchers. An exemplary installation of the platform which also provides several helper applications and detailed instructions for system usage and setup is available at http://dipsbc.molgen.mpg.de. Conclusions DIPSBC is a data integration platform for medium-scale collaboration projects that has been tested already within several research collaborations. Because of its modular design and the incorporation of XML data formats it is highly flexible and easy to use.

Published
2012
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45. A framework for validating AI in precision medicine: considerations from the European ITFoC consortium

Author

Tsopra, Rosy, Fernandez, Xose, Luchinat, Claudio, Alberghina, Lilia, Lehrach, Hans, Vanoni, Marco, Dreher, Felix, Sezerman, O Ugur, Cuggia, Marc, de Tayrac, Marie, Miklasevics, Edvins, Itu, Lucian Mihai, Geanta, Marius, Ogilvie, Lesley, Godey, Florence, Boldisor, Cristian Nicolae, Campillo-Gimenez, Boris, Cioroboiu, Cosmina, Ciusdel, Costin Florian, Coman, Simona, Hijano Cubelos, Oliver, Itu, Alina, Lange, Bodo, Le Gallo, Matthieu, Lespagnol, Alexandra, Mauri, Giancarlo, Soykam, H Okan, Rance, Bastien, Turano, Paola, Tenori, Leonardo, Vignoli, Alessia, Wierling, Christoph, Benhabiles, Nora, Burgun, Anita, Sezerman, O.Ugur, Soykam, H.Okan, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École pratique des hautes études (EPHE), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Institut Curie [Paris], Università degli Studi di Firenze = University of Florence (UniFI), Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Max Planck Institute for Molecular Genetics (MPIMG), Max-Planck-Gesellschaft, Alacris Theranostics GmbH [Berlin] (ATG), Acibadem University, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Riga Stradins University (RSU), Transilvania University of Brasov, Centre for Innovation in Medicine [Bucharest] (CIM), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), Centre de Ressources Biologiques Santé (CRB Santé), Université de Rennes (UR)-CHU Pontchaillou [Rennes]-CRLCC Eugène Marquis (CRLCC), EPIGENETICS Inc. BUDOTEK [Istanbul, Turkey], Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Paris-Saclay, This work was supported by the ITFoC project (Information Technology for the Future of Cancer) – FLAG-ERA support., Malbec, Odile, École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), INSERM, Université de Paris, Sorbonne Université, Centre de Recherche des Cordeliers, Information Sciences to support Personalized Medicine, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Tsopra, R, Fernandez, X, Luchinat, C, Alberghina, L, Lehrach, H, Vanoni, M, Dreher, F, Sezerman, O, Cuggia, M, de Tayrac, M, Miklasevics, E, Itu, L, Geanta, M, Ogilvie, L, Godey, F, Boldisor, C, Campillo-Gimenez, B, Cioroboiu, C, Ciusdel, C, Coman, S, Hijano Cubelos, O, Itu, A, Lange, B, Le Gallo, M, Lespagnol, A, Mauri, G, Soykam, H, Rance, B, Turano, P, Tenori, L, Vignoli, A, Wierling, C, Benhabiles, N, Burgun, A, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP)-École pratique des hautes études (EPHE), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), CHU Pontchaillou [Rennes]-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), Acibadem University Dspace, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-CRLCC Eugène Marquis (CRLCC)

Subjects
Artificial intelligence, MESH: Humans, MESH: Machine Learning, [SDV]Life Sciences [q-bio], Computer applications to medicine. Medical informatics, Precision medicine, Computerized decision support systems, R858-859.7, Cancer, Oncology, Personalized medicine, Algorithms, Humans, Machine Learning, Precision Medicine, Artificial Intelligence, Neoplasms, MESH: Algorithms, Computerized decision support system, MESH: Precision Medicine, [SDV] Life Sciences [q-bio], ComputingMethodologies_PATTERNRECOGNITION, MESH: Artificial Intelligence, [INFO]Computer Science [cs], MESH: Neoplasms, Research Article
Abstract

International audience; Abstract Background Artificial intelligence (AI) has the potential to transform our healthcare systems significantly. New AI technologies based on machine learning approaches should play a key role in clinical decision-making in the future. However, their implementation in health care settings remains limited, mostly due to a lack of robust validation procedures. There is a need to develop reliable assessment frameworks for the clinical validation of AI. We present here an approach for assessing AI for predicting treatment response in triple-negative breast cancer (TNBC), using real-world data and molecular -omics data from clinical data warehouses and biobanks. Methods The European “ITFoC (Information Technology for the Future Of Cancer)” consortium designed a framework for the clinical validation of AI technologies for predicting treatment response in oncology. Results This framework is based on seven key steps specifying: (1) the intended use of AI, (2) the target population, (3) the timing of AI evaluation, (4) the datasets used for evaluation, (5) the procedures used for ensuring data safety (including data quality, privacy and security), (6) the metrics used for measuring performance, and (7) the procedures used to ensure that the AI is explainable. This framework forms the basis of a validation platform that we are building for the “ITFoC Challenge”. This community-wide competition will make it possible to assess and compare AI algorithms for predicting the response to TNBC treatments with external real-world datasets. Conclusions The predictive performance and safety of AI technologies must be assessed in a robust, unbiased and transparent manner before their implementation in healthcare settings. We believe that the consideration of the ITFoC consortium will contribute to the safe transfer and implementation of AI in clinical settings, in the context of precision oncology and personalized care.

Published
2021

46. Sub-Micron Replication of Fused Silica Glass and Amorphous Metals for Tool-Based Manufacturing.

Author

Kluck S, Prediger R, Hambitzer L, Nekoonam N, Dreher F, Luitz M, Lunzer M, Worgull M, Schneider M, Rapp BE, and Kotz-Helmer F

Abstract

The growing importance of submicrometer-structured surfaces across a variety of different fields has driven progress in light manipulation, color diversity, water-repellency, and functional enhancements. To enable mass production, processes like hot-embossing (HE), roll-to-roll replication (R2R), and injection molding (IM) are essential due to their precision and material flexibility. However, these processes are tool-based manufacturing (TBM) techniques requiring metal molds, which are time-consuming and expensive to manufacture, as they mostly rely on galvanoforming using templates made via precision microlithography or two-photon-polymerization (2PP). In this work, a novel approach is demonstrated to replicate amorphous metals from fused silica glass, derived from additive manufacturing and structured using hot embossing and casting, enabling the fabrication of metal insets with features in the range of 300 nm and a surface roughness of below 10 nm. By partially crystallizing the amorphous metal, during the replication process, the insets gain a high hardness of up to 800 HV. The metal molds are successfully used in polymer injection molding using different polymers including polystyrene (PS) and polyethylene (PE) as well as glass nanocomposites. This work is of significant importance to the field as it provides a production method for the increasing demand for sub-micron-structured tooling in the area of polymer replication while substantially reducing their cost of production., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Published
2024
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47. AI-driven discovery of blood xenobiotic biomarkers in neovascular age-related macular degeneration using iterative random forests.

Author

Künzel SE, Frentzel DP, Flesch LTM, Knecht VA, Rübsam A, Dreher F, Schütte M, Dubrac A, Lange B, Yaspo ML, Lehrach H, Joussen AM, and Zeitz O

Abstract

Purpose: To investigate the xenobiotic profiles of patients with neovascular age-related macular degeneration (nAMD) undergoing anti-vascular endothelial growth factor (anti-VEGF) intravitreal therapy (IVT) to identify biomarkers indicative of clinical phenotypes through advanced AI methodologies., Methods: In this cross-sectional observational study, we analyzed 156 peripheral blood xenobiotic features in a cohort of 46 nAMD patients stratified by choroidal neovascularization (CNV) control under anti-VEGF IVT. We employed Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) for measurement and leveraged an AI-driven iterative Random Forests (iRF) approach for robust pattern recognition and feature selection, aligning molecular profiles with clinical phenotypes., Results: AI-augmented iRF models effectively refined the metabolite spectrum by discarding non-predictive elements. Perfluorooctanesulfonate (PFOS) and Ethyl β-glucopyranoside were identified as significant biomarkers through this process, associated with various clinically relevant phenotypes. Unlike single metabolite classes, drug metabolites were distinctly correlated with subretinal fluid presence., Conclusions: This study underscores the enhanced capability of AI, particularly iRF, in dissecting complex metabolomic data to elucidate the xenobiotic landscape of nAMD and environmental impact on the disease. The preliminary biomarkers discovered offer promising directions for personalized treatment strategies, although further validation in broader cohorts is essential for clinical application., (© 2024. The Author(s).)

Published
2024
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48. Exploring the Impact of Saccharin on Neovascular Age-Related Macular Degeneration: A Comprehensive Study in Patients and Mice.

Author

Künzel SE, Pompös IM, Flesch LTM, Frentzel DP, Knecht VA, Winkler S, Skosyrski S, Rübsam A, Dreher F, Kociok N, Schütte M, Dubrac A, Lange B, Yaspo ML, Lehrach H, Strauß O, Joussen AM, and Zeitz O

Subjects
Humans, Mice, Animals, Vascular Endothelial Growth Factor Receptor-1, Saccharin therapeutic use, Vascular Endothelial Growth Factor A genetics, Vascular Endothelial Growth Factor A metabolism, Sweetening Agents, Cross-Sectional Studies, Chromatography, Liquid, Tandem Mass Spectrometry, RNA, Messenger genetics, Intravitreal Injections, Angiogenesis Inhibitors therapeutic use, Choroidal Neovascularization metabolism, Macular Degeneration metabolism
Abstract

Purpose: We aimed to determine the impact of artificial sweeteners (AS), especially saccharin, on the progression and treatment efficacy of patients with neovascular age-related macular degeneration (nAMD) under anti-vascular endothelial growth factor (anti-VEGF-A) treatment., Methods: In a cross-sectional study involving 46 patients with nAMD undergoing intravitreal anti-VEGF therapy, 6 AS metabolites were detected in peripheral blood using liquid chromatography - tandem mass spectrometry (LC-MS/MS). Disease features were statistically tested against these metabolite levels. Additionally, a murine choroidal neovascularization (CNV) model, induced by laser, was used to evaluate the effects of orally administered saccharin, assessing both imaging outcomes and gene expression patterns. Polymerase chain reaction (PCR) methods were used to evaluate functional expression of sweet taste receptors in a retinal pigment epithelium (RPE) cell line., Results: Saccharin levels in blood were significantly higher in patients with well-controlled CNV activity (P = 0.004) and those without subretinal hyper-reflective material (P = 0.015). In the murine model, saccharin-treated mice exhibited fewer leaking laser scars, lesser occurrence of bleeding, smaller fibrotic areas (P < 0.05), and a 40% decrease in mononuclear phagocyte accumulation (P = 0.06). Gene analysis indicated downregulation of inflammatory and VEGFR-1 response genes in the treated animals. Human RPE cells expressed taste receptor type 1 member 3 (TAS1R3) mRNA and reacted to saccharin stimulation with changes in mRNA expression., Conclusions: Saccharin appears to play a protective role in patients with nAMD undergoing intravitreal anti-VEGF treatment, aiding in better pathological lesion control and scar reduction. The murine study supports this observation, proposing saccharin's potential in mitigating pathological VEGFR-1-induced immune responses potentially via the RPE sensing saccharin in the blood stream.

Published
2024
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49. Systemic Blood Proteome Patterns Reflect Disease Phenotypes in Neovascular Age-Related Macular Degeneration.

Author

Künzel SE, Flesch LTM, Frentzel DP, Knecht VA, Rübsam A, Dreher F, Schütte M, Dubrac A, Lange B, Yaspo ML, Lehrach H, Joussen AM, and Zeitz O

Subjects
Humans, Ranibizumab therapeutic use, Vascular Endothelial Growth Factor A metabolism, Proteome, Prospective Studies, Chromatography, Liquid, Cross-Sectional Studies, Proteomics, Tandem Mass Spectrometry, Phenotype, Angiogenesis Inhibitors therapeutic use, Macular Degeneration drug therapy
Abstract

There is early evidence of extraocular systemic signals effecting function and morphology in neovascular age-related macular degeneration (nAMD). The prospective, cross-sectional BIOMAC study is an explorative investigation of peripheral blood proteome profiles and matched clinical features to uncover systemic determinacy in nAMD under anti-vascular endothelial growth factor intravitreal therapy (anti-VEGF IVT). It includes 46 nAMD patients stratified by the level of disease control under ongoing anti-VEGF treatment. Proteomic profiles in peripheral blood samples of every patient were detected with LC-MS/MS mass spectrometry. The patients underwent extensive clinical examination with a focus on macular function and morphology. In silico analysis includes unbiased dimensionality reduction and clustering, a subsequent annotation of clinical features, and non-linear models for recognition of underlying patterns. The model assessment was performed using leave-one-out cross validation. The findings provide an exploratory demonstration of the link between systemic proteomic signals and macular disease pattern using and validating non-linear classification models. Three main results were obtained: (1) Proteome-based clustering identifies two distinct patient subclusters with the smaller one ( n = 10) exhibiting a strong signature for oxidative stress response. Matching the relevant meta-features on the individual patient's level identifies pulmonary dysfunction as an underlying health condition in these patients. (2) We identify biomarkers for nAMD disease features with Aldolase C as a putative factor associated with superior disease control under ongoing anti-VEGF treatment. (3) Apart from this, isolated protein markers are only weakly correlated with nAMD disease expression. In contrast, applying a non-linear classification model identifies complex molecular patterns hidden in a high number of proteomic dimensions determining macular disease expression. In conclusion, so far unconsidered systemic signals in the peripheral blood proteome contribute to the clinically observed phenotype of nAMD, which should be examined in future translational research on AMD.

Published
2023
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50. Thresholds for the presence of glacial megafauna in central Europe during the last 60,000 years.

Author

Sirocko F, Albert J, Britzius S, Dreher F, Martínez-García A, Dosseto A, Burger J, Terberger T, and Haug G

Subjects
Animals, Humans, Europe, Forests, Mammals, Climate, Trees
Abstract

Lake sediment records from Holzmaar and the infilled maar of Auel (Eifel, Germany) are used to reconstruct landscape changes and megafauna abundances. Our data document a forested landscape from 60,000 to 48,000 yr b2k and a stepwise vegetation change towards a glacial desert after 26,000 yr b2k. The Eifel landscape was continuously inhabited from 48,000 to 9000 yr b2k by large mammals, documented by the presence of spores of coprophilous fungi from Sordaria and Sporormiella fungi that grow on fecal remains of the megafauna. Megafauna reached higher numbers during cold stadial climates but was present also during the warmer interstadials. Highest abundance was at 56,500/48,500/38,500/33,000/27,000/21,000/16,200/14,000 yr b2k, i.e. under different climate regimes. Some of these dates were associated with clear human presence, which indicates that megafauna was not overkilled by humans. In contrast, human presence could quite likely have been stimulated by the abundant food supply. Megafauna presence decreased significantly when tree abundance increased during interstadials. The Megafauna disappeared finally at 11,400 yr b2k with the development of the early Holocene forest cover, which appears to be the most important threshold for megafauna presence., (© 2022. The Author(s).)

Published
2022
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