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6. 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

7. 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

10. 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

11. 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

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

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