26 results on '"Fuhrmann, J."'
Search Results
2. LB 02.4 Anti-Platelet Factor 4 Induced Immunothrombosis Independent of Heparin or Vaccination
- Author
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Schönborn, L., primary, Esteban, O., additional, Wesche, J., additional, Dobosz, P., additional, Broto, M., additional, Rovira, S., additional, Fuhrmann, J., additional, Torres, R., additional, Serra, J., additional, Llevadot, R., additional, Lindhoff-Last, E., additional, Hoffmann, T., additional, Alberio, L., additional, Langer, F., additional, Boehme, C., additional, and Greinacher, A., additional
- Published
- 2023
- Full Text
- View/download PDF
3. A monotone numerical flux for quasilinear convection diffusion equation.
- Author
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Chainais-Hillairet, C., Eymard, R., and Fuhrmann, J.
- Subjects
TRANSPORT equation ,BOUNDARY value problems ,LINEAR equations - Abstract
We propose a new numerical 2-point flux for a quasilinear convection–diffusion equation. This numerical flux is shown to be an approximation of the numerical flux derived from the solution of a two-point Dirichlet boundary value problem for the projection of the continuous flux onto the line connecting neighboring collocation points. The later approach generalizes an idea first proposed by Scharfetter and Gummel [IEEE Trans. Electron Devices 16 (1969), pp. 64–77] for linear drift-diffusion equations. We establish first that the new flux satisfies sufficient properties ensuring the convergence of the associate finite volume scheme, while respecting the maximum principle. Then, we pay attention to the long time behavior of the scheme: we show relative entropy decay properties satisfied by the new numerical flux as well as by the generalized Scharfetter-Gummel flux. The proof of these properties uses a generalization of some discrete (and continuous) log-Sobolev inequalities. The corresponding decay of the relative entropy of the continuous solution is proved in the appendix. Some 1D numerical experiments confirm the theoretical results. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
4. Developing an assay to distinguish between HIT and VITT antibodies
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Schönborn, L, additional, Wesche, J, additional, Fuhrmann, J, additional, Esteban, O, additional, Dobosz, P, additional, Broto, M, additional, Serra, J, additional, Llevadot, R, additional, and Greinacher, A, additional
- Published
- 2023
- Full Text
- View/download PDF
5. Predictive performance of multi-model ensemble forecasts of COVID-19 across European nations
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Sherratt, K., Gruson, H., Grah, R., Johnson, H., Niehus, R., Prasse, B., Sandmann, F., Deuschel, J., Wolffram, D., Abbott, S., Ullrich, A., Gibson, G., Ray, E. L., Reich, N. G., Sheldon, D., Wang, Y., Wattanachit, N., Wang, L., Trnka, J., Obozinski, G., Sun, T., Thanou, D., Pottier, L., Krymova, E., Meinke, J. H., Barbarossa, M. V., Leithäuser, N., Mohring, J., Schneider, J., Wlazlo, J., Fuhrmann, J., Lange, B., Rodiah, I., Baccam, P., Gurung, H., Stage, S., Suchoski, B., Budzinski, J., Walraven, R., Villanueva, I., Tucek, V., Smíd, M., Zajícek, M., Pérez Alvarez, C., Reina, B., Bosse, N. I., Meakin, S., Castro, L., Fairchild, G., Michaud, I., Osthus, D., Alaimo Di Loro, P., Maruotti, A., Eclerová, V., Kraus, A., Kraus, D., Pribylova, L., Dimitris, B., Li, M. L., Saksham, S., Dehning, J., Mohr, S., Priesemann, V., Redlarski, G., Bejar, B., Ardenghi, G., Parolini, N., Ziarelli, G., Bock, Wolfgang, Heyder, S., Hotz, T., E. Singh, D., Guzman-Merino, M., Aznarte, J. L., Moriña, D., Alonso, S., Alvarez, E., López, D., Prats, C., Burgard, J. P., Rodloff, A., Zimmermann, T., Kuhlmann, A., Zibert, J., Pennoni, F., Divino, F., Català, M., Lovison, G., Giudici, P., Tarantino, B., Bartolucci, F., Jona Lasinio, G., Mingione, M., Farcomeni, A., Srivastava, A., Montero-Manso, P., Adiga, A., Hurt, B., Lewis, B., Marathe, M., Porebski, P., Venkatramanan, S., Bartczuk, R., Dreger, F., Gambin, A., Gogolewski, K., Gruziel-S?omka, M., Krupa, B., Moszynski, A., Niedzielewski, K., Nowosielski, J., Radwan, M., Rakowski, F., Semeniuk, M., Szczurek, E., Zieli?ski, J., Kisielewski, J., Pabjan, B., Kheifetz, Y., Kirsten, H., Scholz, M., Biecek, P., Bodych, M., Filinski, M., Idzikowski, R., Krueger, T., Ozanski, T., Bracher, J., Funk, S., Sherratt, K., Gruson, H., Grah, R., Johnson, H., Niehus, R., Prasse, B., Sandmann, F., Deuschel, J., Wolffram, D., Abbott, S., Ullrich, A., Gibson, G., Ray, E. L., Reich, N. G., Sheldon, D., Wang, Y., Wattanachit, N., Wang, L., Trnka, J., Obozinski, G., Sun, T., Thanou, D., Pottier, L., Krymova, E., Meinke, J. H., Barbarossa, M. V., Leithäuser, N., Mohring, J., Schneider, J., Wlazlo, J., Fuhrmann, J., Lange, B., Rodiah, I., Baccam, P., Gurung, H., Stage, S., Suchoski, B., Budzinski, J., Walraven, R., Villanueva, I., Tucek, V., Smíd, M., Zajícek, M., Pérez Alvarez, C., Reina, B., Bosse, N. I., Meakin, S., Castro, L., Fairchild, G., Michaud, I., Osthus, D., Alaimo Di Loro, P., Maruotti, A., Eclerová, V., Kraus, A., Kraus, D., Pribylova, L., Dimitris, B., Li, M. L., Saksham, S., Dehning, J., Mohr, S., Priesemann, V., Redlarski, G., Bejar, B., Ardenghi, G., Parolini, N., Ziarelli, G., Bock, Wolfgang, Heyder, S., Hotz, T., E. Singh, D., Guzman-Merino, M., Aznarte, J. L., Moriña, D., Alonso, S., Alvarez, E., López, D., Prats, C., Burgard, J. P., Rodloff, A., Zimmermann, T., Kuhlmann, A., Zibert, J., Pennoni, F., Divino, F., Català, M., Lovison, G., Giudici, P., Tarantino, B., Bartolucci, F., Jona Lasinio, G., Mingione, M., Farcomeni, A., Srivastava, A., Montero-Manso, P., Adiga, A., Hurt, B., Lewis, B., Marathe, M., Porebski, P., Venkatramanan, S., Bartczuk, R., Dreger, F., Gambin, A., Gogolewski, K., Gruziel-S?omka, M., Krupa, B., Moszynski, A., Niedzielewski, K., Nowosielski, J., Radwan, M., Rakowski, F., Semeniuk, M., Szczurek, E., Zieli?ski, J., Kisielewski, J., Pabjan, B., Kheifetz, Y., Kirsten, H., Scholz, M., Biecek, P., Bodych, M., Filinski, M., Idzikowski, R., Krueger, T., Ozanski, T., Bracher, J., and Funk, S.
- Abstract
Methods: We used open-source tools to develop a public European COVID-19 Forecast Hub. We invited groups globally to contribute weekly forecasts for COVID-19 cases and deaths reported by a standardised source for 32 countries over the next 1–4 weeks. Teams submitted forecasts from March 2021 using standardised quantiles of the predictive distribution. Each week we created an ensemble forecast, where each predictive quantile was calculated as the equally-weighted average (initially the mean and then from 26th July the median) of all individual models’ predictive quantiles. We measured the performance of each model using the relative Weighted Interval Score (WIS), comparing models’ forecast accuracy relative to all other models. We retrospectively explored alternative methods for ensemble forecasts, including weighted averages based on models’ past predictive performance. Results: Over 52 weeks, we collected forecasts from 48 unique models. We evaluated 29 models’ forecast scores in comparison to the ensemble model. We found a weekly ensemble had a consistently strong performance across countries over time. Across all horizons and locations, the ensemble performed better on relative WIS than 83% of participating models’ forecasts of incident cases (with a total N=886 predictions from 23 unique models), and 91% of participating models’ forecasts of deaths (N=763 predictions from 20 models). Across a 1–4 week time horizon, ensemble performance declined with longer forecast periods when forecasting cases, but remained stable over 4 weeks for incident death forecasts. In every forecast across 32 countries, the ensemble outperformed most contributing models when forecasting either cases or deaths, frequently outperforming all of its individual component models. Among several choices of ensemble methods we found that the most influential and best choice was to use a median average of models instead of using the mean, regardless of methods of weighting component forecast mod
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- 2023
- Full Text
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6. A personal discussion on conservation, and how to formulate it
- Author
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Franck, Emmanuel, Fuhrmann, Jürgen, Michel-Dansac, Victor, Navoret, Laurent, Franck, E ( Emmanuel ), Fuhrmann, J ( Jürgen ), Michel-Dansac, V ( Victor ), Navoret, L ( Laurent ), Abgrall, Remi; https://orcid.org/0000-0002-5553-7476, Franck, Emmanuel, Fuhrmann, Jürgen, Michel-Dansac, Victor, Navoret, Laurent, Franck, E ( Emmanuel ), Fuhrmann, J ( Jürgen ), Michel-Dansac, V ( Victor ), Navoret, L ( Laurent ), and Abgrall, Remi; https://orcid.org/0000-0002-5553-7476
- Abstract
Since the celebrated theorem of Lax and Wendroff, we know a necessary condition that any numerical scheme for hyperbolic problem should satisfy: it should be written in flux form. A variant can also be formulated for the entropy. Even though some schemes, as for example those using continuous finite element, do not formally cast into this framework, it is a very convenient one. In this paper, we revisit this, introduce a different notion of local conservation which contains the previous one in one space dimension, and explore its consequences. This gives a more flexible framework that allows to get, systematically, entropy stable schemes, entropy dissipative ones, or accommodate more constraints. In particular, we can show that continuous finite element method can be rewritten in the finite volume framework, and all the quantities involved are explicitly computable. We end by presenting the only counter example we are aware of, i.e a scheme that seems not to be rewritten as a finite volume scheme.
- Published
- 2023
7. Predictive performance of multi-model ensemble forecasts of COVID-19 across European nations
- Author
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Sherratt, K, Gruson, H, Grah, R, Johnson, H, Niehus, R, Prasse, B, Sandmann, F, Deuschel, J, Wolffram, D, Abbott, S, Ullrich, A, Gibson, G, L Ray, E, G Reich, N, Sheldon, D, Wang, Y, Wattanachit, N, Wang, L, Trnka, J, Obozinski, G, Sun, T, Thanou, D, Pottier, L, Krymova, E, H Meinke, J, Vittoria Barbarossa, M, Leithäuser, N, Mohring, J, Schneider, J, Włazło, J, Fuhrmann, J, Lange, B, Rodiah, I, Baccam, P, Gurung, H, Stage, S, Suchoski, B, Budzinski, J, Walraven, R, Villanueva, I, Tucek, V, Smid, M, Zajíček, M, Pérez Álvarez, C, Reina, B, I Bosse, N, R Meakin, S, Castro, L, Fairchild, G, Michaud, I, Osthus, D, Alaimo Di Loro, P, Maruotti, A, Eclerová, V, Kraus, A, Kraus, D, Pribylova, L, Dimitris, B, Lingzhi Li, M, Saksham, S, Dehning, J, Mohr, S, Priesemann, V, Redlarski, G, Bejar, B, Ardenghi, G, Parolini, N, Ziarelli, G, Bock, W, Heyder, S, Hotz, T, E Singh, D, Guzman-Merino, M, L Aznarte, J, Moriña, D, Alonso, S, Álvarez, E, López, D, Prats, C, Pablo Burgard, J, Rodloff, A, Zimmermann, T, Kuhlmann, A, Zibert, J, Pennoni, F, Divino, F, Català, M, Lovison, G, Giudici, P, Tarantino, B, Bartolucci, F, Jona Lasinio, G, Mingione, M, Farcomeni, A, Srivastava, A, Montero-Manso, P, Adiga, A, Hurt, B, Lewis, B, Marathe, M, Porebski, P, Venkatramanan, S, P Bartczuk, R, Dreger, F, Gambin, A, Gogolewski, K, Gruziel-Słomka, M, Krupa, B, Moszyński, A, Niedzielewski, K, Nowosielski, J, Radwan, M, Rakowski, F, Semeniuk, M, Szczurek, E, Zieliński, J, Kisielewski, J, Pabjan, B, Kirsten, H, Kheifetz, Y, Scholz, M, Biecek, P, Bodych, M, Filinski, M, Idzikowski, R, Krueger, T, Ozanski, T, Bracher, J, Funk, S, Katharine Sherratt, Hugo Gruson, Rok Grah, Helen Johnson, Rene Niehus, Bastian Prasse, Frank Sandmann, Jannik Deuschel, Daniel Wolffram, Sam Abbott, Alexander Ullrich, Graham Gibson, Evan L Ray, Nicholas G Reich, Daniel Sheldon, Yijin Wang, Nutcha Wattanachit, Lijing Wang, Jan Trnka, Guillaume Obozinski, Tao Sun, Dorina Thanou, Loic Pottier, Ekaterina Krymova, Jan H Meinke, Maria Vittoria Barbarossa, Neele Leithäuser, Jan Mohring, Johanna Schneider, Jaroslaw Włazło, Jan Fuhrmann, Berit Lange, Isti Rodiah, Prasith Baccam, Heidi Gurung, Steven Stage, Bradley Suchoski, Jozef Budzinski, Robert Walraven, Inmaculada Villanueva, Vit Tucek, Martin Smid, Milan Zajíček, Cesar Pérez Álvarez, Borja Reina, Nikos I Bosse, Sophie R Meakin, Lauren Castro, Geoffrey Fairchild, Isaac Michaud, Dave Osthus, Pierfrancesco Alaimo Di Loro, Antonello Maruotti, Veronika Eclerová, Andrea Kraus, David Kraus, Lenka Pribylova, Bertsimas Dimitris, Michael Lingzhi Li, Soni Saksham, Jonas Dehning, Sebastian Mohr, Viola Priesemann, Grzegorz Redlarski, Benjamin Bejar, Giovanni Ardenghi, Nicola Parolini, Giovanni Ziarelli, Wolfgang Bock, Stefan Heyder, Thomas Hotz, David E Singh, Miguel Guzman-Merino, Jose L Aznarte, David Moriña, Sergio Alonso, Enric Álvarez, Daniel López, Clara Prats, Jan Pablo Burgard, Arne Rodloff, Tom Zimmermann, Alexander Kuhlmann, Janez Zibert, Fulvia Pennoni, Fabio Divino, Marti Català, Gianfranco Lovison, Paolo Giudici, Barbara Tarantino, Francesco Bartolucci, Giovanna Jona Lasinio, Marco Mingione, Alessio Farcomeni, Ajitesh Srivastava, Pablo Montero-Manso, Aniruddha Adiga, Benjamin Hurt, Bryan Lewis, Madhav Marathe, Przemyslaw Porebski, Srinivasan Venkatramanan, Rafal P Bartczuk, Filip Dreger, Anna Gambin, Krzysztof Gogolewski, Magdalena Gruziel-Słomka, Bartosz Krupa, Antoni Moszyński, Karol Niedzielewski, Jedrzej Nowosielski, Maciej Radwan, Franciszek Rakowski, Marcin Semeniuk, Ewa Szczurek, Jakub Zieliński, Jan Kisielewski, Barbara Pabjan, Holger Kirsten, Yuri Kheifetz, Markus Scholz, Przemyslaw Biecek, Marcin Bodych, Maciej Filinski, Radoslaw Idzikowski, Tyll Krueger, Tomasz Ozanski, Johannes Bracher, Sebastian Funk, Sherratt, K, Gruson, H, Grah, R, Johnson, H, Niehus, R, Prasse, B, Sandmann, F, Deuschel, J, Wolffram, D, Abbott, S, Ullrich, A, Gibson, G, L Ray, E, G Reich, N, Sheldon, D, Wang, Y, Wattanachit, N, Wang, L, Trnka, J, Obozinski, G, Sun, T, Thanou, D, Pottier, L, Krymova, E, H Meinke, J, Vittoria Barbarossa, M, Leithäuser, N, Mohring, J, Schneider, J, Włazło, J, Fuhrmann, J, Lange, B, Rodiah, I, Baccam, P, Gurung, H, Stage, S, Suchoski, B, Budzinski, J, Walraven, R, Villanueva, I, Tucek, V, Smid, M, Zajíček, M, Pérez Álvarez, C, Reina, B, I Bosse, N, R Meakin, S, Castro, L, Fairchild, G, Michaud, I, Osthus, D, Alaimo Di Loro, P, Maruotti, A, Eclerová, V, Kraus, A, Kraus, D, Pribylova, L, Dimitris, B, Lingzhi Li, M, Saksham, S, Dehning, J, Mohr, S, Priesemann, V, Redlarski, G, Bejar, B, Ardenghi, G, Parolini, N, Ziarelli, G, Bock, W, Heyder, S, Hotz, T, E Singh, D, Guzman-Merino, M, L Aznarte, J, Moriña, D, Alonso, S, Álvarez, E, López, D, Prats, C, Pablo Burgard, J, Rodloff, A, Zimmermann, T, Kuhlmann, A, Zibert, J, Pennoni, F, Divino, F, Català, M, Lovison, G, Giudici, P, Tarantino, B, Bartolucci, F, Jona Lasinio, G, Mingione, M, Farcomeni, A, Srivastava, A, Montero-Manso, P, Adiga, A, Hurt, B, Lewis, B, Marathe, M, Porebski, P, Venkatramanan, S, P Bartczuk, R, Dreger, F, Gambin, A, Gogolewski, K, Gruziel-Słomka, M, Krupa, B, Moszyński, A, Niedzielewski, K, Nowosielski, J, Radwan, M, Rakowski, F, Semeniuk, M, Szczurek, E, Zieliński, J, Kisielewski, J, Pabjan, B, Kirsten, H, Kheifetz, Y, Scholz, M, Biecek, P, Bodych, M, Filinski, M, Idzikowski, R, Krueger, T, Ozanski, T, Bracher, J, Funk, S, Katharine Sherratt, Hugo Gruson, Rok Grah, Helen Johnson, Rene Niehus, Bastian Prasse, Frank Sandmann, Jannik Deuschel, Daniel Wolffram, Sam Abbott, Alexander Ullrich, Graham Gibson, Evan L Ray, Nicholas G Reich, Daniel Sheldon, Yijin Wang, Nutcha Wattanachit, Lijing Wang, Jan Trnka, Guillaume Obozinski, Tao Sun, Dorina Thanou, Loic Pottier, Ekaterina Krymova, Jan H Meinke, Maria Vittoria Barbarossa, Neele Leithäuser, Jan Mohring, Johanna Schneider, Jaroslaw Włazło, Jan Fuhrmann, Berit Lange, Isti Rodiah, Prasith Baccam, Heidi Gurung, Steven Stage, Bradley Suchoski, Jozef Budzinski, Robert Walraven, Inmaculada Villanueva, Vit Tucek, Martin Smid, Milan Zajíček, Cesar Pérez Álvarez, Borja Reina, Nikos I Bosse, Sophie R Meakin, Lauren Castro, Geoffrey Fairchild, Isaac Michaud, Dave Osthus, Pierfrancesco Alaimo Di Loro, Antonello Maruotti, Veronika Eclerová, Andrea Kraus, David Kraus, Lenka Pribylova, Bertsimas Dimitris, Michael Lingzhi Li, Soni Saksham, Jonas Dehning, Sebastian Mohr, Viola Priesemann, Grzegorz Redlarski, Benjamin Bejar, Giovanni Ardenghi, Nicola Parolini, Giovanni Ziarelli, Wolfgang Bock, Stefan Heyder, Thomas Hotz, David E Singh, Miguel Guzman-Merino, Jose L Aznarte, David Moriña, Sergio Alonso, Enric Álvarez, Daniel López, Clara Prats, Jan Pablo Burgard, Arne Rodloff, Tom Zimmermann, Alexander Kuhlmann, Janez Zibert, Fulvia Pennoni, Fabio Divino, Marti Català, Gianfranco Lovison, Paolo Giudici, Barbara Tarantino, Francesco Bartolucci, Giovanna Jona Lasinio, Marco Mingione, Alessio Farcomeni, Ajitesh Srivastava, Pablo Montero-Manso, Aniruddha Adiga, Benjamin Hurt, Bryan Lewis, Madhav Marathe, Przemyslaw Porebski, Srinivasan Venkatramanan, Rafal P Bartczuk, Filip Dreger, Anna Gambin, Krzysztof Gogolewski, Magdalena Gruziel-Słomka, Bartosz Krupa, Antoni Moszyński, Karol Niedzielewski, Jedrzej Nowosielski, Maciej Radwan, Franciszek Rakowski, Marcin Semeniuk, Ewa Szczurek, Jakub Zieliński, Jan Kisielewski, Barbara Pabjan, Holger Kirsten, Yuri Kheifetz, Markus Scholz, Przemyslaw Biecek, Marcin Bodych, Maciej Filinski, Radoslaw Idzikowski, Tyll Krueger, Tomasz Ozanski, Johannes Bracher, and Sebastian Funk
- Abstract
Background: Short-term forecasts of infectious disease contribute to situational awareness and capacity planning. Based on best practice in other fields and recent insights in infectious disease epidemiology, one can maximise forecasts’ predictive performance by combining independent models into an ensemble. Here we report the performance of ensemble predictions of COVID-19 cases and deaths across Europe from March 2021 to March 2022. Methods: We created the European COVID-19 Forecast Hub, an online open-access platform where modellers upload weekly forecasts for 32 countries with results publicly visualised and evaluated. We created a weekly ensemble forecast from the equally-weighted average across individual models’ predictive quantiles. We measured forecast accuracy using a baseline and relative Weighted Interval Score (rWIS). We retrospectively explored ensemble methods, including weighting by past performance. Results: We collected weekly forecasts from 48 models, of which we evaluated 29 models alongside the ensemble model. The ensemble had a consistently strong performance across countries over time, performing better on rWIS than 91% of forecasts for deaths (N=763 predictions from 20 models), and 83% forecasts for cases (N=886 predictions from 23 models). Performance remained stable over a 4-week horizon for death forecasts but declined with longer horizons for cases. Among ensemble methods, the most influential choice came from using a median average instead of the mean, regardless of weighting component models. Conclusions: Our results support combining independent models into an ensemble forecast to improve epidemiological predictions, and suggest that median averages yield better performance than methods based on means. We highlight that forecast consumers should place more weight on incident death forecasts than case forecasts at horizons greater than two weeks. Funding: European Commission, Ministerio de Ciencia, Innovación y Universidades, FEDER; Ag
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- 2023
8. Predictive performance of multi-model ensemble forecasts of COVID-19 across European nations
- Author
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Sherratt, K., primary, Gruson, H., additional, Grah, R., additional, Johnson, H., additional, Niehus, R., additional, Prasse, B., additional, Sandman, F., additional, Deuschel, J., additional, Wolffram, D., additional, Abbott, S., additional, Ullrich, A., additional, Gibson, G., additional, Ray, EL., additional, Reich, NG., additional, Sheldon, D., additional, Wang, Y., additional, Wattanachit, N., additional, Wang, L., additional, Trnka, J., additional, Obozinski, G., additional, Sun, T., additional, Thanou, D., additional, Pottier, L., additional, Krymova, E., additional, Barbarossa, MV., additional, Leithäuser, N., additional, Mohring, J., additional, Schneider, J., additional, Wlazlo, J., additional, Fuhrmann, J., additional, Lange, B., additional, Rodiah, I., additional, Baccam, P., additional, Gurung, H., additional, Stage, S., additional, Suchoski, B., additional, Budzinski, J., additional, Walraven, R., additional, Villanueva, I., additional, Tucek, V., additional, Šmíd, M., additional, Zajícek, M., additional, Pérez Álvarez, C., additional, Reina, B., additional, Bosse, NI., additional, Meakin, S., additional, Di Loro, P. Alaimo, additional, Maruotti, A., additional, Eclerová, V., additional, Kraus, A., additional, Kraus, D., additional, Pribylova, L., additional, Dimitris, B., additional, Li, ML., additional, Saksham, S., additional, Dehning, J., additional, Mohr, S., additional, Priesemann, V., additional, Redlarski, G., additional, Bejar, B., additional, Ardenghi, G., additional, Parolini, N., additional, Ziarelli, G., additional, Bock, W., additional, Heyder, S., additional, Hotz, T., additional, E. Singh, D., additional, Guzman-Merino, M., additional, Aznarte, JL., additional, Moriña, D., additional, Alonso, S., additional, Álvarez, E., additional, López, D., additional, Prats, C., additional, Burgard, JP., additional, Rodloff, A., additional, Zimmermann, T., additional, Kuhlmann, A., additional, Zibert, J., additional, Pennoni, F., additional, Divino, F., additional, Català, M., additional, Lovison, G., additional, Giudici, P., additional, Tarantino, B., additional, Bartolucci, F., additional, Jona Lasinio, G., additional, Mingione, M., additional, Farcomeni, A., additional, Srivastava, A., additional, Montero-Manso, P., additional, Adiga, A., additional, Hurt, B., additional, Lewis, B., additional, Marathe, M., additional, Porebski, P., additional, Venkatramanan, S., additional, Bartczuk, R., additional, Dreger, F., additional, Gambin, A., additional, Gogolewski, K., additional, Gruziel-Slomka, M., additional, Krupa, B., additional, Moszynski, A., additional, Niedzielewski, K., additional, Nowosielski, J., additional, Radwan, M., additional, Rakowski, F., additional, Semeniuk, M., additional, Szczurek, E., additional, Zielinski, J., additional, Kisielewski, J., additional, Pabjan, B., additional, Holger, K., additional, Kheifetz, Y., additional, Scholz, M., additional, Bodych, M., additional, Filinski, M., additional, Idzikowski, R., additional, Krueger, T., additional, Ozanski, T., additional, Bracher, J., additional, and Funk, S., additional
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- 2022
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9. Semiautomatic assessment of immunofluorescence microscopy on blood smears in inherited platelet disorders using artificial intelligence: a proof of concept.
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Scholz, R., Sigel, C. E., Roggenbuck, J., Zaninetti, C., Wesche, J., Fuhrmann, J., Kaderali, L., Hiemann, R., Roggenbuck, D., and Greinacher, A.
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- 2024
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10. Platelet phenotyping by immunofluorescence microscopy on the blood smears in patients with myeloproliferative neoplasms.
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Zaninetti, C., Vater, L., Kaderali, L., Swensson, L., Fuhrmann, J., Wesche, J., Freyer, C., Heidel, F., and Greinacher, A.
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- 2024
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11. Prevalence of GPIIbIIIa-enriched membrane protrusions (Tether) in hospitalized patients.
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Wolff, M., Swensson, L., Wollermann, L., Fuhrmann, J., Klauke, J., and Greinacher, A.
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- 2024
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12. T-19-05: Developing an assay to distinguish between HIT and VITT antibodies.
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Schönborn, L., Wesche, J., Fuhrmann, J., Esteban, O., Dobosz, P., Broto, M., Serra, J., Llevadot, R., and Greinacher, A.
- Published
- 2023
- Full Text
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13. Predictive performance of multi-model ensemble forecasts of COVID-19 across European nations
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Katharine Sherratt, Hugo Gruson, Rok Grah, Helen Johnson, Rene Niehus, Bastian Prasse, Frank Sandmann, Jannik Deuschel, Daniel Wolffram, Sam Abbott, Alexander Ullrich, Graham Gibson, Evan L Ray, Nicholas G Reich, Daniel Sheldon, Yijin Wang, Nutcha Wattanachit, Lijing Wang, Jan Trnka, Guillaume Obozinski, Tao Sun, Dorina Thanou, Loic Pottier, Ekaterina Krymova, Jan H Meinke, Maria Vittoria Barbarossa, Neele Leithäuser, Jan Mohring, Johanna Schneider, Jaroslaw Włazło, Jan Fuhrmann, Berit Lange, Isti Rodiah, Prasith Baccam, Heidi Gurung, Steven Stage, Bradley Suchoski, Jozef Budzinski, Robert Walraven, Inmaculada Villanueva, Vit Tucek, Martin Smid, Milan Zajíček, Cesar Pérez Álvarez, Borja Reina, Nikos I Bosse, Sophie R Meakin, Lauren Castro, Geoffrey Fairchild, Isaac Michaud, Dave Osthus, Pierfrancesco Alaimo Di Loro, Antonello Maruotti, Veronika Eclerová, Andrea Kraus, David Kraus, Lenka Pribylova, Bertsimas Dimitris, Michael Lingzhi Li, Soni Saksham, Jonas Dehning, Sebastian Mohr, Viola Priesemann, Grzegorz Redlarski, Benjamin Bejar, Giovanni Ardenghi, Nicola Parolini, Giovanni Ziarelli, Wolfgang Bock, Stefan Heyder, Thomas Hotz, David E Singh, Miguel Guzman-Merino, Jose L Aznarte, David Moriña, Sergio Alonso, Enric Álvarez, Daniel López, Clara Prats, Jan Pablo Burgard, Arne Rodloff, Tom Zimmermann, Alexander Kuhlmann, Janez Zibert, Fulvia Pennoni, Fabio Divino, Marti Català, Gianfranco Lovison, Paolo Giudici, Barbara Tarantino, Francesco Bartolucci, Giovanna Jona Lasinio, Marco Mingione, Alessio Farcomeni, Ajitesh Srivastava, Pablo Montero-Manso, Aniruddha Adiga, Benjamin Hurt, Bryan Lewis, Madhav Marathe, Przemyslaw Porebski, Srinivasan Venkatramanan, Rafal P Bartczuk, Filip Dreger, Anna Gambin, Krzysztof Gogolewski, Magdalena Gruziel-Słomka, Bartosz Krupa, Antoni Moszyński, Karol Niedzielewski, Jedrzej Nowosielski, Maciej Radwan, Franciszek Rakowski, Marcin Semeniuk, Ewa Szczurek, Jakub Zieliński, Jan Kisielewski, Barbara Pabjan, Holger Kirsten, Yuri Kheifetz, Markus Scholz, Przemyslaw Biecek, Marcin Bodych, Maciej Filinski, Radoslaw Idzikowski, Tyll Krueger, Tomasz Ozanski, Johannes Bracher, Sebastian Funk, Sherratt, K, Gruson, H, Grah, R, Johnson, H, Niehus, R, Prasse, B, Sandmann, F, Deuschel, J, Wolffram, D, Abbott, S, Ullrich, A, Gibson, G, L Ray, E, G Reich, N, Sheldon, D, Wang, Y, Wattanachit, N, Wang, L, Trnka, J, Obozinski, G, Sun, T, Thanou, D, Pottier, L, Krymova, E, H Meinke, J, Vittoria Barbarossa, M, Leithäuser, N, Mohring, J, Schneider, J, Włazło, J, Fuhrmann, J, Lange, B, Rodiah, I, Baccam, P, Gurung, H, Stage, S, Suchoski, B, Budzinski, J, Walraven, R, Villanueva, I, Tucek, V, Smid, M, Zajíček, M, Pérez Álvarez, C, Reina, B, I Bosse, N, R Meakin, S, Castro, L, Fairchild, G, Michaud, I, Osthus, D, Alaimo Di Loro, P, Maruotti, A, Eclerová, V, Kraus, A, Kraus, D, Pribylova, L, Dimitris, B, Lingzhi Li, M, Saksham, S, Dehning, J, Mohr, S, Priesemann, V, Redlarski, G, Bejar, B, Ardenghi, G, Parolini, N, Ziarelli, G, Bock, W, Heyder, S, Hotz, T, E Singh, D, Guzman-Merino, M, L Aznarte, J, Moriña, D, Alonso, S, Álvarez, E, López, D, Prats, C, Pablo Burgard, J, Rodloff, A, Zimmermann, T, Kuhlmann, A, Zibert, J, Pennoni, F, Divino, F, Català, M, Lovison, G, Giudici, P, Tarantino, B, Bartolucci, F, Jona Lasinio, G, Mingione, M, Farcomeni, A, Srivastava, A, Montero-Manso, P, Adiga, A, Hurt, B, Lewis, B, Marathe, M, Porebski, P, Venkatramanan, S, P Bartczuk, R, Dreger, F, Gambin, A, Gogolewski, K, Gruziel-Słomka, M, Krupa, B, Moszyński, A, Niedzielewski, K, Nowosielski, J, Radwan, M, Rakowski, F, Semeniuk, M, Szczurek, E, Zieliński, J, Kisielewski, J, Pabjan, B, Kirsten, H, Kheifetz, Y, Scholz, M, Biecek, P, Bodych, M, Filinski, M, Idzikowski, R, Krueger, T, Ozanski, T, Bracher, J, and Funk, S
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epidemiology ,global health ,none ,General Immunology and Microbiology ,General Neuroscience ,mathematical modeling ,COVID-19 ,infectious diseases forecatsting ,General Medicine ,udc:616 ,General Biochemistry, Genetics and Molecular Biology ,COVID-19, Countries Predictions, Infectious disease, Multivariate Statistical Models, Short-term forecasts ,udc:616-036.22:519.876.5 ,SECS-S/01 - STATISTICA ,infectious diseases forecatsting, epidemiology, mathematical modeling, capacity planning, COVID-19, combining independent models, ensemble forecast ,ensemble forecast ,Settore SECS-S/01 ,napovedovanje nalezljivih bolezni, epidemiologija, matematično modeliranje, načrtovanje zmogljivosti, COVID-19, kombiniranje neodvisnih modelov, skupna napoved ,ddc:600 ,capacity planning ,combining independent models - Abstract
eLife 12, e81916 (2023). doi:10.7554/eLife.81916, Background:Short-term forecasts of infectious disease burden can contribute to situational awareness and aid capacity planning. Based on best practice in other fields and recent insights in infectious disease epidemiology, one can maximise the predictive performance of such forecasts if multiple models are combined into an ensemble. Here, we report on the performance of ensembles in predicting COVID-19 cases and deaths across Europe between 08 March 2021 and 07 March 2022.Methods:We used open-source tools to develop a public European COVID-19 Forecast Hub. We invited groups globally to contribute weekly forecasts for COVID-19 cases and deaths reported by a standardised source for 32 countries over the next 1–4 weeks. Teams submitted forecasts from March 2021 using standardised quantiles of the predictive distribution. Each week we created an ensemble forecast, where each predictive quantile was calculated as the equally-weighted average (initially the mean and then from 26th July the median) of all individual models’ predictive quantiles. We measured the performance of each model using the relative Weighted Interval Score (WIS), comparing models’ forecast accuracy relative to all other models. We retrospectively explored alternative methods for ensemble forecasts, including weighted averages based on models’ past predictive performance.Results:Over 52 weeks, we collected forecasts from 48 unique models. We evaluated 29 models’ forecast scores in comparison to the ensemble model. We found a weekly ensemble had a consistently strong performance across countries over time. Across all horizons and locations, the ensemble performed better on relative WIS than 83% of participating models’ forecasts of incident cases (with a total N=886 predictions from 23 unique models), and 91% of participating models’ forecasts of deaths (N=763 predictions from 20 models). Across a 1–4 week time horizon, ensemble performance declined with longer forecast periods when forecasting cases, but remained stable over 4 weeks for incident death forecasts. In every forecast across 32 countries, the ensemble outperformed most contributing models when forecasting either cases or deaths, frequently outperforming all of its individual component models. Among several choices of ensemble methods we found that the most influential and best choice was to use a median average of models instead of using the mean, regardless of methods of weighting component forecast models.Conclusions:Our results support the use of combining forecasts from individual models into an ensemble in order to improve predictive performance across epidemiological targets and populations during infectious disease epidemics. Our findings further suggest that median ensemble methods yield better predictive performance more than ones based on means. Our findings also highlight that forecast consumers should place more weight on incident death forecasts than incident case forecasts at forecast horizons greater than 2 weeks., Published by eLife Sciences Publications, Cambridge
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- 2023
14. Immunofluorescence microscopy on the blood smear identifies patients with myeloproliferative neoplasms.
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Zaninetti C, Vater L, Kaderali L, Crodel CC, Schnöder TM, Fuhrmann J, Swensson L, Wesche J, Freyer C, Greinacher A, and Heidel FH
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- Humans, Female, Male, Middle Aged, Aged, Adult, Aged, 80 and over, Myeloproliferative Disorders blood, Myeloproliferative Disorders pathology, Myeloproliferative Disorders diagnosis, Microscopy, Fluorescence methods
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- 2024
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15. Bioproduction Platform to Generate Functionalized Disulfide-Constrained Peptide Analogues.
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Hwang S, Balana AT, Martin B, Clarkson M, Di Lello P, Wu H, Li Y, Fuhrmann J, Dagdas Y, Holder P, Schroeder CI, Miller SE, and Gao X
- Abstract
Disulfide-constrained peptides (DCPs) have gained increased attention as a drug modality due to their exceptional stability and combined advantages of large biologics and small molecules. Chemical synthesis, although widely used to produce DCPs, is associated with high cost, both economically and environmentally. To reduce the dependence on solid phase peptide synthesis and the negative environmental footprint associated with it, we present a highly versatile, low-cost, and environmentally friendly bioproduction platform to generate DCPs and their conjugates as well as chemically modified or isotope-labeled DCPs. Using the DCP against the E3 ubiquitin ligase Zinc and Ring Finger 3, MK1-3.6.10, as a model peptide, we have demonstrated the use of bacterial expression, combined with Ser ligation or transglutaminase-mediated XTEN ligation, to produce multivalent MK1-3.6.10 and MK1-3.6.10 with N-terminal functional groups. We have also developed a bioproduction method for the site-specific incorporation of unnatural amino acids into recombinant DCPs by the amber codon suppression system. Lastly, we produced
15 N/13 C-labeled MK1-3.6.10 with high yield and assessed the performance of a semiautomated resonance assignment workflow that could be used to accelerate binding studies and structural characterization of DCPs. This study provides a proof of concept to generate functionalized DCPs using bioproduction, providing a potential solution to alleviate the reliance on hazardous chemicals, reduce the cost, and expedite the timeline for DCP discovery., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)- Published
- 2024
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16. Potency-Enhanced Peptidomimetic VHL Ligands with Improved Oral Bioavailability.
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Wu H, Murray J, Ishisoko N, Frommlet A, Deshmukh G, DiPasquale A, Mulvihill MM, Zhang D, Quinn JG, Blake RA, Fairbrother WJ, and Fuhrmann J
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- Humans, Ligands, Structure-Activity Relationship, Administration, Oral, Animals, Von Hippel-Lindau Tumor Suppressor Protein metabolism, Von Hippel-Lindau Tumor Suppressor Protein chemistry, Peptidomimetics chemistry, Peptidomimetics pharmacokinetics, Peptidomimetics pharmacology, Biological Availability
- Abstract
The von Hippel-Lindau (VHL) protein plays a pivotal role in regulating the hypoxic stress response and has been extensively studied and utilized in the targeted protein degradation field, particularly in the context of bivalent degraders. In this study, we present a comprehensive peptidomimetic structure-activity relationship (SAR) approach, combined with cellular NanoBRET target engagement assays to enhance the existing VHL ligands. Through systematic modifications of the molecule, we identified the 1,2,3-triazole group as an optimal substitute of the left-hand side amide bond that yields 10-fold higher binding activity. Moreover, incorporating conformationally constrained alterations on the methylthiazole benzylamine moiety led to the development of highly potent VHL ligands with picomolar binding affinity and significantly improved oral bioavailability. We anticipate that our optimized VHL ligand, GNE7599 , will serve as a valuable tool compound for investigating the VHL pathway and advancing the field of targeted protein degradation.
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- 2024
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17. Cystine-knot peptide inhibitors of HTRA1 bind to a cryptic pocket within the active site region.
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Li Y, Wei Y, Ultsch M, Li W, Tang W, Tombling B, Gao X, Dimitrova Y, Gampe C, Fuhrmann J, Zhang Y, Hannoush RN, and Kirchhofer D
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- Humans, Peptide Library, Crystallography, X-Ray, Protein Binding, Cystine chemistry, Cystine metabolism, Models, Molecular, High-Temperature Requirement A Serine Peptidase 1 metabolism, High-Temperature Requirement A Serine Peptidase 1 genetics, Catalytic Domain, Peptides chemistry, Peptides metabolism, Peptides pharmacology
- Abstract
Cystine-knot peptides (CKPs) are naturally occurring peptides that exhibit exceptional chemical and proteolytic stability. We leveraged the CKP carboxypeptidase A1 inhibitor as a scaffold to construct phage-displayed CKP libraries and subsequently screened these collections against HTRA1, a trimeric serine protease implicated in age-related macular degeneration and osteoarthritis. The initial hits were optimized by using affinity maturation strategies to yield highly selective and potent picomolar inhibitors of HTRA1. Crystal structures, coupled with biochemical studies, reveal that the CKPs do not interact in a substrate-like manner but bind to a cryptic pocket at the S1' site region of HTRA1 and abolish catalysis by stabilizing a non-competent active site conformation. The opening and closing of this cryptic pocket is controlled by the gatekeeper residue V221, and its movement is facilitated by the absence of a constraining disulfide bond that is typically present in trypsin fold serine proteases, thereby explaining the remarkable selectivity of the CKPs. Our findings reveal an intriguing mechanism for modulating the activity of HTRA1, and highlight the utility of CKP-based phage display platforms in uncovering potent and selective inhibitors against challenging therapeutic targets., (© 2024. The Author(s).)
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- 2024
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18. A mathematical model to assess the effectiveness of test-trace-isolate-and-quarantine under limited capacities.
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Heidecke J, Fuhrmann J, and Barbarossa MV
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- Humans, Quarantine, SARS-CoV-2, Pandemics prevention & control, Contact Tracing, Models, Theoretical, COVID-19, Communicable Diseases
- Abstract
Diagnostic testing followed by isolation of identified cases with subsequent tracing and quarantine of close contacts-often referred to as test-trace-isolate-and-quarantine (TTIQ) strategy-is one of the cornerstone measures of infectious disease control. The COVID-19 pandemic has highlighted that an appropriate response to outbreaks of infectious diseases requires a firm understanding of the effectiveness of such containment strategies. To this end, mathematical models provide a promising tool. In this work, we present a delay differential equation model of TTIQ interventions for infectious disease control. Our model incorporates the assumption of limited TTIQ capacities, providing insights into the reduced effectiveness of testing and tracing in high prevalence scenarios. In addition, we account for potential transmission during the early phase of an infection, including presymptomatic transmission, which may be particularly adverse to a TTIQ based control. Our numerical experiments inspired by the early spread of COVID-19 in Germany demonstrate the effectiveness of TTIQ in a scenario where immunity within the population is low and pharmaceutical interventions are absent, which is representative of a typical situation during the (re-)emergence of infectious diseases for which therapeutic drugs or vaccines are not yet available. Stability and sensitivity analyses reveal both disease-dependent and disease-independent factors that impede or enhance the success of TTIQ. Studying the diminishing impact of TTIQ along simulations of an epidemic wave, we highlight consequences for intervention strategies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Heidecke et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2024
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19. Anti-PF4 immunothrombosis without proximate heparin or adenovirus vector vaccine exposure.
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Schönborn L, Esteban O, Wesche J, Dobosz P, Broto M, Puig SR, Fuhrmann J, Torres R, Serra J, Llevadot R, Palicio M, Wang JJ, Gordon TP, Lindhoff-Last E, Hoffmann T, Alberio L, Langer F, Boehme C, Biguzzi E, Grosse L, Endres M, Liman T, Thiele T, Warkentin TE, and Greinacher A
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- Heparin, Vaccination, Humans, Platelet Factor 4 metabolism, Male, Female, Child, Preschool, Child, Adult, Thrombocytopenia diagnosis, Thrombocytopenia pathology, Antibodies analysis, Thrombosis diagnosis, Thrombosis pathology
- Abstract
Abstract: Platelet-activating anti-platelet factor 4 (PF4)/heparin antibodies and anti-PF4 antibodies cause heparin-induced thrombocytopenia (HIT) and vaccine-induced immune thrombocytopenia and thrombosis (VITT), respectively. Diagnostic and treatment considerations differ somewhat between HIT and VITT. We identified patients with thrombocytopenia and thrombosis without proximate heparin exposure or adenovirus-based vaccination who tested strongly positive by PF4/polyanion enzyme-immunoassays and negative/weakly positive by heparin-induced platelet activation (HIPA) test but strongly positive by PF4-induced platelet activation (PIPA) test (ie, VITT-like profile). We tested these patients by a standard chemiluminescence assay that detects anti-PF4/heparin antibodies found in HIT (HemosIL AcuStar HIT-IgG(PF4-H)) as well as a novel chemiluminescence assay for anti-PF4 antibodies found in VITT. Representative control sera included an exploratory anti-PF4 antibody-positive but HIPA-negative/weak cohort obtained before 2020 (n = 188). We identified 9 patients with a clinical-pathological profile of a VITT-like disorder in the absence of proximate heparin or vaccination, with a high frequency of stroke (arterial, n = 3; cerebral venous sinus thrombosis, n = 4), thrombocytopenia (median platelet count nadir, 49 × 109/L), and hypercoagulability (greatly elevated D-dimer levels). VITT-like serological features included strong reactivity by PIPA (aggregation <10 minutes in 9/9 sera) and positive testing in the novel anti-PF4 chemiluminescence assay (3/9 also tested positive in the anti-PF4/heparin chemiluminescence assay). Our exploratory cohort identified 13 additional patient sera obtained before 2020 with VITT-like anti-PF4 antibodies. Platelet-activating VITT-like anti-PF4 antibodies should be considered in patients with thrombocytopenia, thrombosis, and very high D-dimer levels, even without a proximate exposure to heparin or adenovirus vector vaccines., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
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- 2023
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20. The Novel Yersinia enterocolitica Telomere Phage vB_YenS_P840 Is Closely Related to PY54, but Reveals Some Striking Differences.
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Bräuer JA, Hammerl JA, El-Mustapha S, Fuhrmann J, Barac A, and Hertwig S
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- Prophages genetics, Lysogeny, Telomere, Bacteriophages genetics, Yersinia enterocolitica genetics
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Telomere phages are a small group of temperate phages, whose prophages replicate as a linear plasmid with covalently closed ends. They have been isolated from some Enterobacteriaceae and from bacterial species living in aquatic environments. Phage PY54 was the first Yersinia ( Y. ) enterocolitica telomere phage isolated from a nonpathogenic O:5 strain, but recently a second telomeric Yersinia phage (vB_YenS_P840) was isolated from a tonsil of a wild boar in Germany. Both PY54 and vB_YenS_P840 (P840) have a siphoviridal morphology and a similar genome organization including the primary immunity region immB and telomere resolution site telRL . However, whereas PY54 only possesses one prophage repressor for the lysogenic cycle, vB_YenS_P840 encodes two. The telRL region of this phage was shown to be processed by the PY54 protelomerase under in vivo conditions, but unlike with PY54, a flanking inverted repeat was not required for processing. A further substantial difference between the phages is their host specificity. While PY54 infects Y. enterocolitica strains belonging to the serotypes O:5 and O:5,27, vB_YenS_P840 exclusively lyses O:3 strains. As the tail fiber and tail fiber assembly proteins of the phages differ significantly, we introduced the corresponding genes of vB_YenS_P840 by transposon mutagenesis into the PY54 genome and isolated several mutants that were able to infect both serotypes, O:5,27 and O:3.
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- 2023
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21. Predictive performance of multi-model ensemble forecasts of COVID-19 across European nations.
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Sherratt K, Gruson H, Grah R, Johnson H, Niehus R, Prasse B, Sandmann F, Deuschel J, Wolffram D, Abbott S, Ullrich A, Gibson G, Ray EL, Reich NG, Sheldon D, Wang Y, Wattanachit N, Wang L, Trnka J, Obozinski G, Sun T, Thanou D, Pottier L, Krymova E, Meinke JH, Barbarossa MV, Leithauser N, Mohring J, Schneider J, Wlazlo J, Fuhrmann J, Lange B, Rodiah I, Baccam P, Gurung H, Stage S, Suchoski B, Budzinski J, Walraven R, Villanueva I, Tucek V, Smid M, Zajicek M, Perez Alvarez C, Reina B, Bosse NI, Meakin SR, Castro L, Fairchild G, Michaud I, Osthus D, Alaimo Di Loro P, Maruotti A, Eclerova V, Kraus A, Kraus D, Pribylova L, Dimitris B, Li ML, Saksham S, Dehning J, Mohr S, Priesemann V, Redlarski G, Bejar B, Ardenghi G, Parolini N, Ziarelli G, Bock W, Heyder S, Hotz T, Singh DE, Guzman-Merino M, Aznarte JL, Morina D, Alonso S, Alvarez E, Lopez D, Prats C, Burgard JP, Rodloff A, Zimmermann T, Kuhlmann A, Zibert J, Pennoni F, Divino F, Catala M, Lovison G, Giudici P, Tarantino B, Bartolucci F, Jona Lasinio G, Mingione M, Farcomeni A, Srivastava A, Montero-Manso P, Adiga A, Hurt B, Lewis B, Marathe M, Porebski P, Venkatramanan S, Bartczuk RP, Dreger F, Gambin A, Gogolewski K, Gruziel-Slomka M, Krupa B, Moszyński A, Niedzielewski K, Nowosielski J, Radwan M, Rakowski F, Semeniuk M, Szczurek E, Zielinski J, Kisielewski J, Pabjan B, Holger K, Kheifetz Y, Scholz M, Przemyslaw B, Bodych M, Filinski M, Idzikowski R, Krueger T, Ozanski T, Bracher J, and Funk S
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- Humans, Forecasting, Models, Statistical, Retrospective Studies, Communicable Diseases, COVID-19 diagnosis, COVID-19 epidemiology, Epidemics
- Abstract
Background: Short-term forecasts of infectious disease burden can contribute to situational awareness and aid capacity planning. Based on best practice in other fields and recent insights in infectious disease epidemiology, one can maximise the predictive performance of such forecasts if multiple models are combined into an ensemble. Here, we report on the performance of ensembles in predicting COVID-19 cases and deaths across Europe between 08 March 2021 and 07 March 2022., Methods: We used open-source tools to develop a public European COVID-19 Forecast Hub. We invited groups globally to contribute weekly forecasts for COVID-19 cases and deaths reported by a standardised source for 32 countries over the next 1-4 weeks. Teams submitted forecasts from March 2021 using standardised quantiles of the predictive distribution. Each week we created an ensemble forecast, where each predictive quantile was calculated as the equally-weighted average (initially the mean and then from 26th July the median) of all individual models' predictive quantiles. We measured the performance of each model using the relative Weighted Interval Score (WIS), comparing models' forecast accuracy relative to all other models. We retrospectively explored alternative methods for ensemble forecasts, including weighted averages based on models' past predictive performance., Results: Over 52 weeks, we collected forecasts from 48 unique models. We evaluated 29 models' forecast scores in comparison to the ensemble model. We found a weekly ensemble had a consistently strong performance across countries over time. Across all horizons and locations, the ensemble performed better on relative WIS than 83% of participating models' forecasts of incident cases (with a total N=886 predictions from 23 unique models), and 91% of participating models' forecasts of deaths (N=763 predictions from 20 models). Across a 1-4 week time horizon, ensemble performance declined with longer forecast periods when forecasting cases, but remained stable over 4 weeks for incident death forecasts. In every forecast across 32 countries, the ensemble outperformed most contributing models when forecasting either cases or deaths, frequently outperforming all of its individual component models. Among several choices of ensemble methods we found that the most influential and best choice was to use a median average of models instead of using the mean, regardless of methods of weighting component forecast models., Conclusions: Our results support the use of combining forecasts from individual models into an ensemble in order to improve predictive performance across epidemiological targets and populations during infectious disease epidemics. Our findings further suggest that median ensemble methods yield better predictive performance more than ones based on means. Our findings also highlight that forecast consumers should place more weight on incident death forecasts than incident case forecasts at forecast horizons greater than 2 weeks., Funding: AA, BH, BL, LWa, MMa, PP, SV funded by National Institutes of Health (NIH) Grant 1R01GM109718, NSF BIG DATA Grant IIS-1633028, NSF Grant No.: OAC-1916805, NSF Expeditions in Computing Grant CCF-1918656, CCF-1917819, NSF RAPID CNS-2028004, NSF RAPID OAC-2027541, US Centers for Disease Control and Prevention 75D30119C05935, a grant from Google, University of Virginia Strategic Investment Fund award number SIF160, Defense Threat Reduction Agency (DTRA) under Contract No. HDTRA1-19-D-0007, and respectively Virginia Dept of Health Grant VDH-21-501-0141, VDH-21-501-0143, VDH-21-501-0147, VDH-21-501-0145, VDH-21-501-0146, VDH-21-501-0142, VDH-21-501-0148. AF, AMa, GL funded by SMIGE - Modelli statistici inferenziali per governare l'epidemia, FISR 2020-Covid-19 I Fase, FISR2020IP-00156, Codice Progetto: PRJ-0695. AM, BK, FD, FR, JK, JN, JZ, KN, MG, MR, MS, RB funded by Ministry of Science and Higher Education of Poland with grant 28/WFSN/2021 to the University of Warsaw. BRe, CPe, JLAz funded by Ministerio de Sanidad/ISCIII. BT, PG funded by PERISCOPE European H2020 project, contract number 101016233. CP, DL, EA, MC, SA funded by European Commission - Directorate-General for Communications Networks, Content and Technology through the contract LC-01485746, and Ministerio de Ciencia, Innovacion y Universidades and FEDER, with the project PGC2018-095456-B-I00. DE., MGu funded by Spanish Ministry of Health / REACT-UE (FEDER). DO, GF, IMi, LC funded by Laboratory Directed Research and Development program of Los Alamos National Laboratory (LANL) under project number 20200700ER. DS, ELR, GG, NGR, NW, YW funded by National Institutes of General Medical Sciences (R35GM119582; the content is solely the responsibility of the authors and does not necessarily represent the official views of NIGMS or the National Institutes of Health). FB, FP funded by InPresa, Lombardy Region, Italy. HG, KS funded by European Centre for Disease Prevention and Control. IV funded by Agencia de Qualitat i Avaluacio Sanitaries de Catalunya (AQuAS) through contract 2021-021OE. JDe, SMo, VP funded by Netzwerk Universitatsmedizin (NUM) project egePan (01KX2021). JPB, SH, TH funded by Federal Ministry of Education and Research (BMBF; grant 05M18SIA). KH, MSc, YKh funded by Project SaxoCOV, funded by the German Free State of Saxony. Presentation of data, model results and simulations also funded by the NFDI4Health Task Force COVID-19 (https://www.nfdi4health.de/task-force-covid-19-2) within the framework of a DFG-project (LO-342/17-1). LP, VE funded by Mathematical and Statistical modelling project (MUNI/A/1615/2020), Online platform for real-time monitoring, analysis and management of epidemic situations (MUNI/11/02202001/2020); VE also supported by RECETOX research infrastructure (Ministry of Education, Youth and Sports of the Czech Republic: LM2018121), the CETOCOEN EXCELLENCE (CZ.02.1.01/0.0/0.0/17-043/0009632), RECETOX RI project (CZ.02.1.01/0.0/0.0/16-013/0001761). NIB funded by Health Protection Research Unit (grant code NIHR200908). SAb, SF funded by Wellcome Trust (210758/Z/18/Z)., Competing Interests: KS, HG, RG, HJ, RN, BP, FS, JD, DW, SA, AU, GG, ER, NR, DS, YW, NW, LW, JT, GO, TS, DT, LP, EK, JM, MB, NL, JM, JS, JW, JF, BL, IR, JB, RW, IV, VT, MS, MZ, CP, BR, NB, SM, LC, GF, IM, DO, PA, AM, VE, AK, DK, LP, BD, ML, SS, JD, SM, VP, GR, BB, GA, NP, GZ, WB, SH, TH, DS, MG, JA, DM, SA, EA, DL, CP, JB, AR, TZ, AK, JZ, FP, FD, MC, GL, PG, BT, FB, GJ, MM, AF, AS, PM, AA, BH, BL, MM, PP, SV, RB, FD, AG, KG, MG, BK, AM, KN, JN, MR, FR, MS, ES, JZ, JK, BP, KH, YK, MS, BP, MB, MF, RI, TK, TO, JB, SF No competing interests declared, PB, HG, SS, BS Affiliated with IEM, Inc. The author has no financial interests to declare
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- 2023
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22. Directed evolution identifies high-affinity cystine-knot peptide agonists and antagonists of Wnt/β-catenin signaling.
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Hansen S, Zhang Y, Hwang S, Nabhan A, Li W, Fuhrmann J, Kschonsak Y, Zhou L, Nile AH, Gao X, Piskol R, de Sousa E Melo F, de Sauvage FJ, and Hannoush RN
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- Humans, Low Density Lipoprotein Receptor-Related Protein-6 genetics, Low Density Lipoprotein Receptor-Related Protein-6 metabolism, Wnt Proteins metabolism, Cystine, Ligands, Peptides, Wnt Signaling Pathway, beta Catenin metabolism
- Abstract
Developing peptide-based tools to fine-tune growth signaling pathways, in particular molecules with exquisite selectivity and high affinities, opens up opportunities for cellular reprogramming in tissue regeneration. Here, we present a library based on cystine-knot peptides (CKPs) that incorporate multiple loops for randomization and selection via directed evolution. Resulting binders could be assembled into multimeric structures to fine-tune cellular signaling. An example is presented for the Wnt pathway, which plays a key role in the homeostasis and regeneration of tissues such as lung, skin, and intestine. We discovered picomolar affinity CKP agonists of the human LPR6 receptor by exploring the limits of the topological manipulation of LRP6 dimerization. Structural analyses revealed that the agonists bind at the first β-propeller domain of LRP6, mimicking the natural Wnt inhibitors DKK1 and SOST. However, the CKP agonists exhibit a different mode of action as they amplify the signaling of natural Wnt ligands but do not activate the pathway by themselves. In an alveolosphere organoid model, the CKP agonists induced alveolar stem cell activity. They also stimulated growth in primary human intestinal organoids. The approach described here advances the important frontier of next-generation agonist design and could be applied to other signaling pathways to discover tunable agonist ligands.
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- 2022
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23. National and subnational short-term forecasting of COVID-19 in Germany and Poland during early 2021.
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Bracher J, Wolffram D, Deuschel J, Görgen K, Ketterer JL, Ullrich A, Abbott S, Barbarossa MV, Bertsimas D, Bhatia S, Bodych M, Bosse NI, Burgard JP, Castro L, Fairchild G, Fiedler J, Fuhrmann J, Funk S, Gambin A, Gogolewski K, Heyder S, Hotz T, Kheifetz Y, Kirsten H, Krueger T, Krymova E, Leithäuser N, Li ML, Meinke JH, Miasojedow B, Michaud IJ, Mohring J, Nouvellet P, Nowosielski JM, Ozanski T, Radwan M, Rakowski F, Scholz M, Soni S, Srivastava A, Gneiting T, and Schienle M
- Abstract
Background: During the COVID-19 pandemic there has been a strong interest in forecasts of the short-term development of epidemiological indicators to inform decision makers. In this study we evaluate probabilistic real-time predictions of confirmed cases and deaths from COVID-19 in Germany and Poland for the period from January through April 2021., Methods: We evaluate probabilistic real-time predictions of confirmed cases and deaths from COVID-19 in Germany and Poland. These were issued by 15 different forecasting models, run by independent research teams. Moreover, we study the performance of combined ensemble forecasts. Evaluation of probabilistic forecasts is based on proper scoring rules, along with interval coverage proportions to assess calibration. The presented work is part of a pre-registered evaluation study., Results: We find that many, though not all, models outperform a simple baseline model up to four weeks ahead for the considered targets. Ensemble methods show very good relative performance. The addressed time period is characterized by rather stable non-pharmaceutical interventions in both countries, making short-term predictions more straightforward than in previous periods. However, major trend changes in reported cases, like the rebound in cases due to the rise of the B.1.1.7 (Alpha) variant in March 2021, prove challenging to predict., Conclusions: Multi-model approaches can help to improve the performance of epidemiological forecasts. However, while death numbers can be predicted with some success based on current case and hospitalization data, predictability of case numbers remains low beyond quite short time horizons. Additional data sources including sequencing and mobility data, which were not extensively used in the present study, may help to improve performance., (© 2022. The Author(s).)
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- 2022
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24. Phage vB_YenS_P400, a Novel Virulent Siphovirus of Yersinia enterocolitica Isolated from Deer.
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Hammerl JA, Barac A, Jäckel C, Fuhrmann J, Gadicherla A, and Hertwig S
- Abstract
Phage vB_YenS_P400 isolated from deer, is a virulent siphovirus of Y. enterocolitica , whose circularly permutated genome (46,585 bp) is not substantially related to any other phage deposited in public nucleotide databases. vB_YenS_P400 showed a very narrow host range and exclusively lysed two Y. enterocolitica B4/O:3 strains. Moreover, lytic activity by this phage was only discernible at room temperature. Together with the finding that vB_YenS_P400 revealed a long latent period (90 to 100 min) and low burst size (five to ten), it is not suitable for applications but provides insight into the diversity of Yersinia phages.
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- 2022
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25. Pain, Analgesic Use, and Patient Satisfaction With Spinal Versus General Anesthesia for Hip Fracture Surgery : A Randomized Clinical Trial.
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Neuman MD, Feng R, Ellenberg SS, Sieber F, Sessler DI, Magaziner J, Elkassabany N, Schwenk ES, Dillane D, Marcantonio ER, Menio D, Ayad S, Hassan M, Stone T, Papp S, Donegan D, Marshall M, Jaffe JD, Luke C, Sharma B, Azim S, Hymes R, Chin KJ, Sheppard R, Perlman B, Sappenfield J, Hauck E, Hoeft MA, Tierney A, Gaskins LJ, Horan AD, Brown T, Dattilo J, Carson JL, Looke T, Bent S, Franco-Mora A, Hedrick P, Newbern M, Tadros R, Pealer K, Vlassakov K, Buckley C, Gavin L, Gorbatov S, Gosnell J, Steen T, Vafai A, Zeballos J, Hruslinski J, Cardenas L, Berry A, Getchell J, Quercetti N, Bajracharya G, Billow D, Bloomfield M, Cuko E, Elyaderani MK, Hampton R, Honar H, Khoshknabi D, Kim D, Krahe D, Lew MM, Maheshwer CB, Niazi A, Saha P, Salih A, de Swart RJ, Volio A, Bolkus K, DeAngelis M, Dodson G, Gerritsen J, McEniry B, Mitrev L, Kwofie MK, Belliveau A, Bonazza F, Lloyd V, Panek I, Dabiri J, Chavez C, Craig J, Davidson T, Dietrichs C, Fleetwood C, Foley M, Getto C, Hailes S, Hermes S, Hooper A, Koener G, Kohls K, Law L, Lipp A, Losey A, Nelson W, Nieto M, Rogers P, Rutman S, Scales G, Sebastian B, Stanciu T, Lobel G, Giampiccolo M, Herman D, Kaufman M, Murphy B, Pau C, Puzio T, Veselsky M, Apostle K, Boyer D, Fan BC, Lee S, Lemke M, Merchant R, Moola F, Payne K, Perey B, Viskontas D, Poler M, D'Antonio P, O'Neill G, Abdullah A, Fish-Fuhrmann J, Giska M, Fidkowski C, Guthrie ST, Hakeos W, Hayes L, Hoegler J, Nowak K, Beck J, Cuff J, Gaski G, Haaser S, Holzman M, Malekzadeh AS, Ramsey L, Schulman J, Schwartzbach C, Azefor T, Davani A, Jaberi M, Masear C, Haider SB, Chungu C, Ebrahimi A, Fikry K, Marcantonio A, Shelvan A, Sanders D, Clarke C, Lawendy A, Schwartz G, Garg M, Kim J, Caruci J, Commeh E, Cuevas R, Cuff G, Franco L, Furgiuele D, Giuca M, Allman M, Barzideh O, Cossaro J, D'Arduini A, Farhi A, Gould J, Kafel J, Patel A, Peller A, Reshef H, Safur M, Toscano F, Tedore T, Akerman M, Brumberger E, Clark S, Friedlander R, Jegarl A, Lane J, Lyden JP, Mehta N, Murrell MT, Painter N, Ricci W, Sbrollini K, Sharma R, Steel PAD, Steinkamp M, Weinberg R, Wellman DS, Nader A, Fitzgerald P, Ritz M, Bryson G, Craig A, Farhat C, Gammon B, Gofton W, Harris N, Lalonde K, Liew A, Meulenkamp B, Sonnenburg K, Wai E, Wilkin G, Troxell K, Alderfer ME, Brannen J, Cupitt C, Gerhart S, McLin R, Sheidy J, Yurick K, Chen F, Dragert K, Kiss G, Malveaux H, McCloskey D, Mellender S, Mungekar SS, Noveck H, Sagebien C, Biby L, McKelvy G, Richards A, Abola R, Ayala B, Halper D, Mavarez A, Rizwan S, Choi S, Awad I, Flynn B, Henry P, Jenkinson R, Kaustov L, Lappin E, McHardy P, Singh A, Donnelly J, Gonzalez M, Haydel C, Livelsberger J, Pazionis T, Slattery B, Vazquez-Trejo M, Baratta J, Cirullo M, Deiling B, Deschamps L, Glick M, Katz D, Krieg J, Lessin J, Mojica J, Torjman M, Jin R, Salpeter MJ, Powell M, Simmons J, Lawson P, Kukreja P, Graves S, Sturdivant A, Bryant A, Crump SJ, Verrier M, Green J, Menon M, Applegate R, Arias A, Pineiro N, Uppington J, Wolinsky P, Gunnett A, Hagen J, Harris S, Hollen K, Holloway B, Horodyski MB, Pogue T, Ramani R, Smith C, Woods A, Warrick M, Flynn K, Mongan P, Ranganath Y, Fernholz S, Ingersoll-Weng E, Marian A, Seering M, Sibenaller Z, Stout L, Wagner A, Walter A, Wong C, Orwig D, Goud M, Helker C, Mezenghie L, Montgomery B, Preston P, Schwartz JS, Weber R, Fleisher LA, Mehta S, Stephens-Shields AJ, Dinh C, Chelly JE, Goel S, Goncz W, Kawabe T, Khetarpal S, Monroe A, Shick V, Breidenstein M, Dominick T, Friend A, Mathews D, Lennertz R, Sanders R, Akere H, Balweg T, Bo A, Doro C, Goodspeed D, Lang G, Parker M, Rettammel A, Roth M, White M, Whiting P, Allen BFS, Baker T, Craven D, McEvoy M, Turnbo T, Kates S, Morgan M, Willoughby T, Weigel W, Auyong D, Fox E, Welsh T, Cusson B, Dobson S, Edwards C, Harris L, Henshaw D, Johnson K, McKinney G, Miller S, Reynolds J, Segal BS, Turner J, VanEenenaam D, Weller R, Lei J, Treggiari M, Akhtar S, Blessing M, Johnson C, Kampp M, Kunze K, O'Connor M, Looke T, Tadros R, Vlassakov K, Cardenas L, Bolkus K, Mitrev L, Kwofie MK, Dabiri J, Lobel G, Poler M, Giska M, Sanders D, Schwartz G, Giuca M, Tedore T, Nader A, Bryson G, Troxell K, Kiss G, Choi S, Powell M, Applegate R, Warrick M, Ranganath Y, Chelly JE, Lennertz R, Sanders R, Allen BFS, Kates S, Weigel W, Li J, Wijeysundera DN, Kheterpal S, Moore RH, Smith AK, Tosi LL, Looke T, Mehta S, Fleisher L, Hruslinski J, Ramsey L, Langlois C, Mezenghie L, Montgomery B, Oduwole S, and Rose T
- Subjects
- Aged, Analgesics therapeutic use, Anesthesia, General adverse effects, Canada, Female, Humans, Male, Pain, Pain, Postoperative drug therapy, Patient Satisfaction, Anesthesia, Spinal adverse effects, Hip Fractures surgery
- Abstract
Background: The REGAIN (Regional versus General Anesthesia for Promoting Independence after Hip Fracture) trial found similar ambulation and survival at 60 days with spinal versus general anesthesia for hip fracture surgery. Trial outcomes evaluating pain, prescription analgesic use, and patient satisfaction have not yet been reported., Objective: To compare pain, analgesic use, and satisfaction after hip fracture surgery with spinal versus general anesthesia., Design: Preplanned secondary analysis of a pragmatic randomized trial. (ClinicalTrials.gov: NCT02507505)., Setting: 46 U.S. and Canadian hospitals., Participants: Patients aged 50 years or older undergoing hip fracture surgery., Intervention: Spinal or general anesthesia., Measurements: Pain on postoperative days 1 through 3; 60-, 180-, and 365-day pain and prescription analgesic use; and satisfaction with care., Results: A total of 1600 patients were enrolled. The average age was 78 years, and 77% were women. A total of 73.5% (1050 of 1428) of patients reported severe pain during the first 24 hours after surgery. Worst pain over the first 24 hours after surgery was greater with spinal anesthesia (rated from 0 [no pain] to 10 [worst pain imaginable]; mean difference, 0.40 [95% CI, 0.12 to 0.68]). Pain did not differ across groups at other time points. Prescription analgesic use at 60 days occurred in 25% (141 of 563) and 18.8% (108 of 574) of patients assigned to spinal and general anesthesia, respectively (relative risk, 1.33 [CI, 1.06 to 1.65]). Satisfaction was similar across groups., Limitation: Missing outcome data and multiple outcomes assessed., Conclusion: Severe pain is common after hip fracture. Spinal anesthesia was associated with more pain in the first 24 hours after surgery and more prescription analgesic use at 60 days compared with general anesthesia., Primary Funding Source: Patient-Centered Outcomes Research Institute .
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- 2022
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26. Properties of Two Broad Host Range Phages of Yersinia enterocolitica Isolated from Wild Animals.
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Hammerl JA, Barac A, Erben P, Fuhrmann J, Gadicherla A, Kumsteller F, Lauckner A, Müller F, and Hertwig S
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- Animals, Animals, Wild microbiology, Bacteriophages genetics, Bacteriophages ultrastructure, Host Specificity, Sequence Analysis, DNA, Bacteriophages isolation & purification, Genome, Viral, Yersinia enterocolitica virology
- Abstract
Yersinia ( Y .) enterocolitica and Y. pseudotuberculosis are important zoonotic agents which can infect both humans and animals. To combat these pathogens, the application of strictly lytic phages may be a promising tool. Since only few Yersinia phages have been described yet, some of which demonstrated a high specificity for certain serotypes, we isolated two phages from game animals and characterized them in terms of their morphology, host specificity, lytic activity on two bio-/serotypes and genome composition. The T7-related podovirus vB_YenP_Rambo and the myovirus vB_YenM_P281, which is very similar to a previously described phage PY100, showed a broad host range. Together, they lysed all the 62 tested pathogenic Y. enterocolitica strains belonging to the most important bio-/serotypes in Europe. A cocktail containing these two phages strongly reduced cultures of a bio-/serotype B4/O:3 and a B2/O:9 strain, even at very low MOIs (multiplicity of infection) and different temperatures, though, lysis of bio-/serotype B2/O:9 by vB_YenM_P281 and also by the related phage PY100 only occurred at 37 °C. Both phages were additionally able to lyse various Y. pseudotuberculosis strains at 28 °C and 37 °C, but only when the growth medium was supplemented with calcium and magnesium cations.
- Published
- 2021
- Full Text
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