TY  - JOUR
A1  - Bousquet, Jean
A1  - Anto, Josep M.
A1  - Bachert, Claus
A1  - Haahtela, Tari
A1  - Zuberbier, Torsten
A1  - Czarlewski, Wienczyslawa
A1  - Bedbrook, Anna
A1  - Bosnic‐Anticevich, Sinthia
A1  - Walter Canonica, G.
A1  - Cardona, Victoria
A1  - Costa, Elisio
A1  - Cruz, Alvaro A.
A1  - Erhola, Marina
A1  - Fokkens, Wytske J.
A1  - Fonseca, Joao A.
A1  - Illario, Maddalena
A1  - Ivancevich, Juan‐Carlos
A1  - Jutel, Marek
A1  - Klimek, Ludger
A1  - Kuna, Piotr
A1  - Kvedariene, Violeta
A1  - Le, LTT
A1  - Larenas‐Linnemann, Désirée E.
A1  - Laune, Daniel
A1  - Lourenço, Olga M.
A1  - Melén, Erik
A1  - Mullol, Joaquim
A1  - Niedoszytko, Marek
A1  - Odemyr, Mikaëla
A1  - Okamoto, Yoshitaka
A1  - Papadopoulos, Nikos G.
A1  - Patella, Vincenzo
A1  - Pfaar, Oliver
A1  - Pham‐Thi, Nhân
A1  - Rolland, Christine
A1  - Samolinski, Boleslaw
A1  - Sheikh, Aziz
A1  - Sofiev, Mikhail
A1  - Suppli Ulrik, Charlotte
A1  - Todo‐Bom, Ana
A1  - Tomazic, Peter‐Valentin
A1  - Toppila‐Salmi, Sanna
A1  - Tsiligianni, Ioanna
A1  - Valiulis, Arunas
A1  - Valovirta, Erkka
A1  - Ventura, Maria‐Teresa
A1  - Walker, Samantha
A1  - Williams, Sian
A1  - Yorgancioglu, Arzu
A1  - Agache, Ioana
A1  - Akdis, Cezmi A.
A1  - Almeida, Rute
A1  - Ansotegui, Ignacio J.
A1  - Annesi‐Maesano, Isabella
A1  - Arnavielhe, Sylvie
A1  - Basagaña, Xavier
A1  - D. Bateman, Eric
A1  - Bédard, Annabelle
A1  - Bedolla‐Barajas, Martin
A1  - Becker, Sven
A1  - Bennoor, Kazi S.
A1  - Benveniste, Samuel
A1  - Bergmann, Karl C.
A1  - Bewick, Michael
A1  - Bialek, Slawomir
A1  - E. Billo, Nils
A1  - Bindslev‐Jensen, Carsten
A1  - Bjermer, Leif
A1  - Blain, Hubert
A1  - Bonini, Matteo
A1  - Bonniaud, Philippe
A1  - Bosse, Isabelle
A1  - Bouchard, Jacques
A1  - Boulet, Louis‐Philippe
A1  - Bourret, Rodolphe
A1  - Boussery, Koen
A1  - Braido, Fluvio
A1  - Briedis, Vitalis
A1  - Briggs, Andrew
A1  - Brightling, Christopher E.
A1  - Brozek, Jan
A1  - Brusselle, Guy
A1  - Brussino, Luisa
A1  - Buhl, Roland
A1  - Buonaiuto, Roland
A1  - Calderon, Moises A.
A1  - Camargos, Paulo
A1  - Camuzat, Thierry
A1  - Caraballo, Luis
A1  - Carriazo, Ana‐Maria
A1  - Carr, Warner
A1  - Cartier, Christine
A1  - Casale, Thomas
A1  - Cecchi, Lorenzo
A1  - Cepeda Sarabia, Alfonso M.
A1  - H. Chavannes, Niels
A1  - Chkhartishvili, Ekaterine
A1  - Chu, Derek K.
A1  - Cingi, Cemal
A1  - Correia de Sousa, Jaime
A1  - Costa, David J.
A1  - Courbis, Anne‐Lise
A1  - Custovic, Adnan
A1  - Cvetkosvki, Biljana
A1  - D'Amato, Gennaro
A1  - da Silva, Jane
A1  - Dantas, Carina
A1  - Dokic, Dejan
A1  - Dauvilliers, Yves
A1  - De Feo, Giulia
A1  - De Vries, Govert
A1  - Devillier, Philippe
A1  - Di Capua, Stefania
A1  - Dray, Gerard
A1  - Dubakiene, Ruta
A1  - Durham, Stephen R.
A1  - Dykewicz, Mark
A1  - Ebisawa, Motohiro
A1  - Gaga, Mina
A1  - El‐Gamal, Yehia
A1  - Heffler, Enrico
A1  - Emuzyte, Regina
A1  - Farrell, John
A1  - Fauquert, Jean‐Luc
A1  - Fiocchi, Alessandro
A1  - Fink‐Wagner, Antje
A1  - Fontaine, Jean‐François
A1  - Fuentes Perez, José M.
A1  - Gemicioğlu, Bilun
A1  - Gamkrelidze, Amiran
A1  - Garcia‐Aymerich, Judith
A1  - Gevaert, Philippe
A1  - Gomez, René Maximiliano
A1  - González Diaz, Sandra
A1  - Gotua, Maia
A1  - Guldemond, Nick A.
A1  - Guzmán, Maria‐Antonieta
A1  - Hajjam, Jawad
A1  - Huerta Villalobos, Yunuen R.
A1  - Humbert, Marc
A1  - Iaccarino, Guido
A1  - Ierodiakonou, Despo
A1  - Iinuma, Tomohisa
A1  - Jassem, Ewa
A1  - Joos, Guy
A1  - Jung, Ki‐Suck
A1  - Kaidashev, Igor
A1  - Kalayci, Omer
A1  - Kardas, Przemyslaw
A1  - Keil, Thomas
A1  - Khaitov, Musa
A1  - Khaltaev, Nikolai
A1  - Kleine‐Tebbe, Jorg
A1  - Kouznetsov, Rostislav
A1  - Kowalski, Marek L.
A1  - Kritikos, Vicky
A1  - Kull, Inger
A1  - La Grutta, Stefania
A1  - Leonardini, Lisa
A1  - Ljungberg, Henrik
A1  - Lieberman, Philip
A1  - Lipworth, Brian
A1  - Lodrup Carlsen, Karin C.
A1  - Lopes‐Pereira, Catarina
A1  - Loureiro, Claudia C.
A1  - Louis, Renaud
A1  - Mair, Alpana
A1  - Mahboub, Bassam
A1  - Makris, Michaël
A1  - Malva, Joao
A1  - Manning, Patrick
A1  - Marshall, Gailen D.
A1  - Masjedi, Mohamed R.
A1  - Maspero, Jorge F.
A1  - Carreiro‐Martins, Pedro
A1  - Makela, Mika
A1  - Mathieu‐Dupas, Eve
A1  - Maurer, Marcus
A1  - De Manuel Keenoy, Esteban
A1  - Melo‐Gomes, Elisabete
A1  - Meltzer, Eli O.
A1  - Menditto, Enrica
A1  - Mercier, Jacques
A1  - Micheli, Yann
A1  - Miculinic, Neven
A1  - Mihaltan, Florin
A1  - Milenkovic, Branislava
A1  - Mitsias, Dimitirios I.
A1  - Moda, Giuliana
A1  - Mogica‐Martinez, Maria‐Dolores
A1  - Mohammad, Yousser
A1  - Montefort, Steve
A1  - Monti, Ricardo
A1  - Morais‐Almeida, Mario
A1  - Mösges, Ralph
A1  - Münter, Lars
A1  - Muraro, Antonella
A1  - Murray, Ruth
A1  - Naclerio, Robert
A1  - Napoli, Luigi
A1  - Namazova‐Baranova, Leyla
A1  - Neffen, Hugo
A1  - Nekam, Kristoff
A1  - Neou, Angelo
A1  - Nordlund, Björn
A1  - Novellino, Ettore
A1  - Nyembue, Dieudonné
A1  - O'Hehir, Robyn
A1  - Ohta, Ken
A1  - Okubo, Kimi
A1  - Onorato, Gabrielle L.
A1  - Orlando, Valentina
A1  - Ouedraogo, Solange
A1  - Palamarchuk, Julia
A1  - Pali‐Schöll, Isabella
A1  - Panzner, Peter
A1  - Park, Hae‐Sim
A1  - Passalacqua, Gianni
A1  - Pépin, Jean‐Louis
A1  - Paulino, Ema
A1  - Pawankar, Ruby
A1  - Phillips, Jim
A1  - Picard, Robert
A1  - Pinnock, Hilary
A1  - Plavec, Davor
A1  - Popov, Todor A.
A1  - Portejoie, Fabienne
A1  - Price, David
A1  - Prokopakis, Emmanuel P.
A1  - Psarros, Fotis
A1  - Pugin, Benoit
A1  - Puggioni, Francesca
A1  - Quinones‐Delgado, Pablo
A1  - Raciborski, Filip
A1  - Rajabian‐Söderlund, Rojin
A1  - Regateiro, Frederico S.
A1  - Reitsma, Sietze
A1  - Rivero‐Yeverino, Daniela
A1  - Roberts, Graham
A1  - Roche, Nicolas
A1  - Rodriguez‐Zagal, Erendira
A1  - Rolland, Christine
A1  - Roller‐Wirnsberger, Regina E.
A1  - Rosario, Nelson
A1  - Romano, Antonino
A1  - Rottem, Menachem
A1  - Ryan, Dermot
A1  - Salimäki, Johanna
A1  - Sanchez‐Borges, Mario M.
A1  - Sastre, Joaquin
A1  - Scadding, Glenis K.
A1  - Scheire, Sophie
A1  - Schmid‐Grendelmeier, Peter
A1  - Schünemann, Holger J.
A1  - Sarquis Serpa, Faradiba
A1  - Shamji, Mohamed
A1  - Sisul, Juan‐Carlos
A1  - Sofiev, Mikhail
A1  - Solé, Dirceu
A1  - Somekh, David
A1  - Sooronbaev, Talant
A1  - Sova, Milan
A1  - Spertini, François
A1  - Spranger, Otto
A1  - Stellato, Cristiana
A1  - Stelmach, Rafael
A1  - Thibaudon, Michel
A1  - To, Teresa
A1  - Toumi, Mondher
A1  - Usmani, Omar
A1  - Valero, Antonio A.
A1  - Valenta, Rudolph
A1  - Valentin‐Rostan, Marylin
A1  - Pereira, Marilyn Urrutia
A1  - van der Kleij, Rianne
A1  - Van Eerd, Michiel
A1  - Vandenplas, Olivier
A1  - Vasankari, Tuula
A1  - Vaz Carneiro, Antonio
A1  - Vezzani, Giorgio
A1  - Viart, Frédéric
A1  - Viegi, Giovanni
A1  - Wallace, Dana
A1  - Wagenmann, Martin
A1  - Wang, De Yun
A1  - Waserman, Susan
A1  - Wickman, Magnus
A1  - Williams, Dennis M.
A1  - Wong, Gary
A1  - Wroczynski, Piotr
A1  - Yiallouros, Panayiotis K.
A1  - Yusuf, Osman M.
A1  - Zar, Heather J.
A1  - Zeng, Stéphane
A1  - Zernotti, Mario E.
A1  - Zhang, Luo
A1  - Shan Zhong, Nan
A1  - Zidarn, Mihaela
T1  - ARIA digital anamorphosis: Digital transformation of health and care in airway diseases from research to practice
JF  - Allergy
N2  - Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
KW  - ARIA
KW  - asthma
KW  - CARAT
KW  - digital transformation of health and care
KW  - MASK
KW  - rhinitis
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228339
VL  - 76
IS  - 1
SP  - 168
EP  - 190
ER  - 
TY  - JOUR
A1  - Wangorsch, Gaby
A1  - Butt, Elke
A1  - Mark, Regina
A1  - Hubertus, Katharina
A1  - Geiger, Jörg
A1  - Dandekar, Thomas
A1  - Dittrich, Marcus
T1  - Time-resolved in silico modeling of fine-tuned cAMP signaling in platelets: feedback loops, titrated phosphorylations and pharmacological modulation
N2  - Background: Hemostasis is a critical and active function of the blood mediated by platelets. Therefore, the prevention of pathological platelet aggregation is of great importance as well as of pharmaceutical and medical interest. Endogenous platelet inhibition is predominantly based on cyclic nucleotides (cAMP, cGMP) elevation and subsequent cyclic nucleotide-dependent protein kinase (PKA, PKG) activation. In turn, platelet phosphodiesterases (PDEs) and protein phosphatases counterbalance their activity. This main inhibitory pathway in human platelets is crucial for countervailing unwanted platelet activation. Consequently, the regulators of cyclic nucleotide signaling are of particular interest to pharmacology and therapeutics of atherothrombosis. Modeling of pharmacodynamics allows understanding this intricate signaling and supports the precise description of these pivotal targets for pharmacological modulation. Results: We modeled dynamically concentration-dependent responses of pathway effectors (inhibitors, activators, drug combinations) to cyclic nucleotide signaling as well as to downstream signaling events and verified resulting model predictions by experimental data. Experiments with various cAMP affecting compounds including antiplatelet drugs and their combinations revealed a high fidelity, fine-tuned cAMP signaling in platelets without crosstalk to the cGMP pathway. The model and the data provide evidence for two independent feedback loops: PKA, which is activated by elevated cAMP levels in the platelet, subsequently inhibits adenylyl cyclase (AC) but as well activates PDE3. By multi-experiment fitting, we established a comprehensive dynamic model with one predictive, optimized and validated set of parameters. Different pharmacological conditions (inhibition, activation, drug combinations, permanent and transient perturbations) are successfully tested and simulated, including statistical validation and sensitivity analysis. Downstream cyclic nucleotide signaling events target different phosphorylation sites for cAMP- and cGMP-dependent protein kinases (PKA, PKG) in the vasodilator-stimulated phosphoprotein (VASP). VASP phosphorylation as well as cAMP levels resulting from different drug strengths and combined stimulants were quantitatively modeled. These predictions were again experimentally validated. High sensitivity of the signaling pathway at low concentrations is involved in a fine-tuned balance as well as stable activation of this inhibitory cyclic nucleotide pathway. Conclusions: On the basis of experimental data, literature mining and database screening we established a dynamic in silico model of cyclic nucleotide signaling and probed its signaling sensitivity. Thoroughly validated, it successfully predicts drug combination effects on platelet function, including synergism, antagonism and regulatory loops.
KW  - Vasodilatator-stimuliertes Phosphoprotein
KW  - VASP
KW  - cyclic nucleotide signaling
KW  - silico model
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-69145
ER  -