TY - JOUR A1 - Ruiz-Heredia, Yanira A1 - Sánchez-Vega, Beatriz A1 - Onecha, Esther A1 - Barrio, Santiago A1 - Alonso, Rafael A1 - Carlos Martínez-Avila, Jose A1 - Cuenca, Isabel A1 - Agirre, Xabier A1 - Braggio, Esteban A1 - Hernández, Miguel-T. A1 - Martínez, Rafael A1 - Rosiñol, Laura A1 - Gutierrez, Norma A1 - Martin-Ramos, Marisa A1 - Ocio, Enrique M. A1 - Echeveste, María-Asunción A1 - Pérez de Oteyza, Jaime A1 - Oriol, Albert A1 - Bargay, Joan A1 - Gironella, Mercedes A1 - Ayala, Rosa A1 - Bladé, Joan A1 - Mateos, María-Victoria A1 - Kortum, Klaus M. A1 - Stewart, Keith A1 - García-Sanz, Ramón A1 - San Miguel, Jesús A1 - José Lahuerta, Juan A1 - Martinez-Lopez, Joaquín T1 - Mutational screening of newly diagnosed multiple myeloma patients by deep targeted sequencing JF - Haematologica N2 - no abstract available KW - Copy number changes KW - Survival Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227151 VL - 103 IS - 11 ER - TY - JOUR A1 - Haertle, Larissa A1 - Buenache, Natalia A1 - Cuesta Hernández, Hipólito Nicolás A1 - Simicek, Michal A1 - Snaurova, Renata A1 - Rapado, Inmaculada A1 - Martinez, Nerea A1 - López-Muñoz, Nieves A1 - Sánchez-Pina, José María A1 - Munawar, Umair A1 - Han, Seungbin A1 - Ruiz-Heredia, Yanira A1 - Colmenares, Rafael A1 - Gallardo, Miguel A1 - Sanchez-Beato, Margarita A1 - Piris, Miguel Angel A1 - Samur, Mehmet Kemal A1 - Munshi, Nikhil C. A1 - Ayala, Rosa A1 - Kortüm, Klaus Martin A1 - Barrio, Santiago A1 - Martínez-López, Joaquín T1 - Genetic alterations in members of the proteasome 26S subunit, AAA-ATPase (PSMC) gene family in the light of proteasome inhibitor resistance in multiple myeloma JF - Cancers N2 - For the treatment of Multiple Myeloma, proteasome inhibitors are highly efficient and widely used, but resistance is a major obstacle to successful therapy. Several underlying mechanisms have been proposed but were only reported for a minority of resistant patients. The proteasome is a large and complex machinery. Here, we focus on the AAA ATPases of the 19S proteasome regulator (PSMC1-6) and their implication in PI resistance. As an example of cancer evolution and the acquisition of resistance, we conducted an in-depth analysis of an index patient by applying FISH, WES, and immunoglobulin-rearrangement sequencing in serial samples, starting from MGUS to newly diagnosed Multiple Myeloma to a PI-resistant relapse. The WES analysis uncovered an acquired PSMC2 Y429S mutation at the relapse after intensive bortezomib-containing therapy, which was functionally confirmed to mediate PI resistance. A meta-analysis comprising 1499 newly diagnosed and 447 progressed patients revealed a total of 36 SNVs over all six PSMC genes that were structurally accumulated in regulatory sites for activity such as the ADP/ATP binding pocket. Other alterations impact the interaction between different PSMC subunits or the intrinsic conformation of an individual subunit, consequently affecting the folding and function of the complex. Interestingly, several mutations were clustered in the central channel of the ATPase ring, where the unfolded substrates enter the 20S core. Our results indicate that PSMC SNVs play a role in PI resistance in MM. KW - Multiple Myeloma KW - drug resistance KW - proteasome inhibitors KW - immunoglobulin rearrangement KW - ATPase activity KW - PSMC2 Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-305013 SN - 2072-6694 VL - 15 IS - 2 ER - TY - JOUR A1 - Lupiañez, Carmen B. A1 - Villaescusa, Maria T. A1 - Carvalho, Agostinho A1 - Springer, Jan A1 - Lackner, Michaela A1 - Sánchez-Maldonado, José M. A1 - Canet, Luz M. A1 - Cunha, Cristina A1 - Segura-Catena, Joana A1 - Alcazar-Fuoli, Laura A1 - Solano, Carlos A1 - Fianchi, Luana A1 - Pagano, Livio A1 - Potenza, Leonardo A1 - Aguado, José M. A1 - Luppi, Mario A1 - Cuenca-Estrella, Manuel A1 - Lass-Flörl, Cornelia A1 - Einsele, Hermann A1 - Vázquez, Lourdes A1 - Ríos-Tamayo, Rafael A1 - Loeffler, Jürgen A1 - Jurado, Manuel A1 - Sainz, Juan T1 - Common Genetic Polymorphisms within NF kappa B-Related Genes and the Risk of Developing Invasive Aspergillosis JF - Frontiers in Microbiology N2 - Invasive Aspergillosis (IA) is an opportunistic infection caused by Aspergillus, a ubiquitously present airborne pathogenic mold. A growing number of studies suggest a major host genetic component in disease susceptibility. Here, we evaluated whether 14 single-nucleotide polymorphisms within NFκB1, NFκB2, RelA, RelB, Rel, and IRF4 genes influence the risk of IA in a population of 834 high-risk patients (157 IA and 677 non-IA) recruited through a collaborative effort involving the aspBIOmics consortium and four European clinical institutions. No significant overall associations between selected SNPs and the risk of IA were found in this large cohort. Although a hematopoietic stem cell transplantation (HSCT)-stratified analysis revealed that carriers of the IRF4rs12203592T/T genotype had a six-fold increased risk of developing the infection when compared with those carrying the C allele (ORREC = 6.24, 95%CI 1.25–31.2, P = 0.026), the association of this variant with IA risk did not reach significance at experiment-wide significant threshold. In addition, we found an association of the IRF4AATC and IRF4GGTC haplotypes (not including the IRF4rs12203592T risk allele) with a decreased risk of IA but the magnitude of the association was similar to the one observed in the single-SNP analysis, which indicated that the haplotypic effect on IA risk was likely due to the IRF4rs12203592 SNP. Finally, no evidence of significant interactions among the genetic markers tested and the risk of IA was found. These results suggest that the SNPs on the studied genes do not have a clinically relevant impact on the risk of developing IA. KW - Invasive Aspergillosis KW - genetic polymorphisms KW - susceptibility KW - NFkB-relatedgenes KW - interaction Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165209 VL - 7 IS - 1243 ER - TY - JOUR A1 - Sánchez, Rafael A1 - Thierschmann, Holger A1 - Molenkamp, Laurens W. T1 - Single-electron thermal devices coupled to a mesoscopic gate JF - New Journal of Physics N2 - We theoretically investigate the propagation of heat currents in a three-terminal quantum dot engine. Electron–electron interactions introduce state-dependent processes which can be resolved by energy-dependent tunneling rates. We identify the relevant transitions which define the operation of the system as a thermal transistor or a thermal diode. In the former case, thermal-induced charge fluctuations in the gate dot modify the thermal currents in the conductor with suppressed heat injection, resulting in huge amplification factors and the possible gating with arbitrarily low energy cost. In the latter case, enhanced correlations of the state-selective tunneling transitions redistribute heat flows giving high rectification coefficients and the unexpected cooling of one conductor terminal by heating the other one. We propose quantum dot arrays as a possible way to achieve the extreme tunneling asymmetries required for the different operations. KW - physics KW - quantum dot KW - heat currents KW - thermal devices KW - single-electron tunneling Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172982 VL - 19 ER - 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 - Sierra, Miguel A. A1 - Sánchez, David A1 - Gutierrez, Rafael A1 - Cuniberti, Gianaurelio A1 - Domínguez-Adame, Francisco A1 - Díaz, Elena T1 - Spin-polarized electron transmission in DNA-like systems JF - Biomolecules N2 - The helical distribution of the electronic density in chiral molecules, such as DNA and bacteriorhodopsin, has been suggested to induce a spin–orbit coupling interaction that may lead to the so-called chirality-induced spin selectivity (CISS) effect. Key ingredients for the theoretical modelling are, in this context, the helically shaped potential of the molecule and, concomitantly, a Rashba-like spin–orbit coupling due to the appearance of a magnetic field in the electron reference frame. Symmetries of these models clearly play a crucial role in explaining the observed effect, but a thorough analysis has been largely ignored in the literature. In this work, we present a study of these symmetries and how they can be exploited to enhance chiral-induced spin selectivity in helical molecular systems. KW - chirality-induced spin selectivity KW - helical molecules KW - spin transport KW - spin polarization KW - DNA electronic transport Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193813 SN - 2218-273X VL - 10 IS - 1 ER - TY - JOUR A1 - Moris, Lisa A1 - Van den Broeck, Thomas A1 - Tosco, Lorenzo A1 - Van Baelen, Anthony A1 - Gontero, Paolo A1 - Karnes, Robert Jeffrey A1 - Everaerts, Wouter A1 - Albersen, Maarten A1 - Bastian, Patrick J. A1 - Chlosta, Piotr A1 - Claessens, Frank A1 - Chun, Felix K. A1 - Graefen, Markus A1 - Gratzke, Christian A1 - Kneitz, Burkhard A1 - Marchioro, Giansilvio A1 - Salas, Rafael Sanchez A1 - Tombal, Bertrand A1 - Van Der Poel, Henk A1 - Walz, Jochen Christoph A1 - De Meerleer, Gert A1 - Bossi, Alberto A1 - Haustermans, Karin A1 - Montorsi, Francesco A1 - Van Poppel, Hendrik A1 - Spahn, Martin A1 - Briganti, Alberto A1 - Joniau, Steven T1 - Impact of lymph node burden on survival of high-risk prostate cancer patients following radical prostatectomy and pelvic lymph node dissection JF - Frontiers in Surgery N2 - Aim To determine the impact of the extent of lymph node invasion (LNI) on long-term oncological outcomes after radical prostatectomy (RP). Material and methods In this retrospective study, we examined the data of 1,249 high-risk, non-metastatic PCa patients treated with RP and pelvic lymph node dissection (PLND) between 1989 and 2011 at eight different tertiary institutions. We fitted univariate and multivariate Cox models to assess independent predictors of cancer-specific survival (CSS) and overall survival (OS). The number of positive lymph node (LN) was dichotomized according to the most informative cutoff predicting CSS. Kaplan–Meier curves assessed CSS and OS rates. Only patients with at least 10 LNs removed at PLND were included. This cutoff was chosen as a surrogate for a well performed PNLD. Results Mean age was 65 years (median: 66, IQR 60–70). Positive surgical margins were present in 53.7% (n = 671). Final Gleason score (GS) was 2–6 in 12.7% (n = 158), 7 in 52% (n = 649), and 8–10 in 35.4% (n = 442). The median number of LNs removed during PLND was 15 (IQR 12–17). Of all patients, 1,128 (90.3%) had 0–3 positive LNs, while 126 (9.7%) had ≥4 positive LNs. Patients with 0–3 positive LNs had significantly better CSS outcome at 10-year follow-up compared to patients with ≥4 positive LNs (87 vs. 50%; p < 0.0001). Similar results were obtained for OS, with a 72 vs. 37% (p < 0.0001) survival at 10 years for patients with 0–3 vs. ≥4 positive LNs, respectively. At multivariate analysis, final GS of 8–10, salvage ADT therapy, and ≥4 (vs. <4) positive LNs were predictors of worse CSS and OS. Pathological stage pT4 was an additional predictor of worse CSS. Conclusion Four or more positive LNs, pathological stage pT4, and final GS of 8–10 represent independent predictors for worse CSS in patients with high-risk PCa. Primary tumor biology remains a strong driver of tumor progression and patients having ≥4 positive LNs could be considered an enriched patient group in which novel treatment strategies should be studied. KW - high-risk prostate cancer KW - lymph node dissection KW - positive lymph node KW - prognosis KW - surgery Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-195721 SN - 2296-875X VL - 3 ER -