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358 results on '"Tomek A"'

1. Human DNA polymerase ε is a source of C>T mutations at CpG dinucleotides

Author

Tomkova, Marketa, McClellan, Michael John, Crevel, Gilles, Shahid, Akbar Muhammed, Mozumdar, Nandini, Tomek, Jakub, Shepherd, Emelie, Cotterill, Sue, Schuster-Böckler, Benjamin, and Kriaucionis, Skirmantas

Abstract

C-to-T transitions in CpG dinucleotides are the most prevalent mutations in human cancers and genetic diseases. These mutations have been attributed to deamination of 5-methylcytosine (5mC), an epigenetic modification found on CpGs. We recently linked CpG>TpG mutations to replication and hypothesized that errors introduced by polymerase ε (Pol ε) may represent an alternative source of mutations. Here we present a new method called polymerase error rate sequencing (PER-seq) to measure the error spectrum of DNA polymerases in isolation. We find that the most common human cancer-associated Pol ε mutant (P286R) produces an excess of CpG>TpG errors, phenocopying the mutation spectrum of tumors carrying this mutation and deficiencies in mismatch repair. Notably, we also discover that wild-type Pol ε has a sevenfold higher error rate when replicating 5mCpG compared to C in other contexts. Together, our results from PER-seq and human cancers demonstrate that replication errors are a major contributor to CpG>TpG mutagenesis in replicating cells, fundamentally changing our understanding of this important disease-causing mutational mechanism.

Published
2024
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2. Effect of Asymptomatic and Symptomatic COVID-19 on Acute Ischemic Stroke Revascularization Outcomes

Author

Strambo, Davide, Marto, João Pedro, Ntaios, George, Nguyen, Thanh N., Michel, Patrik, Herzig, Roman, Członkowksa, Anna, Demeestere, Jelle, Yassin Mansour, Ossama, Georgiopoulos, Georgios, Nogueira, Raul G., Salerno, Alexander, Wegener, Susanne, Baumgartner, Philipp, Cereda, Carlo W., Bianco, Giovanni, Beyeler, Morin, Arnold, Marcel, Carrera, Emmanuel, Machi, Paolo, Altersberger, Valerian, Bonati, Leo, Gensicke, Henrik, Bolognese, Manuel, Peters, Nils, Wetzel, Stephan, Magriço, Marta, Nuno Ramos, João, Sargento-Freitas, João, Machado, Rita, Maia, Carolina, Machado, Egídio, Paiva-Nunes, Ana, Ferreira, Patrícia, Pinho-e-Melo, Teresa, Carvalho-Dias, Mariana, Paula, André, Alberto Correia, Manuel, Castro, Pedro, Azevedo, Elsa, Albuquerque, Luís, Nuno-Alves, José, Ferreira-Pinto, Joana, Meira, Torcato, Pereira, Liliana, Rodrigues, Miguel, Araújo, André, Rodrigues, Marta, Rocha, Mariana, Pereira-Fonseca, Ângelo, Ribeiro, Luís, Varela, Ricardo, Cappellari, Manuel, Zivelonghi, Cecilia, Sajeva, Giulia, Zini, Andrea, Gentile, Mauro, Forlivesi, Stefano, Migliaccio, Ludovica, Sessa, Maria, Pezzini, Alessandro, Sangalli, Davide, Zedde, Marialuisa, Pascarella, Rosario, Diamanti, Susanna, Beretta, Simone, Schwarz, Ghil, Frisullo, Giovanni, Marcheselli, Simona, Seners, Pierre, Sabben, Candice, Escalard, Simon, Piotin, Michel, Maier, Benjamin, Charbonnier, Guillaume, Vuillier, Fabrice, Legris, Loic, Cuisenier, Pauline, Vodret, Francesca R., Marnat, Gaultier, Liegey, Jean-Sebastien, Sibon, Igor, Flottmann, Fabian, Broocks, Gabriel, Gloyer, Nils-Ole, Bohmann, Ferdinand O., Hendrik Schaefer, Jan, Nolte, Christian H., Audebert, Heinrich, Siebert, Eberhard, Sykora, Marek, Lang, Wilfried, Ferrari, Julia, Mayer-Suess, Lukas, Knoflach, Michael, Gizewski, Elke-Ruth, Stolp, Jeffrey, Stolze, Lotte J., Coutinho, Jonathan M., Nederkoorn, Paul J., van-den-Wijngaard, Ido, de Meris, Joke, Lemmens, Robin, De Raedt, Sylvie, Vandervorst, Fenne, Pierre Rutgers, Matthieu, Guilmot, Antoine, Dusart, Anne, Bellante, Flavio, Calleja-Castaño, Patricia, Ostos, Fernando, Gonzalez-Ortega, Guillermo, Martín-Jiménez, Paloma, García-Madrona, Sebastian, Cruz-Culebras, Antonio, Vera, Rocio, Matute, Maria-Consuelo, Fuentes, Blanca, Alonso-de-Leciñana, María, Rigual, Ricardo, Díez-Tejedor, Exuperio, Pérez-Sánchez, Soledad, Montaner, Joan, Díaz-Otero, Fernando, Perez de la Ossa, Natalia, Flores-Pina, Belén, Muñoz-Narbona, Lucia, Chamorro, Angel, Rodríguez-Vázquez, Alejandro, Renú, Arturo, Ayo-Martin, Oscar, Hernandez-Fernandez, Francisco, Segura, Tomas, Tejada-Meza, Herbert, Hlaing, Thant, See, Isaiah, Simister, Robert, Werring, David J., Saxhaug Kristoffersen, Espen, Nordanstig, Annika, Jood, Katarina, Rentzos, Alexandros, Šimůnek, Libor, Krajíčková, Dagmar, Krajina, Antonín, Mikulík, Robert, Cviková, Martina, Vinklárek, Jan, Školoudík, David, Roubec, Martin, Hurtikova, Eva, Hrubý, Rostislav, Ostry, Svatopluk, Skoda, Ondrej, Pernicka, Marek, Kočí, Lubomír, Eichlová, Zuzana, Jíra, Martin, Kovář, Martin, Panský, Michal, Mencl, Pavel, Paloušková, Hana, Tomek, Aleš, Janský, Petr, Olšerová, Anna, Šrámek, Martin, Havlíček, Roman, Malý, Petr, Trakal, Lukáš, Fiksa, Jan, Slovák, Matěj, Karliński, Michał, Nowak, Maciej, Sienkiewicz-Jarosz, Halina, Bochynska, Anna, Wrona, Pawel, Homa, Tomasz, Sawczynska, Katarzyna, Slowik, Agnieszka, Wlodarczyk, Ewa, Wiącek, Marcin, Tomaszewska-Lampart, Izabella, Sieczkowski, Bartosz, Bartosik-Psujek, Halina, Bilik, Marta, Bandzarewicz, Anna, Dorobek, Malgorzata, Zielińska-Turek, Justyna, Nowakowska-Kotas, Marta, Obara, Krystian, Urbanowski, Paweł, Budrewicz, Sławomir, Guziński, Maciej, Świtońska, Milena, Rutkowska, Iwona, Sobieszak-Skura, Paulina, Łabuz-Roszak, Beata, Dębiec, Aleksander, Staszewski, Jacek, Stępień, Adam, Zwiernik, Jacek, Wasilewski, Grzegorz, Tiu, Cristina, Terecoasă, Elena-Oana, Radu, Razvan-Alexandru, Negrila, Anca, Dorobat, Bogdan, Panea, Cristina, Tiu, Vlad, Petrescu, Simona, Özcan-Özdemir, Atilla, Mahmoud, Mostafa, El-Samahy, Hussam, Abdelkhalek, Hazem, Al-Hashel, Jasem, Ibrahim Ismail, Ismail, Salmeen, Athari, Ghoreishi, Abdoreza, Sabetay, Sergiu, Gross, Hana, Klein, Piers, Abdalkader, Mohamad, Jabbour, Pascal, El Naamani, Kareem, Tjoumakaris, Stavropoula, Abbas, Rawad, Mohamed, Ghada-A., Chebl, Alex, Min, Jiangyong, Hovingh, Majesta, Tsai, Jenny, Khan, Muhib-A., Nalleballe, Krishna, Onteddu, Sanjeeva, Masoud, Hesham E., Michael, Mina, Kaur, Navreet, Maali, Laith, Abraham, Michael, Khandelwal, Priyank, Bach, Ivo, Ong, Melody, Babici, Denis, Khawaja, Ayaz-M., Hakemi, Maryam, Rajamani, Kumar, Cano-Nigenda, Vanessa, Arauz, Antonio, Amaya, Pablo, Llanos, Natalia, Arango, Akemi, Vences, Miguel A., Barrientos, José-Domingo, Caetano, Rayllene, Targa, Rodrigo, Scollo, Sergio, Yalung, Patrick, Nagendra, Shashank, Gaikwad, Abhijit, and Seo, Kwon-Duk

Published
2024
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3. Pooled multicolour tagging for visualizing subcellular protein dynamics

Author

Reicher, Andreas, Reiniš, Jiří, Ciobanu, Maria, Růžička, Pavel, Malik, Monika, Siklos, Marton, Kartysh, Victoria, Tomek, Tatjana, Koren, Anna, Rendeiro, André F., and Kubicek, Stefan

Abstract

Imaging-based methods are widely used for studying the subcellular localization of proteins in living cells. While routine for individual proteins, global monitoring of protein dynamics following perturbation typically relies on arrayed panels of fluorescently tagged cell lines, limiting throughput and scalability. Here, we describe a strategy that combines high-throughput microscopy, computer vision and machine learning to detect perturbation-induced changes in multicolour tagged visual proteomics cell (vpCell) pools. We use genome-wide and cancer-focused intron-targeting sgRNA libraries to generate vpCell pools and a large, arrayed collection of clones each expressing two different endogenously tagged fluorescent proteins. Individual clones can be identified in vpCell pools by image analysis using the localization patterns and expression level of the tagged proteins as visual barcodes, enabling simultaneous live-cell monitoring of large sets of proteins. To demonstrate broad applicability and scale, we test the effects of antiproliferative compounds on a pool with cancer-related proteins, on which we identify widespread protein localization changes and new inhibitors of the nuclear import/export machinery. The time-resolved characterization of changes in subcellular localization and abundance of proteins upon perturbation in a pooled format highlights the power of the vpCell approach for drug discovery and mechanism-of-action studies.

Published
2024
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4. Delivery of acute ischaemic stroke treatments in the European region in 2019 and 2020

Author

Aguiar de Sousa, Diana, Wilkie, Arlene, Norrving, Bo, Macey, Chris, Bassetti, Claudio, Tiu, Cristina, Roth, Greg, Lunde, Grethe, Christensen, Hanne, Fiehler, Jens, Pezzella, Francesca Romana, Dichgans, Martin, Roaldsen, Melinda B, Kelly, Peter, Mikulik, Robert, Sacco, Simona, Caso, Valeria, Fischer, Urs, Basha, Entela, Yeghiazaryan, Nune, Kiechl, Stefan, Shiraliyeva, Rana, Vanacker, Peter, Bender, Marija, Emilov Tsalta-Mladenov, Mihael, Budincevic, Hrvoje, Tomek, Ales, Kaponides, Georgios, Klingenberg Iversen, Helle, Faiss, Jürgen, Kõrv, Janika, Sairanen, Tiina, Igor, Sibon, Tsiskaridze, Alexander, Ntaios, George, Tsivgoulis, Georgios, Szapary, Laszlo, Logi Thorarinsson, Bjorn, Harbison, Joe, Bornstein, Natan M., Toni, Danilo, Fisnik, Jashari, Karbozova, Kunduz, Miglane, Evija, Dalius, Jatužis, Droste, Dirk, Mallia, Maria, Jevto, Erakovic, Arsovska, Anita, Fromm, Annette, Kobayashi, Adam, Azevedo, Elsa, Groppa, Stanislav, Cristina, Tiu, Guekht, Alla, Zivanovic, Zeljko, Nosal, Vladimir, Zvan, Bojana, López-Cancio, Elena, Pérez de la Ossa, Natàlia, Norrving, Bo, Nedeltchev, Krassen, Vrijhoef, Bert, Akif Topcuoglu, Mehmet, Flomin, Yuriy, Ahmed, Rubina, Shelesko, Andrey, Petrela, Mentor, Zubalova, Lina, Hasanov, Rovshan, Raedt, Sylvie De, Nevena, Mahmutbegović, Peteva Andonova, Silva, Poljakovic, Zdravka, Skoda, Ondrej, Søren Paaske, Johnsen, med. Helmuth Steinmetz, Prof. Dr., Kõrv, Janika, Sairanen, Tiina, Denis, Sablot, Lobjanidze, Nino, Milionis, Haralambos, Mitsias, Panagiotis, Tarkanyi MD, Gabor, Elisabeth Klinke, Marianne, Tanne, David, Luca, Petraglia, Dren, Boshnjaku, Turgumbaev, Dzhamal, Guntis, Karelis, Dalius, Jatužis, Droste, Dirk, Mladen, Debeljevic, Arsovska, Anita, Kurz, Martin, Anna, Czlonkowska, Eremei, Zota, Elena Oana, Terecoasa, Martinov, Mikhail, Jovanović, Dejana, Gdovinova, Zuzana, Zvan, Bojana, López-Cancio, Elena, Camps Renom, Pol, Kwa, Vincent, Murat Arsava, Ethem, Gulyayeva, Maryna, Dharmasiri, Michelle, Basha, Entela, Korompoki, Eleni, Vadikolias, Konstantinos, Bereczki MD, Daniel, Bryndis Einarsdottir, Anna, Afrim, Blyta, Mamytova, Elmira, Kristaps, Jurjans, Daiva, Rastenytė, Costache, Oana, Milovan, Roganovic, Fromm, Annette, Michal, Karlinski, Alexandru, Gasnas, Sorin, Tuta, Fidler, Mikhail, Raičević, Ranko, Zaletel, Marjan, Castellanos, Mar, Gómez-Choco, Manuel, Sirin, Hadiye, Lebedynets, Dmytro, Khaira, Jattinder, Enesi, Eugen, Sahakyan, David, Mammadbayli, Ayten, Lemmens, Robin, Dževdet, Smajlović, Emilov Tsalta-Mladenov, Mihael, Budincevic, Hrvoje, Sramek, Martin, Nabavi, med. Darius, Vibo, Riina, Strbian, Daniel, Aliyev, Rahim, Mikulik, Robert, Ozretic, David, Rocek, Miloslav, Trine, Stavngaard, med. Claus Zimmer, Prof. Dr., Malikov, Vladislav, Lappalainen, Kimmo, Jerome, Berge, Khinikadze, Mirza, Brountzos, Elias, Vilmarsson, Vilhjalmur, Karlis, Kupcs, Marius, Kurminas, Hoffmann, Michel, Grech, Reuben, Marija, Mitric, Kjellevold Wathle, Gaute, Wojciech, Poncyljusz, Igor, Crivorucica, Bogdan, Dorobat, Till, Viktor, Klepanec, Andrej, Milosevic, Zoran, Macho, Juan, Ozdemir, Ozcan, Shchehlov, Dmytro, Dorte, Damgaard, Hermanek, Peter, Sturua, Lela, Siskou, Olga, Tsivgoulis, Georgios, Libruder, Carmit, Indredavik, Bent, Azevedo, Elsa, Elena, Manole, Mijajlović, Milija, Turcani, Peter, Norrving, Bo, Bonati, Leo, Nederkoorn, Paul, Ertuğrul Eğin, Muhammed, Samofalov, Dmytro, Diana, Ose, Rita, Gaidelytė, and Droste, Dirk

Abstract

Introduction: We assessed best available data on access and delivery of acute stroke unit (SU) care, intravenous thrombolysis (IVT) and endovascular treatment (EVT) in the European region in 2019 and 2020.Patients and methods: We compared national data per number of inhabitants and per 100 annual incident first-ever ischaemic strokes (AIIS) in 46 countries. Population estimates and ischaemic stroke incidence were based on United Nations data and the Global Burden of Disease Report 2019, respectively.Results: The estimated mean number of acute SUs in 2019 was 3.68 (95% CI: 2.90–4.45) per one million inhabitants (MIH) with 7/44 countries having less than one SU per one MIH. The estimated mean annual number of IVTs was 21.03 (95% CI: 15.63–26.43) per 100,000 and 17.14% (95% CI: 12.98–21.30) of the AIIS in 2019, with highest country rates at 79.19 and 52.66%, respectively, and 15 countries delivering less than 10 IVT per 100,000. The estimated mean annual number of EVTs in 2019 was 7.87 (95% CI: 5.96–9.77) per 100,000 and 6.91% (95% CI: 5.15–8.67) of AIIS, with 11 countries delivering less than 1.5 EVT per 100,000. Rates of SUs, IVT and EVT were stable in 2020. There was an increase in mean rates of SUs, IVT and EVT compared to similar data from 2016.Conclusion: Although there was an increase in reperfusion treatment rates in many countries between 2016 and 2019, this was halted in 2020. There are persistent major inequalities in acute stroke treatment in the European region. Tailored strategies directed to the most vulnerable regions should be prioritised.

Published
2023
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8. Evaluation of Blood-Brain Barrier Integrity by the Analysis of Dynamic Contrast-Enhanced MRI – a Comparison of Quantitative and Semi-Quantitative Methods.

Author

KALA, David, ŠULC, Vlastimil, OLŠEROVÁ, Anna, SVOBODA, JAN, PRYSIAZHNIUK, Yeva, POŠUSTA, Antonín, KYNČL, Martin, ŠANDA, Jan, TOMEK, Aleš, and OTÁHAL, Jakub

Subjects
BLOOD-brain barrier, MAGNETIC resonance imaging, MORPHOMETRICS, STROKE patients, PARAMETERS (Statistics)
Abstract

Disruption of the blood-brain barrier (BBB) is a key feature of various brain disorders. To assess its integrity a parametrization of dynamic magnetic resonance imaging (DCE MRI) with a contrast agent (CA) is broadly used. Parametrization can be done quantitatively or semi-quantitatively. Quantitative methods directly describe BBB permeability but exhibit several drawbacks such as high computation demands, reproducibility issues, or low robustness. Semi-quantitative methods are fast to compute, simply mathematically described, and robust, however, they do not describe the status of BBB directly but only as a variation of CA concentration in measured tissue. Our goal was to elucidate differences between five semi-quantitative parameters: maximal intensity (Imax), normalized permeability index (NPI), and difference in DCE values between three timepoints: baseline, 5 min, and 15 min (Δ5-0, Δ15-0, Δ15-5) and two quantitative parameters: transfer constant (Ktrans ) and an extravascular fraction (Ve). For the purpose of comparison, we analyzed DCE data of four patients 12-15 days after the stroke with visible CA enhancement. Calculated parameters showed abnormalities spatially corresponding with the ischemic lesion, however, findings in individual parameters morphometrically differed. Ktrans and Ve were highly correlated. Δ5-0 and Δ15-0 were prominent in regions with rapid CA enhancement and highly correlated with Ktrans . Abnormalities in Δ15-5 and NPI were more homogenous with less variable values, smoother borders, and less detail than Ktrans. Moreover, only Δ15-5 and NPI were able to distinguish vessels from extravascular space. Our comparison provides important knowledge for understanding and interpreting parameters derived from DCE MRI by both quantitative and semi-quantitative methods. [ABSTRACT FROM AUTHOR]

Published
2022
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9. Precise modulation of transcription factor levels identifies features underlying dosage sensitivity

Author

Naqvi, Sahin, Kim, Seungsoo, Hoskens, Hanne, Matthews, Harold S., Spritz, Richard A., Klein, Ophir D., Hallgrímsson, Benedikt, Swigut, Tomek, Claes, Peter, Pritchard, Jonathan K., and Wysocka, Joanna

Abstract

Transcriptional regulation exhibits extensive robustness, but human genetics indicates sensitivity to transcription factor (TF) dosage. Reconciling such observations requires quantitative studies of TF dosage effects at trait-relevant ranges, largely lacking so far. TFs play central roles in both normal-range and disease-associated variation in craniofacial morphology; we therefore developed an approach to precisely modulate TF levels in human facial progenitor cells and applied it to SOX9, a TF associated with craniofacial variation and disease (Pierre Robin sequence (PRS)). Most SOX9-dependent regulatory elements (REs) are buffered against small decreases in SOX9 dosage, but REs directly and primarily regulated by SOX9 show heightened sensitivity to SOX9 dosage; these RE responses partially predict gene expression responses. Sensitive REs and genes preferentially affect functional chondrogenesis and PRS-like craniofacial shape variation. We propose that such REs and genes underlie the sensitivity of specific phenotypes to TF dosage, while buffering of other genes leads to robust, nonlinear dosage-to-phenotype relationships.

Published
2023
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10. Mechanical Thrombectomy Global Access For Stroke (MT-GLASS): A Mission Thrombectomy (MT-2020 Plus) Study

Author

Asif, Kaiz S., Otite, Fadar O., Desai, Shashvat M., Herial, Nabeel, Inoa, Violiza, Al-Mufti, Fawaz, Jadhav, Ashutosh P., Dmytriw, Adam A., Castonguay, Alicia, Khandelwal, Priyank, Potter-Vig, Jennifer, Szeder, Viktor, Kulman, Tanzila, Urrutia, Victor, Masoud, Hesham, Toth, Gabor, Limaye, Kaustubh, Aroor, Sushanth, Brinjikji, Waleed, Rai, Ansaar, Pandian, Jeyaraj, Gebreyohanns, Mehari, Leung, Thomas, Mansour, Ossama, Demchuk, Andrew M., Huded, Vikram, Martins, Sheila, Zaidat, Osama, Huo, Xiaochuan, Campbell, Bruce, Sylaja, P.N., Miao, Zhongrong, Saver, Jeffrey, Ortega-Gutierrez, Santiago, Yavagal, Dileep R., Cirio, Juan Jose, Lylyk, Pedro, Ferrario, Angel, Plaghos, Luis Lemme, Arroyo, José, Yan, Bernard, Chandra, Ronil, Ibrahim, Wael Hamed, Alnidawi, Firas, Islam, Sirajee Shafiqul, Shahidullah, Mohammad, Saavedra, Víctor Villarroel, Alverne, Francisco Josà Mont’, Magalhaes, Pedro, Silva, Gisele Sampaio, Sirakov, Stanimir, Kalpachki, Rosen, Alioski, Nurfet, lamou, Eric Gueumekane bila, Shankar, Jai, Stotts, Grant, Rowe, Daidre, Gayle, Francene, de Souza, Romnesh, Ramos, Cristina, GarcÃa, Amaury, Ali, Amza, Sandy, Sherry, Lavados, Pablo M., Rivera, Rodrigo, GUZMÁN, TONY FABIÁN ÁLVAREZ, Villarraga, Alejandro, Estrada, Carolina, Pabon, Boris, Krajina, Antonin, Tomek, Aleš, Adebayo, Philip B, ABDO, GERMAN, Maldonado S, Nelson, Hassan, Farouk, Khedr, Eman M, Khinikadze, Mirza, NADAREISHVILI, ZURAB, Tsiskaridze, Alexander, Syrmos, Nikolaos, Mitsias, Panayiotis, Das, Biplab, Roy, Jayanta, Gupta, Vivek, Gupta, Vipul, Khurana, Dheeraj, Karapurkar, Anil, Stivastava, M.V.Padma, Alurkar, Anand, Sharma, Arvind, Lahoti, Satish, Kumar, Rahul, Kuruttukulam, Gigy Varkey, Sani, Achmad Firdaus, Sari, Ita Muharram, Khassaf, Mustafa, Majid Nassir, Temeem, Sakai, Nobuyuki, Yamagami, Hiroshi, Dababneh, Haitham, Aladham, Farid A., Berdikhojayev, Mynzhylky, Medukhanova, Sabina, Kikano, Raghid, Alaraj, Ali, Ahdab, Rechdi, Zaidi, Wan Asyraf Wan, Kadir, Khairul Azmi Abd, Arauz, Antonio, Gongora, Fernando, Jambaldorj, Ariunaa, XXX, Ganbaatar, Shwe, Zarni Myint, Thit, Win Min, Ranta, Anna, Wu, Teddy, RAYO, ERWIN E., Owolabi, Mayowa, Makanjuola, Akintomiwa, Ahmad, Saima, WASAY, MOHAMMAD, Rashid, Umair, Mernes, Ricardo, Paniagua, Osvaldo, GALLO, MARLA, Moquillaza, Manuel, Collantes, Maria Epifania, Mariano, Manuel M., Kobayashi, Adam, Rodriguez-Mercado, Rafael, Guardia, Rodolfo Alcedo, Imam, Yahia, Ahmed, Ayman Zakaria, Alhazzani, Adel, Al-Jehani, Hosam M., Lee, Wickly, ZELEŇÁK, Kamil, Klepanec, Andrej, KRASTEV, GEORGI, Frol, Senta, Brey, Naeem, Rossouw, Anastasia, De Silva, Prasad, Gunasekera, Harsha, Ranawaka, Udaya, Osman, Haytham, El-Sadig, Sarah M, Suwanwela, Nijasri C., Akarathanawat, Wasan, Tantivatana, Jarturon, Hammami, Nadia, Sassi, Samia Ben, Ozdemir, Atilla Ozcan, Giray, Semih, Lebedynets, Dmytro, Konotopchik, Stanislav, John, Seby, Hussain, Syed Irteza, Novakovic-White, Robin, Ozdemir, Atilla Ozcan, Giray, Semih, Gordon Perue, Gillian L., Then, Ryna, Berrutti, Claudio, Crosa, Roberto, Nguyen, Huy Thang, Le, Huynh Vu, and vu, Tran thanh

Published
2023
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11. Safety and Outcome of Revascularization Treatment in Patients With Acute Ischemic Stroke and COVID-19

Author

Marto, João Pedro, Strambo, Davide, Ntaios, George, Nguyen, Thanh N., Herzig, Roman, Czlonkowska, Anna, Demeestere, Jelle, Mansour, Ossama Yassin, Salerno, Alexander, Wegener, Susanne, Baumgartner, Philipp, Cereda, Carlo W., Bianco, Giovanni, Beyeler, Morin, Arnold, Marcel, Carrera, Emmanuel, Machi, Paolo, Altersberger, Valerian, Bonati, Leo, Gensicke, Henrik, Bolognese, Manuel, Peters, Nils, Wetzel, Stephan, Magriço, Marta, Ramos, João Nuno, Sargento-Freitas, João, Machado, Rita, Maia, Carolina, Machado, Egídio, Nunes, Ana Paiva, Ferreira, Patricia, Pinho e Melo, Teresa, Dias, Mariana Carvalho, Paula, André, Correia, Manuel Alberto, Castro, Pedro, Azevedo, Elsa, Albuquerque, Luís, Alves, José Nuno, Ferreira-Pinto, Joana, Meira, Torcato, Pereira, Liliana, Rodrigues, Miguel, Araujo, Andre Pinho, Rodrigues, Marta, Rocha, Mariana, Pereira-Fonseca, Ângelo, Ribeiro, Luís, Varela, Ricardo, Malheiro, Sofia, Cappellari, Manuel, Zivelonghi, Cecilia, Sajeva, Giulia, Zini, Andrea, Gentile, Mauro, Forlivesi, Stefano, Migliaccio, Ludovica, Sessa, Maria, La Gioia, Sara, Pezzini, Alessandro, Sangalli, Davide, Zedde, Marialuisa, Pascarella, Rosario, Ferrarese, Carlo, Beretta, Simone, Diamanti, Susanna, Schwarz, Ghil, Frisullo, Giovanni, Marcheselli, Simona, Seners, Pierre, Sabben, Candice, Escalard, Simon, Piotin, Michel, Maïer, Benjamin, Charbonnier, Guillaume, Vuillier, Fabrice, Legris, Loïc, Cuisenier, Pauline, Vodret, Francesca R., Marnat, Gaultier, Liegey, Jean-Sebastien, Sibon, Igor, Flottmann, Fabian, Broocks, Gabriel, Gloyer, Nils-Ole, Bohmann, Ferdinand O., Schaefer, Jan Hendrik, Nolte, Christian, Audebert, Heinrich J., Siebert, Eberhard, Sykora, Marek, Lang, Wilfried, Ferrari, Julia, Mayer-Suess, Lukas, Knoflach, Michael, Gizewski, Elke Ruth, Stolp, Jeffrey, Stolze, Lotte J., Coutinho, Jonathan M., Nederkoorn, Paul, van den Wijngaard, Ido, De Meris, Joke, Lemmens, Robin, De Raedt, Sylvie, Vandervorst, Fenne, Rutgers, Matthieu Pierre, Guilmot, Antoine, Dusart, Anne, Bellante, Flavio, Calleja-Castaño, Patricia, Ostos, Fernando, González-Ortega, Guillermo, Martín-Jiménez, Paloma, García-Madrona, Sebastian, Cruz-Culebras, Antonio, Vera, Rocio, Matute, Maria Consuelo, Fuentes, Blanca, Alonso-de-Leciñana, María, Rigual, Ricardo, Díez-Tejedor, Exuperio, Perez-Sanchez, Soledad, Montaner, Joan, Díaz-Otero, Fernando, Pérez-de-la-Ossa, Natalia, Flores-Pina, Belén, Muñoz-Narbona, Lucia, Chamorro, Angel, Rodríguez-Vázquez, Alejandro, Renú, Arturo, Ayo-Martin, Oscar, Hernández-Fernández, Francisco, Segura, Tomas, Tejada-Meza, Herbert, Sagarra-Mur, Daniel, Serrano-Ponz, Marta, Hlaing, Thant, See, Isaiah, Simister, Robert, Werring, David, Kristoffersen, Espen Saxhaug, Nordanstig, Annika, Jood, Katarina, Rentzos, Alexandros, Šimůnek, Libor, Krajíčková, Dagmar, Krajina, Antonín, Mikulik, Robert, Cviková, Martina, Vinklárek, Jan, Školoudík, David, Roubec, Martin, Hurtikova, Eva, Hrubý, Rostislav, Ostry, Svatopluk, Skoda, Ondrej, Pernicka, Marek, Jurak, Lubomir, Eichlová, Zuzana, Jíra, Martin, Kovar, Martin, Panský, Michal, Mencl, Pavel, Palouskova, Hana, Tomek, Aleš, Janský, Petr, Olšerová, Anna, Sramek, Martin, Havlicek, Roman, Malý, Petr, Trakal, Lukáš, Fiksa, Jan, Slovák, Matěj, Karlinski, Michal Adam, Nowak, Maciej, Sienkiewicz-Jarosz, Halina, Bochynska, Anna, Wrona, Pawel, Homa, Tomasz, Sawczynska, Katarzyna, Slowik, Agnieszka, Wlodarczyk, Ewa, Wiacek, Marcin, Tomaszewska-Lampart, Izabella, Sieczkowski, Bartosz, Bartosik-Psujek, Halina, Bilik, Marta, Bandzarewicz, Anna, Dorobek, Malgorzata, Zielinska-Turek, Justyna, Nowakowska-Kotas, Marta, Obara, Krystian, Urbanowski, Paweł, Budrewicz, Slawomir, Guziński, Maciej, Świtońska, Milena, Rutkowska, Iwona, Sobieszak-Skura, Paulina, Labuz-Roszak, Beata M., Debiec, Aleksander, Staszewski, Jacek, Stępień, Adam, Zwiernik, Jacek, Wasilewski, Grzegorz, Tiu, Cristina, Terecoasă, Elena Oana, Radu, Razvan Alexandru, Negrila, Anca, Dorobat, Bogdan, Panea, Cristina, Tiu, Vlad, Petrescu, Simona, Ozdemir, Atilla, Mahmoud, Mostafa, El-Samahy, Hussam, Abdelkhalek, Hazem, Al-Hashel, Jasem, Ismail, Ismail Ibrahim, Salmeen, Athari, Ghoreishi, Abdoreza, Sabetay, Sergiu Ionut, Gross, Hana, Klein, Piers, Abdalkader, Mohamad, Jabbour, Pascal, El Naamani, Kareem, Tjoumakaris, Stavropoula, Abbas, Rawad, Mohamed, Ghada A., Chebl, Alex, Min, Jiangyong, Hovingh, Majesta, Tsai, Jenney P., Khan, Muhib, Nalleballe, Krishna, Onteddu, Sanjeeva, Masoud, Hesham, Michael, Mina, Kaur, Navreet, Maali, Laith, Abraham, Michael G., Khandelwal, Priyank, Bach, Ivo, Ong, Melody, Babici, Denis, Khawaja, Ayaz M., Hakemi, Maryam, Rajamani, Kumar, Cano-Nigenda, Vanessa, Arauz, Antonio, Amaya, Pablo, Llanos, Natalia, Arango, Akemi, Vences, Miguel Ángel, Barrientos Guerra, Jose Dominguo, Caetano, Rayllene, Martins, Rodrigo Targa, Scollo, Sergio Daniel, Yalung, Patrick Matic, Nagendra, Shashank, Gaikwad, Abhijit, Seo, Kwon-Duk, Georgiopoulos, Georgios, Nogueira, Raul G., and Michel, Patrik

Published
2023
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12. Multi-physical contact simulation in Vehicle applications

Author

Schmid, Michal, Tomek, Petr, and Hanus, Petr

Abstract

Multi-physical contact behaviour is important in multiple disciplines related to the automotive industry. Nowadays battery-electric vehicles' (BEV) thermal management systems deal with contact between bodies where mechanical, electric, and thermal interaction occurs. The battery thermal management itself is crucial for cell life, safety, and everyday vehicle performance. Thus, comprehensive and accurate simulation of the multi-physical contact is a vital part of vehicle development. The multi-physical contact is represented by two or more bodies under applied mechanical load and a current or heat conducted throughout the realized contact area. The amount of conducted current/heat or generated Joule heat is the function of the contact area as well as contact pressure, thus the structural simulation should be essential for such thermal management system simulations Most of the current full vehicle battery pack CFD cooling simulations simplified the multi-physical contact as ideal. Detailed contact modelling is time-consuming, hence not applicable for the full vehicle modelling. In this work, a feasible approach based on contact resistance curves was implemented. Furthermore, the work demonstrates the necessity of correct structural contact prediction for a joule heating and thermal solution.

Published
2022
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13. Posterior National Institutes of Health Stroke Scale Improves Prognostic Accuracy in Posterior Circulation Stroke.

Author

Alemseged, Fana, Rocco, Alessandro, Arba, Francesco, Schwabova, Jaroslava Paulasova, Wu, Teddy, Cavicchia, Leone, Ng, Felix, Ng, Jo Lyn, Zhao, Henry, Williams, Cameron, Sallustio, Fabrizio, Balabanski, Anna H., Tomek, Ales, Parson, Mark W., Mitchell, Peter J. MMed, Diomedi, Marina, Yassi, Nawaf, Churilov, Leonid, Davis, Stephen M., and Campbell, Bruce C.V.

Published
2022
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14. Screening and Risk Stratification Strategy Reduced Decompression Sickness Occurrence in Divers With Patent Foramen Ovale.

Author

Honěk, Jakub, Šrámek, Martin, Honěk, Tomáš, Tomek, Aleš, Šefc, Luděk, Januška, Jaroslav, Fiedler, Jiří, Horváth, Martin, Novotný, Štěpán, Brabec, Marek, and Veselka, Josef

Abstract

This paper sought to evaluate the occurrence of decompression sickness (DCS) after the application of a patent foramen ovale (PFO) screening and risk stratification strategy. PFO is associated with an increased risk of DCS. Recently, transcatheter closure was reported to reduce DCS occurrence in divers with a high-grade shunt. However, to date, there are no data regarding the effectiveness of any PFO screening and risk stratification strategy for divers. A total of 829 consecutive divers (age 35.4 ± 10.0 years, 81.5% men) were screened for PFO by means of transcranial color-coded sonography in the DIVE-PFO (Decompression Illness Prevention in Divers with a Patent Foramen Ovale) registry. Divers with a high-grade PFO were offered either catheter-based PFO closure (the closure group) or advised conservative diving (high grades). Divers with a low-grade shunt were advised conservative diving (low grades), whereas those with no PFO continued unrestricted diving (controls). A telephone follow-up was performed. To study the effect of the screening and risk stratification strategy, DCS occurrence before enrollment and during the follow-up was compared. Follow-up was available for 748 (90%) divers. Seven hundred and 2 divers continued diving and were included in the analysis (mean follow-up 6.5 ± 3.5 years). The DCS incidence decreased significantly in all groups, except the controls. During follow-up, there were no DCS events in the closure group; DCS incidence was similar to the controls in the low-grade group (HR: 3.965; 95% CI: 0.558-28.18; P = 0.169) but remained higher in the high-grade group (HR: 26.170; 95% CI: 5.797-118.160; P < 0.0001). The screening and risk stratification strategy using transcranial color-coded sonography was associated with a decrease in DCS occurrence in divers with PFO. Catheter-based PFO closure was associated with a DCS occurrence similar to the controls; the conservative strategy had a similar effect in the low-grade group, but in the high-grade group the DCS incidence remained higher than in all other groups. [Display omitted] [ABSTRACT FROM AUTHOR]

Published
2022
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16. Posterior National Institutes of Health Stroke Scale Improves Prognostic Accuracy in Posterior Circulation Stroke

Author

Alemseged, Fana, Rocco, Alessandro, Arba, Francesco, Schwabova, Jaroslava Paulasova, Wu, Teddy, Cavicchia, Leone, Ng, Felix, Ng, Jo Lyn, Zhao, Henry, Williams, Cameron, Sallustio, Fabrizio, Balabanski, Anna H., Tomek, Ales, Parson, Mark W., Mitchell, Peter J., Diomedi, Marina, Yassi, Nawaf, Churilov, Leonid, Davis, Stephen M., and Campbell, Bruce C.V.

Published
2022
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17. Validating TDP1 as an Inhibition Target for the Development of Chemosensitizers for Camptothecin-Based Chemotherapy Drugs

Author

Leung, Euphemia, Patel, Jinal, Hollywood, Jennifer A., Zafar, Ayesha, Tomek, Petr, Barker, David, Pilkington, Lisa I., van Rensburg, Michelle, Langley, Ries J., Helsby, Nuala A., Squire, Christopher J., Baguley, Bruce C., Denny, William A., Reynisson, Jóhannes, and Leung, Ivanhoe K. H.

Abstract

Cancer chemotherapy sensitizers hold the key to maximizing the potential of standard anticancer treatments. We have a long-standing interest in developing and validating inhibitors of the DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (TDP1) as chemosensitizers for topoisomerase I poisons such as topotecan. Herein, by using thieno[2,3-b]pyridines, a class of TDP1 inhibitors, we showed that the inhibition of TDP1 can restore sensitivity to topotecan, results that are supported by TDP1 knockout cell experiments using CRISPR/Cas9. However, we also found that the restored sensitivity towards topoisomerase I inhibitors is likely regulated by multiple complementary DNA repair pathways. Our results showed that one of these pathways is likely modulated by PARP1, although it is also possible that other redundant and partially overlapping pathways may be involved in the DNA repair process. Our work thus raises the prospect of targeting multiple DNA repair pathways to increase the sensitivity to topoisomerase I inhibitors.

Published
2021
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19. A Complex Interplay Between Pluton Emplacement, Tectonic Deformation, and Plate Kinematics in the Cretaceous Sierra Nevada Magmatic Arc, California

Author

Tomek, Filip, Žák, Jiří, Verner, Kryštof, Ježek, Josef, and Paterson, Scott R.

Abstract

The relation of plate kinematics to the structural record of arc plutons and their host rocks is complex and still not fully understood. We address this issue through a combination of field mapping, structural analysis, anisotropy of magnetic susceptibility analysis, and fabric modeling in the Late Cretaceous Tuolumne Intrusive Complex, Sierra Nevada, California. A pattern of anti‐clockwise rotation from ∼NNW–SSE to WNW–ESE steep foliations and change in fabric ellipsoid shape from oblate to prolate was revealed in successively emplaced Kuna Crest (∼95–92 Ma), Half Dome (∼92–89 Ma), and Cathedral Peak (∼89–84 Ma) granodiorites. The numerical model indicates that the Kuna Crest was emplaced in a transpressional setting with an angle of convergence α= 60–40°, whereas the Half Dome and Cathedral Peak required simultaneous vertical constriction overprinted by transpression with α= 35–15°. This transition, which occurred at ∼92 Ma, is accompanied by a shallowing of the lineation plunge observed also in other ∼88–84 Ma central Sierra Nevada plutons. Provided that the Cretaceous Sierra Nevada arc was constructed during overall dextral transpression, these transitions reflect significant changes in kinematics, where ∼107–92 Ma plutons were emplaced during pure shear‐dominated transpression, which was followed by a transition to wrench‐dominated transpression recorded in ∼92–84 Ma plutons. Such a transition in kinematics is explained as a result of progressively increasing obliquity of the relative convergence of the Farallon plate subducting beneath the North American continental margin, in agreement with most paleogeographic reconstructions. Field mapping, structural analysis, magnetic anisotropy, and fabric modeling were carried out in the Tuolumne Intrusive ComplexChanges in foliation strike, fabric symmetry, and lineation plunge imply a change in the angle of convergenceThe transition from pure shear to wrench‐dominated transpression reflects increasing convergence obliquity of the Farallon plate Field mapping, structural analysis, magnetic anisotropy, and fabric modeling were carried out in the Tuolumne Intrusive Complex Changes in foliation strike, fabric symmetry, and lineation plunge imply a change in the angle of convergence The transition from pure shear to wrench‐dominated transpression reflects increasing convergence obliquity of the Farallon plate

Published
2024
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20. The Invisible Force of Expectation: Angelina Grimke and the Dilemma of Self-Determination in the Early Women's Movement.

Author

TOMEK, BEVERLY C.

Abstract

A pioneer in the women's rights movement, Angelina Grimke is also known for retreating into the home after marrying fellow abolitionist Theodore Dwight Weld, just as her career was at its high point. Before her marriage, such male abolitionists as William Lloyd Garrison and H. C. Wright tried to shape Grimke's career, deliberately or unwittingly ignoring their own patriarchal tendencies toward her. Similarly, fellow abolitionists and historians alike have mourned Grimke's retreat to domestic life as a loss to the antislavery and women's rights movements. Despite outside pressure, Grimke made her own decisions and continued to contribute significantly to the antislavery cause on her own terms, even after she left the lecture circuit. By choosing her own path, Grimke made the ultimate argument for a woman's right to self-determination. [ABSTRACT FROM AUTHOR]

Published
2020
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21. High-grade patent foramen ovale is a risk factor of unprovoked decompression sickness in recreational divers.

Author

Honěk, Jakub, Šrámek, Martin, Šefc, Luděk, Januška, Jaroslav, Fiedler, Jiří, Horváth, Martin, Tomek, Aleš, Novotný, Štěpán, Honěk, Tomáš, and Veselka, Josef

Abstract

• Unprovoked decompression sickness occurs in divers. • High-grade patent foramen ovale (PFO) is a major risk factor. • PFO is a highly prevalent condition in the general population. • Current decompression recommendations might be less safe for divers with a PFO. Patent foramen ovale (PFO), male sex, age, and body mass index (BMI) were all identified as potential risk factors of decompression sickness (DCS). It has been debated whether PFO might cause unprovoked DCS (i.e. without violation of decompression procedure) due to paradoxical embolization of venous gas emboli. To date, there are no data on the incidence or risk factors of unprovoked DCS. This study sought to evaluate the risk factors of unprovoked DCS in recreational divers. A total of 489 consecutive divers were screened for PFO between January 2006 and January 2014 by means of transcranial Doppler. All patients were prospectively included in the study registry. Survival analysis techniques were used to assess for risk factors for unprovoked DCS. Age, sex, BMI, PFO presence, and grade were analyzed. The total sum of dives was used as a measure of time. The group performed a total of 169,411 dives (mean 346 ± 636). Thirty-six (7%) of the divers suffered from an unprovoked DCS. The frequency of PFO was 97.2% in divers with a history of unprovoked DCS and 35.5% in controls (p < 0.001). There was no difference in sex, age, BMI, or total number of dives between the respective groups. In the adjusted Cox proportional hazards model, PFO grade 3 was a major risk factor for unprovoked DCS; there was a slight protective effect of increasing age. We demonstrated that a high-grade PFO was a major risk factor for unprovoked DCS in recreational scuba divers. [ABSTRACT FROM AUTHOR]

Published
2019
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24. Assessment of Pharmacokinetic Interaction Between Letermovir and Fluconazole in Healthy Participants

Author

Adedoyin, Adedayo, Fancourt, Craig, Menzel, Karsten, Zhao, Tian, Tomek, Charles, Panebianco, Deborah, McCrea, Jacqueline B., Stoch, S. Aubrey, and Iwamoto, Marian

Abstract

Letermovir is a prophylactic agent for cytomegalovirus infection and disease in adult cytomegalovirus‐seropositive recipients of allogeneic hematopoietic stem cell transplant. As the antifungal agent fluconazole is administered frequently in transplant recipients, a drug–drug interaction study was conducted between oral letermovir and oral fluconazole. A phase 1 open‐label, fixed‐sequence study was performed in healthy females (N = 14, 19‐55 years). In Period 1, a single dose of fluconazole 400 mg was administered. Following a 14‐day washout, a single dose of letermovir 480 mg was administered (Period 2), and after a 7‐day washout, single doses of fluconazole 400 mg and letermovir 480 mg were coadministered in Period 3. Pharmacokinetics and safety were evaluated. The pharmacokinetics of fluconazole and letermovir were not meaningfully changed following coadministration. Fluconazole geometric mean ratio (GMR; 90% confidence interval [CI]) with letermovir for area under the concentration‐versus‐time curve from time 0 to infinity (AUC0‐∞) was 1.03 (0.99‐1.08); maximum concentration (Cmax) was 0.95 (0.92‐0.99). Letermovir AUC0‐∞GMR (90%CI) was 1.11 (1.01‐1.23), and Cmaxwas 1.06 (0.93‐1.21) following coadministration with fluconazole. Coadministration of fluconazole and letermovir was generally well tolerated.

Published
2021
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25. Insights into the genetic architecture of the human face

Author

White, Julie D., Indencleef, Karlijne, Naqvi, Sahin, Eller, Ryan J., Hoskens, Hanne, Roosenboom, Jasmien, Lee, Myoung Keun, Li, Jiarui, Mohammed, Jaaved, Richmond, Stephen, Quillen, Ellen E., Norton, Heather L., Feingold, Eleanor, Swigut, Tomek, Marazita, Mary L., Peeters, Hilde, Hens, Greet, Shaffer, John R., Wysocka, Joanna, Walsh, Susan, Weinberg, Seth M., Shriver, Mark D., and Claes, Peter

Abstract

The human face is complex and multipartite, and characterization of its genetic architecture remains challenging. Using a multivariate genome-wide association study meta-analysis of 8,246 European individuals, we identified 203 genome-wide-significant signals (120 also study-wide significant) associated with normal-range facial variation. Follow-up analyses indicate that the regions surrounding these signals are enriched for enhancer activity in cranial neural crest cells and craniofacial tissues, several regions harbor multiple signals with associations to different facial phenotypes, and there is evidence for potential coordinated actions of variants. In summary, our analyses provide insights into the understanding of how complex morphological traits are shaped by both individual and coordinated genetic actions.

Published
2021
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27. Low incidence of SARS-CoV-2, risk factors of mortality and the course of illness in the French national cohort of dialysis patients

Author

Couchoud, Cécile, Bayer, Florian, Ayav, Carole, Béchade, Clémence, Brunet, Philippe, Chantrel, François, Frimat, Luc, Galland, Roula, Hourmant, Maryvonne, Laurain, Emmanuelle, Lobbedez, Thierry, Mercadal, Lucile, Moranne, Olivier, Abbassi, Abdelhamid, Debure, Alain, Guerraoui, Abdallah, Benmoussa, Abdelatif, Hamani, Abdelaziz, Ziane, Abdelaziz, Nefti, Abdelhamid, Hadj, Abdelkader, El Amari, Abderrahim, Ghazali, Abderrahmane, Abd El Fatah Mohamed, Abo Bakr, Laradi, Achour, Ben Ahmed, Adel, Sahar, Adel, Pillet, Adele, Lacraz, Adeline, Moinat, Adnan, Massoumi, Afshin, Pardon, Agathe, Beaudoin, Agnes Caillette, Debout, Agnes Chapelet, Mariot, Agnes, Rachi, Ahmed, Afiani, Aida, Boula, Aime Remy, Jalaby, Al, Cremault, Alain, Fournier, Alain, Jeanson, Alain, Lyon, Alain, Nony, Alain, Robert, Alain, Slingeneyer, Alain, Labatide, Alanor Agnes, Sartorius, Albane Brodin, Bensman, Albert, Fournier, Albert, Ranlin, Alex, Sandor, Alex Vido, Colombo, Alexandra, Duhem, Alexandra, Stancu, Alexandra, Dufay, Alexandre, Dumoulin, Alexandre, Ebel, Alexandre, Klein, Alexandre, Martin, Alexandre, Mouneimne, Alexandre, Seidowsky, Alexandre, De Martin, Alfio, Zannier, Alfredo, Aizel, Ali, Hafi, Ali, Diddaoui, Ali Zineddine, Heyani, Alim, Mocanu, Alina, Preda, Alina, Hafi, Aline, Talaszka, Aline, Duquesne, Alyette, Amaouche, Amar, Ghemmour, Amel, Simon, Amelie, Skalli, Amina, Boukadida, Amine, Ragab Eid, Amr Ekhlas, Fedorca, Ana, Baillet, Anabelle, Poyet, Anais, Giorgita, Ancuta Bouffandeau, Ratsimbazafy, Anderson, Pruna, Andre, Argiles, Angel, Testa, Angelo, Vandooren, Ann Karolien, Jolivot, Anne, Labadens, Anne Kolko, Lataste, Anne, Maisin, Anne, Paris, Anne, Sechet, Anne, Wuillai, Anne, Heng, Anne Elisabeth, Josse, Anne Gaelle, Querard, Anne Helene, Reboux, Anne Helene, Adra, Anne Laure, Faller, Anne Laure, Leclerc, Anne Laure, Poitou, Anne Laure, Manucci, Annie Lahoche, Jacquet, Antoine, Pommereau, Antoine, Thierry, Antoine, Adem, Arezki, Chapelet, Arielle, Del Bello, Arnaud, Delezire, Arnaud, Garnier, Arnaud, Guerard, Arnaud, Klisnick, Arnaud, Lionet, Arnaud, Roccabianca, Arnaud, Stolz, Arnaud, Capdeville, Arthur, Allal, Asma, Alrifai, Assem, Diarrassouba, Assetou, Djema, Assia, Carre, Assia Ferhat, Dubrasquet, Astrid Godron, Elmrabet, Atman Haddj, Jegado, Audrey, Thomas, Aurelia Bertholet, Salandre, Aurelie Davourie, Pajot, Aurelie, Lorthioir, Aurelien, Tiple, Aurelien, Sury, Aurore, Abokasem, Ayman, Sarraj, Ayman, Henaoui, Bachir, Chaghouri, Baher, Wehbe, Bassem, Ball, Beatrice, Viron, Beatrice, Issad, Belkassem, Corne, Benedicte Hodemon, Janbon, Benedicte, Deroure, Benjamin, Savenkoff, Benjamin, Jonon, Benoit, Vendrely, Benoit, Djelaleddine, Benyakoub, Ohry, Bernard, Painchart, Bernard, Strullu, Bernard, Temperville, Bernard, Ebikili, Bertin, Hacq, Bertrand, Morel, Bertrand, Aoun, Bilal, Muniz, Blanca, Chlih, Bouchra, Amara, Brahim, Mayor, Brice, Gilson, Brigitte, Llanas, Brigitte, Zins, Brigitte, Bourgeon, Bruno, Coevoet, Bruno, Guery, Bruno, Legallicier, Bruno, Paris, Bruno, Ranchin, Bruno, Seigneuric, Bruno, Dita, Camelia Ghiciuc, Prelipcean, Camelia, Hottelart, Carine Achard, Diet, Carine, Frangie, Carlos, Vela, Carlos, Muresan, Carmina, Deprele, Carole, Araujo, Caroline, Bidault, Caroline, Creput, Caroline, Delclaux, Caroline, Du Halgouet, Caroline, Favennec, Caroline, Freguin, Caroline, Vercel, Caroline Gourraud, Mesguen, Caroline, Obama, Caroline Ndomo, Poitou, Caroline, Dirhold, Caroline Preissig, Roubiou, Caroline, Albert, Catherine, Bessin, Catherine, De Marion Gaja, Catherine, Godart, Catherine, Lasseur, Catherine, Leocardi, Catherine, Lumbroso, Catherine, Melander, Catherine, Michel, Catherine, Maurouard, Catherine Quere, Rouannet, Catherine, Taddei, Catherine, Verove, Cathy, Guiraud, Cecile, Tafelin, Cecile, Baron, Cecile Turc, Formet, Cedric, Pinier, Cedric, De Ste Foy, Celia Lessore, Granolleras, Celine, Bennini, Chaouki, Cartou, Charles, Chazot, Charles, Jouzel, Charlotte, Badid, Cherif, Roubicek, Christa, Viaud, Christel, Verrier, Christelle, Chuet, Christian, Combe, Christian, Dabot, Christian, Duvic, Christian, Emond, Christian, Lagarde, Christian, Lamotte, Christian, Pain, Christian, Mousson, Christiane, Lorriaux, Christie, Beauchamp, Christine, Fumeron, Christine, Le Gurun, Christine, Leroy, Christine, Pietrement, Christine, Richer, Christine, Bouaka, Christophe, Charasse, Christophe, Goupy, Christophe, Ridel, Christophe, Castrale, Cindy, Detourne, Cindy, Francois, Clair, Presne, Claire, Trivin, Claire, Von Kotze, Clarissa, Bernard, Claude, Bonniol, Claude, Desvergnes, Claude, Raharivelina, Claude, Nistor, Claudia, Gueret, Claudine, Lloret, Claudine, Saltiel, Claudine, Rosati, Clelia, Rabate, Clementine, Stanescu, Corina, Ferrandini, Corinne, Guibergia, Corinne, Lemoine, Corinne, Passeron, Corinne, Kahil, Cynthia, Garrouste, Cyril, Van, Cyril Vo, Jolimoy, Cyrille, Kesraoui, Dalila, Jolly, Damien, Thibaudin, Damien, Teboulle, Dan, Daubresse, Daniel, Louvet, Daniel, Rasamimanantsoa, Daniel, Toledano, Daniel, Babici, Daniela, David, Daniela, Dincu, Daniela, Bruno, Danielle, May, Delia, Haussaire, Delphine, Viprey, Delphine Henriet, Bugnon, Denis, Fouque, Denis, Morin, Denis, Nour, Derradji, Mahmoud, Diab Mohamed, Cristescu, Diana Istrati, Aguilera, Didier, Coste, Didier, Hamel, Didier, Le Chapois, Didier, Testou, Didier, Erbilgin, Dilaver, Dahmane, Djamal, Quang, Doan Bui, Bertrand, Dominique, Besnier, Dominique, Blanchier, Dominique, Briffa, Dominique, Caux, Dominique, Durand, Dominique, Fleury, Dominique, Guerrot, Dominique, Hestin, Dominique, Jaubert, Dominique, Joly, Dominique, Lombart, Dominique, Pagniez, Dominique, Pierre, Dominique, Schohn, Dominique, Ikonga, Donatien, Visanica, Dorina, Bazin, Dorothee, Boury, Edouard, Maksour, Edouard, Agbonon, Ekoue, Harrami, Elarbi, Marcu, Elena, Tudorache, Elena, Caniot, Elisabeth, Semjen, Elisabeth, Tomkiewicz, Elisabeth, Scheidt, Elise, Gaboriau, Elke, Lamouroux, Elodie, Guiard, Elsa, Passos, Elsa Martin, Nsembani, Emerson, Fache, Emilie, Kalbacher, Emilie, Pambrun, Emilie, Pincon, Emilie, Launay, Emma Allain, Baron, Emmanuel, Dupuis, Emmanuel, Villar, Emmanuel, Charlin, Emmanuelle, Hecquet, Emmanuelle, Kohler, Emmanuelle, Laurain, Emmanuelle, Rosier, Emmanuelle, Figueroa, Enrique, Azoulay, Eric, Canivet, Eric, Daugas, Eric, Gauthier, Eric, Laruelle, Eric, Le Guen, Eric, Legrand, Eric, Moumas, Eric, Postec, Eric, Prinz, Eric, Renaudineau, Eric, Desport, Estelle, Sutra, Estelle Ricard, Berard, Etienne, Ged, Etienne, Robin, Etienne, Vilaine, Eve, Bargas, Evelyne, Namara, Evelyne Mac, Combarnous, François, Yazbeck, Fatima, Gerard, Fabien, Metivier, Fabien, Parazols, Fabien, Soulis, Fabien, Garnier, Fabrice, Messaoudene, Fadhila Pech, Haidar, Fadi, Boullenger, Fanny, Lepeytre, Fanny, Leroy, Fanny, Frejate, Fares, Bellahsene, Farid, Bellhasene, Farid, Saidani, Farid, Toure, Fatouma, Kriaa, Faycal, Nemmar, Fazia, Vetromile, Fernando, Chalmin, Florence, Lucats, Florence, Sens, Florence, Villemain, Florence, Plasse, Florent, Lebhour, Fouad, Schillinger, Francis, Berge, Franck, Bourdon, Franck, Bridoux, Franck, Reynaud, Franck, Babinet, Francois, Basse, Francois, Chantrel, Francois, Clair, Francois, Coulomb, Francois, De Cornelissen, Francois, Glowacki, Francois, Marchal, Francois, Maurice, Francois, Nobili, Francois, Pourreau, Francois, Provot, Francois, Amani, Francois Roux, Broux, Francoise, Bulte, Francoise, Heibel, Francoise, Leonetti, Francoise, Schott, Francoise Moussion, Le Roy, Frank, Besson, Frederic, Lavainne, Frederic, Tollis, Frederic, Bocquentin, Frederique, Meeus, Frederique, Vecina, Frederique, Von Ey, Friederike, Balit, Gabriel, Choukroun, Gabriel, Gruget, Gabriel, Huchard, Gabriel, Golea, Gabriella, Duneau, Gabrielle, Lefrancois, Gaelle, Pelle, Gaelle, Lebrun, Gaetan, Dumont, Genevieve, Brillet, Georges, Deschenes, Georges, Mourad, Georges, Stamatakis, Georges, Cazajous, Geraldine, D'ythurbide, Geraldine, Wiart, Geraldine Robitaille, Cardon, Gerard, Champion, Gerard, Deschodt, Gerard, Mangenot, Gerard, Motte, Gerard, Schortgen, Gerard, Boulahia, Ghada, Maakaroun, Ghassan, Michel, Ghylene Bourdat, Zanetta, Gilbert, Hufnagel, Gilles, Messier, Gilles, Piccoli, Giorgina, Desvergnes, Gregoire Couvrat, Bobrie, Guillaume, Bonnard, Guillaume, Clement, Guillaume, Jean, Guillaume, Queffeulou, Guillaume, Seret, Guillaume, Vernin, Guillaume, Delavaud, Guy, Lambrey, Guy, Rostoker, Guy, Poussard, Gwenaelle, Kesler, Gwenaelle Roussey, Leon, H., Aboubekr, Habib, Boulechfar, Hacene, Sekhri, Hacene, Hebibi, Hadia, Benalia, Hadjira, Fessi, Hafed, Atchia, Hafsabhai, Bittar, Haiat, Maiza, Hakim, Mazouz, Hakim, El Ali, Hamid, Bougrida, Hammouche, Van Der Pijl, Hans, Lokmane, Hassan, Izzedine, Hassane, Adda, Hassen, De Preneuf, Helene, Leray, Helene, Philippot, Helene, Boulanger, Henri, Merault, Henri, Renaud, Henri, Bonarek, Herve, Maheut, Herve, Nzeyimana, Hilaire, Mehama, Hocine, Zaidi, Hocine, Weclawiak, Hugo, Flodrops, Hugues, Karaaslan, Huseyin, Haskour, Ibrahim, Belhadj, Ihssen, Almoubarak, Imad, Haddad, Imad, Castellano, Ines, Ferrandiz, Ines, Daniliuc, Ioana, Darie, Ioana, Enache, Ioana, Prunescu, Ionut, Djiconkpode, Irenee, Shahapuni, Irina, Bouchoule, Isabelle, Devriendt, Isabelle, Kazes, Isabelle, Kolb, Isabelle, Landru, Isabelle, Poli, Isabelle, Rey, Isabelle, Segalen, Isabelle, Selcer, Isabelle, Vernier, Isabelle, Vrillon, Isabelle, Guenifi, Ismahane, Gheerbrandt, J. Dominique, Potier, Jacky, Becart, Jacques, Cledes, Jacques, Ducros, Jacques, Duvic, Jacques, Fourcade, Jacques, Gaultier, Jacques, Jurine, Jacques, Lebleu, Jacques, Ollier, Jacques, Charles, Jacques Ibsen, Yazji, Jamal, Mansour, Janette, Arnautou, Jean, Brocard, Jean, Carolfi, Jean, Montoriol, Jean, Gouin, Jean Baptiste, Palcoux, Jean Bernard, Bendini, Jean Christophe, Aldigier, Jean Claude, Alphonse, Jean Claude, Delbet, Jean Daniel, Bonne, Jean Francois, Cantin, Jean Francois, De Fremont, Jean Francois, Dessassis, Jean Francois, Subra, Jean Francois, Valentin, Jean Francois, Verdier, Jean Francois, Dion, Jean Jacques, Haultier, Jean Jacques, Montseny, Jean Jacques, Bacri, Jean Louis, Bouchet, Jean Louis, Mahe, Jean Luc, Chalopin, Jean Marc, Gabriel, Jean Marc, Hurot, Jean Marc, Lanau, Jean Marc, Batho, Jean Marie, Coulibaly, Jean Marie, Hardin, Jean Michel, Marc, Jean Michel, Poux, Jean Michel, Rebibou, Jean Michel, Tivollier, Jean Michel, Ottavioli, Jean Noel, Faucon, Jean Paul, Imiela, Jean Paul, Jaulin, Jean Paul, Masselot, Jean Paul, Ortiz, Jean Paul, Bourdenx, Jean Philippe, Devaux, Jean Philippe, Hammelin, Jean Philippe, Rivory, Jean Pierre, Wauquier, Jean Pierre, Larue, Jean Rene, Mondain, Jean Rene, Borde, Jean Sebastien, Virot, Jean Simon, Bosc, Jean Yves, Achiche, Jedjiga, Parasote, Jennifer, Diolez, Jeremie, Harambat, Jerome, Potier, Jerome, Sampol, Jerome, Mustel, Jihad, Lefevre, Jean Jacques, Maurizi, Jocelyne, Gamberoni, Joel, Claudeon, Joelle, Terzic, Joelle, Rogol, Joffrey, Sayegh, Johnny, Cardozo, Jorge, Brasseur, Jose, Guiserix, Jose, Barsumau, Joseph, Albaret, Julie, Beaume, Julie, Attias, Julie Sohier, Dehay, Julien, Hogan, Julien, Journet, Julien, Ott, Julien, Baleynaud, Juliette, Bacchetta, Justine, Faucher, Justine, Yousfi, Kamel, Dardim, Karim, Clabault, Karine, Moreau, Karine, Thomas, Kedna, Sirajedine, Khaled, Chedid, Khalil, El Kaeoui, Khalil, El Karoui, Khalil, Bouachi, Khedidja, Hue, Kheira, El Nasser, Khuzama, Akposso, Kodso, Kunz, Kristian, Bijak, Krzysztof, Kihal, Lilia, Rasoloarijaona, L., Harbouche, Laid, Bencheikh, Larbi, Lamriben, Larbie, Hanafi, Latifa, Parvez, Laura Braun, Champion, Laure, Croze, Laure, Eprinchard, Laure, Patrier, Laure, Nicolet, Laurence, Vrigneaud, Laurence, Duflot, Laurent, Mackaya, Leandre, Chenine, Leila, Odry, Leon, Tamiji, Lili Taghipour, Bouzar, Lilia Antri, Nga Messi, Liliane Ngango, Le Mouellic, Lionel, Mandart, Lise, Weis, Lise, Pouteau, Lise Marie, Georgieva, Lora, Vitanova, Lorita, Chalabi, Lotfi, Delvallez, Luc, Frimat, Luc, Fromentin, Luc, Marty, Luc, Monjot, Luc, Spataru, Luciana, Bessenay, Lucie, Boissinot, Lucie, Wajsbrot, Lucie, Rakoff, Lucien, Lebourg, Ludivine, Perez, Lydie, Lafage, Lyliane, Azzouz, Lynda, Dumoulin, Madeleine, Ouziala, Messaoud, Joseph, Maan, Brahimi, Mabrouk, Fat, Maeva Wong, Fort, Magalie, Nakhla, Magued, Abtahi, Mahdi, Albadawy, Mahen, Alouach, Mahmoud, Mezghani, Mahmoud, Daroux, Maite, Boukelmoune, Maklouf, Dhib, Malek, Touam, Malik, Dubau, Malina, Balde, Mamadou, Khoa, Man Nguyen, Ismer, Manfred, Mehdi, Manolie, Laforet, Manon, Bouiller, Marc, Eugene, Marc, Fila, Marc, Hazzan, Marc, Kribs, Marc, Ladriere, Marc, Lebot, Marc, Padilla, Marc, Souid, Marc, Marraoui, Marcel, Burbach, Maren, Manescu, Maria, Noguera Gonzalez, Maria Eugenia, Revenco, Mariana, Terrasse, Marianne, Essi, Marie, Macher, Marie Alice, Nogier, Marie Beatrice, Cazin, Marie Cecile, Schweitzer Camoin, Marie Christine, Thouret, Marie Christine, Hannaert, Marie Claude, Servel, Marie France, Chabannier, Marie Helene, Coudert Krier, Marie Jeanne, Catoliquot, Marie Noelle, Guillodo, Marie Paule, Gavard, Marie Sophie, Vairon Codaccioni, Marie Xaviere, Rabec, Marina, Freist, Marine, Gauthier, Marion, Lemaire, Marion, Mehrenberger, Marion, Venot, Marion, Pongas, Marios, Diant, Marlene Beaubrun, Levannier, Martial, Bertaux, Martine, Jablonski, Mathieu, Sacquepee, Mathieu, Dargelos, Mathilde, Lemoine, Mathilde, Tamain, Mathilde, Monge, Matthieu, Reberolle, Matthieu, Cousin, Maud, Francois, Maud, Baron, Maurice, Hoffmann, Maxime, Ingwiller, Maxime, Touzot, Maxime, Mohajer, Mederick, Maaz, Mehadji, Hanoy, Melanie, Marroc, Melanie, Cuny, Melodie, Van Der Straaten, Menno, Serveaux, Mf., Basteri, Michel, Chong, Michel Fen, Hecht, Michel, Massad, Michel, Normand, Michel, Olmer, Michel, Tolani, Michel, Tsimaratos, Michel, Hemery, Michele, Kessler, Michele, Esposito, Miguel, Shenouda, Milad, Kareche, Mimi, Khalili, Mina, Diaconita, Mirella, Rifard, Mohamad Khair, Aladib, Mohamed, Belmouaz, Mohamed, Brahim, Mohamed, Diouani, Mohamed, Cherif, Mohamed Fodil, Jamali, Mohamed, Maghlaoua, Mohamed, Meddeb, Mohamed, Ramdane, Mohamed, Rifaat, Mohamed, Islam, Mohamed Sharifull, Abbade, Mohamed Adnan, Amrandi, Mokhtar, Chawki, Mokhtar, Ciobotaru, Monica, Indrieis, Monica, Chanas, Monique, Hoarau, Monique, Tomeh, Monzer, Bellou, Moufida, Bouzernidj, Mouloud, Ammor, Mounia, Guergour, Mounir, Benzakour, Mountassir, Hachicha, Mourad, Coulibaly, Moussa, Smati, Mustafa, Al Morabiti, Mustapha, Amirou, Mustapha, Isnard, Myriam, Pastural, Myriam, Pujo, Myriam, Boumendjel, Nourredine, Majbri, Nabil, Goumri, Nabila, Mingat, Nadege, Bassilios, Nader, Kerkeni, Nadia, Sedrati, Nadia, Soltani, Nadia, Maroun, Nadine, Neyrat, Nadine, Luang, Nahn, El Esper, Najeh, Ammar, Naji, Ghali, Nasredine, Hamdini, Nasser, Noel, Natacha, Potelune, Natacha, Maisonneuve, Nathalie, Pertuiset, Nathalie, Raynal, Nathalie, Vittoz, Nathalie, Terki, Nazim, Castin, Nelly, Nankeu, Nestor, Bouvier, Nicolas, Keller, Nicolas, Legros, Nicolas, Peters, Nicolas, Quirin, Nicolas, Lefrancois, Nicole, Monnier, Nicole, Rance, Nicole, Bruckmann, Niels, Mertens, Noel, Lorcy, Nolwenn, Gilbert, Olivia, Coldefy, Olivier, Drouineau, Olivier, Dunand, Olivier, Fritz, Olivier, Imhoff, Olivier, Kourilsky, Olivier, Lavelle, Olivier, Moranne, Olivier, Papin, Olivier, Roques, Olivier, Le Maner, Ophelie, Benbrahim, Oussamah Fikri, Erina Torres, Pablo Antonio, Urena Torres, Pablo Antonio, Malvezzi, Paolo, Bindi, Pascal, Cluzel, Pascal, Fontanier, Pascal, Wheatley, Pascal, Depraetre, Pascale, Dubosq, Pascale, Halin, Pascale, Sebahoun, Pascale, Siohan, Pascale, Testevuide, Pascale, Deteix, Patrice, Nolen, Patrice, Hue, Patricia, Lemarchand, Patricia, Donnadieu, Patrick, Fievet, Patrick, Fohrer, Patrick, Francais, Patrick, Giraud, Patrick, Hallonet, Patrick, Henri, Patrick, Michaut, Patrick, Michaut, Patrick, Niaudet, Patrick, Pauly, Patrick, Thomas, Patrick, Deleaval, Patrik, Finielz, Paul, Stroumza, Paul, Yverneau, Paule Hardy, Caillard, Pauline, Palacin, Pedro, Aubertin, Perrine, Attias, Philippe, Brunet, Philippe, Chauveau, Philippe, Coindre, Philippe, Coste, Philippe, Dubot, Philippe, Fournier, Philippe, Hiernaux, Philippe, Jousset, Philippe, Yue Wah, Philippe Lan, Lang, Philippe, Le Cacheux, Philippe, Dupont, Philippe Martin, Michel, Philippe, Mirgaine, Philippe, Moriniere, Philippe, Nicoud, Philippe, Rieu, Philippe, Rousseau, Philippe, Sporer, Philippe, Thorel, Philippe, Vanhille, Philippe, Vigeral, Philippe, Zaoui, Philippe, Bataille, Pierre, Brignon, Pierre, Filipozzi, Pierre, Housset, Pierre, Peyronnet, Pierre, Ramperez, Pierre, Vautrin, Pierre, Michel, Pierre Alexandre, Westeel, Pierre Francois, Carron, Pierre Louis, Durand, Pierre Yves, Parent, Pierrot, Seniuta, Piotr, Kuentz, François, Fraoui, Rabah, Tetaz, Rachel, Amaria, Rachid, Bourouma, Rachid, Djeffal, Rachid, Nebbad, Rachida, Allal, Radia, Dimulescu, Radu, Boustani, Rafaat, Mesbah, Rafik, Makdassi, Raifat, Diab, Raji, Puslenghea, Raluca, Roura, Raoul, Khayat, Rateb, Azar, Raymond, Frayssinet, Raymond, Monkam, Regine, Boulahrouz, Rehouni, Boudet, Remi, Demontis, Renato, Gansey, Renaud, Cuvelier, Rene, Schmitt, Renee, Noordally, Reschad, Binaut, Reynald, Latif, Rezkallah, Dufresne, Richard, Montagnac, Richard, Reade, Richard, Genin, Robert, Novo, Robert, Fickl, Rocsana, Dufresne, Roger, Magnol, Roger, Issautier, Roland, Mortelette, Romain, Delaval, Ronan, Lohro, Ronan, M'barga, Roseline, Beau, S., Dupuis, Clémentine, Vidil, Marie Jacques, Hacini, Sabria, Dahmoune, Said, Lekhal, Saliha, Sakso, Salima Ahriz, Saksi, Salima, Citarda, Salvatore, Boubenider, Samir, Kassis, Samuel, Verhille, Sandra, Genestier, Sandrine, Muller, Sandrine, Krid, Saoussen, Richter, Sarah, Delbes, Sebastien, Mailliez, Sebastien, Veillon, Sebastien, Nony, Sébastien, Benarbia, Seddick, Beaudreuil, Severine, Benyaghla, Sidi Ali, Duquennoy, Simon, Baluta, Simona, Boncila, Simona, Mzoughi, Sonia, Ribal, Sonia, Acamer, Sophie, Chauvet, Sophie, Girerd, Sophie, Ozenne, Sophie, Parahy, Sophie, Duval, Sophie Rubens, Taque, Sophie, Menouer, Soraya, Chargui, Soumaya, Bataille, Stanislas, Barbier, Stephane, Billion, Stephane, Roueff, Stephane, Torner, Stephane, Martin, Stephane Jean, Coupel, Stephanie, Cloarec, Sylvie, Lavaud, Sylvie, Leou, Sylvie, Chatelet, T., Onesta, Tania, Benhabib, Tassadit, Bensalem, Tayeb, Dimulescu, Theodora, Sawadogo, Theophile, Hitze, Thibault Dolley, Baranger, Thierry, Boudemaghe, Thierry, Hannedouche, Thierry, Krummel, Thierry, Lobbedez, Thierry, Milcent, Thierry, Dervaux, Thomas, Guincestre, Thomas, Kofman, Thomas, Raphael, Thomas, Sadreux, Thomas, Ulinski, Tim, Roger, Tiphaine Guyon, Serrato, Tomas, Kofman, Tomek, Wong, Tony, Boubia, Toufik, Gbindoun, Ubald Assogba, Khuzaie, Usama, Caudwell, Valerie, Chatelet, Valerie, Crougneau, Valerie, De Precigout, Valerie, Drouillat, Valerie, Galantine, Valerie, Hugot, Valerie Granveau, Leroy, Valerie, Boubia, Veronique, Falque, Veronique, Fournier, Veronique, Queron, Veronique, Viviani, Veronique, Gueuttin, Victor, Panescu, Victor, Calonge, Victorio Menoyo, Nguyen, Viet, Allot, Vincent, Delattre, Vincent, Leduc, Vincent, Pradier, Vincent, Aglae, Violaine Emal, Badulescu, Viorica, Molina, Virginia, Besson, Virginie, Chaigne, Virginie, Jaber, Waddah, Boudi, Wael, El Haggan, Wael, Guillon, Wen Qin, Aneni, Wided Tabbi, Hanf, William, Kohn, Wladimir, Bellenfant, Xavier, Gaudry, Xavier Moreau, Delmas, Yahsou, Knefati, Yannick, Saingra, Yannick, Tirolien, Yannick, Mann, Youssef, Brunak, Yvan, Dimitrov, Yves, Doussy, Yves, Tanter, Yves, Benabid, Zaid, Soltani, Zaara, Boukerroucha, Zacharia, Takla, Zafer, Ramanantsialonina, Zana, Dickson, Zara, Tubail, Zead, Pour, Zoe Koochaki, Boukhalfa, Zohra, and Jacquot, Zohra

Abstract

The aim of this study was to estimate the incidence of COVID-19 disease in the French national population of dialysis patients, their course of illness and to identify the risk factors associated with mortality. Our study included all patients on dialysis recorded in the French REIN Registry in April 2020. Clinical characteristics at last follow-up and the evolution of COVID-19 illness severity over time were recorded for diagnosed cases (either suspicious clinical symptoms, characteristic signs on the chest scan or a positive reverse transcription polymerase chain reaction) for SARS-CoV-2. A total of 1,621 infected patients were reported on the REIN registry from March 16th, 2020 to May 4th, 2020. Of these, 344 died. The prevalence of COVID-19 patients varied from less than 1% to 10% between regions. The probability of being a case was higher in males, patients with diabetes, those in need of assistance for transfer or treated at a self-care unit. Dialysis at home was associated with a lower probability of being infected as was being a smoker, a former smoker, having an active malignancy, or peripheral vascular disease. Mortality in diagnosed cases (21%) was associated with the same causes as in the general population. Higher age, hypoalbuminemia and the presence of an ischemic heart disease were statistically independently associated with a higher risk of death. Being treated at a selfcare unit was associated with a lower risk. Thus, our study showed a relatively low frequency of COVID-19 among dialysis patients contrary to what might have been assumed.

Published
2020
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28. The Integration of BIM in Later Project Life Cycle Phases in Unprepared Environment from FM Perspective.

Author

Matějka, Petr, Kosina, Vít, Tomek, Aleš, Tomek, Radan, Berka, Vilém, and Šulc, Dalibor

Subjects
BUILDING information modeling, CONSTRUCTION projects, SERVICE life, ENVIRONMENTAL impact analysis, CONSTRUCTION industry
Abstract

The article examines the topic of Building Information Modeling (BIM) from the perspective of the owner in an environment that was not prepared correctly for later BIM integration. The paper explains possible benefits of BIM in later project life cycle phases, even when there is no proper BIM environment from preceding phases. The paper also presents three simple case studies of various projects in later project life cycle phases. The BIM model was utilized in these projects for various reasons. The end of the paper presents lessons that were learned and most important findings. [ABSTRACT FROM AUTHOR]

Published
2016
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29. The Invisible Force of Expectation: Angelina Grimke and the Dilemma of Self-Determination in the Early Women's Movement

Author

Tomek, Beverly C.

Abstract

Abstract:A pioneer in the women's rights movement, Angelina Grimke is also known for retreating into the home after marrying fellow abolitionist Theodore Dwight Weld, just as her career was at its high point. Before her marriage, such male abolitionists as William Lloyd Garrison and H. C. Wright tried to shape Grimke's career, deliberately or unwittingly ignoring their own patriarchal tendencies toward her. Similarly, fellow abolitionists and historians alike have mourned Grimke's retreat to domestic life as a loss to the antislavery and women's rights movements. Despite outside pressure, Grimke made her own decisions and continued to con-tribute significantly to the antislavery cause on her own terms, even after she left the lecture circuit. By choosing her own path, Grimke made the ultimate argument for a woman's right to self-determination.

Published
2020

30. First-in-human clinical trial to assess pharmacokinetics, pharmacodynamics, safety, and tolerability of iscalimab, an anti-CD40 monoclonal antibody

Author

Espié, Pascal, He, YanLing, Koo, Phillip, Sickert, Denise, Dupuy, Cyrielle, Chokoté, Edwige, Schuler, Roland, Mergentaler, Heidi, Ristov, Jacinda, Milojevic, Julie, Verles, Aurelie, Groenewegen, Andrea, Auger, Anita, Avrameas, Alexandre, Rotte, Michael, Colin, Laurence, Tomek, Charles S., Hernandez-Illas, Martha, Rush, James S., and Gergely, Peter

Abstract

Iscalimab is a fully human, CD40 pathway blocking, nondepleting monoclonal antibody being developed as an immunosuppressive agent. We describe a first-in-human, randomized, double-blind, placebo-controlled study investigating the safety, tolerability, pharmacokinetics, and pharmacodynamics of iscalimab in healthy subjects and rheumatoid arthritis patients. Healthy subjects (n = 56) received single doses of intravenous iscalimab (0.03, 0.1, 0.3, 1, or 3 mg/kg), or subcutaneous iscalimab (3 mg/kg), or placebo. Rheumatoid arthritis patients (n = 20) received single doses of intravenous iscalimab (10 or 30 mg/kg) or placebo. Iscalimab exhibited target-mediated drug disposition resulting in dose-dependent and nonlinear pharmacokinetics. Complete (≥90%) CD40 receptor occupancy on whole blood B cells was observed at plasma concentrations >0.3-0.4 µg/mL. In subjects receiving 3 mg/kg iscalimab, antibody responses to keyhole limpet hemocyanin were transiently suppressed. CD40 occupancy by iscalimab prevented ex vivo human rCD154-induced expression of CD69 on B cells in whole blood. All doses were generally safe and well tolerated, with no clinically relevant changes in any safety parameters, including no evidence of thromboembolic events. Iscalimab appears to be a promising blocker of the CD40-CD154 costimulatory pathway with potential use in transplantation and other autoimmune diseases.

Published
2020
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31. First‐in‐human clinical trial to assess pharmacokinetics, pharmacodynamics, safety, and tolerability of iscalimab, an anti‐CD40 monoclonal antibody

Author

Espié, Pascal, He, YanLing, Koo, Phillip, Sickert, Denise, Dupuy, Cyrielle, Chokoté, Edwige, Schuler, Roland, Mergentaler, Heidi, Ristov, Jacinda, Milojevic, Julie, Verles, Aurelie, Groenewegen, Andrea, Auger, Anita, Avrameas, Alexandre, Rotte, Michael, Colin, Laurence, Tomek, Charles S., Hernandez‐Illas, Martha, Rush, James S., and Gergely, Peter

Abstract

Iscalimab is a fully human, CD40 pathway blocking, nondepleting monoclonal antibody being developed as an immunosuppressive agent. We describe a first‐in‐human, randomized, double‐blind, placebo‐controlled study investigating the safety, tolerability, pharmacokinetics, and pharmacodynamics of iscalimab in healthy subjects and rheumatoid arthritis patients. Healthy subjects (n = 56) received single doses of intravenous iscalimab (0.03, 0.1, 0.3, 1, or 3 mg/kg), or subcutaneous iscalimab (3 mg/kg), or placebo. Rheumatoid arthritis patients (n = 20) received single doses of intravenous iscalimab (10 or 30 mg/kg) or placebo. Iscalimab exhibited target‐mediated drug disposition resulting in dose‐dependent and nonlinear pharmacokinetics. Complete (≥90%) CD40 receptor occupancy on whole blood B cells was observed at plasma concentrations >0.3‐0.4 µg/mL. In subjects receiving 3 mg/kg iscalimab, antibody responses to keyhole limpet hemocyanin were transiently suppressed. CD40 occupancy by iscalimab prevented ex vivo human rCD154‐induced expression of CD69 on B cells in whole blood. All doses were generally safe and well tolerated, with no clinically relevant changes in any safety parameters, including no evidence of thromboembolic events. Iscalimab appears to be a promising blocker of the CD40‐CD154 costimulatory pathway with potential use in transplantation and other autoimmune diseases. Iscalimab is a promising blocker of the CD40‐CD154 costimulatory pathway with potential use in transplantation and autoimmune diseases.

Published
2020
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32. Psychometric Evaluation of the Parentification Inventory–Swahili Version With Kenyan Adults: Factor Structure, Reliability, and Validity

Author

Hooper, Lisa M., Mugoya, George C. T., Burton, Shelby, and Tomek, Sara

Abstract

The immediate concerns and aftereffects of parentification in the United States are well documented. However, the correlates of parentification in international communities are less known. This psychometric study explored the validity of a Swahili version of the Parentification Inventory (PI; Hooper, 2009) with a sample of 279 Kenyan adults. Factor analysis produced a 3‐factor structure, but with fewer items (N= 17) than in the original PI (N= 22). Recommendations for using the PI–Swahili Version are discussed. Las preocupaciones inmediatas y las secuelas de la parentificación en los Estados Unidos están bien documentadas. Sin embargo, las correlaciones de la parentificación en comunidades internacionales son menos conocidas. Este estudio psicométrico exploró la validez de una versión en suajili del Inventario de Parentificación (PI, por sus siglas en inglés; Hooper, 2009) en una muestra de 279 kenianos adultos. El análisis factorial produjo una estructura de 3 factores, pero con menos elementos (N= 17) que en el PI original (N= 22). Se discuten recomendaciones para el uso de la versión en suajili del PI.

Published
2020
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35. Cytotoxic Lipopeptide Muscotoxin A, Isolated from Soil Cyanobacterium Desmonostoc muscorum, Permeabilizes Phospholipid Membranes by Reducing Their Fluidity

Author

Tomek, Petr, Hrouzek, Pavel, Kuzma, Marek, Sýkora, Jan, Fišer, Radovan, Černý, Jan, Novák, Petr, Bártová, Simona, Šimek, Petr, Hof, Martin, Kavan, Daniel, and Kopecký, Jiří

Abstract

There is mounting evidence that cyanobacterial lipopeptides can kill mammalian cells, presenting a hazard to human health. Unfortunately, their mechanism of toxicity is poorly understood. We have isolated new cyclic undeca-lipopeptides muscotoxin A and B containing unique lipophilic residue 3-amino-2,5-dihydroxydecanoic acid (5-OH Ahdoa). Muscotoxin B was not used for biological studies due to its poor yield. Muscotoxin A was cytotoxic to YAC-1, Sp/2, and HeLa cancer cell lines (LC50ranged from 9.9 to 13.2 μM after 24 h of exposure), causing membrane damage and influx of calcium ions. Subsequently, we studied this lytic mechanism using synthetic liposomes with encapsulated fluorescent probes. Muscotoxin A permeabilized liposomes composed exclusively of phospholipids, demonstrating that no proteins or carbohydrates present in biomembranes are essential for its activity. Paradoxically, the permeabilization activity of muscotoxin A was mediated by a significant reduction in membrane surface fluidity (stiffening), the opposite of that caused by synthetic detergents and cytolytic lipopeptide puwainaphycin F. At 25 °C, muscotoxin A disrupted liposomes with and without cholesterol/sphingomyelin; however, at 37 °C, it was selective against liposomes with cholesterol/sphingomyelin. It appears that both membrane fluidity and organization can affect the lytic activity of muscotoxin A. Our findings strengthen the evidence that cyanobacterial lipopeptides specifically disrupt mammalian cell membranes and bring new insights into the mechanism of this effect.

Published
2024
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36. Psychiatric comorbidity in African patients with epilepsy – Experience from Sierra Leone

Author

M’bayo, Tenema, Tomek, Michal, Kamara, Clifford, and Lisk, Durodami Radcliffe

Abstract

Epilepsy is associated with a significant burden of psychiatric comorbidity, including depression and anxiety disorders. However, paucity of data exists regarding the impact of epilepsy on mental health of patients in the setting of sub-Saharan Africa, where these comorbidities are under-recognized and under-treated. We carried out a cross-sectional descriptive study to investigate the prevalence and determinants of depression and anxiety among people with epilepsy in Sierra Leone.

Published
2024
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37. Multichannel segmentation of planar point clouds using evolving curves

Author

Tomek, Lukáš, Beran, Branislav, Erdélyi, Ján, Honti, Richard, and Mikula, Karol

Abstract

The paper deals with the multichannel curve segmentation of planar point clouds, scanned by a terrestrial laser scanner (TLS), which usually represent walls of buildings. Information derived from the point cloud can be used for quality check of a building (e.g. wall flatness or mutual perpendicularity of walls) or creation of virtual models of buildings. Therefore, segmentation of the planar point cloud into subsets representing the surface of the wall and other structures (e.g. door, electrical outlets) is desired. We describe a mathematical model of evolving planar curves, which is used for the segmentation of the point cloud. The evolution of curves is controlled by the properties of the scanned walls, such as colour and intensity. We discretize the model using the finite-volume method and the semi-implicit Inflow-Implicit/Outflow-Explicit (IIOE) scheme. We demonstrate the functionality of segmentation on real data.

Published
2023
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40. K charakterizaci anarchismu 19. století prostřednictvím jeho vybraných osobností.

Author

TOMEK, VÁCLAV

Abstract

In the second half of the 19th century, anarchism presents itself in certain characteristic signs and manifestations. Although the representatives of anarchism themselves willingly emphasize the originality of their ideas and their resistance to doctrine, their ideas come closer in the radical critique of economic and social relations, in the criticism of the Church and religion, as well as the sharp criticism of the other political parties, but at the same time they differ in their individual accents of their negation of the existing circumstances. The anarchistic level of their critique leads them from individual negation all the way to demands for a radical transformation of society, to different ideas about the nature of revolutionary behaviour, and the character of revolutionary change. From there, various forms and concepts of the future “post-revolution" society, visions of the anticipated freedom, on the character of the new social relations developed. For the characterization of the anarchism of the given period, the personalities of its French representative Pierre-Joseph Proudhon, the Russian revolutionary Mikhail Bakunin, the former German MP Johann Most, the original scientist Peter Kropotkin and the university educated German socialist Gustav Landauer and the entirely differently thinking Young Hegelian Max Stirner were chosen. [ABSTRACT FROM AUTHOR]

Published
2018

41. Intravenous Thrombolysis in Patients with Acute Ischemic Stroke after a Reversal of Dabigatran Anticoagulation with Idarucizumab: A Real-World Clinical Experience.

Author

Šaňák, Daniel, Jakubíček, Stanislava, Černík, David, Herzig, Roman, Kunáš, Zdeněk, Mikulík, Robert, Ostrý, Svatopluk, Reif, Michal, Rohan, Vladimír, Tomek, Aleš, and Veverka, Tomáš

Abstract

Background: Intravenous thrombolysis (IVT) is contraindicated in patients with acute ischemic stroke (AIS) using oral anticoagulants. A specific human monoclonal antibody was introduced to reverse immediately the anticoagulation effect of the direct inhibitor of thrombin, dabigatran. Until now, mostly individual cases presenting with successful IVT after a reversal of dabigatran anticoagulation in patients with AIS were published. Thus, we aimed to report real-world data from clinical practice.Methods: Patients with AIS on dabigatran treated with IVT after antidote reversal were enrolled in the retrospective nationwide study. Neurological deficit was scored using the National Institutes of Health Stroke Scale (NIHSS) and 90-day clinical outcome using modified Rankin scale (mRS) with a score 0-2 for a good outcome. Intracerebral hemorrhage (ICH) was defined as a presence of any sign of bleeding on control imaging after IVT, and symptomatic intracerebral hemorrhage (SICH) was assessed according to the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) criteria.Results: In total, 13 patients (7 men, mean age 70.0 ± 9.1 years) with a median NIHSS admission score of 7 points were analyzed. Of these patients, 61.5% used 2 × 150 mg of dabigatran daily. Antidote was administrated 427 ± 235 minutes after the last intake of dabigatran, with a mean activated prothrombin time of 38.1 ± 27.8 seconds and a mean thrombin time of 72.2 ± 56.1 seconds. Of the 13 patients, 2 had ICH and 1 had SICH, and no other bleeding complications were observed after IVT. Of the total number of patients, 76.9% had a good 3-month clinical outcome and 3 patients (23.1%) died. Recurrent ischemic stroke occurred in 2 patients (15.4%).Conclusion: The data presented in the study support the safety and efficacy of IVT after the reversal of the anticoagulation effect of dabigatran with antidote in a real-world clinical practice. [ABSTRACT FROM AUTHOR]

Published
2018
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43. Données actuelles sur les récidives des glomérulopathies après transplantation rénale.

Author

Kofman, Tomek, Oniszczuk, Julie, Lang, Philippe, Grimbert, Philippe, and Audard, Vincent

Abstract

Résumé La récidive d’une glomérulopathie après transplantation rénale est une cause fréquente de perte du greffon. L’incidence, les facteurs de risque et l’issue de la récurrence sont largement liés à la maladie glomérulaire sous-jacente. L’analyse de la biopsie du greffon est nécessaire afin de confirmer le diagnostic définitif de récidive et initier une thérapie appropriée qui reste dans certains cas un véritable challenge pour prévenir l’échec de la greffe. L’utilisation croissante des biopsies de protocole et les progrès récents dans notre compréhension de la pathogénie de certaines maladies glomérulaires avec l’identification de certains biomarqueurs d’intérêt offrent une occasion unique d’initier une thérapie de protection rénale aux stades précoces de la récidive sur la greffe. Cette revue résume nos connaissances actuelles sur la prise en charge de nombreuses glomérulonéphrites primaires et secondaires récurrentes après transplantation rénale. Recurrence of glomerular disease after renal transplantation is a frequent cause of graft loss. Incidence, risk factors and outcome of recurrence are widely due to the underlying glomerular disease. Graft biopsy analysis is required to confirm the definitive diagnosis of recurrence and to start an appropriate therapy that, in some cases, remains challenging to prevent graft failure. Increased use of protocol biopsy and recent advances in our understanding of the pathogenesis of some glomerular diseases with the identification of some relevant biomarkers provide a unique opportunity to initiate kidney-protective therapy at early stages of recurrence on the graft. This review summarizes our current knowledge on the management of many recurrent primary and secondary glomerulonephritis after kidney transplantation. [ABSTRACT FROM AUTHOR]

Published
2018
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44. LIFE WITH SOVIET TROOPS IN CZECHOSLOVAKIA AND AFTER THEIR WITHDRAWAL.

Author

Tomek, Prokop

Subjects
WAR victims, ARMED Forces
Abstract

The withdrawal of the Soviet Army from Czechoslovakia and dealing with its consequences has taken twenty-five years. Drawing mainly on archival sources, this contribution gives a short overview of the historical background, and the development and current situation of dealing with the difficult heritage of selected former military facilities. The foreign military presence deeply influenced the general attitude of the current Czech population towards foreign military presence. Among the many sites of Soviet military deployment, Milovice and Ralsko, discussed in this article, are distinctive examples, as they show both the opportunities for and limits of the recovery of former military sites. [ABSTRACT FROM AUTHOR]

Published
2017
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47. Warfarin loading dose guided by pharmacogenetics is effective and safe in cardioembolic stroke patients – a randomized, prospective study

Author

Ruzickova, Tereza, Sramek, Martin, Kaplan, Vojtech, Kumstyrova, Simona, Lacinova, Zuzana, Jansky, Petr, Magerova, Hana, Sarbochova, Ivana, Schwabova, Jaroslava Paulasova, Matoska, Vaclav, and Tomek, Ales

Abstract

Warfarin treatment is commonly started with a fixed loading dose that might be associated with an increased risk of bleeding. An individual maintenance dose can then be estimated based on a pharmacogenetic algorithm. Starting treatment with the estimated dose implies a longer time to reach the therapeutic range. Our goal was to compare the safety and efficacy of initiating warfarin treatment with a loading dose guided by pharmacogenetics versus a maintenance dose. The primary endpoint was time in the therapeutic range (TTR) in the first 10 days of treatment. Secondary endpoints were time to the first international normalized ratio (INR) in therapeutic range (2.0–3.0) and occurrence of serious adverse events. Consenting cardioembolic stroke patients were genotyped for CYP2C9(cytochrome P450 2C9 gene) and VKORC1(vitamin K epoxide reductase complex, subunit 1 gene) polymorphisms and a maintenance warfarin dose was estimated. Patients were randomized into two groups. The loading dose group (LDG) patients received twice the estimated dose in the first 2 days of treatment. The maintenance dose group (MDG) patients received the estimated dose directly from day one. The TTR in the first 10 days was significantly higher in the LDG than in the MDG (50.5% vs. 38.3%, p= 0.003). The time to the first INR in this range was significantly shorter in the LDG (5.24 vs. 7.3 days). There were no significant differences in the INR above this range or serious adverse events. Warfarin loading dose guided by pharmacogenetics after recent cardioembolic stroke improved the efficacy of warfarin initiation without increasing the risk of adverse events.

Published
2019
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49. An open-label randomized controlled trial of low-dose corticosteroid plus enteric-coated mycophenolate sodium versus standard corticosteroid treatment for minimal change nephrotic syndrome in adults (MSN Study)

Author

Rémy, Philippe, Audard, Vincent, Natella, Pierre André, Pelle, Gaëlle, Dussol, Bertrand, Leray-Moragues, Helene, Vigneau, Cecile, Bouachi, Khedidja, Dantal, Jacques, Vrigneaud, Laurence, Karras, Alexandre, Pourcine, Frank, Gatault, Philippe, Grimbert, Philippe, Ait Sahlia, Nawelle, Moktefi, Anissa, Daugas, Eric, Rigothier, Claire, Bastuji-Garin, Sylvie, Sahali, Dil, Aldigier, Jean Claude, Bataille, Pierre, Canaud, Bernard, Chauveau, Dominique, Combe, Christian, Choukroun, Gabriel, Cornec-Legall, Emilie, Dahan, Karine, Delahousse, Michel, Desvaux, Dominique, Deteix, Patrice, Durrbach, Antoine, Esnault, Vincent, Essig, Marie, Fievet, Patrick, Frouget, Thierry, Guerrot, Dominique, Godin, Michel, Gontiers-Picard, Annie, Gosselin, Morgane, Hanrotel-Saliou, Catherine, Heng, Anne-Elisabeth, Huart, Antoine, Humbert, Antoine, Kofman, Tomek, Hummel, Aurélie, Lang, Philippe, Laville, Maurice, Lemeur, Yannick, Malvezzi, Paolo, Matignon, Marie, Mesbah, Rafik, Moulin, Bruno, Muller, Sandrine, Olagne, Jerome, Pardon, Agathe, Provot, François, Queffeulou, Guillaume, Plaisier, Emmanuelle, Raimbourg, Quentin, Rieu, Philippe, Stehlé, Thomas, and Vanhille, Philippe

Abstract

First-line therapy of minimal change nephrotic syndrome (MCNS) in adults is extrapolated largely from pediatric studies and consists of high-dose oral corticosteroids. We assessed whether a low corticosteroid dose combined with mycophenolate sodium was superior to a standard oral corticosteroid regimen. We enrolled 116 adults with MCNS in an open-label randomized controlled trial involving 32 French centers. Participants randomly assigned to the test group (n=58) received low-dose prednisone (0.5 mg/kg/day, maximum 40 mg/day) plus enteric-coated mycophenolate sodium 720 mg twice daily for 24 weeks; those who did not achieve complete remission after week 8 were eligible for a second-line regimen (increase in the prednisone dose to 1 mg/kg/day with or without Cyclosporine). Participants randomly assigned to the control group (n=58) received conventional high-dose prednisone (1 mg/kg/day, maximum 80 mg/day) for 24 weeks. The primary endpoint of complete remission after four weeks of treatment was ascertained in 109 participants, with no significant difference between the test and control groups. Secondary outcomes, including remission after 8 and 24 weeks of treatment, did not differ between the two groups. During 52 weeks of follow-up, MCNS relapsed in 15 participants (23.1%) who had achieved the primary outcome. Median time to relapse was similar in the test and control groups (7.1 and 5.1 months, respectively), as was the incidence of serious adverse events. Five participants died from hemorrhage (n=2) or septic shock (n=3), including 2 participants in the test group and 3 in the control group. Thus, in adult patients, treatment with low-dose prednisone plus enteric-coated mycophenolate sodium was not superior to a standard high-dose prednisone regimen to induce complete remission of MCNS.

Published
2018
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50. Mutational signature distribution varies with DNA replication timing and strand asymmetry

Author

Tomkova, Marketa, Tomek, Jakub, Kriaucionis, Skirmantas, and Schuster-Böckler, Benjamin

Abstract

DNA replication plays an important role in mutagenesis, yet little is known about how it interacts with other mutagenic processes. Here, we use somatic mutation signatures—each representing a mutagenic process—derived from 3056 patients spanning 19 cancer types to quantify the strand asymmetry of mutational signatures around replication origins and between early and late replicating regions. We observe that most of the detected mutational signatures are significantly correlated with the timing or direction of DNA replication. The properties of these associations are distinct for different signatures and shed new light on several mutagenic processes. For example, our results suggest that oxidative damage to the nucleotide pool substantially contributes to the mutational landscape of esophageal adenocarcinoma. Together, our results indicate an interaction between DNA replication, the associated damage repair, and most mutagenic processes.

Published
2018
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