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13. Structure and dynamics of [Nb(η5-C5H4SiMe3) 2(η2-H2BR2)] (R2 = O2C6H4, C8H14, H2) complexes. A combined experimental and theoretical study

Author

Antiñolo, Antonio, Carrillo-Hermosilla, Fernando, Fernández-Baeza, Juan, García-Yuste, Santiago, Otero, Antonio, Rodríguez, Ana M., Sánchez-Prada, Javier, Villaseñor, Elena, Gelabert, Ricard, Lluch, José M., Lledós, Agustí, and Comisión Interministerial de Ciencia y Tecnología, CICYT (España) more...

Abstract

Dihydrogen elimination from the reaction of the niobocene trihydride Cp‘2NbH3 (Cp‘ = η5-C5H4SiMe3) and the appropriate borane provides a synthetic route to the new borate-containing niobocene complexes [Nb(η5-C5H4SiMe3)2(η2-H2BR2)] (R2 = O2C6H4 (1), C8H14 (2), H2 (3)). The reaction with H2BO2C6H4 or H2BC8H14 proceeds at mild temperature, and the BH3·THF adduct reacts even at low temperature. Complexes 2 and 3 show dynamic behavior in solution. Spectroscopic and theoretical studies were carried out in order to clarify these dynamic processes. In addition, X-ray diffraction studies of 2 were carried out and the results correlated with the theoretical data. Finally, reactions of Cp‘2Nb(H)(L) (L = CO, CN(2,6-Me2C6H3), tBuOOCHCHCOOtBu) with BH3·THF give rise to the complex 3, with the elimination of the appropriate ancillary ligand L., Financial support from the Spanish Comisión Interministerial de Ciencia y Tecnología (Projects PB98-0915, PB98-0916-CO2-01, and PB-95-0023-CO1-CO2) is acknowledged. more...

Published
2000

14. Insulin-Like Growth Factor-1 Increases Intracellular Calcium Concentration in Human Primary Neuroendocrine Pancreatic Tumor Cells and a Pancreatic Neuroendocrine Tumor Cell Line (BON-1) via R-Type Ca Channels and Regulates Chromogranin A Secretion in BON-1 Cells

Author

Mergler, Stefan, Strauss, Olaf, Strowski, Mathias, Prada, Javier, Drost, Adriana, Langrehr, Jan, Neuhaus, Peter, Wiedenmann, Bertram, and Ploeckinger, Ursula

Subjects
SOMATOMEDIN, CELLULAR control mechanisms, REGULATION of cell growth, GLANDS, BIOLOGICAL transport, NEUROENDOCRINE tumors, OLIGONUCLEOTIDES, HYPOGLYCEMIC agents
Abstract

Insulin-like growth factor 1 (IGF-1) is a potent mitogenic and secretory factor that acts on voltage operated Ca2+ channels (VOCCs). VOCCs are categorized into L-type channels (CaV1.1–1.4), P/Q-type channels (CaV2.1), N-type channels (CaV2.2), R-type channels (CaV2.3), and T-type channels (CaV3.1–3.3). Aside from regulating membrane excitability, VOCCs influence chromogranin A (CgA) secretion in neuroendocrine tumor (NET) cells. It is not known, whether VOCCs play a role in the IGF-1-dependent regulation of CgA secretion in NET cells. We therefore studied the effects of IGF-1 on individual VOCC subtypes and characterized their role in mediating IGF-1-dependent regulation of CgA secretion in NET cells. Using specific modulators of VOCC subtypes, we identified the functional expression of L-, N-, P/Q- and R-type channels in primary as well as permanent models of NET. The IGF-1-induced intracellular Ca2+ increase in NET cells was mainly due to the activation of R-type channel activity. The effects on intracellular calcium, observed in whole-cell patch-clamp recordings and fluorescence imaging, were partially blocked by the specific R-type channel blocker SNX-482 and antisense oligonucleotides against the α1 subunit of this channel. IGF-1 potently induced CgA secretion. The effect of IGF-1 was reduced by both, inhibition of R-type channel activity and a reduction of R-type channel expression using antisense oligonucleotides. Since R-type channels exist in NET cells and couple to both, IGF-1 receptor signaling as well as CgA secretion, pharmacological interference with R-type channels may represent a new therapeutic option by blocking Ca2+ signaling thereby abrogating IGF-1-dependent hypersecretion in NET disease. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR] more...

Published
2005
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16. Significant decreases of interleukin-1α gene expression after application of the serotonin receptor antagonist ondansetron are found to correlate with antiproliferative properties in the acute lymphoblastic leukemia cell line REH.

Author

Prada, Javier and Long, Huayan

Subjects
*LYMPHOBLASTIC leukemia, *GENE expression
Abstract

A letter to the editor is presented about antiproliferative properties in the acute lymphoblastic leukemia cell line REH.

Published
2015
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17. Clonal Diversity and Virulence Factors in Strains of Escherichia coli of the Classic Enteropathogenic Serogroup 0114.

Author

Beutin, Lothar, Ørskov, Ida, Ørskov, Frits, Zimmermann, Sonja, Prada, Javier, Gelderblom, Hans, Stephan, Rudolf, and Whittam, Thomas S.

Abstract

Eighty-eight Escherichia coli strains of the enteropathogenic (EPEC) group 0114 that were isolated from humans and animals in geographically different places and over more than 30 years were examined for virulence markers, O:H serotypes, and for electrophoretic types by multilocus enzyme electrophoresis. Four major genetically tightly related clusters of strains showed close correlation between electrophoretic types and other phenotypic characters. Cluster I contained 35 EPEe class II strains of serotypes 0114:H9 and 0114:H− and 5 enterotoxigenic E. coli belonging to 0114:H21 and 0114:H49. Clusters II and III comprised 36 0114:H4, 0114:H32, and 0114:H− strains; most were of doubtful pathogenicity except one Verotoxin-positive 0114:H4 strain isolated from a human with diarrhea. Cluster IV contained 9 classic EPEC strains of serogroup 0114:H2 that were characterized by localized adherence to HEp-2 cells and by the EPEC adherence factor. [ABSTRACT FROM PUBLISHER] more...

Published
1990

19. Upregulation of reactive oxygen and nitrogen intermediates in Plasmodium berghei infected mice after rescue therapy with chloroquine or artemether.

Author

Prada, Javier, Müller, Simone, Bienzle, Ulrich, Kremsner, Peter G., Prada, J, Müller, S, Bienzle, U, and Kremsner, P G

Subjects
DRUG therapy for malaria, REACTIVE oxygen species, ANIMALS, ANTIMALARIALS, BIOCHEMISTRY, CHLOROQUINE, GENES, HYDROCARBONS, IN situ hybridization, MALARIA, PHENOMENOLOGY, MICE, NITROGEN compounds, OXIDOREDUCTASES, PROTOZOA, SPLEEN
Abstract

Plasmodium berghei ANKA infected C57B1/6 mice develop cerebral malaria at a parasitaemia of 15–25%. When parasitaemia reached 10%, P. berghei infected mice were treated with artemether, chloroquine or clindamycin in order to prevent the occurrence of cerebral malaria. Artemether and chloroquine were highly efficient. Functional tests revealed that zymosan stimulated spleen cells from untreated mice with cerebral malaria showed a slight decrease in their capacity to produce reactive oxygen intermediates (ROI) when compared with naive mice. After artemether or chloroquine treatment, the ROI production was significantly enhanced. The interferon-gamma induced production of reactive nitrogen intermediates (RNI) was slightly elevated in mice with cerebral malaria, but markedly elevated in artemether or chloroquine treated mice when compared with naive mice. Moreover, high levels of inducible nitric oxide synthase gene expression could be detected by in-situ hybridization in spleen sections of mice which had been treated with artemether or chloroquine. These findings suggest that increased production of ROI and RNI after chemotherapy may play a protective role for the host during malaria. [ABSTRACT FROM PUBLISHER] more...

Published
1996
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23. Antiproliferative effect of the serotonin receptor antagonist ondansetron in the acute lymphoblastic leukemia cell line REH.

Author

Prada, Javier, Shalapour, Shabnam, Pfau, Madlen, Henze, Guenter, and Seeger, Karl

Subjects
*CELL culture, *CELLS, *LYMPHOBLASTIC leukemia, *HEALTH outcome assessment, *T-test (Statistics), *TREATMENT effectiveness, *ONDANSETRON
Abstract

A letter o the editor is presented which is concerned with the antiproliferative effect of the serotonin receptor antagonist ondansetron in the acute lymphoblastic leukemia cell line REH.

Published
2011
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28. Effects of pre-operative isolation on postoperative pulmonary complications after elective surgery: an international prospective cohort study

Author

Dmitri Nepogodiev, Joana Ff Simoes, Elizabeth Li, Maria Picciochi, James C Glasbey, Glauco Baiocchi, Ruth Blanco-Colino, Daoud Chaudhry, Ehab AlAmeer, Kariem El-Boghdadly, Funmilola Wuraola, Dhruva Ghosh, Rohan R Gujjuri, Ewen M Harrison, Herman Lule, Haytham Kaafarani, Mohammad Khosravi, Irmgard Kronberger, Sezai Leventoğlu, Harvinder Mann, Kenneth A Mclean, Mengistu Gebreyohanes Mengesha, Maria Marta Modolo, Faustin Ntirenganya, Lisa Norman, Oumaima Outani, Riinu Pius, Peter Pockney, Ahmad Uzair Qureshi, April Camilla Roslani, Sohei Satoi, Catherine Shaw, Aneel Bhangu, Omar M Omar, Waheed-Ul-Rahman Ahmed, Leah Argus, Alasdair Ball, Edward P Bywater, Amanpreet Brar, Brett E Dawson, Irani Duran, Muhammed Elhadi, Conor S Jones, Sivesh K Kamarajah, James M Keatley, Samuel Lawday, Ella J Marson, Riinu Ots, Irène Santos, Elliott H Taylor, Isobel M Trout, Chris Varghese, Mary L Venn, William Xu, Irida Dajti, Arben Gjata, Salah Eddine Oussama Kacimi, Luis Boccalatte, Daniel Cox, Philip Townend, Felix Aigner, Irmgard Elisabeth Kronberger, Elgun Samadov, Amer Alderazi, Kamral Hossain, Greg Padmore, Gabrielle van Ramshorst, Ismaïl Lawani, Anis Cerovac, Samir Delibegovic, Gustavo Mendonça Ataíde Gomes, Igor Lima Buarque, Muhammad Gohar, Mihail Slavchev, Chukwuemeka Nwegbu, Arnav Agarwal, Janet Martin, Joshua Ng-Kamstra, Maricarmen Olivos, Wenhui Lou, Dong-Lin Ren, Jose Andres Calvache, Carlos J Perez Rivera, Ana Danic Hadzibegovic, Tomislav Kopjar, Jakov Mihanovic, Pablo Mijahil Avilés Jiménez, Nikolaos Gouvas, Jaroslav Klat, René Novysedlák, Nicolas Amisi, Peter Christensen, Alaa El-Hussuna, Sylvia Batista, Eddy Lincango-Naranjo, Sameh Emile, Danilo Alfonso Arévalo Sandoval, Hailu Dhufera, Samuel Hailu, Mengistu G Mengesha, Joonas H Kauppila, Alexis P Arnaud, Zaza Demetrashvili, Markus Albertsmeier, Hans Lederhuber, Markus W Löffler, Daniel Kwesi Acquah, Bernard Ofori, Stephen Tabiri, Symeon Metallidis, Georgios Tsoulfas, Maria-Lorena Aguilera-Arevalo, Gustavo Recinos, Tamás Mersich, Dániel Wettstein, Gabriele Kembuan, Peiman Brouki Milan, Mohammad Hossein Khosravi, Masoud Mozafari, Ahmed Hilmi, Helen Mohan, Oded Zmora, Gaetano Gallo, Francesco Pata, Gianluca Pellino, Yuki Fujimoto, Naoto Kuroda, Mohamad K Abou Chaar, Faris Ayasra, Ildar Fakhradiyev, Intisar Hisham Said Hamdun, Jang Jin-Young, Mohammad Jamal, Lina Karout, Aiste Gulla, Fanjandrainy Rasoaherinomenjanahary, Luc Hervé Samison, Iran Irani Durán Sánchez, Diana Samantha Gonzalez, Laura Martinez, María José Martínez, Alejandra Nayen, Antonio Ramos-De la Medina, Jade Nunez, Pueya Rashid Nashidengo, Rakesh Shah, Ashish Lal Shrestha, Pascal Jonker, Schelto Kruijff, Milou Noltes, Pieter Steinkamp, Deborah Wright, Lukman Abdur-Rahman, Adesoji Ademuyiwa, Adewale Adisa, Babatunde Osinaike, Justina Seyi-Olajide, Omolara Williams, Emmanuel Williams, Sofija Pejkova, Zainab Al Balushi, Raza Sayyed, Mustafa Abo Mohsen, Sadi A Abukhalaf, Moises Cukier, Hugo Gomez-Fernandez, Sebastian Shu Yip, Ximena Paola Vasquez Ojeda, Marie Dione Sacdalan, Piotr Major, José Azevedo, Miguel F Cunha, Ahmad Zarour, Eduard-Alexandru Bonci, Ionut Negoi, Sergey Efetov, Viktor Kochetkov, Andrey Litvin, Jc Allen Ingabire, Georges Bucyibaruta, Ntirenganya Faustin, Sosthene Habumuremyi, Alphonsine Imanishimwe, Haragirimana Jean de Dieu, Emmanuel Munyaneza, Isaie Ncogoza, Ehab Alameer, Abdourahmane Ndong, Dejan Radenkovic, Min Hoe Chew, Frederick Koh, James Ngu, Arpád Panyko, Uros Bele, Jurij Aleš Košir, Hassan Daoud, Ana Maria Minaya Bravo, Umesh Jayarajah, Dakshitha Wickramasinghe, Mohammed Elmujtba Adam Essa Adam, Martin Rutegård, Malin Sund, Michel Adamina, Eleftherios Gialamas, Karoline Horisberger, Muhammad Alshaar, Abel Huang, Varut Lohsiriwat, Shane Charles, Haithem Jlassi, Arda Isik, Hervé Monka Lekuya, Slava Kopetskyi, Hayder Alsaadi, Sattar Alshryda, Osaid Alser, Brittany Bankhead-Kendall, Kerry Breen, Hassan Mashbari, Fernando Bonilla Cal, Hamza Al-Naggar, Mayaba Maimbo, Dennis Mazingi, Tom Abbott, Melika Akhbari, Ruth Benson, Shivam Bhanderi, Bruce Biccard, Edward Caruana, Sohini Chakrabortee, Reema Chapatwala, Ainhoa Costas-Chavarri, Andreas K Demetriades, Anant Desai, Salomone Di Saverio, Thomas Drake, John Edwards, Jonathan Evans, Marco Fiore, Samuel Ford, Christina Fotopoulou, Alexander Fowler, Kaori Futaba, Ian Ganly, Harelimana Grace James, Ewen Griffiths, Alessandro Gronchi, Peter Hutchinson, Gabriella Yael Hyman, Joseph Incorvia, Ritu Jain, Michael Jenkinson, Tabassum Khan, Stephen Richard Knight, Angelos Kolias, Søren Kudsk-Iversen, Tsun Yu Kwan, Elaine Leung, Julio Mayol, Siobhan McKay, John G Meara, Emily Mills, Susan Moug, Akshay Patel, Roberto Perinotti, Henry E Rice, Keith Roberts, Andrew Schache, Richard Shaw, Neil Smart, Matthew Stephens, Grant D Stewart, Ella Teasdale, Peter Vaughan-Shaw, Raghavan Vidya, Naomi Wright, Natalie Zimmelman, Ervis Agastra, Dariel Thereska, Sergio Martin Lucchini, Veronica Laudani, Carina Chwat, Ivana Ines Pedraza Salazar, Diana Alejandra Pantoja Pachajoa, Agustin Duro, José Alfredo Calderón Arancibia, Giuliana D'Aulerio, Nagendra Dudi-Venkata, Natasha Egoroff, Shebani Farik, Natalie Lott, Jana-Lee Moss, Sarah Rennie, Lorwai Tan, Uyen Giao Vo, David Watson, David Watters, Tim Bright, Paul Hollington, Xuanyu Zhou, Hidde M Kroon, Anthony Farfus, John Barker, Eleanor Watson, Sean Stevens, Haider Latif, Amanda Caroline Dawson, Alwin Chuan, Vijayaragavan Muralidharan, Enoch Wong, Travis Ackermann, Maurizio Pacilli, Russell Hodgson, Alexander Heriot, Peter Choong, Wendy Brown, Surjit Lidder, Justin Yeung, Luke Traeger, Guillermo Regalo, Ralph Gourlay, Sarit Badiani, Cherry Koh, Soni Putnis, Fayza Haider, Ashrarur Rahman Mitul, Niels Komen, Bert Dhondt, Serge Cappeliez, Manon Pigeolet, Martijn Schoneveld, Jasper Stijns, Wouter Oosterlinck, Nicolas Flamey, Cyrille Kpangon, Mouhamed Agbadebo, S Mèvo Romaric Tobome, Aldo Vieira Barros, Samuel Aguiar Júnior, Heloisa Galvão do Amaral Campos, Jefferson Gross, Felipe José Fernandez Coimbra, Luiz Paulo Kowalski, Fabiana Makdissi, Suely Nakagawa, Joao Pedreira Duprat Neto, Jose Guilherme Vartanian, Guilherme Yazbek, Stenio C Zequi, Ronald Flumignan, Natalia Jaworska, Angela Dell, Harsha Shanthanna, Abdollah Behzadi, Carolyn Nessim, Michelle Mozel, Pascal St-Germain, Crispin Russell, Gary Groot, Najib Safieddine, Duminda Wijeysundera, Antoine Eskander, Sami Chadi, Shawn MacKenzie, Alana Flexman, Fernando Heredia, Julio Villanueva, Sofia Waissbluth, Roberto Macchiavello, Mario I Escudero, Tyare Fuentes, Ximena Mimica, Dinimo Bolivar Saenz, Lina Caicedo, Juan Pablo Alzate, Joaquin Luna, Nestor Fabian Pedraza Alonso, Camilo Ortiz Silva, Juliana Rodriguez, Liliana Silva-Igua, Martha Luz Torres, Lina María Trujillo, Albaro José Nieto Calvache, Julián Balanta-Melo, Rafael Figueroa-Casanova, Oscar-Julián García-Montoya, Carlos Andres Marulanda Toro, Marcela Velez Botero, Maria Clara Mendoza Arango, Eneida Diaz Martinez, Valentina Gutiérrez Perdomo, Emileth Montenegro, Julia Rodriguez-Abreu, Dolores Mejía, Galal Abouelnagah, Sameh Shehata, Ahmed Hossam Eldin Fouad Rida, Ramy A Hassan, Mahmoud M Saad, Mohamed Reda Loaloa, Badr Mostafa, Mohamed Qassem, Mohamed Fahmy, Hesham Abozied, Ahmed Y Azzam, Sherief Ghozy, Asser Sallam, Ahmed Shehta, Mohamed Abdelkhalek, Rehab Samaka, Amr Morsy, Ahmed Elshawadfy Sherif, Abraham Negussie, Tigist Fisseha, Kibruyisfaw Shumbash, Metasebia Abebe, Seid Mohammed Yasin, Yemisirach Bizuneh Akililu, Abebe Megersa, Teshome Tefera, Melatework Assefa, Bahru Atnafu, Bereket Tsegaye, Yoseph Solomon Bezabih, Silamlak Sisay, Kebebe Bekele, Moa Jira, Habtamu Derilo, Eyueal Degefa, Anteneh Tadesse, Melkamu Nidaw, Elise Sarjanoja, Sylvie Testelin, Sophie Boucher, Lionel Jouffret, Zaher Lakkis, Alban Zarzavadjian Le Bian, Luke Harper, Marc Danguy des Déserts, Benoît André, Karem Slim, Romain Verhaeghe, Andrea Police, Edouard Girard, Alexandre Chebaro, Armande Subayi Nkembi, Laurent Arnalsteen, Quentin Ballouhey, Diane Mege, Clement Jeandel, Emilie Duchalais, Pierre-Alban Bouche, Gilles Manceau, Célia Crétolle, Erik Hervieux, Noémie Girard, Agathe Seguin-Givelet, Sebastien Gaujoux, Belinda De Simone, Matthieu Boisson, Damien Bergeat, Fabien Fredon, Francesco Nappi, Radwan Kassir, Aurélien Scalabre, Federico Migliorelli, Anne-Cecile Ezanno, Barbara Seeliger, Charlotte Vaysse, Helene Charbonneau, Vincent Misrai, Olivier Abbo, Martina Aida Angeles, Laurent Brunaud, Ali Modabber, Sebastian Wolf, Carsten Kamphues, Philipp Höhn, Tim R Glowka, Alexander Christopher Rokohl, Ulrich Bork, Georg Fluegen, Raymund E Horch, Andrea Schmedding, Andreas Schnitzbauer, Helge Eberbach, Daniel Schlager, Fritz Spelsberg, Lena Keppler, Andreas Hecker, Susanne Wolfer, Ulrich Ronellenfitsch, Christine Nitschke, Christian Peiper, Ibrahim Hakami, Stefan Welter, Karine Nikolaieva, Andreas Roth, Judith Lindert, Konstantinos Gousias, Anke Rissmann, Valerie Catherine Linz, Nuh Rahbari, Marie-Claire Rassweiler-Seyfried, Anna Eleonora Gut, Jens Gempt, Daniel Reim, Arthur Wagner, Alexander M Keppler, Mircea Gabriel Stoleriu, Tim Saier, Josef Stadler, Julia Christina Kaiser, Stefan M Brunner, Karin Pfister, Jonas Herzberg, Kai Nowak, Tobias Reinhard, Gregor A Stavrou, Alfred Königsrainer, Christian Konrads, Markus Quante, Simon Laban, Silke von Pusch, Markus Hirschburger, Johannes Doerner, Armin Wiegering, Ekaterini Christina Tampaki, Alitza Gutiérrez Ruiz, Alejandra Rodas, Ana Lucía Portilla, Jacqueline Carrera, Amalia Barrios Duarte, Megan Lowey, Sabrina Barillas, Atul Suroy, Dhaivat Vaishnav, Raghunandan Gorantlu Chowdappa, Irappa Madabhavi, Dhananjaya Bhat, Sunil Kumar Venkatappa, Sumit Thakar, Kavitha Jain, Aruna Kumar, Manoj Nagar, Tushar Mishra, Arunkumar Sekar, Anand Gupta, Lileswar Kaman, Madhivanan Karthigeyan, Manjul Tripathi, Ashwin Rammohan, Sudheer Othiyil Vayoth, Anupama Rajanbabu, Anbukkani Subbian, Rahul Gupta, Monish Raut, Nissi Evelyn, R Lavanya Kannaiyan, Anil Matai, Sanjeev Misra, Vishal Bhende, Sathish Muthu, Indranil Ghosh, Abhishek Sharma, Ankur Bajaj, Shiv Rajan, Gaurav Agarwal, Pranay Pawar, Philip Alexander, M Vijayakumar Vijayakumar, Zeeshan Hameed, L Badareesh, Navneet Kumar Chaudhry, Lipika Baliarsing, Satish Dharap, Amruta Kulkarni, Yuvaraja Thyavihally, Rahul Deo Sharma, C S Pramesh, Rajesh Soni, Surya Kumar Dube, Shilpa Sharma, Harvinder Singh, Lovenish Bains, Rahul Ghodke, Ashwani Kumar, Vivek Sodhai, Suvendu Maji, Somprakas Basu, Chandrashekhar Mahakalkar, Ravi Kannan, Asif Mehraj, N Ranganath, Ashish Phadnis, I Yadev, Alfie Kavalakat, Rohin Mittal, Karthik Chandra Vallam, Hamed Akhavizadegan, Esmaeil Rezghi Maleki, Naser Yousefzadeh Kandevani, Hilary Ikele, Catherine McNestry, Christina Fleming, Stephen O'Brien, Sami Abd Elwahab, Niall Davis, Mohsen Javadpour, Brendan McDonnell, Clare O Connor, Jarlath Bolger, Cillian Clancy, Stefanie M Croghan, Noel Donlon, Carolyn Cullinane, Ben Creavin, Muheilan Muheilan, Helen Earley, Syed Mohammad Umar Kabir, Muhammad Fahadullah, Éanna Ryan, Tara Connelly, Daisuke Hashimoto, Majdi Ali Alqudah, Amer Alajalen, Rand Y Omari, Abdulrahman Qasem, Yazan Alawneh, Amer Ahmad, Omar Aladawi, Bourhan Alrayes, Hanan Haidar, Shatha Husain, Faisal Qassem, Adnan Sumadi, Ala'a Abu Salhiyeh, Balqees Mahmoud Al-Manaseer, Zaid Alsunna, Hazim Ra'ed, Faten Reyad Bani Hamad, Amro Abuleil, Elmi Ahmed Mohamed Jimaale, Marah Abu-Mehsen, Noor Olaywah, Omar Wafi, Hazim Ababneh, Luai Abu-Ismail, Almu'atasim Khamees, Ahmad Alkhatib, Raikhan Bolatbekova, Mukhtar Kulimbet, Talgat Nurgozhin, Timur Saliev, Baurzhan Zhussupov, Ydyrys Almabayev, Dilyara Kaidarova, Khalil Tamoos, Ahmed Aqeelah, Alsnosy Abdullah Khalefa Mohammed, Faraj Al Maadany, Ghadah Alkadeeki, Milad Gahwagi, Wafa Aldressi, Mohamed Amnaina, Arowa Hassan Abdulrahman Alansari, Akram Alkaseek, Ghozlan Yagoub, Anass Ben Amer, Marwa Salem, Ayman Almugaddami, Dania Burgan, Mohammed Abdelkabir, Khayriyah Alshareef, Rayet Al Islam Ben Jouira, Ayman Meelad, Ahmad Bouhuwaish, Sumayya Essayah Dwaga, Houda Khalifa, Bushray Almiqlash, Taha Suliaman, Mohammed Alawami, Fras Elhajdawe, Hajir Aboazamazem, Ibrahim Ellojli, Ahmed Msherghi, Ismail Ali Saleh, Mohammed Alayan, Marcel Didier Ndayishyigikiye, Akutu Munyika, Philipp Plarre, David W Borowski, Cameron Wells, Rebecca Teague, Brodie Elliott, David Kieser, Omar Mohyieldin, Nick McIntosh, Cheyaanthan Haran, Jasmin King, Jeong Ha, Matthew James McGuinness, Opeoluwa Adesanya, Julius Olaogun, Akinola Akinmade, Kefas Bwala, Peter Agbonrofo, Akinwale Afolabi, Usang Usang, Sebastian Ekenze, Samson Olori, Taiwo Akeem Lawal, Abiodun Okunlola, Stephen Kache, Danjuma Sale, Lofty-John Anyanwu, Chukwuma Okereke, Musliu Adetola Tolani, Venko Filipce, Lazar Todorovic, Sotir Stavridis, John George Massoud, Sareyah Alsibai, Rizwan Sultan, Humera Naz Altaf, Abu Bakar Hafeez Bhatti, Shahzad Hussain Waqar, Aliya Aziz, Asad Ali Kerawala, Lajpat Rai, Mariyah Anwer, Aiman Tariq, Bushra Ayub, Sami Ullah Niazi, Muhammad Yasir Naseem, Muhammad Zeeshan Sarwar, Muhammad Imran Khokhar, Imdad Ahmad Zahid, Haroon Javaid Majid, Nabila Talat, Muhammad Asif, Muhammad Hamid Chaudhary, Umer Farooq, Siddique Ahmad, Waleed Mabood, Syed Imran Bukhari, Muhammad Tariq, Eesha Yaqoob, Saad Javed, Muhammad Usman Malik, Hassan Nawaz Yaqoob, Glenda Marina Falcon Pacheco, Robinson Mas Melendez, Arazzelly Del Pilar Paucar Urbina, Jose Rios Chiuyari, Carlos Eduardo Otiniano Alvarado, Lorena Fuentes Rivera Lau, Giuliano Borda-Luque, Milagros Niquen-Jimenez, Claudia Arias, Sergio Zegarra, Jenner Betalleluz Pallardel, Regina Amparo Ugarte Oscco, Gian Mendiola, Yahaira Tatiana Carpio Colmenares, Carlos Shiraishi Zapata, Maria Rosa Ortiz, Filipe Castro Borges, Octavio Viveiros, Pedro Serralheiro, Paulo Santos-Costa, Filipa Mendes, Miguel Rocha Melo, Paulo Cardoso, Ana Soares, Rita Gonçalves Pereira, Nelson Silva, André Caiado, Maria Luís Sacras, Pedro Azevedo, Rui Almeida-Reis, João Oliveira, Jorge Nogueiro, Mafalda Sampaio-Alves, Luciana Cidade Costa, Catarina Baía, Ana Cláudia Deus, Rita Branquinho, André Marçal, André Tojal, Silviu Tiberiu Makkai-Popa, Aurel Mironescu, Florin Grama, Elena Adelina Toma, Daniela Filipescu, Nicolae Bacalbasa, Natalia Motas, Sebastian Ionescu, Octav Ginghina, Radu Costea, Narcis Octavian Zarnescu, Radu Drasovean, Mihail-Gabriel Dimofte, Vlad Porumb, Mikhail Kirov, Yegor Molitvin, Vadim Pykhteev, Marianna Raevskaya, Aleksandr Butyrskii, Mushabab Alshahrani, Azah Althumairi, Nasser Alzerwi, Ahmed Al Ameer, Tariq Madkhali, Abddulrahman Saleh Almulhim, Salman Ghazwani, Abdu Ayoub, Othman Iskander, Mohammed Ghunaim, Mohammed Alharthi, Turki M Alzaidi, Mohammad Alyami, Abdulrahman Al Amri, Abdullah AlFakhri, Amal Alhefdhi, Sharfuddin Chowdhury, Thamer Nouh, Ameen Alshehri, Abdulrahman Alzahrani, Yousef Alalawi, Selmy Awad, Ibrahima Konate, Jacques Tendeng, Nan Zun Teo, Sabra Aqil, Cristina Barrena López, Ana Sánchez Mozo, Antonio Rodriguez Infante, Patricia Caja Vivancos, Mikel Prieto, Igor Alberdi San Roman, Laura Gomez Fernandez, Josep Maria Muñoz Vives, Anna Carreras-Castañer, Berta Díaz-Feijoo, Ramon Sieira-Gil, Victor Turrado-Rodriguez, Anna Sánchez López, Santiago Sánchez-Cabús, Marta Jimenez Toscano, MªPilar Canals Sin, Saura García Laura, Oriol Martin Sole, Pedro Palazon Bellver, Sonia Pérez-Bertólez, Jordi Prat-Ortells, Mireia Riba Martínez, Josep Rubio-Palau, Xavier Tarrado, Jorge Nuñez, Veronica Alonso Mendoza, Coro Bescós, Eloy Espin-Basany, Martin Espinosa-Bravo, Daniel Gil-Sala, Susana González-Suárez, Nuria Montferrer Estruch, Lucia Porteiro Mariño, Ana Rodríguez-Tesouro, Fabian Rojas Portilla, M Pilar Tormos Pérez, Inmaculada Vives, Unai Garcia De Cortazar, Kiara Tudela, Aitor Landaluce-Olavarria, Mercedes Estaire Gómez, Jorge Almoguera, Bakarne Ugarte-Sierra, Virginia Jimenez, Marta Bertrand, Laura Cárdenas Puiggrós, Olga Delisau-Puig, Jorge Garcia-Adamez, David Julià Bergkvist, Eloy Maldonado-Marcos, Lucia Diego García, Marta 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Pierre-Alban Bouche, Gilles Manceau, Célia Crétolle, Erik Hervieux, Noémie Girard, Agathe Seguin-Givelet, Sebastien Gaujoux, Belinda De Simone, Matthieu Boisson, Damien Bergeat, Alexis P Arnaud, Fabien Fredon, Francesco Nappi, Radwan Kassir, Aurélien Scalabre, Federico Migliorelli, Romain Verhaeghe, Anne-Cecile Ezanno, Barbara Seeliger, Charlotte Vaysse, Helene Charbonneau, Vincent Misrai, Olivier Abbo, Martina Aida Angeles, Laurent Brunaud, Zaza Demetrashvili, Ali Modabber, Sebastian Wolf, Carsten Kamphues, Philipp Höhn, Tim R Glowka, Alexander Christopher Rokohl, Ulrich Bork, Georg Fluegen, Raymund E Horch, Andrea Schmedding, Andreas Schnitzbauer, Helge Eberbach, Daniel Schlager, Fritz Spelsberg, Lena Keppler, Andreas Hecker, Susanne Wolfer, Ulrich Ronellenfitsch, Christine Nitschke, Christian Peiper, Ibrahim Hakami, Stefan Welter, Karine Nikolaieva, Andreas Roth, Judith Lindert, Konstantinos Gousias, Anke Rissmann, Valerie Catherine Linz, Nuh Rahbari, Marie-Claire Rassweiler-Seyfried, Anna Eleonora Gut, Jens Gempt, Daniel Reim, Arthur Wagner, Markus Albertsmeier, Alexander M Keppler, Mircea Gabriel Stoleriu, Tim Saier, Josef Stadler, Julia Christina Kaiser, Stefan M Brunner, Karin Pfister, Jonas Herzberg, Kai Nowak, Tobias Reinhard, Gregor A Stavrou, Alfred Königsrainer, Christian Konrads, Markus Quante, Simon Laban, Silke von Pusch, Markus Hirschburger, Johannes Doerner, Armin Wiegering, Ekaterini Christina Tampaki, Alitza Gutiérrez Ruiz, Alejandra Rodas, Ana Lucía Portilla, Gustavo Recinos, Maria-Lorena Aguilera-Arevalo, Jacqueline Carrera, Amalia Barrios Duarte, Megan Lowey, Sabrina Barillas, Atul Suroy, Dhaivat Vaishnav, Raghunandan Gorantlu Chowdappa, Irappa Madabhavi, Dhananjaya Bhat, Sunil Kumar Venkatappa, Sumit Thakar, Kavitha Jain, Aruna Kumar, Manoj Nagar, Tushar Mishra, Arunkumar Sekar, Anand Gupta, Lileswar Kaman, Madhivanan Karthigeyan, Manjul Tripathi, Ashwin Rammohan, Sudheer Othiyil Vayoth, Anupama Rajanbabu, Anbukkani Subbian, Rahul Gupta, Monish Raut, Nissi Evelyn, R Lavanya Kannaiyan, Anil Matai, Sanjeev Misra, Vishal Bhende, Sathish Muthu, Indranil Ghosh, Abhishek Sharma, Ankur Bajaj, Shiv Rajan, Gaurav Agarwal, Pranay Pawar, Philip Alexander, M Vijayakumar Vijayakumar, Zeeshan Hameed, L Badareesh, Navneet Kumar Chaudhry, Lipika Baliarsing, Satish Dharap, Amruta Kulkarni, Yuvaraja Thyavihally, Rahul Deo Sharma, C S Pramesh, Rajesh Soni, Surya Kumar Dube, Shilpa Sharma, Harvinder Singh, Lovenish Bains, Rahul Ghodke, Ashwani Kumar, Vivek Sodhai, Suvendu Maji, Somprakas Basu, Chandrashekhar Mahakalkar, Ravi Kannan, Asif Mehraj, N Ranganath, Ashish Phadnis, I Yadev, Alfie Kavalakat, Rohin Mittal, Karthik Chandra Vallam, Hamed Akhavizadegan, Esmaeil Rezghi Maleki, Naser Yousefzadeh Kandevani, Hilary Ikele, Catherine McNestry, Christina Fleming, Stephen O'Brien, Sami Abd Elwahab, Niall Davis, Mohsen Javadpour, Brendan McDonnell, Clare O Connor, Jarlath Bolger, Cillian Clancy, Stefanie M Croghan, Noel Donlon, Carolyn Cullinane, Ben Creavin, Muheilan Muheilan, Helen Earley, Syed Mohammad Umar Kabir, Muhammad Fahadullah, Éanna Ryan, Tara Connelly, Oded Zmora, Daisuke Hashimoto, Majdi Ali Alqudah, Amer Alajalen, Rand Y Omari, Faris Ayasra, Abdulrahman Qasem, Yazan Alawneh, Amer Ahmad, Omar Aladawi, Bourhan Alrayes, Hanan Haidar, Shatha Husain, Faisal Qassem, Adnan Sumadi, Ala'a Abu Salhiyeh, Balqees Mahmoud Al-Manaseer, Zaid Alsunna, Hazim Ra'ed, Faten Reyad Bani Hamad, Amro Abuleil, Mohamad K Abou Chaar, Elmi Ahmed Mohamed Jimaale, Marah Abu-Mehsen, Noor Olaywah, Omar Wafi, Hazim Ababneh, Luai Abu-Ismail, Almu'atasim Khamees, Ahmad Alkhatib, Raikhan Bolatbekova, Mukhtar Kulimbet, Talgat Nurgozhin, Timur Saliev, Baurzhan Zhussupov, Ydyrys Almabayev, Ildar Fakhradiyev, Timur Saliev, Dilyara Kaidarova, Khalil Tamoos, Ahmed Aqeelah, Alsnosy Abdullah Khalefa Mohammed, Faraj Al Maadany, Ghadah Alkadeeki, Milad Gahwagi, Wafa Aldressi, Mohamed Amnaina, Arowa Hassan Abdulrahman Alansari, Akram Alkaseek, Ghozlan Yagoub, Anass Ben Amer, Marwa Salem, Ayman Almugaddami, Dania Burgan, Mohammed Abdelkabir, Khayriyah Alshareef, Rayet Al Islam Ben Jouira, Ayman Meelad, Ahmad Bouhuwaish, Sumayya Essayah Dwaga, Houda Khalifa, Bushray Almiqlash, Taha Suliaman, Mohammed Alawami, Fras Elhajdawe, Hajir Aboazamazem, Ibrahim Ellojli, Ahmed Msherghi, Ismail Ali Saleh, Mohammed Alayan, April Camilla Roslani, Marcel Didier Ndayishyigikiye, Akutu Munyika, Philipp Plarre, David W Borowski, Pueya Rashid Nashidengo, Milou Noltes, Pieter Steinkamp, Cameron Wells, Rebecca Teague, Brodie Elliott, David Kieser, Omar Mohyieldin, Chris Varghese, Nick McIntosh, Cheyaanthan Haran, Sarah Rennie, Jasmin King, Jeong Ha, Matthew James McGuinness, Opeoluwa Adesanya, Julius Olaogun, Akinola Akinmade, Kefas Bwala, Peter Agbonrofo, Akinwale Afolabi, Usang Usang, Sebastian Ekenze, Samson Olori, Taiwo Akeem Lawal, Justina Seyi-Olajide, Abiodun Okunlola, Omolara Williams, Adewale Adisa, Lukman Abdur-Rahman, Stephen Kache, Danjuma Sale, Lofty-John Anyanwu, Chukwuma Okereke, Musliu Adetola Tolani, Venko Filipce, Lazar Todorovic, Sofija Pejkova, Sotir Stavridis, John George Massoud, Sareyah Alsibai, Rizwan Sultan, Humera Naz Altaf, Abu Bakar Hafeez Bhatti, Shahzad Hussain Waqar, Aliya Aziz, Asad Ali Kerawala, Lajpat Rai, Mariyah Anwer, Aiman Tariq, Bushra Ayub, Sami Ullah Niazi, Muhammad Yasir Naseem, Muhammad Zeeshan Sarwar, Muhammad Imran Khokhar, Imdad Ahmad Zahid, Haroon Javaid Majid, Nabila Talat, Muhammad Asif, Muhammad Hamid Chaudhary, Umer Farooq, Siddique Ahmad, Waleed Mabood, Syed Imran Bukhari, Muhammad Tariq, Eesha Yaqoob, Saad Javed, Saad Javed, Muhammad Usman Malik, Hassan Nawaz Yaqoob, Moises Cukier, Glenda Marina Falcon Pacheco, Robinson Mas Melendez, Arazzelly Del Pilar Paucar Urbina, Jose Rios Chiuyari, Carlos Eduardo Otiniano Alvarado, Lorena Fuentes Rivera Lau, Giuliano Borda-Luque, Milagros Niquen-Jimenez, Claudia Arias, Sergio Zegarra, Jenner Betalleluz Pallardel, Regina Amparo Ugarte Oscco, Gian Mendiola, Yahaira Tatiana Carpio Colmenares, Carlos Shiraishi Zapata, Maria Rosa Ortiz, Marie Dione Sacdalan, Piotr Major, Filipe Castro Borges, Octavio Viveiros, Pedro Serralheiro, Paulo Santos-Costa, Filipa Mendes, Miguel Rocha Melo, Paulo Cardoso, Ana Soares, José Azevedo, Rita Gonçalves Pereira, Nelson Silva, André Caiado, Maria Luís Sacras, Pedro Azevedo, Rui Almeida-Reis, Miguel F Cunha, João Oliveira, Jorge Nogueiro, Mafalda Sampaio-Alves, Luciana Cidade Costa, Catarina Baía, Ana Cláudia Deus, Rita Branquinho, André Marçal, André Tojal, Ahmad Zarour, Ahmad Zarour, Silviu Tiberiu Makkai-Popa, Aurel Mironescu, Florin Grama, Elena Adelina Toma, Ionut Negoi, Daniela Filipescu, Nicolae Bacalbasa, Natalia Motas, Sebastian Ionescu, Octav Ginghina, Radu Costea, Narcis Octavian Zarnescu, Radu Drasovean, Eduard-Alexandru Bonci, Mihail-Gabriel Dimofte, Vlad Porumb, Mikhail Kirov, Yegor Molitvin, Andrey Litvin, Vadim Pykhteev, Marianna Raevskaya, Sergey Efetov, Aleksandr Butyrskii, Mushabab Alshahrani, Azah Althumairi, Nasser Alzerwi, Ahmed Al Ameer, Ahmed Al Ameer, Tariq Madkhali, Abddulrahman Saleh Almulhim, Salman Ghazwani, Abdu Ayoub, Othman Iskander, Mohammed Ghunaim, Mohammed Alharthi, Turki M Alzaidi, Azah Althumairi, Mohammad Alyami, Abdulrahman Al Amri, Azah Althumairi, Abdullah AlFakhri, Amal Alhefdhi, Sharfuddin Chowdhury, Thamer Nouh, Ameen Alshehri, Abdulrahman Alzahrani, Yousef Alalawi, Selmy Awad, Ibrahima Konate, Abdourahmane Ndong, Jacques Tendeng, Nan Zun Teo, Frederick Koh, Jurij Aleš Košir, Uros Bele, Sabra Aqil, Cristina Barrena López, Ana Sánchez Mozo, Antonio Rodriguez Infante, Patricia Caja Vivancos, Mikel Prieto, Igor Alberdi San Roman, Laura Gomez Fernandez, Josep Maria Muñoz Vives, Anna Carreras-Castañer, Berta Díaz-Feijoo, Ramon Sieira-Gil, Victor Turrado-Rodriguez, Anna Sánchez López, Santiago Sánchez-Cabús, Marta Jimenez Toscano, MªPilar Canals Sin, Saura García Laura, Oriol Martin Sole, Pedro Palazon Bellver, Sonia Pérez-Bertólez, Jordi Prat-Ortells, Mireia Riba Martínez, Josep Rubio-Palau, Xavier Tarrado, Jorge Nuñez, Veronica Alonso Mendoza, Coro Bescós, Eloy Espin-Basany, Martin Espinosa-Bravo, Daniel Gil-Sala, Susana González-Suárez, Nuria Montferrer Estruch, Jorge Nuñez, Lucia Porteiro Mariño, Ana Rodríguez-Tesouro, Fabian Rojas Portilla, M Pilar Tormos Pérez, Inmaculada Vives, Unai Garcia De Cortazar, Kiara Tudela, Aitor Landaluce-Olavarria, Mercedes Estaire Gómez, Jorge Almoguera, Bakarne Ugarte-Sierra, Virginia Jimenez, Marta Bertrand, Laura Cárdenas Puiggrós, Olga Delisau-Puig, Jorge Garcia-Adamez, David Julià Bergkvist, Eloy Maldonado-Marcos, Lucia Diego García, Marta Roldón Golet, Iván Soto-Darias, Aida Cristina Rahy-Martín, Diego Enjuto, Adolfo Ramos-Luengo, Juan Delgado Fernandez, Carolina Lugo Duarte, Cristina Ojeda Thies, Lucila Marquez, Diana Crego Vita, Jana Dziakova, Ana Maria Minaya Bravo, Jorge Caño Velasco, Olga Mateo-Sierra, Begoña Quintana-Villamandos, Cristina Rey Valcarcel, Javier Rio, Laura Román García de León, Marcello Di Martino, Jorge Prada, Javier Serrano González, Manuel Losada, Jose Tomas Castell Gomez, Ramon Corripio-Sanchez, Alexander Forero-Torres, José Manuel Morales-Puebla, Hanna Perez-Chrzanowska, Santiago Valderrabano Gonzalez, Alvaro Yebes, Ignacio Zapardiel, Manuel Diez Alonso, Nelson Morales Palacios, Alberto Cabañero Sánchez, Fátima Sánchez Fernández, Alfredo Abad Gurumeta, Ane Abad-Motos, Fernando Corella, Javier Ripollés-Melchor, Rosa Sanz-Gonzalez, Marta Alcaraz Fuentes, Maria Teresa Fernández Martín, Pablo Calvo Espino, Milagros Carrasco Prats, Antonio-José Fernández-López, Damián García Escudero, Vanesa Garcia Soria, Jesús Aarón Martínez Alonso, Miguel Ruiz-Marín, Beatriz Gómez Pérez, Joaquin Moya-Angeler, Daniel Fernández Martínez, Heura Llaquet Bayo, Enrique Colás-Ruiz, Susana Bella Romera, M Teresa Gavaldà Pellicé, Misericòrdia Jordà Solé, Enrique Jose Ruiz Velasquez, Bernardo Núñez, Raul Jimenez, Jon Zabaleta, Maria Jose González-Gimeno, Irene Ortega Vázquez, Antonio Perez Ferrer, Rubén Martín-Láez, Marcelo Moreno Suarez, Miguel Angel Freiria Eiras, Irene Ramallo-Solís, Juan-Carlos Gomez-Rosado, Jose Ramon Oliver Guillen, Mar Achalandabaso Boira, Juan Carlos Catalá Bauset, Julio Domenech, Rafael Badenes, Juan Carlos Bernal-Sprekelsen, Jorge Sancho-Muriel, Beatriz De Andrés-Asenjo, Francisco J Tejero-Pintor, Marc Vallve-Bernal, Alba Vazquez Melero, Laura Sánchez Blasco, Jorge Escartin, Victoria Duque Mallén, Selvaratnam Srishankar, Umesh Jayarajah, Charitha Sooriyabandara, Oshan Basnayake, Nalaka Gunawansa, Dakshitha Wickramasinghe, Prabuth Dulanjan Weeraddana, Thanusan Vimalakanthan, Shanthamoorthy Gishanthan, Pramodh Chandrasinghe, Eleftherios Gialamas, Marc-Olivier Sauvain, Ahmad Ghazal, Yusra Al-Sabbagh, Turki Alhassoun, Sara Maa Albared, Antoine Naem, Hareth Alnahr, Ghassan Jisry, Ali Hammed, Arda Isik, Okedi Francis Xaviour, Gaston Turinawe, Isaac Mubezi, Franck K Sikakulya, Andrew Kakeeto, Wilberforce M Kabweru, Hervé Monka Lekuya, Ronald Kiweewa, Herman Lule, Paul Matovu, Otolia Isaac, Mohamed Mashhour, Amin El Helw, Sattar Alshryda, Safeena Kherani, Awadelkarim Mohamed, Ferial Mohamed Ali Abbas, Diary Mohammed, Ehab Aldlyami, Rakesh Kundra, Mohamed Mashhour, Mohamed Mashhour, Antony Louis Rex Michael, Hayder Alsaadi, Kareem S Khalil, Rachel Dbeis, Shafaque Shaikh, Jenny Ferry, Aiman Jamal, Haleema Siddique, Rishi Das, Nikhil Ponugoti, Sivesh K Kamarajah, Pornjittra Rattanasirivilai, Asma Sultana, Frances Mosley, Matthew Chan, Antony Bateman, Gareth Davies-Jones, Fanourios Georgiades, Grant D Stewart, Navid Ahmadi, Aman Coonar, Mariam Baig, Chetan Khatri, Arthika Surendran, Julian Sonksen, Robert Sinnerton, Caitlin Brennan, Gemma Faulkner, Michael Greenhalgh, Hannah Emerson, Kiran Singisetti, Joshua Totty, Michael Wilson, Terence Lo, Harriet Corbett, Ijeoma Okonkwo, Gill Arbane, Kariem El-Boghdadly, Cyrus Kerawala, Chetan Parmar, Tom Abbott, Michael Bath, Funlayo Odejinmi, Jayesh Sagar, Rishi Talwar, Samuel Newman, John Hammond, John Moir, Natalie Duric, Tamas Szakmany, Ahmar Iftikhar Talib, Mina Youssef, Christopher Lewis-Lloyd, Christopher Lewis-Lloyd, Mariam Lami, Khurram Ayub, Benjamin Dean, Supriya Balasubramanya, Sathya Lakpriya, Luke Rogers, Paul Turner, Mark Maher, Kohila Sigamoney, John Edwards, Jihène El Kafsi, John Hardie, David Johnson, Christin Henein, Marianne Hollyman, Ketan Agarwal, Simon Powell, Govind Singh Chauhan, Rakesh Patel, Joel Gagnier, Heather Carmichael, Aurora, Kristofor A Olson, Eric Etchill, Joseph Incorvia, Sameer Hirji, Matthew Naunheim, Frederick Drake, Haytham Kaafarani, Caroline Reinke, Anna Alecci, Dennis Vaysburg, Jennifer Rodriquez, Emily Shih, Vin Shen Ban, Julia Coleman, Henry E Rice, Krista Kaups-Fresno, Emmanouil Giorgakis, Maggie DiNome, Neal Bhutiani, Omar Alnachoukati, Brittany Bankhead-Kendall, Taylor Aiken, Thomas Diehl, Ankush Gosain, Rishi Rattan, Muhammad Owais Abdul Ghani, Nensi Melissa Ruzgar, Anna Liveris, Nina Glass, Charu Paranjape, Theresa Chin, Antonio Meola, Kristina Nicholson, John Squiers, Stephanie Lueckel, Janani Reisenauer, Rachael Callcut, Ahmed Mansour, Allison Berndtson, Lucy Kornblith, Sara Seegert, Paulo Martins, Hamza Al-Naggar, Mohammed Al-Shehari, Ibrahim Al-Raimi, Allan Ngulube, Maphios Siamuchembu, Willard Mushiwokufa, Busisiwe Mlambo, Simbarashe Chinyowa, Ervis Agastra, Enton Bollano, Kostandin Gjyli, Dariel Thereska, Irida Dajti, Jola Kerpaci, Enxhi Vrapi, Lorena Zijaj, Bahraoui Djahida, Belabbes Fatima Zohra, Kouidri Khadidja, Oussama Bali, Nassim Benallel, Ismahene Lalmi, Meriem Abdoun, Nesrine Aouabed, Souad Bouaoud, Kamel Bouchenak, Assia Haif, Zineddine Soualili, Joaquin Bastet, Agustín Bianco, Daniel Capitaine, Jorge Centeno Lozada, Carlos Esquivel, Rodrigo Figueroa, Manuel Garcia, Pablo Martín García, José Ignacio Gerchunoff, Fernando Martinez Iascano, Jose Mondino, María Emilia Muriel, Carmignani Pablo, Martin Passadore, Alejandra Tornini, Rogelio Traverso, Lara Vargas, Gerardo Zanoni, Norberto Berber, Estefanía Cotta, Marcela Di Vincenzo, Esteban Sebastian Gallino, Cecilia Gigena, Bianca Grassano, Veronica Laudani, Ignacio Lugones, Constanza Madrid, Maximiliano Maricic, Antonio Alberto Martinez, Andres Rosso, Pablo Scher, Sofia Tachella, Damaris Idara Anabel Zezular, Carla Abuawad, Agustin Albani Forneris, Carola Allemand, Laura Gisela Alvarez Calzaretta, Luis Boccalatte, Jorge G Boretto, Rocio Boudou, Rodrigo Brandariz, Martin Buljubasich, Arturo Burchakchi, Martin Buttaro, Juan Pablo Campana, Virginia Cano Busnelli, Tomas Carminatti, Agustina Florencia Castro Lalín, Julian Cereghini, María Sol Crespi Amor, Roberto Sebastián Croattini, Maria Sol Fernandez, Marcelo Figari, Uriel Fraidenraij, Diego Gallegos, Agustín Maria García-Mansilla, Marcos Gonzalez, Matias Ignacio Gonzalez, Esteban Gonzalez Salazar, Jeremias Goransky, Guillermo Hernandez Gauna, Felipe Higuera, Fernando Holc, Esteban Gabriel Jauregui, Juan Larrañaga, Juan Liyo, Lionel Llano, Pablo Lobos, Emilia Luzzi, Gustavo Mastroianni, Santiago Miguel Mata-Suarez, Horacio F Mayer, Santiago Mc Loughlin, Efrain Mendoza, Ricardo Esteban Mentz, Pedro Mercado, Pablo Moyano, Florencia Noll, Diego Odetto, Agustina Rene Oliva, Rafael Perez Vidal, Catalina Poggi, Eduardo Jorge Premoli, María Lourdes Ramos, Patricio Rosas, Luciano Rossi, Gustavo Rossi, Jose Saadi, Jordán Scherñuk, Pablo Slullitel, María Verona Stang, María Victoria Taboada, Sebastian Tirapegui, Constanza Uffelmann, Carlos Vaccaro, Roberto Vagni, Ana Clara Valerio, Celeste Soledad Zarratea, Carina Chwat, Silvina Montal, Brian Morris, Pedro Valdez, Fernando Diaz-Couselo,Ricci C, Casadei R, Fruscio, R, Ornaghi, S, Felice Pecoraro, Emanuele Cammarata, Sofia Campanella, Daniela Canzonieri, Adriana Cordova, Federico De Michele, Ettore Dinoto, Mara Franza, Leo Licari, Daniele Matta, Domenico Mirabella, Roberto Pirrello, Pierfrancesco Pugliese, Fernando Rosatti, Giuseppe Salamone, Francesca Toia, Massimiliano Tripoli, Vito Chiantera, Mariano Catello Di Donna, Collaborative, Covidsurg, Collaborative, Globalsurg, Palmisano, Silvia, de Manzini, Nicolo', Simoes, J, Rosati, R, on behalf of COVIDSurg Collaborative, GlobalSurg Collaborative, Aldrighetti, L, Mortini, P, Olmi, S, Medical Oncology, Assoc Surg Training ASiT, European Soc Coloproctology ESCP, EuroSurg, G4 Alliance, GlobalPaedSurg, GICS, ItSURG, ISRC, Italian Soc Colorectal Surg SICCR, PTSurg, S-ECCO, South African Soc, and SpainSurg more...

Subjects
Lung Diseases, Male, Internationality, SARS-Cov-2, COVID-19, surgery, pathways, pre-operative isolation, Settore MED/18 - CHIRURGIA GENERALE, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Lung Disease, ESTUDOS PROSPECTIVOS, Cohort Studies, Patient Isolation, Postoperative Complications, 80 and over, Prospective Studies, Prospective cohort study, 610 Medicine & health, Aged, 80 and over, Incidence (epidemiology), Treatment Outcome, Elective Surgical Procedures, Female, Elective Surgical Procedure, Cohort study, Human, medicine.medical_specialty, Isolation (health care), Preoperative care, NO, Anesthesiology, Preoperative Care, medicine, Humans, Elective surgery, LS7_4, Aged, business.industry, pathway, Surgery, Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10], Prospective Studie, Anesthesiology and Pain Medicine, Human medicine, Postoperative Complication, Cohort Studie, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05–1.36, p=0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3days, with an OR (95%CI) at 4–7days or ≥8days of 1.25 (1.04–1.48), p=0.015 and 1.31 (1.11–1.55), p=0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care. We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05–1.36, p=0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3days, with an OR (95%CI) at 4–7days or ≥8days of 1.25 (1.04–1.48), p=0.015 and 1.31 (1.11–1.55), p=0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care. more...

Published
2021
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32. Synergistic activity of bortezomib and HDACi in preclinical models of B-cell precursor acute lymphoblastic leukemia via modulation of p53, PI3K/AKT, and NF-κB.

Author

Bastian L, Hof J, Pfau M, Fichtner I, Eckert C, Henze G, Prada J, von Stackelberg A, Seeger K, and Shalapour S

Subjects
Animals, Antineoplastic Agents administration & dosage, Apoptosis, Bortezomib, Drug Synergism, Humans, Leukemia, B-Cell genetics, Leukemia, B-Cell pathology, Mice, NF-kappa B genetics, Phosphatidylinositol 3-Kinases genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma pathology, Transcription Factor RelA genetics, Tumor Cells, Cultured, Tumor Suppressor Protein p53 genetics, Xenograft Model Antitumor Assays, Boronic Acids administration & dosage, Histone Deacetylase Inhibitors administration & dosage, Leukemia, B-Cell drug therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Proto-Oncogene Proteins c-akt genetics, Pyrazines administration & dosage
Abstract

Purpose: Relapse of disease and subsequent resistance to established therapies remains a major challenge in the treatment of childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). New therapeutic options, such as proteasome and histone deacetylase inhibitors (HDACi) with a toxicity profile differing from that of conventional cytotoxic agents, are needed for these extensively pretreated patients., Experimental Design: Antiproliferative and proapoptotic effects of combined HDACi/proteasome inhibitor treatments were analyzed using BCP-ALL monocultures, cocultures with primary mesenchymal stroma cells from patients with ALL, and xenograft mouse models. The underlying molecular mechanisms associated with combined treatment were determined by gene expression profiling and protein validation., Results: We identified the proteasome inhibitor bortezomib as a promising combination partner for HDACi due to the substantial synergistic antileukemic activity in BCP-ALL cells after concomitant application. This effect was maintained or even increased in the presence of chemotherapeutic agents. The synergistic effect of combined HDACi/BTZ treatment was associated with the regulation of genes involved in cell cycle, JUN/MAPK, PI3K/AKT, p53, ubiquitin/proteasome, and NF-κB pathways. We observed an activation of NF-κB after bortezomib treatment and the induction of apoptosis-related NF-κB target genes such as TNFαRs after concomitant treatment, indicating a possible involvement of NF-κB as proapoptotic mediator. In this context, significantly lower NF-κB subunits gene expression was detected in leukemia cells from patients who developed a relapse during frontline chemotherapy, compared with those who relapsed after cessation of frontline therapy., Conclusion: These results provide a rationale for the integration of HDACi/BTZ combinations into current childhood BCP-ALL treatment protocols. more...

Published
2013
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33. High VLA-4 expression is associated with adverse outcome and distinct gene expression changes in childhood B-cell precursor acute lymphoblastic leukemia at first relapse.

Author

Shalapour S, Hof J, Kirschner-Schwabe R, Bastian L, Eckert C, Prada J, Henze G, von Stackelberg A, and Seeger K

Subjects
Adolescent, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Asparaginase administration & dosage, Child, Child, Preschool, Daunorubicin administration & dosage, Disease-Free Survival, Drug Resistance, Neoplasm, Humans, Male, Phosphatidylinositol 3-Kinases metabolism, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Prednisone administration & dosage, Proto-Oncogene Proteins c-akt metabolism, Recurrence, Retrospective Studies, Signal Transduction drug effects, Survival Rate, Vincristine administration & dosage, Gene Expression Regulation, Leukemic, Integrin alpha4beta1 biosynthesis, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma metabolism, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma mortality
Abstract

Background: Resistance to therapy and subsequent relapse remain major challenges in the clinical management of relapsed childhood acute lymphoblastic leukemia. As the bone marrow environment plays an important role in survival and chemotherapy resistance of leukemia cells by activating different signaling pathways, such as the VLA-4 and PI3K/Akt pathways, we studied the prognostic and biological impact of VLA-4 expression in leukemia cells from children with relapsed B-cell precursor acute lymphoblastic leukemia and its influence on the sensitivity of the leukemia cells to drugs., Design and Methods: VLA-4 expression was quantified by real-time polymerase chain reaction in leukemia cells from 56 patients with relapsed acute lymphoblastic leukemia enrolled in the ALL-REZ BFM 2002 trial of the Berlin-Frankfurt-Münster study group. Gene expression changes related to VLA-4 expression were investigated by microarray-based mRNA profiling. The effect of VLA-4 signaling on proliferation and drug resistance was studied in co-cultures of leukemia and stromal cells., Results: High expression of VLA-4 at first relapse was associated with adverse prognostic factors, poor molecular response to therapy and significantly worse probabilities of event-free and overall survival. VLA-4 expression was an independent prognostic parameter. Comparing gene expression profiles of leukemia cells with high versus low VLA-4 expression, we identified 27 differentially expressed genes primarily involved in the PI3K/Akt, ephrin and Rho GTPase pathways. Blocking of VLA-4 signaling in combination with cytarabine treatment abolished the growth supportive effect of stromal cells., Conclusions: Our results show that high VLA-4 expression is a marker of poor prognosis and a potential therapeutic target in children with relapsed acute lymphoblastic leukemia and confirm that cellular interactions and biological effects related to VLA-4 play a decisive role in the survival of leukemia cells and response to therapy. (ClinicalTrials.gov identifier: NCT00114348). more...

Published
2011
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