Author: "Laura Fernandez" - Searchworks@Jio Institute Digital Library Search Results

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1. Atorvastatin and telmisartan do not reduce nasopharyngeal carriage of SARS-CoV-2 in mild or moderate COVID-19 in a phase IIb randomized controlled trial

Author: Fabrice Bonnet, Adama Doumbia, Vanessa Machault, Frederic Nogbou Ello, Pantxika Bellecave, Corine Bernice Akpovo, Baba Toumany Sidibe, Laura Fernandez, Antoine Kouamé, Edgard Adjogoua, Mireille Dosso, Serge Niangoran, Valérie Journot, and Serge Paul Eholié
Subjects: SARS-CoV-2, Atorvastatin, Telmisartan, Randomized controlled trial, Medicine, Science
Abstract: Abstract Observational studies suggest a reduction in fatal or severe COVID-19 disease with the use of ACE2 inhibitors and statins. We implemented a randomized controlled tree-arm open label trial evaluating the benefits of adding telmisartan (TLM) or atorvastatin (ATV) to lopinavir boosted ritonavir (LPVr) on the SARS-CoV-2 nasopharyngeal viral load in patients with mild / moderate COVID-19 infection in Côte d’Ivoire. RT-PCR positive COVID-19 patients ≥ 18 years, with general or respiratory symptoms for less than 7 days were randomized (1:1:1) to receive LPVr (400 mg/100 mg twice daily), LPVr + TLM (10 mg once daily) or LPVr + ATV (20 mg once daily) for 10 days. The primary endpoint was viro-inflammatory success defined as a composite variable at day 11: Ct ≥ 40 and C-reactive protein
Published: 2024
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2. Erythropoietin re-wires cognition-associated transcriptional networks

Author: Manvendra Singh, Ying Zhao, Vinicius Daguano Gastaldi, Sonja M. Wojcik, Yasmina Curto, Riki Kawaguchi, Ricardo M. Merino, Laura Fernandez Garcia-Agudo, Holger Taschenberger, Nils Brose, Daniel Geschwind, Klaus-Armin Nave, and Hannelore Ehrenreich
Subjects: Science
Abstract: Abstract Recombinant human erythropoietin (rhEPO) has potent procognitive effects, likely hematopoiesis-independent, but underlying mechanisms and physiological role of brain-expressed EPO remained obscure. Here, we provide transcriptional hippocampal profiling of male mice treated with rhEPO. Based on ~108,000 single nuclei, we unmask multiple pyramidal lineages with their comprehensive molecular signatures. By temporal profiling and gene regulatory analysis, we build developmental trajectory of CA1 pyramidal neurons derived from multiple predecessor lineages and elucidate gene regulatory networks underlying their fate determination. With EPO as ‘tool’, we discover populations of newly differentiating pyramidal neurons, overpopulating to ~200% upon rhEPO with upregulation of genes crucial for neurodifferentiation, dendrite growth, synaptogenesis, memory formation, and cognition. Using a Cre-based approach to visually distinguish pre-existing from newly formed pyramidal neurons for patch-clamp recordings, we learn that rhEPO treatment differentially affects excitatory and inhibitory inputs. Our findings provide mechanistic insight into how EPO modulates neuronal functions and networks.
Published: 2023
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3. Relationship between addictions and obesity, physical activity and vascular aging in young adults (EVA-Adic study): a research protocol of a cross-sectional study

Author: Sara Vicente-Gabriel, Cristina Lugones-Sánchez, Olaya Tamayo-Morales, Alberto Vicente Prieto, Susana González-Sánchez, Sandra Conde Martín, Marta Gómez-Sánchez, Emiliano Rodríguez-Sánchez, Luis García-Ortiz, Leticia Gómez-Sánchez, Manuel A. Gómez-Marcos, EVA-Adic Investigators Group, The members of the EVA-Adic Group, Sara M. Vicente-Gabriel, Alberto Vicente-Prieto, Sandra Conde-Martín, Elena Navarro-Matias, Carmen Patino-Alonso, José A. Maderuelo-Fernández, Angela de Cabo-Laso, Benigna Sanchez-Salgado, and Laura Fernandez-Matas
Subjects: substance-related disorders, gambling, internet use, technology addiction, obesity, healthy lifestyle, Public aspects of medicine, RA1-1270
Abstract: BackgroundBehavioral and substance addictions are prevalent health problems that, alongside obesity, are linked to reduced physical activity and increased sedentary time. Similarly, arterial stiffness and vascular aging are processes that begin gradually at an early age and are closely associated with morbidity and mortality from cardiovascular diseases. The main objective of this study is to analyze how addictions are related to obesity and body fat distribution, physical activity, sedentary time, arterial stiffness and vascular aging, as well as sleep quality, cognitive function and gender differences in young adults aged between 18 and 34 years.MethodsThis cross-sectional descriptive observational study will analyze data from 500 subjects (250 men and 250 women) aged 18–34 without cardiovascular disease, selected by simple random sampling with replacement from the urban population of the city center of Salamanca (34,044 people aged 18–34, with 18,450 women and 15,594 men). Behavioral and substance addictions, as well as sleep quality and cognitive impairment will be assessed using questionnaires. The Pittisburg Sleep Quality Index (PSQI) will be used to measure sleep quality and the Ford questionnaire will be used to measure insomnia in response to stress. For obesity, weight, height, waist and hip circumference, body composition will be measured with the Inbody 230® impedance meter. For physical activity and sedentary time, we will use the Actigraph® accelerometer alongside the international physical activity questionnaire (IPAQ) and the Marshall questionnaire. The Sphygmocor System® will be used for pulse wave analysis and carotid-femoral pulse wave velocity (cfPWV), while the Vasera VS-2000® will measure cardio ankle vascular index (CAVI) and brachial-ankle pulse wave velocity (baPWV). Vascular aging will be calculated with the 10th and 90th percentiles of cfPWV or baPWV. Demographic, analytical variables will be collected, as will data to assess vascular, cardiac, renal, and brain injury.DiscussionAddictions are on the rise in today’s society, affecting the mental health and well-being of those who suffer from them, generating important social problems such as job loss, family dysfunction, debt and social isolation. Together with obesity, they are prevalent health problems in young adults and are associated with lower physical activity and higher sedentary time. Meanwhile, arterial stiffness and vascular aging are processes that begin gradually at an early age and determine morbidity and mortality caused by cardiovascular diseases. The results of this project will allow us to understand the situation regarding behavioral and substance addictions in young adults. Better understanding of these addictions will in turn facilitate the development of more effective prevention strategies and intervention programs, which can then reduce the negative impact at both the individual and societal levels.Clinical trial registration[ClinicalTrials.gov], identifier [NCT05819840].
Published: 2024
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4. 881 Knockdown of neuropilin-1 by third generation antisense oligonucleotides has strong antitumor activity that can be further increased by combination with immune checkpoint inhibitors

Author: Alfred Zippelius, Mélanie Buchi, Richard Klar, Julia Festag, Monika Schell, Sven Michel, Frank Jaschinski, Nicole Kirchhammer, Andre Maaske, Laura Fernandez Rodriguez, and Stefanie Raith
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published: 2023
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5. Exploring the cost-effectiveness of high versus low perioperative fraction of inspired oxygen in the prevention of surgical site infections among abdominal surgery patients in three low- and middle-income countries

Author: Mwayi Kachapila, Mark Monahan, Adesoji O. Ademuyiwa, Yakubu Momohsani Adinoyi, Bruce M. Biccard, Christina George, Dhruva N. Ghosh, James Glasbey, Dion G. Morton, Osaheni Osayomwanbo, Rupert Pearse, Tracy E. Roberts, Atul Suroy, Saidu Yusuf Yakubu, Raymond Oppong, Aneel Bhangu, Maria Lorena Aguilera, Philip Alexander, Sara W. Al-Saqqa, Giuliano Borda-Luque, Ainhoa Costas-Chavarri, Thomas M. Drake, Faustin Ntirenganya, J. Edward Fitzgerald, Stuart J. Fergusson, J.C. Allen Ingabire, Lawani Ismaïl, Hosni Khairy Salem, Anyomih Theophilus Teddy Kojo, Marie Carmela Lapitan, Richard Lilford, Andre L. Mihaljevic, Dion Morton, Alphonse Zeta Mutabazi, Dmitri Nepogodiev, Adewale O. Adisa, Riinu Ots, Francesco Pata, Thomas Pinkney, Tomas Poškus, Ahmad Uzair Qureshi, Antonio Ramos-De la Medina, Sarah Rayne, Catherine A. Shaw, Sebastian Shu, Richard Spence, Neil Smart, Stephen Tabiri, Ewen M. Harrison, Azmina Verjee, Emmy Runigamugabo, Chetan Khatri, Midhun Mohan, Zahra Jaffry, Afnan Altamini, Andrew Kirby, Kjetil Søreide, Gustavo Recinos, Jen Cornick, Maria Marta Modolo, Dushyant Iyer, Sebastian King, Tom Arthur, Sayeda Nazmum Nahar, Ade Waterman, Michael Walsh, Arnav Agarwal, Augusto Zani, Mohammed Firdouse, Tyler Rouse, Qinyang Liu, Juan Camilo Correa, Peep Talving, Mengistu Worku, Alexis Arnaud, Vassilis Kalles, Basant Kumar, Sunil Kumar, Radhian Amandito, Roy Quek, Luca Ansaloni, Ahmed Altibi, Donatas Venskutonis, Justas Zilinskas, Tomas Poskus, John Whitaker, Vanessa Msosa, Yong Yong Tew, Alexia Farrugia, Elaine Borg, Zineb Bentounsi, Tanzeela Gala, Ibrahim Al-Slaibi, Haya Tahboub, Osaid H. Alser, Diego Romani, Sebestian Shu, Piotr Major, Aurel Mironescu, Matei Bratu, Amar Kourdouli, Aliyu Ndajiwo, Abdulaziz Altwijri, Mohammed Ubaid Alsaggaf, Ahmad Gudal, Al Faifi Jubran, Sam Seisay, Bettina Lieske, Irene Ortega, Jenifa Jeyakumar, Kithsiri J. Senanayake, Omar Abdulbagi, Yucel Cengiz, Dmitri Raptis, Yuksel Altinel, Chia Kong, Ella Teasdale, Gareth Irwin, Michael Stoddart, Rakan Kabariti, Sukrit Suresh, Katherine Gash, Ragavan Narayanan, Mayaba Maimbo, Besmir Grizhja, Shpetim Ymeri, Gezim Galiqi, Roberto Klappenbach, Diego Antezana, Alvaro Enrique Mendoza Beleño, Cecilia Costa, Belen Sanchez, Susan Aviles, Claudio Gabriel Fermani, Rubén Balmaceda, Santiago Villalobos, Juan Manuel Carmona, Daniel Hamill, Peter Deutschmann, Simone Sandler, Daniel Cox, Ram Nataraja, Claire Sharpin, Damir Ljuhar, Demi Gray, Morgan Haines, Dush Iyer, Nithya Niranjan, Scott D'Amours, Morvarid Ashtari, Helena Franco, Ashrarur Rahman Mitul, Sabbir Karim, Nowrin F. Aman, Mahnuma Mahfuz Estee, Umme Salma, Joyeta Razzaque, Tasnia Hamid Kanta, Sayeeda Aktar Tori, Shadid Alamin, Swapnil Roy, Shadid Al Amin, Rezaul Karim, Muhtarima Haque, Amreen Faruq, Farhana Iftekhar, Margaret O'Shea, Greg Padmore, Ramesh Jonnalagadda, Andrey Litvin, Aliaksandr Filatau, Dzmitry Paulouski, Maryna Shubianok, Tatsiana Shachykava, Dzianis Khokha, Vladimir Khokha, Fernande Djivoh, Francis Dossou, Djifid Morel Seto, Dansou Gaspard Gbessi, Bruno Noukpozounkou, Yacoubou Imorou Souaibou, Kpèmahouton René Keke, Fred Hodonou, Ernest Yemalin Stephane Ahounou, Thierry Alihonou, Max Dénakpo, Germain Ahlonsou, Alemayehu Ginbo Bedada, Carlos Nsengiyumva, Sandrine Kwizera, Venerand Barendegere, Philip Choi, Simon Stock, Luai Jamal, Georges Azzie, Sameer Kushwaha, Tzu-Ling Chen, Chingwan Yip, Irene Montes, Felipe Zapata, Sebastian Sierra, Maria Isabel Villegas Lanau, Maria Clara Mendoza Arango, Ivan Mendoza Restrepo, Ruben Santiago Restrepo Giraldo, Edgar Domini, Robert Karlo, Jakov Mihanovic, Mohamed Youssef, Hossam Elfeki, Waleed Thabet, Aly Sanad, Gehad Tawfik, Ahmed Zaki, Noran Abdel-Hameed, Mohamed Mostafa, Muhammad Fathi Waleed Omar, Ahmed Ghanem, Emad Abdallah, Adel Denewar, Eman Emara, Eman Rashad, Ahmad Sakr, Rehab Elashry, Sameh Emile, Toqa Khafagy, Sara Elhamouly, Arwa Elfarargy, Amna Mamdouh Mohamed, Ghada Saied Nagy, Abeer Esam, Eman Elwy, Aya Hammad, Salwa Khallaf, Eman Ibrahim, Ahmed Saidbadr, Ahmed Moustafa, Amany Eldosouky Mohammed, Mohammed Elgheriany, Eman Abdelmageed, Eman Abd Al Raouf, Esraa Samir Elbanby, Maha Elmasry, Mahitab Morsy Farahat, Eman Yahya Mansor, Eman Magdy Hegazy, Esraa Gamal, Heba Gamal, Hend Kandil, Doaa Maher Abdelrouf, Mohamed Moaty, Dina Gamal, Nada El-Sagheer, Mohamed Salah, Salma Magdy, Asmaa Salah, Ahmed Essam, Ahmed Ali, Mahmoud Badawy, Sara Ahmed, Mazed Mohamed, Abdelrahman Assal, Mohamed Sleem, Mai Ebidy, Aly Abd Elrazek, Diaaaldin Zahran, Nourhan Adam, Mohamed Nazir, Adel B. Hassanein, Ahmed Ismail, Amira Elsawy, Rana Mamdouh, Mohamed Mabrouk, Lopna Ahmed Mohamed Ahmed, Mohamed Hassab Alnaby, Eman Magdy, Manar Abd-Elmawla, Marwan Fahim, Bassant Mowafy, Moustafa Ibrahim Mahmoud, Meran Allam, Muhammad Alkelani, Noran Halim El Gendy, Mariam Saad Aboul-Naga, Reham Alaa El-Din, Alyaa Halim Elgendy, Mohamed Ismail, Mahmoud Shalaby, Aya Adel Elsharkawy, Mahmoud Elsayed Moghazy, Khaled Hesham Elbisomy, Hend Adel Gawad Shakshouk, Mohamed Fouad Hamed, Mai Mohamed Ebidy, Mostafa Abdelkader, Mohamed Karkeet, Hayam Ahmed, Israa Adel, Mohammad Elsayed Omar, Mohamed Ibrahim, Omar Ghoneim, Omar Hesham, Shimaa Gamal, Karim Hilal, Omar Arafa, Sawsan Adel Awad, Menatalla Salem, Fawzia Abdellatif Elsherif, Nourhan Elsabbagh, Moustafa R. Aboelsoud, Ahmed Hossam Eldin Fouad Rida, Amr Hossameldin, Ethar Hany, Yomna Hosny Asar, Nourhan Anwar, Mohamed Gadelkarim, Samar Abdelhady, Eman Mohamed Morshedy, Reham Saad, Nourhan Soliman, Mahmoud Salama, Eslam Ezzat, Arwa Mohamed, Arwa Ibrahim, Alaa Fergany, Sara Mohammed, Aya Reda, Yomna Allam, Hanan Adel Saad, Afnan Abdelfatah, Aya Mohamed Fathy, Ahmed El-Sehily, Esraa Abdalmageed Kasem, Ahmed Tarek Abdelbaset Hassan, Ahmed Rabeih Mohammed, Abdalla Gamal Saad, Yasmin Elfouly, Nesma Elfouly, Arij Ibrahim, Amr Hassaan, Mohammed Mustafa Mohammed, Ghada Elhoseny, Mohamed Magdy, Esraa Abd Elkhalek, Yehia Zakaria, Tarek Ezzat, Ali Abo El Dahab, Mohamed Kelany, Sara Arafa, Osama Mokhtar Mohamed Hassan, Nermin Mohamed Badwi, Ahmad Saber Sleem, Hussien Ahmed, Kholoud Abdelbadeai, Mohamed Abozed Abdullah, Muhammad Amsyar Auni Lokman, Suraya Bahar, Anan Rady Abdelazeam, Abdelrahman Adelshone, Muhammad Bin Hasnan, Athirah Zulkifli, Siti Nur Alia Kamarulzamil, Abdelaziz Elhendawy, Aliang Latif, Ahmad Bin Adnan, Shahadatul Shaharuddin, Aminah Hanum Haji Abdul Majid, Mahmoud Amreia, Dina Al-Marakby, Mahmoud Salma, Mohamad Jeffrey Bin Ismail, Elissa Rifhan Mohd Basir, Citra Dewi, Mohd Ali, Aya Yehia Ata, Maha Nasr, Asmaa Rezq, Ahmed Sheta, Sherif Tariq, Abd Elkhalek Sallam, Abdelrhman K.Z. Darwish, Sohaila Elmihy, Shady Elhadry, Ahmed Farag, Haidar Hajeh, Abdelaziz Abdelaal, Amro Aglan, Ahmed Zohair, Mahitab Essam, Omar Moussa, Esraa El-Gizawy, Mostafa Samy, Safia Ali, Esraa Elhalawany, Ahmed Ata, Mohamed El Halawany, Mohamed Nashat, Samar Soliman, Alaa Elazab, Mostada Samy, Mohamed A. Abdelaziz, Khaled Ibrahim, Ahmed mohamed Ibrahim, Ammar Gado, Usama Hantour, Esraa Alm Eldeen, Mohamed Reda loaloa, Arwa Abouzaid, Mostafa Ahmed Bahaa Eldin, Eman Hashad, Fathy Sroor, Doaa Gamil, Eman Mahmoud Abdulhakeem, Mahmoud Zakaria, Fawzy Mohamed, Marwan Abubakr, Elsayed Ali, Hesham Magdy, Menna Tallah Ramadan, Mohamed Abdelaty Mohamed, Salma Mansour, Hager Abdul Aziz Amin, Ahmed Rabie Mohamed, Mahmoud Saami, Nada Ahmed Reda Elsayed, Adham Tarek, Sabry Mohy Eldeen Mahmoud, Islam Magdy El Sayed, Amira Reda, Martina Yusuf Shawky, Mohammed Mousa Salem, Shahinaz Alaa El-Din, Noha Abdullah Soliman, Muhammed Talaat, Shahinaz Alaael-Dein, Ahmed Abd Elmoen Elhusseiny, Noha Abdullah, Mohammed Elshaar, Aya AbdelFatah Ibraheem, Hager Abdulaziz, Mohammed Kamal Ismail, Mona Hamdy Madkor, Mohamed Abdelaty, Sara Mahmoud Abdel-Kader, Osama Mohamed Salah, Mahmoud Eldafrawy, Ahmed Zaki Eldeeb, Mostafa Mahmoud Eid, Attia Attia, Khalid Salah El-Dien, Ayman Shwky, Mohamed Adel Badenjki, Abdelrahman Soliman, Samaa Mahmoud Al Attar, Farrag Sayed, Fahd Abdel Sabour, Mohammed G. Azizeldine, Muhammad Shawqi, Abdullah Hashim, Ahmed Aamer, Ahmed Mahmoud Abdelraouf, Mahmoud Abdelshakour, Amal Ibrahim, Basma Mahmoud, Mohamed Ali Mahmoud, Mostafa Qenawy, Ahmed M. Rashed, Ahmed Dahy, Marwa Sayed, Ahmed W. Shamsedine, Bakeer Mohamed, Ahmad Hasan, Mahmoud M. Saad, Khalil Abdul Bassit, Nadia Khalid Abd El-Latif, Nada Elzahed, Ahmed El Kashash, Nada Mohamed Bekhet, Sarah Hafez, Ahmed Gad, Mahmoud Elkhadragy Maher, Ahmed Abd Elsameea, Mohamed Hafez, Ahmad Sabe, Ataa Ahmed, Ahmed Shahine, Khaled Dawood, Shireen Gaafar, Reem Husseiny, Omnia Aboelmagd, Ahmed Soliman, Nourhan Mesbah, Hossam Emadeldin, Amgad Al Meligy, Amira Hassan Bekhet, Doaa Hasan, Khaled Alhady, Ahmad Khaled Sabe, Mahmoud A. Elnajjar, Majed Aboelella, Ward Hamsho, Ihab Hassan, Hala Saad, Galaleldin Abdelazim, Hend Mahmoud, Noha Wael, Ahmedali M. Kandil, Ahmed Magdy, Shimaa Said Elkholy, Badr Eldin Adel, Kareem Dabbour, Saged Elsherbiney, Omar Mattar, Abdulshafi Khaled Abdrabou, Mohammed Yahia Mohamed Aly, Abdelrahman Geuoshy, Ahmedglal Elnagar, Saraibrahim Ahmed, Ibrahem Abdelmotaleb, Amr Ahmed Saleh, Manar Saeed, Shady Mahmoud, Badreldin Adel Tawfik, Samar Adel Ismail, Esraay Zakaria, Mariam O. Gad, Mohamed Salah Elhelbawy, Monica Bassem, Noha Maraie, Nourhan Medhat Elhadary, Nourhan Semeda, Shaza Rabie Mohamed, Hesham Mohammed Bakry, A.A. Essam, Dina Tarek, Khlood Ashour, Alaa Elhadad, Abdulrahman Abdel-Aty, Ibrahim Rakha, Sara Mamdouh Matter, Rasha Abdelhamed, Omar Abdelkader, Ayat Hassaan, Yasmin Soliman, Amna Mohamed, Sara Ghanem, Sara Amr Mohamed Farouk, Eman Mohamed Ibrahim, Esraa El-Taher, Merna Mostafa, Mohamed Fawzy Mahrous Badr, Rofida Elsemelawy, Aya El-Sawy, Ahmad Bakr, Ahmad Abdel Razaq Al Rafati, Sten Saar, Arvo Reinsoo, Nebyou Seyoum, Tewodros Worku, Agazi Fitsum, Matti Tolonen, Ari Leppäniemi, Ville Sallinen, Benoît Parmentier, Matthieu Peycelon, Sabine Irtan, Sabrina Dardenne, Elsa Robert, Betty Maillot, Etienne Courboin, Alexis Pierre Arnaud, Juliette Hascoet, Olivier Abbo, Amir Ait Kaci, Thomas Prudhomme, Quentin Ballouhey, Céline Grosos, Laurent Fourcade, Tolg Cecilia, Colombani Jean-Francois, Francois-Coridon Helene, Xavier Delforge, Elodie Haraux, Bertrand Dousset, Roberto Schiavone, Sebastien Gaujoux, Jean-Baptiste Marret, Aurore Haffreingue, Julien Rod, Mariette Renaux-Petel, Jean-François Lecompte, Jean Bréaud, Pauline Gastaldi, Chouikh Taieb, Raquillet Claire, Echaieb Anis, Nasir Bustangi, Manuel Lopezv, Aurelien Scalabre, Maria Giovanna Grella, Aurora Mariani, Guillaume Podevin, Françoise Schmitt, Erik Hervieux, Aline Broch, Cecile Muller, Dickson Bandoh, Francis Abantanga, Martin Kyereh, Hamza Asumah, Eric Kofi Appiah, Paul Wondoh, Adam Gyedu, Charles Dally, Kwabena Agbedinu, Michael Amoah, Abiboye Yifieyeh, Frank Owusu, Mabel Amoako-Boateng, Makafui Dayie, Richmond Hagan, Sam Debrah, Micheal Ohene-Yeboah, Joe-Nat Clegg-Lampety, Victor Etwire, Jonathan Dakubo, Samuel Essoun, William Bonney, Hope Glover-Addy, Samuel Osei-Nketiah, Joachim Amoako, Niiarmah Adu-Aryee, William Appeadu-Mensah, Antoinette Bediako-Bowan, Florence Dedey, Mattew Ekow, Emmanuel Akatibo, Musah Yakubu, Hope Edem Kofi Kordorwu, Kwasi Asare-Bediako, Enoch Tackie, Kenneth Aaniana, Emmanuel Acquah, Richard Opoku-Agyeman, Anthony Avoka, Kwasi Kusi, Kwame Maison, Frank Enoch Gyamfi, Gandau Naa Barnabas, Saiba Abdul-Latif, Philip Taah Amoako, Anthony Davor, Victor Dassah, Enoch Dagoe, Prince Kwakyeafriyie, Elliot Akoto, Eric Ackom, Ekow Mensah, Ebenezer Takyi Atkins, Christian Lari Coompson, Nikolaos Ivros, Christoforos Ferousis, Vasileios Kalles, Christos Agalianos, Ioannis Kyriazanos, Christos Barkolias, Angelos Tselos, Georgios Tzikos, Evangelos Voulgaris, Dimitrios Lytras, Athanasia Bamicha, Kyriakos Psarianos, Anastasios Stefanopoulos, Ioannis Patoulias, Dimitrios Sfougaris, Ioannis Valioulis, Dimitrios Balalis, Dimitrios Korkolis, Dimitrios K. Manatakis, Georgios Kyrou, Georgios Karabelias, Iason-Antonios Papaskarlatos, Kolonia Konstantina, Nikolaos Zampitis, Stylianos Germanos, Aspasia Papailia, Theodosios Theodosopoulos, Georgios Gkiokas, Magdalini Mitroudi, Christina Panteli, Thomas Feidantsis, Konstantinos Farmakis, Dimitrios Kyziridis, Orestis Ioannidis, Styliani Parpoudi, Georgios Gemenetzis, Stavros Parasyris, Christos Anthoulakis, Nikolaos Nikoloudis, Michail Margaritis, Maria-Lorena Aguilera-Arevalo, Otto Coyoy-Gaitan, Javier Rosales, Luis Tale, Rafael Soley, Emmanuel Barrios, Servio Tulio Torres Rodriguez, Carlos Paz Galvez, Danilo Herrera Cruz, Guillermo Sanchez Rosenberg, Alejandro Matheu, David Monterroso Cohen, Marie Paul, Angeline Charles, Justin Chak Yiu Lam, Man Hon Andrew Yeung, Chi Ying Jacquelyn Fok, Ka Hin Gabriel Li, Anthony Chuk-Him Lai, Yuk Hong Eric Cheung, Hong Yee Wong, Ka Wai Leung, Tien Seng Bryan Lee, Wai Him Lam, Weihei Dao, Stephanie Hiu-wai Kwok, Tsz-Yan Katie Chan, Yung Kok Ng, T.W.C. Mak, Chi Chung Foo, James Yang, Ankur Bhatnagar, Vijaid Upadhyaya, Uday Muddebihal, Wasim Dar, K.C. Janardha, Neerav Aruldas, Fidelis Jacklyn Adella, Anthonius Santoso Rulie, Ferdy Iskandar, Jonny Setiawan, Cicilia Viany Evajelista, Hani Natalie, Arlindawati Suyadi, Rudy Gunawan, Herlin Karismaningtyas, Lusi Padma Sulistianingsih Mata, Ferry Fitriya Ayu Andika, Afifatun Hasanah, T. Ariani Widiastini, Nurlaila Ayu Purwaningsih, Annisa Dewi Fitriana Mukin, Dina Faizatur Rahmah, Hazmi Dwinanda Nurqistan, Hasbi Maulana Arsyad, Novia Adhitama, Wifanto Saditya Jeo, Nathania Sutandi, Audrey Clarissa, Phebe Anggita Gultom, Matthew Billy, Andreass Haloho, Nadya Johanna, Felix Lee, Radin Mohd Nurrahman Radin Dorani, Martha Glynn, Mohammad Alherz, Wennweoi Goh, Haaris A. Shiwani, Lorraine Sproule, Kevin C. Conlon, Miklosh Bala, Asaf Kedar, Luca Turati, Federica Bianco, Francesca Steccanella, Gaetano Gallo, Mario Trompetto, Giuseppe Clerico, Matteo Papandrea, Giuseppe Sammarco, Rosario Sacco, Angelo Benevento, Luisa Giavarini, Mariano Cesare Giglio, Luigi Bucci, Gianluca Pagano, Viviana Sollazzo, Roberto Peltrini, Gaetano Luglio, Arianna Birindelli, Salomone Di Saverio, Gregorio Tugnoli, Miguel Angel Paludi, Pietro Mingrone, Domenica Pata, Francesco Selvaggi, Lucio Selvaggi, Gianluca Pellino, Natale Di Martino, Gianluca Curletti, Paolo Aonzo, Raffaele Galleano, Stefano Berti, Elisa Francone, Silvia Boni, Laura Lorenzon, Annalisa lo Conte, Genoveffa Balducci, Gianmaria Confalonieri, Giovanni Pesenti, Laura Gavagna, Giorgio Vasquez, Simone Targa, Savino Occhionorelli, Dario Andreotti, Giacomo Pata, Andrea Armellini, Deborah Chiesa, Fabrizio Aquilino, Nicola Chetta, Arcangelo Picciariello, Mohamed Abdelkhalek, Andrea Belli, Silvia De Franciscis, Annamaria Bigaran, Alessandro Favero, Stefano M.M. Basso, Paola Salusso, Martina Perino, Sylvie Mochet, Diego Sasia, Francesco Riente, Marco Migliore, David Merlini, Silvia Basilicò, Carlo Corbellini, Veronica Lazzari, Yuri Macchitella, Luigi Bonavina, Daniele Angelieri, Diego Coletta, Federica Falaschi, Marco Catani, Claudia Reali, Mariastella Malavenda, Celeste Del Basso, Sergio Ribaldi, Massimo Coletti, Andrea Natili, Norma Depalma, Immacolata Iannone, Angelo Antoniozzi, Davide Rossi, Daniele Gui, Gerardo Perrotta, Matteo Ripa, Francesco Ruben Giardino, Maurizio Foco, Erika Vicario, Federico Coccolini, Gabriela Elisa Nita, Nicoletta Leone, Andrea Bondurri, Anna Maffioli, Andrea Simioni, Davide De Boni, Sandro Pasquali, Elena Goldin, Elena Vendramin, Eleonora Ciccioli, Umberto Tedeschi, Luca Bortolasi, Paola Violi, Tommaso Campagnaro, Simone Conci, Giovanni Lazzari, Calogero Iacono, Alfredo Gulielmi, Serena Manfreda, Anna Rinaldi, Maria Novella Ringressi, Beatrice Brunoni, Giuseppe Salamone, Mirko Mangiapane, Paolino De Marco, Antonella La Brocca, Roberta Tutino, Vania Silvestri, Leo Licari, Tommaso Fontana, Nicolò Falco, Gianfranco Cocorullo, Mostafa Shalaby, Pierpaolo Sileri, Claudio Arcudi, Isam Bsisu, Khaled Aljboor, Lana Abusalem, Aseel Alnusairat, Ahmad Qaissieh, Emad Al-Dakka, Ali Ababneh, Oday Halhouli, Taha Yusufali, Hussein Mohammed, Justus Lando, Robert Parker, Wairimu Ndegwa, Mantas Jokubauskas, Jolanta Gribauskaite, Justas Kuliavas, Audrius Dulskas, Narimantas E. Samalavicius, Kristijonas Jasaitis, Audrius Parseliunas, Viktorija Nevieraite, Margarita Montrimaite, Evelina Slapelyte, Edvinas Dainius, Romualdas Riauka, Zilvinas Dambrauskas, Andrejus Subocius, Linas Venclauskas, Antanas Gulbinas, Saulius Bradulskis, Simona Kasputyte, Deimante Mikuckyte, Mindaugas Kiudelis, Tomas Jankus, Steponas Petrikenas, Matas Pažuskis, Zigmantas Urniežius, Mantas Vilčinskas, Vincas Jonas Banaitis, Vytautas Gaižauskas, Edvard Grisin, Povilas Mazrimas, Rokas Rackauskas, Mantas Drungilas, Karolis Lagunavicius, Vytautas Lipnickas, Dovilè Majauskyté, Valdemaras Jotautas, Tomas Abaliksta, Laimonas Uščinas, Gintaras Simutis, Adomas Ladukas, Donatas Danys, Erikas Laugzemys, Saulius Mikalauskas, Elena Zdanyte Sruogiene, Petras Višinskas, Reda Žilinskienė, Deividas Dragatas, Andrius Burmistrovas, Zygimantas Tverskis, Arturas Vaicius, Ruta Mazelyte, Antanas Zadoroznas, Nerijus Kaselis, Greta Žiubrytė, Finaritra Casimir Fleur Prudence Rahantasoa, Luc Hervé Samison, Fanjandrainy Rasoaherinomenjanahary, Todisoa Emmanuella Christina Tolotra, Cornelius Mukuzunga, Chimwemwe Kwatiwani, Nelson Msiska, Feng Yih Chai, Siti Mohd Desa Asilah, Khuzaimah Zahid Syibrah, Pui Xin Chin, Afizah Salleh, Nur Zulaika Riswan, April Camilla Roslani, Hoong-Yin Chong, Nora Abdul Aziz, Keat-Seong Poh, Chu-Ann Chai, Sandip Kumar, Mustafa Mohammed Taher, Nik Ritza Kosai, Dayang Nita Abdul Aziz, Reynu Rajan, Rokayah Julaihi, Durvesh Lacthman Jethwani, Muhammad Taqiyuddin Yahaya, Nik Azim Nik Abdullah, Susan Wndy Mathew, Kuet Jun Chung, Milaksh Kumar Nirumal, R. Goh Ern Tze, Syed Abdul Wahhab Eusoffee Wan Ali, Yiing Yee Gan, Jesse Ron Swire Ting, Samuel S.Y. Sii, Kean Leong Koay, Yi Koon Tan, Alvin Ee Zhiun Cheah, Chui Yee Wong, Tuan Nur'Azmah Tuan Mat, Crystal Yern Nee Chow, Prisca A.L. Har, Yishan Der, Fitjerald Henry, Xinwei Low, Ya Theng Neo, Hian Ee Heng, Shu Ning Kong, Cheewei Gan, Yi Ting Mok, Yee Wen Tan, Kandasami Palayan, Mahadevan Deva Tata, Yih Jeng Cheong, Kuhaendran Gunaseelan, Wan Nurul 'Ain Wan Mohd Nasir, Pigeneswaren Yoganathan, Eu Xian Lee, Jian Er Saw, Li Jing Yeang, Pei Ying Koh, Shyang Yee Lim, Shuang Yi Teo, Nicole Grech, Daniela Magri, Kristina Cassar, Christine Mizzi, Malcolm Falzon, Nihaal Shaikh, Ruth Scicluna, Stefan Zammit, Sean Mizzi, Svetlana Doris Brincat, Thelma Tembo, Vu Thanh Hien Le, Tara Grima, Keith Sammut, Kurt Carabott, Ciskje Zarb, Andre Navarro, Thea Dimech, Georgette Marie Camilleri, Isaac Bertuello, Jeffrey Dalli, Karl Bonavia, Samantha Corro-Diaz, Marisol Manriquez-Reyes, Amina Abdelhamid, Abdelmalek Hrora, Sarah Benammi, Houda Bachri, Meryem Abbouch, Khaoula Boukhal, Redouane Mammar Bennai, Abdelkader Belkouchi, Mohamed Sobhi Jabal, Chaymae Benyaiche, Maarten Vermaas, Lucia Duinhouwer, Javier Pastora, Greta Wood, Maria Soledad Merlo, Akinlabi Ajao, Omobolaji Ayandipo, Taiwo Lawal, Abdussemiu Abdurrazzaaq, Muslimat Alada, Abdulrasheed Nasir, James Adeniran, Olufemi Habeeb, Ademola Popoola, Ademola Adeyeye, Ademola Adebanjo, Opeoluwa Adesanya, Adewale Adeniyi, Henry Mendel, Bashir Bello, Umar Muktar, Adedapo Osinowo, Thomas Olagboyega Olajide, Oyindamola Oshati, George Ihediwa, Babajide Adenekan, Victor Nwinee, Felix Alakaloko, Adesoji Ademuyiwa, Olumide Elebute, Abdulrazzaq Lawal, Chris Bode, Mojolaoluwa Olugbemi, Alaba Adesina, Olubukola Faturoti, Oluwatomi Odutola, Oluwaseyi Adebola, Clement Onuoha, Ogechukwu Taiwo, Omolara Williams, Fatai Balogun, Olalekan Ajai, Mobolaji Oludara, Iloba Njokanma, Roland Osuoji, Stephen Kache, Jonathan Ajah, Jerry Makama, Ahmed Adamu, Suleiman Baba, Mohammad Aliyu, Shamsudeen Aliyu, Yahaya Ukwenya, Halima Aliyu, Tunde Sholadoye, Muhammad Daniyan, Oluseyi Ogunsua, Lofty-John Anyanwu, Abdurrahaman Sheshe, Aminu Mohammad, Samson Olori, Philip Mshelbwala, Babatunde Odeyemi, Garba Samson, Oyediran Kehinde Timothy, Sani Ali Samuel, Anthony Ajiboye, Isaac Amole, Olajide Abiola, Akin Olaolorun, Torhild Veen, Arezo Kanani, Kristian Styles, Ragnar Herikstad, Johannes Wiik Larsen, Jon Arne Søreide, Elisabeth Jensen, Mads Gran, Eirik Kjus Aahlin, Tina Gaarder, Peter Wiel Monrad-Hansen, Pål Aksel Næss, Giedrius Lauzikas, Joachim Wiborg, Silje Holte, Knut Magne Augestad, Gurpreet Singh Banipal, Michela Monteleone, Thomas Tetens Moe, Johannes Kurt Schultz, Taher Al-Taher, Ayah Hamdan, Ayman Salman, Rana Saadeh, Aseel Musleh, Dana Jaradat, Soha Abushamleh, Sakhaa Hanoun, Amjad Abu Qumbos, Aseel Hamarshi, Ayman, Taher, Israa Qawasmi, Khalid Qurie, Marwa Altarayra, Mohammad Ghannam, Alaa Shaheen, Azher Herebat, Aram Abdelhaq, Ahmad Shalabi, Maram Abu-Toyour, Fatema Asi, Ala Shamasneh, Anwar Atiyeh, Mousa Mustafa, Rula Zaa'treh, Majd Dabboor, Enas Alaloul, Heba Baraka, Jehad Meqbil, Alaa Al-Buhaisi, Mohamedraed Elshami, Samah Afana, Sahar Jaber, Said Alyacoubi, Yousef Abuowda, Tasneem Idress, Eman Abuqwaider, Sara Al-Saqqa, Alaa Bowabsak, Alaa El Jamassi, Doaa Hasanain, Hadeel Al-Farram, Maram Salah, Aya Firwana, Marwa Hamdan, Israa Awad, Ahmad Ashour, Fayez Elian Al Barrawi, Ahmed Al-Khatib, Maha Al-Faqawi, Mohamed Fares, Amjad Elmashala, Mohammad Adawi, Ihdaa Adawi, Reem Khreishi, Rose Khreishi, Ahed Ghaben, Najwa Nadeem, Muhammad Saqlain, Jibran Abbasy, Abdul Rehman Alvi, Noman Shahzad, Kamran Faisal Bhopal, Zainab Iftikhar, Muhammad Talha Butt, Syed Asaat Ul Razi, Asdaq Ahmed, Ali Khan Niazi, Ibrahim Raza, Fatima Baluch, Ahmed Raza, Ahmad Bani-Sadar, Muhammad Adil, Awais Raza, Mahnoor Javaid, Muhammad Waqar, Maryam Ali Khan, Mohammad Mohsin Arshad, Mohammadasim Amjad, Gustavo Miguel Machain Vega, Jorge Torres Cardozo, Marcelo O´Higgins Roche, Gustavo Rodolfo Pertersen Servin, Helmut Alfredo Segovia Lohse, Larissa Ines Páez Lopez, Ramón Augusto Melo Cardozo, Fernando Espinoza, Angel David Pérez Rojas, Diana Sanchez, Camila Sanchez Samaniego, Shalon Guevara Torres, Alexander Canta Calua, Cesar Razuri, Nadia Ortiz, Xianelle Rodriguez, Nahilia Carrasco, Fridiz Saravia, Hector Shibao Miyasato, María Valcarcel-Saldaña, Ysabel Esthefany Alejos Bermúdez, Juan Carpio, Walter Ruiz Panez, Pedro Angel Toribio Orbegozo, Carolina Guzmán Dueñas, Kevin Turpo Espinoza, Ana Maria Sandoval Barrantes, Jorge Armando Chungui Bravo, Lorena Fuentes-Rivera, Carmen Fernández, Bárbara Málaga, Joselyn Ye, Ricardo Velasquez, Jannin Salcedo, Ana Lucia Contreras-Vergara, Angelica Genoveva Vergara Mejia, Maria Soledad Gonzales Montejo, Marilia Del Carmen Escalante Salas, Willy Alcca Ticona, Marvin Vargas, George Christian Manrique Sila, Robinson Mas, Arazzelly del Pilar Paucar, Armando José Román Velásquez, Alina Robledo-Rabanal, Ludwing Alexander Zeta Solis, Kenny Turpo Espinoza, José Luis Hamasaki Hamaguchi, Erick Samuel Florez Farfan, Linda Alvi Madrid Barrientos, Juan Jaime Herrera Matta, John Jemuel V. Mora, Menold Archee P. Redota, Manuel Francisco Roxas, Maria Jesusa B. Maño, Marie Dione Parreno-Sacdalan, Christel Leanne Almanon, Maciej Walędziak, Rafał Roszkowski, Michał Janik, Anna Lasek, Dorota Radkowiak, Mateusz Rubinkiewicz, Cristina Fernandes, Jose Costa-Maia, Renato Melo, Liviu Muntean, Aurel Sandu Mironescu, Lucian Corneliu Vida, Mariuca Popa, Hogea Mircea, Mihaela Vartic, Bogdan Diaconescu, Matei Razvan Bratu, Ionut Negoi, Mircea Beuran, Cezar Ciubotaru, Norbert Uzabumwana, Dieudonne Duhoranenayo, Elio Jovine, Nicola Zanini, Giovanni Landolfo, Murad Aljiffry, Faisal Idris, Mohammed Saleh A. Alghamdi, Ashraf Maghrabi, Abdulmalik Altaf, Aroub Alkaaki, Ahmad Khoja, Abrar Nawawi, Sondos Turkustani, Eyad Khalifah, Adel Albiety, Sarah Sahel, Reham Alshareef, Mohammed Najjar, Ahmed Alzahrani, Ahmed Alghamdi, Wedyan Alhazmi, Ghiath Al Saied, Mohammed Alamoudi, Muhammed Masood Riaz, Mazen Hassanain, Basmah Alhassan, Abdullah Altamimi, Reem Alyahya, Norah Al Subaie, Fatema Al Bastawis, Afnan Altamimi, Thamer Nouh, Roaa Khan, Milan Radojkovic, Ljiljana Jeremic, Milica Nestorovic, Jia Hao Law, Keith Say Kwang Tan, Ryan Choon Kiat Tan, Joel Kin Tan, Lau Wen Liang Joel, Xue Wei Chan, Faith Qi Hui Leong, Choon Seng Chong, Sharon Koh, Kai Yin Lee, Kuok Chung Lee, Kent Pluke, Britta Dedekind, Puyearashid Nashidengo, Mark Ian Hampton, Johanna Joosten, Sanju Sobnach, Liana Roodt, Anthony Sander, James Pape, Niveshni Maistry, Phumudzo Ndwambi, Kamau Kinandu, Myint Tun, Frederick Du Toit, Quinn Ellison, D.C. Grobler, Sule Burger, Lawrence Bongani Khulu, Rachel Moore, Vicky Jennings, Astrid Leusink, Nazmie Kariem, Juan Gouws, Kathryn Chu, Heather Bougard, Fazlin Noor, Angela Dell, Stephanie Van Straten, Arvin Khamajeet, Serge Kapenda Tshisola, Kalangu Kabongo, Victor Kong, Yoshan Moodley, Frank Anderson, Thandinkosi Madiba, Flip du Plooy, Leila Hartford, Gareth Chilton, Parveen Karjiker, Matlou Ernest Mabitsela, Sibongile Ruth Ndlovu, Maria Badicel, Robert Jaich, Jaime Ruiz-Tovar, Luis Garcia-Florez, Jorge L. Otero-Díez, Virginia Ramos Pérez, Nuria Aguado Suárez, Javier Minguez García, Sara Corral Moreno, Maria Vicenta Collado, Virginia Jiménez Carneros, Javier García Septiem, Mariana Gonzalez, Antonio Picardo, Enrique Esteban, Esther Ferrero, Eloy Espin-Basany, Ruth Blanco-Colino, Valeria Andriola, Lorena Solar García, Elisa Contreras, Carmen García Bernardo, Janet Pagnozzi, Sandra Sanz, Alberto Miyar de León, Asnel Dorismé, Joseluis Rodicio, Aida Suarez, Jessica Stuva, Tamara Diaz Vico, Laura Fernandez-Vega, Carla Soldevila-Verdeguer, Fatima Sena-Ruiz, Natalia Pujol-Cano, Paula Diaz-Jover, José Maria Garcia-Perez, Juan Jose Segura-Sampedro, Cristina Pineño-Flores, David Ambrona-Zafra, Andrea Craus-Miguel, Patricia Jimenez-Morillas, Angela Mazzella, A.B. Jayathilake, S.P.B. Thalgaspitiya, L.S. Wijayarathna, P.M.S.N. Wimalge, Hakeem Ayomi Sanni, Ogheneochuko Okenabirhie, Anmar Homeida, Abobaker Younis, Omer Abdelbagi Omer, Mustafa Abdulaziz, Ali Mussad, Ali Adam, Ida Björklund, Sandra Ahlqvist, Anders Thorell, Fredrik Wogensen, Arestis Sokratous, Michaela Breistrand, Hildur Thorarinsdottir, Johanna Sigurdadottir, Maziar Nikberg, Abbas Chabok, Maria Hjertberg, Peter Elbe, Deborah Saraste, Wiktor Rutkowski, Louise Forlin, Karoliina Niska, Malin Sund, Dennis Oswald, Georgios Peros, Rafael Bluelle, Katharina Reinisch, Daniel Frey, Adrian Palma, Dimitri Aristotle Raptis, Lucius Zumbühl, Markus Zuber, Roger Schmid, Gabriela Werder, Antonio Nocito, Alexandra Gerosa, Silke Mahanty, Lukas Werner Widmer, Julia Müller, Alissa Gübeli, Grzegorz Zuk, Osman Bilgin Gulcicek, Talar Vartanoglu, Emin Kose, Servet Rustu Karahan, Mehmet Can Aydin, Nuri Alper Sahbaz, Ilkay Halicioglu, Halil Alis, Ipek Sapci, Can Adıyaman, Ahmet Murat Pektaş, Turgut Bora Cengiz, Ilkan Tansoker, Vedatcan Işler, Muazzez Cevik, Deniz Mutlu, Volkan Ozben, Berk Baris Ozmen, Sefa Bayram, Sinem Yolcu, Berna Buse Kobal, Ömer Faruk Toto, Haluk Cem Çakaloğlu, Kagan Karabulut, Vahit Mutlu, Bahar Busra Ozkan, Saban Celik, Anil Semiz, Selim Bodur, Enisburak Gül, Busra Murutoglu, Reyyan Yildirim, Bahadir Emre Baki, Ekin Arslan, Mehmet Ulusahin, Ali Guner, Nathan Walker, Nikhita Shrimanker, Simon Cole, Ryan Breslin, Ravi Srinivasan, Mohamed Elshaer, Kristina Hunter, Ahmed Al-Bahrani, Ignatius Liew, Nora Grace Mairs, Alistair Rocke, Lachlan Dick, Mobeen Qureshi, Debkumar Chowdhury, Naomi Wright, Clare Skerritt, Dorothy Kufeji, Adrienne Ho, Tharindra Dissanayake, Athula Tennakoon, Wadah Ali, Shujing Jane Lim, Charlene Tan, Stephen O'Neill, Catrin Jones, Stephen Knight, Dima Nassif, Abhishek Sharma, Oliver Warren, Rebecca White, Aia Mehdi, Nathan Post, Eliana Kalakouti, Enkhbat Dashnyam, Frederick Stourton, Ioannis Mykoniatis, Chelise Currow, Francisca Wong, Ashish Gupta, Veeranna Shatkar, Joshua Luck, Suraj Kadiwar, Alexander Smedley, Rebecca Wakefield, Philip Herrod, James Blackwell, Jonathan Lund, Fraser Cohen, Ashwath Bandi, Stefano Giuliani, Giles Bond-Smith, Theodore Pezas, Neda Farhangmehr, Tomas Urbonas, Miklos Perenyei, Philip Ireland, Natalie Blencowe, Kirk Bowling, David Bunting, Lydia Longstaff, Kenneth Keogh, Hyunjin Jeon, Muhammad Rafaih Iqbal, Shivun Khosla, Anna Jeffery, James Perera, Ahmad Aboelkassem Ibrahem, Tariq Alhammali, Yahya Salama, Shaun Oram, Thomas Kidd, Fraser Cullen, Christopher Owen, Michael Wilson, Seehui Chiu, Hannah Sarafilovic, Jennifer Ploski, Elizabeth Evans, Athar Abbas, Sylvia Kamya, Norzawani Ishak, Carly Bisset, Cedar Andress, Ye Ru Chin, Priya Patel, David Evans, Aidan Haslegrave, Adam Boggon, Kirsten Laurie, Katie Connor, Thomas Mann, Anahita Mansuri, Rachel Davies, Ewen Griffiths, Aized Raza Shahbaz, Calvin Eng, Farhat Din, Ariadne L'Heveder, Esther H.G. Park, Ramanish Ravishankar, Kirsten McIntosh, Jih Dar Yau, Luke Chan, Susan McGarvie, Lingshan Tang, Hui Lim, Suhhuey Yap, Jay Park, Zhan Herr Ng, Shahrukh Mirza, Yun Lin Ang, Luke Walls, Chloe Roy, Simon Paterson-Brown, Julian Camilleri-Brennan, Kenneth Mclean, Michelle S. D'Souza, Savva Pronin, David Ewart Henshall, Eunice Zuling Ter, Dina Fouad, Ashish Minocha, William English, Catrin Morgan, Dominic Townsend, Laura Maciejec, Shareef Mahdi, Onyinye Akpenyi, Elisabeth Hall, Hanaan Caydiid, Zakaria Rob, Tom Abbott, Hew D. Torrance, Robin Johnston, Mohammed Akil Gani, Gianpiero Gravante, Shivanchan Rajmohan, Kiran Majid, Shiva Dindyal, Christopher Smith, Madanmohan Palliyil, Sanjay Patel, Luke Nicholson, Neil Harvey, Katie Baillie, Sam Shillito, Suzanne Kershaw, Rebecca Bamford, Peter Orton, Elke Reunis, Robert Tyler, Wai Cheong Soon, Guled M. Jama, Dharminder Dhillon, Khyati Patel, Shayanthan Nanthakumaran, Rachel Heard, Kar Yan Chen, Behrad Barmayehvar, Uttaran Datta, Sivesh K. Kamarajah, Sharad Karandikar, Sobhana Iftekhar Tani, Eimear Monaghan, Philippa Donnelly, Michael Walker, Jehangirshaw Parakh, Sarah Blacker, Anil Kaul, Arjun Paramasivan, Sameh Farag, Ashrafun Nessa, Salwa Awadallah, Jieqi Lim, James Chean Khun Ng, Ravi P. Kiran, Alice Murray, Eric Etchill, Mohini Dasari, Juan Puyana, Nadeem Haddad, Martin Zielinski, Asad Choudhry, Celeste Caliman, Mieshia Beamon, Therese Duane, Mamta Swaroop, Jonathan Myers, Rebecca Deal, Erik Schadde, Mark Hemmila, Lena Napolitano, Kathleen To, Alex Makupe, Joseph Musowoya, Niels Van Der Naald, Dayson Kumwenda, Alex Reece-Smith, Kars Otten, Anna Verbeek, Marloes Prins, Alibeth Andres Baquero Suarez, Ruben Balmaceda, Chelsea Deane, Emilio Dijan, Mahmoud Elfiky, Laura Koskenvuo, Aurore Thollot, Bernard Limoges, Carmen Capito, Challine Alexandre, Henri Kotobi, Julien Leroux, Kalitha Pinnagoda, Nicolas Henric, Olivier Azzis, Olivier Rosello, Poddevin Francois, Sara Etienne, Philippe Buisson, Sophian Hmila, Joe-Nat Clegg-Lamptey, Osman Imoro, Owusu Emmanuel Abem, Dimitrios Papageorgiou, Vasiliki Soulou, Sabrina Asturias, Lenin Peña, Donal B. O’Connor, Alberto Realis Luc, Alfio Alessandro Russo, Andrea Ruzzenente, Antonio Taddei, Camilla Cona, Corrado Bottini, Giovanni Pascale, Giuseppe Rotunno, Leonardo Solaini, Marco Maria Pascale, Margherita Notarnicola, Mario Corbellino, Michele Sacco, Paolo Ubiali, Roberto Cautiero, Tommaso Bocchetti, Elena Muzio, Vania Guglielmo, Eugenio Morandi, Patrizio Mao, Emilia De Luca, Farah Mahmoud Ali, Justas Žilinskas, Kestutis Strupas, Paulius Kondrotas, Robertas Baltrunas, Juozas Kutkevicius, Povilas Ignatavicius, Choy Ling Tan, Jia Yng Siaw, Sir Young Yam, Ling Wilson, Mohamed Rezal Abdul Aziz, John Bondin, Carmina Diaz Zorrilla, Anass Majbar, Danjuma Sale, Lawal Abdullahi, Olabisi Osagie, Omolara Faboya, Adedeji Fatuga, Agboola Taiwo, Emeka Nwabuoku, Marte Bliksøen, Zain Ali Khan, Jazmin Coronel, Cesar Miranda, Idelso Vasquez, Luis M. Helguero-Santin, Jennifer Rickard, Adesina Adedeji, Saleh Alqahtani, Max Rath, Michael Van Niekerk, Modise Zacharia Koto, Roel Matos-Puig, Leif Israelsson, Tobias Schuetz, Mahmut Arif Yuksek, Meric Mericliler, Mehmet Uluşahin, Bernhard Wolf, Cameron Fairfield, Guo Liang Yong, Katharine Whitehurst, Natalie Redgrave, Caroluce K. Musyoka, James Olivier, Kathryn Lee, Michael Cox, Muhamed M.H. Farhan-Alanie, Rory Callan, Chali Chibuye, Tebian Hassanein Ahmed Ali, Syrine Rekhis, Muna Rommaneh, Zi Hao Sam, Thays Brunelli Pugliesi, Gabriel Pardo, and Ruth Blanco
Subjects: abdominal surgery, cost-effectiveness analysis, global surgery, high fraction of inspired oxygen, low-and middle-income countries, surgical site infection, Anesthesiology, RD78.3-87.3
Abstract: Background: This study assessed the potential cost-effectiveness of high (80–100%) vs low (21–35%) fraction of inspired oxygen (FiO2) at preventing surgical site infections (SSIs) after abdominal surgery in Nigeria, India, and South Africa. Methods: Decision-analytic models were constructed using best available evidence sourced from unbundled data of an ongoing pilot trial assessing the effectiveness of high FiO2, published literature, and a cost survey in Nigeria, India, and South Africa. Effectiveness was measured as percentage of SSIs at 30 days after surgery, a healthcare perspective was adopted, and costs were reported in US dollars ($). Results: High FiO2 may be cost-effective (cheaper and effective). In Nigeria, the average cost for high FiO2 was $216 compared with $222 for low FiO2 leading to a −$6 (95% confidence interval [CI]: −$13 to −$1) difference in costs. In India, the average cost for high FiO2 was $184 compared with $195 for low FiO2 leading to a −$11 (95% CI: −$15 to −$6) difference in costs. In South Africa, the average cost for high FiO2 was $1164 compared with $1257 for low FiO2 leading to a −$93 (95% CI: −$132 to −$65) difference in costs. The high FiO2 arm had few SSIs, 7.33% compared with 8.38% for low FiO2, leading to a −1.05 (95% CI: −1.14 to −0.90) percentage point reduction in SSIs. Conclusion: High FiO2 could be cost-effective at preventing SSIs in the three countries but further data from large clinical trials are required to confirm this.
Published: 2023
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6. Innovation and Technology in Hospitality Sector: Outcome and Performance

Author: Francisco-Jose Molina-Castillo, Angel-Luis Meroño-Cerdán, Carolina Lopez-Nicolas, and Laura Fernandez-Espinar
Subjects: innovation, technology, hospitality, Business, HF5001-6182, Finance, HG1-9999, Economic theory. Demography, HB1-3840
Abstract: This article aims to explain the innovative behaviour of large Spanish companies by comparing the hospitality industry with other service providers and industrial manufacturers. Several hypotheses are proposed and tested for different innovation stages: innovation effort, outcome and performance. The sample includes 2944 Spanish companies with 200 or more employees. Using one-way ANOVA analysis, this study fills an important gap in the impact of innovation and technology on the performance of the hospitality sector. The results show that catering establishments have differentiated innovation behaviours not only to manufacturers but also compared to service providers. The findings support the hypothesis and suggest that hotel companies complement in-house R&D with other innovative activities. Furthermore, hospitality organisations have the highest percentage of innovation revenue due to fewer innovation efforts and innovation outcomes, mainly due to the organisation’s innovations.
Published: 2023
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7. Deletion of SNX9 alleviates CD8 T cell exhaustion for effective cellular cancer immunotherapy

Author: Marcel P. Trefny, Nicole Kirchhammer, Priska Auf der Maur, Marina Natoli, Dominic Schmid, Markus Germann, Laura Fernandez Rodriguez, Petra Herzig, Jonas Lötscher, Maryam Akrami, Jane C. Stinchcombe, Michal A. Stanczak, Andreas Zingg, Melanie Buchi, Julien Roux, Romina Marone, Leyla Don, Didier Lardinois, Mark Wiese, Lukas T. Jeker, Mohamed Bentires-Alj, Jérémie Rossy, Daniela S. Thommen, Gillian M. Griffiths, Heinz Läubli, Christoph Hess, and Alfred Zippelius
Subjects: Science
Abstract: The efficacy of T-cell-based cancer immunotherapies can be compromised by T cell exhaustion. Here the authors develop a human ex vivo exhaustion model and, based on a CRISPR-Cas9 screen, identify SNX9 as a regulator of T cell exhaustion, showing that SNX9 knockout is associated with improved T cell function and anti-tumor activity in preclinical cancer models.
Published: 2023
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8. MeWEHV: Mel and Wave Embeddings for Human Voice Tasks

Author: Andres Carofilis, Laura Fernandez-Robles, Enrique Alegre, and Eduardo Fidalgo
Subjects: Embeddings, HuBERT, speech classification, WavLM, XLSR-Wav2Vec2, YouSpeakers204, Electrical engineering. Electronics. Nuclear engineering, TK1-9971
Abstract: A recent trend in speech processing is the use of embeddings created through machine learning models trained on a specific task with large datasets. By leveraging the knowledge already acquired, these models can be reused in new tasks where the amount of available data is small. This paper proposes a pipeline to create a new model, called Mel and Wave Embeddings for Human Voice Tasks (MeWEHV), capable of generating robust embeddings for speech processing. MeWEHV combines the embeddings generated by a pre-trained raw audio waveform encoder model, and deep features extracted from Mel Frequency Cepstral Coefficients (MFCCs) using Convolutional Neural Networks (CNNs). We evaluate the performance of MeWEHV on three tasks: speaker, language, and accent identification. For the first one, we use the VoxCeleb1, and VBHIR datasets and present YouSpeakers204, a new and publicly available dataset for English speaker identification that contains 19607 audio clips from 204 persons speaking in six different accents, allowing other researchers to work with a very balanced dataset, and to create new models that are robust to multiple accents. For evaluating the language identification task, we use the VoxForge, Common Language, and the LRE17 datasets. Finally, for accent identification, we use the Latin American Spanish Corpora (LASC), Common Voice, and the NISP datasets. Our approach allows a significant increase in the performance of state-of-the-art embedding generation models on all the tested datasets, with a low additional computational cost.
Published: 2023
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9. Dietary Debaryomyces hansenii promotes skin and skin mucus defensive capacities in a marine fish model

Author: Ignasi Sanahuja, Laura Fernandez-Alacid, Silvia Torrecillas, Alberto Ruiz, Eva Vallejos-Vidal, Joana P. Firmino, Felipe E. Reyes-Lopez, Lluis Tort, Dariel Tovar-Ramirez, Antoni Ibarz, and Enric Gisbert
Subjects: Debaryomyces hansenii, skin defense, skin mucus defense, skin mucus associated biomarkers, transcriptomics, yeast probiotic, Immunologic diseases. Allergy, RC581-607
Abstract: The present study explores the effects of two supplementation levels of Debaryomyces hansenii (1.1% and 2.2%) as a probiotic in a reference low fish meal-based diet on the skin mucosal tissue in Sparus aurata. This study includes the evaluation of fish performance coupled with a holistic study of the skin mucosa: i) a transcriptomic study of the skin tissue, and ii) the evaluation of its secreted mucus both in terms of skin mucosal-associated biomarkers and its defensive capacity by means of co-culture analysis with two pathogenic bacteria. Results showed that after 70 days of diet administration, fish fed the diet supplemented with D. hansenii at 1.1% presented increased somatic growth and a better feed conversion ratio, compared to fish fed the control diet. In contrast, fish fed the diet including 2.2% of the probiotic presented intermediate values. Regarding gene regulation, the probiotic administration at 1.1% resulted in 712 differentially expressed genes (DEGs), among which 53.4% and 46.6% were up- and down-regulated, respectively. In particular, D. hansenii modulated some skin biological processes related to immunity and metabolism. Specifically, D. hansenii administration induced a strong modulation of some immune biological-related processes (61 DEGs), mainly involved in B- and T-cell regulatory pathways. Furthermore, dietary D. hansenii promoted the skin barrier function by the upregulation of anchoring junction genes (23 DEGs), which reinforces the physical defense against potential skin damage. In contrast, the skin showed modulated genes related to extracellular exosome and membrane organization (50 DEGs). This modulated functioning is of great interest, particularly in relation to the increased skin mucus defensive capacity observed in the bacterial co-culture in vitro trials, which could be related to the increased modulation and exudation of the innate immune components from the skin cells into the mucus. In summary, the modulation of innate immune parameters coupled with increased skin barrier function and cell trafficking potentiates the skin’s physical barrier and mucus defensive capacity, while maintaining the skin mucosa’s homeostatic immune and metabolic status. These findings confirmed the advantages of D. hansenii supplementation in low fish meal-based diets, demonstrating the probiotic benefits on cultured marine species.
Published: 2023
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10. PB2022: ELTROMBOPAG IN MYELODYSPLASTIC SYNDROME AND CHRONIC MYELOMONOCYTIC LEUKEMIA: A SINGLE-CENTER EXPERIENCE

Author: Amaia Lopez Peña, Marta Sofia Ordas Miguelez, Carmen Rodriguez Lefler, Pablo Estuardo Lopez Gomez, Mar Herrero Gutierrez, Laura Fernandez Cuezva, Jhossyuriel Obregon Membreño, Rita Gonzalez Resina, Laura Villarroya Martínez, Leire Etxebarria Bahillo, Rafael Monleon Gil, Ana Cristina Godoy Molias, Miguel Diaz Morfa, Isabel Izquierdo Garcia, Pilar Delgado Beltran, and Gonzalo Caballero Navarro
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Published: 2023
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11. PB2215: HYDROXYUREA-INDUCED CUTANEUS ADVERSE EVENTS IN PATIENTS WITH ESSENTIAL THROMBOCYTHEMIA: A SINGLE-CENTER EXPERIENCE

Author: Amaia Lopez Peña, Marta Sofia Ordas Miguelez, Carmen Rodriguez Lefler, Jhossyuriel Obregon Membreño, Rita Gonzalez Resina, Laura Fernandez Cuezva, Mar Herrero Gutierrez, Pablo Estuardo Lopez Gomez, Leire Etxebarria Bahillo, Laura Villarroya Martínez, Rafael Monleon Gil, Pilar Delgado Beltran, and Gonzalo Caballero Navarro
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Published: 2023
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12. AnimalTraits - a curated animal trait database for body mass, metabolic rate and brain size

Author: Marie E. Herberstein, Donald James McLean, Elizabeth Lowe, Jonas O. Wolff, Md Kawsar Khan, Kaitlyn Smith, Andrew P. Allen, Matthew Bulbert, Bruno A. Buzatto, Mark D. B. Eldridge, Daniel Falster, Laura Fernandez Winzer, Simon C. Griffith, Joshua S. Madin, Ajay Narendra, Mark Westoby, Martin J. Whiting, Ian J. Wright, and Alexandra J. R. Carthey
Subjects: Science
Abstract: Measurement(s) metabolic rate quantification • body mass • brain size Technology Type(s) metabolic rate measurement • body mass quantification • brain mass brain volume
Published: 2022
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13. Dual TLR9 and PD-L1 targeting unleashes dendritic cells to induce durable antitumor immunity

Author: Alfred Zippelius, Mélanie Buchi, Richard Klar, Julia Festag, Sven Michel, Frank Jaschinski, Sebastian Kobold, Abhishek S Kashyap, Johannes vom Berg, Laura Fernandez-Rodriguez, Chiara Cianciaruso, Ruben Bill, Marcel P Trefny, Nicole Kirchhammer, Rainer H Kohler, Elham Jones, Andre Maaske, Karen O Dixon, and Mikael J Pittet
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Background Although immune checkpoint inhibitors have been a breakthrough in clinical oncology, these therapies fail to produce durable responses in a significant fraction of patients. This lack of long-term efficacy may be due to a poor pre-existing network linking innate and adaptive immunity. Here, we present an antisense oligonucleotide (ASO)-based strategy that dually targets toll-like receptor 9 (TLR9) and programmed cell death ligand 1 (PD-L1), aiming to overcome resistance to anti-PD-L1 monoclonal therapy.Methods We designed a high-affinity immunomodulatory IM-TLR9:PD-L1-ASO antisense oligonucleotide (hereafter, IM-T9P1-ASO) targeting mouse PD-L1 messenger RNA and activating TLR9. Then, we performed in vitro and in vivo studies to validate the IM-T9P1-ASO activity, efficacy, and biological effects in tumors and draining lymph nodes. We also performed intravital imaging to study IM-T9P1-ASO pharmacokinetics in the tumor.Results IM-T9P1-ASO therapy, unlike PD-L1 antibody therapy, results in durable antitumor responses in multiple mouse cancer models. Mechanistically, IM-T9P1-ASO activates a state of tumor-associated dendritic cells (DCs), referred to here as DC3s, which have potent antitumor potential but express the PD-L1 checkpoint. IM-T9P1-ASO has two roles: it triggers the expansion of DC3s by engaging with TLR9 and downregulates PD-L1, thereby unleashing the antitumor functions of DC3s. This dual action leads to tumor rejection by T cells. The antitumor efficacy of IM-T9P1-ASO depends on the antitumor cytokine interleukin-12 (IL-12), produced by DC3s, and Batf3, a transcription factor required for DC development.Conclusions By simultaneously targeting TLR9 and PD-L1, IM-T9P1-ASO amplifies antitumor responses via DC activation, leading to sustained therapeutic efficacy in mice. By highlighting differences and similarities between mouse and human DCs, this study could serve to develop similar therapeutic strategies for patients with cancer.
Published: 2023
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14. Enhancing the Hydrolytic Activity of a Lipase towards Larger Triglycerides through Lid Domain Engineering

Author: Laura Fernandez-Lopez, Sergi Roda, Ana Robles-Martín, Rubén Muñoz-Tafalla, David Almendral, Manuel Ferrer, and Víctor Guallar
Subjects: lipase, lid domain, protein engineering, rational design, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract: Lipases have valuable potential for industrial use, particularly those mostly active against water-insoluble substrates, such as triglycerides composed of long-carbon chain fatty acids. However, in most cases, engineered variants often need to be constructed to achieve optimal performance for such substrates. Protein engineering techniques have been reported as strategies for improving lipase characteristics by introducing specific mutations in the cap domain of esterases or in the lid domain of lipases or through lid domain swapping. Here, we improved the lipase activity of a lipase (WP_075743487.1, or LipMRD) retrieved from the Marine Metagenomics MarRef Database and assigned to the Actinoalloteichus genus. The improvement was achieved through site-directed mutagenesis and by substituting its lid domain (FRGTEITQIKDWLTDA) with that of Rhizopus delemar lipase (previously R. oryzae; UniProt accession number, I1BGQ3) (FRGTNSFRSAITDIVF). The results demonstrated that the redesigned mutants gain activity against bulkier triglycerides, such as glyceryl tridecanoate and tridodecanoate, olive oil, coconut oil, and palm oil. Residue W89 (LipMRD numbering) appears to be key to the increase in lipase activity, an increase that was also achieved with lid swapping. This study reinforces the importance of the lid domains and their amino acid compositions in determining the substrate specificity of lipases, but the generalization of the lid domain swapping between lipases or the introduction of specific mutations in the lid domain to improve lipase activity may require further investigation.
Published: 2023
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15. Evaluating the repetitive mucus extraction effects on mucus biomarkers, mucous cells, and the skin-barrier status in a marine fish model

Author: Ignasi Sanahuja, Pedro M. Guerreiro, Albert Girons, Laura Fernandez-Alacid, and Antoni Ibarz
Subjects: antibacterial activity, skin mucus-associated biomarkers (SMABs), mucous cells, mucus barrier, marine fish, Science, General. Including nature conservation, geographical distribution, QH1-199.5
Abstract: Among all the mucosal barriers, the skin and its surrounding mucus are possibly the main defensive tool against changes in the environment that can be harmful for fish. Due to the extraction of this mucus being less invasive, the study of its production and functions has attracted great interest in recent years. However, there are still many gaps concerning the sampling process as well as the possible alterations in skin integrity and mucus composition. In the current study, the effects of skin mucus extraction were determined by comparing the effects of a single extraction (single extraction group, SEG) with those of three successive extractions separated by 3 days (repetitive extractions group, REG). Intact skin histology without mucus extraction (ØEG) and both plasma and skin mucus biomarkers and antibacterial capacities were also assessed. Regarding the skin histology and skin barrier properties, both the SEG and REG did not show differences in the intact skin. Interestingly, repetitive mucus extractions seemed to activate skin mucus turnover, significantly increasing the number of small-sized mucous cells (cell area< 100 µm2) and reducing the number of large-sized mucous cells (cell area > 150 µm2). Repetitive extractions significantly decreased the amounts of soluble protein and increased cortisol secretion. These metabolites remained unaltered in the plasma, indicating different responses in the plasma and mucus. Despite changes in the mucus biomarkers, antibacterial capacity against pathogenic bacteria (Pseudomonas anguilliseptica and Vibrio anguillarum) was maintained in both the plasma and mucus irrespective of the number of mucus extractions. Overall, the mucus sampling protocol had little effect on skin integrity and mucus antibacterial properties, only modifying the amounts of soluble protein exuded and stimulating mucous cell replacement. This protocol is a feasible and minimally invasive way of studying and monitoring fish health and welfare and can be used as an alternative or a complement to plasma analysis. This methodology can be transferred to farm culture conditions and be very useful for studying threatened species in order to preserve fish welfare.
Published: 2023
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16. Luxury brands: Awareness and image and its influence on loyalty and engagement

Author: Valentín Gallart-Camahort, Eugenio de la Oliva Ramos, and Laura Fernandez-Duran
Subjects: luxury brands, brand awareness, brand image, brand loyalty, engagement., Commerce, HF1-6182, Economic theory. Demography, HB1-3840
Abstract: Since engagement is a relatively new concept in the field of marketing and is not usually included when studying brand equity, this paper aims to analyze what role engagement has in its relationship with the creation of value for luxury brands. A theoretical model was specified and tested by confirmatory factor analysis. Hypothesis have been tested running a structural equations model. Each hypothesis has resulted to be significant. The conclusions obtained from the analysis of the data allow us to describe the effects that occur between the variables, being important for their management so that managers of the luxury companies can increase the value of their brands.
Published: 2021
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17. Sulforaphane Reduces the Chronic Inflammatory Immune Response of Human Dendritic Cells

Author: Laura Fernandez-Prades, Mariano Brasal-Prieto, Gonzalo Alba, Victoria Martin, Sergio Montserrat-de la Paz, Marta Cejudo-Guillen, Consuelo Santa-Maria, Hala Dakhaoui, Beatriz Granados, Francisco Sobrino, Francisca Palomares, and Soledad Lopez-Enriquez
Subjects: nutraceutical, dendritic cells, T lymphocytes, anti-inflammatory response, autophagy, apoptosis, Nutrition. Foods and food supply, TX341-641
Abstract: Background: Sulforaphane (SFN) is an isothiocyanate of vegetable origin with potent antioxidant and immunomodulatory properties. The characterization of its pleiotropic activity in human dendritic cells (DCs) is poorly summarized. The aim of this work was to study the immunomodulatory power of SFN in response to an inflammatory microenvironment on human monocyte-derived DCs (moDCs). Methods: We studied the immunological response induced by SFN. Apoptosis and autophagy assays were performed using flow cytometry on moDCs and a cancer cell line (THP-1). These included moDC maturation, lymphocyte proliferation and cytokine production under different experimental conditions. We investigated whether these results were associated with an inflammatory microenvironment induced by lipopolysaccharides (LPSs). Results: Our results demonstrated that SFN could interact with moDCs, significantly reducing the autophagy process and enhancing apoptosis similarly to cancer cell line THP-1 cells in a chronic inflammatory microenvironment. Under chronic inflammation, SFN modulated the phenotypical characteristics of moDCs, reducing the expression of all markers (CD80, CD83, CD86, HLA-DR and PD-L1). SFN significantly reduced the Th2 proliferative response, with a decrease in the IL-9 and IL-13 levels. Although we did not observe any changes in the regulatory proliferative response, we noted an increase in the IL-10 levels. Conclusions: These findings demonstrate that SFN exerts protective effects against LPS-induced inflammation via the modulation of moDCs/T cells towards a regulatory profile. SFN may be a potential candidate for the treatment of pathologies with an inflammatory profile.
Published: 2023
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18. Re-staging and follow-up of rectal cancer patients with MR imaging when 'Watch-and-Wait' is an option: a practical guide

Author: Inês Santiago, Bernardete Rodrigues, Maria Barata, Nuno Figueiredo, Laura Fernandez, Antonio Galzerano, Oriol Parés, and Celso Matos
Subjects: Rectal cancer, Magnetic resonance imaging, Neoadjuvant therapy, Re-staging, “Watch-and-Wait”, Medical physics. Medical radiology. Nuclear medicine, R895-920
Abstract: Abstract In the past nearly 20 years, organ-sparing when no apparent viable tumour is present after neoadjuvant therapy has taken an increasingly relevant role in the therapeutic management of locally-advanced rectal cancer patients. The decision to include a patient or not in a “Watch-and-Wait” program relies mainly on endoscopic assessment by skilled surgeons, and MR imaging by experienced radiologists. Strict surveillance using the same modalities is required, given the chance of a local regrowth is of approximately 25–30%, almost always surgically salvageable if caught early. Local regrowths occur at the endoluminal aspect of the primary tumour bed in almost 90% of patients, but the rest are deep within it or outside the rectal wall, in which case detection relies solely on MR Imaging. In this educational review, we provide a practical guide for radiologists who are, or intend to be, involved in the re-staging and follow-up of rectal cancer patients in institutions with an established “Watch-and-Wait” program. First, we discuss patient preparation and MR imaging acquisition technique. Second, we focus on the re-staging MR imaging examination and review the imaging findings that allow us to assess response. Third, we focus on follow-up assessments of patients who defer surgery and confer about the early signs that may indicate a sustained/non-sustained complete response, a rectal/extra-rectal regrowth, and the particular prognosis of the “near-complete” responders. Finally, we discuss our proposed report template.
Published: 2021
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19. The Komagataeibacter europaeus GqqA is the prototype of a novel bifunctional N-Acyl-homoserine lactone acylase with prephenate dehydratase activity

Author: Nadine Werner, Katrin Petersen, Christel Vollstedt, Pablo Perez Garcia, Jennifer Chow, Manuel Ferrer, Laura Fernandez-Lopez, Sven Falke, Markus Perbandt, Winfried Hinrichs, Christian Betzel, and Wolfgang R. Streit
Subjects: Medicine, Science
Abstract: Abstract Previously, we reported the isolation of a quorum quenching protein (QQ), designated GqqA, from Komagataeibacter europaeus CECT 8546 that is highly homologous to prephenate dehydratases (PDT) (Valera et al. in Microb Cell Fact 15, 88. https://doi.org/10.1186/s12934-016-0482-y , 2016). GqqA strongly interfered with N-acyl-homoserine lactone (AHL) quorum sensing signals from Gram-negative bacteria and affected biofilm formation in its native host strain Komagataeibacter europaeus. Here we present and discuss data identifying GqqA as a novel acylase. ESI–MS–MS data showed unambiguously that GqqA hydrolyzes the amide bond of the acyl side-chain of AHL molecules, but not the lactone ring. Consistent with this observation the protein sequence does not carry a conserved Zn2+ binding motif, known to be essential for metal-dependent lactonases, but in fact harboring the typical periplasmatic binding protein domain (PBP domain), acting as catalytic domain. We report structural details for the native structure at 2.5 Å resolution and for a truncated GqqA structure at 1.7 Å. The structures obtained highlight that GqqA acts as a dimer and complementary docking studies indicate that the lactone ring of the substrate binds within a cleft of the PBP domain and interacts with polar residues Y16, S17 and T174. The biochemical and phylogenetic analyses imply that GqqA represents the first member of a novel type of QQ family enzymes.
Published: 2021
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20. Colour Neural Descriptors for Instance Retrieval Using CNN Features and Colour Models

Author: Surajit Saikia, Laura Fernandez-Robles, Eduardo Fidalgo Fernandez, and Enrique Alegre
Subjects: Colour neural descriptors, CNN, image retrieval, image representation, Electrical engineering. Electronics. Nuclear engineering, TK1-9971
Abstract: Image representations in the form of neural activations derived from intermediate layers of deep neural networks are the state-of-the-art descriptors for instance based retrieval. However, the problem that persists consists of how to retrieve identical images as the most relevant ones from a large image or video corpus. In this work, we introduce colour neural descriptors that are made of convolutional neural networks (CNN) features obtained by combining different colour spaces and colour channels. In contrast to previous works, which rely on fine-tuning pre-trained networks, we compute the proposed descriptors based on the activations generated from a pretrained VGG-16 network without fine-tuning. Besides, we take advantage of an object detector to optimize our proposed instance retrieval architecture to generate features at both local and global scales. In addition, we introduce a stride based query expansion technique to retrieve objects from multi-view datasets. Finally, we experimentally proved that the proposed colour neural descriptors, obtain state-of-the-art results in Paris 6K, Revisiting-Paris 6k, INSTRE-M and COIL-100 datasets, with mAPs of 81.70, 82.02, 78.8 and 97.9, respectively.
Published: 2021
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21. The bone-degrading enzyme machinery: From multi-component understanding to the treatment of residues from the meat industry

Author: Laura Fernandez-Lopez, Sergio Sanchez-Carrillo, Antonio García-Moyano, Erik Borchert, David Almendral, Sandra Alonso, Isabel Cea-Rama, Noa Miguez, Øivind Larsen, Johannes Werner, Kira S. Makarova, Francisco J. Plou, Thomas G. Dahlgren, Julia Sanz-Aparicio, Ute Hentschel, Gro Elin Kjæreng Bjerga, and Manuel Ferrer
Subjects: Bone microbiome, Bone degradation, Collagenase, Glycosidase, Metagenomics, Osedax mucofloris, Biotechnology, TP248.13-248.65
Abstract: Many microorganisms feed on the tissue and recalcitrant bone materials from dead animals, however little is known about the collaborative effort and characteristics of their enzymes. In this study, microbial metagenomes from symbionts of the marine bone-dwelling worm Osedax mucofloris, and from microbial biofilms growing on experimentally deployed bone surfaces were screened for specialized bone-degrading enzymes. A total of 2,043 taxonomically (closest match within 40 phyla) and functionally (1 proteolytic and 9 glycohydrolytic activities) diverse and non-redundant sequences (median pairwise identity of 23.6%) encoding such enzymes were retrieved. The taxonomic assignation and the median identity of 72.2% to homologous proteins reflect microbial and functional novelty associated to a specialized bone-degrading marine community. Binning suggests that only one generalist hosting all ten targeted activities, working in synergy with multiple specialists hosting a few or individual activities. Collagenases were the most abundant enzyme class, representing 48% of the total hits. A total of 47 diverse enzymes, representing 8 hydrolytic activities, were produced in Escherichia coli, whereof 13 were soluble and active. The biochemical analyses revealed a wide range of optimal pH (4.0–7.0), optimal temperature (5–65 °C), and of accepted substrates, specific to each microbial enzyme. This versatility may contribute to a high environmental plasticity of bone-degrading marine consortia that can be confronted to diverse habitats and bone materials. Through bone-meal degradation tests, we further demonstrated that some of these enzymes, particularly those from Flavobacteriaceae and Marinifilaceae, may be an asset for development of new value chains in the biorefinery industry.
Published: 2021
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22. Metagenomic Mining for Esterases in the Microbial Community of Los Rueldos Acid Mine Drainage Formation

Author: Paula Vidal, Mónica Martínez-Martínez, Laura Fernandez-Lopez, Sergi Roda, Celia Méndez-García, Olga V. Golyshina, Víctor Guallar, Ana I. Peláez, and Manuel Ferrer
Subjects: acidophiles, acidophilic bacteria, acid mine drainage, biodiversity, extremozymes, esterase, Microbiology, QR1-502
Abstract: Acid mine drainage (AMD) systems are extremely acidic and are metal-rich formations inhabited by relatively low-complexity communities of acidophiles whose enzymes remain mostly uncharacterized. Indeed, enzymes from only a few AMD sites have been studied. The low number of available cultured representatives and genome sequences of acidophiles inhabiting AMDs makes it difficult to assess the potential of these environments for enzyme bioprospecting. In this study, using naïve and in silico metagenomic approaches, we retrieved 16 esterases from the α/β-hydrolase fold superfamily with the closest match from uncultured acidophilic Acidobacteria, Actinobacteria (Acidithrix, Acidimicrobium, and Ferrimicrobium), Acidiphilium, and other Proteobacteria inhabiting the Los Rueldos site, which is a unique AMD formation in northwestern Spain with a pH of ∼2. Within this set, only two polypeptides showed high homology (99.4%), while for the rest, the pairwise identities ranged between 4 and 44.9%, suggesting that the diversity of active polypeptides was dominated not by a particular type of protein or highly similar clusters of proteins, but by diverse non-redundant sequences. The enzymes exhibited amino acid sequence identities ranging from 39 to 99% relative to homologous proteins in public databases, including those from other AMDs, thus indicating the potential novelty of proteins associated with a specialized acidophilic community. Ten of the 16 hydrolases were successfully expressed in Escherichia coli. The pH for optimal activity ranged from 7.0 to 9.0, with the enzymes retaining 33–68% of their activities at pH 5.5, which was consistent with the relative frequencies of acid residues (from 54 to 67%). The enzymes were the most active at 30–65°C, retaining 20–61% of their activity under the thermal conditions characterizing Los Rueldos (13.8 ± 0.6°C). The analysis of the substrate specificity revealed the capacity of six hydrolases to efficiently degrade (up to 1,652 ± 75 U/g at pH 8.0 and 30°C) acrylic- and terephthalic-like [including bis(2-hydroxyethyl)-terephthalate, BHET] esters, and these enzymes could potentially be of use for developing plastic degradation strategies yet to be explored. Our assessment uncovers the novelty and potential biotechnological interest of enzymes present in the microbial populations that inhibit the Los Rueldos AMD system.
Published: 2022
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23. Diagnosis and Management of Traumatic Subarachnoid Hemorrhage: Protocol for a Scoping Review

Author: Dylan P Griswold, Laura Fernandez, and A M Rubiano
Subjects: Medicine, Computer applications to medicine. Medical informatics, R858-859.7
Abstract: BackgroundGlobally, 69 million people suffer from traumatic brain injury (TBI) each year and TBI is the most common cause of subarachnoid hemorrhage (SAH). Traumatic SAH (TSAH) has been described as an adverse prognostic factor leading to progressive neurological deterioration and an increase in morbidity and mortality, but there are a limited number of studies which evaluate recent trends in the diagnostic and management of SAH in the context of trauma. ObjectiveThe objective of this scoping review was to understand the extent and type of evidence in relation to the diagnostic criteria and management of TSAH. MethodsThis scoping review will be conducted in accordance with the Joanna Briggs Institute methodology for scoping reviews. A 3-step search strategy (an initial limited search in PubMed and Scopus databases; a main search of EMBASE, Web of Science, EBSCO, MEDLINE; and manual searches of reference lists of included articles) will be utilized. The search will be limited to studies with human participants and published in English, Spanish, and French between 2005 and 2020. This review will consider studies of adolescent and adult patients with SAH secondary to trauma. Study selection will be performed by 2 authors (DG and LF) in a 2-phase process; if any disagreement arises, a third author (AR) will be consulted. Data to be extracted from each study will include population, intervention, comparator and outcome measures, and a summary of findings. Citation screening, full-text review, risk of bias assessment, and extraction of study characteristics and outcomes will be carried out using a web-based software platform that streamlines the production of scoping reviews. ResultsEthics approval is not required for this systematic review, as there will be no patient involvement. The search for this systematic review commenced in December 2020, and we expect to publish the findings in early 2021. The plan for dissemination is to publish review findings in a peer-reviewed journal and present findings at conferences that engage the most pertinent stakeholders. ConclusionsThis scoping review will serve as an initial step in providing more evidence for health care professionals, economists, and policymakers so that they might devote more resources toward this significant problem affecting both health and economic outcomes worldwide. International Registered Report Identifier (IRRID)PRR1-10.2196/26709
Published: 2021
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24. Design and Characterization of In-One Protease-Esterase PluriZyme

Author: Laura Fernandez-Lopez, Sergi Roda, Jose L. Gonzalez-Alfonso, Francisco J. Plou, Víctor Guallar, and Manuel Ferrer
Subjects: esterase, PluriZyme, protease, protein engineering, computational chemistry, cascade reaction, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract: Proteases are abundant in prokaryotic genomes (~10 per genome), but their recovery encounters expression problems, as only 1% can be produced at high levels; this value differs from that of similarly abundant esterases (1–15 per genome), 50% of which can be expressed at good levels. Here, we design a catalytically efficient artificial protease that can be easily produced. The PluriZyme EH1AB1 with two active sites supporting the esterase activity was employed. A Leu24Cys mutation in EH1AB1, remodelled one of the esterase sites into a proteolytic one through the incorporation of a catalytic dyad (Cys24 and His214). The resulting artificial enzyme, EH1AB1C, efficiently hydrolysed (azo)casein at pH 6.5–8.0 and 60–70 °C. The presence of both esterase and protease activities in the same scaffold allowed the one-pot cascade synthesis (55.0 ± 0.6% conversion, 24 h) of L-histidine methyl ester from the dipeptide L-carnosine in the presence of methanol. This study demonstrates that active sites supporting proteolytic activity can be artificially introduced into an esterase scaffold to design easy-to-produce in-one protease-esterase PluriZymes for cascade reactions, namely, the synthesis of amino acid esters from dipeptides. It is also possible to design artificial proteases with good production yields, in contrast to natural proteases that are difficult to express.
Published: 2022
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25. EP-Pred: A Machine Learning Tool for Bioprospecting Promiscuous Ester Hydrolases

Author: Ruite Xiang, Laura Fernandez-Lopez, Ana Robles-Martín, Manuel Ferrer, and Victor Guallar
Subjects: biocatalysts, bioprospecting, esterases/lipases, hydrolases, machine learning, supervised learning, Microbiology, QR1-502
Abstract: When bioprospecting for novel industrial enzymes, substrate promiscuity is a desirable property that increases the reusability of the enzyme. Among industrial enzymes, ester hydrolases have great relevance for which the demand has not ceased to increase. However, the search for new substrate promiscuous ester hydrolases is not trivial since the mechanism behind this property is greatly influenced by the active site’s structural and physicochemical characteristics. These characteristics must be computed from the 3D structure, which is rarely available and expensive to measure, hence the need for a method that can predict promiscuity from sequence alone. Here we report such a method called EP-pred, an ensemble binary classifier, that combines three machine learning algorithms: SVM, KNN, and a Linear model. EP-pred has been evaluated against the Lipase Engineering Database together with a hidden Markov approach leading to a final set of ten sequences predicted to encode promiscuous esterases. Experimental results confirmed the validity of our method since all ten proteins were found to exhibit a broad substrate ambiguity.
Published: 2022
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26. Brain erythropoietin fine-tunes a counterbalance between neurodifferentiation and microglia in the adult hippocampus

Author: Laura Fernandez Garcia-Agudo, Agnes A. Steixner-Kumar, Yasmina Curto, Nadine Barnkothe, Imam Hassouna, Sebastian Jähne, Umer Javed Butt, Katharina Grewe, Martin S. Weber, Kim Green, Silvio Rizzoli, Juan Nacher, Klaus-Armin Nave, and Hannelore Ehrenreich
Subjects: hypoxia, recombinant human EPO, neurogenesis, neurodifferentiation, CSF1R, IL-34, Biology (General), QH301-705.5
Abstract: Summary: In adult cornu ammonis hippocampi, erythropoietin (EPO) expression drives the differentiation of new neurons, independent of DNA synthesis, and increases dendritic spine density. This substantial brain hardware upgrade is part of a regulatory circle: during motor-cognitive challenge, neurons experience “functional” hypoxia, triggering neuronal EPO production, which in turn promotes improved performance. Here, we show an unexpected involvement of resident microglia. During EPO upregulation and stimulated neurodifferentiation, either by functional or inspiratory hypoxia, microglia numbers decrease. Treating mice with recombinant human (rh)EPO or exposure to hypoxia recapitulates these changes and reveals the involvement of neuronally expressed IL-34 and microglial CSF1R. Surprisingly, EPO affects microglia in phases, initially by inducing apoptosis, later by reducing proliferation, and overall dampens microglia activity and metabolism, as verified by selective genetic targeting of either the microglial or pyramidal neuronal EPO receptor. We suggest that during accelerating neuronal differentiation, EPO acts as regulator of the CSF1R-dependent microglia.
Published: 2021
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27. Case Report: Novel SAVI-Causing Variants in STING1 Expand the Clinical Disease Spectrum and Suggest a Refined Model of STING Activation

Author: Bin Lin, Sofia Torreggiani, Dana Kahle, Dax G. Rumsey, Benjamin L. Wright, Marco A. Montes-Cano, Laura Fernandez Silveira, Sara Alehashemi, Jacob Mitchell, Alexander G. Aue, Zheng Ji, Tengchuan Jin, Adriana A. de Jesus, and Raphaela Goldbach-Mansky
Subjects: interferonopathy, autoinflammatory disease, type I interferon, SAVI, STING, whole exome sequencing, Immunologic diseases. Allergy, RC581-607
Abstract: Gain-of-function mutations in STING1 cause the monogenic interferonopathy, SAVI, which presents with early-onset systemic inflammation, cold-induced vasculopathy and/or interstitial lung disease. We identified 5 patients (3 kindreds) with predominantly peripheral vascular disease who harbor 3 novel STING1 variants, p.H72N, p.F153V, and p.G158A. The latter two were predicted by a previous cryo-EM structure model to cause STING autoactivation. The p.H72N variant in exon 3, however, is the first SAVI-causing variant in the transmembrane linker region. Mutations of p.H72 into either charged residues or hydrophobic residues all led to dramatic loss of cGAMP response, while amino acid changes to residues with polar side chains were able to maintain the wild type status. Structural modeling of these novel mutations suggests a reconciled model of STING activation, which indicates that STING dimers can oligomerize in both open and closed states which would obliviate a high-energy 180° rotation of the ligand-binding head for STING activation, thus refining existing models of STING activation. Quantitative comparison showed that an overall lower autoactivating potential of the disease-causing mutations was associated with less severe lung disease, more severe peripheral vascular disease and the absence of a robust interferon signature in whole blood. Our findings are important in understanding genotype-phenotype correlation, designing targeted STING inhibitors and in dissecting differentially activated pathways downstream of different STING mutations.
Published: 2021
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28. Escudo de Blumer: signo diagnóstico de la diseminación a distancia del cáncer gástrico difuso

Author: Aingeru Sarriugarte-Lasarte, Eva García-Alberdi, Oihane Gutierrez-Grijalba, Patricia Mifsut Porcel, and Laura Fernandez Gómez-Cruzado
Subjects: estómago, neoplasias gástricas, adenocarcinoma, linitis plástica, escudo de Blumer, Surgery, RD1-811
Abstract: Introducción. Se conoce como escudo de Blumer al engrosamiento neoplásico del fondo de saco de Douglas, palpable al tacto rectal como una protrusión en forma de resalte, presente en pacientes afectados por carcinomas con infiltración difusa. A pesar de haber sido descrito hace más de un siglo, se trata de un proceso diagnosticado infrecuentemente y con escasa mención en la literatura científica. Es preciso tener un alto nivel de sospecha clínica para correlacionar los síntomas pélvicos con la presencia de un tumor, habitualmente gástrico. Casos clínicos. Presentamos dos pacientes con hallazgo de escudo de Blumer, asociado a cáncer gástrico difuso, uno como diagnóstico primario de enfermedad metastásica y otro como recidiva de la enfermedad, meses después de ser operado. Ambos casos presentan un complejo proceso diagnóstico, en el que prima la sospecha clínica, apoyado sobre pruebas de imagen como tomografía computarizada y resonancia nuclear magnética, ya que tanto las biopsias obtenidas por endoscopia, como las biopsias intraoperatorias fueron negativas. Discusión. En el escudo de Blumer, las células tumorales infiltran el fondo de saco de Douglas de forma difusa por debajo de la serosa, sin necesidad de que existan implantes macroscópicamente visibles en el peritoneo visceral. La infiltración tumoral puede afectar extrínsecamente al recto, causando una estenosis del mismo, lo que produce sintomatología pélvica inespecífica, como tenesmo rectal y proctalgia. Por lo tanto, este ominoso proceso debe ser sospechado en pacientes con sintomatología pélvica, que presenten o hayan presentado cáncer gástrico.
Published: 2021
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29. Surgical site infection after gastrointestinal surgery in children: an international, multicentre, prospective cohort study

Author: Sèbastien Gaujoux, Nebyou Seyoum, Ville Sallinen, Ari Leppäniemi, Andrea Belli, Clare Skerritt, Naomi Wright, Savva Pronin, Azmina Verjee, Thomas Pinkney, Neil Smart, Oliver Warren, Michele Sacco, Arnav Agarwal, Simon Paterson-Brown, David Evans, Philip Choi, Ashish Gupta, Jonathan Myers, Victor Kong, Michael Wilson, Ewen M Harrison, Mircea Beuran, Ionut Negoi, Zahra Jaffry, Leonardo Solaini, Thomas M Drake, Dmitri Nepogodiev, Adesoji O Ademuyiwa, Philip Alexander, Sara W Al-Saqqa, Sule Burger, Kathryn Chu, Dhruv Ghosh, Hosni Khairy Salem, Marie Carmela Lapitan, Ismail Lawani, Maria Lorena Aguilera, Mayaba Maimbo, Alex Makupe, Rachel Moore, Vanessa Msosa, Alphonse Zeta Mutabazi, Riinu Ots, Ahmad Uzair Qureshi, Sarah Rayne, Marie Dione Parreno-Sacdalan, Richard Spence, Stephen Tabiri, Richard Lilford, Dion Morton, Aneel Bhangu, Tom Abbott, Gehad Tawfik, Sebastian King, Alexia Farrugia, Jay Park, Abhishek Sharma, Augusto Zani, Christopher Smith, Jonathan Lund, Stefano Giuliani, John Whitaker, Elaine Borg, Alexis Arnaud, Esther Ferrero, Andrea Ruzzenente, Jennifer Rickard, Yousef Abuowda, Enas Alaloul, Natalie Blencowe, Sanjay Patel, Mark Ian Hampton, Ewen Griffiths, André L Mihaljevic, Elizabeth Evans, Catherine A Shaw, Jennifer Ploski, Mengistu Worku, Ashish Minocha, Shiva Dindyal, Midhun Mohan, Dina Fouad, Christopher Owen, Priya Patel, Sunil Kumar, James Yang, Kevin C Conlon, Sandro Pasquali, Mohamed Mostafa, Yoshan Moodley, Kathryn Lee, James Glasbey, Gareth Irwin, Kjetil Søreide, Catrin Morgan, Ruth Blanco-Colino, Francesco Pata, Gianluca Pellino, Sivesh K Kamarajah, Luke Nicholson, Adesoji Ademuyiwa, Felix Alakaloko, Olumide Elebute, Omolara Faboya, Taiwo Lawal, Omolara Williams, Andrey Litvin, Elodie Haraux, James Olivier, Michael Stoddart, Rebecca White, George Ihediwa, Luigi Bonavina, Chetan Khatri, Stephen O'Neill, Roger Schmid, Stephen Knight, Ahmed Soliman, Carly Bisset, Robert Parker, Rakan Kabariti, Joshua Luck, Guo Liang Yong, Tanzeela Gala, David Bunting, Lydia Longstaff, Ye Ru Chin, J Edward Fitzgerald, Giuliano Borda-Luque, Ainhoa Costas-Chavarri, Faustin Ntirenganya, Stuart J Fergusson, JC Allen Ingabire, Lawani Ismaïl, Anyomih Theophilus Teddy Kojo, Adewale O Adisa, Tomas Poškus, Antonio Ramos-De la Medina, Sebastian Shu, Emmy Runigamugabo, Afnan Altamini, Andrew Kirby, Gustavo Recinos, Jen Cornick, Maria Marta Modolo, Sayeda Nazmum Nahar, Ade Waterman, Ismail Lawini, Mohammed Firdouse, Tyler Rouse, Qinyang Liu, Juan Camilo Correa, Peep Talving, Dushyant Iyer, Tom Arthur, MariaLorena Aguilera, Basant Kumar, Radhian Amandito, Roy Quek, Luca Ansaloni, Ahmed Altibi, Donatas Venskutonis, Justas Zilinskas, YongYong Tew, Ramos-DelaMedina Antonio, Zineb Bent, Ibrahim Al-Slaibi, Haya Tahboub, Osaid H Alser, Diego Romani, Sebestian Shu, Piotr Major, Aurel Mironescu, Matei Bratu, Amar Kourdouli, Saint Kitts, Mohammed Ubaid Alsaggaf, Ahmad Gudal, Al Faifi Jubran, Sierra Leone, Sam Seisay, Bettina Lieske, Irene Ortega, Jenifa Jeyakumar, Kithsiri Senanayake, Omar Abdulbagi, Yucel Cengiz, Dmitri Raptis, Yuksel Altinel, Chia Kong, Ella Teasdale, Sukrit Suresh, Katherine Gash, Mark Scott, Ragavan Narayanan, Besmir Grizhja, Shpetim Ymeri, Gezim Galiqi, Roberto Klappenbach, Diego Antezana, Alvaro Enrique MendozaBeleño, Cecilia Costa, Belen Sanchez, Susan Aviles, Claudio Gabriel Fermani, Rubén Balmaceda, Santiago Villalobos, Juan Manuel Carmona, Daniel Hamill, Peter Deutschmann, Simone Sandler, Daniel Cox, Ram Nataraja, Claire Sharpin, Damir Ljuhar, Demi Gray, Morgan Haines, Dush Iyer, Nithya Niranjan, Scott D'Amours, Morvarid Ashtari, Helena Franco, Ashrarur Rahman Mitul, Sabbir Karim, Nowrin F Aman, Mahnuma Mahfuz Estee, Umme Salma, Joyeta Razzaque, Tasnia Hamidkanta, Sayeedaaktar Tori, Md Shadid Alamin, Swapnil Roy, Md Shadid Al Amin, Muhtarima Haque, Amreen Faruq, Farhana Iftekhar Margaret, Greg Padmore O'Shea, Ramesh Jonnalagadda, Aliaksandr Filatau, Dzmitry Paulouski, Maryna Shubianok, Tatsiana Shachykava, Dzianis Khokha, Vladimir Khokha, Fernande Djivoh, Francis Dossou, Djifid Morel Seto, Dansou Gaspard Gbessi, Bruno Noukpozounkou, Yacoubou Imorou Souaibou, Kpèmahouton René Keke, Fred Hodonou, Ernestyemalinstephane Ahounou, Thierry Alihonou, Max Dénakpo, Germain Ahlonsou, Alemayehu Ginbo Bedada, Carlos Nsengiyumva, Sandrine Kwizera, Venerand Barendegere, Simon Stock, Luai Jamal, Georges Azzie, Sameer Kushwaha, Tzu-Ling Chen, Chingwan Yip, Irene Montes, Felipe Zapata, Sebastian Sierra, Mohamed Youssef, Hossam Elfeki, Waleed Thabet, Aly Sanad, Ahmed Zaki, Noran Abdel-Hameed, Esraa Abd Elkhalek, Yehia Zakaria, Tarek Ezzat, Ali Abo ElDahab, Mohamed Kelany, Sara Arafa, OsamaMokhtar Mohamed Hassan, Nermin Mohamed Badwi, Ahmad Saber Sleem, Hussien Ahmed, Kholoud Abdelbadeai, Mohamed Abozed Abdullah, Muhammadamsyarauni Lokman, Suraya Bahar, Anan Radyabdelazeam, Abdelrahman Adelshone, Muhammad Bin Hasnan, Athirah Zulkifli, Siti NurAlia Kamarulzamil, Abdelaziz Elhendawy, Aliang Latif, Ahmad Bin Adnan, Shahadatul Shaharuddin, Aminah HanumHaji AbdulMajid, Mahmoud Amreia, Dina Al-Marakby, Mahmoud Salma, Mohamadjeffreybin Ismail, Elissa Rifhan MohdBasir, Citra Dewi MohdAli, Aya Yehia Ata, Maha Nasr, Asmaa Rezq, Ahmed Sheta, Sherif Tariq, Abdelkhalek Sallam, Abdelrhman KZ Darwish, Sohaila Elmihy, Shady El Hadry, Ahmed Farag, Haidar Hajah, Abdelaziz Seliem, Amro Aglan, Ahmed Zohair, Mahitab Essam, Omar Moussa, Esraa El-Gizawy, Mostafa Samy, Safia Ali, Esraa Elhalawany, Ahmed Ata, Mohamed Elhalawany, Mohamed Nashat, Samar Soliman, Alaa Elazab, Mostada Samy, Mohamed A Abdelaziz, Khaled Ibrahim, Ahmed mohamed Ibrahim, Ammar Gado, Usama Hantour, Esraa Alm Eldeen, Mohamed Reda loaloa, Arwa Abouzaid, Mostafa Ahmedbahaaeldin, Eman Hashad, Fathy Sroor, Doaa Gamil, Eman Mahmoudabdulhakeem, Mahmoud Zakaria, Fawzy Mohamed, Marwan Abubakr, Elsayed Ali, Hesham Magdy, Mennatallah Ramadan, Mohamed Abdelatymohamed, Salma Mansour, Hager Abdulazizamin, Ahmed Rabiemohamed, Mahmoud Saami, Nada Ahmedredaelsayed, Adham Tarek, Sabry Mohyeldeenmahmoud, Islam MagdyEl Sayed, Amira Reda, Martina Yusufshawky, Mohammed Mousasalem, Shahinaz Alaa El-Din, Noha Abdullah Soliman, Muhammed Talaat, Shahinaz Alaael-Dein AhmedAbdelmoenelhusseiny, Noha Abdullah, Mohammed Elshaar, Aya Abdelfatahibraheem, Hager Abdulaziz, Mohammed Kamal Ismail, Mona Hamdymadkor, Mohamed Abdelaty, Sara Mahmoudabdel Kader, Osama Mohamedsalah, Mahmoud Eldafrawy, Ahmed Zakieldeeb, Mostafa Mahmoudeid, Attia Attia, Khalid Salah El-Dien, Ayman Shwky, Mohamed Adel Badenjki, Abdelrahman Soliman, Samaa Mahmoud Al Attar, Farrag Sayed, Fahd Abdelsabour, Mohammed G Azizeldine, Muhammad Shawqi, Abdullah Hashim, Ahmed Aamer, Ahmed Mahmoud Abdel Raouf, Mahmoud Abdelshakour, Amal Ibrahim, Basma Mahmoud, Mohamed Ali Mahmoud, Mostafa Qenawy, Ahmed M Rashed, Ahmed Dahy, Marwa Sayed, Ahmed W Shamsedine, Bakeer Mohamed, Ahmad Hasan, Mahmoud M Saad, Khalil Abdulbassit, Nadia Khalidabdelatif, Nada Elzahed, Ahmed Elkashash, Sarah Hafez, Ahmed Gad, Mahmoud Elkhadragy Maher, Ahmed Abdelsameea, Mohamed Hafez, Ahmad Sabe, Vassilis Kalles, Nada Mohamed Bekheta, Ataa Ahmed, Ahmed Shahine, Khaled Dawood, Shireen Gaafar, Reem Husseiny, Omnia Aboelmagd, Nourhan Mesbah, Hossam Emadeldin, Amgad Almeligy, Amira Hassan Bekhet, Doaa Hasan, Khaled Alhady, Ahmad Khaled Sabe, Mahmoud A Elnajjar, Majed Aboelella, Ward Hamsho, Ihab Hassan, Hala Saad, Galaleldin Abdelazim, Hend Mahmoud, Noha Wael, Ahmedali M Kandil, Ahmed Magdy, Shimaa Saidelkholy, Badreldineadel Adel, Kareem Dabbour, Saged Elsherbiney, Omar Mattar, Abdulshafi Khaled Abdrabou, Mohammed Yahia mohamedAly, Abdelrahman Geuoshy, Ahmedglal Elnagar, Saraibrahim Ahmed, Ibrahem Abdelmotaleb, Amr Ahmed Saleh, Hesham Mohammedbakry, Manar Saeed, Shady Mahmoud, Badreldinadel Tawfik, Samar Adel Ismail, Esraay Zakaria, Mariam O Gad‏, Mohamedsalah Elhelbawy, Monica Bassem, Nadia Khaledabdel-Latif, Noha Maraie, Nourhan Medhat Elhadary, Nourhan Semeda, Shaza Rabiemohamed, Hesham Mohammed Bakry, AA Essam, Dina Tarek, Khlood Ashour, Alaa Elhadad, Abdulrahman Abdel-Aty, Ibrahim Rakha, Sara Mamdouh Matter, Rasha Abdelhamed, Omar Abdelkader, Ayat Hassaan, Yasmin Soliman, Amna Mohamed, Sara Ghanem, Sara Amr MohamedFarouk, Eman Mohamed Ibrahim, Esraa El-Taher, Merna Mostafa, Mohamedfawzy Mahrousbadr, Rofida Elsemelawy AyaEl-Sawy, Ahmad Bakr, Ahmad Abdel Razaq Al Rafati, Sten Saar, Arvo Reinsoo, Tewodros Worku, Agazi Fitsum, Matti Tolonen, Benoît Parmentier, Matthieu Peycelon, Sabine Irtan, Sabrina Dardenne, Elsa Robert, Betty Maillot, Etienne Courboin, Alexis Pierre Arnaud, Juliette Hascoet, Olivier Abbo, Amir Ait Kaci, Thomas Prudhomme, Quentin Ballouhey, Céline Grosos, Laurent Fourcade, Tolg Cecilia, Colombani Jean-Francois, Francois-Coridon Helene, Xavier Delforge, Bertrand Dousset, Roberto Schiavone, Jean-Baptiste Marret, Aurore Haffreingue, Julien Rod, Mariette Renaux-Petel, Jean-François Lecompte, Jean Bréaud, Pauline Gastaldi, Chouikh Taieb, Raquillet Claire, Echaieb Anis, Nasir Bustangi, Manuel Lopez, Aurelien Scalabre, Maria Giovanna Grella, Aurora Mariani, Guillaume Podevin, Françoise Schmitt, Erik Hervieux, Aline Broch, Cecile Muller, Anyomih Theophilus TeddyKojo, Dickson Bandoh, Francis Abantanga, Martin Kyereh, Hamza Asumah, Eric Kofi Appiah, Paul Wondoh, Adam Gyedu, Charles Dally, Kwabena AgbedinuKwabena AgbedinuMichaelAmoah, Kwabena Agbedinu, Abiboye Yifieyeh, Frank Owusu, Mabel Amoako-Boateng, Makafui Dayie, Richmond Hagan, Sam Debrah, Micheal Ohene-Yeboah, Joe-Nat Clegg-Lampety, Victor Etwire, Jonathan Dakubo, Samuel Essoun, William Bonney, Hope Glover-Addy, Samuel Osei-Nketiah, Joachim Amoako, Niiarmah Adu-Aryee, William Appeadu-Mensah, Antoinette Bediako-Bowan, Florence Dedey, Mattew Ekow, Emmanuel Akatibo, Musah Yakubu, Hope Edem KofiKordorwu, Kwasi Asare-Bediako, Enoch Tackie, Kenneth Aaniana, Emmanuel Acquah, Richard Opoku-Agyeman, Anthony Avoka, Kwasi Kusi, Kwame Mais, Frank Enoch Gyamfi, Gandau Naabarnabas, Saiba Abdul-Latif, Philip Taahamoako, Anthony Davor, Victor Dassah, Enoch Dagoe, Prince Kwakyeafriyie, Elliot Akoto, Eric Ackom, Ekow Mensah, Ebenezer Takyi Atkins, Christian Lari Coompson, Nikolaos Ivros, Christoforos Ferousis, Vasileios Kalles, Christos Agalianos, Ioannis Kyriazanos, Christos Barkolias, Angelos Tselos, Georgios Tzikos, Evangelos Voulgaris, Dimitrios Lytras, Athanasia Bamicha, Kyriakos Psarianos, Anastasios Stefanopoulos, Ioannis Patoulias, Dimitrios Sfougaris, Ioannis Valioulis, Dimitrios Balalis, Dimitrios Korkolis, Dimitrios K Manatakis, Georgios Kyrou, Georgios Karabelias, Iason-Antonios Papaskarlatos, Kolonia Konstantina, Nikolaos Zampitis, Stylianos Germanos, Aspasia Papailia, Theodosios Theodosopoulos, Georgios Gkiokas, Magdalini Mitroudi, Christina Panteli, Thomas Feidantsis, Konstantinos Farmakis, Dimitrios Kyziridis, Orestis Ioannidis, Styliani Parpoudi, Georgios Gemenetzis, Stavros Parasyris, Christos Anthoulakis, Nikolaos Nikoloudis, Michail Margaritis, Maria-Lorena Aguilera-Arevalo, Otto Coyoy-Gaitan, Javier Rosales, Luis Tale, Rafael Soley, Emmanuel Barrios, Servio TulioTorres Rodriguez, Carlos Pazgalvez, Danilo Herreracruz, Guillermo Sanchez Rosenberg, Alejandro Matheu, David Monterroso Cohen, Marie Paul, Angeline Charles, Justin ChakYiu Lam, Man Hon AndrewYeung, Chi Ying JacquelynFok, Ka Hin GabrielLi, Anthony Chuk-Him Lai, Yuk HongEric Cheung, Hong Yee Wong, Ka Wai Leung, Tien Seng BryanLee, Wai Him Lam, Weihei Dao, Stephanie Hiu-wai Kwok, Tsz-Yan Katie Chan, Yung Kok Ng, Chi Chung Foo, Ankur Bhatnagar, Vijaid Upadhyaya, Uday Muddebihal, Wasim Dar, Janardhan, Neerav Aruldas, Fidelis Jacklyn Adella, Anthonius Santoso Rulie, Ferdy Iskandar, Jonny Setiawan, Cicilia Viany Evajelista, Hani Natalie, Arlindawati, Rudy Gunawan, Herlin Karismaningtyas, Lusipadmasulistianingsih Mata, Ferryfitriyaayu Andika, Afifatun Hasanah, T Ariani Widiastini, Nurlailaayu Purwaningsih, Annisa DewiFitriana Mukin, Dinafaizatur Rahmah, Hazmidwinanda Nurqistan, 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Georgettemarie Camilleri, Isaac Bertuello, Jeffrey Dalli, Karl Bonavia, Samantha Corro-Diaz, Marisol Manriquez-Reyes, Antonio Ramos-Dela Medina, Amina Abdelhamid, Abdelmalek Hrora, Sarah Benammi, Houda Bachri, Meryem Abbouch, Khaoula Boukhal, Redouane Mammar Bennai, Abdelkader Belkouchi, Mohamed Sobhi Jabal, Chaymae Benyaiche, Maarten Vermaas, Lucia Duinhouwer, Javier Pastora, Greta Wood, Maria Soledad Merlo, Akinlabi Ajao, Omobolaji Ayandipo, Abdussemiu Abdurrazzaaq, Olufemi Habeeb, Muslimat Alada, Abdulrasheed Nasir, James Adeniran, Ademola Popoola, Ademola Adeyeye, Ademola Adebanjo, Opeoluwa Adesanya, Adewale Adeniyi, Henry Mendel, Bashir Bello, Umar Muktar, Adedapo Osinowo, Thomas Olagboyega Olajide, Oyindamola Oshati, Babajide Adenekan, Victor Nwinee, Abdulrazzaq Lawal, Chris Bode, Mojolaoluwa Olugbemi, Alaba Adesina, Olubukola Faturoti, Oluwatomi Odutola, Oluwaseyi Adebola, Clement Onuoha, Ogechukwu Taiwo, Fatai Balogun, Olalekan Ajai, Mobolaji Oludara, Iloba Njokanma, Roland Osuoji, Stephen Kache, Jonathan Ajah, Jerry Makama, Ahmed Adamu, Suleiman Baba, Mohammad Aliyu, Shamsudeen Aliyu, Yahaya Ukwenya, Halima Aliyu, Tunde Sholadoye, Muhammad Daniyan, Oluseyi Ogunsua, Lofty-John Anyanwu, Abdurrahaman Sheshe, Aminu Mohammad, Samson Dr Olori, Philip Mshelbwala, Babatunde Odeyemi, Garba Samson, Oyediran Kehinde Timothy, Sani Ali Samuel, Anthony Ajiboye, Isaac Amole, Olajide Abiola, Akin Olaolorun, Torhild Veen, Arezo Kanani, Kristian Styles, Ragnar Herikstad, Johannes Wiik Larsen, Jon Arne Søreide, Elisabeth Jensen, Mads Gran, Eirik Kjus Aahlin, Tina Gaarder, Peter Wiel Monrad-Hansen, Pål Aksel Næss, Giedrius Lauzikas, Joachim Wiborg, Silje Holte, Knutmagne Augestad, Gurpreetsingh Banipal, Michela Monteleone, Thomastetens Moe, Johanneskurt Schultz, Taher Al-taher, Ayah Hamdan, Ayman Salman, Rana Saadeh, Aseel Musleh, Dana Jaradat, Soha Abushamleh, Sakhaa Hanoun, Amjad Abu Qumbos, Aseel Hamarshi, Ayman Taher, Israa Qawasmi, Khalid Qurie, Marwa Altarayra, Mohammad Ghannam, Alaa Shaheen, Azher Herebat, Aram Abdelhaq, Ahmad Shalabi, Maram Abu-toyour, Fatema Asi, Ala Shamasneh, Anwar Atiyeh, Mousa Mustafa, Rula Zaa'treh, Majd Dabboor, Heba Baraka, Jehad Meqbil, Alaa Al-buhaisi, Mohamedraed Elshami, Samah Afana, Sahar Jaber, Said Alyacoubi, Tasneem Idress, Eman Abuqwaider, Sara Al-saqqa, Alaa Bowabsak, Alaa Eljamassi, Doaa Hasanain, Hadeel Al-farram, Maram Salah, Aya Firwana, Marwa Hamdan, Israa Awad, Ahmad Ashour, Fayez Elian AlBarrawi, Ahmed Al-khatib, Maha Al-faqawi, Mohamed Fares, Amjad Elmashala, Mohammad Adawi, Ihdaa Adawi, Reem Khreishi, Rose Khreishi, Ahed Ghabe, Najwa Nadeem, Muhammad Saqlain, Jibran Abbasy, Abdul Rehman Alvi, Noman Shahzad, Kamran Faisal, Zainab Iftikhar, Muhammad Talha Butt, Syed Asaat UlRazi, Asdaq Ahmed, Ali Khan Niazi, Ibrahim Raza, Fatima Baluch, Ahmed Raza, Ahmad Bani-Sadar, Muhammad Adil, Awais Raza, Mahnoor Javaid, Muhammad Waqar, Maryamali Khan, Mohammadmohsin Arshad, Mohammadasim Amjad, Gustavo Miguel MachainVega, Jorge Torres Cardozo, Gustavo Rodolfo PertersenServin, Helmut Alfredo SegoviaLohse, Larissa Ines Páezlopez, Ramón Augusto MeloCardozo, Fernando Espinoza, Angel David PérezRojas, Diana Sanchez, Camila Sanchez Samaniego, Shalon Guevara Torres, Alexander Canta Calua, Cesar Razuri, Nadia Ortiz, Xianelle Rodriguez, Nahilia Carrasco, Fridiz Saravia, Hector Shibao Miyasato, María Valcarcel-Saldaña, Ysabel Esthefany AlejosBermúdez, Juan Carpio, Walter Ruizpanez, Pedroangel Toribioorbegozo, Carolina Guzmán Dueñas, Kevin Turpo Espinoza, Ana MariaSandoval Barrantes, Jorge Chungui, Lorena Fuentes-Rivera, Carmen Fernández, Joselyn Ye Bárbara, Ricardo Velasquez, Jannin Salcedo, Ana Lucia Contreras-Vergara, Angelica Genoveva VergaraMejia, Maria Soledad GonzalesMontejo, Mariliadelcarmen Escalantesalas, Willy Alccaticona, Marvin Vargas, Georgechristian Manriquesila, Robinson Mas, Arazzelly del Pilar Paucar, Armando JoséRomán Velásquez, Alina Robledo-Rabanal, Ludwing AlexanderZeta Solis, Kenny Turpo Espinoza, José Luis HamasakiHamaguchi, Erick Samuel FlorezFarfan, Linda Alvi MadridBarrientos, Juan Jaime HerreraMatta, John Jemuel VMora, Menold Archee PRedota, Manuel Francisco Roxas, Maria Jesusa BMaño, Christel Leanne Almanon, Maciej Walędziak, Rafał Roszkowski, Michał Janik, Anna Lasek, Dorota Radkowiak, Mateusz Rubinkiewicz, Cristina Fernandes, Jose Costa-Maia, Renato Melo, Liviu Muntean, Aurel Sandu Mironescu, Lucian Corneliu Vida, Mariuca Popa, Hogea Mircea, Mihaela Vartic, Bogdan Diaconescu, Matei Razvan Bratu, Cezar Ciubotaru, Mutabazi Alphonse, Norbert Uzabumwana, Dieudonne Duhoranenayo, Elio Jovine, Nicola Zanini, Giovanni Landolfo, Murad Aljiffry, Faisal Idris, Mohammed Saleh AAlghamdi, Ashraf Maghrabi, Abdulmalik Altaf, Eyad Khalifah, Adel Albiety, Aroub Alkaaki, Reham Alshareef, Ahmad Khoja, Abrar Nawawi, Mohammed Najjar, Sondos Turkustani, Sarah Sahel, Ahmed Alzahrani, Ahmed Alghamdi, Wedyan Alhazmi, Ghiath Al Saied, Mohammed Alamoudi, Muhammed Masood Riaz, Mazen Hassanain, Basmah Alhassan, Abdullah Altamimi, Reem Alyahya, Norah Alsubaie, Fatema Albastawis, Afnan Altamimi, Thamer Nouh, Roaa Khan, Milan Radojkovic, Ljiljana Jeremic, Milica Nestorovic, Jia Hao Law, Keith Say Kwang Tan, Joel Kin Tan, Lau WenLiang Joel, Xue Wei Chan, Faith QiHui Leong, Choon Seng Chong, Sharon Koh, Kai Yin Lee, Kuok Chung Lee, Kent Pluke, Britta Dedekind, Puyearashid Nashidengo, Johanna Joosten, Sanju Sobnach, Liana Roodt, Anthony Sander, James Pape, Niveshni Maistry, Phumudzo Ndwambi, Kamau Kinandu, Myint Tun, Frederick Du Toit, Quinn Ellison, DC Grobler, Lawrence Bongani Khulu, Vicky Jennings, Astrid Leusink, Nazmie Kariem, Juan Gouws, Heather Bougard, Fazlin Noor, Angela Dell, Stephanie Van Straten, Arvin Khamajeet, Serge Kapenda Tshisola, Kalangu Kabongo, Frank Anderson, Thandinkosi Madiba, Flip du Plooy, Leila Hartford, Gareth Chilton, Parveen Karjiker, Matlouernest Mabitsela, Sibongileruth Ndlovu, Maria Badicel, Robert Jaich, Jaime Ruiz-Tovar, Luis Garcia-Florez, Jorge L. Otero-Díez, Virginia Ramospérez, Nuria Aguadosuárez, Javier Minguez García, Sara Corral Moreno, Maria Vicenta Collado, Virginia Jiménez Carneros, Javier García Septiem, Mariana Gonzalez, Antonio Picardo, Enrique Esteban, Eloy Espin-Basany, Valeria Andriola, Lorena Solargarcía, Elisa Contreras, Carmen Garcíabernardo, Janet Pagnozzi, Sandra Sanz, Alberto Miyardeleón, Asnel Dorismé, Joseluis Rodicio, Aida Suarez, Jessica Stuva, Tamara Diazvico, Laura Fernandez-Vega, Carla Soldevila-Verdeguer, Fatima Sena-Ruiz, Natalia Pujol-Cano, Paula Diaz-Jover, José Maria Garcia-Perez, Juan Jose Segura-Sampedro, Cristina Pineño-Flores, David Ambrona-Zafra, Andrea Craus-Miguel, Patricia Jimenez-Morillas, Angela Mazzella, A.B Jayathilake, S.P.B Thalgaspitiya, L.S. Wijayarathna, P.M.S.N. Wimalge, Hakeem Ayomi Sanni, Aliyu Ndajiwo, Ogheneochuko Okenabirhie, Anmar Homeida, Abobaker Younis, Omer Abdelbagi Omer, Mustafa Abdulaziz, Ali Mussad, Ali M. Gilani, Ida Björklund, Sandra Ahlqvist, Anders Thorell, Fredrik Wogensen, Arestis Sokratous, Michaela Breistrand, Hildur Thorarinsdottir, Johanna Sigurdadottir, Maziar Nikberg, Abbas Chabok, Maria Hjertberg, Peter Elbe, Deborah Saraste, Wiktor Rutkowski, Louise Forlin, Karoliina Niska, Malin Sund, Dennis Oswald, Georgios Peros, Rafael Bluelle, Katharina Reinisch, Daniel Frey, Adrian Palma, Dimitriaristotle Raptis, Lucius Zumbühl, Markus Zuber, Gabriela Werder, Antonio Nocito, Alexandra Gerosa, Silke Mahanty, Lukas Werner Widmer, Julia Müller, Alissa Gübeli, Grzegorz Zuk, Osman Bilgin Gulcicek, Talar Vartanoglu, Emin Kose, Servet Rustu Karahan, Mehmet Can Aydin, Nuri Alper Sahbaz, Ilkay Halicioglu, Halil Alis, Ipek Sapci, Can Adıyaman, Ahmet Murat Pektaş, Turgut Bora Cengiz, Ilkan Tansoker, Vedatcan Işler, Muazzez Cevik, Deniz Mutlu, Volkan Ozben, Berk Baris Ozmen, Sefa Bayram, Sinem Yolcu, Berna Buse Kobal, Ömer Faruk Toto, Haluk Cem Çakaloğlu, Kagan Karabulut, Vahit Mutlu, Bahar Busra Ozkan, Saban Celik, Anil Semiz, Selim Bodur, Enisburak Gül, Busra Murutoglu, Reyyan Yildirim, Bahadir Emre Baki, Ekin Arslan, Mehmet Ulusahin, Ali Guner, Nathan Walker, Nikhita Shrimanker, Simon Cole, Ryan Breslin, Ravi Srinivasan, Mohamed Elshaer, Kristina Hunter, Ahmed Al-Bahrani, Ignatius Liew, Nora Grace Mairs, Alistair Rocke, Lachlan Dick, Mobeen Qureshi, Debkumar Chowdhury, Adrienne Ho, Tharindra Dissanayake, Athula Tennakoon, Wadah Ali, Shujing Jane Lim, Charlene Tan, Catrin Jones, Dima Nassif, Aia Mehdi, Nathan Post, Eliana Kalakouti, Enkhbat Dashnyam, Frederick Stourton, Ioannis Mykoniatis, Chelise Currow, Francisca Wong, Veeranna Shatkar, Suraj Kadiwar, Alexander Smedley, Rebecca Wakefield, Philip Herrod, James Blackwell, Fraser Cohen, Ashwath Bandi, Giles Bond-Smith, Theodore Pezas, Neda Farhangmehr, Tomas Urbonas, Miklos Perenyei, Philip Ireland, Kirk Bowling, Kenneth Keogh, Hyunjin Jeon, Muhammad Rafaih Iqbal, Shivun Khosla, Anna Jeffery, James Perera, Ahmad Aboelkassem Ibrahem, Tariq Alhammali, Yahya Salama, Shaun Oram, Thomas Kidd, Fraser Cullen, Seehui Chiu, Hannah Sarafilovic, Athar Abbas, Sylvia Kamya, Norzawani Ishak, Cedar Andress, Aidan Haslegrave, Adam Boggon, Kirsten Laurie, Katie Connor, Thomas Mann, Anahita Mansuri, Rachel Davies, Aized Raza Shahbaz, Calvin Eng, Farhat Din, Ariadne L'heveder, Esther H.G. Park, Ramanish Ravishankar, Kirsten Mcintosh, Jih Dar Yau, Luke Chan, Susan Mcgarvie, Lingshan Tang, Hui Lim, Suhhuey Yap, Zhanherr Ng, Shahrukh Mirza, Yun Lin Ang, Luke Walls, Chloe Roy, Julian Camilleri-Brennan, Kenneth Mclean, Michelle D'souza, David Ewart Henshall, Eunicezuling Ter, William English, Dominic Townsend, Laura Maciejec, Shareef Mahdi, Onyinye Akpenyi, Elisabeth Hall, Hanaan Caydiid, Zakaria Rob, Hew D Torrance, Robin Johnston, Mohammedakil Gani, Gianpiero Gravante, Shivanchan Rajmohan, Kiran Majid, Madanmohan Palliyil, Neil Harvey, Katie Baillie, Sam Shillito, Suzanne Kershaw, Rebecca Bamford, Peter Orton, Elke Reunis, Robert Tyler, Waicheong Soon, Guled M. Jama, Dharminder Dhillon, Khyati Patel, Shayanthan Nanthakumaran, Rachel Heard, Kar Yan Chen, Behrad Barmayehvar, Uttaran Datta, Sobhana Iftekhartani, Eimear Monaghan, Philippa Donnelly, Michael Walker, Jehangirshaw Parakh, Sarah Blacker, Anil Kaul, Arjun Paramasivan, Sameh Farag, Ashrafun Nessa, Salwa Awadallah, Jieqi Lim, James Cheankhunng, Ravi P. Kiran, Alice Murray, Eric Etchill, Mohini Dasari, Juan Puyana, Nadeem Haddad, Martin Zielinski, Asad Choudhry, Celeste Caliman, Mieshia Beamon, Therese Duane, Mamta Swaroop, Rebecca Deal, Erik Schadde, Mark Hemmila, Lena Napolitano, Kathleen To, Joseph Musowoya, Niels Van Der Naald, Dayson Kumwenda, Alex Reece-Smith, Kars Otten, Anna Verbeek, Marloes Prins, Alibeth Andres Baquero Suarez, Chelsea Deane, Emilio Dijan, Mahmoud Elfiky, Laura Koskenvuo, Aurore Thollot, Bernard Limoges, Carmen Capito, Challine Alexandre, Henri Kotobi, Julien Leroux, Kalitha Pinnagoda, Nicolas Henric, Olivier Azzis, Olivier Rosello, Poddevin Francois, Sara Etienne, Philippe Buisson, Sophian Hmila, Joe-Nat Clegg-Lamptey, Osman Imoro, Owusu Emmanuel Abem, Dimitrios Papageorgiou, Vasiliki Soulou, Sabrina Asturias, Lenin Peña, Donal B O’Connor, Alberto Realis Luc, Alfio Alessandro Russo, Antonio Taddei, Camilla Cona, Corrado Bottini, Giovanni Pascale, Giuseppe Rotunno, Marco Maria Pascale, Margherita Notarnicola, Mario Corbellino, Paolo Ubiali, Roberto Cautiero, Tommaso Bocchetti, Elena Muzio, Vania Guglielmo, Eugenio Morandi, Patrizio Mao, Emilia De Luca, Farah Mahmoud Ali, Kestutis Strupas, Paulius Kondrotas, Robertas Baltrunas, Juozas Kutkevicius, Povilas Ignatavicius, Choy Ling Tan, Jia Yng Siaw, Sir Young Yam, Ling Wilson, Mohamed Rezal Abdul Aziz, John Bondin, Carmina Diaz Zorrilla, Anass Majbar, Danjuma Sale, Lawal Abdullahi, Olabisi Osagie, Adedeji Fatuga, Agboola Taiwo, Emeka Nwabuoku, Marte BliksØen, Zain Ali Khan, Jazmin Coronel, Cesar Miranda, Idelso Vasquez, Luis M. Helguero-Santin, Adesina Adedeji, Saleh Alqahtani, Max Rath, Michael Van Niekerk, Modise Zacharia Koto, Roel Matos-Puig, Leif Israelsson, Tobias Schuetz, Mahmut Arif Yuksek, Meric Mericliler, Bernhard Wolf, Cameron Fairfield, Katharine Whitehurst, Natalie Redgrave, Caroluce K Musyoka, Michael Cox, Muhamed M H Farhan-Alanie, Rory Callan, Chali Chibuye, Tebian Hassanein Ahmed Ali, Syrine Rekhis, Muna Rommaneh, Zi Hao Sam, Thays Brunelli Pugliesi, Gabriel Pardo, and Ruth Blanco
Subjects: Medicine (General), R5-920, Infectious and parasitic diseases, RC109-216
Abstract: Introduction Surgical site infection (SSI) is one of the most common healthcare-associated infections (HAIs). However, there is a lack of data available about SSI in children worldwide, especially from low-income and middle-income countries. This study aimed to estimate the incidence of SSI in children and associations between SSI and morbidity across human development settings.Methods A multicentre, international, prospective, validated cohort study of children aged under 16 years undergoing clean-contaminated, contaminated or dirty gastrointestinal surgery. Any hospital in the world providing paediatric surgery was eligible to contribute data between January and July 2016. The primary outcome was the incidence of SSI by 30 days. Relationships between explanatory variables and SSI were examined using multilevel logistic regression. Countries were stratified into high development, middle development and low development groups using the United Nations Human Development Index (HDI).Results Of 1159 children across 181 hospitals in 51 countries, 523 (45·1%) children were from high HDI, 397 (34·2%) from middle HDI and 239 (20·6%) from low HDI countries. The 30-day SSI rate was 6.3% (33/523) in high HDI, 12·8% (51/397) in middle HDI and 24·7% (59/239) in low HDI countries. SSI was associated with higher incidence of 30-day mortality, intervention, organ-space infection and other HAIs, with the highest rates seen in low HDI countries. Median length of stay in patients who had an SSI was longer (7.0 days), compared with 3.0 days in patients who did not have an SSI. Use of laparoscopy was associated with significantly lower SSI rates, even after accounting for HDI.Conclusion The odds of SSI in children is nearly four times greater in low HDI compared with high HDI countries. Policies to reduce SSI should be prioritised as part of the wider global agenda.
Published: 2020
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30. The NESTORE e-Coach: Designing a Multi-Domain Pathway to Well-Being in Older Age

Author: Leonardo Angelini, Mira El Kamali, Elena Mugellini, Omar Abou Khaled, Christina Röcke, Simone Porcelli, Alfonso Mastropietro, Giovanna Rizzo, Noemi Boqué, Josep Maria del Bas, Filippo Palumbo, Michele Girolami, Antonino Crivello, Canan Ziylan, Paula Subías-Beltrán, Silvia Orte, Carlo Emilio Standoli, Laura Fernandez Maldonado, Maurizio Caon, Martin Sykora, Suzanne Elayan, Sabrina Guye, and Giuseppe Andreoni
Subjects: older adults, virtual coach, healthy lifestyles, pathway, well-being, Technology
Abstract: This article describes the coaching strategies of the NESTORE e-coach, a virtual coach for promoting healthier lifestyles in older age. The novelty of the NESTORE project is the definition of a multi-domain personalized pathway where the e-coach accompanies the user throughout different structured and non-structured coaching activities and recommendations. The article also presents the design process of the coaching strategies, carried out including older adults from four European countries and experts from the different health domains, and the results of the tests carried out with 60 older adults in Italy, Spain and The Netherlands.
Published: 2022
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31. Temperate Bacteriophages (Prophages) in Pseudomonas aeruginosa Isolates Belonging to the International Cystic Fibrosis Clone (CC274)

Author: Antón Ambroa, Lucia Blasco, Carla López-Causapé, Rocio Trastoy, Laura Fernandez-García, Ines Bleriot, Manuel Ponce-Alonso, Olga Pacios, Maria López, Rafael Cantón, Timothy J. Kidd, German Bou, Antonio Oliver, and Maria Tomás
Subjects: prophages, inovirus, siphovirus, Pseudomonas, CC274 clone, cystic fibrosis, Microbiology, QR1-502
Abstract: Bacteriophages are important in bacterial ecology and evolution. Pseudomonas aeruginosa is the most prevalent bacterial pathogen in chronic bronchopulmonary infection in cystic fibrosis (CF). In this study, we used bioinformatics, microbiological and microscopy techniques to analyze the bacteriophages present in 24 P. aeruginosa isolates belonging to the international CF clone (ST274-CC274). Interestingly, we detected the presence of five members of the Inoviridae family of prophages (Pf1, Pf4, Pf5, Pf6, Pf7), which have previously been observed in P. aeruginosa. In addition, we identified a new filamentous prophage, designated Pf8, in the P. aeruginosa AUS411.500 isolate belonging to the international CF clone. We detected only one prophage, never previously described, from the family Siphoviridiae (with 66 proteins and displaying homology with PHAGE_Pseudo_phi297_NC_016762). This prophage was isolated from the P. aeruginosa AUS531 isolate carrying a new gene which is implicated in the phage infection ability, named Bacteriophage Control Infection (bci). We characterized the role of the Bci protein in bacteriophage infection and in regulating the host Quorum Sensing (QS) system, motility and biofilm and pyocyanin production in the P. aeruginosa isogenic mutant AUS531Δbci isolate. The findings may be relevant for the identification of targets in the development of new strategies to control P. aeruginosa infections, particularly in CF patients.
Published: 2020
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32. Capturing waste collection planning expert knowledge in a fitness function through preference learning

Author: Díaz, Laura Fernández, Díaz, Miriam Fernández, Quevedo, José Ramón, and Montañés, Elena
Subjects: Computer Science - Machine Learning, Computer Science - Artificial Intelligence
Abstract: This paper copes with the COGERSA waste collection process. Up to now, experts have been manually designed the process using a trial and error mechanism. This process is not globally optimized, since it has been progressively and locally built as council demands appear. Planning optimization algorithms usually solve it, but they need a fitness function to evaluate a route planning quality. The drawback is that even experts are not able to propose one in a straightforward way due to the complexity of the process. Hence, the goal of this paper is to build a fitness function though a preference framework, taking advantage of the available expert knowledge and expertise. Several key performance indicators together with preference judgments are carefully established according to the experts for learning a promising fitness function. Particularly, the additivity property of them makes the task be much more affordable, since it allows to work with routes rather than with route plannings. Besides, a feature selection analysis is performed over such indicators, since the experts suspect of a potential existing (but unknown) redundancy among them. The experiment results confirm this hypothesis, since the best $C-$index ($98\%$ against around $94\%$) is reached when 6 or 8 out of 21 indicators are taken. Particularly, truck load seems to be a highly promising key performance indicator, together to the travelled distance along non-main roads. A comparison with other existing approaches shows that the proposed method clearly outperforms them, since the $C-$index goes from $72\%$ or $90\%$ to $98\%$.
Published: 2024
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33. BIN1K358R suppresses glial response to plaques in mouse model of Alzheimer's disease

Author: Garcia‐Agudo, Laura Fernandez, Shi, Zechuan, Smith, Ian F, Kramár, Enikö A, Tran, Katelynn, Kawauchi, Shimako, Wang, Shuling, Collins, Sherilyn, Walker, Amber, Shi, Kai‐Xuan, Neumann, Jonathan, Liang, Heidi Yahan, Da Cunha, Celia, Milinkeviciute, Giedre, Morabito, Samuel, Miyoshi, Emily, Rezaie, Narges, Gomez‐Arboledas, Angela, Arvilla, Adrian Mendoza, Ghaemi, Daryan Iman, Tenner, Andrea J, LaFerla, Frank M, Wood, Marcelo A, Mortazavi, Ali, Swarup, Vivek, MacGregor, Grant R, and Green, Kim N
Subjects: Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Alzheimer's Disease, Brain Disorders, Neurodegenerative, Dementia, Acquired Cognitive Impairment, Aging, 2.1 Biological and endogenous factors, Aetiology, Neurological, Mice, Animals, Alzheimer Disease, Plaque, Amyloid, Amyloid beta-Peptides, Neuroglia, Mice, Transgenic, Disease Models, Animal, Alzheimer's disease, astrocytes, BIN1 K358R, inflammation, MODEL-AD, oligodendrocytes, MODEL‐AD, Geriatrics, Clinical sciences, Biological psychology
Abstract: IntroductionThe BIN1 coding variant rs138047593 (K358R) is linked to Late-Onset Alzheimer's Disease (LOAD) via targeted exome sequencing.MethodsTo elucidate the functional consequences of this rare coding variant on brain amyloidosis and neuroinflammation, we generated BIN1K358R knock-in mice using CRISPR/Cas9 technology. These mice were subsequently bred with 5xFAD transgenic mice, which serve as a model for Alzheimer's pathology.ResultsThe presence of the BIN1K358R variant leads to increased cerebral amyloid deposition, with a dampened response of astrocytes and oligodendrocytes, but not microglia, at both the cellular and transcriptional levels. This correlates with decreased neurofilament light chain in both plasma and brain tissue. Synaptic densities are significantly increased in both wild-type and 5xFAD backgrounds homozygous for the BIN1K358R variant.DiscussionThe BIN1 K358R variant modulates amyloid pathology in 5xFAD mice, attenuates the astrocytic and oligodendrocytic responses to amyloid plaques, decreases damage markers, and elevates synaptic densities.HighlightsBIN1 rs138047593 (K358R) coding variant is associated with increased risk of LOAD. BIN1 K358R variant increases amyloid plaque load in 12-month-old 5xFAD mice. BIN1 K358R variant dampens astrocytic and oligodendrocytic response to plaques. BIN1 K358R variant decreases neuronal damage in 5xFAD mice. BIN1 K358R upregulates synaptic densities and modulates synaptic transmission.
Published: 2024

34. Vojta Therapy in Neuromotor Development of Pediatrics Patients with Periventricular Leukomalacia: Case Series

Author: Elena De-La-Barrera-Aranda, Juan Jose Gonzalez-Gerez, Manuel Saavedra-Hernandez, Laura Fernandez-Bueno, Cleofas Rodriguez-Blanco, and Carlos Bernal-Utrera
Subjects: pediatric neurology, physical therapy, non-invasive therapy, vojta therapy, postural control, Medicine (General), R5-920
Abstract: Background and Objectives: Vojta therapy is used by physiotherapists and is based on stimulation through peripheral pressure that leads to the activation of involuntary motor response patterns, thus triggering patterns of reflex locomotion, hence also called reflex locomotion therapy. Objective: To analyze the changes produced by Vojta therapy in the evolution of infant motor development in patients with maturational delay due to periventricular leukomalacia. Materials and methods: One session of Vojta Therapy per week for eleven months, patients’ neuromotor development was evaluated through the Denver II Test and the Baleys Scale. Results: A clinically significant increase in the development of the patients is observed. Conclusions: Neuromotor development seems to generate an adequate progression in the motor area.
Published: 2021
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35. GEF-H1 Signaling upon Microtubule Destabilization Is Required for Dendritic Cell Activation and Specific Anti-tumor Responses

Author: Abhishek S. Kashyap, Laura Fernandez-Rodriguez, Yun Zhao, Gianni Monaco, Marcel P. Trefny, Naohiro Yoshida, Kea Martin, Ashwani Sharma, Natacha Olieric, Pankaj Shah, Michal Stanczak, Nicole Kirchhammer, Sung-Moo Park, Sebastien Wieckowski, Heinz Laubli, Rachid Zagani, Benjamin Kasenda, Michel O. Steinmetz, Hans-Christian Reinecker, and Alfred Zippelius
Subjects: Biology (General), QH301-705.5
Abstract: Summary: Dendritic cell (DC) activation is a critical step for anti-tumor T cell responses. Certain chemotherapeutics can influence DC function. Here we demonstrate that chemotherapy capable of microtubule destabilization has direct effects on DC function; namely, it induces potent DC maturation and elicits anti-tumor immunity. Guanine nucleotide exchange factor-H1 (GEF-H1) is specifically released upon microtubule destabilization and is required for DC activation. In response to chemotherapy, GEF-H1 drives a distinct cell signaling program in DCs dominated by the c-Jun N-terminal kinase (JNK) pathway and AP-1/ATF transcriptional response for control of innate and adaptive immune responses. Microtubule destabilization, and subsequent GEF-H1 signaling, enhances cross-presentation of tumor antigens to CD8 T cells. In absence of GEF-H1, anti-tumor immunity is hampered. In cancer patients, high expression of the GEF-H1 immune gene signature is associated with prolonged survival. Our study identifies an alternate intracellular axis in DCs induced upon microtubule destabilization in which GEF-H1 promotes protective anti-tumor immunity. : Certain chemotherapeutics elicit potent anti-tumor immunity. Kashyap et al. demonstrate that microtubule-destabilizing chemotherapeutics induce maturation of dendritic cells through activation of microtubule-associated protein GEF-H1. This leads to effective priming of CD8 T cells against tumor antigens. GEF-H1 is critical for anti-tumor immunity of microtubule-targeting chemotherapy. Keywords: GEF-H1, lfc, dendritic cells, microtubule-targeting agents, cross presentation, JNK pathway, ansamitocin-P3, plinabulin, immunotherapy, chemotherapy
Published: 2019
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36. Relationship Between the Quorum Network (Sensing/Quenching) and Clinical Features of Pneumonia and Bacteraemia Caused by A. baumannii

Author: Laura Fernandez-Garcia, Antón Ambroa, Lucia Blasco, Ines Bleriot, Maria López, Rocio Alvarez-Marin, Felipe Fernández-Cuenca, Luis Martinez-Martinez, Jordi Vila, Jesús Rodríguez-Baño, Jose Garnacho-Montero, Jose Miguel Cisneros, Alvaro Pascual, Jeronimo Pachón, German Bou, Younes Smani, and Maria Tomás
Subjects: quorum, sensing/quenching, pneumonia, bacteraemia, Acinetobacter, Microbiology, QR1-502
Abstract: Acinetobacter baumannii (Ab) is one of the most important pathogens associated with nosocomial infections, especially pneumonia. Interest in the Quorum network, i.e., Quorum Sensing (QS)/Quorum Quenching (QQ), in this pathogen has grown in recent years. The Quorum network plays an important role in regulating diverse virulence factors such as surface motility and bacterial competition through the type VI secretion system (T6SS), which is associated with bacterial invasiveness. In the present study, we investigated 30 clinical strains of A. baumannii isolated in the “II Spanish Study of A. baumannii GEIH-REIPI 2000-2010” (Genbank Umbrella Bioproject PRJNA422585), a multicentre study describing the relationship between the Quorum network in A. baumannii and the development of pneumonia and associated bacteraemia. Expression of the aidA gene (encoding the AidA protein, QQ enzyme) was lower (P < 0.001) in strains of A. baumannii isolated from patients with bacteraemic pneumonia than in strains isolated from patients with non-bacteraemic pneumonia. Moreover, aidA expression in the first type of strain was not regulated in the presence of environmental stress factors such as the 3-oxo-C12-HSL molecule (substrate of AidA protein, QQ activation) or H2O2 (inhibitor of AidA protein, QS activation). However, in the A. baumannii strains isolated from patients with non-bacteraemic pneumonia, aidA gene expression was regulated by stressors such as 3-oxo-C12-HSL and H2O2. In an in vivo Galleria mellonella model of A. baumannii infection, the A. baumannii ATCC 17978 strain was associated with higher mortality (100% at 24 h) than the mutant, abaI-deficient, strain (carrying a synthetase enzyme of Acyl homoserine lactone molecules) (70% at 24 h). These data suggest that the QS (abaR and abaI genes)/QQ (aidA gene) network affects the development of secondary bacteraemia in pneumonia patients and also the virulence of A. baumannii.
Published: 2018
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37. CaMKIIα Expressing Neurons to Report Activity-Related Endogenous Hypoxia upon Motor-Cognitive Challenge

Author: Umer Javed Butt, Imam Hassouna, Laura Fernandez Garcia-Agudo, Agnes A. Steixner-Kumar, Constanze Depp, Nadine Barnkothe, Matthias R. Zillmann, Anja Ronnenberg, Viktoria Bonet, Sandra Goebbels, Klaus-Armin Nave, and Hannelore Ehrenreich
Subjects: physiological hypoxia, complex running wheel, hippocampus, scRNA-seq, light-sheet microscopy, Hif-1α, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract: We previously introduced the brain erythropoietin (EPO) circle as a model to explain the adaptive ‘brain hardware upgrade’ and enhanced performance. In this fundamental circle, brain cells, challenged by motor-cognitive tasks, experience functional hypoxia, triggering the expression of EPO among other genes. We attested hypoxic cells by a transgenic reporter approach under the ubiquitous CAG promoter, with Hif-1α oxygen-dependent degradation-domain (ODD) fused to CreERT2-recombinase. To specifically focus on the functional hypoxia of excitatory pyramidal neurons, here, we generated CaMKIIα-CreERT2-ODD::R26R-tdTomato mice. Behavioral challenges, light-sheet microscopy, immunohistochemistry, single-cell mRNA-seq, and neuronal cultures under normoxia or hypoxia served to portray these mice. Upon complex running wheel performance as the motor-cognitive task, a distinct increase in functional hypoxic neurons was assessed immunohistochemically and confirmed three-dimensionally. In contrast, fear conditioning as hippocampal stimulus was likely too short-lived to provoke neuronal hypoxia. Transcriptome data of hippocampus under normoxia versus inspiratory hypoxia revealed increases in CA1 CaMKIIα-neurons with an immature signature, characterized by the expression of Dcx, Tbr1, CaMKIIα, Tle4, and Zbtb20, and consistent with accelerated differentiation. The hypoxia reporter response was reproduced in vitro upon neuronal maturation. To conclude, task-associated activity triggers neuronal functional hypoxia as a local and brain-wide reaction mediating adaptive neuroplasticity. Hypoxia-induced genes such as EPO drive neuronal differentiation, brain maturation, and improved performance.
Published: 2021
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38. Lipidómica de membrana aplicada a la personalización de alimentos

Author: Itziar Tueros, Javier Amézaga, Mercedes Caro, Sara Arranz, Patricia Rioja, and Laura Fernandez
Subjects: Nutrition. Foods and food supply, TX341-641, Nutritional diseases. Deficiency diseases, RC620-627
Abstract: III Congreso de Alimentación, Nutrición y Dietética. Combinar la nutrición comunitaria y personalizada: nuevos retos.
Published: 2020

39. Viral Related Tools against SARS-CoV-2

Author: Laura Fernandez-Garcia, Olga Pacios, Mónica González-Bardanca, Lucia Blasco, Inés Bleriot, Antón Ambroa, María López, German Bou, and Maria Tomás
Subjects: SARS-CoV-2, COVID-19, phages, CRISPR, viruses, prevention, Microbiology, QR1-502
Abstract: At the end of 2019, a new disease appeared and spread all over the world, the COVID-19, produced by the coronavirus SARS-CoV-2. As a consequence of this worldwide health crisis, the scientific community began to redirect their knowledge and resources to fight against it. Here we summarize the recent research on viruses employed as therapy and diagnostic of COVID-19: (i) viral-vector vaccines both in clinical trials and pre-clinical phases; (ii) the use of bacteriophages to find antibodies specific to this virus and some studies of how to use the bacteriophages themselves as a treatment against viral diseases; and finally, (iii) the use of CRISPR-Cas technology both to obtain a fast precise diagnose of the patient and also the possible use of this technology as a cure.
Published: 2020
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40. Mechanisms of Tolerance and Resistance to Chlorhexidine in Clinical Strains of Klebsiella pneumoniae Producers of Carbapenemase: Role of New Type II Toxin-Antitoxin System, PemIK

Author: Ines Bleriot, Lucia Blasco, Mercedes Delgado-Valverde, Ana Gual-de-Torrella, Anton Ambroa, Laura Fernandez-Garcia, Maria Lopez, Jesus Oteo-Iglesias, Thomas K. Wood, Alvaro Pascual, German Bou, Felipe Fernandez-Cuenca, and Maria Tomas
Subjects: tolerance, persistence, cross-resistance, toxin-antitoxin system, PemI/PemK, Klebsiella pneumoniae, Medicine
Abstract: Although the failure of antibiotic treatment is normally attributed to resistance, tolerance and persistence display a significant role in the lack of response to antibiotics. Due to the fact that several nosocomial pathogens show a high level of tolerance and/or resistance to chlorhexidine, in this study we analyzed the molecular mechanisms associated with chlorhexidine adaptation in two clinical strains of Klebsiella pneumoniae by phenotypic and transcriptomic studies. These two strains belong to ST258-KPC3 (high-risk clone carrying β-lactamase KPC3) and ST846-OXA48 (low-risk clone carrying β-lactamase OXA48). Our results showed that the K. pneumoniae ST258-KPC3CA and ST846-OXA48CA strains exhibited a different behavior under chlorhexidine (CHLX) pressure, adapting to this biocide through resistance and tolerance mechanisms, respectively. Furthermore, the appearance of cross-resistance to colistin was observed in the ST846-OXA48CA strain (tolerant to CHLX), using the broth microdilution method. Interestingly, this ST846-OXA48CA isolate contained a plasmid that encodes a novel type II toxin/antitoxin (TA) system, PemI/PemK. We characterized this PemI/PemK TA system by cloning both genes into the IPTG-inducible pCA24N plasmid, and found their role in persistence and biofilm formation. Accordingly, the ST846-OXA48CA strain showed a persistence biphasic curve in the presence of a chlorhexidine-imipenem combination, and these results were confirmed by the enzymatic assay (WST-1).
Published: 2020
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41. Strategies to Combat Multidrug-Resistant and Persistent Infectious Diseases

Author: Olga Pacios, Lucia Blasco, Inès Bleriot, Laura Fernandez-Garcia, Mónica González Bardanca, Antón Ambroa, María López, German Bou, and Maria Tomás
Subjects: anti-mdr strategies, anti-persistent treatments, drug repurposing, Therapeutics. Pharmacology, RM1-950
Abstract: Antibiotic failure is one of the most worrying health problems worldwide. We are currently facing an international crisis with several problematic facets: new antibiotics are no longer being discovered, resistance mechanisms are occurring in almost all clinical isolates of bacteria, and recurrent infections caused by persistent bacteria are hampering the successful treatment of infections. In this context, new anti-infectious strategies against multidrug-resistant (MDR) and persistent bacteria, as well as the rescue of Food and Drug Administration (FDA)-approved compounds (drug repurposing), are being explored. Among the highlighted new anti-infectious strategies, in this review, we focus on antimicrobial peptides, anti-virulence compounds, phage therapy, and new molecules. As drugs that are being repurposed, we highlight anti-inflammatory compounds, anti-psychotics, anti-helminthics, anti-cancerous drugs, and statins.
Published: 2020
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42. Cellular Markers of Active Disease and Cure in Different Forms of Leishmania infantum-Induced Disease

Author: Laura Botana, Belén Matía, Juan V. San Martin, Alberto Romero-Maté, Alicia Castro, Laura Molina, Laura Fernandez, Ana Ibarra-Meneses, Marta Aguado, Carmen Sánchez, Luis Horrillo, Carmen Chicharro, Javier Nieto, Sheila Ortega, José Manuel Ruiz-Giardin, Eugenia Carrillo, and Javier Moreno
Subjects: visceral leishmaniasis, cutaneous leishmaniasis, lymphadenopathic leishmaniasis, mucosal leishmaniasis, biomarker, cure, Microbiology, QR1-502
Abstract: Increased numbers of peripheral blood mononucleocytes (PBMC) and increased IFN-γ secretion following in vitro challenge of blood samples with soluble Leishmania antigen (SLA), have been proposed as biomarkers of specific cell-mediated immunity, indicating that treatment of visceral leishmaniasis (VL) has been successful. However, Leishmania infantum infection may manifest as cutaneous leishmaniasis (CL), and less commonly as localized leishmanial lymphadenopathy (LLL) or mucosal leishmaniasis (ML). The present work examines the value of these biomarkers as indicators of cured leishmaniasis presenting in these different forms. Blood samples were collected before and after treatment from patients living in Fuenlabrada (Madrid, Spain), an L. infantum-endemic area recently the center of a leishmaniasis outbreak. All samples were subjected to Leishmania-specific PCR, serological tests (IFAT and rK39-ICT), and the SLA-cell proliferation assay (SLA-CPA), recording PBMC proliferation and the associated changes in IFN-γ production. Differences in the results recorded for the active and cured conditions were only significant for VL. PCR returned positive results in 67% of patients with active VL and in 3% of those with cured leishmaniasis. Similarly, rK39-ICT returned a positive result in 77% of active VL samples vs. 52% in cured VL samples, and IFAT in 90% vs. 56%; in the SLA-CPA, PBMC proliferation was seen in 16% vs. 90%, and an associated increase in IFN-γ production of 14 and 84%, respectively. The present findings reinforce the idea that PBMC proliferation and increased IFN-γ production in SLA-stimulated PBMC provide biomarkers of clinical cure in VL. Other tests are urgently needed to distinguish between the cured and active forms of the other types of clinical leishmaniasis caused by L. infantum.
Published: 2018
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43. The Integrative Conjugative Element (ICE) of Mycoplasma agalactiae: Key Elements Involved in Horizontal Dissemination and Influence of Coresident ICEs

Author: Eric Baranowski, Emilie Dordet-Frisoni, Eveline Sagné, Marie-Claude Hygonenq, Gabriela Pretre, Stéphane Claverol, Laura Fernandez, Laurent Xavier Nouvel, and Christine Citti
Subjects: evolution, functional genomics, horizontal gene transfer, integrative conjugative element, Mycoplasma, Microbiology, QR1-502
Abstract: ABSTRACT The discovery of integrative conjugative elements (ICEs) in wall-less mycoplasmas and the demonstration of their role in massive gene flows within and across species have shed new light on the evolution of these minimal bacteria. Of these, the ICE of the ruminant pathogen Mycoplasma agalactiae (ICEA) represents a prototype and belongs to a new clade of the Mutator-like superfamily that has no preferential insertion site and often occurs as multiple chromosomal copies. Here, functional genomics and mating experiments were combined to address ICEA functions and define the minimal ICEA chassis conferring conjugative properties to M. agalactiae. Data further indicated a complex interaction among coresident ICEAs, since the minimal ICEA structure was influenced by the occurrence of additional ICEA copies that can trans-complement conjugation-deficient ICEAs. However, this cooperative behavior was limited to the CDS14 surface lipoprotein, which is constitutively expressed by coresident ICEAs, and did not extend to other ICEA proteins, including the cis-acting DDE recombinase and components of the mating channel whose expression was detected only sporadically. Remarkably, conjugation-deficient mutants containing a single ICEA copy knocked out in cds14 can be complemented by neighboring cells expressing CDS14. This result, together with those revealing the conservation of CDS14 functions in closely related species, may suggest a way for mycoplasma ICEs to extend their interaction outside their chromosomal environment. Overall, this report provides a first model of conjugative transfer in mycoplasmas and offers valuable insights into understanding horizontal gene transfer in this highly adaptive and diverse group of minimal bacteria. IMPORTANCE Integrative conjugative elements (ICEs) are self-transmissible mobile genetic elements that are key mediators of horizontal gene flow in bacteria. Recently, a new category of ICEs was identified that confer conjugative properties to mycoplasmas, a highly adaptive and diverse group of wall-less bacteria with reduced genomes. Unlike classical ICEs, these mobile elements have no preferential insertion specificity, and multiple mycoplasma ICE copies can be found randomly integrated into the host chromosome. Here, the prototype ICE of Mycoplasma agalactiae was used to define the minimal conjugative machinery and to propose the first model of ICE transfer in mycoplasmas. This model unveils the complex interactions taking place among coresident ICEs and suggests a way for these elements to extend their influence outside their chromosomal environment. These data pave the way for future studies aiming at deciphering chromosomal transfer, an unconventional mechanism of DNA swapping that has been recently associated with mycoplasma ICEs.
Published: 2018
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44. F1 Domain of the Leishmania (Leishmania) donovani Nucleoside Hydrolase Promotes a Th1 Response in Leishmania (Leishmania) infantum Cured Patients and in Asymptomatic Individuals Living in an Endemic Area of Leishmaniasis

Author: Eugenia Carrillo, Laura Fernandez, Ana Victoria Ibarra-Meneses, Micheli L. B. Santos, Dirlei Nico, Paula M. de Luca, Cristiane Bani Correa, Roque Pacheco de Almeida, Javier Moreno, and Clarisa B. Palatnik-de-Sousa
Subjects: human visceral leishmaniasis, cutaneous leishmaniasis, nucleoside hydrolase, B cell epitopes, T cell epitopes, adaptive immunity, Immunologic diseases. Allergy, RC581-607
Abstract: The Leishmania (Leishmania) donovani nucleoside hydrolase NH36 is the main antigen of the Leishmune® vaccine and one of the promising candidates for vaccination against visceral leishmaniasis. The antigenicity of the N-terminal (F1), the central (F2), or the C-terminal recombinant domain (F3) of NH36 was evaluated using peripheral blood mononuclear cells (PBMC) from individuals infected with L. (L.) infantum from an endemic area of visceral leishmaniasis of Spain. Both NH36 and F1 domains significantly increased the PBMC proliferation stimulation index of cured patients and infected asymptomatic individuals compared to healthy controls. Moreover, F1 induced a 19% higher proliferative response than NH36 in asymptomatic exposed subjects. In addition, in patients cured from visceral leishmaniasis, proliferation in response to NH36 and F1 was accompanied by a significant increase of IFN-γ and TNF-α secretion, which was 42–43% higher, in response to F1 than to NH36. The interleukin 17 (IL-17) secretion was stronger in asymptomatic subjects, in response to F1, as well as in cured cutaneous leishmaniasis after NH36 stimulation. While no IL-10 secretion was determined by F1, a granzyme B increase was detected in supernatants from cured patients after stimulation with either NH36 or F1. These data demonstrate that F1 is the domain of NH36 that induces a recall cellular response in individuals with acquired resistance to the infection by L. (L.) infantum. In addition, F1 and NH36 discriminated the IgG3 humoral response in patients with active visceral leishmaniasis due to L. (L.) donovani (Ethiopia) and L. (L.) infantum (Spain) from that of endemic and non-endemic area controls. NH36 showed higher reactivity with sera from L. (L.) donovani-infected individuals, indicating species specificity. We conclude that the F1 domain, previously characterized as an inducer of the Th1 and Th17 responses in cured/exposed patients infected with L. (L.) infantum chagasi, may also be involved in the generation of a protective response against L. (L.) infantum and represents a potential vaccine candidate for the control of human leishmaniasis alone, or in combination with other HLA epitopes/antigens.
Published: 2017
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45. Heterogeneous Tumor Subpopulations Cooperate to Drive Invasion

Author: Anna Chapman, Laura Fernandez del Ama, Jennifer Ferguson, Jivko Kamarashev, Claudia Wellbrock, and Adam Hurlstone
Subjects: Biology (General), QH301-705.5
Abstract: Clonal selection and transcriptional reprogramming (e.g., epithelial-mesenchymal transition or phenotype switching) are the predominant theories thought to underlie tumor progression. However, a “division of labor” leading to cooperation among tumor-cell subpopulations could be an additional catalyst of progression. Using a zebrafish-melanoma xenograft model, we found that in a heterogeneous setting, inherently invasive cells, which possess protease activity and deposit extracellular matrix (ECM), co-invade with subpopulations of poorly invasive cells, a phenomenon we term “cooperative invasion”. Whereas the poorly invasive cells benefit from heterogeneity, the invasive cells switch from protease-independent to an MT1-MMP-dependent mode of invasion. We did not observe changes in expression of the melanoma phenotype determinant MITF during cooperative invasion, thus ruling out the necessity for phenotype switching for invasion. Altogether, our data suggest that cooperation can drive melanoma progression without the need for clonal selection or phenotype switching and can account for the preservation of heterogeneity seen throughout tumor progression.
Published: 2014
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46. Uso profilático de Mitomicina C para inibir a formação de 'haze' após ceratectomia fotorrefrativa em miopias altas resultados após dois anos

Author: Paulo Ricardo Pereira de Oliveira, Laura Fernandez Simão, Sérgio Augusto Falkembach Simão, and James da Costa Marchiori
Subjects: Mitomicina C, Miopia, Procedimentos cirúrgicos oftalmológicos, Opacidade da córnea, Ophthalmology, RE1-994
Abstract: OBJETIVO: Avaliar os resultados a longo prazo da aplicação profilática da Mitomicina C para inibir a formação de opacidade corneana em ceratectomia fotorrefrativa (PRK) em pacientes com miopia alta. MÉTODOS: Estudo retrospectivo, descritivo, longitudinal que compreendeu 59 olhos (30 pacientes) que realizaram cirurgia de PRK com aplicação de Mitomicina C entre janeiro e março de 2008. Os critérios de inclusão dos pacientes foram: equivalente esférico maior do que -4,00 dioptrias, espessura corneana maior do que 480 µm, ausência de cirurgia prévia, de trauma ocular e de enfermidades oculares e sistêmicas. Após realização do PRK, os olhos foram tratados com micro esponja embebida com MMC 0.02% por 20 segundos sobre a área da ablação. Foram realizadas medidas de refração, acuidade visual sem correção, acuidade visual corrigida e observação da opacidade corneana através da lâmpada de fenda nos dois anos de seguimento. RESULTADOS: No pós-operatório, não foram observados efeitos adversos imediatos ou tardios da MMC. Não foi observada opacidade corneana em nenhum olho após dois anos do ato cirúrgico. Em um olho foi observada opacidade grau 2,0 do terceiro até o sexto mês de seguimento. Nos demais olhos, não houve opacidade maior do que 1,0. A acuidade visual não corrigida foi de 20/40 ou melhor em 96,91% dos olhos e de 20/20 em 81,35% dos olhos. A acuidade visual corrigida manteve-se em 57 olhos e houve ganho de uma linha em 2 olhos. CONCLUSÃO: O uso profilático da Mitomicina C a 0,02% após PRK pareceu mostrar-se eficaz na redução de formação de opacidade ocular.
Published: 2011
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47. Desorption of Lipases Immobilized on Octyl-Agarose Beads and Coated with Ionic Polymers after Thermal Inactivation. Stronger Adsorption of Polymers/Unfolded Protein Composites

Author: Jose J. Virgen-Ortíz, Sara G. Pedrero, Laura Fernandez-Lopez, Nerea Lopez-Carrobles, Beatriz C. Gorines, Cristina Otero, and Roberto Fernandez-Lafuente
Subjects: enzyme physical crosslinking with polymers, octyl-agarose, lipase immobilization, enzyme desorption, support reuse, enzyme inactivation, Organic chemistry, QD241-441
Abstract: Lipases from Candida antarctica (isoform B) and Rhizomucor miehei (CALB and RML) have been immobilized on octyl-agarose (OC) and further coated with polyethylenimine (PEI) and dextran sulfate (DS). The enzymes just immobilized on OC supports could be easily released from the support using 2% SDS at pH 7, both intact or after thermal inactivation (in fact, after inactivation most enzyme molecules were already desorbed). The coating with PEI and DS greatly reduced the enzyme release during thermal inactivation and improved enzyme stability. However, using OC-CALB/RML-PEI-DS, the full release of the immobilized enzyme to reuse the support required more drastic conditions: a pH value of 3, a buffer concentration over 2 M, and temperatures above 45 °C. However, even these conditions were not able to fully release the thermally inactivated enzyme molecules from the support, being necessary to increase the buffer concentration to 4 M sodium phosphate and decrease the pH to 2.5. The formation of unfolded protein/polymers composites seems to be responsible for this strong interaction between the octyl and some anionic groups of OC supports. The support could be reused five cycles using these conditions with similar loading capacity of the support and stability of the immobilized enzyme.
Published: 2017
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48. Reversible Immobilization of Lipases on Heterofunctional Octyl-Amino Agarose Beads Prevents Enzyme Desorption

Author: Nazzoly Rueda, Tiago L. Albuquerque, Rocio Bartolome-Cabrero, Laura Fernandez-Lopez, Rodrigo Torres, Claudia Ortiz, Jose C. S. dos Santos, Oveimar Barbosa, and Roberto Fernandez-Lafuente
Subjects: heterofunctional supports, octyl supports, interfacial activation of lipases, ion exchange, enzyme hyperactivation, reversible immobilization, Organic chemistry, QD241-441
Abstract: Two different heterofunctional octyl-amino supports have been prepared using ethylenediamine and hexylendiamine (OCEDA and OCHDA) and utilized to immobilize five lipases (lipases A (CALA) and B (CALB) from Candida antarctica, lipases from Thermomyces lanuginosus (TLL), from Rhizomucor miehei (RML) and from Candida rugosa (CRL) and the phospholipase Lecitase Ultra (LU). Using pH 5 and 50 mM sodium acetate, the immobilizations proceeded via interfacial activation on the octyl layer, after some ionic bridges were established. These supports did not release enzyme when incubated at Triton X-100 concentrations that released all enzyme molecules from the octyl support. The octyl support produced significant enzyme hyperactivation, except for CALB. However, the activities of the immobilized enzymes were usually slightly higher using the new supports than the octyl ones. Thermal and solvent stabilities of LU and TLL were significantly improved compared to the OC counterparts, while in the other enzymes the stability decreased in most cases (depending on the pH value). As a general rule, OCEDA had lower negative effects on the stability of the immobilized enzymes than OCHDA and while in solvent inactivation the enzyme molecules remained attached to the support using the new supports and were released using monofunctional octyl supports, in thermal inactivations this only occurred in certain cases.
Published: 2016
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49. Metallothionein-Like Proteins and Energy Reserve Levels after Ni and Pb Exposure in the Pacific White Prawn Penaeus vannamei

Author: Gabriel Nunez-Nogueira, Catherine Mouneyrac, Alice Muntz, and Laura Fernandez-Bringas
Subjects: Toxicology. Poisons, RA1190-1270
Abstract: This study analyzed the changes in metallothionein-like proteins (MTLPs) and Energy Reserves (ERs) in hepatopancreas and abdominal muscle of the white prawn Penaeus vannamei. Realistic metal concentration exposure for 10 days to Ni and Pb in solution revealed that juvenile prawns partially induce MTLP in hepatopancreas after Pb exposure. Ni was distributed equally between soluble and insoluble fractions, while Pb was present only in the insoluble fraction, suggesting different detoxification strategy. No changes in lipids and glycogen concentration were detected under these experimental conditions in both tissues analyzed. MTLP could not be considered as a suitable indicator for lead exposure in hepatopancreas.
Published: 2010
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50. Erythropoietin re-wires cognition-associated transcriptional networks

Author: Singh, Manvendra, Zhao, Ying, Gastaldi, Vinicius Daguano, Wojcik, Sonja M., Curto, Yasmina, Kawaguchi, Riki, Merino, Ricardo M., Garcia-Agudo, Laura Fernandez, Taschenberger, Holger, Brose, Nils, Geschwind, Daniel, Nave, Klaus-Armin, and Ehrenreich, Hannelore
Published: 2023
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