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1. Muc5ac gastric mucin glycosylation is shaped by FUT2 activity and functionally impacts Helicobacter pylori binding

Author: Jeanna Bugaytsova, Thomas Borén, Joana Gomes, Celso A. Reis, Emmanuel Maes, Anna Shevtsova, Yannick Rossez, Catherine Robbe-Masselot, Ana Magalhães, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Umeå University, CNRS, Université de Lille, Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576, Instituto de Patologia e Imunologia Molecular da Universidade do Porto [IPATIMUP], Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF], Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF], Université de Lille-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), and Instituto de Investigação e Inovação em Saúde
Subjects: 0301 basic medicine, Glycosylation, Helicobacter pylori/metabolism, Mucus/metabolism, Mucin 5AC, Bacterial Adhesion, chemistry.chemical_compound, 0302 clinical medicine, fluids and secretions, Helicobacter, Fucosylation, Gastric Mucosa/metabolism, Mice, Knockout, Infections/microbiology, Multidisciplinary, Fucosyltransferases/genetics, respiratory system, Fucosyltransferases, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Helicobacter pylori/physiology, Protein Binding, Biology, Article, Microbiology in the medical area, Microbiology, Helicobacter Infections, Glycocalyx, 03 medical and health sciences, Lewis Blood Group Antigens, Polysaccharides, Mikrobiologi inom det medicinska området, Gastric mucosa, medicine, Animals, Humans, Polysaccharides/metabolism, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Adhesins, Bacterial, Mucin 5AC/metabolism, Cancer och onkologi, Helicobacter pylori, Gastric Mucins, Mucin, biology.organism_classification, Mucus, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Lewis Blood-Group System/metabolism, Helicobacter Infections/metabolism, Mice, Inbred C57BL, 030104 developmental biology, chemistry, Gastric Mucosa, Cancer and Oncology, Gastric Mucins/metabolism, Fucosyltransferases/metabolism, Adhesins, Bacterial/metabolism
Abstract: The gastrointestinal tract is lined by a thick and complex layer of mucus that protects the mucosal epithelium from biochemical and mechanical aggressions. This mucus barrier confers protection against pathogens but also serves as a binding site that supports a sheltered niche of microbial adherence. The carcinogenic bacteria Helicobacter pylori colonize the stomach through binding to host glycans present in the glycocalyx of epithelial cells and extracellular mucus. The secreted MUC5AC mucin is the main component of the gastric mucus layer, and BabA-mediated binding of H. pylori to MUC5AC confers increased risk for overt disease. In this study we unraveled the O-glycosylation profile of Muc5ac from glycoengineered mice models lacking the FUT2 enzyme and therefore mimicking a non-secretor human phenotype. Our results demonstrated that the FUT2 determines the O-glycosylation pattern of Muc5ac, with Fut2 knock-out leading to a marked decrease in a1,2-fucosylated structures and increased expression of the terminal type 1 glycan structure Lewis-a. Importantly, for the first time, we structurally validated the expression of Lewis-a in murine gastric mucosa. Finally, we demonstrated that loss of mucin FUT2-mediated fucosylation impairs gastric mucosal binding of H. pylori BabA adhesin, which is a recognized feature of pathogenicity. The authors thank Nuno Mendes for excellent technical support at the animal facility of IPATIMUP, University of Porto; Dr. Jacques Bara from the U-673 INSERM, CNRS, Paris, France for providing the PM7, 45M1 and 7LE antibodies; Dr Ingemar Carlstedt, University of Lund, Sweden for providing LUM6-3 and LUM5-1 antibodies and Dr. Ola Söderberg from the Uppsala Universitet, Sweden for support with the PLA experiments. This work was financed by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT - Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Inovação in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274) and the projects with the references FCOMP-01-0124-FEDER 028188 and FCOMP-01-0124-FEDER041276 (EXPL/CTM-BIO/0762/2013, PTDC/BBB-EBI/0786/2012 and PTDC/BBB-EBI/0567/2014). The authors acknowledge the support by Gastric Glyco Explorer Initial Training Network (Seventh Framework Programme GastricGlycoExplorer project, grant number 316929). AM received an individual grant (SFRH/BPD/75871/2011) from FCT, POPH (Programa Operacional Potencial Humano) and FSE (Fundo Social Europeu) and acknowledges EMBO for a Short-Term Fellowship (EMBO ASTF 330-212). The resources provided by the Consortium for Functional Glycomics were funded by NIGMS-GM62116. TB is supported by grants from Vetenskapsrådet/VR, Cancerfonden, and the J.C. Kempe and Seth M. Kempe Memorial Foundation and this work was in part performed within the Umeå Centre for Microbial Research (UCMR), and the Biochemical Imaging Center Umeå (BICU).
Published: 2016
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2. NOS1 mutations cause hypogonadotropic hypogonadism with sensory and cognitive deficits that can be reversed in infantile mice

Author: Konstantina Chachlaki, Andrea Messina, Virginia Delli, Valerie Leysen, Csilla Maurnyi, Chieko Huber, Gaëtan Ternier, Katalin Skrapits, Georgios Papadakis, Sonal Shruti, Maria Kapanidou, Xu Cheng, James Acierno, Jesse Rademaker, Sowmyalakshmi Rasika, Richard Quinton, Marek Niedziela, Dagmar L’Allemand, Duarte Pignatelli, Mirjam Dirlewander, Mariarosaria Lang-Muritano, Patrick Kempf, Sophie Catteau-Jonard, Nicolas J. Niederländer, Philippe Ciofi, Manuel Tena-Sempere, John Garthwaite, Laurent Storme, Paul Avan, Erik Hrabovszky, Alan Carleton, Federico Santoni, Paolo Giacobini, Nelly Pitteloud, Vincent Prevot, CHU Lille, Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), FHU 1,000 Days for Health [Lille], Université de Lille, Université de Lausanne = University of Lausanne (UNIL), National and Kapodistrian University of Athens (NKUA), Lausanne University Hospital, Institute of Experimental Medicine [Budapest] (KOKI), Hungarian Academy of Sciences (MTA), Université de Genève = University of Geneva (UNIGE), Oxford Brookes University, Newcastle University [Newcastle], Poznan University of Medical Sciences [Poland] (PUMS), University of Applied Sciences of Eastern Switzerland (FHO), Universidade do Porto = University of Porto, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Geneva University Hospitals and Geneva University, University Children’s Hospital Zurich, Bern University Hospital [Berne] (Inselspital), University of Bern, Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), Universidad de Córdoba = University of Córdoba [Córdoba], Instituto Maimonides de Investigación Biomédica de Cordoba (IMIBIC), Universidad de Córdoba = University of Córdoba [Córdoba]-Hospital Universitario Reina Sofía, Instituto de Salud Carlos III [Madrid] (ISC), University College of London [London] (UCL), Wolfson Institute for Biomedical Research (WIBR), Université de Clermont-Ferrand, ANR-17-CE16-0015,GRAND,Vieillissement et démence: un rôle hormonal?(2017), and Prevot, Vincent
Subjects: Hypogonadism, General Medicine, Nitric Oxide Synthase Type I, Nitric Oxide, Animals, Cognition, Gonadotropin-Releasing Hormone/genetics, Gonadotropin-Releasing Hormone/metabolism, Humans, Hypogonadism/complications, Hypogonadism/congenital, Hypogonadism/genetics, Mice, Mutant Proteins, Mutation/genetics, Nitric Oxide Synthase Type I/genetics, Nitrites, Gonadotropin-Releasing Hormone, Mutation, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], 610 Medicine & health
Abstract: The nitric oxide (NO) signaling pathway in hypothalamic neurons plays a key role in the regulation of the secretion of gonadotropin-releasing hormone (GnRH), which is crucial for reproduction. We hypothesized that a disruption of neuronal NO synthase (NOS1) activity underlies some forms of hypogonadotropic hypogonadism. Whole-exome sequencing was performed on a cohort of 341 probands with congenital hypogonadotropic hypogonadism to identify ultrarare variants in NOS1 . The activity of the identified NOS1 mutant proteins was assessed by their ability to promote nitrite and cGMP production in vitro. In addition, physiological and pharmacological characterization was carried out in a Nos1 -deficient mouse model. We identified five heterozygous NOS1 loss-of-function mutations in six probands with congenital hypogonadotropic hypogonadism (2%), who displayed additional phenotypes including anosmia, hearing loss, and intellectual disability. NOS1 was found to be transiently expressed by GnRH neurons in the nose of both humans and mice, and Nos1 deficiency in mice resulted in dose-dependent defects in sexual maturation as well as in olfaction, hearing, and cognition. The pharmacological inhibition of NO production in postnatal mice revealed a critical time window during which Nos1 activity shaped minipuberty and sexual maturation. Inhaled NO treatment at minipuberty rescued both reproductive and behavioral phenotypes in Nos1 -deficient mice. In summary, lack of NOS1 activity led to GnRH deficiency associated with sensory and intellectual comorbidities in humans and mice. NO treatment during minipuberty reversed deficits in sexual maturation, olfaction, and cognition in Nos1 mutant mice, suggesting a potential therapy for humans with NO deficiency.
Published: 2022
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3. Heparan Sulfate Biosynthesis and Sulfation Profiles as Modulators of Cancer Signalling and Progression

Author: Catarina Marques, Celso A. Reis, Romain R. Vivès, Ana Magalhães, Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto = University of Porto, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), ANR-15-IDEX-0002,UGA,IDEX UGA(2015), ANR-17-CE11-0040,SULFatAS,Structure et activités des sulfatases extracellulaires SULF(2017), ANR-19-CE13-0031,GlyCON,Décrypter la base biophysique par laquelle les glycosaminoglycanes contrôlent la signalisation des facteurs de croissance pendant le développement : une approche biomimétique(2019), and Universidade do Porto
Subjects: Cancer Research, Cell signaling, Glycan, heparan sulfate binding epitopes, Review, Extracellular matrix, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Sulfation, glycosyltransferases, glycosaminoglycan, Extracellular, cancer, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], RC254-282, sulfotransferases, 030304 developmental biology, Heparan Sulfate Biosynthesis, 0303 health sciences, biology, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, cell signalling, Heparan sulfate, 3. Good health, Cell biology, Oncology, chemistry, 030220 oncology & carcinogenesis, biology.protein, heparan sulfate, Function (biology)
Abstract: Heparan Sulfate Proteoglycans (HSPGs) are important cell surface and Extracellular Matrix (ECM) maestros involved in the orchestration of multiple cellular events in physiology and pathology. These glycoconjugates bind to various bioactive proteins via their Heparan Sulfate (HS) chains, but also through the protein backbone, and function as scaffolds for protein-protein interactions, modulating extracellular ligand gradients, cell signalling networks and cell-cell/cell-ECM interactions. The structural features of HS chains, including length and sulfation patterns, are crucial for the biological roles displayed by HSPGs, as these features determine HS chains binding affinities and selectivity. The large HS structural diversity results from a tightly controlled biosynthetic pathway that is differently regulated in different organs, stages of development and pathologies, including cancer. This review addresses the regulatory mechanisms underlying HS biosynthesis, with a particular focus on the catalytic activity of the enzymes responsible for HS glycan sequences and sulfation motifs, namely D-Glucuronyl C5-Epimerase, N- and O-Sulfotransferases. Moreover, we provide insights on the impact of different HS structural epitopes over HSPG-protein interactions and cell signalling, as well as on the effects of deregulated expression of HS modifying enzymes in the development and progression of cancer. Finally, we discuss the clinical potential of HS biosynthetic enzymes as novel targets for therapy, and highlight the importance of developing new HS-based tools for better patients’ stratification and cancer treatment.
Published: 2021
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4. A global metagenomic map of urban microbiomes and antimicrobial resistance

Author: Nadine Farhat, Tomoki Takeda, Astred Castro, Ken McGrath, Khaliun Sanchir, Iman Hajirasouliha, Eunice So, Laraib Zafar, Diana N. Nunes, Harun Mustafa, Amy Zhang, Priscilla Lisboa, Christian Schori, Marisano James, Jasna Chalangal, Sebastien Halary, Shahryar Rana, Yunmi Lee, Oli Schacher, Liliana Godoy, David A. Coil, Phanthira Pugdeethosal, Michelle D. Williams, German Marchandon, Angela Cantillo, Naoya Takahashi, Christopher Mozsary, Juana Gonzalez, Patrick K. H. Lee, Gerardo de Lamotte, Alessandro Robertiello, Steven Du, Fabienne Velter, Stefan G. Stark, Miguel Carbajo, Vincent Matthys, David A. Westfall, Julia Boeri, Irène Mauricette Mendy, Jonathan Cedillo, Francesco Oteri, Robert W. Crawford, Takayuki Ito, Tina Wunderlin, Maureen Muscat, David Paez-Espino, Carmen Urgiles, Aida Nesimi, Steffen Schaaf, Adan Ramirez-Rojas, Kunihiko Miyake, Christopher E. Mason, Anais Cardenas, Sharah Islam, Diego Benítez, Melissa Pool Pizzi, Kianna Ciaramella, Ciro Borrelli, Riham Islam, Dorottya Nagy-Szakal, Abd-Manaaf Bakere, Ait-hamlat Adel, Olha Lakhneko, Badamnyambuu Iderzorig, Ana Valeria Castro, Adam Phillips, Robert A. Petit, Flavia Corsi, Romain Conte, Krista Ryon, Soojin Jang, Joseph Benson, Fernanda de Souza Gomes Kehdy, Cindy Wang, Nicole Mathews, Jenn-Wei Chen, Rachel Paras, Paulina Pastuszek, Abigail Lyons, Paul Roldán, Muntaha Munia, Pierre Nicolas, Cassie L. Ettinger, Kyrylo Pyrshev, Katterinne N. Mendez, Eduardo Castro-Nallar, Valeriia Dotsenko, Michelle Tuz, Krizzy Mallari, Eileen Png, Yuya Sonohara, Tanja Miketic, Stéphane Delmas, Shu Zhang, Masaki Sato, Yuanting Zheng, Jifeng Zhu, Roland Häusler, Lucie Bittner, Savlatjon Rahmatulloev, Jonathan Foox, Bruno D'Alessandro, Alketa Plaku, Faisal Alquaddoomi, Yang Zhang, Kern Rei Chng, Juliana Lago, Allaeddine Chettouh, Tamera Henry, Houtan Noushmehr, Tranette Gregory, Sara Abdul Majid, Frank J. Kelly, Benjamin Pulatov, Laurie Casalot, Takema Kajita, Lennard Epping, Thais Fernanda Bartelli, Eftar Moniruzzaman, Renee Vivancos-Koopman, Thirumalaisamy P. Velavan, Tracy W. Liu, Yelyzaveta Tymoshenko, Alma Plaku, Nika Gurianova, Ambar Mendez, Anna Tomaselli, Sonia Dorado, Donato Giovannelli, Hira Choudhry, Synti Ng, Sheelta S. Kumar, Jennifer Q. Lu, Weijun Liang, Ellen Koag, Dennis Gankin, Maria João Amorim, Gwenola Simon, Kiyoshi Suganuma, Mikhail Karasikov, Christos A. Ouzounis, Madelyn May, Eran Elhaik, Stephan Ossowski, Kevin Bolzli, Matthew Arthur, Yuya Oto, Jananan Pathmanathan, Salah Mahmoud, Kou Takahashi, Brunna Marques, Kelly French, Felipe Sepúlveda, Shusei Yoshikawa, Paulo Thiago de Souza Santos, Andrew N. Gray, Juliana S Bernardes, Felipe Segato, Björn Brindefalk, George C. Yeh, Jhovana L. Velasco Flores, Jill Sullivan, Silva Baburyan, Denisse Flores, Russell Y. Neches, Sabrina Persaud, Rasheena Wright, Takumi Togashi, Verónica Antelo, Nao Kato, Skye Felice, Tatjana Mustac, Daisy Donnellan, Katerine Carrillo, Anna Litskevitch, Catalina García, Sota Ito, Naya Eady, Andrew Wan, Irene Meng, Sophie Guasco, Danilo Ercolini, Francesca De Filippis, Vincent Lemaire, Luice Fan, Lothar H. Wieler, Mariia Rybak, Jorge Sanchez, Jonathan S. Gootenberg, Itsuki Tomita, Maritza S Mosella, Laura Garcia, Natalka Makogon, Daisy Cheung, Hitler Francois Vasquez Arevalo, Freddy Asenjo, Gabriela P. Branco, Erika Cifuentes, Chloé Dequeker, Aspassia D. Chatziefthimiou, Alexis Terrero, Roy Meoded, Isabelle de Oliveira Moraes, Shaleni K. Singh, Orgil-Erdene Molomjamts, Karishma Miah, Laurent David, Wolfgang Haehr, Dao Phuong Giang, Romain Lannes, Prashanthi Ratnanandan, Ryota Yamanaka, Riccardo Vicedomini, Sadaf Ayaz, Oluwatosin M. Osuolale, Laura E. Vann, Gregory Chem, Andrea Gonzalez, Aszia Burrell, Ariel Chernomoretz, Sakura Ishizuka, Michelle Rivera, Avigdor Nosrati, Michelle B. Chen, Juliette Auvinet, Nils Ordioni, Tomoro Warashina, Guillaume Blanc, Tomislav Ivankovic, Christina Black, Lauren E. Hittle, David Hess-Homeier, Michael Kozhar, Hamood Suliman, Karobi Moitra, Saher Rahiel, Spyridon Gkotzis, Jenny Arevalo, Shaikh B. Iqbal, Beth Mutai, Mohammed Mohsin, Scott Tighe, Sylvie Collin, Yoshitaka Saito, Wayne Menary, Youping Deng, Lucy Lee, Esmeralda Jiminez, Ayuki Watanabe, Nikos C. Kyrpides, Natasha Mohan, Angelika Pupiec, Dedan Githae, Simone Cawthorne, Jonathan A. Eisen, Tomoki Iwashiro, Chiaki Homma, Thomas Saw Aung, Laura Molina, Marcus H. Y. Leung, Ophélie Da Silva, Yan Ling Wong, Hosna Noorzi, Mario Moreno, Alina Butova, Leming Shi, Brian W. Wong, Sarah S. Jackson, Moses Lin, Annabelle Meagher, Pujita Das, Catherine Burke, Mitsuki Ota, Maria Domenica Moccia, Nicolas Sprinsky, Catherine E. Pugh, David C. Green, Fazlina Fauzi, Erdenetsetseg Batdelger, Annie Geiger, Valeria Ventorino, Tolulope Oluwadare, Delisia Cuebas, Catalina Truong, Leonardo Posada, Michael Angelov, Tathiane M. Malta, Amanda Ng, Francesca Nadalin, Arya Hawkins-Zafarnia, Yuh Shiwa, Athena Mitsios, Milton Ozório Moraes, Manolo Laiola, Kalyn Ali, Jaden J.A. Hastings, Ikuto Saito, Maheen Shakil, Chisato Suzuki, Elena M. Vayndorf, Hubert Rehrauer, Ajay Menon, Kaitlan Russell, Aliyah Shari, Rebecca Smith, Gregorio Iraola, Max Priestman, Alan Briones, Silver A. Wolf, Camila Gonzalez-Poblete, Eleonora De Lazzari, Shirley Chiu, Michelle Ki, Irene Hoxie, Marianne Jaubert, Ayantu Jinfessa, Ryan J. King, Nghiem Xuan Hoan, Jalia Bynoe, Jacob Friedman, Aneisa Ramcharan, Pablo Fresia, Cristina Muñoz, Muhammad Afaq, Anyi Tang, Médine Benchouaia, Isabella Kuniko T. Takenaka, Anastasia Chasapi, Areeg Naeem, Hannah Benisty, Cecilia N. Cossio, Nathalie Hüsser, Mahfuza Sabina, Thais S. Sabedot, JoAnn Jacobs, Camila P. E. de Souza, Manuela Oliveira, Jean-Pierre Bouly, Mariko Usui, Wilson Miranda, Natalia Marciniak, Hiram Caballero, Samuel Weekes, Alexandra B. Graf, Emily Leong, Tatyana Nikolayeva, Dominique Thomas, Charlotte Greselle, Cecilia Salazar, Sreya Ray Chaudhuri, Kevin Becher, Sandra Roth, Ryusei Miura, Kari Oline Bøifot, Dimitri Manoir, Oliver Toth, Chandrima Bhattacharya, Manuel Perez, Isha Lamba, Takafumi Tsurumaki, Timothy D. Read, Anna-Lena M. Schinke, Ryan Sankar, Le Huu Song, Narasimha Rao Nedunuri, Emmanuel Dias-Neto, Ana Flávia Costa, Adiell Melamed, Christelle Desnues, Natalie R. Davidson, Aaron E. Darling, Hyung Jun Kim, Josephine Galipon, Jacqueline Orrego, Dimitar Vassilev, Michael Huber, Nur Hazlin Hazrin-Chong, Gaston H. Gonnet, Kaymisha Knights, Osman U. Sezerman, Dmitry Meleshko, Eunice Thambiraja, Jingcheng Yang, Aubin Fleiss, Gloria Nguyen, Katelyn Jackson, Nuria Aventin, Stephanie L. Hyland, Andrea Hässig, Catharine Aquino, Simona Lysakova, Israel O. Osuolale, Kasia Sluzek, Rania Siam, Alina Frolova, Samuel Hernandez, Yui Him Lo, Bazartseren Boldgiv, Ben Young, Maryna Korshevniuk, Majelia Ampadu, Yuk Man Tang, Amanda L. Muehlbauer, Sade Thomas, Gabriel Figueroa, Alexis Rivera, Lisbeth Pineda, Alexandra Dutan, Jennifer M. Tran, Chris K. Deng, Vedbar S. Khadka, Paola Florez de Sessions, Elizabeth Humphries, Hugues Richard, Hiba Naveed, Nora C. Toussaint, Mahshid Khavari, Maria del Mar Vivanco Ruiz, Antonin Thiébaut, Nicolás Rascovan, Marius Dybwad, Orhan Özcan, Lawrence Kwong, David Danko, Shaira Khan, Andrea Tassinari, Silvia Beurmann, Tsoi Ying Lai, Nanami Kubota, Tieliu Shi, Diana Chicas, Evan E. Afshin, Hirokazu Yano, Jonas Krebs, Mayuko Nakagawa, Hyun Jung Lee, Irene González Navarrete, Rachid Ounit, Lucia E. Alvarado-Arnez, Masaki Nasu, Allison Chan, Harilanto Andrianjakarivony, Jennifer Amachee, Mahdi Taye, Wan Chiew Ng, Kathryn O’Brien, Shino Ishikawa, Tristan Bitard-Feildel, Sora Takagi, Felix Hartkopf, Niamh B. O’Hara, Marcos A. S. Fonseca, Subhamitra Pakrashi, Amrit Kaur, Eva Hell, Patricia Vera-Wolf, Naimah Munim, Luiza Ferreira de Araújo, Mizuki Igarashi, Brianna Pompa-Hogan, Alessandra Carbone, Anne-Sophie Benoiston, Eric Helfrich, Michael A. Suarez-Villamil, Omar O. Abudayyeh, Natasha Abdullah, Jaime J. Fuentes, Juan Carlos Forero, Tetiana Yeskova, Denis Bertrand, Sambhawa Priya, Denisse Maldonado, Agier Nicolas, Ana Valeria B Castro, Starr Chatziefthimiou, André Kahles, Aaishah Francis, Fernanda Arredondo, Emilio Tarcitano, Irvind Buttar, Alex Alexiev, Jennifer Molinet, Sarah Shalaby, Itunu A. Oluwadare, Jason Sperry, Katrin Bakhl, Ana M. Cañas, Sofia Ahsanuddin, Miar Elaskandrany, Elodie Laine, Sven Bönigk, Johannes Werner, Stephen Eduard Boja Ruiz, Gargi Dayama, Paulina Buczansla, Brandon Valentine, Bharath Prithiviraj, Toni Bode, Stas Zubenko, Jake Cohen, Guilllaume Jospin, Zulena Saravi, Per O. Ljungdahl, Inderjit Kaur, Mauricio Moldes, Giuseppe KoLoMonaco, Denise Syndercombe Court, Sonia Bouchard, Sonia Losim, Sookwon Moon, Heba Shaaban, Suraj Patel, Sibo Zhu, Sarh Aly, Arif Asyraf Md Supie, LaShonda Dorsey, Juan Guerra, François Baudon, Rantimi A. Olawoyin, Alexia Bordigoni, Iqra Faiz, Mathilde Garcia, Gabriella Mason-Buck, María Gabriela Portilla, Niranjan Nagarajan, Fumie Takahara, Nancy Merino, Watson Andrew, Gina Kim, Yuma Sato, Hyenah Shim, Marie-Laure Jerier, Affifah Saadah Ahmad Kassim, Katerina Kuchin, Daniel Butler, Paweł P. Łabaj, Nadezhda Kobko-Litskevitch, Emmanuel F. Mongodin, Yuto Togashi, Paula Rodríguez, Pilar Lopez Hernandez, Xiaoqing Chen, Maria A. Sierra, Olga Nikolayeva, Manon Loubens, Colleen Conger, Hikaru Shirahata, Chenhao Li, Timothy Donahoe, Youngja Park, Lucia Elena Alvarado Arnez, Salama Chaker, Francisco Chavez, Alessandra Breschi, Jorge L. Sanchez, Kaung Myat San, Nayra Aguilar Rojas, Marcos Abraao, Kai Sasaki, Bryan Nazario, Olena Yemets, Klas I. Udekwu, Lynn M. Schriml, Anisia Peters, Aliaksei Holik, Mark Hernandez, Emile Faure, Malay Bhattacharyya, Josef W. Moser, Núria Andreu Somavilla, María Mercedes Zambrano, Kannan Rajendran, Gabriela E. Albuquerque, Tao Qing, Kazutoshi Tsuda, Ymke De Jong, Princess Osma, Mayra Arauco Livia, Javier Quilez Oliete, Carl Chrispin, Hyun Woo Joo, Ingrid Lafontaine, Nala An, Seisuke Sato, Felipe Segato Dezem, Andrew Maltez Thomas, Alexandre Desert, Xiao Wen Cai, O. Osuolale, Jun Wu, Coral Pardo-Esté, Courtney Robinson, Yuri Matsuzaki, Marina Nieto-Caballero, Cem Meydan, Ralph Schlapbach, Mark Menor, Sofia Castro, Rachel Kwong, Brittany Blyther, Olexandr Lykhenko, Jason R. Schriml, Christian Brion, Jenessa Orpilla, Juan A. Ugalde, Elsy Mankah Ngwa, Álvaro Aranguren, Lauren Mak, Matías Giménez, Ashanti Narce, Torsten Semmler, Stefan I. Tsonev, Abdollahi Nika, Katherine E. Dahlhausen, Monika Devi, Gunnar Rätsch, Oasima Muner, Carla Bello, Muhammad Al-Fath Amran, Anyelic Rosario, Melissa Ortega, Andrea Patrignani, Ante Peros, Elias McComb, Ryo Sato, Ireen Alam, Clara N. Dias, Soma Tanaka, Dayana Calderon, Ran Blekhman, Mathilde Mignotte, Alicia Boyd, Jochen Hecht, Thomas Neff, Xinzhao Tong, Josue Alicea, Kiara Olmeda, Sonia Marinovic, Carme Arnan, Kohei Ito, Samantha L. Goldman, Marianna S. Serpa, Renee Richer, Kaisei Sato, Jordana M. Silva, Akash Keluth Chavan, Sangwan Kim, Laís Pereira Ferreira, Sophie Vacant, Nowshin Sayara, Haruo Suzuki, Madeline Leahy, Juan C. Severyn, Sierra Vincent, Masaru Tomita, Maliha Mamun, Lucinda B. Davenport, Gabriella Oken, Dagmara Lewandowska, Gustavo Adolfo Malca Salas, Andrii Kuklin, Tyler Wong, Charlie Feigin, Eric Minwei Liu, Sonia L. Ghose, Daniela Bezdan, Antonietta La Storia, Juan P. Escalera-Antezana, Nuno Rufino de Sousa, Samuel M. Gerner, Weill Cornell Medicine [New York], Icahn School of Medicine at Mount Sinai [New York] (MSSM), Genome Institute of Singapore (GIS), Centre for Genomic Regulation [Barcelona] (CRG), Universitat Pompeu Fabra [Barcelona] (UPF)-Centro Nacional de Analisis Genomico [Barcelona] (CNAG), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Lawrence Berkeley National Laboratory [Berkeley] (LBNL), AUTRES, Massachusetts Institute of Technology (MIT), Indian Statistical Institute [Kolkata], University of Minnesota System, Universidad Andrés Bello [Santiago] (UNAB), California State University [Sacramento], University of Naples Federico II, University of Hawaii, Institut méditerranéen d'océanologie (MIO), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Toulon (UTLN), Medical Genomics Group, University College of London [London] (UCL)-UCL Cancer Institute, Norwegian Defence Research Establishment (FFI), Lund University [Lund], Institute of Molecular Biology and Genetics of National Academy of Sciences of Ukraine, University of Vienna [Vienna], King‘s College London, University of Colorado [Boulder], Institut Pasteur de Montevideo, Réseau International des Instituts Pasteur (RIIP), Institut Pasteur Korea - Institut Pasteur de Corée, Fudan University [Shanghai], City University of Hong Kong [Hong Kong] (CUHK), Stockholm University, University of Maryland School of Medicine, University of Maryland System, Fundação Oswaldo Cruz (FIOCRUZ), University of São Paulo (USP), Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Barcelona Institute of Science and Technology (BIST), Elizade University, Acibadem Mehmet Ali Aydınlar University, Paléogénomique microbienne - Microbial paleogenomics, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), Robert Koch Institute [Berlin] (RKI), East China Normal University [Shangaï] (ECNU), Cairo University, Vietnamese-German Center for Medical Research, Keio University, Université du Vermont, Universidad del Desarrollo, University of Sofia, University of Alaska [Fairbanks] (UAF), Universitätsklinikum Tübingen - University Hospital of Tübingen, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Corporación Corpogen-Research Center, Biologie Computationnelle et Quantitative = Laboratory of Computational and Quantitative Biology (LCQB), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Weill Cornell Medicine [Cornell University], Cornell University [New York], University of Naples Federico II = Università degli studi di Napoli Federico II, Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Universidade de São Paulo = University of São Paulo (USP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Софийски университет = Sofia University, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universidad Andrés Bello - UNAB (CHILE), Acibadem University Dspace, Danko, D., Bezdan, D., Afshin, E. E., Ahsanuddin, S., Bhattacharya, C., Butler, D. J., Chng, K. R., Donnellan, D., Hecht, J., Jackson, K., Kuchin, K., Karasikov, M., Lyons, A., Mak, L., Meleshko, D., Mustafa, H., Mutai, B., Neches, R. Y., Ng, A., Nikolayeva, O., Nikolayeva, T., Png, E., Ryon, K. A., Sanchez, J. L., Shaaban, H., Sierra, M. A., Thomas, D., Young, B., Abudayyeh, O. O., Alicea, J., Bhattacharyya, M., Blekhman, R., Castro-Nallar, E., Canas, A. M., Chatziefthimiou, A. D., Crawford, R. W., De Filippis, F., Deng, Y., Desnues, C., Dias-Neto, E., Dybwad, M., Elhaik, E., Ercolini, D., Frolova, A., Gankin, D., Gootenberg, J. S., Graf, A. B., Green, D. C., Hajirasouliha, I., Hastings, J. J. A., Hernandez, M., Iraola, G., Jang, S., Kahles, A., Kelly, F. J., Knights, K., Kyrpides, N. C., Labaj, P. P., Lee, P. K. H., Leung, M. H. Y., Ljungdahl, P. O., Mason-Buck, G., Mcgrath, K., Meydan, C., Mongodin, E. F., Moraes, M. O., Nagarajan, N., Nieto-Caballero, M., Noushmehr, H., Oliveira, M., Ossowski, S., Osuolale, O. O., Ozcan, O., Paez-Espino, D., Rascovan, N., Richard, H., Ratsch, G., Schriml, L. M., Semmler, T., Sezerman, O. U., Shi, L., Shi, T., Siam, R., Song, L. H., Suzuki, H., Court, D. S., Tighe, S. W., Tong, X., Udekwu, K. I., Ugalde, J. A., Valentine, B., Vassilev, D. I., Vayndorf, E. M., Velavan, T. P., Wu, J., Zambrano, M. M., Zhu, J., Zhu, S., Mason, C. E., Abdullah, N., Abraao, M., Adel, A. -H., Afaq, M., Al-Quaddoomi, F. S., Alam, I., Albuquerque, G. E., Alexiev, A., Ali, K., Alvarado-Arnez, L. E., Aly, S., Amachee, J., Amorim, M. G., Ampadu, M., Amran, M. A. -F., An, N., Andrew, W., Andrianjakarivony, H., Angelov, M., Antelo, V., Aquino, C., Aranguren, A., Araujo, L. F., Vasquez Arevalo, H. F., Arevalo, J., Arnan, C., Alvarado Arnez, L. E., Arredondo, F., Arthur, M., Asenjo, F., Aung, T. S., Auvinet, J., Aventin, N., Ayaz, S., Baburyan, S., Bakere, A. -M., Bakhl, K., Bartelli, T. F., Batdelger, E., Baudon, F., Becher, K., Bello, C., Benchouaia, M., Benisty, H., Benoiston, A. -S., Benson, J., Benitez, D., Bernardes, J., Bertrand, D., Beurmann, S., Bitard-Feildel, T., Bittner, L., Black, C., Blanc, G., Blyther, B., Bode, T., Boeri, J., Boldgiv, B., Bolzli, K., Bordigoni, A., Borrelli, C., Bouchard, S., Bouly, J. -P., Boyd, A., Branco, G. P., Breschi, A., Brindefalk, B., Brion, C., Briones, A., Buczansla, P., Burke, C. M., Burrell, A., Butova, A., Buttar, I., Bynoe, J., Bonigk, S., Boifot, K. O., Caballero, H., Cai, X. W., Calderon, D., Cantillo, A., Carbajo, M., Carbone, A., Cardenas, A., Carrillo, K., Casalot, L., Castro, S., Castro, A. V., Castro, A., Castro, A. V. B., Cawthorne, S., Cedillo, J., Chaker, S., Chalangal, J., Chan, A., Chasapi, A. I., Chatziefthimiou, S., Chaudhuri, S. R., Chavan, A. K., Chavez, F., Chem, G., Chen, X., Chen, M., Chen, J. -W., Chernomoretz, A., Chettouh, A., Cheung, D., Chicas, D., Chiu, S., Choudhry, H., Chrispin, C., Ciaramella, K., Cifuentes, E., Cohen, J., Coil, D. A., Collin, S., Conger, C., Conte, R., Corsi, F., Cossio, C. N., Costa, A. F., Cuebas, D., D'Alessandro, B., Dahlhausen, K. E., Darling, A. E., Das, P., Davenport, L. B., David, L., Davidson, N. R., Dayama, G., Delmas, S., Deng, C. K., Dequeker, C., Desert, A., Devi, M., Dezem, F. S., Dias, C. N., Donahoe, T. R., Dorado, S., Dorsey, L., Dotsenko, V., Du, S., Dutan, A., Eady, N., Eisen, J. A., Elaskandrany, M., Epping, L., Escalera-Antezana, J. P., Ettinger, C. L., Faiz, I., Fan, L., Farhat, N., Faure, E., Fauzi, F., Feigin, C., Felice, S., Ferreira, L. P., Figueroa, G., Fleiss, A., Flores, D., Velasco Flores, J. L., Fonseca, M. A. S., Foox, J., Forero, J. C., Francis, A., French, K., Fresia, P., Friedman, J., Fuentes, J. J., Galipon, J., Garcia, M., Garcia, L., Garcia, C., Geiger, A., Gerner, S. M., Ghose, S. L., Giang, D. P., Gimenez, M., Giovannelli, D., Githae, D., Gkotzis, S., Godoy, L., Goldman, S., Gonnet, G. H., Gonzalez, J., Gonzalez, A., Gonzalez-Poblete, C., Gray, A., Gregory, T., Greselle, C., Guasco, S., Guerra, J., Gurianova, N., Haehr, W., Halary, S., Hartkopf, F., Hawkins-Zafarnia, A., Hazrin-Chong, N. H., Helfrich, E., Hell, E., Henry, T., Hernandez, S., Hernandez, P. L., Hess-Homeier, D., Hittle, L. E., Hoan, N. X., Holik, A., Homma, C., Hoxie, I., Huber, M., Humphries, E., Hyland, S., Hassig, A., Hausler, R., Husser, N., Petit, R. A., Iderzorig, B., Igarashi, M., Iqbal, S. B., Ishikawa, S., Ishizuka, S., Islam, S., Islam, R., Ito, K., Ito, S., Ito, T., Ivankovic, T., Iwashiro, T., Jackson, S., Jacobs, J., James, M., Jaubert, M., Jerier, M. -L., Jiminez, E., Jinfessa, A., De Jong, Y., Joo, H. W., Jospin, G., Kajita, T., Ahmad Kassim, A. S., Kato, N., Kaur, A., Kaur, I., de Souza Gomes Kehdy, F., Khadka, V. S., Khan, S., Khavari, M., Ki, M., Kim, G., Kim, H. J., Kim, S., King, R. J., Kolomonaco, G., Koag, E., Kobko-Litskevitch, N., Korshevniuk, M., Kozhar, M., Krebs, J., Kubota, N., Kuklin, A., Kumar, S. S., Kwong, R., Kwong, L., Lafontaine, I., Lago, J., Lai, T. Y., Laine, E., Laiola, M., Lakhneko, O., Lamba, I., de Lamotte, G., Lannes, R., De Lazzari, E., Leahy, M., Lee, H., Lee, Y., Lee, L., Lemaire, V., Leong, E., Lewandowska, D., Li, C., Liang, W., Lin, M., Lisboa, P., Litskevitch, A., Liu, E. M., Liu, T., Livia, M. A., Lo, Y. H., Losim, S., Loubens, M., Lu, J., Lykhenko, O., Lysakova, S., Mahmoud, S., Majid, S. A., Makogon, N., Maldonado, D., Mallari, K., Malta, T. M., Mamun, M., Manoir, D., Marchandon, G., Marciniak, N., Marinovic, S., Marques, B., Mathews, N., Matsuzaki, Y., Matthys, V., May, M., Mccomb, E., Meagher, A., Melamed, A., Menary, W., Mendez, K. N., Mendez, A., Mendy, I. M., Meng, I., Menon, A., Menor, M., Meoded, R., Merino, N., Miah, K., Mignotte, M., Miketic, T., Miranda, W., Mitsios, A., Miura, R., Miyake, K., Moccia, M. D., Mohan, N., Mohsin, M., Moitra, K., Moldes, M., Molina, L., Molinet, J., Molomjamts, O. -E., Moniruzzaman, E., Moon, S., de Oliveira Moraes, I., Moreno, M., Mosella, M. S., Moser, J. W., Mozsary, C., Muehlbauer, A. L., Muner, O., Munia, M., Munim, N., Muscat, M., Mustac, T., Munoz, C., Nadalin, F., Naeem, A., Nagy-Szakal, D., Nakagawa, M., Narce, A., Nasu, M., Navarrete, I. G., Naveed, H., Nazario, B., Nedunuri, N. R., Neff, T., Nesimi, A., Ng, W. C., Ng, S., Nguyen, G., Ngwa, E., Nicolas, A., Nicolas, P., Nika, A., Noorzi, H., Nosrati, A., Nunes, D. N., O'Brien, K., O'Hara, N. B., Oken, G., Olawoyin, R. A., Oliete, J. Q., Olmeda, K., Oluwadare, T., Oluwadare, I. A., Ordioni, N., Orpilla, J., Orrego, J., Ortega, M., Osma, P., Osuolale, I. O., Osuolale, O. M., Ota, M., Oteri, F., Oto, Y., Ounit, R., Ouzounis, C. A., Pakrashi, S., Paras, R., Pardo-Este, C., Park, Y. -J., Pastuszek, P., Patel, S., Pathmanathan, J., Patrignani, A., Perez, M., Peros, A., Persaud, S., Peters, A., Phillips, A., Pineda, L., Pizzi, M. P., Plaku, A., Pompa-Hogan, B., Portilla, M. G., Posada, L., Priestman, M., Prithiviraj, B., Priya, S., Pugdeethosal, P., Pugh, C. E., Pulatov, B., Pupiec, A., Pyrshev, K., Qing, T., Rahiel, S., Rahmatulloev, S., Rajendran, K., Ramcharan, A., Ramirez-Rojas, A., Rana, S., Ratnanandan, P., Read, T. D., Rehrauer, H., Richer, R., Rivera, A., Rivera, M., Robertiello, A., Robinson, C., Rodriguez, P., Rojas, N. A., Roldan, P., Rosario, A., Roth, S., Ruiz, M., Boja Ruiz, S. E., Russell, K., Rybak, M., Sabedot, T. S., Sabina, M., Saito, I., Saito, Y., Malca Salas, G. A., Salazar, C., San, K. M., Sanchez, J., Sanchir, K., Sankar, R., de Souza Santos, P. T., Saravi, Z., Sasaki, K., Sato, Y., Sato, M., Sato, S., Sato, R., Sato, K., Sayara, N., Schaaf, S., Schacher, O., Schinke, A. -L. M., Schlapbach, R., Schori, C., Schriml, J. R., Segato, F., Sepulveda, F., Serpa, M. S., De Sessions, P. F., Severyn, J. C., Shakil, M., Shalaby, S., Shari, A., Shim, H., Shirahata, H., Shiwa, Y., Da Silva, O., Silva, J. M., Simon, G., Singh, S. K., Sluzek, K., Smith, R., So, E., Andreu Somavilla, N., Sonohara, Y., Rufino de Sousa, N., Souza, C., Sperry, J., Sprinsky, N., Stark, S. G., La Storia, A., Suganuma, K., Suliman, H., Sullivan, J., Supie, A. A. M., Suzuki, C., Takagi, S., Takahara, F., Takahashi, N., Takahashi, K., Takeda, T., Takenaka, I. K., Tanaka, S., Tang, A., Man Tang, Y., Tarcitano, E., Tassinari, A., Taye, M., Terrero, A., Thambiraja, E., Thiebaut, A., Thomas, S., Thomas, A. M., Togashi, Y., Togashi, T., Tomaselli, A., Tomita, M., Tomita, I., Toth, O., Toussaint, N. C., Tran, J. M., Truong, C., Tsonev, S. I., Tsuda, K., Tsurumaki, T., Tuz, M., Tymoshenko, Y., Urgiles, C., Usui, M., Vacant, S., Vann, L. E., Velter, F., Ventorino, V., Vera-Wolf, P., Vicedomini, R., Suarez-Villamil, M. A., Vincent, S., Vivancos-Koopman, R., Wan, A., Wang, C., Warashina, T., Watanabe, A., Weekes, S., Werner, J., Westfall, D., Wieler, L. H., Williams, M., Wolf, S. A., Wong, B., Wong, Y. L., Wong, T., Wright, R., Wunderlin, T., Yamanaka, R., Yang, J., Yano, H., Yeh, G. C., Yemets, O., Yeskova, T., Yoshikawa, S., Zafar, L., Zhang, Y., Zhang, S., Zhang, A., Zheng, Y., and Zubenko, S.
Subjects: Urban Population, Drug Resistance, Sequence assembly, Microbiologia, microbiome, global health, computer.software_genre, Medical and Health Sciences, shotgun sequencing, BGC, 0302 clinical medicine, Databases, Genetic, 11. Sustainability, Global health, AMR, 11 Medical and Health Sciences, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, built environment, metagenome, antimicrobial resistance, NGS, de novo assembly, biology, Shotgun sequencing, Microbiota, built Environment, Bacterial, Biodiversity, Biological Sciences, 3. Good health, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infection, Biotechnology, Geospatial analysis, [SDV.BID]Life Sciences [q-bio]/Biodiversity, Article, General Biochemistry, Genetics and Molecular Biology, Databases, 03 medical and health sciences, Antibiotic resistance, Genetic, Drug Resistance, Bacterial, International MetaSUB Consortium, Genetics, Humans, Microbiome, 030304 developmental biology, Human Genome, 06 Biological Sciences, 15. Life on land, biology.organism_classification, Resistènica als medicaments antiinfecciosos, SAÚDE PÚBLICA, Genòmica, 13. Climate action, Evolutionary biology, Metagenomics, Antimicrobial Resistance, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, computer, 030217 neurology & neurosurgery, Archaea, Developmental Biology
Abstract: Summary We present a global atlas of 4,728 metagenomic samples from mass-transit systems in 60 cities over 3 years, representing the first systematic, worldwide catalog of the urban microbial ecosystem. This atlas provides an annotated, geospatial profile of microbial strains, functional characteristics, antimicrobial resistance (AMR) markers, and genetic elements, including 10,928 viruses, 1,302 bacteria, 2 archaea, and 838,532 CRISPR arrays not found in reference databases. We identified 4,246 known species of urban microorganisms and a consistent set of 31 species found in 97% of samples that were distinct from human commensal organisms. Profiles of AMR genes varied widely in type and density across cities. Cities showed distinct microbial taxonomic signatures that were driven by climate and geographic differences. These results constitute a high-resolution global metagenomic atlas that enables discovery of organisms and genes, highlights potential public health and forensic applications, and provides a culture-independent view of AMR burden in cities., Graphical abstract, Highlights • Cities possess a consistent “core” set of non-human microbes • Urban microbiomes echo important features of cities and city-life • Antimicrobial resistance genes are widespread in cities • Cities contain many novel bacterial and viral species, This systematic, worldwide catalog of urban microbiomes represents a metagenomic atlas important for understanding the ecology, virulence, and antibiotic resistance of city-specific microbial communities.
Published: 2021
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5. In Silico Logical Modelling to Uncover Cooperative Interactions in Cancer

Author: Claudine Chaouiya, Gianluca Selvaggio, Florence Janody, Microsoft Research, University of Trento [Trento], Computational and Systems Biology [Trento] (COSBI), Microsoft Research-University of Trento [Trento], Institut de Mathématiques de Marseille (I2M), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU), Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), and Universidade do Porto = University of Porto
Subjects: cooperative oncogenesis, Epithelial-Mesenchymal Transition, Computer science, Carcinogenesis, Logic, QH301-705.5, In silico, Context (language use), [SDV.CAN]Life Sciences [q-bio]/Cancer, Computational biology, Review, Models, Biological, Catalysis, Inorganic Chemistry, 03 medical and health sciences, 0302 clinical medicine, Multidisciplinary approach, Neoplasms, medicine, Tumor Microenvironment, Animals, Humans, Logical data model, Computer Simulation, Physical and Theoretical Chemistry, Biology (General), Molecular Biology, QD1-999, Spectroscopy, 030304 developmental biology, 0303 health sciences, Computational model, Organic Chemistry, epithelium to mesenchymal transition, Cancer, General Medicine, medicine.disease, Computer Science Applications, Chemistry, Gain of function, 030220 oncology & carcinogenesis, logical computational model, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], tumour microenvironment, signalling pathways, Logical modelling
Abstract: The multistep development of cancer involves the cooperation between multiple molecular lesions, as well as complex interactions between cancer cells and the surrounding tumour microenvironment. The search for these synergistic interactions using experimental models made tremendous contributions to our understanding of oncogenesis. Yet, these approaches remain labour intensive and challenging. To tackle such a hurdle, an integrative, multidisciplinary effort is required. In this article, we highlight the use of logical computational models combined to experimental validations as an effective approach to identify cooperative mechanisms and therapeutic strategies in the context of cancer biology. In silico models overcome limitations of reductionist approaches by capturing tumour complexity, and by generating powerful testable hypotheses. We review representative examples of logical models reported in the literature and their validation. We then provide further analyses of our logical model of Epithelium to Mesenchymal Transition (EMT), searching for additional cooperative interactions involving inputs from the tumour microenvironment and gain of function mutations in NOTCH.
Published: 2021

6. COVID-19 infection in adult patients with hematological malignancies:a European Hematology Association Survey (EPICOVIDEHA)

Author: Pagano, Livio, Salmanton-García, Jon, Marchesi, Francesco, Busca, Alessandro, Corradini, Paolo, Hoenigl, Martin, Klimko, Nikolai, Koehler, Philipp, Pagliuca, Antonio, Passamonti, Francesco, Verga, Luisa, Víšek, Benjamin, Ilhan, Osman, Nadali, Gianpaolo, Weinbergerová, Barbora, Córdoba-Mascuñano, Raúl, Marchetti, Monia, Collins, Graham P., Farina, Francesca, Cattaneo, Chiara, Cabirta, Alba, Gomes-Silva, Maria, Itri, Federico, van Doesum, Jaap, Ledoux, Marie-Pierre, Čerňan, Martin, Jakšić, Ozren, Duarte, Rafael F., Magliano, Gabriele, Omrani, Ali S., Fracchiolla, Nicola S., Kulasekararaj, Austin, Valković, Toni, Poulsen, Christian Bjørn, Machado, Marina, Glenthøj, Andreas, Stoma, Igor, Ráčil, Zdeněk, Piukovics, Klára, Navrátil, Milan, Emarah, Ziad, Sili, Uluhan, Maertens, Johan, Blennow, Ola, Bergantim, Rui, García-Vidal, Carolina, Prezioso, Lucia, Guidetti, Anna, del Principe, Maria Ilaria, Popova, Marina, de Jonge, Nick, Ormazabal-Vélez, Irati, Fernández, Noemí, Falces-Romero, Iker, Cuccaro, Annarosa, Meers, Stef, Buquicchio, Caterina, Antić, Darko, Al-Khabori, Murtadha, García-Sanz, Ramón, Biernat, Monika M., Tisi, Maria Chiara, Sal, Ertan, Rahimli, Laman, Čolović, Natasa, Schönlein, Martin, Calbacho, Maria, Tascini, Carlo, Miranda-Castillo, Carolina, Khanna, Nina, Méndez, Gustavo-Adolfo, Petzer, Verena, Novák, Jan, Besson, Caroline, Duléry, Rémy, Lamure, Sylvain, Nucci, Marcio, Zambrotta, Giovanni, Žák, Pavel, Seval, Guldane Cengiz, Bonuomo, Valentina, Mayer, Jiří, López-García, Alberto, Sacchi, Maria Vittoria, Booth, Stephen, Ciceri, Fabio, Oberti, Margherita, Salvini, Marco, Izuzquiza, Macarena, Nunes-Rodrigues, Raquel, Ammatuna, Emanuele, Obr, Aleš, Herbrecht, Raoul, Núñez-Martín-Buitrago, Lucía, Mancini, Valentina, Shwaylia, Hawraa, Sciumè, Mariarita, Essame, Jenna, Nygaard, Marietta, Batinić, Josip, Gonzaga, Yung, Regalado-Artamendi, Isabel, Karlsson, Linda Katharina, Shapetska, Maryia, Hanakova, Michaela, El-Ashwah, Shaimaa, Borbényi, Zita, Çolak, Gökçe Melis, Nordlander, Anna, Dragonetti, Giulia, Maraglino, Alessio Maria Edoardo, Rinaldi, Amelia, De Ramón-Sánchez, Cristina, Cornely, Oliver A., Finizio, Olimpia, Fazzi, Rita, Sapienza, Giuseppe, Chauchet, Adrien, Van Praet, Jens, Prattes, Juergen, Dargenio, Michelina, Rossi, Cédric, Shirinova, Ayten, Malak, Sandra, Tafuri, Agostino, Ommen, Hans-Beier, Bologna, Serge, Khedr, Reham Abdelaziz, Choquet, Sylvain, Joly, Bertrand, Ceesay, M. Mansour, Philippe, Laure, Kho, Chi Shan, Desole, Maximilian, Tsirigotis, Panagiotis, Otašević, Vladimir, Borducchi, Davimar M. M., Antoniadou, Anastasia, Gaziev, Javid, Almaslamani, Muna A., García-Poutón, Nicole, Paterno, Giovangiacinto, Torres-López, Andrea, Tarantini, Giuseppe, Mellinghoff, Sibylle, Gräfe, Stefanie, Börschel, Niklas, Passweg, Jakob, Merelli, Maria, Barać, Aleksandra, Wolf, Dominik, Shaikh, Mohammad Usman, Thiéblemont, Catherine, Bernard, Sophie, Funke, Vaneuza Araújo Moreira, Daguindau, Etienne, Khostelidi, Sofya, Nucci, Fabio Moore, Martín-González, Juan-Alberto, Landau, Marianne, Soussain, Carole, Laureana, Cécile, Lacombe, Karine, Kohn, Milena, Aliyeva, Gunay, Piedimonte, Monica, Fouquet, Guillemette, Rêgo, Mayara, Hoell-Neugebauer, Baerbel, Cartron, Guillaume, Pinto, Fernando, Alburquerque, Ana Munhoz, Passos, Juliana, Yilmaz, Asu Fergun, Redondo-Izal, Ana-Margarita, Altuntaş, Fevzi, Heath, Christopher, Kolditz, Martin, Schalk, Enrico, Guolo, Fabio, Karthaus, Meinolf, Della Pepa, Roberta, Vinh, Donald, Noël, Nicolas, Deau Fischer, Bénédicte, Drenou, Bernard, Mitra, Maria Enza, Meletiadis, Joseph, Bilgin, Yavuz M., Jindra, Pavel, Espigado, Ildefonso, Drgoňa, Ľuboš, Serris, Alexandra, Di Blasi, Roberta, Ali, Natasha, EPICOVIDEHA working group, [missing], Pagano, Livio, Salmanton-Garcia, Jon, Marchesi, Francesco, Busca, Alessandro, Corradini, Paolo, Hoenigl, Martin, Klimko, Nikolai, Koehler, Philipp, Pagliuca, Antonio, Passamonti, Francesco, Verga, Luisa, Visek, Benjamin, Ilhan, Osman, Nadali, Gianpaolo, Weinbergerova, Barbora, Cordoba-Mascunano, Raul, Marchetti, Monia, Collins, Graham P., Farina, Francesca, Cattaneo, Chiara, Cabirta, Alba, Gomes-Silva, Maria, Itri, Federico, van Doesum, Jaap, Ledoux, Marie-Pierre, Cernan, Martin, Jaksic, Ozren, Duarte, Rafael F., Magliano, Gabriele, Omrani, Ali S., Fracchiolla, Nicola S., Kulasekararaj, Austin, Valkovic, Toni, Poulsen, Christian Bjorn, Machado, Marina, Glenthoj, Andreas, Stoma, Igor, Racil, Zdenek, Piukovics, Klara, Navratil, Milan, Emarah, Ziad, Sili, Uluhan, Maertens, Johan, Blennow, Ola, Bergantim, Rui, Garcia-Vidal, Carolina, Prezioso, Lucia, Guidetti, Anna, del Principe, Maria Ilaria, Popova, Marina, de Jonge, Nick, Ormazabal-Velez, Irati, Fernandez, Noemi, Falces-Romero, Iker, Cuccaro, Annarosa, Meers, Stef, Buquicchio, Caterina, Antic, Darko, Al-Khabori, Murtadha, Garcia-Sanz, Ramon, Biernat, Monika M., Tisi, Maria Chiara, Sal, Ertan, Rahimli, Laman, Colovic, Natasa, Schonlein, Martin, Calbacho, Maria, Tascini, Carlo, Miranda-Castillo, Carolina, Khanna, Nina, Mendez, Gustavo-Adolfo, Petzer, Verena, Novak, Jan, Besson, Caroline, Dulery, Remy, Lamure, Sylvain, Nucci, Marcio, Zambrotta, Giovanni, Zak, Pavel, Seval, Guldane Cengiz, Bonuomo, Valentina, Mayer, Jiri, Lopez-Garcia, Alberto, Sacchi, Maria Vittoria, Booth, Stephen, Ciceri, Fabio, Oberti, Margherita, Salvini, Marco, Izuzquiza, Macarena, Nunes-Rodrigues, Raquel, Ammatuna, Emanuele, Obr, Ales, Herbrecht, Raoul, Nunez-Martin-Buitrago, Lucia, Mancini, Valentina, Shwaylia, Hawraa, Sciume, Mariarita, Essame, Jenna, Nygaard, Marietta, Batinic, Josip, Gonzaga, Yung, Regalado-Artamendi, Isabel, Karlsson, Linda Katharina, Shapetska, Maryia, Hanakova, Michaela, El-Ashwah, Shaimaa, Borbenyi, Zita, Colak, Gokce Melis, Nordlander, Anna, Dragonetti, Giulia, Maraglino, Alessio Maria Edoardo, Rinaldi, Amelia, De Ramon-Sanchez, Cristina, Cornely, Oliver A., Pagano, L., Salmanton-Garcia, J., Marchesi, F., Busca, A., Corradini, P., Hoenigl, M., Klimko, N., Koehler, P., Pagliuca, A., Passamonti, F., Verga, L., Visek, B., Ilhan, O., Nadali, G., Weinbergerova, B., Cordoba-Mascunano, R., Marchetti, M., Collins, G. P., Farina, F., Cattaneo, C., Cabirta, A., Gomes-Silva, M., Itri, F., van Doesum, J., Ledoux, M. -P., Cernan, M., Jaksic, O., Duarte, R. F., Magliano, G., Omrani, A. S., Fracchiolla, N. S., Kulasekararaj, A., Valkovic, T., Poulsen, C. B., Machado, M., Glenthoj, A., Stoma, I., Racil, Z., Piukovics, K., Navratil, M., Emarah, Z., Sili, U., Maertens, J., Blennow, O., Bergantim, R., Garcia-Vidal, C., Prezioso, L., Guidetti, A., del Principe, M. I., Popova, M., de Jonge, N., Ormazabal-Velez, I., Fernandez, N., Falces-Romero, I., Cuccaro, A., Meers, S., Buquicchio, C., Antic, D., Al-Khabori, M., Garcia-Sanz, R., Biernat, M. M., Tisi, M. C., Sal, E., Rahimli, L., Colovic, N., Schonlein, M., Calbacho, M., Tascini, C., Miranda-Castillo, C., Khanna, N., Mendez, G. -A., Petzer, V., Novak, J., Besson, C., Dulery, R., Lamure, S., Nucci, M., Zambrotta, G., Zak, P., Seval, G. C., Bonuomo, V., Mayer, J., Lopez-Garcia, A., Sacchi, M. V., Booth, S., Ciceri, F., Oberti, M., Salvini, M., Izuzquiza, M., Nunes-Rodrigues, R., Ammatuna, E., Obr, A., Herbrecht, R., Nunez-Martin-Buitrago, L., Mancini, V., Shwaylia, H., Sciume, M., Essame, J., Nygaard, M., Batinic, J., Gonzaga, Y., Regalado-Artamendi, I., Karlsson, L. K., Shapetska, M., Hanakova, M., El-Ashwah, S., Borbenyi, Z., Colak, G. M., Nordlander, A., Dragonetti, G., Maraglino, A. M. E., Rinaldi, A., De Ramon-Sanchez, C., Cornely, O. A., Finizio, O., Fazzi, R., Sapienza, G., Chauchet, A., Van Praet, J., Prattes, J., Dargenio, M., Rossi, C., Shirinova, A., Malak, S., Tafuri, A., Ommen, H. -B., Bologna, S., Khedr, R. A., Choquet, S., Joly, B., Ceesay, M. M., Philippe, L., Kho, C. S., Desole, M., Tsirigotis, P., Otasevic, V., Borducchi, D. M. M., Antoniadou, A., Gaziev, J., Almaslamani, M. A., Garcia-Pouton, N., Paterno, G., Torres-Lopez, A., Tarantini, G., Mellinghoff, S., Grafe, S., Borschel, N., Passweg, J., Merelli, M., Barac, A., Wolf, D., Shaikh, M. U., Thieblemont, C., Bernard, S., Funke, V. A. M., Daguindau, E., Khostelidi, S., Nucci, F. M., Martin-Gonzalez, J. -A., Landau, M., Soussain, C., Laureana, C., Lacombe, K., Kohn, M., Aliyeva, G., Piedimonte, M., Fouquet, G., Rego, M., Hoell-Neugebauer, B., Cartron, G., Pinto, F., Alburquerque, A. M., Passos, J., Yilmaz, A. F., Redondo-Izal, A. -M., Altuntas, F., Heath, C., Kolditz, M., Schalk, E., Guolo, F., Karthaus, M., Della Pepa, R., Vinh, D., Noel, N., Deau Fischer, B., Drenou, B., Mitra, M. E., Meletiadis, J., Bilgin, Y. M., Jindra, P., Espigado, I., Drgona, L., Serris, A., Di Blasi, R., Ali, N., Stem Cell Aging Leukemia and Lymphoma (SALL), Salvy-Córdoba, Nathalie, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), University Hospital of Cologne [Cologne], Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, IFO - Istituto Nazionale Tumori Regina Elena [Roma] (IRE), Città della Salute e della Scienza University-Hospital, IRCCS Istituto Nazionale dei Tumori [Milano], University of California [San Diego] (UC San Diego), University of California (UC), Medical University of Graz, Odessa National I.I.Mechnikov University, Faculty of Medicine [Cologne], University Hospital of Cologne [Cologne]-University of Cologne, King's College Hospital (KCH), Universitá degli Studi dell’Insubria = University of Insubria [Varese] (Uninsubria), Dipartimento di Medicina e Chirurgia = School of Medicine and Surgery [Monza], Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Faculty of Medicine in Hradec Kralove [Republique Tchèque], Charles University [Prague] (CU), Ankara University School of Medicine [Turkey], Azienda Ospedaliera Universitaria Integrata of Verona, Masaryk University [Brno] (MUNI), Fundación Jiménez Díaz, Fundacion Jimenez Diaz [Madrid] (FJD), Ospedale SS Antonio e Biagio e Cesare Arrigo, Churchill Hospital Oxford Centre for Haematology, IRCCS San Raffaele Scientific Institute [Milan, Italie], ASST Spedali Civili of Brescia, Vall d'Hebron Institute of Oncology [Barcelone] (VHIO), Vall d'Hebron University Hospital [Barcelona], Universitat Autònoma de Barcelona (UAB), Instituto Português de Oncologia de Lisboa Francisco Gentil, Ospedale San Luigi Gonzaga, University Medical Center Groningen [Groningen] (UMCG), Institut de Cancérologie de Strasbourg Europe (ICANS), Palacky University Olomouc, Zagreb School of Medicine [Zagreb, Croatia] (Dubrava University Hospital), University of Zagreb, Hospital Universitario Puerta de Hierro-Majadahonda [Madrid, Spain], ASST Great Metropolitan Niguarda / ASST Grande Ospedale Metropolitano Niguarda [Milan, Italia], Hamad Medical Corporation [Doha, Qatar], Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, University of Rijeka, Croatian Cooperative Group for Hematological Diseases (CROHEM), Zealand University Hospital [Roskilde, Denmark], Hospital General Universitario 'Gregorio Marañón' [Madrid], Department of Clinical Microbiology [Rigshospitalet], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Homieĺ State Medical University (GSMU), Institute of Hematology and Blood Transfusion [Prague, Czech Republic], University of Szeged [Szeged], University Hospital Ostrava, Mansoura University [Egypt], Marmara University [Kadıköy - İstanbul], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Karolinska University Hospital [Stockholm], Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto = University of Porto, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Hospital de São João [Porto], Faculdade de Medicina da Universidade do Porto (FMUP), Clinic Barcelona Hospital Universitari, Department of Public Health and Cell Biology, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy, Pavlov First Saint Petersburg State Medical University [St. Petersburg], Vrije Universiteit Medical Centre (VUMC), Vrije Universiteit Amsterdam [Amsterdam] (VU), Complejo Hospitalario de Navarra, Hospital Universitario Marqués de Valdecilla [Santander], La Paz University Hospital, Azienda Usl Toscana centro [Firenze], AZ Klina, Clinical Center of Serbia (KCS), University of Belgrade [Belgrade], Sultan Qaboos University Hospital, Partenaires INRAE, Hospital Universitario de Salamanca, Servicio de Haematologia, Centro de Investigación del Cáncer-IBMCC (USAL-CSIC), University of Wrocław [Poland] (UWr), San Bortolo Hospital, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Hospital Universitario 12 de Octubre [Madrid], Azienda Sanitaria Universitaria Friuli Centrale (ASU FC), Universidad Rey Juan Carlos [Madrid] (URJC), University of Basel (Unibas), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), University Hospital Kralovské Vinohrady, Centre Hospitalier de Versailles André Mignot (CHV), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Département Hématologie biologique [CHRU Montpellier], Pôle Biologie-Pathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Universidade Federal do Estado do Rio de Janeiro (UNIRIO), San Gerardo Hospital of Monza, Oxford NIHR Biomedical Research Centre, IRCCS Ospedale San Raffaele [Milan, Italy], Assi Sette Llaghi Varese, Instituto Português de Oncologia do Porto / Portuguese Oncology Institute of Porto (IPO Porto), University Hospital Olomouc [Czech Republic], ASST Grande Ospedale Metropolitano Niguarda, University Hospital Centre Zagreb, Instituto Nacional do Câncer, Copenhagen University Hospital, Republican Scientific and Practical Center (RSPC) for organ and Tissue Transplantation, Minsk, Republican Scientific and Practical Center (RSPC) for Organ and Transplantation, German Centre for Infection Research (DZIF), Gilead Sciences, Pagano, Livio [0000-0001-8287-928X], Salmanton-García, Jon [0000-0002-6766-8297], Marchesi, Francesco [0000-0001-6353-2272], Busca, Alessandro [0000-0001-5361-5613], Corradini, Paolo [0000-0002-9186-1353], Hoenigl, Martin [0000-0002-1653-2824], Klimko, Nikolay [0000-0001-6095-7531], Koehler, Philipp [0000-0002-7386-7495], Pagliuca, Antonio [0000-0003-2519-0333], Passamonti, Francesco [0000-0001-8068-5289], Verga, Luisa [0000-0003-1142-8435], Víšek, Benjamin [0000-0001-8268-452X], Ilhan, Osman [0000-0003-1665-372X], Weinbergerová, Barbora [0000-0001-6460-2471], Córdoba, Raúl [0000-0002-7654-8836], Marchetti, Monia [0000-0001-7615-0572], Farina, Francesca [0000-0002-5124-6970], Cattaneo, Chiara [0000-0003-0031-3237], Cabirta, Alba [0000-0001-7198-8894], Gomes-Silva, Maria [0000-0002-6993-2450], Itri, Federico [0000-0002-3532-5281], Doesum, Jaap van [0000-0003-0214-3219], Ledoux, Marie-Pierre [0000-0002-3261-3616], Čerňan, Martin [0000-0003-2345-1229], Jakšić, Ozren [0000-0003-4026-285X], Magliano, Gabriel [0000-0002-9129-1530], Omrani, Ali S. [0000-0001-5309-6358], Fracchiolla, Nicola S. [0000-0002-8982-8079], Kulasekararaj, Austin G. [0000-0003-3180-3570], Valković, Toni [0000-0001-6083-8815], Poulsen, Christian Bjørn [0000-0001-9785-1378], Machado, Marina [0000-0002-8370-2248], Glenthøj, Andrea [0000-0003-2082-0738], Stoma, Igor [0000-0003-0483-7329], Ráčil, Zdeněk [0000-0003-3511-4596], Piukovics, Klára [0000-0003-4480-3131], Emarah, Ziad [0000-0003-0622-2598], Sili, Uluhan [0000-0002-9939-9298], Maertens, Johan [0000-0003-4257-5980], Bergantim, Rui [0000-0002-7811-9509], García-Vidal, Carolina [0000-0002-8915-0683], Prezioso, Lucia [0000-0003-1660-4960], Principe, Maria Ilaria del [0000-0002-3958-0669], Popova, Marina [0000-0001-8536-5495], Jonge, Nick de [0000-0002-9901-0887], Ormazabal-Vélez, Irati [0000-0003-1141-5546], Falces-Romero, Iker [0000-0001-5888-7706], Cuccaro, Annarosa [0000-0002-0237-1839], Meers, Stef [0000-0003-1754-2175], Buquicchio, Caterina [0000-0002-3683-5953], Antić, Darko [0000-0002-2608-1342], Al-Khabori, Murtadha [0000-0002-2937-8838], García-Sanz, Ramón [0000-0003-4120-2787], Biernat, Monika [0000-0003-3161-3398], Tisi, Maria Chiara [0000-0001-8231-6700], Sal, Ertan [0000-0003-2761-2675], Rahimli, Laman [0000-0003-2266-445X], Schönlein, Martin [0000-0002-1010-0975], Calbacho, María [0000-0001-8106-4863], Tascini, Carlo [0000-0001-9625-6024], Miranda-Castillo, Carolina [0000-0001-8763-9576], Khanna, Nina [0000-0002-2642-419X], Méndez, Gustavo-Adolfo [0000-0003-0514-7004], Petzer, Verena [0000-0002-9205-1440], Besson, Caroline [0000-0003-4364-7173], Duléry, Rémy [0000-0002-5024-1713], Lamure, Sylvain [0000-0001-5980-305X], Nucci, Marcio [0000-0003-4867-0014], Zambrotta, Giovanni [0000-0002-8612-2994], Žák, Pavel [0000-0003-4465-5343], Cengiz Seval, Guldane [0000-0001-9433-2054], Bonuomo, Valentina [0000-0001-6491-8337], Mayer, Jiří [0000-0003-0567-9887], López-García, Alberto [0000-0002-5354-5261], Sacchi, Maria Vittoria [0000-0001-8133-3357], Booth, Stephen [0000-0003-2687-0234], Ciceri, Fabio [0000-0003-0873-0123], Nunes-Rodrigues, Raquel [0000-0002-8347-4281], Ammatuna, Emanuele [0000-0001-8247-4901], Obr, Aleš [0000-0002-6758-3074], Herbrecht, Raoul [0000-0002-9381-4876], Shwaylia, Hawraa [0000-0002-4098-6092], Sciumè, Mariarita [0000-0001-7958-4966], Essame, Jenna [0000-0003-0926-5577], Batinić, Josip [0000-0001-5595-9911], Gonzaga, Yung [0000-0003-1416-2118], Regalado-Artamendi, Isabel [0000-0002-9673-9015], Karlsson, Linda Katharina [0000-0003-3317-7550], Shapetska, Maryia [0000-0002-1223-9161], El-Ashwah, Shaimaa [0000-0003-2210-1534], Çolak, Gökçe Melis [0000-0002-7662-7454], Dragonetti, Giulia [0000-0003-1775-6333], Rinaldi, Amelia [0000-0002-8211-5076], Ramón, Cristina de [0000-0002-8167-6410], Cornely, Oliver A. [0000-0001-9599-3137], Institut Català de la Salut, [Pagano L] Hematology, Fondazione Policlinico Universitario Agostino Gemelli - IRCCS – Università Cattolica del Sacro Cuore, Rome, Italy. Università Cattolica del Sacro Cuore, Rome, Italy. [Salmanton-García J] Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Excellence Center for Medical Mycology (ECMM), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany. Cologne Excellence Cluster On Cellular Stress Responses in Aging Associated Diseases (CECAD), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany. [Marchesi F] Hematology and Stem Cell Transplant Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy. [Busca A] Stem Cell Transplant Center, AOU Citta’ Della Salute E Della Scienza, Turin, Italy. [Corradini P] University of Milan and Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy. [Hoenigl M] Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, San Diego, CA, USA. Clinical and Translational Fungal Working Group, University of California San Diego, La Jolla, CA, USA. Section of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Medical University of Graz, Graz, Austria. [Cabirta A, Izuzquiza M] Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Experimental Hematology, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain, Vall d'Hebron Barcelona Hospital Campus, Hematology, Salmanton-García, Jon, Klimko, Nikolay, Víšek, Benjamin, Weinbergerová, Barbora, Córdoba, Raúl, Doesum, Jaap van, Čerňan, Martin, Jakšić, Ozren, Magliano, Gabriel, Kulasekararaj, Austin G., Valković, Toni, Poulsen, Christian Bjørn, Glenthøj, Andrea, Ráčil, Zdeněk, Piukovics, Klára, García-Vidal, Carolina, Principe, Maria Ilaria del, Jonge, Nick de, Ormazabal-Vélez, Irati, Antić, Darko, García-Sanz, Ramón, Biernat, Monika, Schönlein, Martin, Calbacho, María, Méndez, Gustavo-Adolfo, Duléry, Rémy, Žák, Pavel, Cengiz Seval, Guldane, Mayer, Jiří, López-García, Alberto, Obr, Aleš, Sciumè, Mariarita, Batinić, Josip, Çolak, Gökçe Melis, Ramón, Cristina de, and Universidad de Sevilla. Departamento de Medicina
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Male, Cancer Research, MESH: Registries, Epidemiology, MESH: Hospitalization, Hematological malignancies, Otros calificadores::Otros calificadores::/complicaciones [Otros calificadores], MESH: Aged, 80 and over, MESH: Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Risk Factors, Malalties - Factors de risc, Risk of mortality, Medicine and Health Sciences, virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], 80 and over, Medicine, MESH: COVID-19, Registries, Sang - Malalties - Complicacions, RC254-282, Cause of death, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Interna medicina, MESH: Aged, Aged, 80 and over, Hematology, MESH: Middle Aged, Mortality rate, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Myeloid leukemia, Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Middle Aged, CANCER, Europe, Hospitalization, Intensive Care Units, Oncology, MESH: Young Adult, Hematologic Neoplasms, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Infektologija, Life Sciences & Biomedicine, Adult, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, COVID-19, EHA, Pandemic, Aged, Humans, SARS-CoV-2, Young Adult, técnicas de investigación::métodos epidemiológicos::estadística como asunto::probabilidad::riesgo::factores de riesgo [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], [SDV.CAN] Life Sciences [q-bio]/Cancer, Intensive care, Internal medicine, Diseases of the blood and blood-forming organs, MESH: SARS-CoV-2, neoplasias::neoplasias por localización::neoplasias hematológicas [ENFERMEDADES], Molecular Biology, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Internal Medicine, pandemic, hematological malignancies, epidemiology, MESH: Humans, Science & Technology, business.industry, Myelodysplastic syndromes, Research, MESH: Adult, Neoplasms::Neoplasms by Site::Hematologic Neoplasms [DISEASES], medicine.disease, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Infectology, Settore MED/15, MESH: Male, Settore MED/15 - MALATTIE DEL SANGUE, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, COVID-19 (Malaltia) - Diagnòstic, MESH: Intensive Care Units, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], MESH: Europe, RC633-647.5, business, MESH: Female, Other subheadings::Other subheadings::/complications [Other subheadings], MESH: Hematologic Neoplasms
Abstract: Background Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. Results The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value, EPICOVIDEHA has received funds from Optics COMMITTM (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223).
Published: 2021
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7. Orally administrated chitosan microspheres bind Helicobacter pylori and decrease gastric infection in mice

Author: Henriques, Patrícia, Costa, Lia, Seabra, Catarina, Antunes, Bernardo, Silva-Carvalho, Ricardo, Junqueira-Neto, Susana, Maia, André, Oliveira, Pedro, Magalhães, Ana, Reis, Celso, Gärtner, Fátima, Touati, Eliette, Gomes, Joana, Costa, Paulo, Martins, M Cristina L, Gonçalves, Inês, Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto, Instituto de Engenharia Biomédica [Porto, Portugal] (INEB), Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Instituto de Biologia Molecular e Celular - institute for molecular and cell biology [Porto, Portugal] (IBMC), Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Faculdade de Medicina da Universidade do Porto (FMUP), Pathogenèse de Helicobacter / Helicobacter Pathogenesis, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Pharmaceutical Technology Laboratory [Porto], Faculdade de Farmácia da Universidade do Porto (FFUP), Universidade do Porto-Universidade do Porto, This work was financed by PTDC/CTM-BIO/4043/2014 and by Portuguese funds from FCT UID/BIM/04293/2019, UID/Multi/04378/2019, EXPL/CTM-BIO/0762/2013 and by L'OrealPortugal/FCT/UNESCO. Authors wish to thank FCT for Inês C. Gonçalves research position (IF/01479/2015), Patricia C. Henriques PhD grant (SFRH/BD/120154/2016) and Catarina L. Seabra PhD grant (SFRH/BD/89001/2012)., The authors acknowledge the support of i3S Scientific Platforms, namely the Bioimaging Center for Biomaterials and Regenerative Therapies (b.IMAGE), and the BioSciences Screening for the imaging data acquisition using equipment maintained by the platforms, both members of the PPBI (PPBI-POCI-01-0145-feder-022122), and CCGEN and Paula Magalhães, for the help during the PCR analysis., Universidade do Porto = University of Porto, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Universidade do Porto = University of Porto-Universidade do Porto = University of Porto
Subjects: Biomaterials, Bacteria adhesion, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, In vivo, Mucoadhesion, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Microparticles, [SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials
Abstract: International audience; Persistent Helicobacter pylori (H. pylori) infection is related to 90% of gastric cancers. With bacterial resistance rising and treatment inefficiency affecting 15% of the patients, alternative treatments urge. Chitosan microspheres (ChMics) have been proposed as an H. pylori-binding system. This work evaluates ChMics biocompatibility, mucopenetration and capacity to treat H. pylori infection in mice after oral administration. ChMics of different size (XL, ∼120 µm and XS, ∼40 µm) and degree of acetylation (6% and 16%) were developed and revealed to be able to adhere both human and mouse-adapted H. pylori strains without cytotoxicity towards human gastric cells. Ex vivo studies showed that smaller (XS) microspheres penetrate further within the gastric foveolae, suggesting their ability to reach deeply adherent bacteria. In vivo assays showed 88% reduction of infection when H. pylori-infected mice (C57BL/6) were treated with more mucoadhesive XL6 and XS6 ChMics. Overall, ChMics clearly demonstrate ability to reduce H. pylori gastric infection in mice, with chitosan degree of acetylation being a dominant factor over microspheres' size on H. pylori removal efficiency. These results evidence the strong potential of this strategy as an antibiotic-free approach to fight H. pylori infection, where microspheres are orally administered, bind H. pylori in the stomach, and remove them through the gastrointestinal tract. STATEMENT OF SIGNIFICANCE: Approximately 90% of gastric cancers are caused by the carcinogenic agent Helicobacter pylori, which infects >50% of the world population. Bacterial resistance, reduced antibiotic bioavailability, and the intricate distribution of bacteria in mucus and within gastric foveolae hamper the success of most strategies to fight H. pylori. We demonstrate that an antibiotic-free therapy based on bare chitosan microspheres that bind and remove H. pylori from stomach can achieve 88% reduction of infection from H. pylori-infected mice. Changing size and mucoadhesive properties, microspheres can reach different areas of gastric mucosa: smaller and less mucoadhesive can penetrate deeper into the foveolae. This promising, simple and inexpensive strategy paves the way for a faster bench-to-bedside transition, therefore holding great potential for clinical application.
Published: 2020
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8. Loss of functional E-cadherin renders cells more resistant to the apoptotic agent taxol in vitro

Author: Suriano, Gianpaolo [Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), 4200 Porto (Portugal) and Genetic Pathology Evaluation Centre of the Department of Pathology and Prostate Centre at Vancouver General Hospital, Department of Pathology, British Columbia Cancer Agency and University of British Columbia, Vancouver (Canada)]
Published: 2005
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9. Population genetics-informed meta-analysis in seven genes associated with risk to dengue fever disease

Author: Anavaj Sakuntabhai, Luísa Pereira, Verónica Fernandes, María G. Guzmán, Beatriz Sierra, Isabelle Casademont, Nourdin Harich, Bruno Cavadas, Marisa Oliveira, Lotfi Cherni, Nicole Pedro, Farida Alshamali, Fanny Koeth, Diana P. Saraiva, Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Génétique fonctionnelle des Maladies infectieuses - Functional Genetics of Infectious Diseases, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Dubai Police General Headquarters, Université Chouaib Doukkali (UCD), Université de Tunis El Manar (UTM), Université de Monastir - University of Monastir (UM), Pedro Kouri Institute of Tropical Medicine, Génomique évolutive, modélisation et santé (CNRS-UMR2000), Faculdade de Medicina da Universidade do Porto (FMUP), The research leading to these results has received funding from the European Commission Seventh Framework Programme [FP7/2007-2013] for the DENFREE project under Grant Agreement no. 282378. MO has a PhD grant from FCT (The Portuguese Foundation for Science and Technology - SFRH/BD/95626/2013). IPATIMUP integrates the i3S Research Unit, which is partially supported by FCT, FEDER and COMPETE (PEst-C/SAU/LA0003/2013)., European Project: 282378,EC:FP7:HEALTH,FP7-HEALTH-2011-single-stage,DENFREE(2012), Universidade do Porto = University of Porto, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Génomique évolutive, modélisation et santé (GEMS)
Subjects: Genetic Markers, 0301 basic medicine, Microbiology (medical), Candidate gene, Genotype, Population, Population genetics, Disease, Biology, Polymorphism, Single Nucleotide, Microbiology, Worldwide diversity, Dengue fever, Dengue, 03 medical and health sciences, Genetic drift, Dengue disease, Genetics, medicine, Humans, Genetic Predisposition to Disease, education, Global risk, Molecular Biology, Ecology, Evolution, Behavior and Systematics, Genetic association, education.field_of_study, Odds ratio, East Asian and Latin American cohorts, medicine.disease, 3. Good health, Meta-analysis, 030104 developmental biology, Infectious Diseases, Gene Expression Regulation, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Demography
Abstract: International audience; Population genetics theory predicted that rare frequent markers would be the main contributors for heritability of complex diseases, but meta-analyses of genome-wide association studies are revealing otherwise common markers, present in all population groups, as the identified candidate genes. In this work, we applied a population-genetics informed meta-analysis to 10 markers located in seven genes said to be associated with dengue fever disease. Seven markers (in PLCE1, CD32, CD209, OAS1 and OAS3 genes) have high-frequency and the other three (in MICB and TNFA genes) have intermediate frequency. Most of these markers have high discriminatory power between population groups, but their frequencies follow the rules of genetic drift, and seem to have not been under strong selective pressure. There was a good agreement in directional consistency across trans-ethnic association signals, in East Asian and Latin American cohorts, with heterogeneity generated by randomness between studies and especially by low sample sizes. This led to confirm the following significant associations: with DF, odds ratio of 0.67 for TNFA-rs1800629-A; with DHF, 0.82 for CD32-rs1801274-G; with DSS, 0.55 for OAS3-rs2285933-G, 0.80 for PLCE1-rs2274223-G and 1.32 for MICB-rs3132468-C. The overall genetic risks confirmed sub-Saharan African populations and descendants as the best protected against the severer forms of the disease, while Southeast and Northeast Asians are the least protected ones. European and close neighbours are the best protected against dengue fever, while, again, Southeast and Northeast Asians are the least protected ones. These risk scores provide important predictive information for the largely na\"ive European and North American regions, as well as for Africa where misdiagnosis with other hemorrhagic diseases is of concern.
Published: 2018
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10. Latin Americans show wide-spread Converso ancestry and imprint of local Native ancestry on physical appearance

Author: Juan C. Chacon-Duque, Hugo Villamil-Ramírez, Giovanni Poletti, Samuel Canizales-Quinteros, Mirsha Quinto-Sánchez, Maria Cátira Bortolini, Maria-Laura Parolin, Macarena Fuentes-Guajardo, Francisco Rothhammer, Rolando González-José, Valeria Villegas, Francisco Mauro Salzano, Javier Mendoza-Revilla, Verónica Gomes, Caio Cesar Silva de Cerqueira, Cheryl A. Winkler, José R. Sandoval, Carla Gallo, Elena Llop, Rosenda I. Peñaloza-Espinosa, Vanessa Granja, Daniel Corach, Lavinia Schuler-Faccini, Yali Xue, Garrett Hellenthal, Mercedes Villena, Virginia Ramallo, Victor Acuña-Alonzo, Gabriel Bedoya, Paola Everardo Martínez, Karla Sandoval, Andres Ruiz-Linares, David J. Balding, Claudio M. Bravi, Pedro Moral, Jean-Michel Dugoujon, Tábita Hünemeier, António Amorim, Malena Hurtado, Kaustubh Adhikari, René Vasquez, Julio Molina, Leonor Gusmão, Ramiro Barrantes, Carlos Resende, Jorge Gómez-Valdés, Alberto Salazar-Granara, Héctor Rangel-Villalobos, William Klitz, Rodrigo Barquera, Molecular Genetics Laboratory, Escuela Nacional de Antropologia y Historia, Departamento de Genética, Universidade Federal do Rio Grande do Sul [Porto Alegre] (UFRGS)-Instituto de Biociencias, Instituto Boliviano de Biologıa de la Altura, Universidad Autonoma Tomas Frias, Facultad de Medicina & Instituto de Alta Investigacion, Universidad de Tarapaca-Universidade de Chile, School of Human Evolution and Social Change, Arizona State University [Tempe] (ASU), Instituto Multidisciplinario de Biología Celular [La Plata] (IMBICE), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET)-Universidad Nacional de la Plata [Argentine] (UNLP)-Comisión de Investigaciones Científicas [Buenos Aires] (CIC), Centro de Investigaciones Biomédicas de Guatemala, Servicio de Huellas Digitales Genéticas [Buenos Aires], Facultad de Farmacia y Bioquímica [Buenos Aires] (FFYB), Universidad de Buenos Aires [Buenos Aires] (UBA)-Universidad de Buenos Aires [Buenos Aires] (UBA), Escuela de Biologia, Universidad Nacional de Costa Rica, Population Genetics, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Universidade de Lisboa (ULISBOA), Human Evolution, The Wellcome Trust Sanger Institute [Cambridge], Anthropologie Moléculaire et Imagerie de Synthèse (AMIS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), University of Barcelona, Unit of Molecular Biology and Genomic Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán - National Institute of Medical Science and Nutrition Salvador Zubiran [Mexico], Laboratorio de Genética Molecular, Universidad de Antioquia = University of Antioquia [Medellín, Colombia], University College of London [London] (UCL), Dept of Genetics, Evolution and Environment [London] (UCL-GEE), Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Instituto de Investigação e Inovação em Saúde, Universidade de Lisboa = University of Lisbon (ULISBOA), and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)
Subjects: haplotype, Latin Americans, Biología, [SHS.ANTHRO-BIO]Humanities and Social Sciences/Biological anthropology, purl.org/pe-repo/ocde/ford#1.03.00 [https], Human physical appearance, Colonialism, migration, CONVERSO JEWS, purl.org/becyt/ford/1 [https], Genética y Herencia, 0302 clinical medicine, genetics, Nose / anatomy & histology, East mediterranean, lcsh:Science, 0303 health sciences, Genealogy, Geography, Indians, South American / genetics, American Indian, Genetic structure, CIENCIAS NATURALES Y EXACTAS, Latin americans, Science, purl.org/pe-repo/ocde/ford#1.06.03 [https], Human Migration, Nose, Article, Ciencias Biológicas, 03 medical and health sciences, Indians, North American / genetics, parasitic diseases, Humans, human, purl.org/becyt/ford/1.6 [https], Mexico, Historical record, 030304 developmental biology, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], Indians, South American, ANCESTRY INFORMATIVE, Environmental adaptation, South America, Converso jews, LATIN AMERICANS, Haplotypes, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Ancestry informative, purl.org/pe-repo/ocde/ford#1.04.00 [https], Indians, North American, lcsh:Q, 030217 neurology & neurosurgery, anatomy and histology
Abstract: Historical records and genetic analyses indicate that Latin Americans trace their ancestry mainly to the intermixing (admixture) of Native Americans, Europeans and Sub-Saharan Africans. Using novel haplotype-based methods, here we infer sub-continental ancestry in over 6,500 Latin Americans and evaluate the impact of regional ancestry variation on physical appearance. We find that Native American ancestry components in Latin Americans correspond geographically to the present-day genetic structure of Native groups, and that sources of non-Native ancestry, and admixture timings, match documented migratory flows. We also detect South/East Mediterranean ancestry across Latin America, probably stemming mostly from the clandestine colonial migration of Christian converts of non-European origin (Conversos). Furthermore, we find that ancestry related to highland (Central Andean) versus lowland (Mapuche) Natives is associated with variation in facial features, particularly nose morphology, and detect significant differences in allele frequencies between these groups at loci previously associated with nose morphology in this sample., Latin Americans trace their ancestry to the admixture of Native Americans, Europeans and Sub-Saharan Africans. Here, the authors develop a novel haplotype-based approach and analyse over 6,500 Latin Americans to infer the geographically-detailed genetic structure of this population.
Published: 2018
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11. Oncology research in late twentieth century and turn of the century Portugal: a scientometric approach to its institutional and semantic dimensions

Author: Alberto Cambrosio, Fatima Cardoso, Carmen Jerónimo, Leonor David, Jean-Philippe Cointet, João Arriscado Nunes, Oriana Rainho Brás, Universidade Técnica de Lisboa, ASPIC-Portuguese Association for Cancer Research, Partenaires INRAE, Laboratoire Interdisciplinaire Sciences, Innovations, Sociétés (LISIS), Institut National de la Recherche Agronomique (INRA)-Université Paris-Est Marne-la-Vallée (UPEM)-ESIEE Paris-Centre National de la Recherche Scientifique (CNRS), Department of Social Studies of Medicine (SSOM), McGill University = Université McGill [Montréal, Canada], Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Universidade do Porto, Universidade de Coimbra, Champalimaud Foundation, Portuguese Oncology Institute, Fundacao Calouste Gulbenkian, Bristol Myers Squibb, Médialab (Sciences Po) (Médialab), Sciences Po (Sciences Po), Centre de sociologie des organisations (CSO), Sciences Po (Sciences Po)-Centre National de la Recherche Scientifique (CNRS), Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Department of Medical Oncology, Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Department of Genetics, Cancer Epigenetics Group, Research Center of the Portuguese Oncology Institute, Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar (ICBAS), and Universidade do Porto = University of Porto
Subjects: Oncology, Economic growth, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Translational research, Semantic networks, Oncology research, Library and Information Sciences, 050905 science studies, [SHS]Humanities and Social Sciences, [SHS.HISPHILSO]Humanities and Social Sciences/History, Philosophy and Sociology of Sciences, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Institutional collaboration networks, media_common.cataloged_instance, Sociology, European union, media_common, [SHS.STAT]Humanities and Social Sciences/Methods and statistics, [SHS.SOCIO]Humanities and Social Sciences/Sociology, Portugal, 05 social sciences, Scientometrics, Twenty-First Century, General Social Sciences, language.human_language, 3. Good health, Computer Science Applications, Developmental dynamics, 030220 oncology & carcinogenesis, South american, language, 0509 other social sciences, Portuguese, Period (music)
Abstract: International audience; This paper analyses the developmental dynamics of oncology research in Portugal during the second half of the twentieth century and early twenty first century. Grounding its conclusions in a scientometric analysis of a database of publications covering the period 1976-2015, the paper shows how the expansion of oncology research from the end of the 1990s through the 2000s is closely related to science and technology policy decisions in the country. The main actors of the institutional evolution of the field are public organizations, both hospital and academia/research-based, frequently working together. Portuguese oncology research focused especially on organ-based cancers, underlining the strong link between the laboratory and the clinic. Accordingly, translational research is a major trend in oncology research, as evidenced by the analysis of publications in major journals and inter-citation maps. Networks of institutional co-authorships show the importance of regional and international collaborations. The collaboration patterns over time reveal the importance of national and European collaborations during the initial years covered by our publication database, in line with the major impact of Portugal's integration into the European Union, and a growing importance of regional collaborations, as well as with North and South American institutions in more recent years. Portugal provides a case study of how twentieth century policies at the national and European levels have impacted on the evolution of oncology research in countries from southern Europe.
Published: 2017
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12. Evidence-Based Clinical Use of Nanoscale Extracellular Vesicles in Nanomedicine

Author: Guillaume van Niel, Carla Oliveira, Roberto Furlan, Ihsan Gursel, Anabela Cordeiro da Silva, Edit I. Buzás, Samir El Andaloussi, Eva Rohde, Alicia Llorente, Hernando A. del Portillo, Graça Raposo, Bernd Giebel, An Hendrix, Maja Kosanović, Lorraine O'Driscoll, Natasa Zarovni, Apolonija Bedina Zavec, Stefano Fais, Bertrand Kaeffer, Giovanni Camussi, Gabriella Pocsfalvi, María Yáñez-Mó, Irina Nazarenko, Tanja Ficko Trček, Marei Sammar, Lawrence Rajendran, Marjo Yliperttula, Antonio Marcilla, Francesc E. Borràs, Marilena E. Lekka, Joana Carvalho, Georg Lipps, Pia Siljander, Veronika Kralj-Iglič, Francesco Cappello, M. Helena Vasconcelos, Mariantonia Logozzi, Istituto Superiore di Sanità, Trinity College Dublin, Hospital Germans Trias I Pujol, Department of Genetics, Cell- and Immunobiology, Semmelweis University, Universita di Torino, Università degli Studi di Palermo, Institute of Molecular Pathology and Immunology, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Institute for Molecular and Cell Biology, University of Porto Medical School, Hospital Clínic de Barcelona, Karolinska Institutet [Stockholm], University of Oxford [Oxford], Lek Pharmaceuticals d.d., a Sandoz Company, San Raffaele Scientific Institute, Ghent University Hospital, Bilkent University [Ankara], University of Ljubljana, Physiologie des Adaptations Nutritionnelles (PhAN), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), University of Belgrade, University of Ioannina, University of Applied Sciences and Arts Northwestern Switzerland (HES-SO), Universitat de València (UV), ORT Braude College, Partenaires INRAE, Oslo University Hospital [Oslo], University of Freiburg [Freiburg], Universidade do Porto, Consiglio Nazionale delle Ricerche (CNR), Universität Zürich [Zürich] = University of Zurich (UZH), Biologie Cellulaire et Cancer, Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Curie [Paris], Paracelsus Medical University, University of Salzburg, University of Helsinki, Univ Porto IPATIMUP, Inst Mol Pathol & Immunol, P-4200135 Oporto, Portugal, Univ Porto IPATIMUP, Inst Invest & Inovacao Saude i3S, P-4200135 Oporto, Portugal, Hospital Sta Cristina, Exosomics Siena SpA, National Institute of Chemistry, Institute for Transfusion Medicine, University Hospital Essen, Universität Duisburg-Essen [Essen], Fais, S., O'Driscoll, L., Borras, F., Buzas, E., Camussi, G., Cappello, F., Carvalho, J., Cordeiro Da Silva, A., Del Portillo, H., El Andaloussi, S., Ficko Trček, T., Furlan, R., Hendrix, A., Gursel, I., Kralj-Iglic, V., Kaeffer, B., Kosanovic, M., Lekka, M., Lipps, G., Logozzi, M., Marcilla, A., Sammar, M., Llorente, A., Nazarenko, I., Oliveira, C., Pocsfalvi, G., Rajendran, L., Raposo, G., Rohde, E., Siljander, P., Van Niel, G., Vasconcelos, M., Yáñez-Mó, M., Yliperttula, M., Zarovni, N., Zavec, A., and Giebel, B.
Subjects: 0301 basic medicine, Medical nanotechnology, Physiology, Medizin, General Physics and Astronomy, xxx xxx, Cell Communication, Exosomes, Regenerative medicine, Theranostic Nanomedicine, Membrane microparticle, Engineering (all), Drug Delivery Systems, Pathophysiological, Cell-Derived Microparticles, Caveolae, Diagnosis, General Materials Science, Lipid raft, Phospholipids, Clinical Trials as Topic, Phospholipid membrane, Vesicle, General Engineering, Science and Technology, Materials Science (all), Physics and Astronomy (all), 3. Good health, Cell biology, Intercellular communications, Clinical trial (topic), Nanomedicine, Drug delivery, [SDV.IMM]Life Sciences [q-bio]/Immunology, Human, Endosome, Drug delivery system, Nanotechnology, Biology, Program diagnostics, 03 medical and health sciences, Extracellular Vesicles, Animals, Humans, Therapeutic agents, Settore BIO/16 - Anatomia Umana, Animal, Recent researches, Microvesicles, Cell membranes, Exosome, 030104 developmental biology, International cooperation, Membrane microdomains
Abstract: collaboration au projet H2020 European Cooperation in Science and Technology (COST) program European Network on Microvesicles and Exosomes in Health and Disease (ME-HAD); International audience; Recent research has demonstrated that all body fluids assessed contain substantial amounts of vesicles that range in size from 30 to 1000 nm and that are surrounded by phospholipid membranes containing different membrane microdomains such as lipid rafts and caveolae. The most prominent representatives of these so-called extracellular vesicles (EVs) are nanosized exosomes (70-150 nm), which are derivatives of the endosomal system, and microvesicles (100-1000 nm), which are produced by outward budding of the plasma membrane. Nanosized EVs are released by almost all cell types and mediate targeted intercellular communication under physiological and pathophysiological conditions. Containing cell-type specific signatures, EVs have been proposed as biomarkers in a variety of diseases. Furthermore, according to their physical functions, EVs of selected cell types have been used as therapeutic agents in immune therapy, vaccination trials, regenerative medicine, and drug delivery. Undoubtedly, the rapidly emerging field of basic and applied EV research will significantly influence the biomedicinal landscape in the future. In this Perspective, we, a network of European scientists from clinical, academic, and industry settings collaborating through the H2020 European Cooperation in Science and Technology (COST) program European Network on Microvesicles and.Exosomes in Health and Disease (ME-HAD), demonstrate the high potential of nanosized EVs for both diagnostic and therapeutic (i.e., theranostic) areas of nanomedicine.
Published: 2016
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13. Helicobacter pylori Activates Matrix Metalloproteinase 10 in Gastric Epithelial Cells via EGFR and ERK-mediated Pathways

Author: Dionyssios N. Sgouras, Manuel A. S. Santos, Rui M. Ferreira, Ceu Figueiredo, Ioanna S. Sougleri, Ines Pinto-Ribeiro, Maria José Oliveira, Angela M. Costa, Laura Carreto, Fátima Carneiro, Marina S. Leite, Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Laboratoire de microbiologie médicale = Laboratory of Medical Microbiology [Athènes], Institut Pasteur Hellénique, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Instituto de Engenharia Biomédica (INEB), Faculdade de Medicina da Universidade do Porto (FMUP), Universidade de Aveiro, Hospital de São João [Porto], This work was supported by the European Regional Development Fund (FEDER)–Portugal (through Programa Operacional Factores de Competitividade–COMPETE), Fundação para a Ciência e a Tecnologia (project PTDC/BIA-MIC/116890/2010 and fellowships SFRH/BPD/109446/2015 [to A. M. C.], SFRH/BPD/84084/2012 [to R. M. F.], SFHRH/BD/110803/2015 [to I. P.-R.], and SFRH/BPD/110065/2015 [to M. L.]), the Hellenic Society of Gastrointestinal Oncology and Experimental Research Center–ELPEN (scholarship to I. S. S.), and the InfeNeutra project, KRIPIS National Strategic Reference Framework, Ministry of Culture and Education of Greece (ESPA 2007–2013, MIS 450598 to I. S. S.)., We thank Armando Castro, Manuel Moutinho, and Armindo Pereira (Department of Pathology, CHSJ) for technical support., European Project: 116890,FCT::,PTDC/2010,PTDC/BIA-MIC/116890/2010(2012), and Universidade do Porto = University of Porto
Subjects: 0301 basic medicine, MAPK/ERK pathway, Male, Small interfering RNA, MAP Kinase Kinase 4, MESH: Helicobacter pylori/pathogenicity, MESH: Gastric Mucosa/microbiology, Receptor tyrosine kinase, Invasion, Immunology and Allergy, MESH: ErbB Receptors/metabolism, MESH: Middle Aged, biology, Kinase, Middle Aged, invasion, CagA, ErbB Receptors, MESH: Gastric Mucosa/enzymology, Infectious Diseases, medicine.anatomical_structure, Female, MMP-10, MESH: Bacterial Proteins/metabolism, Proto-oncogene tyrosine-protein kinase Src, MESH: Antigens, Bacterial/metabolism, MESH: Enzyme Activation, MESH: Cell Line, Tumor, MAP Kinase Signaling System, Virulence Factors, EGFR, Cell Line, 03 medical and health sciences, Bacterial Proteins, Matrix Metalloproteinase 10, Cell Line, Tumor, Gastric mucosa, medicine, MESH: MAP Kinase Signaling System, Humans, MESH: MAP Kinase Kinase 4/metabolism, Antigens, Bacterial, MESH: Humans, Helicobacter pylori, MESH: Virulence Factors/metabolism, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, biology.organism_classification, bacterial infections and mycoses, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, digestive system diseases, MESH: Male, MESH: Cell Line, Enzyme Activation, 030104 developmental biology, Gastric Mucosa, Immunology, Cancer research, biology.protein, MESH: Matrix Metalloproteinase 10/metabolism, MESH: Female
Abstract: International audience; Helicobacter pylori colonizes the human stomach and increases the risk for peptic ulcer disease and gastric carcinoma. H. pylori upregulates the expression and activity of several matrix metalloproteinases (MMPs) in cell lines and in the gastric mucosa. The aim of this study was to explore the mechanisms leading to upregulation of MMP10 in gastric epithelial cells induced by H. pylori. Infection of gastric cells with H. pylori led to an increase in levels of MMP-10 messenger RNA, protein secretion, and activity. cagA knockout mutants or CagA phosphorylation-defective mutants failed to increase MMP10 expression. These results were confirmed in infection experiments with clinical isolates with known cagA status and in human gastric biopsy specimens. Treatment of cells with chemical inhibitors of the receptor tyrosine kinase EGFR and the kinase Src abrogated H. pylori-induced MMP10 expression. Inhibitors of ERK1/2 and JNK kinases abolished and significantly decreased H. pylori-induced MMP10 expression, respectively, whereas inhibition of the kinase p38 had no effect. Finally, inhibition of MMP10 expression by small interfering RNA led to a decrease in the gastric cell-invasive phenotype mediated by the infection. In conclusion, CagA-positive H. pylori strains stimulate MMP10 expression. MMP-10 modulation occurs via EGFR activation in a process that involves Src, ERK, and JNK pathways. MMP-10 may be implicated in H. pylori-mediated extracellular matrix remodeling.
Published: 2015
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14. OCT-1 is over-expressed in intestinal metaplasia and intestinal gastric carcinomas and binds to, but does not transactivate, CDX2 in gastric cells

Author: Isabelle Van Seuningen, Patrícia Mesquita, José Domingues de Almeida, Elisabete Silva, Nuno Mendes, Raquel Almeida, Filipe Santos-Silva, Leonor David, Celso A. Reis, Michal Shoshkes, Faculdade de Medicina, VAN SEUNINGEN, ISABELLE, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Mucines Epitheliales : du Gene a la Fonction, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Faculdade de Medicina da Universidade do Porto (FMUP), Universidade do Porto = University of Porto, and Universidade do Porto
Subjects: genetic structures, [SDV]Life Sciences [q-bio], Chronic gastritis, Electrophoretic Mobility Shift Assay, Biology, Transfection, Pathology and Forensic Medicine, 03 medical and health sciences, Transactivation, 0302 clinical medicine, Stomach Neoplasms, Tumor Cells, Cultured, medicine, Gastric mucosa, Humans, CDX2 Transcription Factor, Promoter Regions, Genetic, CDX2, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Homeodomain Proteins, Ciências da Saúde, Metaplasia, 0303 health sciences, Expression vector, Stomach, Transdifferentiation, Health sciences, Intestinal metaplasia, medicine.disease, eye diseases, digestive system diseases, Neoplasm Proteins, 3. Good health, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Gastric Mucosa, Gastritis, 030220 oncology & carcinogenesis, Chronic Disease, embryonic structures, Trans-Activators, Cancer research, sense organs, Precancerous Conditions, Octamer Transcription Factor-1
Abstract: Intestinal metaplasia (IM) is a preneoplastic lesion of the stomach in which there is transdifferentiation of the gastric mucosa to an intestinal phenotype. The caudal-related homeobox gene CDX2 encodes an intestine-specific transcription factor crucial for the regulation of proliferation and differentiation of intestinal cells. In addition, CDX2 is involved in the induction of IM in the stomach. The aim of this study was to access the putative involvement of OCT-1 in the induction of CDX2 expression de novo in gastric mucosa leading to the onset of IM. OCT-1 protein expression was evaluated by immunohistochemistry in 31 biopsies with chronic gastritis, 15 biopsies with foci of IM and adjacent gastric mucosa and 42 gastric carcinomas. Furthermore, we evaluated OCT-1 binding by electrophoretic mobility shift assay and activation of the CDX2 promoter by co-transfecting a CDX2 promoter/reporter construct with an OCT-1 expression vector in two gastric carcinoma cell lines, GP220 and MKN45. Our results show that OCT-1 is expressed in chronic gastritis, particularly when it is adjacent to IM and is expressed in 87% of IM foci. Furthermore, 74% of the gastric carcinomas were positive for OCT-1 and a strong association was observed between OCT-1 expression and intestinal-type carcinoma. We identified that OCT-1 binds to the CDX2 promoter, although we could not see a transactivation effect in gastric carcinoma cell lines. In conclusion, we observed increased OCT-1 expression in IM and in intestinal gastric carcinomas and identified the capacity of OCT-1 to bind to the CDX2 promoter, although we could not demonstrate a direct effect of OCT-1 in the transactivation of CDX2. Copyright (c) 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Published: 2005
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15. Gastric cancer: Basic aspects

Author: Silvia Molina-Castro, Ceu Figueiredo, Joana Pereira-Marques, José Carlos Machado, Christine Varon, Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Universidad de Costa Rica (UCR), Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto = University of Porto, and Varon, Christine
Subjects: 0301 basic medicine, Carcinogenesis, [SDV]Life Sciences [q-bio], DNMT3B, gastric cancer stem cells, Bioinformatics, 03 medical and health sciences, 0302 clinical medicine, Stomach Neoplasms, microRNA, Genetic predisposition, medicine, Humans, Gene silencing, Epigenetics, Cell Proliferation, marker, biology, digestive, oral, and skin physiology, Gastroenterology, Cancer, General Medicine, Helicobacter pylori, biology.organism_classification, medicine.disease, digestive system diseases, microRNAs, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, Infectious Diseases, 030220 oncology & carcinogenesis, Neoplastic Stem Cells, immune checkpoint inhibition, PDX1, molecular classification, Signal Transduction
Abstract: International audience; Gastric cancer is one of the most incident and deadliest malignancies in the world. Gastric cancer is a heterogeneous disease and the end point of a long and multistep process, which results from the stepwise accumulation of numerous (epi)genetic alterations, leading to dysregulation of oncogenic and tumor suppressor pathways. Gastric cancer stem cells have emerged as fundamental players in cancer development and as contributors to gastric cancer heterogeneity. For this special issue, we will report last year's update on the gastric cancer molecular classification, and in particular address the gastric cancer groups who could benefit from immune checkpoint therapy. We will also review the latest advances on gastric cancer stem cells, their properties as gastric cancer markers and therapeutic targets, and associated signaling pathways. The understanding of the molecular basis underlying gastric cancer heterogeneity and of the role played by gastric cancer stem cells in cancer development and heterogeneity is of major significance, not only for identifying novel targets for cancer prevention and treatment, but also for clinical management and patient stratification for targeted therapies.
Published: 2017
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16. Membrane-lipids anti-bacterial and anti-tumoral therapies revisited: an example with Helicobacter pylori infection

Author: Correia, M., Machado, J.C., Touati, Eliette, Pathogenèse de Helicobacter, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Faculdade de Medicina da Universidade do Porto (FMUP), Universidade do Porto, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Universidade do Porto = University of Porto
Subjects: n-3 Polyunsaturated fatty acids, Docosahexaenoic acid, Cholesterol, Helicobacter pylori, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, ComputingMilieux_MISCELLANEOUS, statins
Abstract: International audience
Published: 2013

17. Malaria: looking for selection signatures in the human PKLR gene region

Author: Machado, Patricia, Pereira, Rui, Rocha, Ana Mafalda, Anco, Licínio, Fernandes, Natércia, Miranda, Juliana, Ribeiro, M. Letícia, Do Rosário, Virgílio E., Amorim, António, Gusmão, Leonor, Arez, Ana Paula, Malaria, Centre for Malaria and Tropical Diseases, Instituto de Higiene e Medicina Tropical (CMDT.LA/IHMT), Population Genetics, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Instituto de Medicina Legal, Universidade de Santiago de Compostela [Spain] (USC ), Sequencing Service, Anthropology, Centre of Research in Anthropology in Health, Universidade de Coimbra, Haematology, Centro Hospitalar e Universitário [Coimbra], Faculty of Medicine, Universidade Eduardo Mondlane, Central Hospital of Maputo, Paediatrics, and Paediatric Hospital David Bernardino
Subjects: parasitic diseases, Medicine
Abstract: International audience; The genetic component of susceptibility to malaria is both complex and multigenic and the better-known protective polymorphisms are those involving erythrocyte-specific structural proteins and enzymes. in vivo and in vitro data have suggested that pyruvate kinase deficiency, which causes a nonspherocytic haemolytic anaemia, could be protective against malaria severity in humans, but this hypothesis remains to be tested. In the present study, we conducted a combined analysis of Short Tandem Repeats (STRs) and Single Nucleotide Polymorphisms (SNPs) in the pyruvate kinase-encoding gene (PKLR) and adjacent regions (chromosome 1q21) to look for malaria selective signatures in two sub-Saharan African populations, from Angola and Mozambique, in several groups with different malaria infection outcome. A European population from Portugal, including a control and a pyruvate kinase-deficient group, was used for comparison. Data from STR and SNP loci spread along the PKLR gene region showed a considerably higher differentiation between African and Portuguese populations than that usually found for neutral markers. In addition, a wider region showing strong linkage disequilibrium was found in an uncomplicated malaria group, and a haplotype was found to be associated with this clinical group. Altogether, this data suggests that malaria selective pressure is acting in this genomic region.
Published: 2010
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18. Key elements of the BMP/SMAD pathway co-localize with CDX2 in intestinal metaplasia and regulate CDX2 expression in human gastric cell lines

Author: I. Van Seuningen, Rutger J. Jacobs, Vânia Camilo, G. R. van den Brink, Leonor David, Rita Barros, Nuno Mendes, Bruno Pereira, Isabelle Duluc, Paula Paulo, Filipe Santos-Silva, Raquel Almeida, Jean-Noël Freund, Maria Azevedo, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), De l'homéostasie tissulaire au cancer et à l'inflammation, Institut National de la Santé et de la Recherche Médicale (INSERM), Leiden University Medical Center (LUMC), Faculdade de Medicina da Universidade do Porto (FMUP), Universidade do Porto = University of Porto, Mucines Epitheliales : du Gene a la Fonction, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, VAN SEUNINGEN, ISABELLE, Universidade do Porto, and Gastroenterology and Hepatology
Subjects: Pathology, medicine.medical_specialty, Chromatin Immunoprecipitation, animal structures, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Blotting, Western, Bone Morphogenetic Protein 2, SMAD, Bone Morphogenetic Protein 4, Biology, Bone morphogenetic protein, Pathology and Forensic Medicine, Smad1 Protein, 03 medical and health sciences, 0302 clinical medicine, Stomach Neoplasms, Transforming Growth Factor beta, Cell Line, Tumor, medicine, Humans, CDX2 Transcription Factor, RNA, Small Interfering, CDX2, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Smad4 Protein, Regulation of gene expression, Homeodomain Proteins, 0303 health sciences, Reverse Transcriptase Polymerase Chain Reaction, Growth factor, Carcinoma, Intestinal metaplasia, medicine.disease, Immunohistochemistry, BMPR1A, digestive system diseases, 3. Good health, [SDV] Life Sciences [q-bio], Gene Expression Regulation, Neoplastic, 030220 oncology & carcinogenesis, embryonic structures, Bone Morphogenetic Proteins, Cancer research, Ectopic expression, RNA Interference
Abstract: Helicobacter pylori infection induces intestinal metaplasia of the stomach, a preneoplastic lesion associated with an increased risk for gastric cancer development. Intestinal metaplasia is induced by the intestine-specific transcription factor CDX2 but the mechanisms responsible for this ectopic expression have never been described. We hypothesized that the BMP/SMAD pathway has a role in CDX2 regulation, in this context, for the following reasons: (1) the BMP pathway is crucial for normal intestinal differentiation and (2) there is an influx of BMP2 and BMP4-producing cells to the stomach upon Helicobacter pylori infection. We evaluated the expression of key elements of the BMP pathway in human stomach specimens with IM. Growth factor treatments, with BMP2 and BMP4, were performed in cultured cells and a knock-down experiment of SMAD4 was done using RNAi. We showed overexpression in IM of BMP2/4, BMPR1A, and SMAD4 in 56% of IM foci, and pSMAD1/5/8 in 100% of IM foci as compared to adjacent mucosa. In vitro, treatment of AGS cells with BMP2 and BMP4 increased endogenous CDX2 expression as well as the intestinal differentiation markers MUC2 and LI-cadherin. On the other hand, SMAD4 knock-down led to decreased endogenous CDX2, MUC2, and LI-cadherin in AGS. Treatment of the SMAD4 knock-down cells had no influence on CDX2 expression as opposed to wild-type cells. A 9.3 kb CDX2 promoter could be transactivated by SMAD4 and SMAD1 in a cell-dependent manner. In conclusion, we identified for the first time that the BMP pathway is active in intestinal metaplasia and that BMP2 and BMP4 regulate CDX2 expression and promote intestinal differentiation through the canonical signal transducers.
Published: 2008
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19. The c.156_157insAlu rearrangement accounts for more than one-fourth of deleterious BRCA mutations in northern/central Portugal

Author: Peixoto, Ana, Santos, Catarina, Rocha, Patrícia, Pinheiro, Manuela, Príncipe, Sofia, Pereira, Deolinda, Rodrigues, Helena, Castro, Fernando, Abreu, Joaquim, Gusmão, Leonor, Amorim, António, Teixeira, Manuel R., Department of Genetics, Portuguese Oncology Institute, Department of Medical Oncology, Department of Surgical Oncology, Institute of Molecular Pathology and Immunology, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Faculty of Sciences, Universidade do Porto, and Institute of Biomedical Sciences (ICBAS)
Subjects: c.156_157insAlu mutation, Breast cancer, Hereditary predisposition
Abstract: International audience; We evaluated the contribution of an Alu insertion in exon 3 (c.156_157insAlu) to inherited predisposition to breast/ovarian cancer in 208 families originated mostly from northern/central Portugal. We identified the c.156_157insAlu mutation in 14 families and showed that it accounts for more that one-fourth of deleterious / mutations in breast/ovarian cancer families originated from this part of the country. This mutation originates exon 3 skipping and we demonstrated its pathogenic effect by showing that the full length transcript is derived only from the wild type allele in carriers, that it is absent in 262 chromosomes from healthy blood donors, and that it co-segregates with the disease. Polymorphic microsatellite markers were used for haplotype analysis in three informative families. In two of the three families one haplotype was shared for all but two markers, whereas in the third family all markers telomeric to differed from that observed in the other two. Although the c.156_157insAlu mutation has so far only been identified in Portuguese breast/ovarian cancer families, screening of this rearrangement in other populations will allow evaluation of whether or not it is a population-specific founder mutation and a more accurate estimation of its distribution and age.
Published: 2008
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20. A mathematical framework for genetic relatedness analysis involving X chromosome aneuploidies.

Author: Faustino M, Gusmão L, Amorim A, Kling D, and Pinto N
Subjects: Humans, Female, Male, Klinefelter Syndrome genetics, Trisomy genetics, Sex Chromosome Aberrations, Turner Syndrome genetics, Models, Genetic, Pedigree, Genotype, Sex Chromosome Disorders of Sex Development, Chromosomes, Human, X, Aneuploidy
Abstract: The unique features of the X chromosome can be crucial to complement autosomal profiling or to disentangle complex kinship problems, providing in some cases a similar or even greater power than autosomes in paternity/maternity investigations. While theoretical and informatics approaches for pairwise X-linked kinship analyses are well established for euploid individuals, these are still lacking for individuals with an X chromosome aneuploidy. To trigger the fulfilment of this gap, this research presents a mathematical framework that enables the quantification of DNA evidence in pairwise kinship analyses, involving two non-inbred individuals, one of whom with a non-mosaic X chromosome aneuploidy: Trisomy X (47, XXX), Klinefelter (47, XXY) or Turner (45, X0) syndrome. As previously developed for a regular number of chromosomes, this approach relies on the probability of related individuals sharing identical-by-descent (IBD) alleles at one specific locus and it can be applied to any set of independently transmitted markers, with no gametic association in the population. The kinship hypotheses mostly considered in forensic casework are specifically addressed in this work, but the reasoning and procedure can be applied to virtually any pairwise kinship problem under the referred assumptions. Algebraic formulae for joint genotypic probabilities cover all the possible genotypic configurations and pedigrees. Compared with the analyses assuming individuals with a regular number of chromosomes, complicating factors rely on the different possibilities for both the parental origin of the error (either maternal or paternal), and the type of error occurred (either meiotic or post-zygotic mitotic). These imply that a non-inbred female with Triple X or a male with Klinefelter syndrome may carry two IBD alleles at the same locus. Thus, and contrarily to what occurs for the standard case, IBD partitions depend not only on the kinship hypothesis under analysis but also on the genotypic configuration of the analyzed individuals. For some cases, parameters of interest can be inferred, while for others recommended values based on the available literature are provided. This work is the starting point to analyze X-chromosomal data under the scope of kinship problems, involving individuals with aneuploidies, as it will enhance the quantification of the DNA evidence not only in forensics but also in the medical genetics field. We hope it will trigger the development of approaches including other complicating factors, as a greater number of individuals, possibility of the occurrence of mutations and/or silent alleles, as well as the analysis of linked markers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Published: 2025
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21. TERTmonitor Efficacy and Performance in Detecting Mutations by Droplet Digital PCR.

Author: Bessa-Gonçalves M, Brás JP, Jesus TT, Prazeres H, Soares P, and Vinagre J
Subjects: Humans, Real-Time Polymerase Chain Reaction methods, Real-Time Polymerase Chain Reaction standards, Promoter Regions, Genetic, Male, Female, Sensitivity and Specificity, Aged, Middle Aged, Telomerase genetics, Urinary Bladder Neoplasms genetics, Mutation
Abstract: Background: The screening of TERT promoter ( TERTp ) mutations is essential in cancer research and diagnostics, due to its prevalence in tumours associated with low self-renewal rates. TERTmonitor is a diagnosis kit primarily designed for real-time qPCR qualitative detection of -124C>T and -146C>T TERTp mutations, which are highly prevalent in several malignancies, particularly in bladder carcinoma., Objective: This study aims to investigate TERTmonitor performance in droplet digital PCR (ddPCR) in urine samples from bladder cancer patients., Methods: A total of 45 urine samples were examined by real-time qPCR and ddPCR techniques, and their performances were compared., Results: TERTmonitor had similar performance in both real-time qPCR and ddPCR platforms. Specifically, the methods exhibited a concordance rate of 95.45% and 90% for -124C>T and -146C>T mutations, respectively. Importantly, an enhanced sensitivity in certain scenarios was exhibited by ddPCR when compared to real-time qPCR, detecting mutations that the latter failed to identify in approximately 4.55% and 10% of the samples for -124C>T and -146C>T mutations, respectively. This enhanced sensitivity of ddPCR was particularly evident in samples with low-frequency mutations., Conclusions: The findings highlight the usefulness of TERTmonitor for cancer surveillance either in real-time qPCR or ddPCR platforms.
Published: 2024
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22. Unraveling the Significance of DGCR8 and miRNAs in Thyroid Carcinoma.

Author: Rodrigues L, Da Cruz Paula A, Soares P, and Vinagre J
Subjects: Humans, RNA-Binding Proteins metabolism, Cell Differentiation, Mutation genetics, MicroRNAs genetics, MicroRNAs metabolism, Thyroid Neoplasms genetics
Abstract: MicroRNAs (miRNAs) act as negative regulators for protein-coding gene expression impacting cell proliferation, differentiation, and survival. These miRNAs are frequently dysregulated in cancer and constitute classes of blood-based biomarkers useful for cancer detection and prognosis definition. In thyroid cancer (TC), the miRNA biogenesis pathway plays a pivotal role in thyroid gland formation, ensuring proper follicle development and hormone production. Several alterations in the miRNA biogenesis genes are reported as a causality for miRNA dysregulation. Mutations in microprocessor component genes are linked to an increased risk of developing TC; in particular, a recurrent mutation affecting DGCR8 , the E518K. In this review, we explore these novel findings and resume the current state-of-the-art in miRNAs in thyroid carcinomas.
Published: 2024
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23. Cyto-Histological Profile of MicroRNAs as Diagnostic Biomarkers in Differentiated Thyroid Carcinomas.

Author: Matos ML, Pinto M, Alves M, Canberk S, Gonçalves A, Bugalho MJ, Papoila AL, and Soares P
Subjects: Humans, Proto-Oncogene Proteins B-raf genetics, Reproducibility of Results, Thyroid Cancer, Papillary diagnosis, Thyroid Cancer, Papillary genetics, Biomarkers, MicroRNAs metabolism, Carcinoma, Papillary diagnosis, Carcinoma, Papillary genetics, Carcinoma, Papillary pathology, Thyroid Neoplasms diagnosis, Thyroid Neoplasms genetics, Thyroid Neoplasms pathology
Abstract: Introduction: The repertoire of microRNAs (miRNAs) in thyroid carcinomas starts to be elucidated. Among differentiated thyroid carcinomas (DTCs), papillary thyroid carcinoma (PTC) is the most frequent. The assessment of miRNAs expression may contribute to refine the pre-surgical diagnosis in order to obtain a personalized and more effective treatment for patients., Aims: This study aims to evaluate (1) the miRNAs in a series of DTCs, and their association with the presence of selected genetic mutations in order to improve diagnosis and predict the biologic behavior of DTC/PTC. (2) The reliability of molecular tests in Ultrasound-guided Fine Needle Aspiration Cytology (US-FNAC) for a more precise preoperative diagnosis., Material and Methods: This series includes 176 samples (98 cytology and 78 histology samples) obtained from 106 patients submitted to surgery, including 13 benign lesions (controls) and 93 DTCs (cases). The microRNA expression was assessed for miR-146b, miR-221, miR-222, and miR-15a through quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). The results were analyzed by the 2 -ΔΔCT method, using miR16 as an endogenous control. Regarding PTC diagnosis, the discriminative ability of miRNAs expression was assessed by the area under the Receiver Operating Characteristic Curve (AUC). In PTCs, the association of miRNAs expression, clinicopathological features, and genetic mutations ( BRAF , RAS, and TERTp ) was evaluated., Results/discussion: All the analyzed miRNAs presented a tendency to be overexpressed in DTCs/PTCs when compared with benign lesions, both in cytology and histology samples. In cytology, miRNAs expression levels were higher in malignant tumors than in benign tumors. In histology, the discriminative abilities regarding PTC diagnosis were as follows: miR-146b (AUC 0.94, 95% CI 0.87-1), miR-221 (AUC 0.79, 95% CI 0.68-0.9), miR-222 (AUC 0.76, 95% CI 0.63-0.89), and miR-15a (AUC 0.85, 95% CI 0.74-0.97). miR-146b showed 89% sensitivity (se) and 87% specificity (sp); miR-221 se = 68.4, sp = 90; miR-222 se = 73, sp = 70; and mi-R15a se = 72, sp = 80. MicroRNAs were associated with worst-prognosis clinicopathological characteristics in PTCs ( p < 0.05), particularly for miR-222. Our data reveal a significant association between higher expression levels of miR-146b, miR-221, and miR-222 in the presence of the BRAF mutation ( p < 0.001) and miR-146b ( p = 0.016) and miR-221 ( p = 0.010) with the RAS mutation, suggesting an interplay of these mutations with miRNAs expression. Despite this study having a relatively small sample size, overexpression of miRNAs in cytology may contribute to a more precise preoperative diagnosis. The miRNAs presented a good discriminative ability in PTC diagnosis. The association between the miRNAs expression profile and genetic alterations can be advantageous for an accurate diagnosis of DTCs/PTCs in FNAC.
Published: 2024
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24. Loss of RAS Mutations in Liquid Biopsies of Patients With Multi-Treated Metastatic Colorectal Cancer.

Author: Albuquerque J, Neto da Silva D, Padrão T, Leal-Costa L, Bizarro R, Correia J, Baptista C, Machete M, Prazeres G, Margarido I, Fernandes G, Simões P, Timóteo T, Lopes F, Godinho J, Moreira-Pinto J, Rodrigues T, Faria A, Pulido C, Cirnes L, Teixeira JA, and Passos Coelho JL
Subjects: Humans, Retrospective Studies, Antibodies, Monoclonal therapeutic use, Liquid Biopsy, Mutation, Colorectal Neoplasms drug therapy, Colorectal Neoplasms genetics, Colorectal Neoplasms pathology, Antineoplastic Agents therapeutic use, Colonic Neoplasms, Rectal Neoplasms
Abstract: Background: Liquid biopsy (LB) is a non-invasive tool to evaluate the heterogeneity of tumors. Since RAS mutations (RAS-mut) play a major role in resistance to antiepidermal growth factor receptor inhibitors (EGFR) monoclonal antibodies (Mabs), serial monitoring of RAS-mut with LB may be useful to guide treatment. The main aim of this study was to evaluate the prognostic value of the loss of RAS-mut (NeoRAS-wt) in LB, during the treatment of metastatic colorectal cancer (mCRC)., Methods: A retrospective study was conducted on patients with mCRC between January 2018 and December 2021. RAS-mut were examined in tissue biopsy, at mCRC diagnosis, and with LB, during treatment., Results: Thirty-nine patients with RAS-mut mCRC were studied. LB was performed after a median of 3 lines (0-7) of systemic treatment including anti-vascular endothelial growth factor (anti-VEGF) Mabs. NeoRAS-wt was detected in 13 patients (33.3%); 9 (69.2%) of them received further treatment with anti-EGFR Mabs with a disease control rate of 44.4%. Median overall survival (OS), from the date of LB testing, was 20 months in the NeoRAS-wt group and 9 months in the persistent RAS-mut group (log-rank 2.985; P = .08), with a 12-month OS of 84.6% and 57.7%, respectively. NeoRAS-wt was identified as a predictor of survival (HR = 0.29; P = .007), with an 11-month improvement in median OS and a 71% decrease in risk of death, in heavily pretreated patients., Conclusions: In conclusion, monitoring clonal evolution in mCRC by LB may provide an additional treatment line for patients with NeoRAS-wt in advanced disease., (© The Author(s) 2023. Published by Oxford University Press.)
Published: 2024
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25. Comparative Cyto-Histological Genetic Profile in a Series of Differentiated Thyroid Carcinomas.

Author: Matos ML, Pinto M, Alves M, Canberk S, Gonçalves A, Bugalho MJ, Papoila AL, and Soares P
Abstract: Introduction: Molecular tests can contribute to improve the preoperative diagnosis of thyroid nodules. Tests available are expensive and not adapted to different populations., Aim: This study aimed to compare the cyto-histological genetic profile and to evaluate the reliability of molecular tests using ultrasound-guided fine needle aspiration cytology (US-FNAC) in accurately diagnosing differentiated thyroid carcinomas (DTCs) and predicting biologic behavior of papillary thyroid carcinomas (PTCs)., Materials and Methods: The series included 259 patients with paired cyto-histological samples totaling 518 samples. The genetic alterations were analyzed via PCR/Sanger sequencing. The association with clinicopathologic features was evaluated in PTCs., Results/discussion: From the 259 patients included, histologies were 50 (19.3%) benign controls and 209 (80.7%) DTC cases, from which 182 were PTCs; cytologies were 5.8% non-diagnostic, 18.2% benign, 39% indeterminate, and 37.1% malignant. In histology, indeterminate nodules ( n = 101) were 22.8% benign and 77.2% malignant. Mutation frequencies in cytology and histology specimens were, respectively, TERTp : 3.7% vs. 7.9%; BRAF : 19.5% vs. 25.1%; and RAS : 11% vs. 17.5%. The overall cyto-histological agreement of the genetic mutations was 94.9%, with Cohen's k = 0.67, and in indeterminate nodules agreement was 95.7%, k = 0.64. The identified mutations exhibited a discriminative ability in diagnosing DTC with a specificity of 100% for TERTp and BRAF , and of 94% for RAS , albeit with low sensitivity. TERTp and BRAF mutations were associated with aggressive clinicopathological features and tumor progression in PTCs ( p < 0.001). The obtained good cyto-histological agreement suggests that molecular analysis via US-FNAC may anticipate the genetic profile and the behavior of thyroid tumors, confirming malignancy and contributing to referring patients to surgery.
Published: 2024
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26. Investigating USP42 Mutation as Underlying Cause of Familial Non-Medullary Thyroid Carcinoma.

Author: Teixeira E, Fernandes C, Bungărdean M, Paula ADC, Lima RT, Batista R, Vinagre J, Sobrinho-Simões M, Máximo V, and Soares P
Subjects: Humans, Caspase 3 genetics, Genetic Predisposition to Disease, Mutation, Thiolester Hydrolases genetics, Tumor Suppressor Protein p53 genetics, Thyroid Cancer, Papillary genetics, Thyroid Neoplasms genetics, Thyroid Neoplasms pathology, Ubiquitin-Specific Proteases genetics
Abstract: In a family with Familial Non-Medullary Thyroid Carcinoma (FNMTC), our investigation using Whole-Exome Sequencing (WES) uncovered a novel germline USP42 mutation [ p.(Gly486Arg) ]. USP42 is known for regulating p53, cell cycle arrest, and apoptosis, and for being reported as overexpressed in breast and gastric cancer patients. Recently, a USP13 missense mutation was described in FNMTC, suggesting a potential involvement in thyroid cancer. Aiming to explore the USP42 mutation as an underlying cause of FNMTC, our team validated the mutation in blood and tissue samples from the family. Using immunohistochemistry, the expression of USP42, Caspase-3, and p53 was assessed. The USP42 gene was silenced in human thyroid Nthy-Ori 3-1 cells using siRNAs. Subsequently, expression, viability, and morphological assays were conducted. p53, Cyclin D1, p21, and p27 proteins were evaluated by Western blot. USP42 protein was confirmed in all family members and was found to be overexpressed in tumor samples, along with an increased expression of p53 and cleaved Caspase-3. siRNA-mediated USP42 downregulation in Nthy-Ori 3-1 cells resulted in reduced cell viability, morphological changes, and modifications in cell cycle-related proteins. Our results suggest a pivotal role of USP42 mutation in thyroid cell biology, and this finding indicates that USP42 may serve as a new putative target in FNMTC.
Published: 2024
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27. Personalized Medicine in Medullary Thyroid Carcinoma: A Broad Review of Emerging Treatments.

Author: Martins RS, Jesus TT, Cardoso L, Soares P, and Vinagre J
Abstract: Medullary thyroid carcinoma (MTC) arises from parafollicular cells in the thyroid gland, and although rare, it represents an aggressive type of thyroid cancer. MTC is recognized for its low mutational burden, with point mutations in RET or RAS genes being the most common oncogenic events. MTC can be resistant to cytotoxic chemotherapy, and multitarget kinase inhibitors (MKIs) have been considered a treatment option. They act by inhibiting the activities of specific tyrosine kinase receptors involved in tumor growth and angiogenesis. Several tyrosine kinase inhibitors are approved in the treatment of advanced MTC, including vandetanib and cabozantinib. However, due to the significant number of adverse events, debatable efficiency and resistance, there is a need for novel RET-specific TKIs. Newer RET-specific TKIs are expected to overcome previous limitations and improve patient outcomes. Herein, we aim to review MTC signaling pathways, the most recent options for treatment and the applications for personalized medicine.
Published: 2023
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28. Considerations in comparing intestinal- and diffuse-type gastric adenocarcinomas.

Author: Piazuelo MB, Carneiro F, and Camargo MC
Subjects: Humans, Intestines pathology, Helicobacter Infections, Helicobacter pylori, Adenocarcinoma diagnosis, Stomach Neoplasms diagnosis, Stomach Neoplasms pathology
Published: 2023
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29. Engaging European society at the forefront of cancer research and care: How discussions at the 5 th Gago Conference on European Science policy led to the Heidelberg Manifesto

Author: Baumann M, Celis J, Ringborg U, Heitor M, Berns A, Albreht T, Arabadjiev J, Boutros M, Brandenburg M, Canhao H, Carneiro F, Chomienne C, De Lorenzo F, Eggermont AMM, Font A, Garralda E, Goulart M, Henrique R, Lawler M, Maier-Hein L, Meunier F, Oberst S, Oliveira P, Papatriantafyllou M, Schüz J, Solary E, Valencia A, Vargas R, Weiderpass E, and Wilking N
Subjects: Humans, Europe, Germany, Policy, Neoplasms therapy
Abstract: European cancer research stakeholders met in October 2022 in Heidelberg, Germany, at the 5 th Gago conference on European Cancer Policy, to discuss the current cancer research and cancer care policy landscape in Europe. Meeting participants highlighted gaps in the existing European programmes focusing on cancer research, including Europe's Beating Cancer Plan (EBCP), the Mission on Cancer (MoC), Understanding Cancer (UNCAN.eu), and the joint action CRANE, and put forward the next priorities, in the form of the Heidelberg Manifesto for cancer research. This meeting report presents all discussions that shed light on how infrastructures can be effectively shaped for translational, prevention, clinical and outcomes cancer research, with a focus on implementation and sustainability and while engaging patients and the public. In addition, we summarize recommendations on how to introduce frameworks for the digitalization of European cancer research. Finally, we discuss what structures, commitment, and resources are needed to establish a collaborative cancer research environment in Europe to achieve the scale required for innovation., (© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
Published: 2023
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30. Activation of an actin signaling pathway in pre-malignant mammary epithelial cells by P-cadherin is essential for transformation.

Author: Faria L, Canato S, Jesus TT, Gonçalves M, Guerreiro PS, Lopes CS, Meireles I, Morais-de-Sá E, Paredes J, and Janody F
Subjects: Humans, Signal Transduction, Cadherins, Epithelial Cells metabolism, Serum Response Factor genetics, Serum Response Factor metabolism, Actins metabolism, Trans-Activators metabolism
Abstract: Alterations in the expression or function of cell adhesion molecules have been implicated in all steps of tumor progression. Among those, P-cadherin is highly enriched in basal-like breast carcinomas, playing a central role in cancer cell self-renewal, collective cell migration and invasion. To establish a clinically relevant platform for functional exploration of P-cadherin effectors in vivo, we generated a humanized P-cadherin Drosophila model. We report that actin nucleators, Mrtf and Srf, are main P-cadherin effectors in fly. We validated these findings in a human mammary epithelial cell line with conditional activation of the SRC oncogene. We show that, prior to promoting malignant phenotypes, SRC induces a transient increase in P-cadherin expression, which correlates with MRTF-A accumulation, its nuclear translocation and the upregulation of SRF target genes. Moreover, knocking down P-cadherin, or preventing F-actin polymerization, impairs SRF transcriptional activity. Furthermore, blocking MRTF-A nuclear translocation hampers proliferation, self-renewal and invasion. Thus, in addition to sustaining malignant phenotypes, P-cadherin can also play a major role in the early stages of breast carcinogenesis by promoting a transient boost of MRTF-A-SRF signaling through actin regulation., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2023. Published by The Company of Biologists Ltd.)
Published: 2023
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31. DGCR8 Microprocessor Subunit Mutation and Expression Deregulation in Thyroid Lesions.

Author: Rodrigues L, Canberk S, Macedo S, Soares P, and Vinagre J
Subjects: Humans, RNA-Binding Proteins genetics, RNA-Binding Proteins metabolism, Thyroid Gland metabolism, RNA, Messenger, Mutation, MicroRNAs genetics, MicroRNAs metabolism, Neoplasms
Abstract: DGCR8 emerged recently as miRNAs biogenesis pathway protein with a highlighted role in thyroid disease. This study aimed to characterize this miRNA biogenesis component, in particular the p.(E518K) mutation and DGCR8 expression in a series of thyroid lesions. The series of thyroid lesions was genotyped for the c.1552G>A p.(E518K) mutation. When frozen tissue was available, DGCR8 mRNA expression was analysed by qPCR. Formalin-fixed paraffin-embedded tissues were studied for DGCR8 immunoexpression. We present for the first time the p.(E518K) mutation in a case of poorly differentiated thyroid carcinoma and present the deregulation of DGCR8 expression at mRNA level in follicular-patterned tumours. The obtained data solidify DGCR8 as another important player of miRNA-related gene mutations in thyroid tumorigenesis, particularly in follicular-patterned thyroid tumours.
Published: 2022
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32. Aggressive nonfunctioning pituitary neuroendocrine tumors.

Author: Portovedo S, Neto LV, Soares P, Carvalho DP, Takiya CM, and Miranda-Alves L
Subjects: Humans, Transcription Factors, World Health Organization, Neuroendocrine Tumors pathology, Pituitary Neoplasms genetics, Pituitary Neoplasms pathology
Abstract: Nonfunctioning pituitary neuroendocrine tumors (NF-PitNETs) are tumors that are not associated with clinical evidence of hormonal hypersecretion. According to the World Health Organization (WHO), there are some subtypes of PitNETs that exhibit more aggressive behavior than others. Among the types of potentially aggressive PitNETs, three are nonfunctional: silent sparsely granulated somatotropinomas, silent corticotropinomas, and poorly differentiated PIT-1 lineage tumors. Several biological markers have been investigated in NF-PitNETs. However, there is no single biomarker able to independently predict aggressive behavior in NF-PitNETs. Thus, a more complex and multidisciplinary proposal of a comprehensive definition of aggressive NF-PitNETs is necessary. Here, we suggest a combined and more complete criterion for the NF-PitNETs classification. We propose that aggressiveness is due to a multifactorial combination, and we emphasize the need to include new emerging markers that are involved in the aggressiveness of NF-PitNETs and the need to identify., (© 2022. The Author(s), under exclusive licence to The Japan Society of Brain Tumor Pathology.)
Published: 2022
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33. Editorial: Glycans: Masters of immunity, from cancers to inflammatory disease.

Author: Beatson R, Läubli H, Pearce OMT, and Reis CA
Subjects: Humans, Neoplasms, Polysaccharides
Abstract: Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Published: 2022
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34. Environmentally relevant dose of the endocrine disruptor tributyltin disturbs redox balance in female thyroid gland.

Author: Andrade MN, Melo-Paiva FD, Teixeira MP, Lima-Junior NC, Soares P, Graceli JB, Carvalho DP, Morris EAR, Ferreira ACF, and Miranda-Alves L
Subjects: Animals, Collagen metabolism, Estrogen Receptor alpha metabolism, Female, Iodides metabolism, Mammals metabolism, Oxidation-Reduction, Rats, Rats, Wistar, Sulfhydryl Compounds metabolism, Superoxide Dismutase metabolism, Thyroid Gland metabolism, Endocrine Disruptors toxicity, Trialkyltin Compounds toxicity
Abstract: Tributyltin (TBT) is an endocrine disruptor used as a biocide in nautical paints. Even though many TBT effects in marine species are known, data in mammals are scarce, especially regarding the thyroid gland. The present study aimed to evaluate the effect of a subchronic exposure to TBT on thyroid oxidative stress of female Wistar rats. Rats received vehicle (control group), 200 or 1000 ng TBT/kg body weight/day for 40 days. After euthanasia, one part of the thyroids were collected in order to assess iodide uptake; activity and/or mRNA expression of thyroperoxidase (TPO) and dual oxidases (DUOXs); activity and/or mRNA expression of catalase, glutathione peroxidase, superoxide dismutase and NADPH oxidase 4 (CAT, GPx, SOD and NOX4); 4-hydroxynonenal (4-HNE) expression and total thiol groups levels; and mRNA expression of estrogen receptors alpha and beta (ERα and ERβ). The remaining part of the thyroid was processed for morphological analysis of estrogen receptor alpha (ERα) and for collagen deposition. Iodide uptake was not changed with treatments. TPO activity and expression were increased in the TBT1000 group (259.81% and 95.17%). The activity, but not mRNA, of CAT (17.36% TBT200; 27.10% TBT1000) and GPx (29.24% TBT200; 28.97% TBT1000) were decreased by TBT. SOD and NADPH oxidase activity, as well as thiol group and 4-HNE levels remained unchanged. Interstitial collagen deposition increased in the TBT200 group (39.54%). The mRNA expression of ERα increased in TBT-treated rats (44.87% TBT200; 36.43% TBT1000), while protein expression was increased but not reaching significance (TBT1000, p = 0.056) by TBT. Therefore, our results show that TBT increases TPO expression and reduces antioxidant enzyme activities in the thyroid gland leading to oxidative stress. Some of these effects could be mediated by the ERα pathway., (Copyright © 2022 Elsevier B.V. All rights reserved.)
Published: 2022
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35. Exosomal glypican-1 discriminates pancreatic ductal adenocarcinoma from chronic pancreatitis.

Author: Moutinho-Ribeiro P, Adem B, Batista I, Silva M, Silva S, Ruivo CF, Morais R, Peixoto A, Coelho R, Costa-Moreira P, Lopes S, Vilas-Boas F, Durães C, Lopes J, Barroca H, Carneiro F, Melo SA, and Macedo G
Subjects: Biomarkers, Tumor, CA-19-9 Antigen, Diagnosis, Differential, Glypicans, Humans, Prospective Studies, Carcinoma, Pancreatic Ductal diagnosis, Carcinoma, Pancreatic Ductal pathology, Pancreatic Neoplasms diagnosis, Pancreatic Neoplasms pathology, Pancreatitis, Chronic diagnosis
Abstract: Background and Aims: Pancreatic ductal adenocarcinoma (PDAC) diagnosis can be difficult in a chronic pancreatitis (CP) background, especially in its mass forming presentation. We aimed to assess the accuracy of glypican-1-positive circulating exosomes (GPC1 + crExos) to distinguish PDAC from CP versus the state-of-the-art CA 19-9 biomarker., Methods: This was a unicentric prospective cohort. Endoscopic ultrasound with fine-needle aspiration or biopsy and blood tests (GPC1 + crExos and serum CA 19-9) were performed., Results: The cohort comprised 60 PDAC and 29 CP (7 of which mass forming - MF) patients. Median levels of GPC1 + crExos were significantly higher in PDAC (99.7%) versus CP (28.4%; p<0.0001) with an AUROC of 0.96 with 98.3% sensitivity and 86.2% specificity for a cut-off of 45.0% (p<0.0001); this outperforms CA 19-9 AUROC of 0.82 with 78.3% sensitivity and 65.5% specificity at a cut-off of 37 U/mL (p<0.0001). The superiority of% GPC1+crExos over CA 19-99 in differentiating PDAC from CP was observed in both early (stage I) and advanced tumors (stages II-IV)., Conclusion: Levels of GPC1 + crExos coupled to beads enable differential diagnosis between PDAC and CP including its mass-forming presentation., Competing Interests: Declaration of Competing Interest S. A. M. has ownership interests (patents). All other authors disclosed no potential conflicts of interest or financial relationships relevant to this publication., (Copyright © 2021. Published by Elsevier Ltd.)
Published: 2022
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36. Hereditary Leiomyomatosis and Renal Cell Cancer-Recognizing Patterns May Save Lives.

Author: Catarina T, Quental MS, Brandão JR, and Silva-Ramos M
Abstract: In 2001, Finish investigators described a rare familiar syndrome characterized by an inherited susceptibility to cutaneous leiomyomas, uterine leiomyomas, and renal cell carcinoma (RCC). Hereditary leiomyomatosis and renal cell cancer (HLRCC) is now linked to a germline mutation in the fumarate hydratase ( FH ) gene that encodes a Krebs cycle enzyme, transforming fumarate to malate. The accumulation of fumarate, an oncometabolite, promotes tumorigenesis. We present a case of a 41-year-old female diagnosed with HLRCC after a radical nephrectomy due to renal cell cancer. Genetic analyses confirmed a novel FH mutation. Close follow-up allowed for a precocious diagnosis of a metachronous renal tumor and later a hepatic metastasis. Her family was also counseled and offered genetic testing. As observed in this case, the diagnosis of HLRCC is of paramount importance for patients and their families: there is a 15% cumulative lifetime risk of developing RCC, which frequently occurs in young patients and metastasizes at an early stage. Implementing a regular follow-up with adequate imaging examinations may help save lives., Competing Interests: None, (Copyright: Tavares C, et al.)
Published: 2022
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37. Mechanobiology of Colorectal Cancer.

Author: Brás MM, Sousa SR, Carneiro F, Radmacher M, and Granja PL
Abstract: In this review, the mechanobiology of colorectal cancer (CRC) are discussed. Mechanotransduction of CRC is addressed considering the relationship of several biophysical cues and biochemical pathways. Mechanobiology is focused on considering how it may influence epithelial cells in terms of motility, morphometric changes, intravasation, circulation, extravasation, and metastization in CRC development. The roles of the tumor microenvironment, ECM, and stroma are also discussed, taking into account the influence of alterations and surface modifications on mechanical properties and their impact on epithelial cells and CRC progression. The role of cancer-associated fibroblasts and the impact of flow shear stress is addressed in terms of how it affects CRC metastization. Finally, some insights concerning how the knowledge of biophysical mechanisms may contribute to the development of new therapeutic strategies and targeting molecules and how mechanical changes of the microenvironment play a role in CRC disease are presented.
Published: 2022
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38. Multidimensional chromatin profiling of zebrafish pancreas to uncover and investigate disease-relevant enhancers.

Author: Bordeira-Carriço R, Teixeira J, Duque M, Galhardo M, Ribeiro D, Acemel RD, Firbas PN, Tena JJ, Eufrásio A, Marques J, Ferreira FJ, Freitas T, Carneiro F, Goméz-Skarmeta JL, and Bessa J
Subjects: Animals, Chromatin genetics, Genome-Wide Association Study, Pancreas, Enhancer Elements, Genetic genetics, Zebrafish genetics
Abstract: The pancreas is a central organ for human diseases. Most alleles uncovered by genome-wide association studies of pancreatic dysfunction traits overlap with non-coding sequences of DNA. Many contain epigenetic marks of cis-regulatory elements active in pancreatic cells, suggesting that alterations in these sequences contribute to pancreatic diseases. Animal models greatly help to understand the role of non-coding alterations in disease. However, interspecies identification of equivalent cis-regulatory elements faces fundamental challenges, including lack of sequence conservation. Here we combine epigenetic assays with reporter assays in zebrafish and human pancreatic cells to identify interspecies functionally equivalent cis-regulatory elements, regardless of sequence conservation. Among other potential disease-relevant enhancers, we identify a zebrafish ptf1a distal-enhancer whose deletion causes pancreatic agenesis, a phenotype previously found to be induced by mutations in a distal-enhancer of PTF1A in humans, further supporting the causality of this condition in vivo. This approach helps to uncover interspecies functionally equivalent cis-regulatory elements and their potential role in human disease., (© 2022. The Author(s).)
Published: 2022
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39. Subacute and low-dose tributyltin exposure disturbs the mammalian hypothalamus-pituitary-thyroid axis in a sex-dependent manner.

Author: Rodrigues-Pereira P, Andrade MN, Santos-Silva AP, Teixeira MP, Soares P, Graceli JB, de Carvalho DP, Dias GRM, Ferreira ACF, and Miranda-Alves L
Subjects: Animals, Female, Hypothalamus, Male, Mammals, Rats, Rats, Wistar, Trialkyltin Compounds, Hypothalamo-Hypophyseal System, Thyroid Gland
Abstract: Tributyltin (TBT) is an endocrine disruptor chemical (EDC) capable of altering the proper function of the hypothalamus-pituitary thyroid (HPT) axis. This study aimed to evaluate the subacute effects of TBT on the HPT axis of male and female rats. A dose of 100 ng/kg/day TBT was used in both sexes over a 15-day period, and the morphophysiology and gene expression of the HPT axis were assessed. TBT exposure increased the body weight in both sexes, while food efficiency increased - only in male rats. It was also possible to note alterations in the thyroid, with the presence of a stratified epithelium, cystic degeneration, and increased interstitial collagen deposition. A reduction in T3 and T4 levels was only observed in TBT male rats. A reduction in TSH levels was observed in TBT female rats. Evaluating mRNA expression, we observed a decrease in hepatic D1 and TRH mRNA levels in TBT female rats. An increase in D2 mRNA expression in the hypothalamus was observed in TBT male rats. Additionally, no significant changes in TRH or hepatic D1 mRNA expression in TBT male rats or in hypothalamic D1 and D2 mRNA expression in TBT female rats were observed. Thus, we can conclude that TBT has different toxicological effects on male and female rats by altering thyroid gland morphophysiology, leading to abnormal HPT axis function, and even at subacute and low doses, it may be involved in complex endocrine and metabolic disorders., (Copyright © 2022 Elsevier Inc. All rights reserved.)
Published: 2022
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40. Retrospective study of canine cutaneous tumors submitted to a diagnostic pathology laboratory in Northern Portugal (2014-2020).

Author: Martins AL, Canadas-Sousa A, Mesquita JR, Dias-Pereira P, Amorim I, and Gärtner F
Abstract: Background: Cutaneous neoplastic diseases are the most and second-most frequently reported tumors in male and female dogs, respectively. The aims of this study were to report the occurrence of canine cutaneous tumors in a pathology laboratory located in Northern Portugal between 2014 and 2020, and to characterize and categorize the anatomical locations, breed, age, and sex of the animals affected with different types of neoplasms., Results: Throughout the 7-year study, 1,185 cases were diagnosed as cutaneous tumors, with 62.9% being classified as benign, and 37.1% as malignant. Mast cell tumors (22.7%) were the most frequently diagnosed tumor type, followed by benign soft tissue tumors (9.7%), sebaceous gland tumors (8.1%), vascular tumors (7.9%) and soft tissue sarcomas (7.6%). Cutaneous tumors commonly exhibited multicentric occurrence (14.6%) followed by single occurrence in hindlimb (12.1%), forelimb (8.6%), buttock (7.1%), abdominal (6.5%) and costal (5.2%) areas. The odds of developing cutaneous neoplasia were higher with increasing age (p < 0.001). Females had an increased odds of developing skin tumors compared to males (crude OR = 2.99, 95% (2.51, 3.55); adj OR = 2.93, 95% (2.46, 3.49). Purebred dogs, as a group, showed a reduced odds of developing cutaneous tumors when compared to mixed-breed dogs (crude OR = 0.63, 95% (0.53, 0.74); adj OR = 0.75, 95% (0.62, 0.89)., Conclusions: Mast cell tumors, benign soft tissue tumors and sebaceous tumors were the most common histotypes encountered. The epidemiological survey achieved with this study demonstrates the relative frequency of different types of tumors in this particular population. Furthermore, the results herein achieved can act as a basis or a beneficial reference for local veterinarians helping in the establishment of a preliminary and presumptive diagnosis of canine cutaneous tumors histotypes. Skin tumors are the most and second-most frequently reported tumors in male and female dogs, respectively. The aim of this study was to report the occurrence of canine skin tumors in a diagnostic pathology laboratory located in Northern Portugal, between 2014-2020 and to characterize the anatomical distributions, breed, age, and sex of the animals affected by different skin tumors. During this period, 1,185 cases were diagnosed as skin tumors; 62.9% were diagnosed as benign, while 37.1% were malignant. Mast cell tumors (22.7%) were the most frequently diagnosed neoplasia, followed by benign soft tissue tumors (9.7%), sebaceous gland tumors (8.1%), vascular tumors (7.9%) and soft tissue sarcomas (7.6%). Skin tumors commonly developed in more than one location (14.6%) followed by solitary development in hindlimb (12.1%), forelimb (8.6%), buttock (7.1%), abdominal (6.5%) and costal (5.2%) areas. An increased odds of developing skin neoplasms as the patient's age increase was detected. Females showed an increased odds in comparison to male dogs. Purebred dogs presented decreased odds for developing skin tumors in comparison to mixed-breed dogs. The information relevance achieved with this study demonstrates the relative frequency of different types of tumors in this particular population, acting as a basis or a beneficial reference for regional veterinarians when providing an initial diagnosis of canine skin tumors., (© 2022. The Author(s).)
Published: 2022
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41. Recent insights into the use of immune checkpoint inhibitors in gastric cancer.

Author: Rodrigues S and Figueiredo C
Abstract: Gastric cancer (GC) is the fifth most incident and the fourth deadliest cancer worldwide. GC is a heterogeneous disease from the histological and molecular standpoints. This malignancy is mostly diagnosed at advanced stages of the disease, where the available therapeutic interventions are not effective. The emergence of immunotherapy has transformed the landscape of cancer treatment, including GC, and currently immune checkpoint inhibitors have been approved for the treatment of patients with recurrent/metastatic GC. This review summarizes the main clinical trials evaluating the use of immune checkpoint inhibitors in GC. It also highlights the potential of biomarkers for patient selection for GC immune checkpoint inhibition therapy, including programmed cell death ligand 1 expression and tumor mutational burden, and characteristics of the GC molecular classification, such as microsatellite instability status and Epstein-Barr virus infection, as predictors of response to blockade of the programmed cell death 1/programmed cell death ligand 1 axis., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of PBJ-Associação Porto Biomedical/Porto Biomedical Society. All rights reserved.)
Published: 2022
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42. Helicobacter species binding to the human gastric mucosa.

Author: Matos R, Sousa HS, Nogueiro J, Magalhães A, Reis CA, Carneiro F, Amorim I, Haesebrouck F, and Gärtner F
Subjects: Animals, Gastric Mucosa, Humans, Gastritis, Helicobacter, Helicobacter Infections, Helicobacter pylori
Abstract: Helicobacter pylori infects half of the world population, being associated with several gastric disorders, such as chronic gastritis and gastric carcinoma. The Helicobacter genus also includes other gastric helicobacters, such as H. heilmannii¸ H. ailurogastricus, H. suis, H. felis, H. bizzozeronii, and H. salomonis. These gastric helicobacters colonize both the human and animal stomach. The prevalence of gastric non-Helicobacter pylori Helicobacter (NHPH) species in humans has been described as low, and the in vitro binding to the human gastric mucosa was never assessed. Herein, human gastric tissue sections were used for the evaluation of the tissue glycophenotype and for the binding of gastric NHPH strains belonging to different species. Histopathological evaluation showed that 37.5% of the patients enrolled in our cohort presented chronic gastritis, while the presence of neutrophil or eosinophilic activity (chronic active gastritis) was observed in 62.5% of the patients. The secretor phenotype was observed in 68.8% of the individuals, based on the expression of Lewis B antigen and binding of the UleX lectin. The in vitro binding assay showed that all the NHPH strains evaluated were able to bind, albeit in low frequency, to the human gastric mucosa. The H. heilmannii, H. bizzozeronii, and H. salomonis strains displayed the highest binding ability both to the gastric superficial epithelium and to the deep glands. Interestingly, we observed binding of NHPH to the gastric mucosa of individuals with severe chronic inflammation and intestinal metaplasia, suggesting that NHPH binding may not be restricted to the healthy gastric mucosa or slight chronic gastritis. Furthermore, the in vitro binding of NHPH strains was observed both in secretor and non-secretor individuals in a similar frequency. In conclusion, this study is the first report of the in vitro binding ability of gastric NHPH species to the human gastric mucosa. The results suggest that other glycans, besides the Lewis antigens, could be involved in the bacterial adhesion mechanism; however, the molecular intervenients remain unknown., (© 2021 John Wiley & Sons Ltd.)
Published: 2022
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43. Clinical utility of TGFB1 and its receptors ( TGFBR1 and TGFBR2 ) in thyroid nodules: evaluation based on single nucleotide polymorphisms and mRNA analysis.

Author: Peres KC, Teodoro L, Amaral LHP, Teixeira ES, Barreto IS, de Freitas LLL, Maximo V, Assumpção LVM, Bufalo NE, and Ward LS
Subjects: Humans, Polymorphism, Single Nucleotide, RNA, Messenger genetics, Thyroid Neoplasms, Tumor Microenvironment, Receptor, Transforming Growth Factor-beta Type I genetics, Receptor, Transforming Growth Factor-beta Type II genetics, Thyroid Nodule genetics, Transforming Growth Factor beta1 genetics
Abstract: Objective: Abnormalities involving the TGFB1 gene and its receptors are common in several types of cancer and often related to tumor progression. We investigated the role of single nucleotide polymorphisms (SNP) in the susceptibility to cancer, their impact on its features, as well as the role of mRNA expression of these genes in thyroid malignancy., Methods: We genotyped TGFB1 , TGFBR1 , and TGFBR2 SNPs in 157 papillary thyroid cancer (PTC) patients and 200 healthy controls. Further, we investigated RNA samples of 47 PTC and 80 benign nodules, searching for differential mRNA expression., Results: SNPs rs1800472 and rs1800469 were associated with characteristics of PTC aggressiveness. Effect predictor software analysis of nonsynonymous SNP rs1800472 indicated increasing protein stability and post-translational changes. TGFB1 mRNA expression was upregulated in PTC and downregulated in benign samples, differentiating malignant from benign nodules (p<0.0001); PTC from goiter (p<0.0001); and PTC from FA (p<0.0001). TGFBR1 mRNA expression was upregulated in goiter and PTC, but downregulated in FA, distinguishing PTC from goiter (p=0.0049); PTC from FA (p<0.0001); and goiter from FA (p=0.0267). On the other hand, TGFBR2 was downregulated in all histological types analyzed and was not able to differentiate thyroid nodules., Conclusion: TGFB1 polymorphism rs1800472 may confer greater activity to TGF-β1 in the tumor microenvironment, favoring PTC aggressiveness. Evaluation of TGFB1 and TGFBR1 mRNA levels may be useful to identify malignancy in thyroid nodules.
Published: 2021
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44. Influence of PICALM and CLU risk variants on beta EEG activity in Alzheimer's disease patients.

Author: Maturana-Candelas A, Gómez C, Poza J, Rodríguez-González V, Pablo VG, Lopes AM, Pinto N, and Hornero R
Subjects: Aged, Aged, 80 and over, Alzheimer Disease physiopathology, Brain, Female, Genetic Predisposition to Disease, Genotype, Humans, Male, Alzheimer Disease genetics, Clusterin genetics, Electroencephalography, Monomeric Clathrin Assembly Proteins genetics
Abstract: PICALM and CLU genes have been linked to alterations in brain biochemical processes that may have an impact on Alzheimer's disease (AD) development and neurophysiological dynamics. The aim of this study is to analyze the relationship between the electroencephalographic (EEG) activity and the PICALM and CLU alleles described as conferring risk or protective effects on AD patients and healthy controls. For this purpose, EEG activity was acquired from: 18 AD patients and 12 controls carrying risk alleles of both PICALM and CLU genes, and 35 AD patients and 12 controls carrying both protective alleles. Relative power (RP) in the conventional EEG frequency bands (delta, theta, alpha, beta, and gamma) was computed to quantify the brain activity at source level. In addition, spatial entropy (SE) was calculated in each band to characterize the regional distribution of the RP values throughout the brain. Statistically significant differences in global RP and SE at beta band (p-values < 0.05, Mann-Whitney U-test) were found between genotypes in the AD group. Furthermore, RP showed statistically significant differences in 58 cortical regions out of the 68 analyzed in AD. No statistically significant differences were found in the control group at any frequency band. Our results suggest that PICALM and CLU AD-inducing genotypes are involved in physiological processes related to disruption in beta power, which may be associated with physiological disturbances such as alterations in beta-amyloid and neurotransmitter metabolism., (© 2021. The Author(s).)
Published: 2021
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45. Risk Factors for Breast Cancer, Overall and by Tumor Subtype, among Women from Mozambique, Sub-Saharan Africa.

Author: Brandão M, Guisseve A, Damasceno A, Bata G, Silva-Matos C, Alberto M, Ferro J, Garcia C, Zaqueu C, Lorenzoni C, Leitão D, Soares O, Gudo-Morais A, Schmitt F, Morais S, Tulsidás S, Carrilho C, and Lunet N
Subjects: Adult, Aged, Aged, 80 and over, Biopsy, Fine-Needle, Body Mass Index, Breast Neoplasms diagnosis, Breast Neoplasms pathology, Case-Control Studies, Educational Status, Female, Humans, Incidence, Middle Aged, Mozambique epidemiology, Prevalence, Risk Assessment statistics & numerical data, Risk Factors, Young Adult, Breast pathology, Breast Neoplasms epidemiology, Obesity epidemiology
Abstract: Background: Breast cancer incidence is rising in Africa, but there are scare data regarding risk factors in this region. We assessed the relation between risk factors and the occurrence of breast cancer, overall and by tumor subtype in women from Mozambique., Methods: The associations between education, number of births, height, weight, body mass index (BMI), and breast cancer risk among 138 cases (participants from the Moza-BC cohort) and 638 controls from the general population (from a World Health Organization stepwise approach to surveillance survey), recruited during 2014 to 2017, were investigated. Adjusted ORs (aOR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression., Results: Multiparity (≥6 vs. 0-1 live births) was a protective factor for the development of hormone receptor (HR)-positive (aOR = 0.22; 95% CI, 0.08-0.64) and HR-positive/HER2-negative tumors (aOR = 0.20; 95% CI, 0.06-0.68), whereas a higher educational level (≥8 vs. 0 schooling years) increased breast cancer risk across all subtypes (overall aOR = 1.98; 95% CI, 1.04-3.80). Higher weight and BMI were associated with a higher breast cancer risk among postmenopausal women (per 1-kg increase: aOR = 1.05; 95% CI, 1.02-1.08; per 1-kg/m 2 increase: aOR = 1.11; 95% CI, 1.04-1.18, respectively), but were protective in premenopausal women (aOR = 0.98; 95% CI, 0.96-0.99; aOR = 0.95; 95% CI, 0.91-0.99, respectively), regardless of subtype. Higher height increased the risk of HR-negative tumors in postmenopause (per 10-cm increase: aOR = 2.81; 95% CI, 1.41-6.03)., Conclusion: These results demonstrate the etiological heterogeneity of breast cancer among native African women, namely regarding the differential effect of multiparity, education, and body parameters in breast cancer risk., Impact: As the prevalence of obesity grows, these findings are important to inform public health policies on cancer prevention, by highlighting obesity as a modifiable risk factor for breast cancer among African women., (©2021 American Association for Cancer Research.)
Published: 2021
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46. Adhesion of Helicobacter Species to the Human Gastric Mucosa: A Deep Look Into Glycans Role.

Author: Matos R, Amorim I, Magalhães A, Haesebrouck F, Gärtner F, and Reis CA
Abstract: Helicobacter species infections may be associated with the development of gastric disorders, such as gastritis, peptic ulcers, intestinal metaplasia, dysplasia and gastric carcinoma. Binding of these bacteria to the gastric mucosa occurs through the recognition of specific glycan receptors expressed by the host epithelial cells. This review addresses the state of the art knowledge on these host glycan structures and the bacterial adhesins involved in Helicobacter spp. adhesion to gastric mucosa colonization. Glycans are expressed on every cell surface and they are crucial for several biological processes, including protein folding, cell signaling and recognition, and host-pathogen interactions. Helicobacter pylori is the most predominant gastric Helicobacter species in humans. The adhesion of this bacterium to glycan epitopes present on the gastric epithelial surface is a crucial step for a successful colonization. Major adhesins essential for colonization and infection are the blood-group antigen-binding adhesin (BabA) which mediates the interaction with fucosylated H-type 1 and Lewis B glycans, and the sialic acid-binding adhesin (SabA) which recognizes the sialyl-Lewis A and X glycan antigens. Since not every H. pylori strain expresses functional BabA or SabA adhesins, other bacterial proteins are most probably also involved in this adhesion process, including LabA (LacdiNAc-binding adhesin), which binds to the LacdiNAc motif on MUC5AC mucin. Besides H. pylori, several other gastric non- Helicobacter pylori Helicobacter s (NHPH), mainly associated with pigs ( H. suis ) and pets ( H. felis , H. bizzozeronii, H. salomonis, and H. heilmannii ) , may also colonize the human stomach and cause gastric disease, including gastritis, peptic ulcers and mucosa-associated lymphoid tissue (MALT) lymphoma. These NHPH lack homologous to the major known adhesins involved in colonization of the human stomach. In humans, NHPH infection rate is much lower than in the natural hosts. Differences in the glycosylation profile between gastric human and animal mucins acting as glycan receptors for NHPH-associated adhesins, may be involved. The identification and characterization of the key molecules involved in the adhesion of gastric Helicobacter species to the gastric mucosa is important to understand the colonization and infection strategies displayed by different members of this genus., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Matos, Amorim, Magalhães, Haesebrouck, Gärtner and Reis.)
Published: 2021
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47. African genetic diversity and adaptation inform a precision medicine agenda.

Author: Pereira L, Mutesa L, Tindana P, and Ramsay M
Subjects: Genetic Predisposition to Disease, Genetic Variation, Genetics, Population, Humans, Black People genetics, Evolution, Molecular, Precision Medicine
Abstract: The deep evolutionary history of African populations, since the emergence of modern humans more than 300,000 years ago, has resulted in high genetic diversity and considerable population structure. Selected genetic variants have increased in frequency due to environmental adaptation, but recent exposures to novel pathogens and changes in lifestyle render some of them with properties leading to present health liabilities. The unique discoverability potential from African genomic studies promises invaluable contributions to understanding the genomic and molecular basis of health and disease. Globally, African populations are understudied, and precision medicine approaches are largely based on data from European and Asian-ancestry populations, which limits the transferability of findings to the continent of Africa. Africa needs innovative precision medicine solutions based on African data that use knowledge and implementation strategies aligned to its climatic, cultural, economic and genomic diversity.
Published: 2021
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48. Heparan Sulfate Glycosaminoglycans: (Un)Expected Allies in Cancer Clinical Management.

Author: Faria-Ramos I, Poças J, Marques C, Santos-Antunes J, Macedo G, Reis CA, and Magalhães A
Subjects: Animals, Biomarkers, Tumor, Cell Differentiation, Cell Membrane metabolism, Cell Proliferation, Extracellular Matrix metabolism, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Heparitin Sulfate metabolism, Humans, Ligands, Mice, Neoplasm Invasiveness, Neoplasm Metastasis, Neovascularization, Pathologic metabolism, Signal Transduction, Glycosaminoglycans chemistry, Heparitin Sulfate chemistry, Neoplasms metabolism, Neoplasms therapy
Abstract: In an era when cancer glycobiology research is exponentially growing, we are witnessing a progressive translation of the major scientific findings to the clinical practice with the overarching aim of improving cancer patients' management. Many mechanistic cell biology studies have demonstrated that heparan sulfate (HS) glycosaminoglycans are key molecules responsible for several molecular and biochemical processes, impacting extracellular matrix properties and cellular functions. HS can interact with a myriad of different ligands, and therefore, hold a pleiotropic role in regulating the activity of important cellular receptors and downstream signalling pathways. The aberrant expression of HS glycan chains in tumours determines main malignant features, such as cancer cell proliferation, angiogenesis, invasion and metastasis. In this review, we devote particular attention to HS biological activities, its expression profile and modulation in cancer. Moreover, we highlight HS clinical potential to improve both diagnosis and prognosis of cancer, either as HS-based biomarkers or as therapeutic targets.
Published: 2021
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49. Review of the current information on erectile dysfunction in hypertensive males with 40 years of age or older.

Author: Teixeira E and Soares P
Abstract: Hypertension (HT) is a prevalent disease, which origin frequently remains undetermined. Antihypertensive treatment (AHT) has been linked with erectile dysfunction (ED), mainly in middle-aged and older males. On the other side, some drugs used in AHT seem to be themselves associated with ED as a secondary effect. This led to the search of coadjuvant therapies for hypertensive patients with ED, considering that both illnesses cause high physical, psychological and economic burden. While the association between AHT and ED has been approached several times, the direct association between blood pressure and ED remains unclear. This review aims to summarize the current knowledge on the relationship between HT, AHT and ED specifically in males with age ≥40 years., Competing Interests: Authors have declared no conflict of interest., (Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of PBJ-Associação Porto Biomedical/Porto Biomedical Society. All rights reserved.)
Published: 2020
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50. Molecular Aspects of Thyroid Calcification.

Author: Ferreira LB, Gimba E, Vinagre J, Sobrinho-Simões M, and Soares P
Subjects: Animals, Calcification, Physiologic, Humans, Models, Biological, Osteopontin metabolism, Thyroid Neoplasms pathology, Calcinosis genetics, Thyroid Gland pathology
Abstract: In thyroid cancer, calcification is mainly present in classical papillary thyroid carcinoma (PTC) and in medullary thyroid carcinoma (MTC), despite being described in benign lesions and in other subtypes of thyroid carcinomas. Thyroid calcifications are classified according to their diameter and location. At ultrasonography, microcalcifications appear as hyperechoic spots ≤ 1 mm in diameter and can be named as stromal calcification, bone formation, or psammoma bodies (PBs), whereas calcifications > 1 mm are macrocalcifications. The mechanism of their formation is still poorly understood. Microcalcifications are generally accepted as a reliable indicator of malignancy as they mostly represent PBs. In order to progress in terms of the understanding of the mechanisms behind calcification occurring in thyroid tumors in general, and in PTC in particular, we decided to use histopathology as the basis of the possible cellular and molecular mechanisms of calcification formation in thyroid cancer. We explored the involvement of molecules such as runt-related transcription factor-2 (Runx-2), osteonectin/secreted protein acidic and rich in cysteine (SPARC), alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteopontin (OPN) in the formation of calcification. The present review offers a novel insight into the mechanisms underlying the development of calcification in thyroid cancer.
Published: 2020
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