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2. Combining germline, tissue and liquid biopsy analysis by comprehensive genomic profiling to improve the yield of actionable variants in a real-world cancer cohort

Author

Vanni, I., Pastorino, L., Andreotti, V., Comandini, D., Fornarini, G., Grassi, M., Puccini, A., Tanda, E. T., Pastorino, A., Martelli, V., Mastracci, L., Grillo, F., Cabiddu, F., Guadagno, A., Coco, S., Allavena, E., Barbero, F., Bruno, W., Dalmasso, B., Bellomo, S. E., Marchiò, C., Spagnolo, F., Sciallero, S., Berrino, E., and Ghiorzo, P.

Published
2024
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5. Long Covid: a global health issue – a prospective, cohort study set in four continents

Author

Synne Jenum, Renaud Tamisier, Clark D Russell, Rachel Evans, Piero Valentini, Sylvain Diamantis, Dominique Deplanque, Jordi Rello, Agnes Meybeck, Maxime Hentzien, Clotilde Allavena, André Cabié, Firouzé Bani-Sadr, Patrick Rossignol, Lionel Piroth, Mathieu Blot, Marie-Pierre Debray, François Angoulvant, Marc Leone, Ewen M Harrison, Maria Zambon, Michael Edelstein, Florentia Kaguelidou, Marc Lambert, Olivier Lairez, Tom Solomon, Carrol Gamble, Laura Marsh, Christiana Kartsonaki, Natalie Wright, Behzad Nadjm, Srinivas Murthy, Gail Carson, Jake Dunning, Laura Merson, Peter Horby, Timothy M Uyeki, Piero Olliaro, Guillermo Maestro de la Calle, Stephen R Knight, Thomas M Drake, Marlene Murris, Aurore Bousquet, Kenneth A McLean, Hugues Cordel, Marc Fabre, Laurence Bouillet, Katrina Hann, Xavier Duval, James Lee, Christian Rabaud, Paul Klenerman, Jean-Christophe Lucet, Jean-François Timsit, Jennifer Lee, David J Lowe, Nicolas Terzi, Saad Nseir, Gwenhaël Colin, Steve Webb, Kalynn Kennon, Caroline Mudara, Diana Hernández, Yazdan Yazdanpanah, Jean-François Payen, Samreen Ijaz, Joanne McPeake, Meera Chand, Catherine A Shaw, Cameron J Fairfield, Bruno Levy, Eric D'ortenzio, Pierre Delobel, Tiphaine Goulenok, Bronner P Gonçalves, Arnaud Scherpereel, Danilo Buonsenso, Mark G Pritchard, Susanne Dudman, Adrien Auvet, Caterina Caminiti, Debby Bogaert, Elisabeth Botelho-Nevers, Amandine Gagneux-Brunon, Merce Jourdain, Sue Smith, Jia Wei, Antoine Khalil, Clément Le Bihan, Nathalie Pansu, Vincent Le Moing, Victor Fomin, Christophe Fraser, Daniel Munblit, William Greenhalf, François-Xavier Lescure, Nicolas Carlier, Saye Khoo, Annemarie B Docherty, Christopher A Green, Riinu Pius, Louise Sigfrid, Sophie Halpin, Clare Jackson, Antonia Ho, Malcolm G Semple, Andrew Dagens, Carlo Palmieri, Lance Turtle, Zeno Bisoffi, Thomas Flament, Julie Mankikian, Romain Basmaci, Peter Openshaw, Rob Fowler, Tom Fletcher, Adrien Lemaignen, Pierre Tattevin, Christelle Delmas, Hélène Espérou, Claire Lévy-Marchal, Olivier Picone, Jeanne Sibiude, Cecile Yelnik, Michelle Girvan, Piero L Olliaro, Beatrice Alex, Benjamin Bach, Wendy S Barclay, Graham S Cooke, Ana da Silva Filipe, Alexander J Mentzer, Alison M Meynert, Mahdad Noursadeghi, Shona C Moore, Massimo Palmarini, William A Paxton, Georgios Pollakis, David L Robertson, Vanessa Sancho-Shimizu, Janet T Scott, Shiranee Sriskandan, David Stuart, Charlotte Summers, Emma C Thomson, Ryan S Thwaites, Lance C W Turtle, Hayley Hardwick, Wilna Oosthuyzen, Fiona Griffiths, Jo Dalton, Egle Saviciute, Stephanie Roberts, Janet Harrison, Marie Connor, Gary Leeming, Ross Hendry, Victoria Shaw, Jade Ghosn, Lucille Blumberg, Nicolas Benech, Odile Launay, Yoan Lavie-Badie, Minh Le, Elise Artaud-Macari, Muge Cevik, Nicola Latronico, Mylène Maillet, Didier Laureillard, Ben Morton, Claire Hastie, Nicholas Sedillot, Anne-Sophie Boureau, Laurent Abel, Guillaume Martin-Blondel, Valérie Garrait, Isabelle Delacroix, Andrea Cortegiani, Jean-Benoît Arlet, Raphaël Borie, Kévin Bouiller, Vincent Langlois, Mélanie Roriz, Vincent Dubée, John H Amuasi, Madiha Hashmi, Edwin Jesudason, Jan Cato Holter, Anders Benjamin Kildal, Luis Felipe Reyes, Anna Beltrame, Sulaiman Lakoh, Stéphanie Fry, Lynsey Goodwin, Laurent Plantier, Anna Casey, Denis Malvy, Nina Jamieson, François Dubos, Jean-Sébastien Hulot, Paola Rodari, Frank Bloos, Cécile Tromeur, Paul Loubet, Marina Esposito-Farèse, France Mentré, Valérie Gaborieau, Cécile Goujard, Vincent Thibault, Adam Ali, Sadie Kelly, Fernando A Bozza, Bertrand Dussol, Marion Schneider, Marielle Buisson, Yves Levy, Carine Roy, Walter Picard, Olivier Sanchez, Nazir Lone, Antoine Kimmoun, Roberto Roncon-Albuquerque, Nathan Peiffer-Smadja, Julien Poissy, Lila Bouadma, Bruno Lina, Maude Bouscambert, Alexandre Gaymard, Gilles Peytavin, Jeremie Guedj, Claire Andrejak, Cedric Laouenan, Anissa Chair, Samira Laribi, Marie-Capucine Tellier, Sandrine Couffin-Cadiergues, Ventzislava Petrov-Sanchez, Alpha Diallo, Sarah Tubiana, Patrick Imbert, Emmanuelle Mercier, Waasila Jassat, Arsene Kpangon, Dominique Luton, Simone Piva, Sophie Mahy, Pierre-Adrien Bolze, Sarah Moore, Raphael Favory, Andrea Angheben, Andrea Rossanese, Matthew Hall, Johann Auchabie, Christophe Rapp, Vincent Peigne, Fredrik Müller, Christl A Donnelly, François Goehringer, Elodie Curlier, Catherine Chirouze, Vegard Skogen, Stéphane Jaureguiberry, Laurent Bitker, Hodane Yonis, Laurent Mandelbrot, Jérémie Pasquier, Bato Hammarström, Thushan de Silva, Polina Bugaeva, Julie Chas, Dario Sinatti, Arne Søraas, Murray Wham, Sara Clohisey, Seán Keating, Thibault Chiarabini, Agnes Sommet, Hugues Aumaître, Charlotte Charpentier, Sylvie LeGac, Sarah E McDonald, Jeanne Truong, Anne-Hélène Boivin, Mariachiara Ippolito, Ellen Pauley, Diane Descamps, Sérgio Gaião, Stéphane Lasry, Amanda Rojek, Charlotte Salmon Gandonniere, Sebastien Preau, Benoit Thill, Karine Faure, Denis Garot, Grégory Corvaisier, Elsa Nyamankolly, Merete Ellingjord-Dale, Eva Geraud, Barbara Wanjiru Citarella, Kévin Alexandre, Nathalie Allou, Séverine Ansart, Laurène Azemar, Cecile Azoulay, Delphine Bachelet, Claudine Badr, Valeria Balan, Marie Bartoli, Joaquín Baruch, Jules Bauer, Alexandra Bedossa, Husna Begum, Marine Beluze, Delphine Bergeaud, Giulia Bertoli, Simon Bessis, Sybille Bevilcaqua, Karine Bezulier, Krishna Bhavsar, Laetitia Bodenes, Isabela Bolaños, Olivier Bouchaud, Sabelline Bouchez, Camile Bouisse, Marielle Boyer-Besseyre, Axelle Braconnier, Ingrid G Bustos, Denis Butnaru, Eder Caceres, Cyril Cadoz, Valentine Campana, Pauline Caraux-Paz, Thierry Carmoi, Marie-Christine Carret, Maire-Laure Casanova, Guylaine Castor-Alexandre, François-Xavier Catherine, Minerva Cervantes-Gonzalez, Catherine Chakveatze, Jean-Marc Chapplain, Antoine Cheret, Bernard Cholley, Marie-Charlotte Chopin, Roxane Courtois, Stéphanie Cousse, Alexa Debard, Nathalie DeCastro, Romain Decours, Eve Defous, Karen Delavigne, Elisa Demonchy, Emmanuelle Denis, Mathilde Desvallées, Kévin Didier, Jean-Luc Diehl, Vincent Dinot, Fara Diop, Alphonsine Diouf, Félix Djossou, Céline Dorival, Nathalie Dournon, Murray Dryden, Alexandre Ducancelle, Paul Dunand, Brigitte Elharrar, Philippine Eloy, Isabelle Enderle, Ilka Engelmann, Vincent Enouf, Olivier Epaulard, Manuel Etienne, Isabelle Fabre, François-Xavier Ferrand, Eglantine Ferrand Devouge, Nicolas Ferriere, Céline Ficko, Erwan Fourn, Rostane Gaci, Jean-Charles Gagnard, Esteban Garcia-Gallo, Tristan Gigante, Guillermo Giordano, Valérie Gissot, Petr Glybochko, Marie Gominet, Isabelle Gorenne, Laure Goubert, Pascal Granier, Segolène Greffe, Martin Guego, Romain Guery, Anne Guillaumot, Laurent Guilleminault, Thomas Guimard, Ali Hachemi, Nadir Hadri, Rebecca Hamidfar, Lars Heggelund, Rupert Higgins, Hikombo Hitoto, Alexandre Hoctin, Isabelle Hoffmann, Ikram Houas, Margaux Isnard, Danielle Jaafar, Salma Jaafoura, Julien Jabot, Florence Jego, Cédric Joseph, Ouifiya Kafif, Sabina Kali, Younes Kerroumi, Marie Lachatre, Marie Lacoste, Marie Lagrange, Fabrice Laine, Antonio Lalueza, Marie Langelot-Richard, Delphine Lariviere, Andy Law, Laurent Lefebvre, Bénédicte Lefebvre, Benjamin Lefèvre, Jean-Daniel Lelievre, Véronique Lemee, Anthony Lemeur, Quentin Lepiller, Olivier Lesens, Mathieu Lesouhaitier, Geoffrey Liegeon, Guillaume Lingas, Sylvie Lion-Daolio, Marine Livrozet, Bouchra Loufti, Guillame Louis, Liem Luong, Moïse Machado, Gabriel Macheda, Rafael Mahieu, Thomas Maitre, Victoria Manda, Aldric Manuel, Samuel Markowicz, Martin Martinot, Mathieu Mattei, Laurence Maulin, Thierry Mazzoni, Cécile Mear-Passard, Antoine Merckx, Mayka Mergeay-Fabre, Vanina Meysonnier, Mehdi Mezidi, Isabelle Michelet, Lucia Moro, Julien Moyet, Jimmy Mullaert, Nadège Neant, Nikita Nekliudov, Anthony Nghi, Duc Nguyen, Nadia Ouamara, Rachida Ouissa, Eric Oziol, Justine Pages Maïder Pagadoy, Aurélie Papadopoulos, Bruno Pastene, Christelle Paul, Florent Peelman, Daniel Perez, Thomas Perpoint, Vincent Pestre, Ryadh Pokeerbux, Diane Ponscarme, Marie Rafiq, Blandine Rammaert, Stanislas Rebaudet, Sarah Redl, Anne-Sophie Resseguier, Matthieu Revest, Laurent Richier, Patrick Rispal, Karine Risso, Olivier Robineau, Manuel Rosa-Calatrava, Benoît Roze, Hélène Salvator, Pierre-François Sandrine, Benjamine Sarton, Eric Senneville, Albert Sotto, Sarah Stabler, Andrey Svistunov, Coralie Tardivon, François Téoulé, Olivier Terrier, Simon-Djamel Thiberville, Peter S Timashev, Noémie Tissot, Tiffany Trouillon, Christelle Tual, Noémie Vanel, Charline Vauchy, Aurélie Veislinger, Fanny Vuotto, Aurélie Wiedemann, Marion Zabbe, David Zucman, Silvio Hamacher, Ekaterina Pazukhina, Allegra Chatterjee, Kyle Gomez, Matteo Puntoni, Oksana Kruglova, Yock Ping Chow, Yash Doshi, Sara Isabel Duque Vallejo, Elsa D Ibáñez-Prada, Yuli V Fuentes, Margaret E O'Hara, Tigist Menkir, Amal Abrous, Younes Ait Tamlihat, Aliya Mohammed Alameen, Marta Alessi, Kazali Enagnon Alidjnou, Jean Baptiste Assie, Eyvind W Axelsen, John Kenneth Baillie, José Luis Bernal Sobrino, Sonja Hjellegjerde Brunvoll, Roar Bævre-Jensen, Jose Andres Calvache, Léo Chenard, Juan Luis Cruz Bermúdez, Jaime Cruz Rojo, Charlene Da Silveira, John Arne Dahl, Etienne De Montmollin, Cristina De Rose, Fernanda Dias Da Silva, Thomas Drake, Amiel A Dror, Anne Margarita Dyrhol-Riise, Linn Margrete Eggesbø, Mohammed El Sanharawi, William Finlayson, Aline-Marie Florence, Linda Gail Skeie, Noelia García Barrio, Anatoliy Gavrylov, Louis Gerbaud Morlaes, Yanay Gorelik, Mette Stausland Istre, Silje Bakken Jørgensen, Karl Trygve Kalleberg, Beathe Kiland Granerud, Eyrun Floerecke Kjetland Kjetland, Gry Kloumann Bekken, Galyna Kutsyna, Nadhem Lafhej, Cyril Le Bris, Georges Le Falher, Lucie Le Fevre, Quentin Le Hingrat, Marion Le Maréchal, Soizic Le Mestre, Gwenaël Le Moal, Hervé Le Nagard, Sophie Letrou, Wei Shen Lim, Andreas Lind, Carlos Lumbreras Bermejo, Miles Lunn, Olga Martynenko, Roberta Meta, Lina Morales Cely, Clara Mouton Perrot, Alamin Mustafa, Karl Erik Müller, Ebrahim Ndure, Anders Benteson Nygaard, Claudia Milena Orozco-Chamorro, Paul Otiku, Miguel Pedrera Jiménez, Frank Olav Pettersen, Chiara Piubelli, Víctor Quirós González, Else Quist-Paulsen, Dag Henrik Reikvam, Antonia Ricchiuto, Aleksander Rygh Holten, Nadia Saidani, Pablo Serrano Balazote, Nassima Si Mohammed, Lene Bergendal Solberg, Edouard Soum, Elisabetta Spinuzza, Trude Steinsvik, Birgitte Stiksrud, Mathew Thorpe, Vadim Tieroshyn, Kristian Tonby, Anders Tveita, Sylvie Van Der Werf, Paul Henri Wicky, Ibrahim Richard Bangura, Leonardo Bastos, Daniel Cassaglia, Barbara Citarella, Sarah Duque, Anne Margarita Dyrhol Riise, Annelies Gillesen, Bronner P Goncalvez, Margareta O’Hara, Lars Hegelund, Aquiles Henriquez Trujillo, Elsa D Ibañez, Jane Ireson, Oksana Krugalova, Sam Lissaeur, Sinnadurai Manohan, Prasan K Panda, Daniel R Plotkin, Liliana Resende, Sergio Ruiz Saltana, Steffi Ryckaert, Girish Sindhwani Pulm, and Caroline Vika

Subjects
Medicine (General), R5-920, Infectious and parasitic diseases, RC109-216
Abstract

Introduction A proportion of people develop Long Covid after acute COVID-19, but with most studies concentrated in high-income countries (HICs), the global burden is largely unknown. Our study aims to characterise long-term COVID-19 sequelae in populations globally and compare the prevalence of reported symptoms in HICs and low-income and middle-income countries (LMICs).Methods A prospective, observational study in 17 countries in Africa, Asia, Europe and South America, including adults with confirmed COVID-19 assessed at 2 to

Published
2024
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6. Combining germline, tissue and liquid biopsy analysis by comprehensive genomic profiling to improve the yield of actionable variants in a real-world cancer cohort

Author

I. Vanni, L. Pastorino, V. Andreotti, D. Comandini, G. Fornarini, M. Grassi, A. Puccini, E. T. Tanda, A. Pastorino, V. Martelli, L. Mastracci, F. Grillo, F. Cabiddu, A. Guadagno, S. Coco, E. Allavena, F. Barbero, W. Bruno, B. Dalmasso, S. E. Bellomo, C. Marchiò, F. Spagnolo, S. Sciallero, E. Berrino, and P. Ghiorzo

Subjects
Next-generation sequencing, Circulating cell-free DNA, Germline pathogenic variants, Droplet digital pcr (ddPCR), Targeted therapy, Clinically actionable variants, Medicine
Abstract

Abstract Background Comprehensive next-generation sequencing is widely used for precision oncology and precision prevention approaches. We aimed to determine the yield of actionable gene variants, the capacity to uncover hereditary predisposition and liquid biopsy appropriateness instead of, or in addition to, tumor tissue analysis, in a real-world cohort of cancer patients, who may benefit the most from comprehensive genomic profiling. Methods Seventy-eight matched germline/tumor tissue/liquid biopsy DNA and RNA samples were profiled using the Hereditary Cancer Panel (germline) and the TruSight Oncology 500 panel (tumor tissue/cfDNA) from 23 patients consecutively enrolled at our center according to at least one of the following criteria: no available therapeutic options; long responding patients potentially fit for other therapies; rare tumor; suspected hereditary cancer; primary cancer with high metastatic potential; tumor of unknown primary origin. Variants were annotated for OncoKB and AMP/ASCO/CAP classification. Results The overall yield of actionable somatic and germline variants was 57% (13/23 patients), and 43.5%, excluding variants previously identified by somatic or germline routine testing. The accuracy of tumor/cfDNA germline-focused analysis was demonstrated by overlapping results of germline testing. Five germline variants in BRCA1, VHL, CHEK1, ATM genes would have been missed without extended genomic profiling. A previously undetected BRAF p.V600E mutation was emblematic of the clinical utility of this approach in a patient with a liver undifferentiated embryonal sarcoma responsive to BRAF/MEK inhibition. Conclusions Our study confirms the clinical relevance of performing extended parallel tumor DNA and cfDNA testing to broaden therapeutic options, to longitudinally monitor cfDNA during patient treatment, and to uncover possible hereditary predisposition following tumor sequencing in patient care.

Published
2024
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7. Immune profiles of pre-frail people living with HIV-1: a prospective longitudinal study

Author

Lucy Kundura, Renaud Cezar, Sandrine Gimenez, Manuela Pastore, Christelle Reynes, Albert Sotto, Jacques Reynes, Clotilde Allavena, Laurence Meyer, Alain Makinson, and Pierre Corbeau

Subjects
Immunologic diseases. Allergy, RC581-607, Geriatrics, RC952-954.6
Abstract

Abstract Background People living with HIV (PLWH) are at risk of frailty, which is predictive for death. As an overactivity of the immune system is thought to fuel frailty, we characterized the immune activation profiles linked to frailty. Methods We quantified twenty-seven activation markers in forty-six virological responders (four females and forty-two males; median age, 74 years; median duration of infection, 24 years; median duration of undetectability, 13 years), whose frailty was determined according to the Fried criteria. T cell and NK cell activation was evaluated by flow cytometry, using a panel of cell surface markers. Soluble markers of inflammation, and monocyte activation and endothelial activation were measured by ELISA. The participants’ immune activation was profiled by an unsupervised double hierarchical clustering analysis. We used ANOVA p-values to rank immunomarkers most related to Fried score. A Linear Discriminant Analysis (LDA) was performed to link immune activation markers to frailty. Results 41% of the participants were pre-frail, including 24% with a Fried score of 1, and 17% with a Fried score of 2. ANOVA identified the 14 markers of T cell, monocyte, NK cell, endothelial activation, and inflammation the most linked to Fried 3 classes. The LDA performed with these 14 markers was capable of discriminating volunteers according to their Fried score. Two out of the 5 immune activation profiles revealed by the hierarchical clustering were linked to and predictive of pre-frailty. These two profiles were characterized by a low percentage of CD4 T cells and a high percentage of CD8 T cells, activated CD4 T cells, CD8 T cells, and NK cells, and inflammation. Conclusions We identified a particular immune activation profile associated with pre-frailty in PLWH. Profiling participants at risk of developing frailty might help to tailor the screening and prevention of medical complications fueled by loss of robustness. Further studies will indicate whether this frailty signature is specific or not of HIV infection, and whether it also precedes frailty in the general population.

Published
2024
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8. Engagement of the Mannose Receptor by Tumoral Mucins Activates an Immune Suppressive Phenotype in Human Tumor-Associated Macrophages

Author

P. Allavena, M. Chieppa, G. Bianchi, G. Solinas, M. Fabbri, G. Laskarin, and A. Mantovani

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Tumor-Associated Macrophages (TAMs) are abundantly present in the stroma of solid tumors and modulate several important biological processes, such as neoangiogenesis, cancer cell proliferation and invasion, and suppression of adaptive immune responses. Myeloid C-type lectin receptors (CLRs) constitute a large family of transmembrane carbohydrate-binding receptors that recognize pathogens as well as endogenous glycoproteins. Several lines of evidence demonstrate that some CLRs can inhibit the immune response. In this study we investigated TAM-associated molecules potentially involved in their immune suppressive activity. We found that TAMs isolated from human ovarian carcinoma samples predominantly express the CLRs Dectin-1, MDL-1, MGL, DCIR, and most abundantly the Mannose Receptor (MR). Components of carcinomatous ascites and purified tumoral mucins (CA125 and TAG-72) bound the MR and induced its internalization. MR engagement by tumoral mucins and by an agonist anti-MR antibody modulated cytokine production by TAM toward an immune-suppressive profile: increase of IL-10, absence of IL-12, and decrease of the Th1-attracting chemokine CCL3. This study highlights that tumoral mucin-mediated ligation of the MR on infiltrating TAM may contribute to their immune suppressive phenotype.

Published
2010
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9. Disseminated Rasamsonia argillacea complex infection presenting as intraventricular brain hemorrhage in a German shepherd dog in Australia

Author

Christopher Skinner, Rachel Allavena, Karon Hoffmann, Mirrim Kelly-Bosma, Sarah Kidd, and Christine Thomson

Subjects
Systemic mycosis, MRI, Geosmithia, Talaromyces, Angiotropism, Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

A German Shepherd Dog diagnosed with Rasamsonia argillacea based on fungal culture and DNA sequencing, is the first documented case in Australia, and the Southern Hemisphere. This species is part of R. argillacea complex, which is an emerging concern in immunocompromised human and veterinary patients. Intraventricular brain hemorrhage, noted on MRI, has not been reported previously in a dog with fungal encephalitis. The patient was euthanized due to progression of clinical signs before a final diagnosis was made, so no treatment was attempted in this case.

Published
2024
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10. Characteristics and outcomes of COVID-19 patients admitted to hospital with and without respiratory symptoms

Author

Barbara Wanjiru Citarella, Christiana Kartsonaki, Elsa D. Ibáñez-Prada, Bronner P. Gonçalves, Joaquin Baruch, Martina Escher, Mark G. Pritchard, Jia Wei, Fred Philippy, Andrew Dagens, Matthew Hall, James Lee, Demetrios James Kutsogiannis, Evert-Jan Wils, Marília Andreia Fernandes, Bharath Kumar Tirupakuzhi Vijayaraghavan, Prasan Kumar Panda, Ignacio Martin-Loeches, Shinichiro Ohshimo, Arie Zainul Fatoni, Peter Horby, Jake Dunning, Jordi Rello, Laura Merson, Amanda Rojek, Michel Vaillant, Piero Olliaro, Luis Felipe Reyes, S.A. Moharam, Sabriya Abdalasalam, Alaa Abdalfattah Abdalhadi, Naana Reyam Abdalla, Walaa Abdalla, Almthani Hamza Abdalrheem, Ashraf Abdalsalam, Saedah Abdeewi, Esraa Hassan Abdelgaum, Mohamed Abdelhalim, Mohammed Abdelkabir, Israa Abdelrahman, Sheryl Ann Abdukahil, Lamees Adil Abdulbaqi, Salaheddin Abdulhamid, Widyan Abdulhamid, Nurul Najmee Abdulkadir, Eman Abdulwahed, Rawad Abdunabi, Ryuzo Abe, Laurent Abel, Ahmed Mohammed Abodina, Amal Abrous, Lara Absil, Kamal Abu Jabal, Nashat Abu Salah, Abdurraouf Abusalama, Tareg Abdallah Abuzaid, Subhash Acharya, Andrew Acker, Elisabeth Adam, Safia Adem, Manuella Ademnou, Francisca Adewhajah, Diana Adrião, Anthony Afum-Adjei Awuah, Melvin Agbogbatey, Saleh Al Ageel, Aya Mustafa Ahmed, Musaab Mohammed Ahmed, Shakeel Ahmed, Zainab Ahmed Alaraji, Abdulrahman Ahmed Elhefnawy Enan, Reham Abdelhamid Ahmed Khalil, Ali Mostafa Ahmed Mohamed Abdelaziz, Kate Ainscough, Eka Airlangga, Tharwat Aisa, Ali Aisha, Bugila Aisha, Ali Ait Hssain, Younes Ait Tamlihat, Takako Akimoto, Ernita Akmal, Chika Akwani, Eman Al Qasim, Ahmed Alajeeli, Ahmed Alali, Razi Alalqam, Aliya Mohammed Alameen, Mohammed Al-Aquily, Zinah A. Alaraji, Khalid Albakry, Safa Albatni, Angela Alberti, Osama Aldabbourosama, Tala Al-dabbous, Amer Aldhalia, Abdulkarim Aldoukali, Senthilkumar Alegesan, Marta Alessi, Beatrice Alex, Kévin Alexandre, Abdulrahman Al-Fares, Asil Alflite, Huda Alfoudri, Qamrah Alhadad, Hoda Salem Alhaddad, Maali Khalid Mohamed Abdalla Alhasan, Ahmad Nabil Alhouri, Hasan Alhouri, Adam Ali, Imran Ali, Maha TagElser Mohammed Ali, Syed Ali Abbas, Yomna Ali Abdelghafar, Naseem Ali Sheikh, Kazali Enagnon Alidjnou, Mahmoud Aljadi, Sarah Aljamal, Mohammed Alkahlout, Akram Alkaseek, Qabas Alkhafajee, Clotilde Allavena, Nathalie Allou, Lana Almasri, Abdulrahman Almjersah, Raja Ahmed Alqandouz, Walaa Alrfaea, Moayad Alrifaee, Rawan Alsaadi, Yousef Al-Saba'a, Entisar Alshareea, Eslam Alshenawy, Aneela Altaf, João Melo Alves, João Alves, Rita Alves, Joana Alves Cabrita, Maria Amaral, Amro Essam Amer, Nur Amira, Amos Amoako Adusei, John Amuasi, Roberto Andini, Claire Andrejak, Andrea Angheben, François Angoulvant, Sophia Ankrah, Séverine Ansart, Sivanesen Anthonidass, Massimo Antonelli, Carlos Alexandre Antunes de Brito, Ardiyan Apriyana, Yaseen Arabi, Irene Aragao, Francisco Arancibia, Carolline Araujo, Antonio Arcadipane, Patrick Archambault, Lukas Arenz, Jean-Benoît Arlet, Christel Arnold-Day, Lovkesh Arora, Rakesh Arora, Elise Artaud-Macari, Diptesh Aryal, Angel Asensio, Elizabeth A. Ashley, Muhammad Ashraf, Muhammad Sheharyar Ashraf, Abir Ben Ashur, Franklin Asiedu-Bekoe, Namra Asif, Mohammad Asim, Grace Assi, Jean Baptiste Assie, Amirul Asyraf, Fouda Atangana, Ahmed Atia, Minahel Atif, Asia Atif Abdelrhman Abdallahrs, Anika Atique, Moad Atlowly, AM Udara Lakshan Attanyake, Johann Auchabie, Hugues Aumaitre, Adrien Auvet, Abdelmalek Awad Ali Mohammed, Eyvind W. Axelsen, Ared Ayad, Ahmed Ayman Hassan Helmi, Laurène Azemar, Mohammed Azizeldin, Cecile Azoulay, Hakeem Babatunde, Benjamin Bach, Delphine Bachelet, Claudine Badr, Roar Bævre-Jensen, Nadia Baig, John Kenneth Baillie, J Kevin Baird, Erica Bak, Agamemnon Bakakos, Nazreen Abu Bakar, Hibah Bileid Bakeer, Ashraf Bakri, Andriy Bal, Mohanaprasanth Balakrishnan, Irene Bandoh, Firouzé Bani-Sadr, Renata Barbalho, Nicholas Yuri Barbosa, Wendy S. Barclay, Saef Umar Barnett, Michaela Barnikel, Helena Barrasa, Cleide Barrigoto, Marie Bartoli, Joaquín Baruch, Romain Basmaci, Muhammad Fadhli Hassin Basri, AbdAlkarim Batool, Denise Battaglini, Jules Bauer, Diego Fernando Bautista Rincon, Denisse Bazan Dow, Abigail Beane, Alexandra Bedossa, Ker Hong Bee, Husna Begum, Sylvie Behilill, Albertus Beishuizen, Aleksandr Beljantsev, David Bellemare, Anna Beltrame, Beatriz Amorim Beltrão, Marine Beluze, Nicolas Benech, Lionel Eric Benjiman, Suzanne Bennett, Luís Bento, Jan-Erik Berdal, Lamis Berdeweel, Delphine Bergeaud, Hazel Bergin, Giulia Bertoli, Lorenzo Bertolino, Simon Bessis, Sybille Bevilcaqua, Karine Bezulier, Amar Bhatt, Krishna Bhavsar, Isabella Bianchi, Claudia Bianco, Sandra Bichoka, Farah Nadiah Bidin, Felwa Bin Humaid, Mohd Nazlin Bin Kamarudin, Muhannud Binnawara, Zeno Bisoffi, Patrick Biston, Laurent Bitker, Mustapha Bittaye, Jonathan Bitton, Pablo Blanco-Schweizer, Catherine Blier, Frank Bloos, Mathieu Blot, Filomena Boccia, Laetitia Bodenes, Debby Bogaert, Anne-Hélène Boivin, Ariel Bolanga, Isabela Bolaños, Pierre-Adrien Bolze, François Bompart, Aurelius Bonifasius, Joe Bonney, Diogo Borges, Raphaël Borie, Hans Martin Bosse, Elisabeth Botelho-Nevers, Lila Bouadma, Olivier Bouchaud, Sabelline Bouchez, Damien Bouhour, Kévin Bouiller, Laurence Bouillet, Camile Bouisse, Latsaniphone Bountthasavong, Anne-Sophie Boureau, John Bourke, Maude Bouscambert, Aurore Bousquet, Marielle Boyer-Besseyre, Maria Boylan, Fernando Augusto Bozza, Axelle Braconnier, Cynthia Braga, Timo Brandenburger, Filipa Brás Monteiro, Luca Brazzi, Dorothy Breen, Patrick Breen, David Brewster, Kathy Brickell, Tessa Broadley, Helen Brotherton, Alex Browne, Nicolas Brozzi, Sonja Hjellegjerde Brunvoll, Marjolein Brusse-Keizer, Petra Bryda, Nina Buchtele, Polina Bugaeva, Marielle Buisson, Danilo Buonsenso, Erlina Burhan, Donald Buri, Aidan Burrell, Ingrid G. Bustos, Denis Butnaru, André Cabie, Susana Cabral, Joana Cabrita, Eder Caceres, Cyril Cadoz, Rui Caetano Garcês, Kate Calligy, Jose Andres Calvache, João Camões, Valentine Campana, Paul Campbell, Josie Campisi, Cecilia Canepa, Mireia Cantero, Janice Caoili, Pauline Caraux-Paz, Sheila Cárcel, Filipa Cardoso, Filipe Cardoso, Nelson Cardoso, Sofia Cardoso, Simone Carelli, Nicolas Carlier, Thierry Carmoi, Gayle Carney, Inês Carqueja, Marie-Christine Carret, François Martin Carrier, Ida Carroll, Gail Carson, Maire-Laure Casanova, Mariana Cascão, Siobhan Casey, José Casimiro, Bailey Cassandra, Silvia Castañeda, Nidyanara Castanheira, Guylaine Castor-Alexandre, Ivo Castro, Ana Catarino, François-Xavier Catherine, Paolo Cattaneo, Roberta Cavalin, Giulio Giovanni Cavalli, Alexandros Cavayas, Adrian Ceccato, Masaneh Ceesay, Shelby Cerkovnik, Minerva Cervantes-Gonzalez, Muge Cevik, Anissa Chair, Catherine Chakveatze, Adrienne Chan, Meera Chand, Jean-Marc Chapplain, Charlotte Charpentier, Julie Chas, Muhammad Mobin Chaudry, Jonathan Samuel Chávez Iñiguez, Anjellica Chen, Yih-Sharng Chen, Léo Chenard, Matthew Pellan Cheng, Antoine Cheret, Thibault Chiarabini, Julian Chica, Suresh Kumar Chidambaram, Leong Chin Tho, Catherine Chirouze, Davide Chiumello, Sung-Min Cho, Bernard Cholley, Danoy Chommanam, Marie-Charlotte Chopin, Yock Ping Chow, Ting Soo Chow, Nathaniel Christy, Hiu Jian Chua, Jonathan Chua, Jose Pedro Cidade, José Miguel Cisneros Herreros, Anna Ciullo, Jennifer Clarke, Rolando Claure-Del Granado, Sara Clohisey, Cassidy Codan, Caitriona Cody, Jennifer Coles, Megan Coles, Gwenhaël Colin, Michael Collins, Pamela Combs, Jennifer Connolly, Marie Connor, Anne Conrad, Elaine Conway, Graham S. Cooke, Hugues Cordel, Amanda Corley, Sabine Cornelis, Alexander Daniel Cornet, Arianne Joy Corpuz, Andrea Cortegiani, Grégory Corvaisier, Camille Couffignal, Sandrine Couffin-Cadiergues, Roxane Courtois, Stéphanie Cousse, Juthaporn Cowan, Rachel Cregan, Gloria Crowl, Jonathan Crump, Claudina Cruz, Marc Csete, Ailbhe Cullen, Matthew Cummings, Gerard Curley, Elodie Curlier, Colleen Curran, Paula Custodio, Ana da Silva Filipe, Charlene Da Silveira, Al-Awwab Dabaliz, John Arne Dahl, Darren Dahly, Umberto D'Alessandro, Peter Daley, Zaina Dalloul, Heidi Dalton, Jo Dalton, Seamus Daly, Juliana Damas, Joycelyn Dame, Cammandji Damien, Nick Daneman, Jorge Dantas, Frédérick D'Aragon, Gillian de Loughry, Diego de Mendoza, Etienne De Montmollin, Rafael Freitas de Oliveira França, Ana Isabel de Pinho Oliveira, Rosanna De Rosa, Cristina De Rose, Thushan de Silva, Peter de Vries, Jillian Deacon, David Dean, Alexa Debard, Bianca DeBenedictis, Marie-Pierre Debray, Nathalie DeCastro, William Dechert, Romain Decours, Eve Defous, Isabelle Delacroix, Alexandre Delamou, Eric Delaveuve, Karen Delavigne, Nathalie M. Delfos, Ionna Deligiannis, Andrea Dell'Amore, Christelle Delmas, Pierre Delobel, Corine Delsing, Elisa Demonchy, Emmanuelle Denis, Dominique Deplanque, Pieter Depuydt, Diane Descamps, Mathilde Desvallées, Santi Dewayanti, Pathik Dhangar, Alpha Diallo, Souleymane Taran Diallo, Sylvain Diamantis, André Dias, Fernanda Dias Da Silva, Rodrigo Diaz, Juan Jose Diaz, Priscila Diaz, Bakary K. Dibba, Kévin Didier, Jean-Luc Diehl, Wim Dieperink, Jérôme Dimet, Vincent Dinot, Fara Diop, Alphonsine Diouf, Yael Dishon, Cedric Djadda, Félix Djossou, Annemarie B. Docherty, Helen Doherty, Arjen M. Dondorp, Christl A. Donnelly, Yoann Donohue, Sean Donohue, Peter Doran, Céline Dorival, Eric D'Ortenzio, Yash Doshi, Phouvieng Douangdala, James Joshua Douglas, Renee Douma, Nathalie Dournon, Joanne Downey, Mark Downing, Thomas Drake, Aoife Driscoll, Ibrahim Kwaku Duah, Claudio Duarte Fonseca, Vincent Dubee, François Dubos, Audrey Dubot-Pérès, Alexandre Ducancelle, Toni Duculan, Susanne Dudman, Abhijit Duggal, Paul Dunand, Mathilde Duplaix, Emanuele Durante-Mangoni, Lucian Durham, III, Bertrand Dussol, Juliette Duthoit, Xavier Duval, Anne Margarita Dyrhol-Riise, Sim Choon Ean, Ada Ebo, Marco Echeverria-Villalobos, Michael Edelstein, Siobhan Egan, Linn Margrete Eggesbø, Khadeja Ehzaz, Carla Eira, Mohammed El Sanharawi, Marwan El Sayed, Mohammed Elabid, Mohamed Bashir Elagili, Subbarao Elapavaluru, Mohammad Elbahnasawy, Sohail Elboshra, Brigitte Elharrar, Jacobien Ellerbroek, Merete Ellingjord-Dale, Hamida ELMagrahi, Mohammad Muatasm Elmubark, Loubna Elotmani, Lauren Eloundou, Philippine Eloy, Basma Elshaikhy, Tarek Elshazly, Wafa Elsokni, Aml Ahmed Eltayeb, Iqbal Elyazar, Zarief Kamel Emad, Hussein Embarek, Isabelle Enderle, Tomoyuki Endo, Gervais Eneli, Chan Chee Eng, Ilka Engelmann, Vincent Enouf, Olivier Epaulard, Haneen Esaadi, Mariano Esperatti, Hélène Esperou, Catarina Espírito Santo, Marina Esposito-Farese, Rachel Essaka, Lorinda Essuman, João Estevão, Manuel Etienne, Anna Greti Everding, Mirjam Evers, Isabelle Fabre, Marc Fabre, Ismaila Fadera, Asgad Osman Abdalla Fadlalla, Amna Faheem, Arabella Fahy, Cameron J. Fairfield, Zul Fakar, Komal Fareed, Pedro Faria, Ahmed Farooq, Hanan Fateena, Mohamed Fathi, Salem Fatima, Karine Faure, Raphaël Favory, Mohamed Fayed, Niamh Feely, Jorge Fernandes, Susana Fernandes, François-Xavier Ferrand, Eglantine Ferrand Devouge, Joana Ferrão, Mário Ferraz, Benigno Ferreira, Isabel Ferreira, Bernardo Ferreira, Sílvia Ferreira, Nicolas Ferriere, Céline Ficko, Claudia Figueiredo-Mello, William Finlayson, Thomas Flament, Tom Fletcher, Aline-Marie Florence, Letizia Lucia Florio, Brigid Flynn, Deirdre Flynn, Jean Foley, Victor Fomin, Tatiana Fonseca, Patricia Fontela, Karen Forrest, Simon Forsyth, Denise Foster, Giuseppe Foti, Berline Fotso, Erwan Fourn, Robert A. Fowler, Marianne Fraher, Diego Franch-Llasat, Christophe Fraser, John F. Fraser, Marcela Vieira Freire, Ana Freitas Ribeiro, Craig French, Caren Friedrich, Ricardo Fritz, Stéphanie Fry, Nora Fuentes, Masahiro Fukuda, G. Argin, Valérie Gaborieau, Rostane Gaci, Massimo Gagliardi, Jean-Charles Gagnard, Amandine Gagneux-Brunon, Abdou Gai, Sérgio Gaião, Linda Gail Skeie, Adham Mohamed Galal Mohamed Ramadan, Phil Gallagher, Carrol Gamble, Yasmin Gani, Arthur Garan, Rebekha Garcia, Julia Garcia-Diaz, Esteban Garcia-Gallo, Navya Garimella, Denis Garot, Valérie Garrait, Basanta Gauli, Anatoliy Gavrylov, Alexandre Gaymard, Johannes Gebauer, Eva Geraud, Louis Gerbaud Morlaes, Nuno Germano, Malak Ghemmeid, Praveen Kumar Ghisulal, Jade Ghosn, Marco Giani, Tristan Gigante, Elaine Gilroy, Guillermo Giordano, Michelle Girvan, Valérie Gissot, Gezy Giwangkancana, Daniel Glikman, Petr Glybochko, Eric Gnall, Geraldine Goco, François Goehringer, Siri Goepel, Jean-Christophe Goffard, Jin Yi Goh, Brigitta Golács, Jonathan Golob, Kyle Gomez, Joan Gómez-Junyent, Marie Gominet, Alicia Gonzalez, Patricia Gordon, Isabelle Gorenne, Laure Goubert, Cécile Goujard, Tiphaine Goulenok, Margarite Grable, Jeronimo Graf, Edward Wilson Grandin, Pascal Granier, Giacomo Grasselli, Lorenzo Grazioli, Christopher A. Green, Courtney Greene, William Greenhalf, Segolène Greffe, Domenico Luca Grieco, Matthew Griffee, Fiona Griffiths, Ioana Grigoras, Albert Groenendijk, Fassou Mathias Grovogui, Heidi Gruner, Yusing Gu, Jérémie Guedj, Martin Guego, Anne-Marie Guerguerian, Daniela Guerreiro, Romain Guery, Anne Guillaumot, Laurent Guilleminault, Maisa Guimarães de Castro, Thomas Guimard, Marieke Haalboom, Daniel Haber, Ali Hachemi, Abdurrahman Haddud, Nadir Hadri, Wael Hafez, Fakhir Raza Haidri, Fatima Mhd Rida Hajij, Sheeba Hakak, Adam Hall, Sophie Halpin, Shaher Hamdan, Abdelhafeez Hamdi, Jawad Hameed, Ansley Hamer, Raph L. Hamers, Rebecca Hamidfar, Bato Hammarström, Naomi Hammond, Terese Hammond, Lim Yuen Han, Matly Hanan, Rashan Haniffa, Kok Wei Hao, Hayley Hardwick, Ewen M. Harrison, Janet Harrison, Samuel Bernard Ekow Harrison, Alan Hartman, Sulieman Hasan, Mohammad Ali Nabil Hasan, Mohd Shahnaz Hasan, Junaid Hashmi, Madiha Hashmi, Amoni Hassan, Ebtisam Hassanin, Muhammad Hayat, Ailbhe Hayes, Leanne Hays, Jan Heerman, Lars Heggelund, Ahmed Helmi, Ross Hendry, Martina Hennessy, Aquiles Rodrigo Henriquez-Trujillo, Maxime Hentzien, Diana Hernandez, Andrew Hershey, Liv Hesstvedt, Astarini Hidayah, Eibhlin Higgins, Rupert Higgins, Samuel Hinton, Hiroaki Hiraiwa, Haider Hirkani, Hikombo Hitoto, Antonia Ho, Yi Bin Ho, Alexandre Hoctin, Isabelle Hoffmann, Wei Han Hoh, Oscar Hoiting, Rebecca Holt, Jan Cato Holter, Juan Pablo Horcajada, Ikram Houas, Mabrouka Houderi, Catherine L. Hough, Stuart Houltham, Jimmy Ming-Yang Hsu, Jean-Sébastien Hulot, Abby Hurd, Iqbal Hussain, Aliae Mohamed Hussein, Mahmood Hussein, Fatima Ibrahim, Bashir Ibran, Samreen Ijaz, M. Arfan Ikram, Carlos Cañada Illana, Patrick Imbert, Muhammad Imran Ansari, Rana Imran Sikander, Hugo Inácio, Carmen Infante Dominguez, Yun Sii Ing, Mariachiara Ippolito, Vera Irawany, Sarah Isgett, Tiago Isidoro, Nadiah Ismail, Margaux Isnard, Mette Stausland Istre, Junji Itai, Daniel Ivulich, Danielle Jaafar, Salma Jaafoura, Hamza Jaber, Julien Jabot, Clare Jackson, Abubacarr Jagne, Stéphane Jaureguiberry, Denise Jaworsky, Florence Jego, Anilawati Mat Jelani, Synne Jenum, Ruth Jimbo-Sotomayor, Ong Yiaw Joe, Ruth Noemí Jorge García, Silje Bakken Jørgensen, Cédric Joseph, Mark Joseph, Swosti Joshi, Mercé Jourdain, Philippe Jouvet, Anna Jung, Hanna Jung, Dafsah Juzar, Ouifiya Kafif, Florentia Kaguelidou, Neerusha Kaisbain, Thavamany Kaleesvran, Sabina Kali, Karl Trygve Kalleberg, Smaragdi Kalomoiri, Muhammad Aisar Ayadi Kamaluddin, Armand Saloun Kamano, Zul Amali Che Kamaruddin, Nadiah Kamarudin, Kavita Kamineni, Darshana Hewa Kandamby, Kong Yeow Kang, Darakhshan Kanwal, Dyah Kanyawati, Mohamed Karghul, Pratap Karpayah, Todd Karsies, Daisuke Kasugai, Kevin Katz, Christy Kay, Lamees Kayyali, Seán Keating, Pulak Kedia, Andrea Kelly, Aoife Kelly, Claire Kelly, Niamh Kelly, Sadie Kelly, Yvelynne Kelly, Maeve Kelsey, Kalynn Kennon, Sommay Keomany, Maeve Kernan, Younes Kerroumi, Sharma Keshav, Shams Khail, Sarah Khaled, Imrana Khalid, Antoine Khalil, Irfan Khan, Quratul Ain Khan, Sushil Khanal, Abid Khatak, Krish Kherajani, Michelle E. Kho, Denisa Khoo, Ryan Khoo, Saye Khoo, Muhammad Nasir Khoso, Amin Khuwaja, Khor How Kiat, Yuri Kida, Peter Kiiza, Beathe Kiland Granerud, Anders Benjamin Kildal, Jae Burm Kim, Antoine Kimmoun, Detlef Kindgen-Milles, Nobuya Kitamura, Eyrun Floerecke Kjetland Kjetland, Paul Klenerman, Rob Klont, Gry Kloumann Bekken, Stephen R. Knight, Robin Kobbe, Paa Kobina Forson, Chamira Kodippily, Malte Kohns Vasconcelos, Sabin Koirala, Mamoru Komatsu, Franklina Korkor Abebrese, Volkan Korten, Stephanie Kouba, Mohamed Lamine Kourouma, Karifa Kourouma, Arsène Kpangon, Karolina Krawczyk, Ali Kredan, Vinothini Krishnan, Sudhir Krishnan, Oksana Kruglova, Anneli Krund, Pei Xuan Kuan, Ashok Kumar, Deepali Kumar, Ganesh Kumar, Mukesh Kumar, Dinesh Kuriakose, Ethan Kurtzman, Demetrios Kutsogiannis, Galyna Kutsyna, Ama Kwakyewaa Bedu-Addo, Sylvie Kwedi, Konstantinos Kyriakoulis, Marie Lachatre, Marie Lacoste, John G. Laffey, Nadhem Lafhej, Marie Lagrange, Fabrice Laine, Olivier Lairez, Sanjay Lakhey, Marc Lambert, François Lamontagne, Marie Langelot-Richard, Vincent Langlois, Eka Yudha Lantang, Marina Lanza, Cédric Laouénan, Samira Laribi, Delphine Lariviere, Stéphane Lasry, Sakshi Lath, Naveed Latif, Youssef Latifeh, Odile Launay, Didier Laureillard, Yoan Lavie-Badie, Andy Law, Cassie Lawrence, Teresa Lawrence, Minh Le, Clément Le Bihan, Cyril Le Bris, Georges Le Falher, Lucie Le Fevre, Quentin Le Hingrat, Marion Le Maréchal, Soizic Le Mestre, Gwenaël Le Moal, Vincent Le Moing, Hervé Le Nagard, Ema Leal, Marta Leal Santos, Biing Horng Lee, Heng Gee Lee, Su Hwan Lee, Jennifer Lee, Todd C. Lee, Yi Lin Lee, Gary Leeming, Bénédicte Lefebvre, Laurent Lefebvre, Benjamin Lefèvre, Sylvie LeGac, Merili-Helen Lehiste, Jean-Daniel Lelievre, François Lellouche, Adrien Lemaignen, Véronique Lemee, Anthony Lemeur, Gretchen Lemmink, Ha Sha Lene, Jenny Lennon, Rafael León, Marc Leone, Tanel Lepik, Quentin Lepiller, François-Xavier Lescure, Olivier Lesens, Mathieu Lesouhaitier, Amy Lester-Grant, Andrew Letizia, Sophie Letrou, Bruno Levy, Yves Levy, Claire Levy-Marchal, Katarzyna Lewandowska, Erwan L'Her, Gianluigi Li Bassi, Janet Liang, Ali Liaquat, Geoffrey Liegeon, Kah Chuan Lim, Wei Shen Lim, Chantre Lima, Bruno Lina, Lim Lina, Andreas Lind, Maja Katherine Lingad, Guillaume Lingas, Sylvie Lion-Daolio, Keibun Liu, Marine Livrozet, Patricia Lizotte, Antonio Loforte, Navy Lolong, Leong Chee Loon, Diogo Lopes, Dalia Lopez-Colon, Anthony L. Loschner, Paul Loubet, Bouchra Loufti, Guillame Louis, Silvia Lourenco, Lara Lovelace-Macon, Lee Lee Low, Marije Lowik, Jia Shyi Loy, Jean Christophe Lucet, Carlos M. Luna, Olguta Lungu, Miles Lunn, Liem Luong, Nestor Luque, Dominique Luton, Olavi Maasikas, Moïse Machado, Sara Machado, Gabriel Macheda, Mustafa Magzoub, Rafael Mahieu, Sophie Mahy, Ana Raquel Maia, Lars S. Maier, Oumou Maiga Ascofare, Mylène Maillet, Thomas Maitre, Nimisha Abdul Majeed, Maximilian Malfertheiner, Nadia Malik, Paddy Mallon, Fernando Maltez, Denis Malvy, Victoria Manda, Laurent Mandelbrot, Frank Manetta, Julie Mankikian, Edmund Manning, Aldric Manuel, Veronika Maráczi, Ceila Maria Sant′Ana Malaque, Flávio Marino, Samuel Markowicz, Ana Marques, Catherine Marquis, Laura Marsh, Brian Marsh, Megan Marshal, John Marshall, Celina Turchi Martelli, Dori-Ann Martin, Emily Martin, Guillaume Martin-Blondel, Alessandra Martinelli, F. Eduardo Martinez, Martin Martinot, Alejandro Martín-Quiros, Ana Martins, João Martins, Nuno Martins, Caroline Martins Rego, Gennaro Martucci, Olga Martynenko, Eva Miranda Marwali, Marsilla Marzukie, David Maslove, Sabina Mason, Sobia Masood, Fatma Masoud, Moise Massoma, Palmer Masumbe, Mohd Basri Mat Nor, Moshe Matan, Henrique Mateus Fernandes, Meghena Mathew, Christina Mathew, Mathieu Mattei, Laurence Maulin, Juergen May, Javier Maynar, Mayfong Mayxay, Thierry Mazzoni, Lisa Mc Sweeney, Colin McArthur, Naina McCann, Peter McCanny, Aine McCarthy, Anne McCarthy, Colin McCloskey, Rachael McConnochie, Sherry McDermott, Sarah E. McDonald, Aine McElroy, Samuel McElwee, Natalie McEvoy, Allison McGeer, Kenneth A. McLean, Paul McNally, Bairbre McNicholas, Edel Meaney, Cécile Mear-Passard, Maggie Mechlin, Nastia Medombou, Omar Mehkri, Ferruccio Mele, Luis Melo, Kashif Ali Memon, João João Mendes, Ogechukwu Menkiti, Kusum Menon, France Mentré, Alexander J. Mentzer, Emmanuelle Mercier, Noémie Mercier, Antoine Merckx, Mayka Mergeay-Fabre, Blake Mergler, António Mesquita, Roberta Meta, Osama Metwally, Agnès Meybeck, Dan Meyer, Alison M. Meynert, Vanina Meysonnier, Mehdi Mezidi, Céline Michelanglei, Isabelle Michelet, Efstathia Mihelis, Vladislav Mihnovit, Duha Milad Abdullah, Jennene Miller, Hugo Miranda-Maldonado, Nor Arisah Misnan, Nik Nur Eliza Mohamed, Nouralsabah Mohamed, Tahira Jamal Mohamed, Alaa Mohamed Ads, Ahmed Reda Mohamed Elsayed Abdelhalim, Libya Mohammed, Shrouk Fawze Mohammed Mostafa, Manahil Omer Abdelrahman Mohammedahmed, Omer Abdullah Mohammedelhassan, Asma Moin, Walaa Mokhtar, Elena Molinos, Brenda Molloy, Mary Mone, Agostinho Monteiro, Claudia Montes, Giorgia Montrucchio, Sarah Moore, Shona C. Moore, Lina Morales Cely, Marwa Morgom, Lucia Moro, Catherine Motherway, Ana Motos, Hugo Mouquet, Clara Mouton Perrot, Julien Moyet, Suleiman Haitham Mualla, Mohamed Muftah, Aisha Kalsoom Mufti, Ng Yong Muh, Mo'nes Muhaisen, Dzawani Muhamad, Jimmy Mullaert, Fredrik Müller, Karl Erik Müller, Daniel Munblit, Syed Muneeb Ali, Nadeem Munir, Laveena Munshi, Aisling Murphy, Patrick Murray, Marlène Murris, Srinivas Murthy, Himed Musaab, Alamin Mustafa, Mus'ab Mustafa, Dana Mustafa, Himasha Muvindi, Dimitra Melia Myrodia, Farah Nadia Mohd-Hanafiah, Behzad Nadjm, Dave Nagpal, Alex Nagrebetsky, Blanka Nagybányai-Nagy, Herwin Nanda Boudoin, Mangala Narasimhan, Nageswaran Narayanan, Prashant Nasa, Rashid Nasim Khan, Ahmad Nasrallah, Adel Gerges Nassif Metri, Alasdair Nazerali-Maitland, Nadège Neant, Holger Neb, Nikita Nekliudov, Matthew Nelder, Erni Nelwan, Raul Neto, Emily Neumann, Wing Yiu Ng, Pauline Yeung Ng, Anthony Nghi, Duc Nguyen, Orna Ni Choileain, Niamh Ni Leathlobhair, Nerissa Niba, Alistair D. Nichol, Prompak Nitayavardhana, Stephanie Nonas, Nurul Amani Mohd Noordin, Nurul Faten Izzati Norharizam, Anita North, Alessandra Notari, Mahdad Noursadeghi, Adam Nowinski, Saad Nseir, Leonard Numfor, Nurnaningsih Nurnaningsih, Dwi Utomo Nusantara, Elsa Nyamankolly, Anders Benteson Nygaard, Fionnuala O. Brien, Annmarie O. Callaghan, Annmarie O'Callaghan, Giovanna Occhipinti, Derbrenn OConnor, Max O'Donnell, Lawrence Ofori-Boadu, Tawnya Ogston, Takayuki Ogura, Tak-Hyuk Oh, Sophie O'Halloran, Katie O'Hearn, Sally-Ann Ohene, João Oliveira, Larissa Oliveira, Piero L. Olliaro, Cinderella Omar Rageh Elnaggar, Alsarrah Ali Mohammed Omer, Pierre Ondobo, David S.Y. Ong, Jee Yan Ong, Wilna Oosthuyzen, Anne Opavsky, Peter Openshaw, Saijad Orakzai, Claudia Milena Orozco-Chamorro, Jamel Ortoleva, Mohamed Osama Elsayed Soliman, Javier Osatnik, Linda O'Shea, Miriam O'Sullivan, Eman Othman, Siti Zubaidah Othman, Nadia Ouamara, Rachida Ouissa, Micheal Owusu, Ama Akyampomaa Owusu-Asare, Eric Oziol, Maïder Pagadoy, Justine Pages, Amanda Palacios, Massimo Palmarini, Giovanna Panarello, Hem Paneru, Lai Hui Pang, Mauro Panigada, Nathalie Pansu, Aurélie Papadopoulos, Rachael Parke, Melissa Parker, Jérémie Pasquier, Bruno Pastene, Fabian Patauner, Drashti Patel, Mohan Dass Pathmanathan, Luís Patrão, Patricia Patricio, Lisa Patterson, Rajyabardhan Pattnaik, Christelle Paul, Mical Paul, Jorge Paulos, William A. Paxton, Jean-François Payen, Sandra L. Peake, Kalaiarasu Peariasamy, Giles J. Peek, Florent Peelman, Nathan Peiffer-Smadja, Vincent Peigne, Mare Pejkovska, Paolo Pelosi, Ithan D. Peltan, Rui Pereira, Daniel Perez, Thomas Perpoint, Antonio Pesenti, Vincent Pestre, Lenka Petrou, Michele Petrovic, Ventzislava Petrov-Sanchez, Frank Olav Pettersen, Gilles Peytavin, Richard Odame Philips, Ooyanong Phonemixay, Soulichanya Phoutthavong, Michael Piagnerelli, Walter Picard, Olivier Picone, Maria de Piero, Djura Piersma, Carlos Pimentel, Raquel Pinto, Catarina Pires, Lionel Piroth, Ayodhia Pitaloka, Chiara Piubelli, Riinu Pius, Simone Piva, Laurent Plantier, Hon Shen Png, Julien Poissy, Ryadh Pokeerbux, Sergio Poli, Georgios Pollakis, Diane Ponscarme, Diego Bastos Porto, Andra-Maris Post, Douwe F. Postma, Pedro Povoa, Diana Póvoas, Jeff Powis, Sofia Prapa, Viladeth Praphasiri, Sébastien Preau, Christian Prebensen, Jean-Charles Preiser, Anton Prinssen, Gamage Dona Dilanthi Priyadarshani, Lucia Proença, Sravya Pudota, Bambang Pujo Semedi, Mathew Pulicken, Peter Puplampu, Gregory Purcell, Luisa Quesada, Vilmaris Quinones-Cardona, Else Quist-Paulsen, Mohammed Quraishi, Fadi Qutishat, Maia Rabaa, Christian Rabaud, Ebenezer Rabindrarajan, Aldo Rafael, Marie Rafiq, Abdelrahman Ragab, Mutia Rahardjani, Arslan Rahat Ullah, Ahmad Kashfi Haji Ab Rahman, Rozanah Abd Rahman, Fernando Rainieri, Giri Shan Rajahram, Pratheema Ramachandran, Nagarajan Ramakrishnan, José Ramalho, Ahmad Afiq Ramli, Blandine Rammaert, Grazielle Viana Ramos, Asim Rana, Rajavardhan Rangappa, Ritika Ranjan, Christophe Rapp, Aasiyah Rashan, Thalha Rashan, Ghulam Rasheed, Menaldi Rasmin, Indrek Rätsep, Cornelius Rau, Tharmini Ravi, Ali Raza, Andre Real, Stanislas Rebaudet, Sarah Redl, Brenda Reeve, Attaur Rehman, Muhammad Osama Rehman Khalid, Dag Henrik Reikvam, Renato Reis, Jonathan Remppis, Martine Remy, Hongru Ren, Hanna Renk, Anne-Sophie Resseguier, Matthieu Revest, Oleksa Rewa, Maria Ines Ribeiro, Antonia Ricchiuto, David Richardson, Denise Richardson, Laurent Richier, Siti Nurul Atikah Ahmad Ridzuan, Ana L. Rios, Asgar Rishu, Patrick Rispal, Karine Risso, Maria Angelica Rivera Nuñez, Chiara Robba, André Roberto, Stephanie Roberts, Charles Roberts, David L. Robertson, Olivier Robineau, Anna Roca, Ferran Roche-Campo, Paola Rodari, Simão Rodeia, Bernhard Roessler, Claire Roger, Pierre-Marie Roger, Roberto Roncon-Albuquerque, Jr., Mélanie Roriz, Manuel Rosa-Calatrava, Michael Rose, Dorothea Rosenberger, Andrea Rossanese, Matteo Rossetti, Patrick Rossignol, Carine Roy, Benoît Roze, Desy Rusmawatiningtyas, Clark D. Russell, Maeve Ryan, Steffi Ryckaert, Aleksander Rygh Holten, Isabela Saba, Sairah Sadaf, Musharaf Sadat, Valla Sahraei, Abdurraouf Said, Nadia Saidani, Pranya Sakiyalak, Fodé Bangaly Sako, Moamen Salah, Ali Alaa Salah Eldin Mohamed Abbas, Nawal Salahuddin, Leonardo Salazar, Jodat Saleem, Mohammed Saleh Alyasiri, Talat Ahmed Abu Salem, Gabriele Sales, Charlotte Salmon Gandonniere, Hélène Salvator, Dana Samardali, Shaden Samardali, Yehia Samir Shaaban Aly Orabi, Emely Sanchez, Olivier Sanchez, Kizy Sanchez de Oliveira, Angel Sanchez-Miralles, Vanessa Sancho-Shimizu, Gyan Sandhu, Zulfiqar Sandhu, Pierre-François Sandrine, Oana Săndulescu, Marlene Santos, Shirley Sarfo-Mensah, Bruno Sarmento Banheiro, Iam Claire E. Sarmiento, Benjamine Sarton, Ankana Satya, Sree Satyapriya, Rumaisah Satyawati, Egle Saviciute, Yen Tsen Saw, Justin Schaffer, Tjard Schermer, Arnaud Scherpereel, Marion Schneider, János Schnur, Stephan Schroll, Michael Schwameis, Gary Schwartz, Janet T. Scott, James Scott-Brown, Nicholas Sedillot, Tamara Seitz, Jaganathan Selvanayagam, Mageswari Selvarajoo, Malcolm G. Semple, Rasidah Bt Senian, Eric Senneville, Claudia Sepulveda, Filipa Sequeira, Tânia Sequeira, Ary Serpa Neto, Ellen Shadowitz, Syamin Asyraf Shahidan, Hamza Shahla, Laila Shalabi, Haitam Shames, Anuraj Shankar, Shaikh Sharjeel, Pratima Sharma, Catherine A. Shaw, Victoria Shaw, John Robert Sheenan, Dr. Rajesh Mohan Shetty, Rohan Shetty, Mohiuddin Shiekh, Nobuaki Shime, Keiki Shimizu, Sally Shrapnel, Shubha Kalyan Shrestha, Pramesh Sundar Shrestha, Hoi Ping Shum, Nassima Si Mohammed, Ng Yong Siang, Moses Siaw-Frimpong, Jeanne Sibiude, Bountoy Sibounheuang, Nidhal Siddig, Atif Siddiqui, Maqsood Ahmed Siddiqui, Louise Sigfrid, Fatoumata Sillah, Piret Sillaots, Catarina Silva, Maria Joao Silva, Rogério Silva, Benedict Sim Lim Heng, Wai Ching Sin, Dario Sinatti, Mahendra Singh, Punam Singh, Pompini Agustina Sitompul, Karisha Sivam, Vegard Skogen, Sue Smith, Benjamin Smood, Coilin Smyth, Morgane Snacken, Dominic So, Tze Vee Soh, Lene Bergendal Solberg, Joshua Solomon, Tom Solomon, Emily Somers, Agnès Sommet, Myung Jin Song, Rima Song, Tae Song, Jack Song Chia, Arne Søraas, Albert Sotto, Edouard Soum, Ana Chora Sousa, Marta Sousa, Maria Sousa Uva, Vicente Souza-Dantas, Mamadou Saliou Sow, Alexandra Sperry, Elisabetta Spinuzza, B. P. Sanka Ruwan Sri Darshana, Shiranee Sriskandan, Sarah Stabler, Thomas Staudinger, Stephanie-Susanne Stecher, Trude Steinsvik, Ymkje Stienstra, Birgitte Stiksrud, Eva Stolz, Amy Stone, Anca Streinu-Cercel, Adrian Streinu-Cercel, Geoff Strong, Ami Stuart, David Stuart, Richa Su, Decy Subekti, Gabriel Suen, Jacky Y. Suen, Prasanth Sukumar, Asfia Sultana, Charlotte Summers, Dubravka Supic, Deepashankari Suppiah, Magdalena Surovcová, Atie Suwarti, Andrey Svistunov, Sarah Syahrin, Augustina Sylverken, Konstantinos Syrigos, Jaques Sztajnbok, Konstanty Szuldrzynski, Shirin Tabrizi, Fabio S. Taccone, Lysa Tagherset, Shahdattul Mawarni Taib, Sara Taleb, Cheikh Talla, Jelmer Talsma, Renaud Tamisier, Maria Lawrensia Tampubolon, Kim Keat Tan, Yan Chyi Tan, Hiroyuki Tanaka, Taku Tanaka, Hayato Taniguchi, Huda Taqdees, Arshad Taqi, Coralie Tardivon, Yousef Tarek Kamal Mostafa, Ali Tarhabat, Pierre Tattevin, M Azhari Taufik, Hassan Tawfik, Tze Yuan Tee, João Teixeira, Sofia Tejada, Marie-Capucine Tellier, Sze Kye Teoh, Vanessa Teotonio, François Téoulé, Olivier Terrier, Nicolas Terzi, Hubert Tessier-Grenier, Adrian Tey, Alif Adlan Mohd Thabit, Anand Thakur, Zhang Duan Tham, Suvintheran Thangavelu, Elmi Theron, Vincent Thibault, Simon-Djamel Thiberville, Benoît Thill, Jananee Thirumanickam, Niamh Thompson, Shaun Thompson, Emma C. Thomson, David Thomson, Mathew Thorpe, Surain Raaj Thanga Thurai, Ryan S. Thwaites, Paul Tierney, Vadim Tieroshyn, Peter S. Timashev, Jean-François Timsit, Noémie Tissot, Fiona Toal, Jordan Zhien Yang Toh, Maria Toki, Kristian Tonby, Sia Loong Tonnii, Marta Torre, Antoni Torres, Margarida Torres, Rosario Maria Torres Santos-Olmo, Hernando Torres-Zevallos, Aboubacar Tounkara, Michael Towers, Fodé Amara Traoré, Tony Trapani, Cécile Tromeur, Ioannis Trontzas, Tiffany Trouillon, Jeanne Truong, Christelle Tual, Sarah Tubiana, Helen Tuite, Alexis F. Turgeon, Jean-Marie Turmel, Lance C.W. Turtle, Anders Tveita, Pawel Twardowski, Makoto Uchiyama, PG Ishara Udayanga, Andrew Udy, Roman Ullrich, Alberto Uribe, Asad Usman, Effua Usuf, Timothy M. Uyeki, Cristinava Vajdovics, Piero Valentini, Luís Val-Flores, Stijn Van de Velde, Marcel van den Berge, Machteld van der Feltz, Job van der Palen, Paul van der Valk, Nicky Van Der Vekens, Peter Van der Voort, Sylvie Van Der Werf, Laura van Gulik, Jarne Van Hattem, Carolien van Netten, Ilonka van Veen, Noémie Vanel, Henk Vanoverschelde, Michael Varrone, Shoban Raj Vasudayan, Charline Vauchy, Pavan Kumar Vecham, Shaminee Veeran, Aurélie Veislinger, Sebastian Vencken, Sara Ventura, Annelies Verbon, José Ernesto Vidal, César Vieira, Deepak Vijayan, Judit Villar, Pierre-Marc Villeneuve, Andrea Villoldo, Gayatri Vishwanathan, Benoit Visseaux, Hannah Visser, Chiara Vitiello, Manivanh Vongsouvath, Harald Vonkeman, Fanny Vuotto, Suhaila Abdul Wahab, Noor Hidayu Wahab, Nadirah Abdul Wahid, Marina Wainstein, Laura Walsh, Wan Fadzlina Wan Muhd Shukeri, Chih-Hsien Wang, Steve Webb, Katharina Weil, Tan Pei Wen, Hassi Wesam, Sanne Wesselius, T. Eoin West, Murray Wham, Bryan Whelan, Nicole White, Paul Henri Wicky, Aurélie Wiedemann, Surya Otto Wijaya, Keith Wille, Sue Willems, Bailey Williams, Patricia J. Williams, Virginie Williams, Jessica Wittman, Calvin Wong, Xin Ci Wong, Yew Sing Wong, Teck Fung Wong, Natalie Wright, Lim Saio Xian, Ioannis Xynogalas, Siti Rohani Binti Mohd Yakop, Masaki Yamazaki, Elizabeth Yarad, Yazdan Yazdanpanah, Nicholas Yee Liang Hing, Abdelrahman Yehia Mahmoud Abdelaal, Cécile Yelnik, Chian Hui Yeoh, Stephanie Yerkovich, Touxiong Yiaye, Toshiki Yokoyama, Hodane Yonis, Obada Yousif, Saptadi Yuliarto, Akram Zaaqoq, Marion Zabbe, Gustavo E. Zabert, Kai Zacharowski, Masliza Zahid, Maram Zahran, Nor Zaila Binti Zaidan, Maria Zambon, Miguel Zambrano, Alberto Zanella, Nurul Zaynah, Hiba Zayyad, Alexander Zoufaly, and David Zucman

Subjects
COVID-19, Non-respiratory symptoms, Respiratory symptoms, Risk factors, Mortality, Science (General), Q1-390, Social sciences (General), H1-99
Abstract

Background: COVID-19 is primarily known as a respiratory illness; however, many patients present to hospital without respiratory symptoms. The association between non-respiratory presentations of COVID-19 and outcomes remains unclear. We investigated risk factors and clinical outcomes in patients with no respiratory symptoms (NRS) and respiratory symptoms (RS) at hospital admission. Methods: This study describes clinical features, physiological parameters, and outcomes of hospitalised COVID-19 patients, stratified by the presence or absence of respiratory symptoms at hospital admission. RS patients had one or more of: cough, shortness of breath, sore throat, runny nose or wheezing; while NRS patients did not. Results: Of 178,640 patients in the study, 86.4 % presented with RS, while 13.6 % had NRS. NRS patients were older (median age: NRS: 74 vs RS: 65) and less likely to be admitted to the ICU (NRS: 36.7 % vs RS: 37.5 %). NRS patients had a higher crude in-hospital case-fatality ratio (NRS 41.1 % vs. RS 32.0 %), but a lower risk of death after adjusting for confounders (HR 0.88 [0.83–0.93]). Conclusion: Approximately one in seven COVID-19 patients presented at hospital admission without respiratory symptoms. These patients were older, had lower ICU admission rates, and had a lower risk of in-hospital mortality after adjusting for confounders.

Published
2024
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11. Mannose-modified hyaluronic acid nanocapsules for the targeting of tumor-associated macrophages

Author

Fernández-Mariño, Iago, Anfray, Clément, Crecente-Campo, Jose, Maeda, Akihiro, Ummarino, Aldo, Teijeiro-Valiño, Carmen, Blanco-Martinez, Dario, Mpambani, Francis, Poul, Laurence, Devalliere, Julie, Germain, Matthieu, Correa, Juan, Fernandez-Villamarin, Marcos, Allavena, Paola, Fernandez-Megia, Eduardo, Alonso, María José, and Andón, Fernando Torres

Published
2023
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12. Anthropogenic and environmental factors associated with koala deaths due to dog attacks and vehicle collisions in South-East Queensland, Australia, 2009–2013

Author

Ravi Bandara Dissanayake, Mark Stevenson, Viviana Gonzalez Astudillo, Rachel Allavena, and Joerg Henning

Subjects
Medicine, Science
Abstract

Abstract Populations of the iconic Australian koala are under constant decline. Their deaths are associated with rapid and extensive urbanization and the fragmentation of habitat areas. Using citizen science data on reported koala mortalities, we quantified the association between anthropogenic and environmental factors and the two leading causes of koala deaths, dog attacks and vehicle collisions. We achieved this objective using a case–control study design to compare the odds of exposure to a given risk factor for cases (a given cause of death) with the odds of exposure to a given risk factor for controls (all other causes of death). Koala deaths due to dog attacks were positively associated with registered dog population density and negatively associated with lot density whereas koala deaths due to vehicle collisions were positively associated with road density (road length per square kilometer) and negatively associated with human population density and distance to primary and secondary roads. The results of this research can be used to develop strategies to mitigate the risk of deaths due to dog attacks, for example by conducting educational awareness programs, promoting registration of dogs and discouraging free roaming of dogs. In a similar manner, in high-risk areas for vehicle collisions, over- or underpasses can be built to facilitate safe movement of koalas for road crossings or speed limits could be introduced to reduce the likelihood of premature koala deaths due to vehicle collisions.

Published
2023
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13. Polymeric nanocapsules loaded with poly(I:C) and resiquimod to reprogram tumor-associated macrophages for the treatment of solid tumors

Author

Clément Anfray, Carmen Fernández Varela, Aldo Ummarino, Akihiro Maeda, Marina Sironi, Sara Gandoy, Jose Brea, María Isabel Loza, Sergio León, Alfonso Calvo, Juan Correa, Eduardo Fernandez-Megia, María José Alonso, Paola Allavena, José Crecente-Campo, and Fernando Torres Andón

Subjects
polymeric nanocapsules, poly(I:C), resiquimod (R848), tumor-associated macrophages (TAMs), toll-like receptor (TLR), antitumoral immunotherapy, Immunologic diseases. Allergy, RC581-607
Abstract

BackgroundIn the tumor microenvironment (TME), tumor-associated macrophages (TAMs) play a key immunosuppressive role that limits the ability of the immune system to fight cancer. Toll-like receptors (TLRs) ligands, such as poly(I:C) or resiquimod (R848) are able to reprogram TAMs towards M1-like antitumor effector cells. The objective of our work has been to develop and evaluate polymeric nanocapsules (NCs) loaded with poly(I:C)+R848, to improve drug stability and systemic toxicity, and evaluate their targeting and therapeutic activity towards TAMs in the TME of solid tumors.MethodsNCs were developed by the solvent displacement and layer-by-layer methodologies and characterized by dynamic light scattering and nanoparticle tracking analysis. Hyaluronic acid (HA) was chemically functionalized with mannose for the coating of the NCs to target TAMs. NCs loaded with TLR ligands were evaluated in vitro for toxicity and immunostimulatory activity by Alamar Blue, ELISA and flow cytometry, using primary human monocyte-derived macrophages. For in vivo experiments, the CMT167 lung cancer model and the MN/MCA1 fibrosarcoma model metastasizing to lungs were used; tumor-infiltrating leukocytes were evaluated by flow cytometry and multispectral immunophenotyping.ResultsWe have developed polymeric NCs loaded with poly(I:C)+R848. Among a series of 5 lead prototypes, protamine-NCs were selected based on their physicochemical properties (size, charge, stability) and in vitro characterization, showing good biocompatibility on primary macrophages and ability to stimulate their production of T-cell attracting chemokines (CXCL10, CCL5) and to induce M1-like macrophages cytotoxicity towards tumor cells. In mouse tumor models, the intratumoral injection of poly(I:C)+R848-protamine-NCs significantly prevented tumor growth and lung metastasis. In an orthotopic murine lung cancer model, the intravenous administration of poly(I:C)+R848-prot-NCs, coated with an additional layer of HA-mannose to improve TAM-targeting, resulted in good antitumoral efficacy with no apparent systemic toxicity. While no significant alterations were observed in T cell numbers (CD8, CD4 or Treg), TAM-reprogramming in treated mice was confirmed by the relative decrease of interstitial versus alveolar macrophages, having higher CD86 expression but lower CD206 and Arg1 expression in the same cells, in treated mice.ConclusionMannose-HA-protamine-NCs loaded with poly(I:C)+R848 successfully reprogram TAMs in vivo, and reduce tumor progression and metastasis spread in mouse tumors.

Published
2024
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15. Sport and self-esteem in people living with HIV: a cross-sectional study

Author

Lucia Grandiere Perez, Clotilde Allavena, Solène Sécher, Sylvain Durand, Antoine Grégoire, Yves-Marie Vandamme, Hikombo Hitoto, Sophie Leautez-Nainville, Christophe Michau, and Eric Billaud

Subjects
HIV, Sport, Self-esteem, Fatigue, Pain, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background In the general population, sport activity is associated with better health and better self-esteem. Among people living with HIV (PLHIV), sport activity could also be associated with better self-esteem. The main objective of our study was to assess the association between sport activity and self-esteem among people living with HIV. The secondary objectives were to evaluate the associations between sport activity with fatigue as well as with pain. Methods We performed a cross-sectional observational study among PLHIV in our region (Pays de la Loire in France). Each adult seen in routine HIV care was invited to participate in the study. Participants were invited to fill out self-questionnaires about sport activity, self-esteem, fatigue, and pain. The 2 groups of participants with and without sport activity were compared with a T Student test for self-esteem, fatigue, and pain scales. Results Among the 1160 people included in the study, 47% performed sport activity. The self-esteem score was better in the “sporting group” compared with the “non sporting group” (Rosenberg mean scale 32.7 ± 5.1/40 vs 31.9 ± 5 p = 0.01). The Functional Assessment of Chronic Illness Therapy Fatigue scale showed a lower fatigue in the sporting group than in the non-sporting group (mean total score 125 ± 22 vs 118 ± 24 p

Published
2022
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16. Spontaneous Lesions of Endangered Geriatric Julia Creek Dunnarts (Sminthopsis douglasi, Archer 1979) with Emphasis in Reproductive Pathology

Author

Viviana Gonzalez-Astudillo, Andrea Schaffer-White, Lawrence Noble, Patricia O’Hara, Peter Murray, Tamsin S. Barnes, and Rachel Allavena

Subjects
aging, captive breeding, Dasyuridae, lymphoma, marsupial, senescence, Veterinary medicine, SF600-1100
Abstract

Julia Creek dunnarts are an endangered species of carnivorous marsupials and the focus of multiple conservation strategies involving significant resources such as captive breeding programs. Despite the relevance for conservation, no study to date has focused on evaluating geriatric diseases in dunnarts. This study describes the pathology findings in a group of one wild and thirty-five captive-born, mostly geriatric Julia Creek dunnarts that failed to produce offspring over multiple breeding periods. A total of 20 females and 16 males were submitted for a postmortem examination, with ages ranging from 9 to 42 and 12 to 42 months for females and males, respectively. Of these, 10 had unremarkable findings. The most common condition in females was cystic glandular hyperplasia (n = 8), typical of hormonal dysregulation profiles in senescence, particularly hyperestrogenism. Rarely, cutaneous disease represented by unidentified dermal round cell infiltrates was observed in females (n = 2). Primary reproductive hormonal dysregulation was also suspected in males diagnosed with testicular degeneration, aspermatogenesis and/or atrophy (n = 3). Cutaneous round cell infiltrates, possibly compatible with epitheliotropic lymphomas, were seen in males (n = 3), and 2/3 affected males also had concurrent testicular degeneration or atrophy, indicating male sex could be a predictor for lymphoid neoplasia in aged dunnarts, especially in individuals with concurrent testosterone-luteinizing hormone dysregulation as it occurs in gonadectomized animals. The role of an underlying viral etiology is also explored. This study is the first to describe major spontaneous diseases in endangered aged Julia Creek dunnarts, providing an important understanding of senescence and geriatric diseases within a conservation context.

Published
2024
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17. Effect of a Lactobacilli-Based Direct-Fed Microbial Product on Gut Microbiota and Gastrointestinal Morphological Changes

Author

John I. Alawneh, Hena Ramay, Timothy Olchowy, Rachel Allavena, Martin Soust, and Rafat Al Jassim

Subjects
direct-fed microbials, GIT morphology, calves, live weight, diversity, microbiota, Veterinary medicine, SF600-1100, Zoology, QL1-991
Abstract

The calf’s gastrointestinal tract (GIT) microbiome undergoes rapid shifts during early post-natal life, which can directly affect calf performance. The objectives of this study were to characterise and compare differences in the establishment and succession of GIT microbiota, GIT morphological changes, and the growth of dairy calves from birth until weaned. Forty-four newborn Holstein-Friesian calves were randomly selected and assigned to Treatment (TRT) and Control (CON) groups. The TRT group calves received a once-daily dose of a direct-fed microbial (DFM) liquid product containing Lacticaseibacillus paracasei, Lentilactobacillus buchneri, and Lacticaseibacillus casei, all formerly known as Lactobacillus. Fresh faecal samples were manually taken from the rectum of all calves, and gross necropsy was performed on the forestomachs and gastrointestinal tracts. Bacterial DNA was extracted from frozen faecal samples for 16S rRNA gene amplicon sequencing. Calves in the TRT group had greater live weights (p = 0.02) at weaning compared with calves in the CON group (mean = 69.18 kg, SD = 13.37 kg). The average daily live weight gain (ADG) and total feed intake were similar between the two groups. Calves in the TRT group had greater duodenum, abomasum, and reticulum weights (p = 0.05). Rumen and intestinal development (p < 0.05) and faecal microbial diversity (p < 0.05) were more pronounced in the TRT group. The relative abundances of eight genera differed (p < 0.001) between the groups. Supplementing calves with the LAB-based DFM increased live weight at weaning and had a more pronounced effect on the development of rumen and the gastrointestinal tract and on microbiota diversity and evenness. Future work is needed to better understand the potential association of LAB-DFM products on gut mucosa-associated microbiota.

Published
2024
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18. Important functional role of the protein osteopontin in the progression of malignant pleural mesothelioma

Author

Elisabeth Digifico, Marco Erreni, Laura Mannarino, Sergio Marchini, Aldo Ummarino, Clément Anfray, Luca Bertola, Camilla Recordati, Daniela Pistillo, Massimo Roncalli, Paola Bossi, Paolo Andrea Zucali, Maurizio D’Incalci, Cristina Belgiovine, and Paola Allavena

Subjects
osteopontin (OPN), MPM (malignant pleural mesothelioma), immune system and cancer, immunotherapy, novel therapeutic approach, Immunologic diseases. Allergy, RC581-607
Abstract

BackgroundMalignant Pleural Mesothelioma (MPM) is an aggressive cancer of the mesothelial lining associated with exposure to airborne non-degradable asbestos fibers. Its poor response to currently available treatments prompted us to explore the biological mechanisms involved in its progression. MPM is characterized by chronic non-resolving inflammation; in this study we investigated which inflammatory mediators are mostly expressed in biological tumor samples from MPM patients, with a focus on inflammatory cytokines, chemokines and matrix components.MethodsExpression and quantification of Osteopontin (OPN) was detected in tumor and plasma samples of MPM patients by mRNA, immunohistochemistry and ELISA. The functional role of OPN was investigated in mouse MPM cell lines in vivo using an orthotopic syngeneic mouse model.ResultsIn patients with MPM, the protein OPN was significantly more expressed in tumors than in normal pleural tissues and predominantly produced by mesothelioma cells; plasma levels were elevated in patients and associated with poor prognosis. However, modulation of OPN levels was not significantly different in a series of 18 MPM patients receiving immunotherapy with durvalumab alone or with pembrolizumab in combination with chemotherapy, some of whom achieved a partial clinical response. Two established murine mesothelioma cell lines: AB1 and AB22 of sarcomatoid and epithelioid histology, respectively, spontaneously produced high levels of OPN. Silencing of the OPN gene (Spp1) dramatically inhibited tumor growth in vivo in an orthotopic model, indicating that OPN has an important promoting role in the proliferation of MPM cells. Treatment of mice with anti-CD44 mAb, blocking a major OPN receptor, significantly reduced tumor growth in vivo.ConclusionThese results demonstrate that OPN is an endogenous growth factor for mesothelial cells and inhibition of its signaling may be helpful to restrain tumor progression in vivo. These findings have translational potential to improve the therapeutic response of human MPM.

Published
2023
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19. In vivo performance of a rare earth free Mg–Zn–Ca alloy manufactured using twin roll casting for potential applications in the cranial and maxillofacial fixation devices

Author

Matthew S. Dargusch, Nagasivamuni Balasubramani, Nan Yang, Sean Johnston, Yahia Ali, Gui Wang, Jeffrey Venezuela, Jiwon Carluccio, Cora Lau, Rachel Allavena, Daniel Liang, Karine Mardon, and Qingsong Ye

Subjects
Mg–Zn–Ca alloy, Twin-roll strip casting, In vivo degradation, Biocompatibility, Biodegradable implants, Materials of engineering and construction. Mechanics of materials, TA401-492, Biology (General), QH301-705.5
Abstract

A magnesium alloy containing essential, non-toxic, biodegradable elements such as Ca and Zn has been fabricated using a novel twin-roll casting process (TRC). Microstructure, mechanical properties, in vivo corrosion and biocompatibility have been assessed and compared to the properties of the rare earth (RE) element containing WE43 alloy. TRC Mg-0.5 wt% Zn- 0.5 wt% Ca exhibited fine grains with an average grain size ranging from 70 to 150 μm. Mechanical properties of a TRC Mg-0.5Zn-0.5Ca alloy showed an ultimate tensile strength of 220 MPa and ductility of 9.3%. The TRC Mg-0.5Zn-0.5Ca alloy showed a degradation rate of 0.51 ± 0.07 mm/y similar to that of the WE43 alloy (0.47 ± 0.09 mm/y) in the rat model after 1 week of implantation. By week 4 the biodegradation rates of both alloys studied were lowered and stabilized with fewer gas pockets around the implant. The histological analysis shows that both WE43 and TRC Mg-0.5Zn-0.5Ca alloy triggered comparable tissue healing responses at respective times of implantation. The presence of more organized scarring tissue around the TRC Mg-0.5Zn-0.5Ca alloys suggests that the biodegradation of the RE-free alloy may be more conducive to the tissue proliferation and remodelling process.

Published
2022
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20. Economic impact of generic antiretrovirals in France for HIV patients’ care: a simulation between 2019 and 2023

Author

Romain Demeulemeester, Nicolas Savy, Michaël Mounié, Laurent Molinier, Cyrille Delpierre, Pierre Dellamonica, Clotilde Allavena, Pascal Pugliesse, Lise Cuzin, Philippe Saint-Pierre, and Nadège Costa

Subjects
HIV, Generic antiretrovirals, Economic evaluation, Simulations, Agent-based model, Public aspects of medicine, RA1-1270
Abstract

Abstract Background In a context where the economic burden of HIV is increasing as HIV patients now have a close to normal lifespan, the availability of generic antiretrovirals commonly prescribed in 2017 and the imminence of patent expiration are expected to provide substantial savings in the coming years. This article aims to assess the economic impact of these generic antiretrovirals in France and specifically over a five-year period. Methods An agent-based model was developed to simulate patient trajectories and treatment use over a five-year period. By comparing the results of costs for trajectories simulated under different predefined scenarios, a budget impact model can be created and sensitivity analyses performed on several parameters of importance. Results The potential economic savings from 2019 to 2023 generated by generic antiretrovirals range from €309 million when the penetration rate of generics is set at 10% to €1.5 billion at 70%. These savings range from €984 million to €993 million as the delay between patent and generic marketing authorisation varies from 10 to 15 years, and from €965 million to €993 million as the Negotiated Price per Unit (NPU) of generics at market-entry varies from 40 to 50% of the NPU for patents. Discussion This economic savings simulation could help decision makers to anticipate resource allocations for further innovation in antiretrovirals therapies as well as prevention, especially by funding the Pre-Exposure Prophylaxis (PrEP) or HIV screening.

Published
2022
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21. Insights into heat treatments of biodegradable Mg-Y-Nd-Zr alloys in clinical settings: Unveiling roles of β' and β1 nanophases and latent in vivo hydrogen evolution.

Author

Dargusch, Matthew, Wang, Yuan, Sha, Chuhan, Yang, Nan, Chen, Xingrui, Venezuela, Jeffrey, Otte, Joseph, Johnston, Sean, Lau, Cora, Allavena, Rachel, Mardon, Karine, McCaroll, Ingrid, and Cairney, Julie

Abstract

Heat treatment serves as a viable strategy to effectively mitigate the intense corrosion of biodegradable WE43 alloys. However, limited comprehension of the passivation mechanisms underlying heat treatment and the dilemma to quantitatively examine the evolution of hydrogen gas in vivo introduce uncertainties in designing heat treatments for developing clinically applicable WE43. This work aims to advance this knowledge by applying cutting-edge atom probe tomography to provide atomic-scale insights into the passivation roles of rare earth (RE)-rich β 1 (Mg 3 (Y, Nd)) and β' (Mg 12 NdY) nanophases induced by T6 heat treatment at 250 °C, and employing machine learning-based image analysis techniques to quantitatively unveil WE43's in vivo gas evolution during a 12-week implantation. It was found that nanosized β 1 and β' phases can effectively improve WE43′s corrosion resistance by inducing an accelerated passivation effect on the surface and confining the distribution of hydrogen ions in the matrix. Female rats presented slightly higher corrosion rates than male rats in weeks 1 and 4 but lower hydrogen gas volumes in vivo , while male rats possessed a superior ability to metabolise hydrogen gas in vivo. Notably, latent gas evolution against the corrosion rates was found which peaked at week 4 and subsided at week 12 despite the gradually decreased corrosion rates from week 1 to 12. This study offers insights for engineering heat treatments to develop clinically applicable WE43 with acceptable corrosion rates and in vivo gas generation at various implantation stages. The study aimed to reveal the role of β 1 and β' nanophases on the good corrosion resistance of WE43. The influence of these nanophases on WE43′s corrosion performance has not been totally understood. Similarly, the understanding of hydrogen gas evolution as it relates to the magnesium implant's corrosion rate lacks clarity. Atom probe tomography (APT) indicates β 1 and β' nanophases trap hydrogen, removing H 2 from the lattice and disabling its catalytic role in Mg oxidation. Machine learning-aided analyses of computed tomography (CT) scan images indicate latent gas evolution, contradicting the monotonic in vivo H 2 evolution that is widely accepted. [Display omitted] [ABSTRACT FROM AUTHOR]

Published
2024
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22. Raltegravir 1200 mg once daily as maintenance therapy in virologically suppressed HIV-1 infected adults: QDISS open-label trial

Author

Nolwenn Hall, Clotilde Allavena, Christine Katlama, Alexandra Jobert, Jean-Michel Molina, Eric Cua, Firouzé Bani-Sadr, Laurent Hocqueloux, Claudine Duvivier, Dominique Merrien, Hitoto Hikombo, Elisabeth André-Garnier, Aurélie Gaultier, François Raffi, and the QDISS Study Group

Subjects
HIV-1 infection, Raltegravir, Once daily, Integrase inhibitor, Maintenance, Switch, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background Raltegravir (RAL) has favorable tolerability and safety profile, with few and manageable drug interactions. The use of RAL 1200 mg once daily (qd) for first-line therapy is well established. We assessed efficacy and safety of RAL 1200 mg qd, as part of triple combined antiretroviral therapy (cART), for maintenance strategy. Methods The QDISS trial (NCT03195452) was a 48-week multicenter, single-arm, open-label study designed to evaluate the ability of 2 NRTIs + RAL 1200 mg qd to maintain virological suppression in HIV-1 infected subjects on a stable cART with 2 NRTIs and a third agent for at least 6 months. The primary endpoint was the proportion of participants with HIV-1 RNA

Published
2022
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23. Pathology and pathogenesis of cutaneous lesions in beef cattle associated with buffalo fly infestation

Author

Muhammad Noman Naseem, Rachel Allavena, Ali Raza, Constantin Constantinoiu, Michael McGowan, Conny Turni, Muhammad Kamran, Ala E. Tabor, and Peter James

Subjects
haematobia, Stephanofilaria, buffalo fly, skin lesions, histopathology, Veterinary medicine, SF600-1100
Abstract

Haematobia irritans exigua, commonly known as buffalo fly, is the major hematophagous ectoparasite of north Australian cattle herds. Lesions associated with buffalo fly infestation are generally alopecic, hyperkeratotic, or scab encrusted wounds with variable hemorrhagic ulceration. Buffalo flies can transmit a filarial nematode, Stephanofilaria sp., which has been implicated in the pathogenesis of buffalo fly lesions, but Stephanofilaria infection has not been detected in all lesions suggesting that other causal factors may be involved. This study characterized the pathology of buffalo fly lesions to identify the role of Stephanofilaria in lesion development, as well as to identify other potential agents. Lesion biopsies were collected from north and south Queensland and tested for the presence of Stephanofilaria by qPCR. Each lesion was scored grossly (0–4) for hemorrhage, ulceration, exudation, and alopecia. Lesions were also scored microscopically (0–4) for epidermal and dermal damage and inflammatory characters. Stephanofilaria infection was detected in 31% of lesion biopsies. Grossly, Stephanofilaria-infected lesions had significantly larger lesion area and higher scores for alopecia and hyperkeratosis than lesions where no nematodes were found (P < 0.05). Histologically, epidermal, dermal, and adnexal damage was significantly higher in Stephanofilaria infected lesions than lesions without nematodes. Eosinophils, macrophages, and lymphocytes were significantly more abundant in Stephanofilaria positive lesions as compared to negative lesions. This study also noted bacterial infection with colonies of coccoid bacteria, observed in skin sections from 19 lesions. Grossly, lesions with bacterial infection had significantly higher ulceration scores compared to Stephanofilaria positive lesions, and histologically epidermal disruption was significantly greater in bacteria-infected lesions. We found no evidence of bacteria or Stephanofilaria infection in 49% of the lesions assessed and tissue damage patterns and eosinophilic inflammation suggested hypersensitivity to buffalo fly feeding as a possible cause of these lesions. These findings suggest that although the presence of Stephanofilaria infection may increase the severity of lesion pathology, it is not essential for lesion development. These outcomes also suggest a potential role of bacteria and hypersensitivity in pathogenesis of some lesion. A better understanding of buffalo fly lesion etiology will contribute to the optimal treatment and control programmes.

Published
2023
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27. Estimating koala density from incidental koala sightings in South‐East Queensland, Australia (1997–2013), using a self‐exciting spatio‐temporal point process model

Author

Ravi Bandara Dissanayake, Emanuele Giorgi, Mark Stevenson, Rachel Allavena, and Joerg Henning

Subjects
citizen science, koala, modeling, population, Queensland, Ecology, QH540-549.5
Abstract

Abstract The koala, Phascolarctos cinereus, is an iconic Australian wildlife species facing a rapid decline in South‐East Queensland (SEQLD). For conservation planning, the ability to estimate the size of koala populations is crucial. Systematic surveys are the most common approach to estimate koala populations but because of their cost they are often restricted to small geographic areas and are conducted infrequently. Public interest and participation in the collection of koala sighting data is increasing in popularity, but such data are generally not used for population estimation. We modeled monthly sightings of koalas reported by members of the public from 1997 to 2013 in SEQLD by developing a self‐exciting spatio‐temporal point process model. This allowed us to account for characteristics that are associated with koala presence (which vary over both space and time) while accounting for detection bias in the koala sighting process and addressing spatial clustering of observations. The density of koalas varied spatially due to the heterogeneous nature of koala habitat in SEQLD, with a mean density of 0.0019 koalas per km2 over the study period. The percentage of land areas with very low densities (0–0.0005 koalas per km2) remained similar throughout the study period representing, on average, 66% of the total study area. The approach described in this paper provides a useful starting point to allow greater use to be made of incidental koala sighting data. We propose that the model presented here could be used to combine systematic koala survey data (which is spatially restricted, but more precise) with koala sighting data (which is incidental and often biased by nature, but often collected over large geographical areas). Our approach could also be adopted for modeling the density of other wildlife species where data is collected in the same manner.

Published
2021
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28. Paediatric COVID-19 mortality: a database analysis of the impact of health resource disparity

Author

Nick Daneman, John Marshall, Vinod Kumar, Aasiyah Rashan, Jérôme Dimet, Sylvain Diamantis, John F Fraser, Dominique Deplanque, Anne Conrad, François Lellouche, Heidi Gruner, Detlef Kindgen-Milles, Agnes Meybeck, Maxime Hentzien, Clotilde Allavena, André Cabié, Firouzé Bani-Sadr, Patrick Rossignol, Arjen M Dondorp, Rashan Haniffa, Harald Vonkeman, Lionel Piroth, Mathieu Blot, Yaseen Arabi, Marie-Pierre Debray, François Angoulvant, Marc Leone, Maria Zambon, Florentia Kaguelidou, Marc Lambert, Olivier Lairez, Tom Solomon, Carrol Gamble, Laura Marsh, David Richardson, Christiana Kartsonaki, Philippe Jouvet, Asgar Rishu, Eman Al Qasim, Rachael Parke, Srinivas Murthy, Alistair Nichol, Calum Semple, Colin McArthur, Gail Carson, Jake Dunning, Laura Merson, Peter Horby, David Maslove, Nadia Malik, Stephen R Knight, Annelies Verbon, Oana Sândulescu, Patrick Archambault, Paul McNally, Marlene Murris, Aurore Bousquet, Kenneth A McLean, Hugues Cordel, Marc Fabre, Laurence Bouillet, Melissa Parker, Xavier Duval, Amanda Corley, James Lee, Kusum Menon, Christian Rabaud, Paul Klenerman, Jean-François Timsit, Jennifer Lee, Nicolas Terzi, Saad Nseir, Gwenhaël Colin, Steve Webb, Kalynn Kennon, Caroline Mudara, Diana Hernández, Yazdan Yazdanpanah, Elias Iosifidis, Emmanuel Roilides, Yi Lin Lee, Pieter Depuydt, Jean-François Payen, Ana Martins, Samreen Ijaz, Meera Chand, Wei Shen Lim, Bruno Levy, Eric D'ortenzio, Jean-Charles Preiser, Pierre Delobel, Claudia Figueiredo-Mello, Jaques Sztajnbok, Ana Freitas Ribeiro, Tiphaine Goulenok, Bronner P Gonçalves, Arnaud Scherpereel, Chloe Donohue, Carlo Giaquinto, Karolina Nowicka, Adrien Auvet, Debby Bogaert, Elisabeth Botelho-Nevers, Amandine Gagneux-Brunon, Merce Jourdain, Anne McCarthy, Todd C Lee, António Mesquita, Sue Smith, Jia Wei, Jenny Lennon, Antoine Khalil, Nathalie Pansu, Victor Fomin, Audrey Barrelet, Christophe Fraser, Daniel Munblit, Robert A Fowler, William Greenhalf, François-Xavier Lescure, Nicolas Carlier, Saye Khoo, Riinu Pius, Lisa Norman, Louise Sigfrid, Sophie Halpin, Clare Jackson, Antonia Ho, Andrew Dagens, Thomas Flament, Julie Mankikian, Romain Basmaci, Peter Openshaw, Mary Copland, Brenda Reeve, William Dechert, Patricia Lizotte, Felwa Bin Humaid, Tom Fletcher, Adrien Lemaignen, Pierre Tattevin, Christelle Delmas, Hélène Espérou, Claire Lévy-Marchal, Olivier Picone, Jeanne Sibiude, Cecile Yelnik, Olivia V Swann, Michelle Girvan, Piero L Olliaro, Beatrice Alex, Benjamin Bach, Alexander J Mentzer, Mahdad Noursadeghi, Shona C Moore, Massimo Palmarini, Georgios Pollakis, Vanessa Sancho-Shimizu, Shiranee Sriskandan, David Stuart, Charlotte Summers, Ryan S Thwaites, Hayley Hardwick, Wilna Oosthuyzen, Fiona Griffiths, Jo Dalton, Egle Saviciute, Stephanie Roberts, Janet Harrison, Marie Connor, Gary Leeming, Ross Hendry, Victoria Shaw, Jade Ghosn, Lucille Blumberg, Nicolas Benech, James Scott-Brown, Odile Launay, Todd Karsies, Yoan Lavie-Badie, Minh Le, Elise Artaud-Macari, Mylène Maillet, Huda Alfoudri, Djura Piersma, Didier Laureillard, Graham S. Cooke, Nicholas Sedillot, Anne-Sophie Boureau, Tony Trapani, Laurent Abel, Samuel Hinton, Sally Shrapnel, Heidi Dalton, Guillaume Martin-Blondel, Valérie Garrait, Isabelle Delacroix, Samantha Lissauer, Malte Kohns Vasconcelos, Oleksa Rewa, Erlina Burhan, Sara Machado, Jean-Benoît Arlet, Raphaël Borie, Kévin Bouiller, Vincent Langlois, Mélanie Roriz, Mical Paul, Vincent Dubée, Erwan L'her, Michael Rose, Luis Felipe Reyes, Anna Beltrame, Stéphanie Fry, Andrew Udy, Laurent Plantier, Jean-Christophe Goffard, Denis Malvy, Nina Jamieson, Irfan Khan, François Dubos, Jean-Sébastien Hulot, Paola Rodari, Paul Campbell, Abigail Beane, Cécile Tromeur, Paul Loubet, Marina Esposito-Farèse, France Mentré, Valérie Gaborieau, Anne-Marie Guerguerian, Cécile Goujard, Vincent Thibault, Rodrigo Díaz, Patricia Gordon, Sadie Kelly, Bertrand Dussol, Simon Forsyth, Marion Schneider, Nathalie Gault, Marielle Buisson, Yves Levy, Prasan Kumar Panda, Marjolein Brusse-Keizer, Carine Roy, Walter Picard, Tom Drake, Paul Tierney, Olivier Sanchez, Antoine Kimmoun, David Thomson, Nathan Peiffer-Smadja, Julien Poissy, Lila Bouadma, Bruno Lina, Maude Bouscambert, Alexandre Gaymard, Gilles Peytavin, Jeremie Guedj, Claire Andrejak, Cedric Laouenan, Anissa Chair, Samira Laribi, Marie-Capucine Tellier, Sandrine Couffin-Cadiergues, Soizic Le Mestre, Ventzislava Petrov-Sanchez, Alpha Diallo, NoéMie Mercier, Sarah Tubiana, Marion Noret, Oriane Puechal, Caroline Semaille, Patrick Imbert, Jonathan Remppis, Emmanuelle Mercier, Rui Pereira, Sylvie Van Der Werf, Waasila Jassat, Arsene Kpangon, Dominique Luton, Sophie Mahy, Pierre-Adrien Bolze, Sarah Moore, Adrienne Chan, Raphael Favory, Daniel Mathieu, Andrea Angheben, Andrea Rossanese, Matthew Hall, Johann Auchabie, Mohammed Quraishi, Katharina Weil, Hanna Renk, Hans Martin Bosse, Christophe Rapp, Vincent Peigne, Tae Song, Dewi Guellec, Mark G. Pritchard, Adrian Streinu-Cercel, Christl A Donnelly, François Goehringer, Elodie Curlier, Catherine Chirouze, Stéphane Jaureguiberry, Ary Serpa Neto, Jose Andres Calvache, Laurent Bitker, Hodane Yonis, Neerusha Kaisbain, Coline Jaud-Fischer, Laurent Mandelbrot, Jérémie Pasquier, Juliette Patrier, Gianluigi Li Bassi, Sheryl Ann Abdukahil, Jia Shyi Loy, Filipe Cardoso, Diptesh Aryal, Polina Bugaeva, Evert-Jan Wils, Stephanie Yerkovich, Julie Chas, Thushan de Silva, Ruth Lyons, Murray Wham, Sara Clohisey, Seán Keating, Thibault Chiarabini, Agnes Sommet, Hugues Aumaître, Sylvie LeGac, Sarah E McDonald, Jeanne Truong, Camille Couffignal, Anne-Hélène Boivin, Timo Brandenburger, Diane Descamps, Tala Al-Dabbous, Mark Joseph, Hwa Jin Cho, Desy Rusmawatiningtyas, Muhammad Rayhan, Christel Arnold-Day, Navy Lolong, Ernita Akmal, Menaldi Rasmin, Daniel Marino, Neurinda Permata Kusumastuti, Stéphane Lasry, Amanda Rojek, Sebastien Preau, Jean-Marie Turmel, Nowneet Kumar Bhat, Cynthia Braga, Pavan Kumar Vecham, Benoit Thill, Karine Faure, Denis Garot, Grégory Corvaisier, Elsa Nyamankolly, Joshua Solomon, Emma Clarke, Patricia Fontela, Eva Geraud, Eva Miranda Marwali, Aria Kekalih, Saptadi Yuliarto, Dyah Kanya Wati, Ivy Cerelia Valerie, Maureen Masha, Jolanta Popielska, Anca Streinu-Cercel, Mohan Dass Pathmanathan, Barbara Wanjiru Citarella, Heidi Jean Dalton, Nurul Najmee Abdulkadir, Lara Absil, Subhash Acharya, Diana Adrião, Younes Ait Tamlihat, Kévin Alexandre, Kazali Enagnon Alidjnou, Nathalie Allou, Rita Alves, Joana Alves Cabrita, Maria Amaral, Nur Amira, Phoebe Ampaw, Séverine Ansart, Sivanesen Anthonidass, Carlos Alexandre Brito, Ardiyan Apriyana, Carolline Araujo, Muhammad Ashraf, Jean Baptiste Assie, Amirul Asyraf, Anika Atique, AM Udara Attanyake, Laurène Azemar, Cecile Azoulay, Delphine Bachelet, Claudine Badr, J. Kenneth Baillie, Nazreen Abu Bakar, Mohanaprasanth Balakrishnan, Valeria Balan, Renata Barbalho, Wendy S. Barclay, Saef Umar Barnett, Marie Bartoli, Joaquín Baruch, Muhammad Fadhli Basri, Jules Bauer, Diego Fernando Rincon, Alexandra Bedossa, Ker Hong Bee, Husna Begum, Sylvie Behilill, Albertus Beishuizen, Marine Beluze, Lionel Eric Benjiman, Dehbia Benkerrou, Delphine Bergeaud, José Luis Sobrino, Giulia Bertoli, Simon Bessis, Sybille Bevilcaqua, Karine Bezulier, Krishna Bhavsar, Farah Nadiah Bidin, Mohd Nazlin Kamarudin, François Bissuel, Jonathan Bitton, Laetitia Bodenes, Isabela Bolaños, François Bompart, Diogo Borges, Olivier Bouchaud, Sabelline Bouchez, Dounia Bouhmani, Damien Bouhour, Camile Bouisse, Jason Bouziotis, Bianca Boxma, Marielle Boyer-Besseyre, Fernando Augusto Bozza, Axelle Braconnier, Kathy Brickell, Aidan Burrell, Ingrid G Bustos, Denis Butnaru, Eder Caceres, Cyril Cadoz, Rui Caetano Garcês, Valentine Campana, Pauline Caraux-Paz, Chiara Simona Cardellino, Sofia Cardoso, Filipa Cardoso, Thierry Carmoi, Marie-Christine Carret, François Martin Carrier, Maire-Laure Casanova, Mariana Cascão, José Casimiro, Nidyanara Castanheira, Guylaine Castor-Alexandre, François-Xavier Catherine, Paolo Cattaneo, Roberta Cavalin, Minerva Cervantes-Gonzalez, Catherine Chakveatze, Christelle Chantalat Auger, Jean-Marc Chapplain, Anjellica Chen, Matthew Pellan Cheng, Antoine Cheret, Julian Chica, Suresh Kumar Chidambaram, Leong Chin Tho, Bernard Cholley, Marie-Charlotte Chopin, Ting Soo Chow, Hiu Jian Chua, Jonathan Chua, Alexandra Coelho, Megan Coles, Pamela Combs, Sabine Cornelis, Alexander Daniel Cornet, Arianne Joy Corpuz, Emma Costigan, Roxane Courtois, Stéphanie Cousse, Rachel Cregan, Sabine Croonen, Claudina Cruz, Juan Luis Bermúdez, Jaime Cruz Rojo, Paula Custodio, Ana Silva Filipe, Charlene Da Silveira, Juliana Damas, Corinne Daniel, Emmanuelle A Dankwa, Jorge Dantas, Etienne De Montmollin, Rafael Freitas França, Peter de Vries, Jillian Deacon, Alexa Debard, Nathalie DeCastro, Lauren Deconninck, Romain Decours, Eve Defous, Eric Delaveuve, Karen Delavigne, Corine Delsing, Elisa Demonchy, Emmanuelle Denis, Mathilde Desvallées, Santi Dewayanti, Pathik Dhanger, André Dias, Kévin Didier, Jean-Luc Diehl, Wim Dieperink, Vincent Dinot, Fara Diop, Alphonsine Diouf, Yael Dishon, Félix Djossou, Annemarie B. Docherty, Maria Donnelly, Céline Dorival, James Joshua Douglas, Nathalie Dournon, Murray Dryden, Claudio Duarte Fonseca, Alexandre Ducancelle, Paul Dunand, Sim Choon Ean, Mohammed El Sanharawi, Brigitte Elharrar, Philippine Eloy, Isabelle Enderle, Chan Chee Eng, Ilka Engelmann, Vincent Enouf, Olivier Epaulard, Martina Escher, Catarina Espírito Santo, João Estevão, Manuel Etienne, Nadia Ettalhaoui, Mirjam Evers, Isabelle Fabre, Amna Faheem, Arabella Fahy, Cameron J. Fairfield, Pedro Faria, Ahmed Farooq, Hanan Fateena, Jorge Fernandes, Marília Andreia Fernandes, François-Xavier Ferrand, Eglantine Ferrand Devouge, Joana Ferrão, Mário Ferraz, Bernardo Ferreira, Nicolas Ferriere, Céline Ficko, Clara Flateau, Tatiana Fonseca, Erwan Fourn, Robert A. Fowler, Marcela Vieira Freire, Rostane Gaci, Jean-Charles Gagnard, Yasmin Gani, Noelia García Barrio, Esteban Garcia-Gallo, Louis Gerbaud Morlaes, Nuno Germano, Jess Gibson, Tristan Gigante, Morgane Gilg, Guillermo Giordano, Valérie Gissot, Daniel Glikman, Petr Glybochko, Geraldine Goco, Siri Goepel, Jin Yi Goh, Marie Gominet, Bronner P. Gonçalves, Isabelle Gorenne, Laure Goubert, Pascal Granier, Christopher A. Green, Courtney Greene, Segolène Greffe, Albert Groenendijk, Anja Grosse Lordemann, Yusing Gu, Martin Guego, Daniela Guerreiro, Romain Guery, Anne Guillaumot, Laurent Guilleminault, Thomas Guimard, Marieke Haalboom, Daniel Haber, Hannah Habraken, Ali Hachemi, Nadir Hadri, Fakhir Haidri, Ansley Hamer, Rebecca Hamidfar, Lim Yuen Han, Kok Wei Hao, Ewen M. Harrison, Lars Heggelund, Astarini Hidayah, Rupert Higgins, Hikombo Hitoto, Yi Bin Ho, Alexandre Hoctin, Isabelle Hoffmann, Wei Han Hoh, Ikram Houas, Catherine L. Hough, Jimmy Ming-Yang Hsu, Arfan Ikram, Hajnal-Gabriela Illes, Hugo Inácio, Yun Sii Ing, Sarah Isgett, Tiago Isidoro, Nadiah Ismail, Margaux Isnard, Danielle Jaafar, Salma Jaafoura, Julien Jabot, Pierre Jaquet, Florence Jego, Anilawati Mat Jelani, Ong Yiaw Joe, Cédric Joseph, Swosti Joshi, Dafsah Juzar, Ouifiya Kafif, Thavamany Kaleesvran, Sabina Kali, Muhammad Aisar Kamaluddin, Zul Amali Kamaruddin, Nadiah Kamarudin, Kong Yeow Kang, Pratap Karpayah, Anant Kataria, Kevin Katz, Yvelynne Kelly, Younes Kerroumi, Sharma Keshav, Coralie Khan, Quratul Ain Khan, Sushil Khanal, Abid Khatak, Ryan Khoo, Denisa Khoo, Khor How Kiat, Peter Kiiza, Rob Klont, Gry Kloumann Bekken, Robin Kobbe, Chamira Kodippily, Vinothini Krishnan, Ganesh Kumar, Bharath Kumar Vijayaraghavan, Demetrios Kutsogiannis, Marie Lachatre, Marie Lacoste, Marie Lagrange, Fabrice Laine, Antonio Lalueza, Marie Langelot-Richard, Marina Lanza, Delphine Lariviere, Andy Law, Teresa Lawrence, Clément Le Bihan, Cyril Le Bris, Georges Le Falher, Lucie Le Fevre, Quentin Le Hingrat, Marion Le Maréchal, Gwenaël Le Moal, Vincent Le Moing, Hervé Le Nagard, Paul Le Turnier, Ema Leal, Marta Leal Santos, Heng Gee Lee, Biing Horng Lee, Laurent Lefebvre, Bénédicte Lefebvre, Benjamin Lefèvre, Jean-Daniel Lelievre, Véronique Lemee, Anthony Lemeur, Ha Sha Lene, Quentin Lepiller, Olivier Lesens, Mathieu Lesouhaitier, Geoffrey Liegeon, Kah Chuan Lim, Lim Lina, Guillaume Lingas, Sylvie Lion-Daolio, Marine Livrozet, Leong Chee Loon, Diogo Lopes, Anthony L. Loschner, Bouchra Loufti, Guillame Louis, Lee Lee Low, Marije Lowik, Jean Christophe Lucet, Carlos Lumbreras Bermejo, Liem Luong, Oryane Mabiala, Moïse Machado, Gabriel Macheda, Hashmi Madiha, Guillermo Maestro de la Calle, Rafael Mahieu, Thomas Maitre, Fernando Maltez, Victoria Manda, Jose M. Mandei, Edmund Manning, Aldric Manuel, Ceila Sant'Ana Malaque, Samuel Markowicz, Celina Turchi Martelli, Martin Martinot, Caroline Martins Rego, Marsilla Marzukie, Sabina Mason, Sobia Masood, Basri Mat Nor, Moshe Matan, Mathieu Mattei, Romans Matulevics, Laurence Maulin, Thierry Mazzoni, Cécile Mear-Passard, Ogechukwu Menkiti, Antoine Merckx, Mayka Mergeay-Fabre, Alison M. Meynert, Vanina Meysonnier, Amina Meziane, Mehdi Mezidi, Céline Michelanglei, Isabelle Michelet, Nor Arisah Misnan, Tahira Jamal Mohamed, Nik Nur Mohamed, Asma Moin, Agostinho Monteiro, Claudia Montes, Lina Morales Cely, Lucia Moro, Hugo Mouquet Ben Morton, Clara Mouton Perrot, Julien Moyet, Ng Yong Muh, Dzawani Muhamad, Jimmy Mullaert, Karl Erik Müller, Himed Musaab, Himasha Muvindi, Gugapriyaa Muyandy, Nadège Neant, Nikita Nekliudov, Raul Neto, Anthony Nghi, Duc Nguyen, Nurul Amani Noordin, Nurul Faten Norharizam, Nurnaningsih Nurnaningsih, Annmarie O'Callaghan, Katie O'Hearn, Agnieszka Oldakowska, Piero L. Olliaro, David S.Y. Ong, Jee Yan Ong, Saijad Orakzai, Claudia Milena Orozco-Chamorro, Linda O'Shea, Siti Zubaidah Othman, Nadia Ouamara, Rachida Ouissa, Eric Oziol, Justine Pages Maïder Pagadoy, Lai Hui Pang, Aurélie Papadopoulos, Bruno Pastene, Christelle Paul, Jorge Paulos, William A. Paxton, Kalaiarasu Peariasamy, Miguel Pedrera Jiménez, Florent Peelman, Ithan D. Peltan, Daniel Perez, Thomas Perpoint, Vincent Pestre, Michele Petrovic, Scott Pharand, Carola Pierobon, Carlos Pimentel, Raquel Pinto, Catarina Pires, Isabelle Pironneau, Hon Shen Png, Ryadh Pokeerbux, Maria Pokorska-Spiewak, Diane Ponscarme, Douwe F. Postma, Diana Póvoas, Gamage Dona Priyadarshani, Vilmaris Quinones-Cardona, Víctor Quirós González, Marie Rafiq, Rozanah Abd Rahman, Ahmad Kashfi Rahman, Giri Shan Rajahram, Nagarajan Ramakrishnan, José Ramalho, Ahmad Afiq Ramli, Blandine Rammaert, Grazielle Viana Ramos, Thalha Rashan, Cornelius Rau, Tharmini Ravi, Stanislas Rebaudet, Sarah Redl, Attaur Rehman, Martine Remy, Hongru Ren, Anne-Sophie Resseguier, Matthieu Revest, Laurent Richier, Siti Nurul Ridzuan, Ana L Rios, Patrick Rispal, Karine Risso, David L. Robertson, Olivier Robineau, Pierre-Marie Roger, Juliette Romaru, Manuel Rosa-Calatrava, Bénédicte Rossignol, Stella Rousset, Benoît Roze, Clark D. Russell, Musharaf Sadat, Valla Sahraei, Maximilien Saint-Gilles, Stéphane Sallaberry, Charlotte Salmon Gandonniere, Hélène Salvator, Zulfiqar Sandhu, Pierre-François Sandrine, Shirley Sarfo-Mensah, Benjamine Sarton, Parthena Savvidou, Yen Tsen Saw, Janet T. Scott, Jaganathan Selvanayagam, Mageswari Selvarajoo, Malcolm G. Semple, Rasidah Bt Senian, Eric Senneville, Tânia Sequeira, Pablo Serrano Balazote, Ellen Shadowitz, Syamin Asyraf Shahidan, Mohammad Shamsah, Shaikh Sharjeel, Catherine A. Shaw, Ashraf Sheharyar, Mohiuddin Shiekh, Nassima Si Mohammed, Ng Yong Siang, Benedict Sim Heng, Karisha Sivam, Morgane Snacken, Tze Vee Soh, Rima Song, Azlan Mat Soom, Albert Sotto, B. P Edouard Soum, Sanka Sri Darshana, Sarah Stabler, Ymkje Stienstra, Jacky Y. Suen, Deepashankari Suppiah, Andrey Svistunov, Sarah Syahrin, Shirin Tabrizi, Fabio S. Taccone, Lysa Tagherset, Shahdattul Mawarni Taib, Ewa Talarek, Kim Keat Tan, Yan Chyi Tan, Coralie Tardivon, M Azhari Taufik, Richard S. Tedder, Tze Yuan Tee, João Teixeira, Sze Kye Teoh, François Téoulé, Olivier Terrier, Hubert Tessier-Grenier, Alif Adlan Thabit, Zhang Duan Tham, Suvintheran Thangavelu, Simon-Djamel Thiberville, Jananee Thirumanickam, Emma C. Thomson, Surain Raaj Thurai, Peter S Timashev, Noémie Tissot, Jordan Zhien Toh, Sia Loong Tonnii, Marta Torre, Margarida Torres, Théo Treoux, Tiffany Trouillon, Christelle Tual, Lance C.W. Turtle, PG Ishara Udayanga, Timothy M. Uyeki, Luís Val-Flores, Amélie Valran, Marcel van den Berge, Job van der Palen, Paul van der Valk, Peter Van der Voort, Jarne Van Hattem, Carolien van Netten, Ilonka van Veen, Noémie Vanel, Shoban Raj Vasudayan, Charline Vauchy, Shaminee Veeran, Aurélie Veislinger, James Vickers, José Ernesto Vidal, César Vieira, Benoit Visseaux, Fanny Vuotto, Noor Hidayu Wahab, Suhaila Abdul Wahab, Nadirah Abdul Wahid, Tan Pei Wen, Sanne Wesselius, Nicole White, Paul Henri Wicky, Aurélie Wiedemann, Calvin Wong, Xin Ci Wong, Yew Sing Wong, Teck Fung Wong, Gan Ee Xian, Lim Saio Xian, Kuan Pei Xuan, Siti Rohani Yakop, Nicholas Yee Hing, Chian Hui Yeoh, Obada Yousif, Marion Zabbe, Masliza Zahid, Maram Zahran, Nor Zaila Zaidan, Konrad Zawadka, Nurul Zaynah, Hiba Zayyad, and David Zucman

Subjects
Pediatrics, RJ1-570
Abstract

Background The impact of the COVID-19 pandemic on paediatric populations varied between high-income countries (HICs) versus low-income to middle-income countries (LMICs). We sought to investigate differences in paediatric clinical outcomes and identify factors contributing to disparity between countries.Methods The International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) COVID-19 database was queried to include children under 19 years of age admitted to hospital from January 2020 to April 2021 with suspected or confirmed COVID-19 diagnosis. Univariate and multivariable analysis of contributing factors for mortality were assessed by country group (HICs vs LMICs) as defined by the World Bank criteria.Results A total of 12 860 children (3819 from 21 HICs and 9041 from 15 LMICs) participated in this study. Of these, 8961 were laboratory-confirmed and 3899 suspected COVID-19 cases. About 52% of LMICs children were black, and more than 40% were infants and adolescent. Overall in-hospital mortality rate (95% CI) was 3.3% [=(3.0% to 3.6%), higher in LMICs than HICs (4.0% (3.6% to 4.4%) and 1.7% (1.3% to 2.1%), respectively). There were significant differences between country income groups in intervention profile, with higher use of antibiotics, antivirals, corticosteroids, prone positioning, high flow nasal cannula, non-invasive and invasive mechanical ventilation in HICs. Out of the 439 mechanically ventilated children, mortality occurred in 106 (24.1%) subjects, which was higher in LMICs than HICs (89 (43.6%) vs 17 (7.2%) respectively). Pre-existing infectious comorbidities (tuberculosis and HIV) and some complications (bacterial pneumonia, acute respiratory distress syndrome and myocarditis) were significantly higher in LMICs compared with HICs. On multivariable analysis, LMIC as country income group was associated with increased risk of mortality (adjusted HR 4.73 (3.16 to 7.10)).Conclusion Mortality and morbidities were higher in LMICs than HICs, and it may be attributable to differences in patient demographics, complications and access to supportive and treatment modalities.

Published
2022
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29. A Multicentre Epidemiologic Study of Sudden and Unexpected Death in Adult Cats and Dogs in Australia

Author

Mirrim Kelly-Bosma, Joerg Henning, Mark Haworth, Richard Ploeg, Lucy Woolford, Alison Neef, Shubhagata Das, and Rachel Allavena

Subjects
pathology, post-mortem, necropsy, sudden death, companion animal, cat, Veterinary medicine, SF600-1100
Abstract

Sudden and unexpected death (SUD) is a common reason for animals to undergo post-mortem examination. There is limited literature examining the causes of SUD in cats and dogs, and no research specific to Australia. The purpose of this study was to investigate the epidemiology and pathology of SUD in cats and dogs in a multicentric study across Australia. Retrospective post-mortem reports of SUD in cats and dogs were obtained from four veterinary schools in Australia distributed across four states. The frequency of SUD between institutes ranged from 2.1% to 6.5%. Dogs composed the majority of the study population (76%), and males outnumbered females, particularly in the feline subpopulation. After necropsy, 37% of SUD remained cause unknown, the largest category in both cats and dogs. When cause was identified, cardiovascular disease was most common in both species, followed by gastrointestinal disease in dogs, and trauma in cats. In dogs, multinomial logistic regression identified age as a risk factor significantly associated with the four largest categories of SUD. This study identified causes of SUD in Australian cats and dogs, including novel causes not previously reported. Further, this study revealed a higher rate of unsolved SUD in Australia than can be found in the literature from other countries.

Published
2023
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30. Macrophages and cancer stem cells: a malevolent alliance

Author

Paola Allavena, Elisabeth Digifico, and Cristina Belgiovine

Subjects
Cancer stem cells, Tumor associated macrophages, Stemness, GPNMB, Therapeutics. Pharmacology, RM1-950, Biochemistry, QD415-436
Abstract

Abstract Myeloid cells infiltrating tumors are gaining ever growing attention in the last years because their pro-tumor and immunosuppressive functions are relevant for disease progression and therapeutic responses. The functional ambiguity of tumor-associated macrophages (TAMs), mostly promoting tumor evolution, is a challenging hurdle. This is even more evident in the case of cancer stem cells (CSCs); as active participants in the specialized environment of the cancer stem cell niche, TAMs initiate a reciprocal conversation with CSCs. TAMs contribute to protect CSCs from the hostile environment (exogenous insults, toxic compounds, attacks from the immune cells), and produce several biologically active mediators that modulate crucial developmental pathways that sustain cancer cell stemness. In this review, we have focused our attention on the interaction between TAMs and CSCs; we describe how TAMs impact on CSC biology and, in turn, how CSCs exploit the tissue trophic activity of macrophages to survive and progress. Since CSCs are responsible for therapy resistance and tumor recurrence, they are important therapeutic targets. In view of the recent success in oncology obtained by stimulating the immune system, we discuss some macrophage-targeted therapeutic strategies that may also affect the CSCs and interrupt their malevolent alliance.

Published
2021
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31. Greyhound morbidity and mortality in Australia: A descriptive analysis of reported data from regulatory racing agencies

Author

Vysie Chang, Kris Descovich, Joerg Henning, and Rachel Allavena

Subjects
greyhound dogs, animal welfare, regulations and policy, racetracks, animal euthanasia, injury, Veterinary medicine, SF600-1100
Abstract

Commercial greyhound racing is legal in Australia but controversial due to concerns around animal welfare. To make evidence-based recommendations of animal welfare standards, a comprehensive analysis of available data on race events, animal health, injuries and fatalities is required. We undertook a review of publicly available data and reports published by official greyhound racing bodies for the purpose of determining how morbidity and mortality events associated with dog training and racing could be benchmarked. 6 years of available data from stewards' reports, quarterly and annual reports were descriptively analyzed from New South Wales, Victoria and Queensland. Whole-of-life tracking for individual dogs was sparse. Although stewards' reports were published in all three states, the availability of aggregated quarterly and annual reports varied. When available these provided additional information such as injury incidents standardized per thousand starts. In Queensland, quarterly and annual reports provided an overview of greyhound mortality and morbidity rates. In contrast with Victoria, quarterly reports were unavailable and only annual reports were published, meaning quarterly trends could not be determined. Therefore, injuries categorized by severity that were routinely included in quarterly reports in Queensland and New South Wales were unavailable in Victoria. Our findings demonstrate that data recording and reporting practices must be standardized to accurately evaluate whether animal welfare standards are being met in the Australian greyhound racing industry. Our recommendation is to have national standardized reporting of injuries and deaths, and a publicly available database for whole-of-life tracking for individual racing greyhounds.

Published
2022
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32. Role of Staphylococcus agnetis and Staphylococcus hyicus in the Pathogenesis of Buffalo Fly Skin Lesions in Cattle

Author

Muhammad Noman Naseem, Conny Turni, Rosalind Gilbert, Ali Raza, Rachel Allavena, Michael McGowan, Constantin Constantinoiu, Chian Teng Ong, Ala E. Tabor, and Peter James

Subjects
Staphylococcus agnetis, Staphylococcus hyicus, Haematobia, buffalo fly lesions, cattle, exfoliative toxin, Microbiology, QR1-502
Abstract

ABSTRACT Buffalo flies (Haematobia irritans exigua) are hematophagous ectoparasites of cattle causing production and welfare impacts in northern Australian herds. Skin lesions associated with buffalo fly infestation and Stephanofilaria nematode infection are manifested as focal dermatitis or ulcerated areas, most commonly on the medial canthus of the eye, along the lateral and ventral neck, and on the abdomen of cattle. For closely related horn flies (Haematobia irritans irritans), Staphylococcus aureus has been suggested as a contributing factor in the development of lesions. To investigate the potential role of bacterial infection in the pathogenesis of buffalo fly lesions, swabs were taken from lesions and normal skin, and bacteria were also isolated from surface washings of buffalo flies and surface-sterilized homogenized flies. Bacterial identification was conducted by matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) and strain typing by repetitive sequence-based PCR (rep-PCR) and DNA sequencing to determine species similarity and virulence factors. Of 50 bacterial isolates collected from lesions, 38 were identified as Staphylococcus agnetis and 12 as Staphylococcus hyicus, whereas four isolates from normal skin were S. hyicus and one was Mammaliicoccus sciuri. Of the Staphylococcus isolates isolated from buffalo flies, five were identified as S. agnetis and three as S. hyicus. Fifty percent of the buffalo fly isolates had rep-PCR genotypic patterns identical to those of the lesion isolates. Genome sequencing of 16 S. agnetis and four S. hyicus isolates revealed closely similar virulence factor profiles, with all isolates possessing exfoliative toxin A and C genes. The findings from this study suggest the involvement of S. agnetis and S. hyicus in buffalo fly lesion pathogenesis. This should be taken into account in the development of effective treatment and control strategies for lesions. IMPORTANCE Skin lesions in cattle associated with feeding by Haematobia fly species are a significant welfare issue in Australia, North and South America, and Europe. The development of these lesions has been attributed to a number of causal factors, but the exact etiology and pathogenesis were unclear. This study characterized Staphylococcus agnetis and Staphylococcus hyicus strains from cattle skin lesions and in vector flies and demonstrated their role in the pathogenesis of these lesions. These findings will aid the development of targeted and more effective treatment and control strategies for lesions associated with fly infestation in cattle.

Published
2022
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33. Pentraxin 3 is a stromally-derived biomarker for detection of pancreatic ductal adenocarcinoma

Author

Michelle R. Goulart, Jennifer Watt, Imran Siddiqui, Rita T. Lawlor, Ahmet Imrali, Christine Hughes, Amina Saad, Joanne ChinAleong, Chris Hurt, Catrin Cox, Roberto Salvia, Alberto Mantovani, Tatjana Crnogorac-Jurcevic, Somnath Mukherjee, Aldo Scarpa, Paola Allavena, and Hemant M. Kocher

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Pancreatic ductal adenocarcinoma (PDAC), characterized by dense desmoplastic stroma laid down by pancreatic stellate cells (PSC), has no reliable diagnostic biomarkers for timely detection. A multi-center cohort of PDAC patients and controls (chronic pancreatitis, intra-ductal papillary neoplasms, gallstones and otherwise healthy) donated serum in an ethically approved manner. Serum PTX3 above 4.34 ng/mL has a higher sensitivity (86%, 95% confidence interval (CI): 65–97%) and specificity (86%, 95% CI: 79–91%), positive predictive value (97%) and likelihood ratio (6.05), and is superior when compared to serum CA19-9 and CEA for detection of PDAC. In vitro and ex vivo analyses of PTX3, in human PDAC samples, PSCs, cell lines and transgenic mouse model for PDAC, suggest that PTX3 originates from stromal cells, mainly PSC. In activated PSC, PTX3 secretion could be downregulated by rendering PSC quiescent using all-trans-retinoic acid (ATRA). PTX3 organizes hyaluronan in conjunction with tumor necrosis factor-stimulated gene 6 (TSG-6) and facilitates stellate and cancer cell invasion. In SCALOP clinical trial (ISRCTN96169987) testing chemo-radiotherapy without stromal targeting, PTX3 had no prognostic or predictive role. However, in STARPAC clinical trial (NCT03307148), stromal modulation by ATRA even at first dose is accompanied with serum PTX3 response in patients who later go on to demonstrate disease control but not those in whom the disease progresses. PTX3 is a putative stromally-derived biomarker for PDAC which warrants further testing in prospective, larger, multi-center cohorts and within clinical trials targeting stroma.

Published
2021
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34. Equine Crofton Weed (Ageratina spp.) Pneumotoxicity: What Do We Know and What Do We Need to Know?

Author

Frances Marie Shapter, José Luis Granados-Soler, Allison J. Stewart, Francois Rene Bertin, and Rachel Allavena

Subjects
horse, lung, fibrosis, pneumonia, toxic plant, pulmonary fibrosis, Veterinary medicine, SF600-1100, Zoology, QL1-991
Abstract

Crofton weed (Ageratina adenophora) is a global and highly invasive weed, with ingestion causing severe respiratory disease in horses, leading to irreversible and untreatable pulmonary fibrosis and oedema. While reports of equine pneumotoxicity remain common in Australia and New Zealand, equine pneumotoxicity may be underdiagnosed in other countries where Crofton weed is endemic but poorly differentiated. The pathogenesis of Crofton weed toxicity following ingestion has been well described in a number of different animal models, including rodents, rabbits, and goats. However, induced toxicity is organ-selective across different animal species, and these vastly differ from the pathogenesis described in horses, both clinically and after experimental exposure. Sources of variation may include species-specific susceptibility to different toxins present in the plant, different mechanistic processes of toxicity, and species differences in toxin biotransformation and bioactivation across different organs. Considering disease severity and Crofton weed’s invasiveness globally, assessing published toxicological and exposure data is necessary to advance research, identify specific toxins for horses, and possible prophylactic and therapeutic strategies. This review presents an overview of the available literature on equine toxicity, parallels between toxicity in horses and other animal species, and important aspects to be included in the future research agenda.

Published
2023
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35. The Development of Cutaneous Lesions in Tropically Adapted Beef Cattle Is Associated with Hypersensitive Immune Response to Buffalo Fly Antigens

Author

Muhammad Noman Naseem, Ali Raza, Muhammad Kamran, Rachel Allavena, Constantin Constantinoiu, Michael McGowan, Conny Turni, Ala E. Tabor, and Peter James

Subjects
Haematobia, Cattle skin lesions, Stephanofilaria, buffalo fly, hypersensitivity, Veterinary medicine, SF600-1100, Zoology, QL1-991
Abstract

This study investigated the role of cattle immune responses in the pathogenesis of buffalo fly (Haematobia irritans exigua) (BF) lesions. Brangus steers phenotyped for lesion development were divided into three groups: high lesion susceptibility (HL), low lesion susceptibility (LL) and no lesions (NL), based on lesion severity scores. Each steer was injected intradermally with different concentrations of BF, Onchocerca gibsoni (Og), and Musca domestica (Md) antigens. At 1 h post-injection, wheal areas at BF injection sites were found to be significantly larger in HL than NL cattle, but there were no significant differences (p < 0.05) found between either the HL or NL cattle and LL cattle. At 24, 48, and 72 h post-injection, the skinfold thickness response to both BF and Md antigens was significantly greater in the HL group than the NL group. However, skin thickness was significantly greater for the BF antigens than the Md antigens (p < 0.05). There were no significant differences found between the LL and NL animals in response to the BF antigens at any time, and no significant differences were determined between any of the lesion groups in response to the Og antigens. Histological examination of skin sections taken from the BF antigen injection sites in HL cattle at 72 h post-injection revealed necrosis of the epidermis and superficial dermis, along with severe eosinophilic inflammation. This study suggests that differences in the hypersensitivity to BF antigens underlie differences amongst the cattle in their susceptibility to the development of BF lesions, and breeding for immune-related biomarkers may assist in selecting more BF lesion-resistant cattle.

Published
2023
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37. Effects of the Anti-Tumor Agents Trabectedin and Lurbinectedin on Immune Cells of the Tumor Microenvironment

Author

Paola Allavena, Cristina Belgiovine, Elisabeth Digifico, Roberta Frapolli, and Maurizio D’Incalci

Subjects
tumor-associated macrophages, trabectedin, lurbinectedin, tumor micro-environment, immunity, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Immune cells in the tumor micro-environment (TME) establish a complex relationship with cancer cells and may strongly influence disease progression and response to therapy. It is well established that myeloid cells infiltrating tumor tissues favor cancer progression. Tumor-Associated Macrophages (TAMs) are abundantly present at the TME and actively promote cancer cell proliferation and distant spreading, as well as contribute to an immune-suppressive milieu. Active research of the last decade has provided novel therapeutic approaches aimed at depleting TAMs and/or at reprogramming their functional activities. We reported some years ago that the registered anti-tumor agent trabectedin and its analogue lurbinectedin have numerous mechanisms of action that also involve direct effects on immune cells, opening up new interesting points of view. Trabectedin and lurbinectedin share the unique feature of being able to simultaneously kill cancer cells and to affect several features of the TME, most notably by inducing the rapid and selective apoptosis of monocytes and macrophages, and by inhibiting the transcription of several inflammatory mediators. Furthermore, depletion of TAMs alleviates the immunosuppressive milieu and rescues T cell functional activities, thus enhancing the anti-tumor response to immunotherapy with checkpoint inhibitors. In view of the growing interest in tumor-infiltrating immune cells, the availability of antineoplastic compounds showing immunomodulatory effects on innate and adaptive immunity deserves particular attention in the oncology field.

Published
2022
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38. Incidence of cervical, breast and colorectal cancers between 2010 and 2015 in people living with HIV in France.

Author

Teresa Rojas Rojas, Isabelle Poizot-Martin, David Rey, Claudine Duvivier, Firouzé Bani-Sadr, André Cabie, Pierre Delobel, Christine Jacomet, Clotilde Allavena, Tristan Ferry, Pascal Pugliese, Marc-Antoine Valantin, Isabelle Lamaury, Laurent Hustache-Matthieu, Anne Fresard, Tamazighth Houyou, Thomas Huleux, Antoine Cheret, Alain Makinson, Véronique Obry-Roguet, Caroline Lions, Maria Patrizia Carrieri, Camelia Protopopescu, and Dat’AIDS Study Group

Subjects
Medicine, Science
Abstract

BackgroundWe aimed to evaluate the incidence rates between 2010 and 2015 for invasive cervical cancer (ICC), breast cancer (BC), and colorectal cancer (CRC) in people living with HIV (PLWH) in France, and to compare them with those in the French general population. These cancers are targeted by the national cancer-screening program.SettingThis is a retrospective study based on the longitudinal data of the French Dat'AIDS cohort.MethodsStandardized incidence ratios (SIR) for ICC and BC, and incidence rates for all three cancers were calculated overall and for specific sub-populations according to nadir CD4 cell count, HIV transmission category, HIV diagnosis period, and HCV coinfection.ResultsThe 2010-2015 CRC incidence rate was 25.0 [95% confidence interval (CI): 18.6-33.4] per 100,000 person-years, in 44,642 PLWH (both men and women). Compared with the general population, the ICC incidence rate was significantly higher in HIV-infected women both overall (SIR = 1.93, 95% CI: 1.18-3.14) and in the following sub-populations: nadir CD4 ≤ 200 cells/mm3 (SIR = 2.62, 95% CI: 1.45-4.74), HIV transmission through intravenous drug use (SIR = 5.14, 95% CI: 1.93-13.70), HCV coinfection (SIR = 3.52, 95% CI: 1.47-8.47) and HIV diagnosis before 2000 (SIR = 2.06, 95% CI: 1.07-3.97). Conversely, the BC incidence rate was significantly lower in the study sample than in the general population (SIR = 0.56, 95% CI: 0.42-0.73).ConclusionThe present study showed no significant linear trend between 2010 and 2015 in the incidence rates of the three cancers explored in the PLWH study sample. Specific recommendations for ICC screening are still required for HIV-infected women and should focus on sub-populations at greatest risk.

Published
2022
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39. High syphilis prevalence and incidence in people living with HIV and Preexposure Prophylaxis users: A retrospective review in the French Dat'AIDS cohort.

Author

Thomas Lemmet, Laurent Cotte, Clotilde Allavena, Thomas Huleux, Claudine Duvivier, Hélène Laroche, André Cabie, Pascal Pugliese, Thomas Jovelin, Marine Maurel, Cyrille Delpierre, and David Rey

Subjects
Medicine, Science
Abstract

BackgroundIn the past years, we observed a sharp increase of Syphilis, especially among male who have sex with male (MSM), either HIV-infected, or on pre-exposure prophylaxis (PrEP). Our aim was to assess syphilis prevalence and incidence among people living with HIV (PLWH) and PrEP users.MethodsPLWH were included from 2010 to 2020 and PrEP users from 2016 to 2020 from the Dat'AIDS French cohort. We calculated syphilis prevalence and incidences for first infections, re-infections, and iterative infections (> 2 times). T-Tests, Wilcoxon tests and Chi2 test were used for descriptive analysis and multivariate logistic regression models were used to estimate Odds ratios (OR) and 95% confidence intervals (95% CI) for factors associated with syphilis.ResultsAmong the 8 583 PLWH, prevalence of subject with past or present syphilis was 19.9%. These subjects were more likely MSM or transgender and aged over 35 years, but prevalence was lower in AIDS subjects. Same pattern was seen for incident infection and re-infection. Incidence was 3.8 per 100 person-years for infection and 6.5 per 100 person-years for re-infection. Among 1 680 PrEP users, syphilis prevalence was 25.8%, with an estimated 7.2% frequency of active syphilis. Risk of syphilis infection was higher in male and increased with age. Incidence was 11.2 per 100 person-years for infection and 11.1 per 100 person-years for re-infection.ConclusionSyphilis prevalence and incidence were high, especially in older MSM with controlled HIV infection and PrEP users, enhancing the need to improve syphilis screening and behavioral risk reduction counseling among high-risk subjects.

Published
2022
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41. Determinants of Second Primary Cancer Type in Survivors of Virus-Related and Non-Virus-Related Cancer Living With HIV in the French Dat’AIDS Cohort

Author

Isabelle Poizot-Martin, Caroline Lions, Clotilde Allavena, Pierre Delobel, Anne Fresard, Sylvie Brégigeon, Teresa Rojas, Cyrille Delpierre, and Alain Makinson

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Objectives People who survive after primary cancer are at an increased risk for subsequent primary cancers. We aimed to investigate the possible determinants of second primary cancer (SPC) in HIV-positive cancer survivors. Methods This was a multicenter retrospective study using longitudinal data from the French Dat’AIDS cohort. Subjects who developed at least 2 primary cancers were selected. Cancer cases were identified using ICD10 codes and distributed in 3 cancer categories: AIDS-defining cancer (ADC), virus-related non-ADC (VR-NADC), and virus-unrelated-NADC (VU-NADC). The possible determinants considered were the first primary cancer category, sex, age, HIV transmission route, duration of HIV infection follow-up, duration of ART exposure, nadir CD4 + T cell count, and hepatitis C and hepatitis B serostatus. Results Among the 44642 patients in the Dat’AIDS cohort, 4855 were diagnosed with cancer between 1 December 1983 and 31 December 2015, of whom 444 (9.1%) developed at least 2 primary cancers: 130 ADCs, 85 VR-NADCs, and 229 VU-NADCs. A longer delay between the first primary cancer and the SPC was associated with an increased risk of occurrence of a VR-NADC rather than a secondary ADC. Having had a first primary VU-NADC, an older age, and a longer delay between the HIV diagnosis and the first primary cancer as well as between the first primary cancer and the SPC were associated with an increased risk of VU-NADC rather than ADC. Conclusion SPCs are now a major concern in HIV-positive cancer survivors justifying the development of monitoring strategies after a first cancer.

Published
2021
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44. Intratumoral combination therapy with poly(I:C) and resiquimod synergistically triggers tumor-associated macrophages for effective systemic antitumoral immunity

Author

Alberto Mantovani, Marco Erreni, Paola Allavena, Diego Serrano, Miriam Redrado, Francisco Exposito, Alfonso Calvo, Clément Anfray, Francesco Mainini, Elisabeth Digifico, Akihiro Maeda, Marina Sironi, Achille Anselmo, Aldo Ummarino, Sara Gandoy, Marvin Martens, Susana Bravo, and Fernando Torres Andón

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published
2021
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45. Simple and effective bacterial-based intratumoral cancer immunotherapy

Author

Teresa Neeman, Desmond Yip, Rachel Allavena, Jane E Dahlstrom, Christina S E Carroll, Erin R Andrew, Laeeq Malik, Kathryn F Elliott, Moira Brennan, James Meyer, Alexander Hintze, Andrew A Almonte, Cassandra Lappin, Philip MacPherson, Klaus-Martin Schulte, Rohit Tamhane, Elizabeth W Herbert, Maurice Orange, and Aude M Fahrer

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published
2021
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46. Predicting koala (Phascolarctos cinereus) distribution from incidental sighting data in South-East Queensland, Australia

Author

Ravi Bandara Dissanayake, Mark Stevenson, Rachel Allavena, and Joerg Henning

Subjects
Koala, Species distribution, Search effort, Citizen science, Bias correction, Ecology, QH540-549.5
Abstract

Species distribution maps are important tools for wildlife conservation planning and management. To model koala distributions, usually, a spatially representative sample of koala populations is collected through systematic field surveys. Details of koala sightings collected by members of the public could potentially be used to develop species distribution models if appropriate analytical approaches are applied to address the inherent biases in such datasets. We developed a stepwise approach for applying bias correction techniques to estimate and map koala distributions. Using a Boosted regression tree approach, we modelled indirectly the search effort made by observers to identify or sight koalas. Land lot density (58%) and human population density (19%) had the strongest positive impact on the indirect search effort, while the distances to roads were negatively associated with the indirect search effort. To estimate the koala distribution across South-East Queensland, we then developed models describing koala habitat (environmental model), access to koala habitat (accessibility model) and the search effort (search effort model), with the latter including the indirect search effort covariate. Finally, we corrected the estimates derived from these models (bias-corrected search effort and accessibility model). Three independent statistical modelling approaches (Lasso penalty Poisson regression, Down-weighted Poisson regression, and Maximum entropy) were used to compare the five koala distribution models. Based on assessments of areas under curves, the predictive accuracy of models improved when area accessibility and search effort were included. Overall, the spatial extent of koala distributions increased in the prediction maps when models were corrected for accessibility and indirect search effort (except for Down-weighted Poisson regression).

Published
2021
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47. The value of long-term citizen science data for monitoring koala populations

Author

Ravi Bandara Dissanayake, Mark Stevenson, Rachel Allavena, and Joerg Henning

Subjects
Medicine, Science
Abstract

Abstract The active collection of wildlife sighting data by trained observers is expensive, restricted to small geographical areas and conducted infrequently. Reporting of wildlife sightings by members of the public provides an opportunity to collect wildlife data continuously over wider geographical areas, at lower cost. We used individual koala sightings reported by members of the public between 1997 and 2013 in South-East Queensland, Australia (n = 14,076 koala sightings) to describe spatial and temporal trends in koala presence, to estimate koala sighting density and to identify biases associated with sightings. Temporal trends in sightings mirrored the breeding season of koalas. Sightings were high in residential areas (63%), followed by agricultural (15%), and parkland (12%). The study area was divided into 57,780 one-square kilometer grid cells and grid cells with no sightings of koalas decreased over time (from 35% to 21%) indicative of a greater level of spatial overlap of koala home ranges and human activity areas over time. The density of reported koala sightings decreased as distance from primary and secondary roads increased, indicative of a higher search effort near roads. Our results show that koala sighting data can be used to refine koala distribution and population estimates derived from active surveying, on the condition that appropriate bias correction techniques are applied. Collecting koala absence and search effort information and conducting repeated searches for koalas in the same areas are useful approaches to improve the quality of sighting data in citizen science programs.

Published
2019
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48. Innate and Adaptive Responses of Intratumoral Immunotherapy with Endosomal Toll-Like Receptor Agonists

Author

Fernando Torres Andón, Sergio Leon, Aldo Ummarino, Esther Redin, Paola Allavena, Diego Serrano, Clément Anfray, and Alfonso Calvo

Subjects
toll-like receptors, TLR agonists, intratumoral administration, antitumoral immunotherapy, tumor associated macrophages, Biology (General), QH301-705.5
Abstract

Toll-like receptors (TLRs) are natural initial triggers of innate and adaptive immune responses. With the advent of cancer immunotherapy, nucleic acids engineered as ligands of endosomal TLRs have been investigated for the treatment of solid tumors. Despite promising results, their systemic administration, similarly to other immunotherapies, raises safety issues. To overcome these problems, recent studies have applied the direct injection of endosomal TLR agonists in the tumor and/or draining lymph nodes, achieving high local drug exposure and strong antitumor response. Importantly, intratumoral delivery of TLR agonists showed powerful effects not only against the injected tumors but also often against uninjected lesions (abscopal effects), resulting in some cases in cure and antitumoral immunological memory. Herein, we describe the structure and function of TLRs and their role in the tumor microenvironment. Then, we provide our vision on the potential of intratumor versus systemic delivery or vaccination approaches using TLR agonists, also considering the use of nanoparticles to improve their targeting properties. Finally, we collect the preclinical and clinical studies applying intratumoral injection of TLR agonists as monotherapies or in combination with: (a) other TLR or STING agonists; (b) other immunotherapies; (c) radiotherapy or chemotherapy; (d) targeted therapies.

Published
2022
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49. Evaluation of a Probability-Based Predictive Tool on Pathologist Agreement Using Urinary Bladder as a Pilot Tissue

Author

Emily Jones, Solomon Woldeyohannes, Fernanda Castillo-Alcala, Brandon N. Lillie, Mee-Ja M. Sula, Helen Owen, John Alawneh, and Rachel Allavena

Subjects
predictive modeling, inter-pathologist agreement, glass slides, whole-slide images, bladder disease, concurrence, Veterinary medicine, SF600-1100
Abstract

Inter-pathologist variation is widely recognized across human and veterinary pathology and is often compounded by missing animal or clinical information on pathology submission forms. Variation in pathologist threshold levels of resident inflammatory cells in the tissue of interest can further decrease inter-pathologist agreement. This study applied a predictive modeling tool to bladder histology slides that were assessed by four pathologists: first without animal and clinical information, then with this information, and finally using the predictive tool. All three assessments were performed twice, using digital whole-slide images (WSI) and then glass slides. Results showed marked variation in pathologists’ interpretation of bladder slides, with kappa agreement values of 7–37% without any animal or clinical information, 23–37% with animal signalment and history, and 31–42% when our predictive tool was applied, for digital WSI and glass slides. The concurrence of test pathologists to the reference diagnosis was 60% overall. This study provides a starting point for the use of predictive modeling in standardizing pathologist agreement in veterinary pathology. It also highlights the importance of high-quality whole-slide imaging to limit the effect of digitization on inter-pathologist agreement and the benefit of continued standardization of tissue assessment in veterinary pathology.

Published
2022
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50. Epidemiology and Survival of Dogs Diagnosed with Splenic Lymphoid Hyperplasia, Complex Hyperplasia, Stromal Sarcoma and Histiocytic Sarcoma

Author

Cleide H. Spröhnle-Barrera, Jayne McGhie, Rachel E. Allavena, Helen C. Owen, Chiara Palmieri, and Tamsin S. Barnes

Subjects
spleen, fibrohistiocytic nodules, lymphoid hyperplasia, complex hyperplasia, dog, sarcoma, Veterinary medicine, SF600-1100, Zoology, QL1-991
Abstract

Canine splenic fibrohistiocytic nodules traditionally encompassed benign lymphoid hyperplasia, complex hyperplasia, and malignant fibrous histiocytoma. The latter has been recently re-classified into histiocytic sarcoma and stromal sarcoma. Reliable indicators of post-splenectomy survival and demographic factors predisposing to the four types of nodules are not completely understood. This study aims to estimate frequency, survival times, and identify risk factors of splenectomized dogs diagnosed with lymphoid hyperplasia, complex hyperplasia, histiocytic sarcoma, and stromal sarcoma using medical records containing histopathological diagnosis from the VetCompass Australia database (1989–2018), which collects demographic, and clinical information from veterinary clinics. Out of 693 dogs, 315 were diagnosed with fibrohistiocytic nodules, mostly lymphoid hyperplasia (169/693, 24.4%), followed by stromal sarcoma (59/693, 8.5%), complex hyperplasia (55/693, 7.9%), and histiocytic sarcoma (32/693, 4.6%). Dogs aged 8–10 years were more likely to be diagnosed with histiocytic or stromal sarcoma than lymphoid hyperplasia. Dogs diagnosed with lymphoid hyperplasia had a longer survival time than those with other diagnoses (median > 2 years). Dogs diagnosed with histiocytic sarcoma had longer survival times (median 349 days) than stromal sarcoma (median 166 days). Results suggest that knowledge of the type of splenic fibrohistiocytic nodule, patients’ age, and sex can be used to increase prognostic accuracy.

Published
2022
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