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1. Is the Italian university ready for a gender leap? A regional perspective

Author

Negri, Ilia and Mezzetti, Maura

Subjects
Physics - Physics and Society
Abstract

A discussion on the readiness of Italian universities to address gender-related issues from a regional standpoint is proposed. A statistical analysis is conducted on data of all scholars enrolled in Italian universities from 2000 to 2023 to investigate why the glass ceiling of the full professor position remains so challenging to break in almost all scientific fields and across all regions of Italy.

Published
2024

2. Perazzo $n$-folds and the weak Lefschetz property

Author

Mezzetti, Emilia and Miró-Roig, Rosa M.

Subjects
Mathematics - Commutative Algebra, Mathematics - Algebraic Geometry, 14J70, 14M05, 13E10
Abstract

In this paper, we determine the maximum $h_{max}$ and the minimum $h_{min}$ of the Hilbert vectors of Perazzo algebras $A_F$, where $F$ is a Perazzo polynomial of degree $d$ in $n+m+1$ variables. These algebras always fail the Strong Lefschetz Property. We determine the integers $n,m,d$ such that $h_{max}$ (resp. $h_{min}$) is unimodal, and we prove that $A_F$ always fails the Weak Lefschetz Property if its Hilbert vector is maximum, while it satisfies the Weak Lefschetz Property if it is minimum, unimodal, and satisfies an additional mild condition. We determine the minimal free resolution of Perazzo algebras associated to Perazzo threefolds in $\mathbb P^4$ with minimum Hilbert vectors. Finally we pose some open problems in this context. Dedicated to Enrique Arrondo on the occasion of his $60^{th}$ birthday., Comment: 24 pages, to be published in Rendiconti del Circolo Matematico di Palermo Series 2

Published
2024

9. Effects of dry-off or continuous lactation in Alpine and Saanen dairy goats carrying single or double kids on peripartum metabolic profile, performances, and milk composition

Author

Matteo Mezzetti, Andrea Minuti, Luca Cattaneo, Erminio Trevisi, Fabio Bencetti, and Fiorenzo Piccioli-Cappelli

Subjects
dairy goats, acute phase response, inflammation, energy metabolism, dry-off, Animal culture, SF1-1100
Abstract

Dairy goat’s lactation persistence forces farmers at limiting nutrient supply to reduce yield at dry-off. Omitting dry period could be a solution, but metabolic effects of this practice have never been tested. Eight Alpine (AL) and 12 Saanen (SA) goats approaching their second kidding blocked by breed and number of kids carried (single - SIN - or double - DOU) were allocated to one out of two groups (4 AL and 6 SA; 5 SIN and 5 DOU in each group). At −42 ± 7 days from kidding (DFK), they were either dried off (DR) or milked continuously until kidding (CL). Body condition score (BCS) was assessed, and blood samples were collected at −10, −3, 5, 12, and 29 DFK to determine metabolic profile. Milk yield and composition were assessed at −56, 7, 31, 62, and 97 DFK. Compared with DR, CL had higher plasma reactive oxygen metabolites and liver enzymes. Compared with DR counterparts, AL-CL had higher nonesterified fatty acids (NEFA) at −10, whereas SA-CL had lower NEFA at −3 DFK. CL goats had lower BCS, higher plasma beta-hydroxybutyrate (BHB) and urea before kidding, but higher glucose at −3 and 5, lower NEFA at 5 and 12, and higher BCS at 29 DFK. CL goats had lower haptoglobin and myeloperoxidase at −3 and 5 DFK, paired with higher albumin, cholesterol, and paraoxonase at 12 DFK. Omitting dry period mitigated the inflammatory condition around kidding in dairy goats, possibly accounting for an improved energy balance in early lactation, despite body reserve mobilisation prepartum was greater under continuous lactation.

Published
2024
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10. DebateKG: Automatic Policy Debate Case Creation with Semantic Knowledge Graphs

Author

Roush, Allen and Mezzetti, David

Subjects
Computer Science - Computation and Language, Computer Science - Artificial Intelligence, Computer Science - Information Retrieval, Computer Science - Machine Learning
Abstract

Recent work within the Argument Mining community has shown the applicability of Natural Language Processing systems for solving problems found within competitive debate. One of the most important tasks within competitive debate is for debaters to create high quality debate cases. We show that effective debate cases can be constructed using constrained shortest path traversals on Argumentative Semantic Knowledge Graphs. We study this potential in the context of a type of American Competitive Debate, called Policy Debate, which already has a large scale dataset targeting it called DebateSum. We significantly improve upon DebateSum by introducing 53180 new examples, as well as further useful metadata for every example, to the dataset. We leverage the txtai semantic search and knowledge graph toolchain to produce and contribute 9 semantic knowledge graphs built on this dataset. We create a unique method for evaluating which knowledge graphs are better in the context of producing policy debate cases. A demo which automatically generates debate cases, along with all other code and the Knowledge Graphs, are open-sourced and made available to the public here: https://huggingface.co/spaces/Hellisotherpeople/DebateKG, Comment: 8 pages, Accepted to The 4th New Frontiers in Summarization Workshop (EMNLP 2023), System Demonstration paper

Published
2023

11. ‘In bella grafia’. Six Centuries of Manuscripts from the Biblioteca Manfrediana

Author

Corinna Mezzetti

Subjects
faenza, manfrediana library, manuscripts, Bibliography. Library science. Information resources
Abstract

After the emergency caused by the flood in Romagna in May 2023, the Manfrediana Library decided to dedicate an exhibition to the manuscript heritage, with an evocative journey through more than six centuries of history: from 12th-century fragments, recovered from the bindings of notarial registers, through famous medieval codices, such as Bonadies' collection of music and Felice Feliciano's epigraphic sylloge, to the testimonies of the eighteenth, nineteenth and twentieth centuries, with the unpublished novel by the American journalist Edward Prime-Stevenson.

Published
2024
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15. Hilbert functions and Jordan type of Perazzo Artinian algebras

Author

Abdallah, Nancy, Altafi, Nasrin, De Poi, Pietro, Fiorindo, Luca, Iarrobino, Anthony, Marques, Pedro Macias, Mezzetti, Emilia, Miró-Roig, Rosa M., and Nicklasson, Lisa

Subjects
Mathematics - Commutative Algebra, Mathematics - Algebraic Geometry, 13E10 (primary), 13D40, 14M05, 13H10
Abstract

We study Hilbert functions, Lefschetz properties, and Jordan type of Artinian Gorenstein algebras associated to Perazzo hypersurfaces in projective space. The main focus lies on Perazzo threefolds, for which we prove that the Hilbert functions are always unimodal. Further we prove that the Hilbert function determines whether the algebra is weak Lefschetz, and we characterize those Hilbert functions for which the weak Lefschetz property holds. By example, we verify that the Hilbert functions of Perazzo fourfolds are not always unimodal. In the particular case of Perazzo threefolds with the smallest possible Hilbert function, we give a description of the possible Jordan types for multiplication by any linear form., Comment: 23 pages

Published
2023

16. Poteri, patrimoni, scritture: l'abbazia di Pomposa tra esarcato e regno (secoli IX-XII). Una introduzione

Author

Giovanni Isabella and Corinna Mezzetti

Subjects
Pomposa, secoli IX-XII, regno italico, esarcato, monasteri regi, documentazione, Medieval history, D111-203
Abstract

Lo scopo del contributo è quello di introdurre la sezione monografica, frutto del convegno Poteri patrimoni scritture. L'abbazia di Pomposa tra esarcato e regno (secoli IX-XI), organizzato nell’ambito del progetto scientifico ‘Cantiere Pomposa’. Gli autori, dopo aver tracciato un breve bilancio degli studi sul patrimonio manoscritto di Pomposa, che affondano le radici nell’erudizione ecclesiastica del secolo XVIII, sottolineano l’importanza del cambio di prospettiva, da locale a sovralocale, e dell’attenzione all’assegnazione dei beni fiscali ai monasteri regi per comprendere le vicende politico-istituzionali e culturali dell’importante abbazia del delta padano nei secoli centrali del medioevo.

Published
2024
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17. Pomposa, Comacchio, Ferrara: tabellioni e notai (secoli X-XII)

Author

Corinna Mezzetti

Subjects
Notariato, secoli X-XII, abbazia di Pomposa, Ferrara, documenti medievali, scrittura, Medieval history, D111-203
Abstract

Il notariato ferrarese altomedievale è a tutt'oggi un campo di indagine inesplorato, per la conservazione di tante carte ferraresi fuori da Ferrara e la loro limitata disponibilità in edizione critica. A partire dal cantiere di lavoro sulle carte dell'archivio dell'abbazia di Pomposa, il contributo si propone di tentare alcune, prime riflessioni su tabellioni e notai ferraresi tra X e XII secolo. Entro l'universo della prassi documentaria ravennate di tradizione romanica, che rimane orgogliosamente conservatrice fin quasi alle soglie del XIII secolo, le mosse dei professionisti della periferia ferrarese si mostrano più aperti a innovazioni e influenze esterne. E l'analisi delle carte e degli scrittori, aggregabili nelle due aree attorno a Ferrara e Comacchio, viene condotta sul filo di intitolazioni, qualifiche professionali, fatti di scrittura e ornamentazione, per mettere in fila qualche punto e dare avvio allo studio dei notai ferraresi attraverso la forma e il tenore delle loro carte.

Published
2024
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18. TechRank

Author

Mezzetti, Anita, Maréchal, Loïc, David, Dimitri Percia, Lacube, William, Gillard, Sébastien, Tsesmelis, Michael, Maillart, Thomas, and Mermoud, Alain

Subjects
Quantitative Finance - Computational Finance
Abstract

We introduce TechRank, a recursive algorithm based on a bi-partite graph with weighted nodes. We develop TechRank to link companies and technologies based on the method of reflection. We allow the algorithm to incorporate exogenous variables that reflect an investor's preferences. We calibrate the algorithm in the cybersecurity sector. First, our results help estimate each entity's influence and explain companies' and technologies' ranking. Second, they provide investors with a quantitative optimal ranking of technologies and thus, help them design their optimal portfolio. We propose this method as an alternative to traditional portfolio management and, in the case of private equity investments, as a new way to price assets for which cash flows are not observable.

Published
2022

19. Perazzo 3-folds and the weak Lefschetz property

Author

Fiorindo, Luca, Mezzetti, Emilia, and Miró-Roig, Rosa M.

Subjects
Mathematics - Algebraic Geometry, Mathematics - Commutative Algebra, 14J70, 14N07, 13E10
Abstract

We deal with Perazzo 3-folds in $\mathbb P^4$, i.e. hypersurfaces $X=V(f)\subset \mathbb P^4$ of degree $d$ defined by a homogeneous polynomial $f(x_0,x_1,x_2,u,v)=p_0(u,v)x_0+p_1(u,v)x_1+p_2(u,v)x_2+g(u,v)$, where $p_0,p_1,p_2$ are algebraically dependent but linearly independent forms of degree $d-1$ in $u,v$, and $g$ is a form in $u,v$ of degree $d$. Perazzo 3-folds have vanishing hessian and, hence, the associated graded artinian Gorenstein algebra $A_f$ fails the strong Lefschetz property. In this paper, we determine the maximum and minimum Hilbert function of $A_f$ and we prove that if $A_f$ has maximal Hilbert function it fails the weak Lefschetz property, while it satisfies the weak Lefschetz property when it has minimum Hilbert function. In addition, we classify all Perazzo 3-folds in $\mathbb P^4$ such that $A_f$ has minimum Hilbert function., Comment: 21 pages; final version to be published in Journal of Algebra

Published
2022

20. Pencils of singular quadrics of constant rank and their orbits

Author

Boralevi, Ada and Mezzetti, Emilia

Subjects
Mathematics - Algebraic Geometry, 14C21, 14M15, 14L30, 14F06
Abstract

We give a geometric description of singular pencils of quadrics of constant rank, relating them to the splitting type of some naturally associated vector bundles on $\mathbb{P}^1$. Then we study their orbits in the Grassmannian of lines, under the natural action of the general linear group., Comment: Dedicated to Giorgio Ottaviani on the occasion of his 60th birthday. 17 pages, 2 figures

Published
2022

21. Machine Learning Decision Support for Macronutrients in Neonatal Parenteral Nutrition

Author

Setareh Derakhshandara, Valentina Franzoni, Daniele Mezzetti, and Valentina Poggioni

Subjects
Machine learning, intelligent decision systems, neonatal intensive care, AI for decision in healthcare, machine learning for parenteral nutrition, infant nutrition, Electrical engineering. Electronics. Nuclear engineering, TK1-9971
Abstract

Parenteral nutrition plays a crucial role in the care of hospitalized patients in the neonatal intensive care unit. Determining the appropriate amount and composition of parenteral nutrition bag for each infant is a complex and individualized process. Using a dataset of 1210 neonatal intensive-care unit patients of the University Hospital of Perugia, collected over 17 years, this work aims to establish the basis for an evidence-based decision support system to reduce the time and effort required for manual calculations from doctors working in such a critical emergency environment. After the data was presented, we compared different machine learning techniques (i.e., random forest, gradient boosting machine, support vector machine, multilayer perceptron) that could predict nutritional requirements. We discuss the feasibility of the proposed approach, evaluating the methods in terms of their explainability, and using performance measures (i.e., RMSE, $R^{2}$ ). Preliminary results revealed promising predictive ability for macronutrients and volume of parenteral bags. These findings highlight the potential of machine learning as a valuable tool for nutritional outcome estimation in neonatal clinical practice.

Published
2024
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23. TechRank: A Network-Centrality Approach for Informed Cybersecurity-Investment

Author

Mezzetti, Anita, David, Dimitri Percia, Maillart, Thomas, Tsesmelis, Michael, and Mermoud, Alain

Subjects
Computer Science - Cryptography and Security, Computer Science - Computers and Society
Abstract

The cybersecurity technological landscape is a complex ecosystem in which entities -- such as companies and technologies -- influence each other in a non-trivial manner. Measuring the influence between entities is a tenet for informed technological investments in critical infrastructure. To study the mutual influence of companies and technologies from the cybersecurity field, we consider a bi-partite graph that links both sets of entities. Each node in this graph is weighted by applying a recursive algorithm based on the method of reflection. This endeavor helps to measure the impact of an entity on the cybersecurity market. Our results help researchers measure more precisely the magnitude of influence of each entity, and allows decision-makers to devise more informed investment strategies, according to their portfolio preferences. Finally, a research agenda is suggested, with the aim of allowing tailor-made investments by arbitrarily calibrating specific features of both types of entities., Comment: 7 pages, 2 figures

Published
2021

24. From by-products to new application opportunities: the enhancement of the leaves deriving from the fruit plants for new potential healthy products

Author

Lucia Regolo, Francesca Giampieri, Maurizio Battino, Yasmany Armas Diaz, Bruno Mezzetti, Maria Elexpuru-Zabaleta, Cristina Mazas, Kilian Tutusaus, and Luca Mazzoni

Subjects
circular economy, leaves, bioactive compounds, health, food industry, cosmetics, Nutrition. Foods and food supply, TX341-641
Abstract

In the last decades, the world population and demand for any kind of product have grown exponentially. The rhythm of production to satisfy the request of the population has become unsustainable and the concept of the linear economy, introduced after the Industrial Revolution, has been replaced by a new economic approach, the circular economy. In this new economic model, the concept of “the end of life” is substituted by the concept of restoration, providing a new life to many industrial wastes. Leaves are a by-product of several agricultural cultivations. In recent years, the scientific interest regarding leaf biochemical composition grew, recording that plant leaves may be considered an alternative source of bioactive substances. Plant leaves’ main bioactive compounds are similar to those in fruits, i.e., phenolic acids and esters, flavonols, anthocyanins, and procyanidins. Bioactive compounds can positively influence human health; in fact, it is no coincidence that the leaves were used by our ancestors as a natural remedy for various pathological conditions. Therefore, leaves can be exploited to manufacture many products in food (e.g., being incorporated in food formulations as natural antioxidants, or used to create edible coatings or films for food packaging), cosmetic and pharmaceutical industries (e.g., promising ingredients in anti-aging cosmetics such as oils, serums, dermatological creams, bath gels, and other products). This review focuses on the leaves’ main bioactive compounds and their beneficial health effects, indicating their applications until today to enhance them as a harvesting by-product and highlight their possible reuse for new potential healthy products.

Published
2024
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25. Bacille Calmette-Guérin vaccination to prevent febrile and respiratory illness in adults (BRACE): secondary outcomes of a randomised controlled phase 3 trialResearch in context

Author

Laure F. Pittet, Nicole L. Messina, Ellie McDonald, Francesca Orsini, Simone Barry, Marc Bonten, John Campbell, Julio Croda, Mariana G. Croda, Margareth Dalcolmo, Kaya Gardiner, Amanda Gwee, Bruno Jardim, Marcus V.G. Lacerda, Michaela Lucas, David J. Lynn, Laurens Manning, Kirsten P. Perrett, Jeffrey J. Post, Cristina Prat-Aymerich, Peter C. Richmond, Jorge L. Rocha, Jesus Rodriguez-Baño, Adilia Warris, Nicholas J. Wood, Andrew Davidson, Nigel Curtis, Tenaya Jamieson, Nicole Messina, Thilanka Morawakage, Susan Perlen, Kirsten Perrett, Laure Pittet, Amber Sastry, Jia Wei Teo, Katherine Lee, Cecilia Moore, Suzanna Vidmar, Rashida Ali, Ross Dunn, Peta Edler, Grace Gell, Casey Goodall, Richard Hall, Ann Krastev, Nathan La, Nick McPhate, Thao Nguyen, Jack Ren, Luke Stevens, Ahmed Alamrousi, Rhian Bonnici, Thanh Dang, Susie Germano, Jenny Hua, Rebecca McElroy, Monica Razmovska, Scott Reddiex, Xiaofang Wang, Jeremy Anderson, Kristy Azzopardi, Vicki Bennett-Wood, Anna Czajko, Nadia Mazarakis, Conor McCafferty, Frances Oppedisano, Belinda Ortika, Casey Pell, Leena Spry, Ryan Toh, Sunitha Velagapudi, Amanda Vlahos, Ashleigh Wee-Hee, Pedro Ramos, Karina De La Cruz, Dinusha Gamage, Anushka Karunanayake, Isabella Mezzetti, Benjamin Ong, Ronita Singh, Enoshini Sooriyarachchi, Suellen Nicholson, Natalie Cain, Rianne Brizuela, Han Huang, Veronica Abruzzo, Morgan Bealing, Patricia Bimboese, Kirsty Bowes, Emma Burrell, Joyce Chan, Jac Cushnahan, Hannah Elborough, Olivia Elkington, Kieran Fahey, Monique Fernandez, Catherine Flynn, Sarah Fowler, Marie Gentile Andrit, Bojana Gladanac, Catherine Hammond, Norine Ma, Sam Macalister, Emmah Milojevic, Jesutofunmi Mojeed, Jill Nguyen, Liz O'Donnell, Nadia Olivier, Isabelle Ooi, Stephanie Reynolds, Lisa Shen, Barb Sherry, Judith Spotswood, Jamie Wedderburn, Angela Younes, Donna Legge, Jason Bell, Jo Cheah, Annie Cobbledick, Kee Lim, Sonja Elia, Lynne Addlem, Anna Bourke, Clare Brophy, Nadine Henare, Narelle Jenkins, Francesca Machingaifa, Skye Miller, Kirsten Mitchell, Sigrid Pitkin, Kate Wall, Paola Villanueva, Nigel Crawford, Wendy Norton, Niki Tan, Thilakavathi Chengodu, Diane Dawson, Victoria Gordon, Tony Korman, Jess O'Bryan, Sophie Agius, Samantha Bannister, Jess Bucholc, Alison Burns, Beatriz Camesella, John Carlin, Marianna Ciaverella, Maxwell Curtis, Stephanie Firth, Christina Guo, Matthew Hannan, Erin Hill, Sri Joshi, Katherine Lieschke, Megan Mathers, Sasha Odoi, Ashleigh Rak, Chris Richards, Leah Steve, Carolyn Stewart, Eva Sudbury, Helen Thomson, Emma Watts, Fiona Williams, Angela Young, Penny Glenn, Andrew Kaynes, Amandine Philippart De Floy, Sandy Buchanan, Thijs Sondag, Ivy Xie, Harriet Edmund, Bridie Byrne, Tom Keeble, Belle Ngien, Fran Noonan, Michelle Wearing-Smith, Alison Clarke, Pemma Davies, Oliver Eastwood, Alric Ellinghaus, Rachid Ghieh, Zahra Hilton, Emma Jennings, Athina Kakkos, Iris Liang, Katie Nicol, Sally O'Callaghan, Helen Osman, Gowri Rajaram, Sophia Ratcliffe, Victoria Rayner, Ashleigh Salmon, Angela Scheppokat, Aimee Stevens, Rebekah Street, Nicholas Toogood, Nicholas Wood, Twinkle Bahaduri, Therese Baulman, Jennifer Byrne, Candace Carter, Mary Corbett, Aiken Dao, Maria Desylva, Andrew Dunn, Evangeline Gardiner, Rosemary Joyce, Rama Kandasamy, Craig Munns, Lisa Pelayo, Ketaki Sharma, Katrina Sterling, Caitlin Uren, Clinton Colaco, Mark Douglas, Kate Hamilton, Adam Bartlett, Brendan McMullan, Pamela Palasanthiran, Phoebe Williams, Justin Beardsley, Nikki Bergant, Renier Lagunday, Kristen Overton, Jeffrey Post, Yasmeen Al-Hindawi, Sarah Barney, Anthony Byrne, Lee Mead, Marshall Plit, David Lynn, Saoirse Benson, Stephen Blake, Rochelle Botten, Tee Yee Chern, Georgina Eden, Liddy Griffith, Jane James, Miriam Lynn, Angela Markow, Domenic Sacca, Natalie Stevens, Steve Wesselingh, Catriona Doran, Alice Sawka, Sue Evans, Louise Goodchild, Christine Heath, Meredith Krieg, Helen Marshall, Mark McMillan, Mary Walker, Peter Richmond, Nelly Amenyogbe, Christina Anthony, Annabelle Arnold, Beth Arrowsmith, Rym Ben-Othman, Sharon Clark, Jemma Dunnill, Nat Eiffler, Krist Ewe, Carolyn Finucane, Lorraine Flynn, Camille Gibson, Lucy Hartnell, Elysia Hollams, Heidi Hutton, Lance Jarvis, Jane Jones, Jan Jones, Karen Jones, Jennifer Kent, Tobias Kollmann, Debbie Lalich, Wenna Lee, Rachel Lim, Sonia McAlister, Fiona McDonald, Andrea Meehan, Asma Minhaj, Lisa Montgomery, Melissa O'Donnell, Jaslyn Ong, Joanne Ong, Kimberley Parkin, Glady Perez, Catherine Power, Shadie Rezazadeh, Holly Richmond, Sally Rogers, Nikki Schultz, Margaret Shave, Patrycja Skut, Lisa Stiglmayer, Alexandra Truelove, Ushma Wadia, Rachael Wallace, Justin Waring, Michelle England, Erin Latkovic, Susan Herrmann, Marcus Lacerda, Paulo Henrique Andrade, Fabiane Bianca Barbosa, Dayanne Barros, Larissa Brasil, Ana Greyce Capella, Ramon Castro, Erlane Costa, Dilcimar de Souza, Maianne Dias, José Dias, Klenilson Ferreira, Paula Figueiredo, Thamires Freitas, Ana Carolina Furtado, Larissa Gama, Vanessa Godinho, Cintia Gouy, Daniele Hinojosa, Tyane Jardim, Joel Junior, Augustto Lima, Bernardo Maia, Adriana Marins, Kelry Mazurega, Tercilene Medeiros, Rosangela Melo, Marinete Moraes, Elizandra Nascimento, Juliana Neves, Maria Gabriela Oliveira, Thais Oliveira, Ingrid Oliveira, Arthur Otsuka, Rayssa Paes, Handerson Pereira, Gabrielle Pereira, Christiane Prado, Evelyn Queiroz, Laleyska Rodrigues, Bebeto Rodrigues, Vanderson Sampaio, Anna Gabriela Santos, Daniel Santos, Tilza Santos, Evelyn Santos, Ariandra Sartim, Ana Beatriz Silva, Juliana Silva, Emanuelle Silva, Mariana Simão, Caroline Soares, Antonny Sousa, Alexandre Trindade, Fernando Val, Adria Vasconcelos, Heline Vasconcelos, Carolinne Abreu, Katya Martinez Almeida, Camila Bitencourt de Andrade, Jhenyfer Thalyta Campos Angelo, Ghislaine Gonçalvez de Araújo Arcanjo, Bianca Maria Silva Menezes Arruda, Wellyngthon Espindola Ayala, Adelita Agripina Refosco Barbosa, Felipe Zampieri Vieira Batista, Fabiani de Morais Batista, Miriam de Jesus Costa, Mariana Garcia Croda, Lais Alves da Cruz, Roberta Carolina Pereira Diogo, Rodrigo Cezar Dutra Escobar, Iara Rodrigues Fernandes, Leticia Ramires Figueiredo, Leandro Galdino Cavalcanti Gonçalves, Sarita Lahdo, Joyce dos Santos Lencina, Guilherme Teodoro de Lima, Bruna Tayara LEOPOLDINA MEIRELES, Debora Quadros Moreira, Lilian Batista Silva Muranaka, Adriely de Oliveira, Karla Regina Warszawski de Oliveira, Matheus Vieira de Oliveira, Roberto Dias de Oliveira, Andrea Antonia Souza de Almeida dos Reis Pereira, Marco Puga, Caroliny Veron Ramos, Thaynara Haynara Souza da Rosa, Karla Lopes dos Santos, Claudinalva Ribeiro dos Santos, Dyenyffer Stéffany Leopoldina dos Santos, Karina Marques Santos, Paulo César Pereira da Silva, Paulo Victor Rocha da Silva, Débora dos Santos Silva, Patricia Vieira da Silva, Bruno Freitas da Rosa Soares, Mariana Gazzoni Sperotto, Mariana Mayumi Tadokoro, Daniel Tsuha, Hugo Miguel Ramos Vieira, Margareth Maria Pretti Dalcolmo, Cíntia Maria Lopes Alves da Paixão, Gabriela Corrêa E Castro, Simone Silva Collopy, Renato da Costa Silva, Samyra Almeida da Silveira, Alda Maria Da-Cruz, Alessandra Maria da Silva Passos de Carvalho, Rita de Cássia Batista, Maria Luciana Silva De Freitas, Aline Gerhardt de Oliveira Ferreira, Ana Paula Conceição de Souza, Paola Cerbino Doblas, Ayla Alcoforado da Silva dos Santos, Vanessa Cristine de Moraes dos Santos, Dayane Alves dos Santos Gomes, Anderson Lage Fortunato, Adriano Gomes-Silva, Monique Pinto Gonçalves, Paulo Leandro Garcia Meireless Junior, Estela Martins da Costa Carvalho, Fernando do Couto Motta, Ligia Maria Olivo de Mendonça, Girlene dos Santos Pandine, Rosa Maria Plácido Pereira, Ivan Ramos Maia, Jorge Luiz da Rocha, João Victor Paiva Romano, Glauce dos Santos, Erica Fernandes da Silva, Marilda Agudo Mendonça Teixeira de Siqueira, Ágatha Cristinne Prudêncio Soares, Sandra Franch Arroyo, Henny Ophorst-den Besten, Anna Boon, Karin M. Brakke, Axel Janssen, Marijke A.H. Koopmans, Toos Lemmens, Titia Leurink, Engelien Septer-Bijleveld, Kimberly Stadhouders, Darren Troeman, Marije van der Waal, Marjoleine van Opdorp, Nicolette van Sluis, Beatrijs Wolters, Jan Kluytmans, Jannie Romme, Wouter van den Bijllaardt, Linda van Mook, M.M.L (Miranda) van Rijen, P.M.G. Filius, Jet Gisolf, Frances Greven, Danique Huijbens, Robert Jan Hassing, R.C. Pon, Lieke Preijers, J.H. van Leusen, Harald Verheij, Wim Boersma, Evelien Brans, Paul Kloeg, Kitty Molenaar-Groot, Nhat Khanh Nguyen, Nienke Paternotte, Anke Rol, Lida Stooper, Helga Dijkstra, Esther Eggenhuizen, Lucas Huijs, Simone Moorlag, Mihai Netea, Eva Pranger, Esther Taks, Jaap ten Oever, Rob ter Heine, Kitty Blauwendraat, Bob Meek, Isil Erkaya, Houda Harbech, Nienke Roescher, Rifka Peeters, Menno te Riele, Carmen Zhou, Esther Calbo, Cristina Badia Marti, Emma Triviño Palomares, Tomás Perez Porcuna, Anabel Barriocanal, Ana Maria Barriocanal, Irma Casas, Jose Dominguez, Maria Esteve, Alicia Lacoma, Irene Latorre, Gemma Molina, Barbara Molina, Antoni Rosell, Sandra Vidal, Lydia Barrera, Natalia Bustos, Ines Portillo Calderón, David Gutierrez Campos, Jose Manuel Carretero, Angel Dominguez Castellano, Renato Compagnone, Encarnacion Ramirez de Arellano, Almudena de la Serna, Maria Dolores del Toro Lopez, Marie-Alix Clement Espindola, Ana Belen Martin Gutierrez, Alvaro Pascual Hernandez, Virginia Palomo Jiménez, Elisa Moreno, Nicolas Navarrete, Teresa Rodriguez Paño, Jesús Rodríguez-Baño, Enriqueta Tristán, Maria Jose Rios Villegas, Atsegiñe Canga Garces, Erika Castro Amo, Raquel Coya Guerrero, Josune Goikoetxea, Leticia Jorge, Cristina Perez, María Carmen Fariñas Álvarez, Manuel Gutierrez Cuadra, Francisco Arnaiz de las Revillas Almajano, Pilar Bohedo Garcia, Teresa Giménez Poderos, Claudia González Rico, Blanca Sanchez, Olga Valero, Noelia Vega, Anna Barnes, Helen Catterick, Tim Cranston, Phoebe Dawe, Emily Fletcher, Liam Fouracre, Alison Gifford, Neil Gow, John Kirkwood, Christopher Martin, Amy McAnew, Marcus Mitchell, Georgina Newman, Abby O'Connell, Jakob Onysk, Lynne Quinn, Shelley Rhodes, Samuel Stone, Lorrie Symons, Harry Tripp, Darcy Watkins, Bethany Whale, Alex Harding, Gemma Lockhart, Kate Sidaway-Lee, Sam Hilton, Sarah Manton, Daniel Webber-Rookes, Rachel Winder, James Moore, Freya Bateman, Michael Gibbons, Bridget Knight, Julie Moss, Sarah Statton, Josephine Studham, Lydia Hall, Will Moyle, and Tamsin Venton

Subjects
Bacille Calmette-Guérin (BCG) vaccine, Immunity, Heterologous, Health personnel, Randomised controlled trial, Primary prevention, Medicine (General), R5-920
Abstract

Summary: Background: Bacille Calmette-Guérin (BCG) vaccination has off-target (non-specific) effects that are associated with protection against unrelated infections and decreased all-cause mortality in infants. We aimed to determine whether BCG vaccination prevents febrile and respiratory infections in adults. Methods: This randomised controlled phase 3 trial was done in 36 healthcare centres in Australia, Brazil, the Netherlands, Spain, and the United Kingdom. Healthcare workers were randomised to receive BCG-Denmark (single 0.1 ml intradermal injection) or no BCG in a 1:1 ratio using a web-based procedure, stratified by stage, site, age, and presence of co-morbidity. The difference in occurrence of febrile or respiratory illness were measured over 12 months (prespecified secondary outcome) using the intention-to-treat (ITT) population. This trial is registered with ClinicalTrials.gov, NCT04327206. Findings: Between March 30, 2020, and April 1, 2021, 6828 healthcare workers were randomised to BCG-Denmark (n = 3417) or control (n = 3411; no intervention or placebo) groups. The 12-month adjusted estimated risk of ≥1 episode of febrile or respiratory illness was 66.8% in the BCG group (95% CI 65.3%–68.2%), compared with 63.4% in the control group (95% CI 61.8%–65.0%), a difference of +3.4 percentage points (95% CI +1.3% to +5.5%; p 0.002). The adjusted estimated risk of a severe episode (defined as being incapacitated for ≥3 consecutive days or hospitalised) was 19.4% in the BCG group (95% CI 18.0%–20.7%), compared with 18.8% in the control group (95% CI 17.4%–20.2%) a difference of +0.6 percentage points (95% CI −1.3% to +2.5%; p 0.6). Both groups had a similar number of episodes of illness, pneumonia, and hospitalisation. There were three deaths, all in the control group. There were no safety concerns following BCG vaccination. Interpretation: In contrast to the beneficial off-target effects reported following neonatal BCG in infants, a small increased risk of symptomatic febrile or respiratory illness was observed in the 12 months following BCG vaccination in adults. There was no evidence of a difference in the risk of severe disease. Funding: Bill & Melinda Gates Foundation, Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children's Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare, the National Health and Medical Research Council, the Swiss National Science Foundation and individual donors.

Published
2024
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26. Specific and off-target immune responses following COVID-19 vaccination with ChAdOx1-S and BNT162b2 vaccines—an exploratory sub-study of the BRACE trialResearch in context

Author

Nicole L. Messina, Susie Germano, Rebecca McElroy, Rhian Bonnici, Branka Grubor-Bauk, David J. Lynn, Ellie McDonald, Suellen Nicholson, Kirsten P. Perrett, Laure F. Pittet, Rajeev Rudraraju, Natalie E. Stevens, Kanta Subbarao, Nigel Curtis, Andrew Davidson, Kaya Gardiner, Amanda Gwee, Tenaya Jamieson, Nicole Messina, Thilanka Morawakage, Susan Perlen, Kirsten Perrett, Laure Pittet, Amber Sastry, Jia Wei Teo, Francesca Orsini, Katherine Lee, Cecilia Moore, Suzanna Vidmar, Rashida Ali, Ross Dunn, Peta Edler, Grace Gell, Casey Goodall, Richard Hall, Ann Krastev, Nathan La, Nick McPhate, Thao Nguyen, Jack Ren, Luke Stevens, Ahmed Alamrousi, Thanh Dang, Jenny Hua, Monica Razmovska, Scott Reddiex, Xiaofang Wang, Jeremy Anderson, Kristy Azzopardi, Vicki Bennett-Wood, Anna Czajko, Nadia Mazarakis, Conor McCafferty, Frances Oppedisano, Belinda Ortika, Casey Pell, Leena Spry, Ryan Toh, Sunitha Velagapudi, Amanda Vlahos, Ashleigh Wee-Hee, Pedro Ramos, Karina De La Cruz, Dinusha Gamage, Anushka Karunanayake, Isabella Mezzetti, Benjamin Ong, Ronita Singh, Enoshini Sooriyarachchi, Natalie Cain, Rianne Brizuela, Han Huang, Veronica Abruzzo, Morgan Bealing, Patricia Bimboese, Kirsty Bowes, Emma Burrell, Joyce Chan, Jac Cushnahan, Hannah Elborough, Olivia Elkington, Kieran Fahey, Monique Fernandez, Catherine Flynn, Sarah Fowler, Marie Gentile Andrit, Bojana Gladanac, Catherine Hammond, Norine Ma, Sam Macalister, Emmah Milojevic, Jesutofunmi Mojeed, Jill Nguyen, Liz O’Donnell, Nadia Olivier, Isabelle Ooi, Stephanie Reynolds, Lisa Shen, Barb Sherry, Judith Spotswood, Jamie Wedderburn, Angela Younes, Donna Legge, Jason Bell, Jo Cheah, Annie Cobbledick, Kee Lim, Sonja Elia, Lynne Addlem, Anna Bourke, Clare Brophy, Nadine Henare, Narelle Jenkins, Francesca Machingaifa, Skye Miller, Kirsten Mitchell, Sigrid Pitkin, Kate Wall, Paola Villanueva, Nigel Crawford, Wendy Norton, Niki Tan, Thilakavathi Chengodu, Diane Dawson, Victoria Gordon, Tony Korman, Jess O’Bryan, Sophie Agius, Samantha Bannister, Jess Bucholc, Alison Burns, Beatriz Camesella, John Carlin, Marianna Ciaverella, Maxwell Curtis, Stephanie Firth, Christina Guo, Matthew Hannan, Erin Hill, Sri Joshi, Katherine Lieschke, Megan Mathers, Sasha Odoi, Ashleigh Rak, Chris Richards, Leah Steve, Carolyn Stewart, Eva Sudbury, Helen Thomson, Emma Watts, Fiona Williams, Angela Young, Penny Glenn, Andrew Kaynes, Amandine Philippart De Floy, Sandy Buchanan, Thijs Sondag, Ivy Xie, Harriet Edmund, Bridie Byrne, Tom Keeble, Belle Ngien, Fran Noonan, Michelle Wearing-Smith, Alison Clarke, Pemma Davies, Oliver Eastwood, Alric Ellinghaus, Rachid Ghieh, Zahra Hilton, Emma Jennings, Athina Kakkos, Iris Liang, Katie Nicol, Sally O’Callaghan, Helen Osman, Gowri Rajaram, Sophia Ratcliffe, Victoria Rayner, Ashleigh Salmon, Angela Scheppokat, Aimee Stevens, Rebekah Street, Nicholas Toogood, Nicholas Wood, Twinkle Bahaduri, Therese Baulman, Jennifer Byrne, Candace Carter, Mary Corbett, Aiken Dao, Maria Desylva, Andrew Dunn, Evangeline Gardiner, Rosemary Joyce, Rama Kandasamy, Craig Munns, Lisa Pelayo, Ketaki Sharma, Katrina Sterling, Caitlin Uren, Clinton Colaco, Mark Douglas, Kate Hamilton, Adam Bartlett, Brendan McMullan, Pamela Palasanthiran, Phoebe Williams, Justin Beardsley, Nikki Bergant, Renier Lagunday, Kristen Overton, Jeffrey Post, Yasmeen Al-Hindawi, Sarah Barney, Anthony Byrne, Lee Mead, Marshall Plit, David Lynn, Saoirse Benson, Stephen Blake, Rochelle Botten, Tee Yee Chern, Georgina Eden, Liddy Griffith, Jane James, Miriam Lynn, Angela Markow, Domenic Sacca, Natalie Stevens, Steve Wesselingh, Catriona Doran, Simone Barry, Alice Sawka, Sue Evans, Louise Goodchild, Christine Heath, Meredith Krieg, Helen Marshall, Mark McMillan, Mary Walker, Peter Richmond, Nelly Amenyogbe, Christina Anthony, Annabelle Arnold, Beth Arrowsmith, Rym Ben-Othman, Sharon Clark, Jemma Dunnill, Nat Eiffler, Krist Ewe, Carolyn Finucane, Lorraine Flynn, Camille Gibson, Lucy Hartnell, Elysia Hollams, Heidi Hutton, Lance Jarvis, Jane Jones, Jan Jones, Karen Jones, Jennifer Kent, Tobias Kollmann, Debbie Lalich, Wenna Lee, Rachel Lim, Sonia McAlister, Fiona McDonald, Andrea Meehan, Asma Minhaj, Lisa Montgomery, Melissa O’Donnell, Jaslyn Ong, Joanne Ong, Kimberley Parkin, Glady Perez, Catherine Power, Shadie Rezazadeh, Holly Richmond, Sally Rogers, Nikki Schultz, Margaret Shave, Patrycja Skut, Lisa Stiglmayer, Alexandra Truelove, Ushma Wadia, Rachael Wallace, Justin Waring, Michelle England, Erin Latkovic, Laurens Manning, Susan Herrmann, Michaela Lucas, Marcus Lacerda, Paulo Henrique Andrade, Fabiane Bianca Barbosa, Dayanne Barros, Larissa Brasil, Ana Greyce Capella, Ramon Castro, Erlane Costa, Dilcimar de Souza, Maianne Dias, José Dias, Klenilson Ferreira, Paula Figueiredo, Thamires Freitas, Ana Carolina Furtado, Larissa Gama, Vanessa Godinho, Cintia Gouy, Daniele Hinojosa, Bruno Jardim, Tyane Jardim, Joel Junior, Augustto Lima, Bernardo Maia, Adriana Marins, Kelry Mazurega, Tercilene Medeiros, Rosangela Melo, Marinete Moraes, Elizandra Nascimento, Juliana Neves, Maria Gabriela Oliveira, Thais Oliveira, Ingrid Oliveira, Arthur Otsuka, Rayssa Paes, Handerson Pereira, Gabrielle Pereira, Christiane Prado, Evelyn Queiroz, Laleyska Rodrigues, Bebeto Rodrigues, Vanderson Sampaio, Anna Gabriela Santos, Daniel Santos, Tilza Santos, Evelyn Santos, Ariandra Sartim, Ana Beatriz Silva, Juliana Silva, Emanuelle Silva, Mariana Simão, Caroline Soares, Antonny Sousa, Alexandre Trindade, Fernando Val, Adria Vasconcelos, Heline Vasconcelos, Julio Croda, Carolinne Abreu, Katya Martinez Almeida, Camila Bitencourt de Andrade, Jhenyfer Thalyta Campos Angelo, Ghislaine Gonçalvez de Araújo Arcanjo, Bianca Maria Silva Menezes Arruda, Wellyngthon Espindola Ayala, Adelita Agripina Refosco Barbosa, Felipe Zampieri Vieira Batista, Fabiani de Morais Batista, Miriam de Jesus Costa, Mariana Garcia Croda, Lais Alves da Cruz, Roberta Carolina Pereira Diogo, Rodrigo Cezar Dutra Escobar, Iara Rodrigues Fernandes, Leticia Ramires Figueiredo, Leandro Galdino Cavalcanti Gonçalves, Sarita Lahdo, Joyce dos Santos Lencina, Guilherme Teodoro de Lima, Larissa Santos Matos, Bruna Tayara Leopoldina Meireles, Debora Quadros Moreira, Lilian Batista Silva Muranaka, Adriely de Oliveira, Karla Regina Warszawski de Oliveira, Matheus Vieira de Oliveira, Roberto Dias de Oliveira, Andrea Antonia Souza de Almeida dos Reis Pereira, Marco Puga, Caroliny Veron Ramos, Thaynara Haynara Souza da Rosa, Karla Lopes dos Santos, Claudinalva Ribeiro dos Santos, Dyenyffer Stéffany Leopoldina dos Santos, Karina Marques Santos, Paulo César Pereira da Silva, Paulo Victor Rocha da Silva, Débora dos Santos Silva, Patricia Vieira da Silva, Bruno Freitas da Rosa Soares, Mariana Gazzoni Sperotto, Mariana Mayumi Tadokoro, Daniel Tsuha, Hugo Miguel Ramos Vieira, Margareth Maria Pretti Dalcolmo, Cíntia Maria Lopes Alves da Paixão, Gabriela Corrêa E Castro, Simone Silva Collopy, Renato da Costa Silva, Samyra Almeida da Silveira, Alda Maria Da-Cruz, Alessandra Maria da Silva Passos de Carvalho, Rita de Cássia Batista, Maria Luciana Silva De Freitas, Aline Gerhardt de Oliveira Ferreira, Ana Paula Conceição de Souza, Paola Cerbino Doblas, Ayla Alcoforado da Silva dos Santos, Vanessa Cristine de Moraes dos Santos, Dayane Alves dos Santos Gomes, Anderson Lage Fortunato, Adriano Gomes-Silva, Monique Pinto Gonçalves, Paulo Leandro Garcia Meireless Junior, Estela Martins da Costa Carvalho, Fernando do Couto Motta, Ligia Maria Olivo de Mendonça, Girlene dos Santos Pandine, Rosa Maria Plácido Pereira, Ivan Ramos Maia, Jorge Luiz da Rocha, João Victor Paiva Romano, Glauce dos Santos, Erica Fernandes da Silva, Marilda Agudo Mendonça Teixeira de Siqueira, Ágatha Cristinne Prudêncio Soares, Marc Bonten, Sandra Franch Arroyo, Henny Ophorst-den Besten, Anna Boon, Karin M. Brakke, Axel Janssen, Marijke A.H. Koopmans, Toos Lemmens, Titia Leurink, Cristina Prat-Aymerich, Engelien Septer-Bijleveld, Kimberly Stadhouders, Darren Troeman, Marije van der Waal, Marjoleine van Opdorp, Nicolette van Sluis, Beatrijs Wolters, Jan Kluytmans, Jannie Romme, Wouter van den Bijllaardt, Linda van Mook, M.M.L (Miranda) van Rijen, Margreet Filius, Jet Gisolf, Frances Greven, Danique Huijbens, Robert Jan Hassing, Roos Pon, Lieke Preijers, Joke van Leusen, Harald Verheij, Wim Boersma, Evelien Brans, Paul Kloeg, Kitty Molenaar-Groot, Nhat Khanh Nguyen, Nienke Paternotte, Anke Rol, Lida Stooper, Helga Dijkstra, Esther Eggenhuizen, Lucas Huijs, Simone Moorlag, Mihai Netea, Eva Pranger, Esther Taks, Jaap ten Oever, Rob ter Heine, Kitty Blauwendraat, Bob Meek, Isil Erkaya, Houda Harbech, Nienke Roescher, Rifka Peeters, Menno te Riele, Carmen Zhou, Esther Calbo, Cristina Badia Marti, Emma Triviño Palomares, Tomás Perez Porcuna, Anabel Barriocanal, Ana Maria Barriocanal, Irma Casas, Jose Dominguez, Maria Esteve, Alicia Lacoma, Irene Latorre, Gemma Molina, Barbara Molina, Antoni Rosell, Sandra Vidal, Lydia Barrera, Natalia Bustos, Ines Portillo Calderón, David Gutierrez Campos, Jose Manuel Carretero, Angel Dominguez Castellano, Renato Compagnone, Encarnacion Ramirez de Arellano, Almudena de la Serna, Maria Dolores del Toro Lopez, Marie-Alix Clement Espindola, Ana Belen Martin Gutierrez, Alvaro Pascual Hernandez, Virginia Palomo Jiménez, Elisa Moreno, Nicolas Navarrete, Teresa Rodriguez Paño, Jesús Rodríguez-Baño, Enriqueta Tristán, Maria Jose Rios Villegas, Atsegiñe Canga Garces, Erika Castro Amo, Raquel Coya Guerrero, Josune Goikoetxea, Leticia Jorge, Cristina Perez, María Carmen Fariñas Álvarez, Manuel Gutierrez Cuadra, Francisco Arnaiz de las Revillas Almajano, Pilar Bohedo Garcia, Teresa Giménez Poderos, Claudia González Rico, Blanca Sanchez, Olga Valero, Noelia Vega, John Campbell, Anna Barnes, Helen Catterick, Tim Cranston, Phoebe Dawe, Emily Fletcher, Liam Fouracre, Alison Gifford, John Kirkwood, Christopher Martin, Amy McAnew, Marcus Mitchell, Georgina Newman, Abby O’Connell, Jakob Onysk, Lynne Quinn, Shelley Rhodes, Samuel Stone, Lorrie Symons, Harry Tripp, Adilia Warris, Darcy Watkins, Bethany Whale, Alex Harding, Gemma Lockhart, Kate Sidaway-Lee, Sam Hilton, Sarah Manton, Daniel Webber-Rookes, Rachel Winder, James Moore, Freya Bateman, Michael Gibbons, Bridget Knight, Julie Moss, Sarah Statton, Josephine Studham, Lydia Hall, Will Moyle, and Tamsin Venton

Subjects
Vaccine, Off-target, Immunoregulation, Cytokine, SARS-CoV-2, Heterologous immunity, Medicine, Medicine (General), R5-920
Abstract

Summary: Background: The COVID-19 pandemic led to the rapid development and deployment of several highly effective vaccines against SARS-CoV-2. Recent studies suggest that these vaccines may also have off-target effects on the immune system. We sought to determine and compare the off-target effects of the adenovirus vector ChAdOx1-S (Oxford-AstraZeneca) and modified mRNA BNT162b2 (Pfizer-BioNTech) vaccines on immune responses to unrelated pathogens. Methods: Prospective sub-study within the BRACE trial. Blood samples were collected from 284 healthcare workers before and 28 days after ChAdOx1-S or BNT162b2 vaccination. SARS-CoV-2-specific antibodies were measured using ELISA, and whole blood cytokine responses to specific (SARS-CoV-2) and unrelated pathogen stimulation were measured by multiplex bead array. Findings: Both vaccines induced robust SARS-CoV-2 specific antibody and cytokine responses. ChAdOx1-S vaccination increased cytokine responses to heat-killed (HK) Candida albicans and HK Staphylococcus aureus and decreased cytokine responses to HK Escherichia coli and BCG. BNT162b2 vaccination decreased cytokine response to HK E. coli and had variable effects on cytokine responses to BCG and resiquimod (R848). After the second vaccine dose, BNT162b2 recipients had greater specific and off-target cytokine responses than ChAdOx1-S recipients. Interpretation: ChAdOx1-S and BNT162b2 vaccines alter cytokine responses to unrelated pathogens, indicative of potential off-target effects. The specific and off-target effects of these vaccines differ in their magnitude and breadth. The clinical relevance of these findings is uncertain and needs further study. Funding: Bill & Melinda Gates Foundation, National Health and Medical Research Council, Swiss National Science Foundation and the Melbourne Children’s. BRACE trial funding is detailed in acknowledgements.

Published
2024
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27. Metabolic and inflammatory responses reveal different adaptation to the transition period challenges in Holstein, Brown Swiss, and Simmental dairy cows

Author

A. Catellani, M. Mezzetti, A. Minuti, L. Cattaneo, and E. Trevisi

Subjects
acute phase response, liver function, metabolism, milk yield, peripartum, Animal culture, SF1-1100
Abstract

Twelve Holstein (HOL), 9 Brown Swiss (BRO), and 9 Simmental (SIM) dairy cows raised in the same barn and managed identically were enrolled to characterise the responses to the transition period. From −21 to 28 d from calving (DFC), body condition score (BCS) and milk yield were measured, and blood samples were collected to assess plasma biomarkers of metabolism, minerals, liver function, inflammation, and oxidative status. Compared with SIM, HOL and BRO had higher milk yield during the first week of lactation. HOL had the highest milk yield from the second to the fourth week and the lowest BCS at 28 DFC. SIM had the highest BCS and the highest plasma creatinine and P, reflecting a greater attitude to gain muscle mass. Compared with SIM, BRO and HOL had lower plasma fructosamine, indicating reduced glucose availability driven by lactose synthesis. SIM had the mildest acute phase response at the onset of lactation, as suggested by the lowest ceruloplasmin concentration. HOL had the highest cholesterol and paraoxonase concentrations, and the greatest interleukin-1β production by leukocytes following ex-vivo stimulation, suggesting that they had the quickest resolution of the acute phase response due to the fastest immune cell activation. BRO had the highest concentration of reactive oxygen metabolites, ceruloplasmin, bilirubin, glutamate-oxaloacetate transaminase, γ-glutamyl transferase, and β-hydroxybutyrate, and the lowest concentration of paraoxonase, reflecting the strongest activation of leukocytes and the most severe acute phase response. Together, these results highlight different metabolic and inflammatory conditions around calving in the three explored breeds.HIGHLIGHTS Holstein, Brown Swiss, and Simmental are dairy breeds selected for different purposes. These three breeds have different productivity, and metabolic and inflammatory responses during the transition period. Understanding the differences among breeds might improve their management, nutrition, and productivity in commercial dairy farms.

Published
2023
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29. Togliatti systems associated to the dihedral group and the weak Lefschetz property

Author

Colarte-Gómez, Liena, Mezzetti, Emilia, Miró-Roig, Rosa M., and Salat-Moltó, Martí

Subjects
Mathematics - Algebraic Geometry, Mathematics - Commutative Algebra
Abstract

In this note, we study Togliatti systems generated by invariants of the dihedral group $D_{2d}$ acting on $k[x_{0},x_{1},x_{2}]$. This leads to the first family of non monomial Togliatti systems, which we call $GT-$systems with group $D_{2d}$. We study their associated varieties $S_{D_{2d}}$, called $GT-$surfaces with group $D_{2d}$. We prove that they are arithmetically Cohen-Macaulay surfaces whose homogeneous ideal, $I(S_{D_{2d}})$, is minimally generated by quadrics and we find a minimal free resolution of $I(S_{D_{2d}})$., Comment: To appear in Israel Journal of Mathematics

Published
2021

30. The FveFT2 florigen/FveTFL1 antiflorigen balance is critical for the control of seasonal flowering in strawberry while FveFT3 modulates axillary meristem fate and yield.

Author

Gaston, Amèlia, Potier, Aline, Alonso, Marie, Sabbadini, Silvia, Delmas, Frédéric, Tenreira, Tracey, Cochetel, Noé, Labadie, Marc, Prévost, Pierre, Folta, Kevin, Mezzetti, Bruno, Hernould, Michel, Rothan, Christophe, and Denoyes, Béatrice

Subjects
Fragaria (strawberry), antiflorigen, axillary meristem, branching, florigen, flowering, plant architecture, yield, Florigen, Flowers, Fragaria, Gene Expression Regulation, Plant, Meristem, Plant Proteins, Reproduction, Seasons
Abstract

Plant architecture is central in determining crop yield. In the short-day species strawberry, a crop vegetatively propagated by daughter-plants produced by stolons, fruit yield is further dependent on the trade-off between sexual reproduction (fruits) and asexual reproduction (daughter-plants). Both are largely dependent on meristem identity, which establishes the development of branches, stolons and inflorescences. Floral initiation and plant architecture are modulated by the balance between two related proteins, FLOWERING LOCUS T (FT) and TERMINAL FLOWER 1 (TFL1). We explored in woodland strawberry the role of the uncharacterised FveFT2 and FveFT3 genes and of the floral repressor FveTFL1 through gene expression analyses, grafting and genetic transformation (overexpression and gene editing). We demonstrate the unusual properties of these genes. FveFT2 is a nonphotoperiodic florigen permitting short-day (SD) flowering and FveTFL1 is the long-hypothesised long-day systemic antiflorigen that contributes, together with FveFT2, to the photoperiodic regulation of flowering. We additionally show that FveFT3 is not a florigen but promotes plant branching when overexpressed, that is likely to be through changing axillary meristem fate, therefore resulting in a 3.5-fold increase in fruit yield at the expense of stolons. We show that our findings can be translated into improvement of cultivated strawberry in which FveFT2 overexpression significantly accelerates flowering.

Published
2021

32. Sleep Quality and Its Relationship to Anxiety and Hardiness in a Cohort of Frontline Italian Nurses during the First Wave of the COVID-19 Pandemic

Author

Samuele Baldassini Rodriguez, Yari Bardacci, Khadija El Aoufy, Marco Bazzini, Christian Caruso, Gian Domenico Giusti, Andrea Mezzetti, Alberto Lucchini, Pasquale Iozzo, Andrea Guazzini, Camilla Elena Magi, Paolo Iovino, Yari Longobucco, Laura Rasero, and Stefano Bambi

Subjects
insomnia, healthcare workers, healthcare professionals, nurses, hardiness, COVID-19, Nursing, RT1-120
Abstract

Introduction: The COVID-19 pandemic has had a considerable impact on the psychological and psychopathological status of the population and health care workers in terms of insomnia, anxiety, depression, and post-traumatic stress disorder. The primary aim of this study was to describe and evaluate the impact of the pandemic on insomnia levels of a cohort of Italian nurses, particularly those involved in the care of COVID-19 patients. The secondary aim was to identify the interaction between insomnia and hardiness, anxiety, and sleep disturbances. Materials and Methods: A descriptive–exploratory study was conducted using an online survey during the first wave of the COVID-19 pandemic (March to July 2020). The questionnaire consisted of multiple-choice, open-ended, closed, and semi-closed questions. The psychometric tools administered were the Dispositional Resilience Scale (DRS-15), the State–Trait Anxiety Inventory (STAI-Y), and the Insomnia Severity Index (ISI). Results: a cohort of 1167 nurses fully completed the questionnaire (86.2% of total respondents). The insomnia scale survey showed an increase in post-pandemic scores compared to those before the pandemic, implying that insomnia levels increased after the first pandemic wave. Insomnia scores were directly correlated with anxiety levels (r = 0.571; p ≤ 0.05) and inversely correlated with hardiness levels (r = −0.324; p < 0.001). Multivariate analysis revealed the following protective factors: not having worked in COVID-19 wards, high levels of hardiness (commitment), and the presence of high pre-pandemic insomnia disorder. The main risk factor for insomnia reported in the analysis was a high anxiety score. Discussion and Conclusion: Anxiety represented the main risk factor for insomnia severity in our sample, while hardiness was confirmed as a protective factor. Thus, it is necessary to design further studies to identify additional risk factors for poor sleep quality and to develop educational courses and strategies aimed at enhancing rest and sleep quality, especially for frontline nurses.

Published
2023
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33. On the arithmetic Cohen-Macaulayness of varieties parameterized by Togliatti systems

Author

Colarte-Gómez, Liena, Mezzetti, Emilia, and Miró-Roig, Rosa M.

Subjects
Mathematics - Algebraic Geometry
Abstract

Given any diagonal cyclic subgroup $\Lambda \subset GL(n+1,k)$ of order $d$, let $I_d\subset k[x_0,\ldots, x_n]$ be the ideal generated by all monomials $\{m_{1},\ldots, m_{r}\}$ of degree $d$ which are invariants of $\Lambda$. $I_d$ is a monomial Togliatti system, provided $r \leq \binom{d+n-1}{n-1}$, and in this case the projective toric variety $X_d$ parameterized by $(m_{1},\ldots, m_{r})$ is called a $GT$-variety with group $\Lambda$. We prove that all these $GT$-varieties are arithmetically Cohen-Macaulay and we give a combinatorial expression of their Hilbert functions. In the case $n=2$, we compute explicitly the Hilbert function, polynomial and series of $X_d$. We determine a minimal free resolution of its homogeneous ideal and we show that it is a binomial prime ideal generated by quadrics and cubics. We also provide the exact number of both types of generators. Finally, we pose the problem of determining whether a surface parameterized by a Togliatti system is aCM. We construct examples that are aCM and examples that are not., Comment: To appear in Annali di Matematica Pura ed Applicata. Minor correction in the Introduction

Published
2020
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34. Quadric surfaces in the Pfaffian hypersurface in $\mathbb{P}^{14}$

Author

Boralevi, Ada, Fania, Maria Lucia, and Mezzetti, Emilia

Subjects
Mathematics - Algebraic Geometry, 15A30, 14N05, 14F05, 14M15
Abstract

We study smooth quadric surfaces in the Pfaffian hypersurface in $\mathbb{P}^{14}$ parameterising $6 \times 6$ skew-symmetric matrices of rank at most 4, not intersecting the Grassmannian $\mathbb{G}(1,5)$. Such surfaces correspond to quadratic systems of skew-symmetric matrices of size 6 and constant rank 4, and give rise to a globally generated vector bundle $E$ on the quadric. We analyse these bundles and their geometry, relating them to linear congruences of lines in $\mathbb{P}^5$., Comment: 18 pages

Published
2020

35. Contracting over persistent information

Author

Zhao, Wei, Mezzetti, Claudio, Renou, Ludovic, and Tomala, Tristan

Subjects
Economics - Theoretical Economics
Abstract

We consider a dynamic moral hazard problem between a principal and an agent, where the sole instrument the principal has to incentivize the agent is the disclosure of information. The principal aims at maximizing the (discounted) number of times the agent chooses a particular action, e.g., to work hard. We show that there exists an optimal contract, where the principal stops disclosing information as soon as its most preferred action is a static best reply for the agent or else continues disclosing information until the agent perfectly learns the principal's private information. If the agent perfectly learns the state, he learns it in finite time with probability one; the more patient the agent, the later he learns it.

Published
2020

36. Turning bad into good: a water-splitting-active hole transporting material to preserve the performance of perovskite solar cells in humid environments

Author

Kim, Min, Alfano, Antonio, Perotto, Giovanni, Serri, Michele, Dengo, Nicola, Mezzetti, Alessandro, Gross, Silvia, Prato, Mirko, Salerno, Marco, Sorrentino, Roberto, Meneghesso, Gaudenzio, Di Fonzo, Fabio, Petrozza, Annamaria, Gatti, Teresa, and Lamberti, Francesco

Subjects
Physics - Applied Physics, Condensed Matter - Materials Science
Abstract

Lead halide perovskite-based photoactive layers are nowadays employed for a large number of optoelectronic applications, from solar cells to photodetectors and light-emitting diodes, because of their excellent absorption, emission and charge-transport properties. Unfortunately, their commercialization is still hindered by an intrinsic instability towards classical environmental conditions. Water in particular promotes fast decomposition, leading to a drastic decrease in device performance. An innovative functional approach to overcome this major issue could derive from integrating water-splitting active species within charge extracting layers adjacent to the perovskite photoactive layer, converting incoming water molecules into molecular oxygen and hydrogen before they reach this last one, thus preserving device performance in time. In this work we report for the first time on a perovskite-ancillary layer based on CuSCN nanoplateletes dispersed in a p-type semiconducting polymeric matrix, combining hole extraction/transport properties with good water-oxidation activity, that transforms incoming water molecules and further triggers the in situ p-doping of the conjugated polymer by means of the produced dioxygen, further improving transport of photogenerated charges. This composite layer enables the long-term stabilization of a mixed cation lead halide perovskite within a direct solar cell architecture, maintaining a stable performance for 28 days in high-moisture simulated conditions. Our findings demonstrate that the engineering of a hole extraction layer with water-splitting active additives represent a valuable strategy to mitigate the degradation of perovskite solar cells exposed to atmospheric humidity. A similar approach could be employed in the future to improve stabilities of other optoelectronic devices based on water-sensitive species.

Published
2020

37. Spray‐induced gene silencing for disease control is dependent on the efficiency of pathogen RNA uptake

Author

Qiao, Lulu, Lan, Chi, Capriotti, Luca, Ah‐Fong, Audrey, Sanchez, Jonatan Nino, Hamby, Rachael, Heller, Jens, Zhao, Hongwei, Glass, N Louise, Judelson, Howard S, Mezzetti, Bruno, Niu, Dongdong, and Jin, Hailing

Subjects
Emerging Infectious Diseases, Infectious Diseases, Genetics, 2.2 Factors relating to the physical environment, Aetiology, Infection, Zero Hunger, Ascomycota, Botrytis, Colletotrichum, Gene Silencing, Plant Diseases, RNA Interference, RNA, Double-Stranded, Rhizoctonia, spray&#8208, induced gene silencing, small RNA, RNA interference, double&#8208, stranded RNA, uptake efficiency, double-stranded RNA, spray-induced gene silencing, Biological Sciences, Technology, Medical and Health Sciences, Biotechnology
Abstract

Recent discoveries show that fungi can take up environmental RNA, which can then silence fungal genes through environmental RNA interference. This discovery prompted the development of Spray-Induced Gene Silencing (SIGS) for plant disease management. In this study, we aimed to determine the efficacy of SIGS across a variety of eukaryotic microbes. We first examined the efficiency of RNA uptake in multiple pathogenic and non-pathogenic fungi, and an oomycete pathogen. We observed efficient double-stranded RNA (dsRNA) uptake in the fungal plant pathogens Botrytis cinerea, Sclerotinia sclerotiorum, Rhizoctonia solani, Aspergillus niger and Verticillium dahliae, but no uptake in Colletotrichum gloeosporioides, and weak uptake in a beneficial fungus, Trichoderma virens. For the oomycete plant pathogen, Phytophthora infestans, RNA uptake was limited and varied across different cell types and developmental stages. Topical application of dsRNA targeting virulence-related genes in pathogens with high RNA uptake efficiency significantly inhibited plant disease symptoms, whereas the application of dsRNA in pathogens with low RNA uptake efficiency did not suppress infection. Our results have revealed that dsRNA uptake efficiencies vary across eukaryotic microbe species and cell types. The success of SIGS for plant disease management can largely be determined by the pathogen's RNA uptake efficiency.

Published
2021

39. Emerging Parameters Justifying a Revised Quality Concept for Cow Milk

Author

Matteo Mezzetti, Matilde Maria Passamonti, Margherita Dall’Asta, Giuseppe Bertoni, Erminio Trevisi, and Paolo Ajmone Marsan

Subjects
cheesemaking, composition, environment, flavor, human health, sustainability, Chemical technology, TP1-1185
Abstract

Milk has become a staple food product globally. Traditionally, milk quality assessment has been primarily focused on hygiene and composition to ensure its safety for consumption and processing. However, in recent years, the concept of milk quality has expanded to encompass a broader range of factors. Consumers now also consider animal welfare, environmental impact, and the presence of additional beneficial components in milk when assessing its quality. This shifting consumer demand has led to increased attention on the overall production and sourcing practices of milk. Reflecting on this trend, this review critically explores such novel quality parameters, offering insights into how such practices meet the modern consumer’s holistic expectations. The multifaceted aspects of milk quality are examined, revealing the intertwined relationship between milk safety, compositional integrity, and the additional health benefits provided by milk’s bioactive properties. By embracing sustainable farming practices, dairy farmers and processors are encouraged not only to fulfill but to anticipate consumer standards for premium milk quality. This comprehensive approach to milk quality underscores the necessity of adapting dairy production to address the evolving nutritional landscape and consumption patterns.

Published
2024
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40. Bacillus Calmette-Guérin vaccination for protection against recurrent herpes labialis: a nested randomised controlled trialResearch in context

Author

Laure F. Pittet, Cecilia L. Moore, Ellie McDonald, Simone Barry, Marc Bonten, John Campbell, Julio Croda, Margareth Dalcolmo, Andrew Davidson, Mark W. Douglas, Kaya Gardiner, Amanda Gwee, Bruno Jardim, Marcus V.G. Lacerda, Michaela Lucas, David J. Lynn, Laurens Manning, Roberto D. de Oliveira, Kirsten P. Perrett, Cristina Prat-Aymerich, Peter C. Richmond, Jorge L. Rocha, Jesus Rodriguez-Baño, Adilia Warris, Nicholas J. Wood, Nicole L. Messina, Nigel Curtis, Tenaya Jamieson, Nicole Messina, Thilanka Morawakage, Susan Perlen, Kirsten Perrett, Laure Pittet, Amber Sastry, Jia Wei Teo, Francesca Orsini, Katherine Lee, Cecilia Moore, Suzanna Vidmar, Rashida Ali, Ross Dunn, Peta Edler, Grace Gell, Casey Goodall, Richard Hall, Ann Krastev, Nathan La, Nick McPhate, Thao Nguyen, Jack Ren, Luke Stevens, Ahmed Alamrousi, Rhian Bonnici, Thanh Dang, Susie Germano, Jenny Hua, Rebecca McElroy, Monica Razmovska, Scott Reddiex, Xiaofang Wang, Jeremy Anderson, Kristy Azzopardi, Vicki Bennett-Wood, Anna Czajko, Nadia Mazarakis, Conor McCafferty, Frances Oppedisano, Belinda Ortika, Casey Pell, Leena Spry, Ryan Toh, Sunitha Velagapudi, Amanda Vlahos, Ashleigh Wee-Hee, Pedro Ramos, Karina De La Cruz, Dinusha Gamage, Anushka Karunanayake, Isabella Mezzetti, Benjamin Ong, Ronita Singh, Enoshini Sooriyarachchi, Suellen Nicholson, Natalie Cain, Rianne Brizuela, Han Huang, Veronica Abruzzo, Morgan Bealing, Patricia Bimboese, Kirsty Bowes, Emma Burrell, Joyce Chan, Jac Cushnahan, Hannah Elborough, Olivia Elkington, Kieran Fahey, Monique Fernandez, Catherine Flynn, Sarah Fowler, Marie Gentile Andrit, Bojana Gladanac, Catherine Hammond, Norine Ma, Sam Macalister, Emmah Milojevic, Jesutofunmi Mojeed, Jill Nguyen, Liz O'Donnell, Nadia Olivier, Isabelle Ooi, Stephanie Reynolds, Lisa Shen, Barb Sherry, Judith Spotswood, Jamie Wedderburn, Angela Younes, Donna Legge, Jason Bell, Jo Cheah, Annie Cobbledick, Kee Lim, Sonja Elia, Lynne Addlem, Anna Bourke, Clare Brophy, Nadine Henare, Narelle Jenkins, Francesca Machingaifa, Skye Miller, Kirsten Mitchell, Sigrid Pitkin, Kate Wall, Paola Villanueva, Nigel Crawford, Wendy Norton, Niki Tan, Thilakavathi Chengodu, Diane Dawson, Victoria Gordon, Tony Korman, Jess O'Bryan, Sophie Agius, Samantha Bannister, Jess Bucholc, Alison Burns, Beatriz Camesella, John Carlin, Marianna Ciaverella, Maxwell Curtis, Stephanie Firth, Christina Guo, Matthew Hannan, Erin Hill, Sri Joshi, Katherine Lieschke, Megan Mathers, Sasha Odoi, Ashleigh Rak, Chris Richards, Leah Steve, Carolyn Stewart, Eva Sudbury, Helen Thomson, Emma Watts, Fiona Williams, Angela Young, Penny Glenn, Andrew Kaynes, Amandine Philippart De Floy, Sandy Buchanan, Thijs Sondag, Ivy Xie, Harriet Edmund, Bridie Byrne, Tom Keeble, Belle Ngien, Fran Noonan, Michelle Wearing-Smith, Alison Clarke, Pemma Davies, Oliver Eastwood, Alric Ellinghaus, Rachid Ghieh, Zahra Hilton, Emma Jennings, Athina Kakkos, Iris Liang, Katie Nicol, Sally O'Callaghan, Helen Osman, Gowri Rajaram, Sophia Ratcliffe, Victoria Rayner, Ashleigh Salmon, Angela Scheppokat, Aimee Stevens, Rebekah Street, Nicholas Toogood, Nicholas Wood, Twinkle Bahaduri, Therese Baulman, Jennifer Byrne, Candace Carter, Mary Corbett, Aiken Dao, Maria Desylva, Andrew Dunn, Evangeline Gardiner, Rosemary Joyce, Rama Kandasamy, Craig Munns, Lisa Pelayo, Ketaki Sharma, Katrina Sterling, Caitlin Uren, Clinton Colaco, Mark Douglas, Kate Hamilton, Adam Bartlett, Brendan McMullan, Pamela Palasanthiran, Phoebe Williams, Justin Beardsley, Nikki Bergant, Renier Lagunday, Kristen Overton, Jeffrey Post, Yasmeen Al-Hindawi, Sarah Barney, Anthony Byrne, Lee Mead, Marshall Plit, David Lynn, Saoirse Benson, Stephen Blake, Rochelle Botten, Tee Yee Chern, Georgina Eden, Liddy Griffith, Jane James, Miriam Lynn, Angela Markow, Domenic Sacca, Natalie Stevens, Steve Wesselingh, Catriona Doran, Alice Sawka, Sue Evans, Louise Goodchild, Christine Heath, Meredith Krieg, Helen Marshall, Mark McMillan, Mary Walker, Peter Richmond, Nelly Amenyogbe, Christina Anthony, Annabelle Arnold, Beth Arrowsmith, Rym Ben-Othman, Sharon Clark, Jemma Dunnill, Nat Eiffler, Krist Ewe, Carolyn Finucane, Lorraine Flynn, Camille Gibson, Lucy Hartnell, Elysia Hollams, Heidi Hutton, Lance Jarvis, Jane Jones, Jan Jones, Karen Jones, Jennifer Kent, Tobias Kollmann, Debbie Lalich, Wenna Lee, Rachel Lim, Sonia McAlister, Fiona McDonald, Andrea Meehan, Asma Minhaj, Lisa Montgomery, Melissa O'Donnell, Jaslyn Ong, Joanne Ong, Kimberley Parkin, Glady Perez, Catherine Power, Shadie Rezazadeh, Holly Richmond, Sally Rogers, Nikki Schultz, Margaret Shave, Patrycja Skut, Lisa Stiglmayer, Alexandra Truelove, Ushma Wadia, Rachael Wallace, Justin Waring, Michelle England, Erin Latkovic, Susan Herrmann, Marcus Lacerda, Paulo Henrique Andrade, Fabiane Bianca Barbosa, Dayanne Barros, Larissa Brasil, Ana Greyce Capella, Ramon Castro, Erlane Costa, Dilcimar de Souza, Maianne Dias, José Dias, Klenilson Ferreira, Paula Figueiredo, Thamires Freitas, Ana Carolina Furtado, Larissa Gama, Vanessa Godinho, Cintia Gouy, Daniele Hinojosa, Tyane Jardim, Joel Junior, Augustto Lima, Bernardo Maia, Adriana Marins, Kelry Mazurega, Tercilene Medeiros, Rosangela Melo, Marinete Moraes, Elizandra Nascimento, Juliana Neves, Maria Gabriela Oliveira, Thais Oliveira, Ingrid Oliveira, Arthur Otsuka, Rayssa Paes, Handerson Pereira, Gabrielle Pereira, Christiane Prado, Evelyn Queiroz, Laleyska Rodrigues, Bebeto Rodrigues, Vanderson Sampaio, Anna Gabriela Santos, Daniel Santos, Tilza Santos, Evelyn Santos, Ariandra Sartim, Ana Beatriz Silva, Juliana Silva, Emanuelle Silva, Mariana Simão, Caroline Soares, Antonny Sousa, Alexandre Trindade, Fernando Val, Adria Vasconcelos, Heline Vasconcelos, Carolinne Abreu, Katya Martinez Almeida, Camila Bitencourt de Andrade, Jhenyfer Thalyta Campos Angelo, Ghislaine Gonçalvez de Araújo Arcanjo, Bianca Maria Silva Menezes Arruda, Wellyngthon Espindola Ayala, Adelita Agripina Refosco Barbosa, Felipe Zampieri Vieira Batista, Fabiani de Morais Batista, Miriam de Jesus Costa, Mariana Garcia Croda, Lais Alves da Cruz, Roberta Carolina Pereira Diogo, Rodrigo Cezar Dutra Escobar, Iara Rodrigues Fernandes, Leticia Ramires Figueiredo, Leandro Galdino Cavalcanti Gonçalves, Sarita Lahdo, Joyce dos Santos Lencina, Guilherme Teodoro de Lima, Larissa Santos Matos, Bruna Tayara Leopoldina Meireles, Debora Quadros Moreira, Lilian Batista Silva Muranaka, Adriely de Oliveira, Karla Regina Warszawski de Oliveira, Matheus Vieira de Oliveira, Roberto Dias de Oliveira, Andrea Antonia Souza de Almeida dos Reis Pereira, Marco Puga, Caroliny Veron Ramos, Thaynara Haynara Souza da Rosa, Karla Lopes dos Santos, Claudinalva Ribeiro dos Santos, Dyenyffer Stéffany Leopoldina dos Santos, Karina Marques Santos, Paulo César Pereira da Silva, Paulo Victor Rocha da Silva, Débora dos Santos Silva, Patricia Vieira da Silva, Bruno Freitas da Rosa Soares, Mariana Gazzoni Sperotto, Mariana Mayumi Tadokoro, Daniel Tsuha, Hugo Miguel Ramos Vieira, Margareth Maria Pretti Dalcolmo, Cíntia Maria Lopes Alves da Paixão, Gabriela Corrêa E Castro, Simone Silva Collopy, Renato da Costa Silva, Samyra Almeida da Silveira, Alda Maria Da-Cruz, Alessandra Maria da Silva Passos de Carvalho, Rita de Cássia Batista, Maria Luciana Silva De Freitas, Aline Gerhardt de Oliveira Ferreira, Ana Paula Conceição de Souza, Paola Cerbino Doblas, Ayla Alcoforado da Silva dos Santos, Vanessa Cristine de Moraes dos Santos, Dayane Alves dos Santos Gomes, Anderson Lage Fortunato, Adriano Gomes-Silva, Monique Pinto Gonçalves, Paulo Leandro Garcia Meireless Junior, Estela Martins da Costa Carvalho, Fernando do Couto Motta, Ligia Maria Olivo de Mendonça, Girlene dos Santos Pandine, Rosa Maria Plácido Pereira, Ivan Ramos Maia, Jorge Luiz da Rocha, João Victor Paiva Romano, Glauce dos Santos, Erica Fernandes da Silva, Marilda Agudo Mendonça Teixeira de Siqueira, Ágatha Cristinne Prudêncio Soares, Sandra Franch Arroyo, Henny Ophorst-den Besten, Anna Boon, Karin M. Brakke, Axel Janssen, Marijke A.H. Koopmans, Toos Lemmens, Titia Leurink, Engelien Septer-Bijleveld, Kimberly Stadhouders, Darren Troeman, Marije van der Waal, Marjoleine van Opdorp, Nicolette van Sluis, Beatrijs Wolters, Jan Kluytmans, Jannie Romme, Wouter van den Bijllaardt, Linda van Mook, M.M.L (Miranda) van Rijen, P.M.G. Filius, Jet Gisolf, Frances Greven, Danique Huijbens, Robert Jan Hassing, R.C. Pon, Lieke Preijers, J.H. van Leusen, Harald Verheij, Wim Boersma, Evelien Brans, Paul Kloeg, Kitty Molenaar-Groot, Nhat Khanh Nguyen, Nienke Paternotte, Anke Rol, Lida Stooper, Helga Dijkstra, Esther Eggenhuizen, Lucas Huijs, Simone Moorlag, Mihai Netea, Eva Pranger, Esther Taks, Jaap ten Oever, Rob ter Heine, Kitty Blauwendraat, Bob Meek, Isil Erkaya, Houda Harbech, Nienke Roescher, Rifka Peeters, Menno te Riele, Carmen Zhou, Esther Calbo, Cristina Badia Marti, Emma Triviño Palomares, Tomás Perez Porcuna, Anabel Barriocanal, Ana Maria Barriocanal, Irma Casas, Jose Dominguez, Maria Esteve, Alicia Lacoma, Irene Latorre, Gemma Molina, Barbara Molina, Antoni Rosell, Sandra Vidal, Lydia Barrera, Natalia Bustos, Ines Portillo Calderón, David Gutierrez Campos, Jose Manuel Carretero, Angel Dominguez Castellano, Renato Compagnone, Encarnacion Ramirez de Arellano, Almudena de la Serna, Maria Dolores del Toro Lopez, Marie-Alix Clement Espindola, Ana Belen Martin Gutierrez, Alvaro Pascual Hernandez, Virginia Palomo Jiménez, Elisa Moreno, Nicolas Navarrete, Teresa Rodriguez Paño, Jesús Rodríguez-Baño, Enriqueta Tristán, Maria Jose Rios Villegas, Atsegiñe Canga Garces, Erika Castro Amo, Raquel Coya Guerrero, Josune Goikoetxea, Leticia Jorge, Cristina Perez, María Carmen Fariñas Álvarez, Manuel Gutierrez Cuadra, Francisco Arnaiz de las Revillas Almajano, Pilar Bohedo Garcia, Teresa Giménez Poderos, Claudia González Rico, Blanca Sanchez, Olga Valero, Noelia Vega, Anna Barnes, Helen Catterick, Tim Cranston, Phoebe Dawe, Emily Fletcher, Liam Fouracre, Alison Gifford, John Kirkwood, Christopher Martin, Amy McAnew, Marcus Mitchell, Georgina Newman, Abby O'Connell, Jakob Onysk, Lynne Quinn, Shelley Rhodes, Samuel Stone, Lorrie Symons, Harry Tripp, Darcy Watkins, Bethany Whale, Alex Harding, Gemma Lockhart, Kate Sidaway-Lee, Sam Hilton, Sarah Manton, Daniel Webber-Rookes, Rachel Winder, James Moore, Freya Bateman, Michael Gibbons, Bridget Knight, Julie Moss, Sarah Statton, Josephine Studham, Lydia Hall, Will Moyle, and Tamsin Venton

Subjects
Herpes simplex virus, Cold sore, Herpes labialis, Bacille Calmette-Guérin, Mycobacterium bovis, Prevention, Medicine (General), R5-920
Abstract

Summary: Background: Recurrences of herpes simplex virus (HSV) in the orofacial region (herpes labialis or cold sores) impact quality-of-life. We aimed to study whether the bacille Calmette-Guérin (BCG) vaccine can attenuate cold sore recurrences through off-target immunomodulatory effects. Methods: In this nested randomised controlled trial within the multicentre, phase 3 BRACE trial, 6828 healthcare workers were randomised in 36 sites in Australia, the Netherlands, Spain, the United Kingdom and Brazil, to receive BCG-Denmark or no BCG (1:1 ratio using a web-based procedure) and followed for 12 months with 3-monthly questionnaires. Exclusion criteria included contraindication to BCG vaccine or previous vaccination with BCG within the past year, any other live-attenuated vaccine within the last month, or any COVID-specific vaccine. The intervention group received one intradermal dose of 0.1 mL of BCG-Denmark corresponding to 2−8 x 105 colony forming units of Mycobacterium bovis, Danish strain 1331. The primary outcome was the difference in restricted mean survival time (i.e., time to first cold-sore recurrence), in participants with frequent recurrent herpes labialis (≥4 recurrences/year), analysed by intention-to-treat. Secondary outcomes addressed additional questions, including analyses in other sub-populations. Adverse events were monitored closely during the first 3 months and were reported in all participants who received one dose of study drug according to intervention received. The BRACE trial is registered with ClinicalTrials.gov, NCT04327206. Findings: Between March 30, 2020 and February 18, 2021, 84 individuals with frequent recurrent cold sores were randomly assigned to BCG (n = 38) or control (n = 46). The average time to first cold-sore recurrence was 1.55 months longer in the BCG group (95% CI 0.27–2.82, p = 0.02) than the control group (hazard ratio 0.54, 95% CI 0.32–0.91; intention-to-treat). The beneficial effect of BCG was greater in the as-treated population (difference 1.91 months, 95% CI 0.69–3.12, p = 0.003; hazard ratio 0.45, 95% CI 0.26–0.76). In prespecified subgroup analyses, only sex modified the treatment effect (interaction p = 0.007), with benefit restricted to males. Over 12 months, a greater proportion of participants in the BCG group compared with the control group reported a decrease in duration (61% vs 21%), severity (74% vs 21%), frequency (55% vs 21%), and impact on quality of life (42% vs 15%) of cold sore recurrences. In participants who had ever had a cold sore, there was also a decrease in self-reported burden of recurrences in the BCG group. In participants who had never had a cold sore, there was an increased risk of a first episode in the BCG group (risk difference 1.4%; 95% CI 0.3–2.6%, p = 0.02). There were no safety concerns. Interpretation: BCG-Denmark vaccination had a beneficial effect on herpes labialis, particularly in males with frequent recurrences, but may increase the risk of a first cold sore. Funding: Bill & Melinda Gates Foundation, the Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children's Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare, and individual donors.

Published
2023
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41. Analysis of Drug Utilization in Patients with Psoriasis: A Real-World Retrospective Study Among the Italian Population

Author

Perrone V, Losi S, Sabatino S, Mezzetti M, Dovizio M, Sangiorgi D, and Degli Esposti L

Subjects
psoriasis systemic medications, psoriasis biological drugs, tnf inhibitors, il inhibitors, treatment optimization, real word evidence., Dermatology, RL1-803
Abstract

Valentina Perrone,1 Serena Losi,2 Silvia Sabatino,2 Maurizio Mezzetti,3 Melania Dovizio,1 Diego Sangiorgi,1 Luca Degli Esposti1 1CliCon S.r.l., Società Benefit-Health Economics and Outcomes Research, Bologna, 40137, Italy; 2Eli Lilly Italy S.p.A, Sesto Fiorentino, Italy; 3Eli Lilly Italy S.p.A, Rome, ItalyCorrespondence: Valentina Perrone, CliCon S.r.l., Società Benefit-Health Economics and Outcomes Research, Via Murri 9, Bologna, 40137, Italy, Tel +39 544 38393, Fax +39 544 212699, Email valentina.perrone@clicon.itPurpose: An Italian real-world retrospective study was conducted in patients with psoriasis (PSO) to evaluate their characteristics, treatment patterns, and biological/targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) drug utilization.Patients and Methods: The retrospective analysis was carried out on real-world data collected from administrative databases of selected Italian health-departments; the dataset covered approximately 22% of the Italian population. PSO patients (identified by PSO hospitalization, and/or active exemption code and/or a topical anti-psoriatic medication prescription) were included. In prevalent patients identified during 2017– 2018-2019-2020, baseline characteristics and treatment patterns were investigated. Moreover, b/tsDMARD drug utilization (focusing on persistence, monthly dosage, and mean duration between prescriptions) was evaluated in bionaïve patients included during 2015 and 2018.Results: PSO was diagnosed in 241,552 (in 2017), 269,856 (in 2018), 293,905 (in 2019) and 301,639 (in 2020) patients. At the index date, almost 50% of patients had not received systemic medications, and 2% had received biological treatment. Among the b/tsDMARD-treated patients, a decrease in the use of tumour necrosis factor (TNF) inhibitors (60.0– 36.4%, from 2017 to 2020) and an increase in the use of interleukin (IL) inhibitors (36.3– 50.6%, from 2017 to 2020) were observed. In 2018, the persistence rates of TNF inhibitors and IL inhibitors in bionaïve patients ranged from 60.8– 79.7% and 83.3– 87.9%, respectively.Conclusion: This real-world study of PSO drug utilization in Italy showed that a significant number of patients were not treated with systemic medications and only 2% of patients were treated with biologics. An increase in the use of IL inhibitors and a decrease in the prescription of TNF inhibitors over years were found. Patients treated with biologics were highly persistent with treatment. These data provide insight into routine clinical practice for PSO patients in Italy, suggesting that the optimization of treatment for PSO still represents an unmet medical need.Keywords: psoriasis systemic medications, psoriasis biological drugs, TNF inhibitors, IL inhibitors, treatment optimization, real world evidence

Published
2023

44. Effect of a feed additive containing yeast cell walls, clove and coriander essential oils and Hibiscus sabdariffa administered to mid-lactating dairy cows on productive performance, rumen fluid composition and metabolic conditions

Author

Matteo Mezzetti, Michele Premi, Andrea Minuti, Paolo Bani, Vincenzo Lopreiato, and Erminio Trevisi

Subjects
nutraceuticals, rumen fermentation, milk yield, hibiscus sabdariffa, essential oils, Animal culture, SF1-1100
Abstract

Thirty-six multiparous Holstein mid-lactating cows were housed in 6 pens (6 cows/pen) and allocated in two groups (3 pens/group), receiving a control total mixed ration (CTR), or the same diet supplemented with a feed additive (TRT). Between 15 and 35 days from enrolment (DFE) the dry matter intake (DMI) of each pen, and the individual milk yield (MY), rumination time (RT), the compositions of milk and rumen fluid and the metabolic profile of plasma were monitored regularly. At 35 DFE, cows started a 1-week wash-up period prior to the changeover. Data were analysed with a mixed model using repeated measures. Cows receiving the additive had higher DMI and MY (p

Published
2022
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45. A bibliometric review of Persea americana Mill. (Lauraceae): A green gold in agroindustry

Author

Rahimah Zakaria, Patricia Vit, Adi Wijaya, Asma Hayati Ahmad, Zahiruddin Othman, and Bruno Mezzetti

Subjects
avocado, persea americana, bibliometric analysis, bibliometrix, vosviewer, Agriculture (General), S1-972, Food processing and manufacture, TP368-456
Abstract

Avocado's global acceptance has grown, resulting in expanding cultivation, agricultural development, and significant marketing efforts. Publicizing avocado also targets its by-products' nutritional and functional benefits. This is the first bibliometric analysis for avocado. It aims to provide a descriptive structure to identify collaborative patterns and emerging themes in avocado research. Based on the search string used in the article b, the study retrieved 2576 documents from the Scopus database for further analysis. For comparison, we separated the data into two study periods: 1916–2011 and 2012–2021. BibliometriX and VOSviewer software were used to examine the descriptive structure and collaborative patterns, as well as to create maps based on network data. When we compared the two study periods, we identified a changing pattern in descriptive structure, collaboration and research trends. Based on the identified emergent themes of the last decade, we propose that future research focuses on the functional and medicinal properties of avocado, postharvest management and its biological control, plant cultivars and diseases, and physicochemical properties of avocado and its by-products. Further bibliographic support revealed that, in addition to the fruit pulp, non-edible parts of Persea americana (bark, leaves, peel, seeds, and stem), and oil have remarkable concentrations of bioactive compounds with potential biological activity for health benefits.

Published
2022
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47. Circulant matrices and Galois-Togliatti systems

Author

De Poi, Pietro, Mezzetti, Emilia, Michałek, Mateusz, Miró-Roig, Rosa Maria, and Nevo, Eran

Subjects
Mathematics - Commutative Algebra, Mathematics - Algebraic Geometry, Mathematics - Combinatorics, 15B05, 15A05, 13E10, 14M25
Abstract

The goal of this article is to compare the coefficients in the expansion of the permanent with those in the expansion of the determinant of a three-lines circulant matrix. As an application we prove a conjecture concerning the minimality of Galois-Togliatti systems.

Published
2018

48. Strongly Coupled Dark Energy Cosmologies yielding large mass Primordial Black Holes

Author

Bonometto, S. A., Mainini, R., and Mezzetti, M.

Subjects
Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract

Large primordial Black Hole (PBH) formation is enhanced if strongly coupled scalar and spinor fields ($\Phi$ and $\psi$) are a stable cosmic component since the primeval radiative expansion (SCDEW models). In particular, we show that PBH formation is easier at a specific time, i.e., when the asymptotic mass $m_H$, acquired by the $\psi$ field at the higgs scale, becomes dominant, so that the typical BH mass $M_{BH}$ depends on $m_H$ value. For instance, if $m_H \sim 100\,$ eV $(1$ keV$)$ and the coupling $\beta \sim 8.35 (37)$, PBH with $M_{BH} \simeq 10^7-10^8 $ $(10^3-10^4)\, M_\odot$ could form. The very mechanism enhancing PBH formation also causes technical difficulties to evaluate the transfer function of SCDEW models at high $k$. A tentative solution of this problem leaves only minor discrepancies from $\Lambda$CDM, also at these scales, gradually vanishing for greater $m_H$ values. We conclude that, for suitable parameter choices, SCDEW models could be the real physics underlying $\Lambda$ CDM, so overcoming its fine tuning and coincidence problems, with the extra bonus of yielding large BH seeds., Comment: 15 pages, 15 figures; accepted for publication in MNRAS. Updated to match accepted version

Published
2018
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49. On the Coefficients of the Permanent and the Determinant of a Circulant Matrix. Applications

Author

Colarte, Liena, Mezzetti, Emilia, Miró-Roig, Rosa Maria, and Salat, Martí

Subjects
Mathematics - Algebraic Geometry, Mathematics - Commutative Algebra, Mathematics - Combinatorics
Abstract

Let $d(N )$ (resp. $p(N )$) be the number of summands in the determinant (resp. permanent) of an $N\times N$ circulant matrix $A = (a_{ij} )$ given by $a_{ij} = X_{i+j}$ where $i + j$ should be considered $\mod N$ . This short note is devoted to prove that $d(N ) = p(N )$ if and only if $N$ is a prime power. We then give an application to homogeneous monomial ideals failing the Weak Lefschetz property., Comment: Proc. AMS, to appear

Published
2018

50. Efficient protocol of de novo shoot organogenesis from somatic embryos for grapevine genetic transformation

Author

Luca Capriotti, Angela Ricci, Barbara Molesini, Bruno Mezzetti, Tiziana Pandolfini, Irene Piunti, and Silvia Sabbadini

Subjects
Vitis vinifera, somatic embryogenesis, Agrobacterium tumefaciens, in vitro organogenesis, transformation efficiency, Plant culture, SB1-1110
Abstract

Plant genetic transformation is a powerful tool that can facilitate breeding programs for disease tolerance, abiotic stress, fruit production, and quality by preserving the characteristics of fruit tree elite genotypes. However, most grapevine cultivars worldwide are considered recalcitrant, and most available genetic transformation protocols involve regeneration by somatic embryogenesis, which often requires the continuous production of new embryogenic calli. Cotyledons and hypocotyls derived from flower-induced somatic embryos of the Vitis vinifera cultivars Ancellotta and Lambrusco Salamino, in comparison with the model cultivar Thompson Seedless, are here validated for the first time as starting explants for in vitro regeneration and transformation trials. Explants were cultured on two different MS-based culture media, one having a combination of 4.4 µM BAP and 0.49 µM IBA (M1), and the other only supplemented with 13.2 µM BAP (M2). The competence to regenerate adventitious shoots was higher in cotyledons than in hypocotyls on both M1 and M2. M2 medium increased significantly the average number of shoots only in Thompson Seedless somatic embryo-derived explants. This efficient regeneration strategy, that proposes a combination of somatic embryogenesis and organogenesis, has been successfully exploited in genetic engineering experiments. Ancellotta and Lambrusco Salamino cotyledons and hypocotyls produced the highest number of calli expressing eGFP when cultured on M2 medium, while for Thompson Seedless both media tested were highly efficient. The regeneration of independent transgenic lines of Thompson Seedless was observed from cotyledons cultured on both M1 and M2 with a transformation efficiency of 12 and 14%, respectively, and from hypocotyls on M1 and M2 with a transformation efficiency of 6 and 12%, respectively. A single eGFP fluorescent adventitious shoot derived from cotyledons cultured on M2 was obtained for Ancellotta, while Lambrusco Salamino showed no regeneration of transformed shoots. In a second set of experiments, using Thompson Seedless as the model cultivar, we observed that the highest number of transformed shoots was obtained from cotyledons explants, followed by hypocotyls and meristematic bulk slices, confirming the high regeneration/transformation competences of somatic embryo-derived cotyledons. The independent transformed shoots obtained from the cultivars Thompson Seedless and Ancellotta were successfully acclimatized in the greenhouse and showed a true-to-type phenotype. The novel in vitro regeneration and genetic transformation protocols optimized in this study will be useful for the application of new and emerging modern biotechnologies also to other recalcitrant grapevine genotypes.

Published
2023
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