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1. Identifying latent disease factors differently expressed in patient subgroups using group factor analysis

Author

Ferreira, Fabio S., Ashburner, John, Bouzigues, Arabella, Suksasilp, Chatrin, Russell, Lucy L., Foster, Phoebe H., Ferry-Bolder, Eve, van Swieten, John C., Jiskoot, Lize C., Seelaar, Harro, Sanchez-Valle, Raquel, Laforce, Robert, Graff, Caroline, Galimberti, Daniela, Vandenberghe, Rik, de Mendonca, Alexandre, Tiraboschi, Pietro, Santana, Isabel, Gerhard, Alexander, Levin, Johannes, Sorbi, Sandro, Otto, Markus, Pasquier, Florence, Ducharme, Simon, Butler, Chris R., Ber, Isabelle Le, Finger, Elizabeth, Tartaglia, Maria C., Masellis, Mario, Rowe, James B., Synofzik, Matthis, Moreno, Fermin, Borroni, Barbara, Kaski, Samuel, Rohrer, Jonathan D., and Mourao-Miranda, Janaina

Subjects
Statistics - Machine Learning, Computer Science - Machine Learning
Abstract

In this study, we propose a novel approach to uncover subgroup-specific and subgroup-common latent factors addressing the challenges posed by the heterogeneity of neurological and mental disorders, which hinder disease understanding, treatment development, and outcome prediction. The proposed approach, sparse Group Factor Analysis (GFA) with regularised horseshoe priors, was implemented with probabilistic programming and can uncover associations (or latent factors) among multiple data modalities differentially expressed in sample subgroups. Synthetic data experiments showed the robustness of our sparse GFA by correctly inferring latent factors and model parameters. When applied to the Genetic Frontotemporal Dementia Initiative (GENFI) dataset, which comprises patients with frontotemporal dementia (FTD) with genetically defined subgroups, the sparse GFA identified latent disease factors differentially expressed across the subgroups, distinguishing between "subgroup-specific" latent factors within homogeneous groups and "subgroup common" latent factors shared across subgroups. The latent disease factors captured associations between brain structure and non-imaging variables (i.e., questionnaires assessing behaviour and disease severity) across the different genetic subgroups, offering insights into disease profiles. Importantly, two latent factors were more pronounced in the two more homogeneous FTD patient subgroups (progranulin (GRN) and microtubule-associated protein tau (MAPT) mutation), showcasing the method's ability to reveal subgroup-specific characteristics. These findings underscore the potential of sparse GFA for integrating multiple data modalities and identifying interpretable latent disease factors that can improve the characterization and stratification of patients with neurological and mental health disorders., Comment: 38 pages, 14 figures

Published
2024

2. Post-acute COVID-19 outcomes including participant-reported long COVID: amubarvimab/romlusevimab versus placebo in the ACTIV-2 trial

Author

Evering, Teresa H, Moser, Carlee, Jilg, Nikolaus, Ritz, Justin, Wohl, David A, Li, Jonathan Z, Margolis, David, Javan, Arzhang Cyrus, Eron, Joseph J, Currier, Judith S, Daar, Eric S, Smith, Davey M, Hughes, Michael D, Chew, Kara W, Chew, Kara, Smith, David, Daar, Eric, Wohl, David, Currier, Judith, Eron, Joseph, Hughes, Michael, Giganti, Mark, Hosey, Lara, Roa, Jhoanna, Patel, Nilam, Colsh, Kelly, Rwakazina, Irene, Beck, Justine, Sieg, Scott, Li, Jonathan, Fletcher, Courtney, Fischer, William, Ignacio, Rachel Bender, Cardoso, Sandra, Corado, Katya, Jagannathan, Prasanna, Perelson, Alan, Pillay, Sandy, Riviere, Cynthia, Singh, Upinder, Taiwo, Babafemi, Gottesman, Joan, Newell, Matthew, Pedersen, Susan, Dragavon, Joan, Jennings, Cheryl, Greenfelder, Brian, Murtaugh, William, Kosmyna, Jan, Gapara, Morgan, Shahkolahi, Akbar, Lacal, Verónica, Salusso, Diego, Nuñez, Sebastian, Rodriguez, Marcelo Rodrigo, Laborde, Luciana, Papasidero, Marcelo, Wehbe, Luis, Gonzalez, Mariana, Voena, Felicitas Fernandez, Alvarez, Tomas, Lopez, Amaru, Huhn, Virginia, Nores, Ulises D'Andrea, Dieser, Pablo, Bordese, Fernando, Mussi, Marisa, de Carvalho Santana, Rodrigo, Bárbaro, Adriana Aparecida Tiraboschi, Santos, Breno, de Cássia Alves Lira, Rita, da Silva, Andre Luiz Machado, Cardoso, Sandra Wagner, Ribeiro, Maria Pia Diniz, Soliva, Nathália, Vasconcellos, Eduardo, Ribeiro, Jorge Eurico, Enéas, Miriam Amaral, Pinto, Jorge, de Morais Caporali, Julia Fonseca, Ferreira, Flávia Gomes Faleiro, Martinez, Norma Erendira Rivera, Lopez, Victor Casildo Bohorquez, Frias, Melchor Victor, Fetalvero, Krystle, Maranan, Alyxzza, Rosa, Jennifer, Coetzer, Thomas, Mohata, Maureen, Lalloo, Umesh, Madlala, Penelope, Pillay-Ramaya, Larisha, and Bennet, Jaclyn Ann

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Trials and Supportive Activities, Infectious Diseases, Coronaviruses, Clinical Research, Emerging Infectious Diseases, Prevention, 6.1 Pharmaceuticals, Good Health and Well Being, COVID-19, Monoclonal antibodies, Outpatient treatment, Clinical trial, Post COVID conditions, Long COVID, Post-acute sequelae of SARS-CoV-2 infection, ACTIV-2/A5401 Study Team, Clinical sciences, Health services and systems, Public health
Abstract

BackgroundIt is unknown if early COVID-19 monoclonal antibody (mAb) therapy can reduce risk of Long COVID. The mAbs amubarvimab/romlusevimab were previously demonstrated to reduce risk of hospitalization/death by 79%. This study assessed the impact of amubarvimab/romlusevimab on late outcomes, including Long COVID.MethodsNon-hospitalized high-risk adults within 10 days of COVID-19 symptom onset enrolled in a randomized, double-blind, placebo-controlled phase 2/3 trial of amubarvimab/romlusevimab for COVID-19 treatment. Late symptoms, assessed using a participant-completed symptom diary, were a pre-specified exploratory endpoint. The primary outcome for this analysis was the composite of Long COVID by participant self-report (presence of COVID-19 symptoms as recorded in the diary at week 36) or hospitalization or death by week 36. Inverse probability weighting (IPW) was used to address incomplete outcome ascertainment, giving weighted risk ratios (wRR) comparing amubarvimab/romlusevimab to placebo.FindingsParticipants received amubarvimab/romlusevimab (n = 390) or placebo (n = 390) between January and July 2021. Median age was 49 years, 52% were female, 18% Black/African American, 49% Hispanic/Latino, and 9% COVID-19-vaccinated at entry. At week 36, 103 (13%) had incomplete outcome ascertainment, and 66 (17%) on amubarvimab/romlusevimab and 92 (24%) on placebo met the primary outcome (wRR = 0.70, 95% confidence interval (CI) 0.53-0.93). The difference was driven by fewer hospitalizations/deaths with amubarvimab/romlusevimab (4%) than placebo (13%). Among 652 participants with available diary responses, 53 (16%) on amubarvimab/romlusevimab and 44 (14%) on placebo reported presence of Long COVID.InterpretationAmubarvimab/romlusevimab treatment, while highly effective in preventing hospitalizations/deaths, did not reduce risk of Long COVID. Additional interventions are needed to prevent Long COVID.FundingNational Institute of Allergy and Infectious Diseases of the National Institutes of Health. Amubarvimab and romlusevimab supplied by Brii Biosciences.

Published
2024

3. Clinical validity of the Italian adaptation of the Uniform Data Set Neuropsychological Test Battery (I-UDSNB) in Mild Cognitive Impairment and Alzheimer’s Disease

Author

Conca, Francesca, Esposito, Valentina, Catricalà, Eleonora, Manenti, Rosa, L’Abbate, Federica, Quaranta, Davide, Giuffrè, Guido Maria, Rossetto, Federica, Solca, Federica, Orso, Beatrice, Inguscio, Emanuela, Crepaldi, Valeria, De Matteis, Maddalena, Rotondo, Emanuela, Manera, Marina, Caruso, Giulia, Catania, Valentina, Canu, Elisa, Rundo, Francesco, Cotta Ramusino, Matteo, Filippi, Massimo, Fundarò, Cira, Piras, Federica, Arighi, Andrea, Tiraboschi, Pietro, Stanzani Maserati, Michelangelo, Pardini, Matteo, Poletti, Barbara, Silani, Vincenzo, Marra, Camillo, Di Tella, Sonia, Cotelli, Maria, Lodi, Raffaele, Tagliavini, Fabrizio, and Cappa, Stefano Francesco

Published
2024
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5. Diagnostic accuracy of research criteria for prodromal frontotemporal dementia

Author

Benussi, Alberto, Premi, Enrico, Grassi, Mario, Alberici, Antonella, Cantoni, Valentina, Gazzina, Stefano, Archetti, Silvana, Gasparotti, Roberto, Fumagalli, Giorgio G., Bouzigues, Arabella, Russell, Lucy L., Samra, Kiran, Cash, David M., Bocchetta, Martina, Todd, Emily G., Convery, Rhian S., Swift, Imogen, Sogorb-Esteve, Aitana, Heller, Carolin, van Swieten, John C., Jiskoot, Lize C., Seelaar, Harro, Sanchez-Valle, Raquel, Moreno, Fermin, Laforce, Robert Jr., Graff, Caroline, Synofzik, Matthis, Galimberti, Daniela, Rowe, James B., Masellis, Mario, Tartaglia, Maria Carmela, Finger, Elizabeth, Vandenberghe, Rik, Mendonça, Alexandre, Tiraboschi, Pietro, Butler, Chris R., Santana, Isabel, Gerhard, Alexander, Le Ber, Isabelle, Pasquier, Florence, Ducharme, Simon, Levin, Johannes, Sorbi, Sandro, Otto, Markus, Padovani, Alessandro, Rohrer, Jonathan D., and Borroni, Barbara

Published
2024
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6. Sound Symbolic Execution via Abstract Interpretation and its Application to Security

Author

Tiraboschi, Ignacio, Rezk, Tamara, and Rival, Xavier

Subjects
Computer Science - Programming Languages, D.3.0
Abstract

Symbolic execution is a program analysis technique commonly utilized to determine whether programs violate properties and, in case violations are found, to generate inputs that can trigger them. Used in the context of security properties such as noninterference, symbolic execution is precise when looking for counterexample pairs of traces when insecure information flows are found, however it is sound only up to a bound thus it does not allow to prove the correctness of programs with executions beyond the given bound. By contrast, abstract interpretation-based static analysis guarantees soundness but generally lacks the ability to provide counterexample pairs of traces. In this paper, we propose to weave both to obtain the best of two worlds. We demonstrate this with a series of static analyses, including a static analysis called RedSoundRSE aimed at verifying noninterference. RedSoundRSE provides both semantically sound results and the ability to derive counterexample pairs of traces up to a bound. It relies on a combination of symbolic execution and abstract domains inspired by the well known notion of reduced product. We formalize RedSoundRSE and prove its soundness as well as its relative precision up to a bound. We also provide a prototype implementation of RedSoundRSE and evaluate it on a sample of challenging examples., Comment: 29 pages, 8 figures. Published in the 24th International Conference on Verification, Model Checking, and Abstract Interpretation (VMCAI 2023)

Published
2023
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7. Post-acute COVID-19 outcomes including participant-reported long COVID: amubarvimab/romlusevimab versus placebo in the ACTIV-2 trialResearch in context

Author

Teresa H. Evering, Carlee Moser, Nikolaus Jilg, Justin Ritz, David A. Wohl, Jonathan Z. Li, David Margolis, Arzhang Cyrus Javan, Joseph J. Eron, Judith S. Currier, Eric S. Daar, Davey M. Smith, Michael D. Hughes, Kara W. Chew, Kara Chew, David (Davey) Smith, Eric Daar, David Wohl, Judith Currier, Joseph Eron, Michael Hughes, Mark Giganti, Lara Hosey, Jhoanna Roa, Nilam Patel, Kelly Colsh, Irene Rwakazina, Justine Beck, Scott Sieg, Jonathan Li, Courtney Fletcher, William Fischer, Rachel Bender Ignacio, Sandra Cardoso, Katya Corado, Prasanna Jagannathan, Alan Perelson, Sandy Pillay, Cynthia Riviere, Upinder Singh, Babafemi Taiwo, Joan Gottesman, Matthew Newell, Susan Pedersen, Joan Dragavon, Cheryl Jennings, Brian Greenfelder, William Murtaugh, Jan Kosmyna, Morgan Gapara, Akbar Shahkolahi, Verónica Lacal, Diego Salusso, Sebastian Nuñez, Marcelo Rodrigo Rodriguez, Luciana Laborde, Marcelo Papasidero, Luis Wehbe, Mariana Gonzalez, Felicitas Fernandez Voena, Tomas Alvarez, Amaru Lopez, Virginia Huhn, Ulises D'Andrea Nores, Pablo Dieser, Fernando Bordese, Marisa Mussi, Rodrigo de Carvalho Santana, Adriana Aparecida Tiraboschi Bárbaro, Breno Santos, Rita de Cássia Alves Lira, Andre Luiz Machado da Silva, Sandra Wagner Cardoso, Maria Pia Diniz Ribeiro, Nathália Soliva, Eduardo Vasconcellos, Jorge Eurico Ribeiro, Miriam Amaral Enéas, Jorge Pinto, Julia Fonseca de Morais Caporali, Flávia Gomes Faleiro Ferreira, Norma Erendira Rivera Martinez, Victor Casildo Bohorquez Lopez, Melchor Victor Frias, Krystle Fetalvero, Alyxzza Maranan, Jennifer Rosa, Thomas Coetzer, Maureen Mohata, Sr., Umesh Lalloo, Penelope Madlala, Larisha Pillay-Ramaya, Jaclyn Ann Bennet, Noluthando Mwelase, Nokuphiwa Mbhele, Frederick Petrick, Leonard Joubert, Rose Mbali, Sr., Natasha Joseph, Mmatsie Manentsa, Eugene van der Walt, Mduduzi Sandile Lawrance Masilela, Zinhle Zwane, Tendai Chiperera, Lerato Mohapi, Suri Moonsamy, Usha Singh, Kirsten McHarry, Elizma Snyman, Pieter Lennox, James Craig Innes, Oteng Letlape, Olebogeng Jonkane, William Brumskine, Tania Adonis, Ni Ni Sein, Modulakgotla Sebe, Yacoob Vahed, Nazreen Jeewa Hussen, Ismail Mitha, Vasundhara Cheekati, Purna Cheekati, Christie Lummus, Samuel Idarraga, Andrew Kim, David N. Pham, Wei-Hsin Kao, Michael M. Pfeffer, Miriam Batule Dominguez, Anju Malik, Anna Bryan, Melanie Arnold, Idania Fernandez, Cinzia Karpf, Aniuska Ruiz, David Taylor, Eric Folkens, Jennifer Manne, Sigal Yawetz, Cheryl Keenan, Emeka Eziri, Carl Fichtenbaum, Jenifer Baer, Sarah Trentman, Robert Call, Leroy Vaughan, Aaron Milstone, Jamie Alex Slandzicki, Jessica Wallan, Clinton Guillory, Nancy Andrews, Leslie Hughes, Jonathan Berardi, Celine Arar, Randall Quinn, Jorge P. Amaya, Marissa Gomez-Martinez, Luis Cantu, Monica Betancourt-Garcia, Nwora Lance Okeke, Charles M. Burns, Fadi Haddad, Victoria Haddad, Augusto Focil, Griselda Rosas, Susana Moyano, Yaneicy Gonzalez Rojas, Ahmad Aswad, Yevgeniy Bukhman, Manish Jain, Eugene Bukhman, Humam Farah, Rebekah McClain, Sadia Shaik, Timothy Hatlen, Deepa Gotur, Joseph Surber, Jeffrey Kingsley, April Pixler, Alex Zopo, Jack Herman, Craig Herman, Ramon Leon, Boris Nikolov, Fernando Gonzalez Vergara, Ana I. Gonzalez, Noemi Gonzalez, Michael Gelman, Olga Andriunas, Zarema Jagizarov, Jan Westerman, David Davis, Donna Sherer, Kelly Dooley, Becky Becker, Adaliah Wilkins, Jose Pérez, Eloy Roman, Heriberto Fernández, Bharat Mocherla, Kelly Beck, Valarie Maldonado, Jennifer Veltman, Rajesh Gandhi, Katrina Shea, Matthew Planchon, Laura Bogan Herpel, Kaushlendra K. Tripathi, Donald C. Day, John Pullman, Sr., Erin Williams-Leber, Misty Johnson, Michelle Hecker, Ann Avery, Keila Hoover, George W. Monlux, Elizabeth Juneja, Jr., Arthur Wernick, Karelia Ruiz, Maureen Hernández, Yadilys Pérez, Babafemi O. Taiwo, Claudia Hawkins, Baiba Berzins, Carlos Malvestutto, Heather Harber, Robyn Cicarella, Edwin DeJesus, Charlotte-Paige Rolle, Almena L. Free, Sallie D. Pulliam, Debra Weinstein, Rosa M. Suarez, Ezequiel Socorro, Estefania Socorro, Gene Neytman, Raymond Easley, Mariam Aziz, Joan Swiatek, Avish Nagpal, Breanna Kompelien, Kathryn McEvoy, Susan E. Hoover, Allison Lutz, Jessica Just, Manuel Hernandez, Yanly B. Victoria, Gabriel Rodriguez, Divya Pathak, Joshua J. Ordway, Megan Heffner, Patrick Weston, Khalilah Weston, Madhu Choudhary, Jennifer Sullivano, Olayemi Osiyemi, Myriam Izquierdo, Odelsey Torna, Brian Clemency, Renoj Varughese, Joshua Lynch, Aleen Khodabakhshian, Samantha Fortier, Christopher Coyne, Alexandrea Cronin, Constance Benson, Steven Hendrickx, Rosemarie Ramirez, Anne Luetkemeyer, Suzanne Hendler, Dennis Dentoni-Lasofsky, Mobeen Rathore, Saniyyah Mahmoudi, Amna Riaz, Mario Castro, Leslie Spikes, Chase Hall, Jonathan Oakes, Amy James Loftis, Pablo Tebas, William Short, Michael P. Dube, Saahir Khan, Luis M. Mendez, Sarah McGuffin, Chris Jonsson, Mamta K. Jain, Smruthi Senthil, Kimberly Turner-Gray, Sanjay Mehta, Mary Lewinski, Masoud Azizad, Christopher Chow, Lisa Nakatani, Derrick Williamson, Hisham Atriss, Matthew Caloura, Midhun Malla, Hannah Hazard-Jenkins, Aimee Wilkin, Jamraus Fayssoux, Hannah Seagle, Rachel Presti, and Alem Haile

Subjects
COVID-19, Monoclonal antibodies, Outpatient treatment, Clinical trial, Post COVID conditions, Long COVID, Medicine (General), R5-920
Abstract

Summary: Background: It is unknown if early COVID-19 monoclonal antibody (mAb) therapy can reduce risk of Long COVID. The mAbs amubarvimab/romlusevimab were previously demonstrated to reduce risk of hospitalization/death by 79%. This study assessed the impact of amubarvimab/romlusevimab on late outcomes, including Long COVID. Methods: Non-hospitalized high-risk adults within 10 days of COVID-19 symptom onset enrolled in a randomized, double-blind, placebo-controlled phase 2/3 trial of amubarvimab/romlusevimab for COVID-19 treatment. Late symptoms, assessed using a participant-completed symptom diary, were a pre-specified exploratory endpoint. The primary outcome for this analysis was the composite of Long COVID by participant self-report (presence of COVID-19 symptoms as recorded in the diary at week 36) or hospitalization or death by week 36. Inverse probability weighting (IPW) was used to address incomplete outcome ascertainment, giving weighted risk ratios (wRR) comparing amubarvimab/romlusevimab to placebo. Findings: Participants received amubarvimab/romlusevimab (n = 390) or placebo (n = 390) between January and July 2021. Median age was 49 years, 52% were female, 18% Black/African American, 49% Hispanic/Latino, and 9% COVID-19-vaccinated at entry. At week 36, 103 (13%) had incomplete outcome ascertainment, and 66 (17%) on amubarvimab/romlusevimab and 92 (24%) on placebo met the primary outcome (wRR = 0.70, 95% confidence interval (CI) 0.53–0.93). The difference was driven by fewer hospitalizations/deaths with amubarvimab/romlusevimab (4%) than placebo (13%). Among 652 participants with available diary responses, 53 (16%) on amubarvimab/romlusevimab and 44 (14%) on placebo reported presence of Long COVID. Interpretation: Amubarvimab/romlusevimab treatment, while highly effective in preventing hospitalizations/deaths, did not reduce risk of Long COVID. Additional interventions are needed to prevent Long COVID. Funding: National Institute of Allergy and Infectious Diseases of the National Institutes of Health. Amubarvimab and romlusevimab supplied by Brii Biosciences.

Published
2024
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8. Safety and Efficacy of Combination SARS-CoV-2 Neutralizing Monoclonal Antibodies Amubarvimab Plus Romlusevimab in Nonhospitalized Patients With COVID-19

Author

Evering, Teresa H, Chew, Kara W, Giganti, Mark J, Moser, Carlee, Pinilla, Mauricio, Wohl, David Alain, Currier, Judith S, Eron, Joseph J, Javan, Arzhang Cyrus, Bender Ignacio, Rachel, Margolis, David, Zhu, Qing, Ma, Ji, Zhong, Lijie, Yan, Li, D’Andrea Nores, Ulises, Hoover, Keila, Mocherla, Bharat, Choudhary, Manish C, Deo, Rinki, Ritz, Justin, Fischer, William A, Fletcher, Courtney V, Li, Jonathan Z, Hughes, Michael D, Smith, Davey, Daar, Eric S, Hosey, Lara, Roa, Jhoanna, Patel, Nilam, Colsh, Kelly, Rwakazina, Irene, Beck, Justine, Sieg, Scott, Cardoso, Sandra, Corado, Katya, Jagannathan, Prasanna, Jilg, Nikolaus, Perelson, Alan, Pillay, Sandy, Riviere, Cynthia, Singh, Upinder, Taiwo, Babafemi, Gottesman, Joan, Newell, Matthew, Pedersen, Susan, Dragavon, Joan, Jennings, Cheryl, Greenfelder, Brian, Murtaugh, William, Kosmyna, Jan, Gapara, Morgan, Shahkolahi, Akbar, Lacal, Verónica, Salusso, Diego, Nuñez, Sebastian, Rodrigo Rodriguez, Marcelo, Laborde, Luciana, Papasidero, Marcelo, Wehbe, Luis, Gonzalez, Mariana, Fernandez Voena, Felicitas, Alvarez, Tomas, Lopez, Amaru, Huhn, Virginia, Dieser, Pablo, Bordese, Fernando, Mussi, Marisa, de Carvalho Santana, Rodrigo, Bárbaro, Adriana Aparecida Tiraboschi, Santos, Breno, de Cássia Alves Lira, Rita, da Silva, Andre Luiz Machado, Ribeiro, Maria Pia Diniz, Soliva, Nathália, Vasconcellos, Eduardo, Ribeiro, Jorge Eurico, Enéas, Miriam Amaral, and Pinto, Jorge

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Prevention, Patient Safety, Infectious Diseases, Clinical Trials and Supportive Activities, Vaccine Related, Lung, Emerging Infectious Diseases, Clinical Research, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Infection, Good Health and Well Being, Adult, Humans, Female, Middle Aged, Male, COVID-19, SARS-CoV-2, Antibodies, Monoclonal, Antibodies, Viral, Double-Blind Method, ACTIV-2/A5401 Study Team, Medical and Health Sciences, General & Internal Medicine, Clinical sciences
Abstract

BackgroundDevelopment of safe and effective SARS-CoV-2 therapeutics is a high priority. Amubarvimab and romlusevimab are noncompeting anti-SARS-CoV-2 monoclonal antibodies with an extended half-life.ObjectiveTo assess the safety and efficacy of amubarvimab plus romlusevimab.DesignRandomized, placebo-controlled, phase 2 and 3 platform trial. (ClinicalTrials.gov: NCT04518410).SettingNonhospitalized patients with COVID-19 in the United States, Brazil, South Africa, Mexico, Argentina, and the Philippines.PatientsAdults within 10 days onset of symptomatic SARS-CoV-2 infection who are at high risk for clinical progression.InterventionCombination of monoclonal antibodies amubarvimab plus romlusevimab or placebo.MeasurementsNasopharyngeal and anterior nasal swabs for SARS-CoV-2, COVID-19 symptoms, safety, and progression to hospitalization or death.ResultsEight-hundred and seven participants who initiated the study intervention were included in the phase 3 analysis. Median age was 49 years (quartiles, 39 to 58); 51% were female, 18% were Black, and 50% were Hispanic or Latino. Median time from symptom onset at study entry was 6 days (quartiles, 4 to 7). Hospitalizations and/or death occurred in 9 (2.3%) participants in the amubarvimab plus romlusevimab group compared with 44 (10.7%) in the placebo group, with an estimated 79% reduction in events (P

Published
2023

10. Clinical validity of the Italian adaptation of the Uniform Data Set Neuropsychological Test Battery (I-UDSNB) in Mild Cognitive Impairment and Alzheimer’s Disease

Author

Francesca Conca, Valentina Esposito, Eleonora Catricalà, Rosa Manenti, Federica L’Abbate, Davide Quaranta, Guido Maria Giuffrè, Federica Rossetto, Federica Solca, Beatrice Orso, Emanuela Inguscio, Valeria Crepaldi, Maddalena De Matteis, Emanuela Rotondo, Marina Manera, Giulia Caruso, Valentina Catania, Elisa Canu, Francesco Rundo, Matteo Cotta Ramusino, Massimo Filippi, Cira Fundarò, Federica Piras, Andrea Arighi, Pietro Tiraboschi, Michelangelo Stanzani Maserati, Matteo Pardini, Barbara Poletti, Vincenzo Silani, Camillo Marra, Sonia Di Tella, Maria Cotelli, Raffaele Lodi, Fabrizio Tagliavini, and Stefano Francesco Cappa

Subjects
Neuropsychological tests, UDS, Alzheimer’s Disease, Mild Cognitive Impairment, Cognition, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background The identification and staging of Alzheimer’s Disease (AD) represent a challenge, especially in the prodromal stage of Mild Cognitive Impairment (MCI), when cognitive changes can be subtle. Worldwide efforts were dedicated to select and harmonize available neuropsychological instruments. In Italy, the Italian Network of Neuroscience and Neuro-Rehabilitation has promoted the adaptation of the Uniform Data Set Neuropsychological Test Battery (I-UDSNB), collecting normative data from 433 healthy controls (HC). Here, we aimed to explore the ability of I-UDSNB to differentiate between a) MCI and HC, b) AD and HC, c) MCI and AD. Methods One hundred thirty-seven patients (65 MCI, 72 AD) diagnosed after clinical-neuropsychological assessment, and 137 HC were included. We compared the I-UDSNB scores between a) MCI and HC, b) AD and HC, c) MCI and AD, with t-tests. To identify the test(s) most capable of differentiating between groups, significant scores were entered in binary logistic and in stepwise regressions, and then in Receiver Operating Characteristic curve analyses. Results Two episodic memory tests (Craft Story and Five Words test) differentiated MCI from HC subjects; Five Words test, Semantic Fluency (vegetables), and TMT-part B differentiated AD from, respectively, HC and MCI. Conclusions Our findings indicate that the I-UDSNB is a suitable tool for the harmonized and concise assessment of patients with cognitive decline, showing high sensitivity and specificity for the diagnosis of MCI and AD.

Published
2024
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11. Network structure and transcriptomic vulnerability shape atrophy in frontotemporal dementia

Author

Shafiei, Golia, Bazinet, Vincent, Dadar, Mahsa, Manera, Ana L, Collins, D Louis, Dagher, Alain, Borroni, Barbara, Sanchez-Valle, Raquel, Moreno, Fermin, Laforce, Robert, Graff, Caroline, Synofzik, Matthis, Galimberti, Daniela, Rowe, James B, Masellis, Mario, Tartaglia, Maria Carmela, Finger, Elizabeth, Vandenberghe, Rik, de Mendonça, Alexandre, Tagliavini, Fabrizio, Santana, Isabel, Butler, Chris, Gerhard, Alex, Danek, Adrian, Levin, Johannes, Otto, Markus, Sorbi, Sandro, Jiskoot, Lize C, Seelaar, Harro, van Swieten, John C, Rohrer, Jonathan D, Misic, Bratislav, Ducharme, Simon, Initiative, Frontotemporal Lobar Degeneration Neuroimaging, Rosen, Howard, Dickerson, Bradford C, Domoto-Reilly, Kimoko, Knopman, David, Boeve, Bradley F, Boxer, Adam L, Kornak, John, Miller, Bruce L, Seeley, William W, Gorno-Tempini, Maria-Luisa, McGinnis, Scott, Mandelli, Maria Luisa, Initiative, GENetic Frontotemporal dementia, Esteve, Aitana Sogorb, Nelson, Annabel, Bouzigues, Arabella, Heller, Carolin, Greaves, Caroline V, Cash, David, Thomas, David L, Todd, Emily, Benotmane, Hanya, Zetterberg, Henrik, Swift, Imogen J, Nicholas, Jennifer, Samra, Kiran, Russell, Lucy L, Bocchetta, Martina, Shafei, Rachelle, Convery, Rhian S, Timberlake, Carolyn, Cope, Thomas, Rittman, Timothy, Benussi, Alberto, Premi, Enrico, Gasparotti, Roberto, Archetti, Silvana, Gazzina, Stefano, Cantoni, Valentina, Arighi, Andrea, Fenoglio, Chiara, Scarpini, Elio, Fumagalli, Giorgio, Borracci, Vittoria, Rossi, Giacomina, Giaccone, Giorgio, Di Fede, Giuseppe, Caroppo, Paola, Tiraboschi, Pietro, Prioni, Sara, Redaelli, Veronica, Tang-Wai, David, Rogaeva, Ekaterina, Castelo-Branco, Miguel, Freedman, Morris, Keren, Ron, Black, Sandra, Mitchell, Sara, Shoesmith, Christen, Bartha, Robart, Rademakers, Rosa, van der Ende, Emma, Poos, Jackie, Papma, Janne M, Giannini, Lucia, and van Minkelen, Rick

Subjects
Biomedical and Clinical Sciences, Health Sciences, Psychology, Acquired Cognitive Impairment, Dementia, Aging, Neurodegenerative, Frontotemporal Dementia (FTD), Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Brain Disorders, Alzheimer's Disease, Aetiology, 2.1 Biological and endogenous factors, Neurological, Humans, Frontotemporal Dementia, Transcriptome, Brain, Pick Disease of the Brain, Atrophy, Connectome, Magnetic Resonance Imaging, Neuropsychological Tests, Frontotemporal Lobar Degeneration Neuroimaging Initiative, GENetic Frontotemporal dementia Initiative, connectome, disease epicentre, frontotemporal dementia, gene expression, network spreading, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery, Biomedical and clinical sciences, Health sciences
Abstract

Connections among brain regions allow pathological perturbations to spread from a single source region to multiple regions. Patterns of neurodegeneration in multiple diseases, including behavioural variant of frontotemporal dementia (bvFTD), resemble the large-scale functional systems, but how bvFTD-related atrophy patterns relate to structural network organization remains unknown. Here we investigate whether neurodegeneration patterns in sporadic and genetic bvFTD are conditioned by connectome architecture. Regional atrophy patterns were estimated in both genetic bvFTD (75 patients, 247 controls) and sporadic bvFTD (70 patients, 123 controls). First, we identified distributed atrophy patterns in bvFTD, mainly targeting areas associated with the limbic intrinsic network and insular cytoarchitectonic class. Regional atrophy was significantly correlated with atrophy of structurally- and functionally-connected neighbours, demonstrating that network structure shapes atrophy patterns. The anterior insula was identified as the predominant group epicentre of brain atrophy using data-driven and simulation-based methods, with some secondary regions in frontal ventromedial and antero-medial temporal areas. We found that FTD-related genes, namely C9orf72 and TARDBP, confer local transcriptomic vulnerability to the disease, modulating the propagation of pathology through the connectome. Collectively, our results demonstrate that atrophy patterns in sporadic and genetic bvFTD are jointly shaped by global connectome architecture and local transcriptomic vulnerability, providing an explanation as to how heterogenous pathological entities can lead to the same clinical syndrome.

Published
2023

12. Temporal order of clinical and biomarker changes in familial frontotemporal dementia

Author

Staffaroni, Adam M, Quintana, Melanie, Wendelberger, Barbara, Heuer, Hilary W, Russell, Lucy L, Cobigo, Yann, Wolf, Amy, Goh, Sheng-Yang Matt, Petrucelli, Leonard, Gendron, Tania F, Heller, Carolin, Clark, Annie L, Taylor, Jack Carson, Wise, Amy, Ong, Elise, Forsberg, Leah, Brushaber, Danielle, Rojas, Julio C, VandeVrede, Lawren, Ljubenkov, Peter, Kramer, Joel, Casaletto, Kaitlin B, Appleby, Brian, Bordelon, Yvette, Botha, Hugo, Dickerson, Bradford C, Domoto-Reilly, Kimiko, Fields, Julie A, Foroud, Tatiana, Gavrilova, Ralitza, Geschwind, Daniel, Ghoshal, Nupur, Goldman, Jill, Graff-Radford, Jonathon, Graff-Radford, Neill, Grossman, Murray, Hall, Matthew G. H, Hsiung, Ging-Yuek, Huey, Edward D, Irwin, David, Jones, David T, Kantarci, Kejal, Kaufer, Daniel, Knopman, David, Kremers, Walter, Lago, Argentina Lario, Lapid, Maria I, Litvan, Irene, Lucente, Diane, Mackenzie, Ian R, Mendez, Mario F, Mester, Carly, Miller, Bruce L, Onyike, Chiadi U, Rademakers, Rosa, Ramanan, Vijay K, Ramos, Eliana Marisa, Rao, Meghana, Rascovsky, Katya, Rankin, Katherine P, Roberson, Erik D, Savica, Rodolfo, Tartaglia, M. Carmela, Weintraub, Sandra, Wong, Bonnie, Cash, David M, Bouzigues, Arabella, Swift, Imogen J, Peakman, Georgia, Bocchetta, Martina, Todd, Emily G, Convery, Rhian S, Rowe, James B, Borroni, Barbara, Galimberti, Daniela, Tiraboschi, Pietro, Masellis, Mario, Finger, Elizabeth, van Swieten, John C, Seelaar, Harro, Jiskoot, Lize C, Sorbi, Sandro, Butler, Chris R, Graff, Caroline, Gerhard, Alexander, Langheinrich, Tobias, Laforce, Robert, Sanchez-Valle, Raquel, de Mendonça, Alexandre, Moreno, Fermin, Synofzik, Matthis, Vandenberghe, Rik, Ducharme, Simon, Le Ber, Isabelle, Levin, Johannes, Danek, Adrian, Otto, Markus, Pasquier, Florence, Santana, Isabel, and Kornak, John

Published
2022

13. Diagnostic accuracy of research criteria for prodromal frontotemporal dementia

Author

Alberto Benussi, Enrico Premi, Mario Grassi, Antonella Alberici, Valentina Cantoni, Stefano Gazzina, Silvana Archetti, Roberto Gasparotti, Giorgio G. Fumagalli, Arabella Bouzigues, Lucy L. Russell, Kiran Samra, David M. Cash, Martina Bocchetta, Emily G. Todd, Rhian S. Convery, Imogen Swift, Aitana Sogorb-Esteve, Carolin Heller, John C. van Swieten, Lize C. Jiskoot, Harro Seelaar, Raquel Sanchez-Valle, Fermin Moreno, Robert Jr. Laforce, Caroline Graff, Matthis Synofzik, Daniela Galimberti, James B. Rowe, Mario Masellis, Maria Carmela Tartaglia, Elizabeth Finger, Rik Vandenberghe, Alexandre Mendonça, Pietro Tiraboschi, Chris R. Butler, Isabel Santana, Alexander Gerhard, Isabelle Le Ber, Florence Pasquier, Simon Ducharme, Johannes Levin, Sandro Sorbi, Markus Otto, Alessandro Padovani, Jonathan D. Rohrer, Barbara Borroni, and Genetic Frontotemporal dementia Initiative (GENFI)

Subjects
Prodromal, MCBMI, Frontotemporal dementia, Diagnostic criteria, Diagnostic accuracy, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background The Genetic Frontotemporal Initiative Staging Group has proposed clinical criteria for the diagnosis of prodromal frontotemporal dementia (FTD), termed mild cognitive and/or behavioral and/or motor impairment (MCBMI). The objective of the study was to validate the proposed research criteria for MCBMI-FTD in a cohort of genetically confirmed FTD cases against healthy controls. Methods A total of 398 participants were enrolled, 117 of whom were carriers of an FTD pathogenic variant with mild clinical symptoms, while 281 were non-carrier family members (healthy controls (HC)). A subgroup of patients underwent blood neurofilament light (NfL) levels and anterior cingulate atrophy assessment. Results The core clinical criteria correctly classified MCBMI vs HC with an AUC of 0.79 (p < 0.001), while the addition of either blood NfL or anterior cingulate atrophy significantly increased the AUC to 0.84 and 0.82, respectively (p < 0.001). The addition of both markers further increased the AUC to 0.90 (p < 0.001). Conclusions The proposed MCBMI criteria showed very good classification accuracy for identifying the prodromal stage of FTD.

Published
2024
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16. Correction: Italian adaptation of the Uniform Data Set Neuropsychological Test Battery (I‑UDSNB 1.0): development and normative data

Author

Conca, Francesca, Esposito, Valentina, Rundo, Francesco, Quaranta, Davide, Muscio, Cristina, Manenti, Rosa, Caruso, Giulia, Lucca, Ugo, Galbussera, Alessia Antonella, Di Tella, Sonia, Baglio, Francesca, L’Abbate, Federica, Canu, Elisa, Catania, Valentina, Filippi, Massimo, Mattavelli, Giulia, Poletti, Barbara, Silani, Vincenzo, Lodi, Raffaele, De Matteis, Maddalena, Maserati, Michelangelo Stanzani, Arighi, Andrea, Rotondo, Emanuela, Tanzilli, Antonio, Pace, Andrea, Garramone, Federica, Cavaliere, Carlo, Pardini, Matteo, Rizzetto, Cristiano, Sorbi, Sandro, Perri, Roberta, Tiraboschi, Pietro, Canessa, Nicola, Cotelli, Maria, Ferri, Raffaele, Weintraub, Sandra, Marra, Camillo, Tagliavini, Fabrizio, Catricalà, Eleonora, and Cappa, Stefano Francesco

Published
2023
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18. Extending the phenotypic spectrum assessed by the CDR plus NACC FTLD in genetic frontotemporal dementia

Author

Kiran Samra, Georgia Peakman, Amy M. MacDougall, Arabella Bouzigues, Caroline V. Greaves, Rhian S. Convery, John C. vanSwieten, Lize Jiskoot, Harro Seelaar, Fermin Moreno, Raquel Sanchez‐Valle, Robert Laforce, Caroline Graff, Mario Masellis, Maria Carmela Tartaglia, James B. Rowe, Barbara Borroni, Elizabeth Finger, Matthis Synofzik, Daniela Galimberti, Rik Vandenberghe, Alexandre deMendonça, Chris R. Butler, Alexander Gerhard, Simon Ducharme, Isabelle Le Ber, Pietro Tiraboschi, Isabel Santana, Florence Pasquier, Johannes Levin, Markus Otto, Sandro Sorbi, Jonathan D. Rohrer, Lucy L. Russell, and Genetic FTD Initiative (GENFI)

Subjects
C9orf72, frontotemporal dementia, genetics, progranulin, tau, Neurology. Diseases of the nervous system, RC346-429, Geriatrics, RC952-954.6
Abstract

Abstract INTRODUCTION We aimed to expand the range of the frontotemporal dementia (FTD) phenotypes assessed by the Clinical Dementia Rating Dementia Staging Instrument plus National Alzheimer's Coordinating Center Behavior and Language Domains (CDR plus NACC FTLD). METHODS Neuropsychiatric and motor domains were added to the standard CDR plus NACC FTLD generating a new CDR plus NACC FTLD‐NM scale. This was assessed in 522 mutation carriers and 310 mutation‐negative controls from the Genetic Frontotemporal dementia Initiative (GENFI). RESULTS The new scale led to higher global severity scores than the CDR plus NACC FTLD: 1.4% of participants were now considered prodromal rather than asymptomatic, while 1.3% were now considered symptomatic rather than asymptomatic or prodromal. No participants with a clinical diagnosis of an FTD spectrum disorder were classified as asymptomatic using the new scales. DISCUSSION Adding new domains to the CDR plus NACC FTLD leads to a scale that encompasses the wider phenotypic spectrum of FTD with further work needed to validate its use more widely. Highlights The new Clinical Dementia Rating Dementia Staging Instrument plus National Alzheimer's Coordinating Center Behavior and Language Domains neuropsychiatric and motor (CDR plus NACC FTLD‐NM) rating scale was significantly positively correlated with the original CDR plus NACC FTLD and negatively correlated with the FTD Rating Scale (FRS). No participants with a clinical diagnosis in the frontotemporal dementia spectrum were classified as asymptomatic with the new CDR plus NACC FTLD‐NM rating scale. Individuals had higher global severity scores with the addition of the neuropsychiatric and motor domains. A receiver operating characteristic analysis of symptomatic diagnosis showed nominally higher areas under the curve for the new scales.

Published
2024
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19. Emergency medicine residents in the war zone: organizing humanitarian expeditions to train healthcare personnel during the conflict in Ukraine

Author

Giovanni Cappa, Valeria Mauri, Erika Negrello, Bruno Barcella, Flavia Resta, Valentina Angeli, Stefania Marconi, Lorenzo Tiraboschi, Paolo Minzioni, Andrea Pietrabissa, Ferdinando Auricchio, and Stefano Perlini

Subjects
Humanitarian expedition, Stop the bleed, 3d printing, tactical medicine, Tactical Combat Casualty Care, Medicine (General), R5-920
Abstract

Dear Editor, When faced with a crisis, particularly when it involves humanitarian aid, emergency medicine (EM) practitioners push themselves to question, “How can we help?” and “To the best of our knowledge and skills, what can we truly do?”. The mindset of EM personnel is presumably one of "How can I help in these situations?" and, more crucially, "How can I help the most effectively?". To answer these questions, we present our experience in Ukraine. [...]

Published
2024
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20. Arsenite and arsenate stress differently affect auxin distribution in rice roots and brassinosteroids restore it sustaining root system plasticity

Author

D. Piacentini, C. Bellini, A. Peduzzi, B. Casentini, C. Tiraboschi, A. Cacciotti, M.M. Altamura, G. Falasca, and F. Della Rovere

Subjects
Arsenite, Arsenate, Auxin, Brassinosteroids, Rice, Root system plasticity, Plant ecology, QK900-989
Abstract

Rice is a worldwide cultivated crop that serves as an important source of food for the human population, but it is also the simplest route for arsenic (As) contamination of the food chain. The As inorganic forms, arsenate [As(V)] and arsenite [As(III)], are the highly toxic As species found in the soil and the most easily absorbed by the roots. The absorption of As(V) prevails in aerobic soils while that of As(III) is favored in anaerobic soils. As(V) is converted to As(III) in the roots, although small amounts of As(V) also remain in the plant organs. The root system is the first target of the action of both As forms. The mechanisms of action of As(V) and As(III) are still widely unknown. Understanding them is essential for selecting rice genotypes with a lower capacity of As uptake and transport to the caryopses, thus improving food safety. Auxin is the phytohormone necessary for the development and plasticity of the root system, and its action is modulated by endogenous/exogenous brassinosteroids (BRs), mainly under stress conditions. The research aim was to deepen the knowledge of the mechanisms triggered by As(III) or As(V) in rice roots with particular attention to the role played by the interaction between auxin transport and BRs. We show that As(III) is the main As species present in rice roots regardless of the As(III) or As(V) forms supplied to the growing medium. Arsenic alters auxin distribution in both adventitious and lateral roots, but strongly in the latter ones. The application of an exogenous BR, the 24-epibrassinolide (eBL), combined with As(III) or As(V) strongly increases the expression of the OsPIN2 and OsAUX1 genes involved in auxin transport, thus contributing to restore the correct auxin distribution altered by As, and mainly by As(III), with higher effects on the LRs. Moreover, eBL increases the antioxidant activity in the roots in the presence of As, but only when combined with As(V).

Published
2024
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21. Genotyping and clonal origin of Sporothrix brasiliensis in human sporotrichosis cases in Argentina

Author

Norma B. Fernandez, Bram Spruijtenburg, Iris N. Tiraboschi, Jacques F. Meis, Ana Lugo, María Cecilia López Joffre, and Eelco F.J. Meijer

Subjects
Sporothrix brasiliensis, Sporotrichosis, Zoonosis, Genotyping, Argentina, Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

Sporothrix brasiliensis is considered a highly virulent emerging pathogen that causes sporotrichosis in humans, mainly after zoonotic transmission from infected cats. The epidemic of this zoonosis that originated from Brazil has spread in the last decades, generating hyperendemic regions in Latin America. We present two cases of human sporotrichosis causes by S. brasiliensis in Buenos Aires, Argentina, with good clinical response to differing treatments after contact with sick cats. Using Short tandem repeat (STR) genotyping, the two S. brasiliensis cases appear to be introduced from Brazil and likely originate from the same source.

Published
2024
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22. Long-term efficacy and safety of a treatment strategy for HIV infection using protease inhibitor monotherapy: 8-year routine clinical care follow-up from a randomised, controlled, open-label pragmatic trial (PIVOT)Research in context

Author

Nicholas I. Paton, Wolfgang Stöhr, Alejandro Arenas-Pinto, Amanda Clarke, Ian Williams, Margaret Johnson, Chloe Orkin, Fabian Chen, Vincent Lee, Alan Winston, Mark Gompels, Julie Fox, Karen Sanders, David T. Dunn, Martin Fisher, Wendy Hadley, David Stacey, Pat Byrne, Nahum De Esteban, Pierre Pellegrino, Lewis Haddow, James Hand, Carl De Souza, Lisa Murthen, Andrew Crawford-Jones, Ruth Wilson, Elizabeth Green, John Masterson, Kamlesh Patel, Rebecca Howe, Scott Mullaney, Louise Jennings, Nicholas Beeching, Rebecca Tamaklo, Alistair Teague, Isabelle Jendrulek, Juan Manuel Tiraboschi, Ed Wilkins, Yvonne Clowes, Andrew Thompson, Gary Brook, Manoj Trivedi, Kazeem Aderogba, Martin Jones, Andrew DeBurgh-Thomas, Liz Jones, Iain Reeves, Sifiso Mguni, David Chadwick, Pauline Spence, Nellie Nkhoma, Zoe Warwick, Suzanne Price, Sally Read, Elbushra Herieka, James Walker, Ruth Woodward, John Day, Laura Hilton, Veerakathy Harinda, Helen Blackman, Phillip Hay, Wendy Mejewska, Olanike Okolo, Edmund Ong, Karen Martin, Lee Munro, David Dockrell, Lynne Smart, Jonathan Ainsworth, Anele Waters, Stephen Kegg, Sara McNamara, Steve Taylor, Gerry Gilleran, Brian Gazzard, Jane Rowlands, Sris Allan, Rumun Sandhu, Nigel O'Farrell, Sheena Quaid, Fabiola Martin, Caroline Bennett, Moses Kapembwa, Jane Minton, James Calderwood, Frank Post, Lucy Campbell, Emily Wandolo, Adrian Palfreeman, Linda Mashonganyika, Thambiah Balachandran, Memory Kakowa, Rebecca O'Connell, Cheryl Tanawa, Sinna Jebakumar, Lesley Hagger, Say Quah, Sinead McKernan, Charles Lacey, Sarah Douglas, Sarah Russell-Sharpe, Christine Brewer, Clifford Leen, Sheila Morris, Sharmin Obeyesekera, Shirley Williams, Nelson David, Mark Roberts, Julie Wollaston, Nicholas Paton, Karen Scott, David Dunn, Emma Beaumont, Sue Fleck, Mark Hall, Susie Hennings, Ischa Kummeling, Sara Martins, Ellen Owen-Powell, Fionna van Hooff, Livia Vivas, Ellen White, Brian Angus, Andrew Freedman, Ben Cromerty, Danielle Mercey, Sarah Fidler, Estee Torok, Abdel Babiker, Tim Peto, David Lalloo, Andrew Phillips, and Robert James

Subjects
HIV, Randomised, Protease inhibitor monotherapy, Simplification, Darunavir, Medicine (General), R5-920
Abstract

Summary: Background: Treatment-simplification strategies are important tools for patient-centred management. We evaluated long-term outcomes from a PI monotherapy switch strategy. Methods: Eligible participants attending 43 UK treatment centres had a viral load (VL) below 50 copies/ml for at least 24 weeks on combination ART. Participants were randomised to maintain ongoing triple therapy (OT) or switch to a strategy of physician-selected PI monotherapy (PI-mono) with prompt return to combination therapy if VL rebounded. The primary outcome, previously reported, was loss of future drug options after 3 years, defined as new intermediate/high level resistance to at least one drug to which the participant's virus was considered sensitive at trial entry. Here we report resistance and disease outcomes after further extended follow-up in routine care. The study was registered as ISRCTN04857074. Findings: We randomised 587 participants to OT (291) or PI-mono (296) between Nov 4, 2008, and July 28, 2010 and followed them for a median of more than 8 years (100 months) until 2018. At the end of this follow-up time, one or more future drug options had been lost in 7 participants in the OT group and 6 in the PI-mono group; estimated cumulative risk by 8 years of 2.7% and 2.1% respectively (difference −0.6%, 95% CI −3.2% to 2.0%). Only one PI-mono participant developed resistance to the protease inhibitor they were taking (atazanavir). Serious clinical events (death, serious AIDS, and serious non-AIDS) were infrequent; reported in a total of 12 (4.1%) participants in the OT group and 23 (7.8%) in the PI-mono group (P = 0.08) over the entire follow-up period. Interpretation: A strategy of PI monotherapy, with regular VL monitoring and prompt reintroduction of combination treatment following rebound, preserved future treatment options. Findings confirm the high genetic barrier to resistance of the PI drug class that makes them well suited for creative, patient-centred, treatment-simplification approaches. The possibility of a small excess risk of serious clinical events with the PI monotherapy strategy cannot be excluded. Funding: The National Institute for Health Research Health Technology Assessment programme.

Published
2024
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23. Differential diagnosis of neurodegenerative dementias with the explainable MRI based machine learning algorithm MUQUBIA

Author

Silvia De Francesco, Claudio Crema, Damiano Archetti, Cristina Muscio, Robert I. Reid, Anna Nigri, Maria Grazia Bruzzone, Fabrizio Tagliavini, Raffaele Lodi, Egidio D’Angelo, Brad Boeve, Kejal Kantarci, Michael Firbank, John-Paul Taylor, Pietro Tiraboschi, Alberto Redolfi, and the RIN – Neuroimaging Network

Subjects
Medicine, Science
Abstract

Abstract Biomarker-based differential diagnosis of the most common forms of dementia is becoming increasingly important. Machine learning (ML) may be able to address this challenge. The aim of this study was to develop and interpret a ML algorithm capable of differentiating Alzheimer’s dementia, frontotemporal dementia, dementia with Lewy bodies and cognitively normal control subjects based on sociodemographic, clinical, and magnetic resonance imaging (MRI) variables. 506 subjects from 5 databases were included. MRI images were processed with FreeSurfer, LPA, and TRACULA to obtain brain volumes and thicknesses, white matter lesions and diffusion metrics. MRI metrics were used in conjunction with clinical and demographic data to perform differential diagnosis based on a Support Vector Machine model called MUQUBIA (Multimodal Quantification of Brain whIte matter biomArkers). Age, gender, Clinical Dementia Rating (CDR) Dementia Staging Instrument, and 19 imaging features formed the best set of discriminative features. The predictive model performed with an overall Area Under the Curve of 98%, high overall precision (88%), recall (88%), and F1 scores (88%) in the test group, and good Label Ranking Average Precision score (0.95) in a subset of neuropathologically assessed patients. The results of MUQUBIA were explained by the SHapley Additive exPlanations (SHAP) method. The MUQUBIA algorithm successfully classified various dementias with good performance using cost-effective clinical and MRI information, and with independent validation, has the potential to assist physicians in their clinical diagnosis.

Published
2023
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24. The Employer's Perspective of Practice-Based Doctorates: A Paradigm Change

Author

Tiraboschi, Michele

Abstract

This article will focus on the epistemological, cultural, normative problems as well as the design principles related to the so-called practice-based doctorates. Given the extreme complexity of the topic, the author will deal with it by using the "Five Ws' and One H", allowing for an expedient exposition. In the conclusions, guidelines and a future orientation for the full development and implementation of practice-based doctorates will be provided.

Published
2019

25. Language impairment in the genetic forms of behavioural variant frontotemporal dementia

Author

Samra, Kiran, MacDougall, Amy M., Bouzigues, Arabella, Bocchetta, Martina, Cash, David M., Greaves, Caroline V., Convery, Rhian S., van Swieten, John C., Seelaar, Harro, Jiskoot, Lize, Moreno, Fermin, Sanchez-Valle, Raquel, Laforce, Robert, Graff, Caroline, Masellis, Mario, Tartaglia, Maria Carmela, Rowe, James B., Borroni, Barbara, Finger, Elizabeth, Synofzik, Matthis, Galimberti, Daniela, Vandenberghe, Rik, de Mendonça, Alexandre, Butler, Christopher R., Gerhard, Alexander, Ducharme, Simon, Le Ber, Isabelle, Tiraboschi, Pietro, Santana, Isabel, Pasquier, Florence, Levin, Johannes, Otto, Markus, Sorbi, Sandro, Rohrer, Jonathan D., and Russell, Lucy L.

Published
2023
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26. Loss of brainstem white matter predicts onset and motor neuron symptoms in C9orf72 expansion carriers: a GENFI study

Author

Pérez-Millan, Agnès, Borrego-Écija, Sergi, van Swieten, John C., Jiskoot, Lize, Moreno, Fermin, Laforce, Robert, Graff, Caroline, Masellis, Mario, Tartaglia, Maria Carmela, Rowe, James B., Borroni, Barbara, Finger, Elizabeth, Synofzik, Matthis, Galimberti, Daniela, Vandenberghe, Rik, de Mendonça, Alexandre, Butler, Chris R., Gerhard, Alexander, Ducharme, Simon, Le Ber, Isabelle, Santana, Isabel, Pasquier, Florence, Levin, Johannes, Otto, Markus, Sorbi, Sandro, Tiraboschi, Pietro, Seelaar, Harro, Langheinrich, Tobias, Rohrer, Jonathan D., Sala-Llonch, Roser, and Sánchez-Valle, Raquel

Published
2023
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27. Motor symptoms in genetic frontotemporal dementia: developing a new module for clinical rating scales

Author

Samra, Kiran, MacDougall, Amy M., Peakman, Georgia, Bouzigues, Arabella, Bocchetta, Martina, Cash, David M., Greaves, Caroline V., Convery, Rhian S., van Swieten, John C., Jiskoot, Lize, Seelaar, Harro, Moreno, Fermin, Sanchez-Valle, Raquel, Laforce, Robert, Graff, Caroline, Masellis, Mario, Tartaglia, Carmela, Rowe, James B., Borroni, Barbara, Finger, Elizabeth, Synofzik, Matthis, Galimberti, Daniela, Vandenberghe, Rik, de Mendonça, Alexandre, Butler, Chris R., Gerhard, Alexander, Ducharme, Simon, Le Ber, Isabelle, Tiraboschi, Pietro, Santana, Isabel, Pasquier, Florence, Levin, Johannes, Otto, Markus, Sorbi, Sandro, Rohrer, Jonathan D., and Russell, Lucy L.

Published
2023
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28. Impact of seed amplification assay and surface-enhanced Raman spectroscopy combined approach on the clinical diagnosis of Alzheimer’s disease

Author

Cristiano D’Andrea, Federico Angelo Cazzaniga, Edoardo Bistaffa, Andrea Barucci, Marella de Angelis, Martina Banchelli, Edoardo Farnesi, Panagis Polykretis, Chiara Marzi, Antonio Indaco, Pietro Tiraboschi, Giorgio Giaccone, Paolo Matteini, and Fabio Moda

Subjects
Alzheimer’s disease, Amyloid-β protein, Seed amplification assay, Surface-enhanced Raman spectroscopy, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background The current diagnosis of Alzheimer’s disease (AD) is based on a series of analyses which involve clinical, instrumental and laboratory findings. However, signs, symptoms and biomarker alterations observed in AD might overlap with other dementias, resulting in misdiagnosis. Methods Here we describe a new diagnostic approach for AD which takes advantage of the boosted sensitivity in biomolecular detection, as allowed by seed amplification assay (SAA), combined with the unique specificity in biomolecular recognition, as provided by surface-enhanced Raman spectroscopy (SERS). Results The SAA-SERS approach supported by machine learning data analysis allowed efficient identification of pathological Aβ oligomers in the cerebrospinal fluid of patients with a clinical diagnosis of AD or mild cognitive impairment due to AD. Conclusions Such analytical approach can be used to recognize disease features, thus allowing early stratification and selection of patients, which is fundamental in clinical treatments and pharmacological trials.

Published
2023
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29. Unraveling the effects of maternal breastfeeding duration and exclusive breast milk on children’s cognitive abilities in early childhood

Author

Gabrielle Garon-Carrier, Gabriel Arantes Tiraboschi, Jonathan Y. Bernard, Célia Matte-Gagné, Angélique Laurent, Annie Lemieux, and Caroline Fitzpatrick

Subjects
breastfeeding, breast milk, formula, memory-span, math skills, longitudinal design, Public aspects of medicine, RA1-1270
Abstract

BackgroundThis study investigated the putative associations between mothers’ use of exclusive breast milk and the duration of breastfeeding with child cognitive development.MethodsThis study is based on 2,210 Canadian families with children assessed longitudinally from age 4 to 7 years on their memory-span and math skills. These cognitive abilities were measured with standardized tasks. Breastfeeding practices were collected via maternal reports. We applied propensity scores to control the social selection bias for breastfeeding.ResultsResults adjusted for propensity scores and sample weight revealed no significant differences between non-breastfed children with those being non-exclusively breastfed for 5 months or less, and with children being exclusively breastfed for 9.2 months on average, on their early math skills and memory-span. We found that children who were non-exclusively breastfed for 6.8 months on average had a slightly higher levels of memory-span at age 4 than children who were never breastfed, and this small but significant difference lasted up to age 7.ConclusionOur findings suggest no significant differences between children being exclusively breastfed and those fed with formula on their early math skills and memory-span. The encouragement of breastfeeding to promote child cognitive school readiness may, in some case (non-exclusive breastfeeding for more than 5 months), show a small but long-lasting advantage in early memory-span.

Published
2023
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30. Adolescent internet use predicts higher levels of generalized and social anxiety symptoms for girls but not boys

Author

Gabriel A. Tiraboschi, Gabrielle Garon-Carrier, Jonathan Smith, and Caroline Fitzpatrick

Subjects
Screen media use, Adolescent internet use, Generalized anxiety, Social anxiety, Cross-lagged panel model, Sex differences, Medicine
Abstract

Past research suggests that internet use can increase the risks of internalizing symptoms in adolescents. However, bidirectional relationships between adolescent internet use and anxiety symptoms have received very little attention. Furthermore, few studies have examined these links according to sex. The present study attempts to fill this gap by investigating longitudinal associations between Canadian boys’ and girls’ internet use and symptoms of generalized anxiety and social anxiety using data from the Quebec longitudinal Study of Child Development. A sample of 1324 adolescents (698 girls, 626 boys) self-reported the number of hours per week they spent on the internet and their symptoms of generalized and social anxiety at ages 15 and 17. We estimated two cross-lagged panel models with social or generalized anxiety symptoms and internet use at age 15 predicting those same variables at age 17. Sex was used as a grouping variable and socioeconomic status was included as a control variable. Internet use at 15 predicted generalized and social anxiety symptoms at age 17 in girls, but not boys. Social and generalized anxiety symptoms at age 15 did not predict internet use at age 17 for both boys and girls. These results suggest that internet use can be a significant risk factor for the development of anxiety symptoms in adolescent girls. Girls may be more vulnerable to the negative effects of internet use due to increased sensitivity to social comparisons. Thus, helping girls develop healthier internet use habits should be a target for promoting their mental health.

Published
2023
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31. Geosmin suppresses defensive behaviour and elicits unusual neural responses in honey bees

Author

Florencia Scarano, Mukilan Deivarajan Suresh, Ettore Tiraboschi, Amélie Cabirol, Morgane Nouvian, Thomas Nowotny, and Albrecht Haase

Subjects
Medicine, Science
Abstract

Abstract Geosmin is an odorant produced by bacteria in moist soil. It has been found to be extraordinarily relevant to some insects, but the reasons for this are not yet fully understood. Here we report the first tests of the effect of geosmin on honey bees. A stinging assay showed that the defensive behaviour elicited by the bee’s alarm pheromone component isoamyl acetate (IAA) is strongly suppressed by geosmin. Surprisingly, the suppression is, however, only present at very low geosmin concentrations, and disappears at higher concentrations. We investigated the underlying mechanisms at the level of the olfactory receptor neurons by means of electroantennography, finding the responses to mixtures of geosmin and IAA to be lower than to pure IAA, suggesting an interaction of both compounds at the olfactory receptor level. Calcium imaging of the antennal lobe (AL) revealed that neuronal responses to geosmin decreased with increasing concentration, correlating well with the observed behaviour. Computational modelling of odour transduction and coding in the AL suggests that a broader activation of olfactory receptor types by geosmin in combination with lateral inhibition could lead to the observed non-monotonic increasing–decreasing responses to geosmin and thus underlie the specificity of the behavioural response to low geosmin concentrations.

Published
2023
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32. Occipital atrophy signature in prodromal Lewy bodies disease

Author

Alice Galli, Andrea Pilotto, Benedetta Chiarini, Marcello Giunta, Daniele Corbo, Clara Tirloni, Daniel Ferreira, Enrico Premi, Alessandro Lupini, Cinzia Zatti, Laura Bonanni, Pietro Tiraboschi, Roberto Gasparotti, and Alessandro Padovani

Subjects
cortical thickness, MRI, occipital atrophy, prodromal DLB, voxel‐based morphometry, Neurology. Diseases of the nervous system, RC346-429, Geriatrics, RC952-954.6
Abstract

Abstract INTRODUCTION Dementia with Lewy bodies (DLB) is typically characterized by parietal, temporal, and occipital atrophy, but less is known about the newly defined prodromal phases. The objective of this study was to evaluate structural brain alterations in prodromal DLB (p‐DLB) as compared to healthy controls (HC) and full‐blown dementia (DLB‐DEM). METHODS The study included 42 DLB patients (n = 20 p‐DLB; n = 22 DLB‐DEM) and 27 HC with a standardized neurological assessment and 3‐tesla magnetic resonance imaging. Voxel‐wise analyses on gray‐matter and cortical thickness were implemented to evaluate differences between p‐DLB, DLB‐DEM, and HC. RESULTS p‐DLB and DLB‐DEM exhibited reduced occipital and posterior parieto‐temporal volume and thickness, extending from prodromal to dementia stages. Occipital atrophy was more sensitive than insular atrophy in differentiating p‐DLB and HC. Occipital atrophy correlated to frontotemporal structural damage increasing from p‐DLB to DLB‐DEM. DISCUSSION Occipital and posterior‐temporal structural alterations are an early signature of the DLB continuum and correlate with a long‐distance pattern of atrophy.

Published
2023
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33. Combined 18F‐FDG PET‐CT markers in dementia with Lewy bodies

Author

Maria Vittoria Mattoli, Fabrizio Cocciolillo, Piero Chiacchiaretta, Francesco Dotta, Gianluca Trevisi, Claudia Carrarini, Astrid Thomas, Stefano Sensi, Andrea Delli Pizzi, Angelo Domenico Di Nicola, Adolfo Di Crosta, Nicola Mammarella, Alessandro Padovani, Andrea Pilotto, Fabio Moda, Pietro Tiraboschi, Gianluigi Martino, and Laura Bonanni

Subjects
18F‐FDG, artificial intelligence, biomarkers, dementia, Lewy body dementia, machine learning, Neurology. Diseases of the nervous system, RC346-429, Geriatrics, RC952-954.6
Abstract

Abstract INTRODUCTION 18F‐Fluoro‐deoxyglucose–positron emission tomography (FDG‐PET) is a supportive biomarker in dementia with Lewy bodies (DLB) diagnosis and its advanced analysis methods, including radiomics and machine learning (ML), were developed recently. The aim of this study was to evaluate the FDG‐PET diagnostic performance in predicting a DLB versus Alzheimer's disease (AD) diagnosis. METHODS FDG‐PET scans were visually and semi‐quantitatively analyzed in 61 patients. Radiomics and ML analyses were performed, building five ML models: (1) clinical features; (2) visual and semi‐quantitative PET features; (3) radiomic features; (4) all PET features; and (5) overall features. RESULTS At follow‐up, 34 patients had DLB and 27 had AD. At visual analysis, DLB PET signs were significantly more frequent in DLB, having the highest diagnostic accuracy (86.9%). At semi‐quantitative analysis, the right precuneus, superior parietal, lateral occipital, and primary visual cortices showed significantly reduced uptake in DLB. The ML model 2 had the highest diagnostic accuracy (84.3%). DISCUSSION FDG‐PET is a valuable tool in DLB diagnosis, having visual and semi‐quantitative analyses with the highest diagnostic accuracy at ML analyses.

Published
2023
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34. Expanding HIV clinical monitoring: the role of CD4, CD8, and CD4/CD8 ratio in predicting non-AIDS eventsResearch in context

Author

Javier Martínez-Sanz, Jorge Díaz-Álvarez, Marta Rosas, Raquel Ron, José Antonio Iribarren, Enrique Bernal, Félix Gutiérrez, Andrés Ruiz Sancho, Noemi Cabello, Julián Olalla, Santiago Moreno, Sergio Serrano-Villar, Inma Jarrín, David Dalmau, M. Luisa Navarro, M. Isabel González, Federico Garcia, Eva Poveda, Jose Antonio Iribarren, Rafael Rubio, Francesc Vidal, Juan Berenguer, Juan González, M. Ángeles Muñoz-Fernández, Inmaculada Jarrín, Cristina Moreno, Marta Rava, Rebeca Izquierdo, Elba Mauleón, Joaquín Portilla, Irene Portilla, Esperanza Merino, Gema García, Iván Agea, José Sánchez-Payá, Juan Carlos Rodríguez, Livia Giner, Sergio Reus, Vicente Boix, Diego Torrus, Verónica Pérez, Julia Portilla, Juan Luís Gómez, Jehovana Hernández, Ana López Lirola, Dácil García, Felicitas Díaz-Flores, M. Mar Alonso, Ricardo Pelazas, M. Remedios Alemán, Víctor Asensi, María Eugenia Rivas Carmenado, Tomás Suarez-Zarracina, Federico Pulido, Otilia Bisbal, M. Asunción Hernando, David Rial, María de Lagarde, Octavio Arce, Adriana Pinto, Laura Bermejo, Mireia Santacreu, Roser Navarro, Candela Gonzalez, M. José Aramburu, Xabier Camino, Miguel Ángel von Wichmann, Miguel Ángel Goenaga, M. Jesús Bustinduy, Harkaitz Azkune, Maialen Ibarguren, Xabier Kortajarena, Ignacio Álvarez-Rodriguez, Leire Gil, Lourdes Martínez, Catalina Robledano, Mar Masiá, Sergio Padilla, Araceli Adsuar, Rafael Pascual, Marta Fernández, Antonio Galiana, José Alberto García, Xavier Barber, Vanessa Agullo, Javier Garcia Abellán, Reyes Pascual, Guillermo Telenti, Lucia Guillén, Ángela Botella, Roberto Muga, Arantza Sanvisens, Daniel Fuster, Isabel Gutierrez, Juan Carlos López, Margarita Ramírez, Belén Padilla, Paloma Gijón, Teresa Aldamiz-Echevarría, Francisco Tejerina, Cristina Diez, Leire Pérez, Chiara Fanciulli, Saray Corral, Anna Martí, Joaquín Peraire, Consuelo Viladés, Montserrat Vargas, Montserrat Olona, Anna Rull, Verónica Alba, Elena Yeregui, Jenifer Masip, Graciano García-Pardo, Frederic Gómez Bertomeu, Sonia Espineira, Marta Montero, Sandra Cuéllar, Marino Blanes, María Tasias, Eva Calabuig, Miguel Salavert, Juan Fernández, Inmaculada Segarra, Juan González-García, Ana Delgado, Francisco Arnalich, José Ramón Arribas, Jose Ignacio Bernardino, Juan Miguel Castro, Luis Escosa, Pedro Herranz, Victor Hontañón, Silvia García-Bujalance, Milagros García, Alicia González-Baeza, M. Luz Martín-Carbonero, Mario Mayoral, M. Jose Mellado, Rafael Esteban, Rocío Montejano, M. Luisa Montes, Victoria Moreno, Ignacio Pérez-Valero, Berta Rodés, Guadalupe Rúa, Talía Sainz, Elena Sendagorta, Eulalia Valencia, Carmen Busca, Joanna Cano, Julen Cardiñanos, Rosa de Miguel, Jose Ramón Blanco, Laura Pérez-Martínez, José Antonio Oteo, Valvanera Ibarra, Luis Metola, Mercedes Sanz, Piedad Arazo, Gloria Sampériz, Marina Martinez, Angels Jaén, Montse Sanmartí, Mireia Cairó, Javier Martinez-Lacasa, Pablo Velli, Roser Font, Mariona Xercavins, Noemí Alonso, Francesco Aiello, María Rivero, Beatriz Piérola, Maider Goikoetxea, María Gracia, Carlos Ibero, Estela Moreno, Jesús Repáraz, Gemma Navarro, Manel Cervantes Garcia, Sonia Calzado Isbert, Marta Navarro Vilasaro, Belen Lopez Garcia, Ignacio de los Santos, Alejandro de los Santos, Jesús Sanz, Lucio García-Fraile, Enrique Martín, Ildefonso Sánchez-Cerrillo, Marta Calvet, Ana Barrios, Azucena Bautista, Carmen Sáez, Marianela Ciudad, Ángela Gutiérrez, Santos del Campo, José Luis Casado, Fernando Dronda, Ana Moreno, M. Jesús Pérez, Sergio Serrano, Ma Jesús Vivancos, Alejandro Vallejo, Matilde Sanchez, Jose Antonio Pérez-Molina, José Manuel Hermida, Antonia Alcaraz, Joaquín Bravo, Ángeles Muñoz, Cristina Tomás, Mónica Martínez, M. Carmen Villalba, Federico García, Clara Martínez, José Hernández, Leopoldo Muñoz Medina, Marta Álvarez, Natalia Chueca, David Vinuesa, Adolfo de Salazar, Ana Fuentes, Emilio Guirao, Laura Viñuela, Andrés Ruiz-Sancho, Francisco Anguita, Jorge Del Romero, Montserrat Raposo, Carmen Rodríguez, Teresa Puerta, Juan Carlos Carrió, Mar Vera, Juan Ballesteros, Oskar Ayerdi, Begoña Baza, Eva Orviz, Antonio Antela, Elena Losada, Melchor Riera, María Peñaranda, M. Angels Ribas, Antoni A. Campins, Mercedes Garcia-Gazalla, Francisco J. Fanjul, Javier Murillas, Francisco Homar, Helem H. Vilchez, Luisa Martin, Antoni Payeras, Jesús Santos, María López, Crisitina Gómez, Isabel Viciana, Rosario Palacios, Luis Fernando López-Cortés, Nuria Espinosa, Cristina Roca, Silvia Llaves, Juan Manuel Tiraboschi, Arkaitz Imaz, Ana Karina Silva, María Saumoy, Sofía Catalina Scévola, Adrián Curran, Vicenç Falcó, Jordi Navarro, Joaquin Burgos, Paula Suanzes, Jorge García, Vicente Descalzo, Patricia Álvarez, Bibiana Planas, Marta Sanchiz, Lucía Rodríguez, M José Sánchez, Javier Pérez, Alfonso del Arco, Javier de la Torre, José Luis Prada, Onofre Juan Martínez, Lorena Martinez, Francisco Jesús Vera, Josefina García, Begoña Alcaraz, Antonio Jesús Sánchez Guirao, Alvaro Mena, Angeles Castro, Berta Pernas, Pilar Vázquez, Soledad López, Sofía Ibarra, Guillermo García, Josu Mirena, Oscar Luis Ferrero, Josefina López, M. Mar Cámara, Mireia de la Peña, Miriam Lopez, Iñigo Lopez, Itxaso Lombide, Victor Polo, Joana de Miguel, Carlos Galera, Marian Fernández, Helena Albendin, Antonia Castillo, Asunción Iborra, Antonio Moreno, M. Angustias Merlos, Asunción Vidal, Concha Amador, Francisco Pasquau, Concepcion Gil, Jose Tomás Algado, Inés Suarez-García, Eduardo Malmierca, Patricia González-Ruano, M. Pilar Ruiz, José Francisco Pascual, Elena Sáez, Luz Balsalobre, M. Villa López, Mohamed Omar, Carmen Herrero, M. Amparo Gómez, Miguel Alberto de Zarraga, Desiré Pérez, Vicente Estrada, Nieves Sanz, Noemí Cabello, Jorge Vergas García, Maria Jose Núñez, Iñigo Sagastagoitia, Miguel Górgolas, Alfonso Cabello, Beatriz Álvarez, Laura Prieto, Irene Carrillo, José Sanz, Alberto Arranz, Cristina Hernández, María Novella, M. José Galindo, Ana Ferrer, Antonio Rivero Román, Inma Ruíz, Antonio Rivero Juárez, Pedro López, Isabel Machuca, Mario Frias, Ángela Camacho, Ignacio Pérez, Diana Corona, Miguel Cervero, Rafael Torres, Juan Antonio Pineda, Pilar Rincón, Juan Macías, Luis Miguel Real, Anais Corma, Alejandro Gonzalez-Serna, Alexandre Pérez, Luis Morano, Celia Miralles, Antonio Ocampo, Guillermo Pousada, Lucía Patiño, Carlos Dueñas, Sara Gutiérrez, Elena Tapia, Cristina Novoa, Xjoylin Egües, and Pablo Telleria

Subjects
HIV, Non-AIDS events, Neoplasia, Cardiovascular event, CD4/CD8 ratio, Medicine, Medicine (General), R5-920
Abstract

Summary: Background: While a low CD4/CD8 ratio during HIV treatment correlates with immunosenescence, its value in identifying patients at an increased risk for clinical events remains unclear. Methods: We analyzed data from the CoRIS cohort to determine whether CD4 count, CD8 count, and CD4/CD8 ratio at year two of antiretroviral therapy (ART) could predict the risk of serious non-AIDS events (SNAEs) during the next five years. These included major adverse cardiovascular events, non-AIDS-defining malignancies, and non-accidental deaths. We used pooled logistic regression with inverse probability weighting to estimate the survival curves and cumulative risk of clinical events. Findings: The study included 4625 participants, 83% male, of whom 200 (4.3%) experienced an SNAE during the follow-up period. A CD4/CD8 ratio

Published
2023
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35. Research criteria for the diagnosis of prodromal dementia with Lewy bodies

Author

McKeith, Ian G, Ferman, Tanis J, Thomas, Alan J, Blanc, Frédéric, Boeve, Bradley F, Fujishiro, Hiroshige, Kantarci, Kejal, Muscio, Cristina, O'Brien, John T, Postuma, Ronald B, Aarsland, Dag, Ballard, Clive, Bonanni, Laura, Donaghy, Paul, Emre, Murat, Galvin, James E, Galasko, Douglas, Goldman, Jennifer G, Gomperts, Stephen N, Honig, Lawrence S, Ikeda, Manabu, Leverenz, James B, Lewis, Simon JG, Marder, Karen S, Masellis, Mario, Salmon, David P, Taylor, John Paul, Tsuang, Debby W, Walker, Zuzana, Tiraboschi, Pietro, and Group, for the prodromal DLB Diagnostic Study

Subjects
Alzheimer's Disease Related Dementias (ADRD), Acquired Cognitive Impairment, Lewy Body Dementia, Neurodegenerative, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Mental Health, Aging, Brain Disorders, Dementia, Alzheimer's Disease, Neurological, Humans, Lewy Body Disease, Prodromal Symptoms, prodromal DLB Diagnostic Study Group, Clinical Sciences, Cognitive Sciences, Neurology & Neurosurgery
Abstract

The prodromal phase of dementia with Lewy bodies (DLB) includes (1) mild cognitive impairment (MCI), (2) delirium-onset, and (3) psychiatric-onset presentations. The purpose of our review is to determine whether there is sufficient information yet available to justify development of diagnostic criteria for each of these. Our goal is to achieve evidence-based recommendations for the recognition of DLB at a predementia, symptomatic stage. We propose operationalized diagnostic criteria for probable and possible mild cognitive impairment with Lewy bodies, which are intended for use in research settings pending validation for use in clinical practice. They are compatible with current criteria for other prodromal neurodegenerative disorders including Alzheimer and Parkinson disease. Although there is still insufficient evidence to propose formal criteria for delirium-onset and psychiatric-onset presentations of DLB, we feel that it is important to characterize them, raising the index of diagnostic suspicion and prioritizing them for further investigation.

Published
2020

36. Dissolution susceptibility of glass-like carbon versus crystalline graphite in high-pressure aqueous fluids and implications for the behavior of organic matter in subduction zones

Author

Tumiati, Simone, Tiraboschi, Carla, Miozzi, Francesca, Vitale-Brovarone, Alberto, Manning, Craig E, Sverjensky, Dimitri A, Milani, Sula, and Poli, Stefano

Subjects
COH fluids, Deep carbon cycle, Experimental petrology, Graphitic carbon, Carbonaceous matter, Geochemistry & Geophysics, Geochemistry, Geology, Physical Geography and Environmental Geoscience
Published
2020

37. CSF glial markers are elevated in a subset of patients with genetic frontotemporal dementia

Author

Ione O. C. Woollacott, Imogen J. Swift, Aitana Sogorb‐Esteve, Carolin Heller, Kathryn Knowles, Arabella Bouzigues, Lucy L. Russell, Georgia Peakman, Caroline V. Greaves, Rhian Convery, Amanda Heslegrave, James B. Rowe, Barbara Borroni, Daniela Galimberti, Pietro Tiraboschi, Mario Masellis, Maria Carmela Tartaglia, Elizabeth Finger, John C. vanSwieten, Harro Seelaar, Lize Jiskoot, Sandro Sorbi, Chris R. Butler, Caroline Graff, Alexander Gerhard, Robert Laforce, Raquel Sanchez‐Valle, Alexandre deMendonça, Fermin Moreno, Matthis Synofzik, Rik Vandenberghe, Simon Ducharme, Isabelle Le Ber, Johannes Levin, Markus Otto, Florence Pasquier, Isabel Santana, Henrik Zetterberg, Jonathan D. Rohrer, and the Genetic FTD Initiative, GENFI

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background Neuroinflammation has been shown to be an important pathophysiological disease mechanism in frontotemporal dementia (FTD). This includes activation of microglia, a process that can be measured in life through assaying different glia‐derived biomarkers in cerebrospinal fluid. However, only a few studies so far have taken place in FTD, and even fewer focusing on the genetic forms of FTD. Methods We investigated the cerebrospinal fluid concentrations of TREM2, YKL‐40 and chitotriosidase using immunoassays in 183 participants from the Genetic FTD Initiative (GENFI) study: 49 C9orf72 (36 presymptomatic, 13 symptomatic), 49 GRN (37 presymptomatic, 12 symptomatic) and 23 MAPT (16 presymptomatic, 7 symptomatic) mutation carriers and 62 mutation‐negative controls. Concentrations were compared between groups using a linear regression model adjusting for age and sex, with 95% bias‐corrected bootstrapped confidence intervals. Concentrations in each group were correlated with the Mini‐Mental State Examination (MMSE) score using non‐parametric partial correlations adjusting for age. Age‐adjusted z‐scores were also created for the concentration of markers in each participant, investigating how many had a value above the 95th percentile of controls. Results Only chitotriosidase in symptomatic GRN mutation carriers had a concentration significantly higher than controls. No group had higher TREM2 or YKL‐40 concentrations than controls after adjusting for age and sex. There was a significant negative correlation of chitotriosidase concentration with MMSE in presymptomatic GRN mutation carriers. In the symptomatic groups, for TREM2 31% of C9orf72, 25% of GRN, and 14% of MAPT mutation carriers had a concentration above the 95th percentile of controls. For YKL‐40 this was 8% C9orf72, 8% GRN and 0% MAPT mutation carriers, whilst for chitotriosidase it was 23% C9orf72, 50% GRN, and 29% MAPT mutation carriers. Conclusions Although chitotriosidase concentrations in GRN mutation carriers were the only significantly raised glia‐derived biomarker as a group, a subset of mutation carriers in all three groups, particularly for chitotriosidase and TREM2, had elevated concentrations. Further work is required to understand the variability in concentrations and the extent of neuroinflammation across the genetic forms of FTD. However, the current findings suggest limited utility of these measures in forthcoming trials.

Published
2022
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38. Associative Learning of Quantitative Mechanosensory Stimuli in Honeybees

Author

Heather Strelevitz, Ettore Tiraboschi, and Albrecht Haase

Subjects
proboscis extension, honeybee, mechanosensation, learning, decision making, automation, Science
Abstract

The proboscis extension response (PER) has been widely used to evaluate honeybees’ (Apis mellifera) learning and memory abilities, typically by using odors and visual cues for the conditioned stimuli. Here we asked whether honeybees could learn to distinguish between different magnitudes of the same type of stimulus, given as two speeds of air flux. By taking advantage of a novel automated system for administering PER experiments, we determined that the bees were highly successful when the lower air flux was rewarded and less successful when the higher flux was rewarded. Importantly, since our method includes AI-assisted analysis, we were able to consider subthreshold responses at a high temporal resolution; this analysis revealed patterns of rapid generalization and slowly acquired discrimination between the rewarded and unrewarded stimuli, as well as indications that the high air flux may have been mildly aversive. The learning curve for these mechanosensory stimuli, at least when the lower flux is rewarded, more closely mimics prior data from olfactory PER studies rather than visual ones, possibly in agreement with recent findings that the insect olfactory system is also sensitive to mechanosensory information. This work demonstrates a new modality to be used in PER experiments and lays the foundation for deeper exploration of honeybee cognitive processes when posed with complex learning challenges.

Published
2024
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39. Author Correction: Differential diagnosis of neurodegenerative dementias with the explainable MRI based machine learning algorithm MUQUBIA

Author

Silvia De Francesco, Claudio Crema, Damiano Archetti, Cristina Muscio, Robert I. Reid, Anna Nigri, Maria Grazia Bruzzone, Fabrizio Tagliavini, Raffaele Lodi, Egidio D’Angelo, Brad Boeve, Kejal Kantarci, Michael Firbank, John-Paul Taylor, Pietro Tiraboschi, Alberto Redolfi, and the RIN – Neuroimaging Network

Subjects
Medicine, Science
Published
2024
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40. Anomia is present pre-symptomatically in frontotemporal dementia due to MAPT mutations

Author

Bouzigues, Arabella, Russell, Lucy L., Peakman, Georgia, Bocchetta, Martina, Greaves, Caroline V., Convery, Rhian S., Todd, Emily, Rowe, James B., Borroni, Barbara, Galimberti, Daniela, Tiraboschi, Pietro, Masellis, Mario, Tartaglia, Maria Carmela, Finger, Elizabeth, van Swieten, John C., Seelaar, Harro, Jiskoot, Lize, Sorbi, Sandro, Butler, Chris R., Graff, Caroline, Gerhard, Alexander, Langheinrich, Tobias, Laforce, Robert, Sanchez-Valle, Raquel, de Mendonça, Alexandre, Moreno, Fermin, Synofzik, Matthis, Vandenberghe, Rik, Ducharme, Simon, Le Ber, Isabelle, Levin, Johannes, Danek, Adrian, Otto, Markus, Pasquier, Florence, Santana, Isabel, and Rohrer, Jonathan D.

Published
2022
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41. SCN1A overexpression, associated with a genomic region marked by a risk variant for a common epilepsy, raises seizure susceptibility

Author

Silvennoinen, Katri, Gawel, Kinga, Tsortouktzidis, Despina, Pitsch, Julika, Alhusaini, Saud, van Loo, Karen M. J., Picardo, Richard, Michalak, Zuzanna, Pagni, Susanna, Martins Custodio, Helena, Mills, James, Whelan, Christopher D., de Zubicaray, Greig I., McMahon, Katie L., van der Ent, Wietske, Kirstein-Smardzewska, Karolina J., Tiraboschi, Ettore, Mudge, Jonathan M., Frankish, Adam, Thom, Maria, Wright, Margaret J., Thompson, Paul M., Schoch, Susanne, Becker, Albert J., Esguerra, Camila V., and Sisodiya, Sanjay M.

Published
2022
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42. Accuracy of the clinical diagnosis of dementia with Lewy bodies (DLB) among the Italian Dementia Centers: a study by the Italian DLB study group (DLB-SINdem)

Author

Russo, Mirella, Carrarini, Claudia, Di Iorio, Angelo, Pellegrino, Raffaello, Bruni, Amalia Cecilia, Caratozzolo, Salvatore, Chiari, Annalisa, Pretta, Stefano, Marra, Camillo, Cotelli, Maria Sofia, Arighi, Andrea, Fumagalli, Giorgio G., Cataruzza, Tatiana, Caso, Francesca, Paci, Cristina, Rosso, Mara, Amici, Serena, Giannandrea, David, Pilotto, Andrea, Luzzi, Simona, Castellano, Annalisa, D’antonio, Fabrizia, Luca, Antonina, Gelosa, Giorgio, Piccoli, Tommaso, Mauri, Marco, Agosta, Federica, Babiloni, Claudio, Borroni, Barbara, Bozzali, Marco, Filippi, Massimo, Galimberti, Daniela, Monastero, Roberto, Muscio, Cristina, Parnetti, Lucilla, Perani, Daniela, Serra, Laura, Silani, Vincenzo, Tiraboschi, Pietro, Cagnin, Annachiara, Padovani, Alessandro, and Bonanni, Laura

Published
2022
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43. Italian adaptation of the Uniform Data Set Neuropsychological Test Battery (I-UDSNB 1.0): development and normative data

Author

Francesca Conca, Valentina Esposito, Francesco Rundo, Davide Quaranta, Cristina Muscio, Rosa Manenti, Giulia Caruso, Ugo Lucca, Alessia Antonella Galbussera, Sonia Di Tella, Francesca Baglio, Federica L’Abbate, Elisa Canu, Valentina Catania, Massimo Filippi, Giulia Mattavelli, Barbara Poletti, Vincenzo Silani, Raffaele Lodi, Maddalena De Matteis, Michelangelo Stanzani Maserati, Andrea Arighi, Emanuela Rotondo, Antonio Tanzilli, Andrea Pace, Federica Garramone, Carlo Cavaliere, Matteo Pardini, Cristiano Rizzetto, Sandro Sorbi, Roberta Perri, Pietro Tiraboschi, Nicola Canessa, Maria Cotelli, Raffaele Ferri, Sandra Weintraub, Camillo Marra, Fabrizio Tagliavini, Eleonora Catricalà, and Stefano Francesco Cappa

Subjects
Neuropsychological tests, UDS, Alzheimer’s disease, Cognition, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background Neuropsychological testing plays a cardinal role in the diagnosis and monitoring of Alzheimer’s disease. A major concern is represented by the heterogeneity of the neuropsychological batteries currently adopted in memory clinics and healthcare centers. The current study aimed to solve this issue. Methods Following the initiative of the University of Washington’s National Alzheimer’s Coordinating Center (NACC), we presented the Italian adaptation of the Neuropsychological Test Battery of the Uniform Data Set (I-UDSNB). We collected data from 433 healthy Italian individuals and employed regression models to evaluate the impact of demographic variables on the performance, deriving the reference norms. Results Higher education and lower age were associated with a better performance in the majority of tests, while sex affected only fluency tests and Digit Span Forward. Conclusions The I-UDSNB offers a valuable and harmonized tool for neuropsychological testing in Italy, to be used in clinical and research settings.

Published
2022
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45. Early neurotransmitters changes in prodromal frontotemporal dementia: A GENFI study

Author

Enrico Premi, Marta Pengo, Irene Mattioli, Valentina Cantoni, Juergen Dukart, Roberto Gasparotti, Emanuele Buratti, Alessandro Padovani, Martina Bocchetta, Emily G. Todd, Arabella Bouzigues, David M. Cash, Rhian S. Convery, Lucy L. Russell, Phoebe Foster, David L. Thomas, John C. van Swieten, Lize C. Jiskoot, Harro Seelaar, Daniela Galimberti, Raquel Sanchez-Valle, Robert Laforce, Jr, Fermin Moreno, Matthis Synofzik, Caroline Graff, Mario Masellis, Maria Carmela Tartaglia, James B. Rowe, Kamen A. Tsvetanov, Rik Vandenberghe, Elizabeth Finger, Pietro Tiraboschi, Alexandre de Mendonça, Isabel Santana, Chris R. Butler, Simon Ducharme, Alexander Gerhard, Johannes Levin, Markus Otto, Sandro Sorbi, Isabelle Le Ber, Florence Pasquier, Jonathan D. Rohrer, Barbara Borroni, Aitana Sogorb Esteve, Carolin Heller, Caroline V. Greaves, Henrik Zetterberg, Imogen J. Swift, Kiran Samra, Rachelle Shafei, Carolyn Timberlake, Thomas Cope, Timothy Rittman, Andrea Arighi, Chiara Fenoglio, Elio Scarpini, Giorgio Fumagalli, Vittoria Borracci, Giacomina Rossi, Giorgio Giaccone, Giuseppe Di Fede, Paola Caroppo, Sara Prioni, Veronica Redaelli, David Tang-Wai, Ekaterina Rogaeva, Miguel Castelo-Branco, Morris Freedman, Ron Keren, Sandra Black, Sara Mitchell, Christen Shoesmith, Robart Bartha, Rosa Rademakers, Jackie Poos, Janne M. Papma, Lucia Giannini, Rick van Minkelen, Yolande Pijnenburg, Benedetta Nacmias, Camilla Ferrari, Cristina Polito, Gemma Lombardi, Valentina Bessi, Michele Veldsman, Christin Andersson, Hakan Thonberg, Linn Öijerstedt, Vesna Jelic, Paul Thompson, Tobias Langheinrich, Albert Lladó, Anna Antonell, Jaume Olives, Mircea Balasa, Nuria Bargalló, Sergi Borrego-Ecija, Ana Verdelho, Carolina Maruta, Catarina B. Ferreira, Gabriel Miltenberger, Frederico Simões do Couto, Alazne Gabilondo, Ana Gorostidi, Jorge Villanua, Marta Cañada, Mikel Tainta, Miren Zulaica, Myriam Barandiaran, Patricia Alves, Benjamin Bender, Carlo Wilke, Lisa Graf, Annick Vogels, Mathieu Vandenbulcke, Philip Van Damme, Rose Bruffaerts, Koen Poesen, Pedro Rosa-Neto, Serge Gauthier, Agnès Camuzat, Alexis Brice, Anne Bertrand, Aurélie Funkiewiez, Daisy Rinaldi, Dario Saracino, Olivier Colliot, Sabrina Sayah, Catharina Prix, Elisabeth Wlasich, Olivia Wagemann, Sandra Loosli, Sonja Schönecker, Tobias Hoegen, Jolina Lombardi, Sarah Anderl-Straub, Adeline Rollin, Gregory Kuchcinski, Maxime Bertoux, Thibaud Lebouvier, Vincent Deramecourt, Beatriz Santiago, Diana Duro, Maria João Leitão, Maria Rosario Almeida, Miguel Tábuas-Pereira, and Sónia Afonso

Subjects
Frontotemporal dementia, Frontotemporal lobar degeneration, Genes, Magnetic resonance imaging, Positron emission tomography, Neurotransmitters, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Background: Neurotransmitters deficits in Frontotemporal Dementia (FTD) are still poorly understood. Better knowledge of neurotransmitters impairment, especially in prodromal disease stages, might tailor symptomatic treatment approaches. Methods: In the present study, we applied JuSpace toolbox, which allowed for cross-modal correlation of Magnetic Resonance Imaging (MRI)-based measures with nuclear imaging derived estimates covering various neurotransmitter systems including dopaminergic, serotonergic, noradrenergic, GABAergic and glutamatergic neurotransmission.We included 392 mutation carriers (157 GRN, 164 C9orf72, 71 MAPT), together with 276 non-carrier cognitively healthy controls (HC). We tested if the spatial patterns of grey matter volume (GMV) alterations in mutation carriers (relative to HC) are correlated with specific neurotransmitter systems in prodromal (CDR® plus NACC FTLD = 0.5) and in symptomatic (CDR® plus NACC FTLD≥1) FTD. Results: In prodromal stages of C9orf72 disease, voxel-based brain changes were significantly associated with spatial distribution of dopamine and acetylcholine pathways; in prodromal MAPT disease with dopamine and serotonin pathways, while in prodromal GRN disease no significant findings were reported (p

Published
2023
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46. Serological testing for Hansen’s disease diagnosis: Clinical significance and performance of IgA, IgM, and IgG antibodies against Mce1A protein

Author

Filipe Rocha Lima, Mateus Mendonça Ramos Simões, Gabriel Martins da Costa Manso, Diana Mota Toro, Vanderson Mayron Granemann Antunes, Giovani Cesar Felisbino, Gabriela Ferreira Dias, Lee W. Riley, Sérgio Arruda, Natália Aparecida de Paula, Helena Barbosa Lugão, Fernanda André Martins Cruz Perecin, Norma Tiraboschi Foss, and Marco Andrey Cipriani Frade

Subjects
Hansen’s disease, testing, serological, diagnosis, Mce1A, antibodies, Medicine (General), R5-920
Abstract

Hansen’s disease (HD) is an infectious, treatable, and chronic disease. It is the main cause of infectious peripheral neuropathy. Due to the current limitations of laboratory tests for the diagnosis of HD, early identification of infected contacts is an important factor that would allow us to control the magnitude of this disease in terms of world public health. Thus, a cross-sectional study was conducted in the Brazilian southeast with the objective of evaluating humoral immunity and describing the accuracy of the immunoassay based on IgA, IgM, and IgG antibodies against surface protein Mce1A of Mycobacterium, the predictive potential of these molecules, the clinical significance of positivity, and the ability to segregate new HD cases (NC; n = 200), contacts (HHC; n = 105), and healthy endemic controls (HEC; n = 100) as compared to α-PGL-I serology. α-Mce1A levels for all tested antibodies were significantly higher in NC and HHC than in HEC (p 0.85) for screening HD patients. Among HD patients (NC), positivity was 77.5% for IgA α-Mce1A ELISA, 76.5% for IgM, and 61.5% for IgG, while α-PGL-I serology showed only 28.0% positivity. Multivariate PLS-DA showed two defined clusters for the HEC and NC groups [accuracy = 0.95 (SD = 0.008)] and the HEC and HHC groups [accuracy = 0.93 (SD = 0.011)]. IgA was the antibody most responsible for clustering HHC as compared to NC and HEC, evidencing its usefulness for host mucosal immunity and as an immunological marker in laboratory tests. IgM is the key antibody for the clustering of NC patients. Positive results with high antibody levels indicate priority for screening, new clinical and laboratory evaluations, and monitoring of contacts, mainly with antibody indexes ≥2.0. In light of recent developments, the incorporation of new diagnostic technologies permits to eliminate the main gaps in the laboratory diagnosis of HD, with the implementation of tools of greater sensitivity and accuracy while maintaining satisfactory specificity.

Published
2023
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48. Cognitive composites for genetic frontotemporal dementia: GENFI-Cog

Author

Poos, Jackie M., Moore, Katrina M., Nicholas, Jennifer, Russell, Lucy L., Peakman, Georgia, Convery, Rhian S., Jiskoot, Lize C., van der Ende, Emma, van den Berg, Esther, Papma, Janne M., Seelaar, Harro, Pijnenburg, Yolande A. L., Moreno, Fermin, Sanchez-Valle, Raquel, Borroni, Barbara, Laforce, Robert, Masellis, Mario, Tartaglia, Carmela, Graff, Caroline, Galimberti, Daniela, Rowe, James B., Finger, Elizabeth, Synofzik, Matthis, Vandenberghe, Rik, de Mendonça, Alexandre, Tiraboschi, Pietro, Santana, Isabel, Ducharme, Simon, Butler, Chris, Gerhard, Alexander, Levin, Johannes, Danek, Adrian, Otto, Markus, Le Ber, Isabel, Pasquier, Florence, van Swieten, John C., and Rohrer, Jonathan D.

Published
2022
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49. Italian adaptation of the Uniform Data Set Neuropsychological Test Battery (I-UDSNB 1.0): development and normative data

Author

Conca, Francesca, Esposito, Valentina, Rundo, Francesco, Quaranta, Davide, Muscio, Cristina, Manenti, Rosa, Caruso, Giulia, Lucca, Ugo, Galbussera, Alessia Antonella, Di Tella, Sonia, Baglio, Francesca, L’Abbate, Federica, Canu, Elisa, Catania, Valentina, Filippi, Massimo, Mattavelli, Giulia, Poletti, Barbara, Silani, Vincenzo, Lodi, Raffaele, De Matteis, Maddalena, Stanzani Maserati, Michelangelo, Arighi, Andrea, Rotondo, Emanuela, Tanzilli, Antonio, Pace, Andrea, Garramone, Federica, Cavaliere, Carlo, Pardini, Matteo, Rizzetto, Cristiano, Sorbi, Sandro, Perri, Roberta, Tiraboschi, Pietro, Canessa, Nicola, Cotelli, Maria, Ferri, Raffaele, Weintraub, Sandra, Marra, Camillo, Tagliavini, Fabrizio, Catricalà, Eleonora, and Cappa, Stefano Francesco

Published
2022
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50. Subducted organic matter buffered by marine carbonate rules the carbon isotopic signature of arc emissions

Author

S. Tumiati, S. Recchia, L. Remusat, C. Tiraboschi, D. A. Sverjensky, C. E. Manning, A. Vitale Brovarone, A. Boutier, D. Spanu, and S. Poli

Subjects
Science
Abstract

The carbon isotopic signature of CO2 released from marine sediments subducted beneath volcanic arcs does not reflect their organic/inorganic fraction, but instead the fluid-rock ratios and the redox conditions in force at the top of the slab.

Published
2022
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