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1. Prioritized mass spectrometry increases the depth, sensitivity and data completeness of single-cell proteomics

Author

R. Gray Huffman, Andrew Leduc, Christoph Wichmann, Marco Di Gioia, Francesco Borriello, Harrison Specht, Jason Derks, Saad Khan, Luke Khoury, Edward Emmott, Aleksandra A. Petelski, David H. Perlman, Jürgen Cox, Ivan Zanoni, and Nikolai Slavov

Subjects
Cell Biology, Molecular Biology, Biochemistry, Biotechnology
Abstract

Major aims of single-cell proteomics include increasing the consistency, sensitivity and depth of protein quantification, especially for proteins and modifications of biological interest. Here, to simultaneously advance all these aims, we developed prioritized Single-Cell ProtEomics (pSCoPE). pSCoPE consistently analyzes thousands of prioritized peptides across all single cells (thus increasing data completeness) while maximizing instrument time spent analyzing identifiable peptides, thus increasing proteome depth. These strategies increased the sensitivity, data completeness and proteome coverage over twofold. The gains enabled quantifying protein variation in untreated and lipopolysaccharide-treated primary macrophages. Within each condition, proteins covaried within functional sets, including phagosome maturation and proton transport, similarly across both treatment conditions. This covariation is coupled to phenotypic variability in endocytic activity. pSCoPE also enabled quantifying proteolytic products, suggesting a gradient of cathepsin activities within a treatment condition. pSCoPE is freely available and widely applicable, especially for analyzing proteins of interest without sacrificing proteome coverage. Support for pSCoPE is available at http://scp.slavovlab.net/pSCoPE.

Published
2023
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2. miRNA-23a modulates sodium-hydrogen exchanger 1 expression: studies in medullary thick ascending limb of salt-induced hypertensive rats

Author

Patrizia Lombari, Massimo Mallardo, Oriana Petrazzuolo, Joseph Amruthraj Nagoth, Giuseppe Fiume, Roberto Scanni, Anna Iervolino, Sara Damiano, Annapaola Coppola, Margherita Borriello, Diego Ingrosso, Alessandra F Perna, Miriam Zacchia, Francesco Trepiccione, Giovambattista Capasso, Lombari, Patrizia, Mallardo, Massimo, Petrazzuolo, Oriana, Nagoth, Joseph Amruthraj, Fiume, Giuseppe, Scanni, Roberto, Iervolino, Anna, Damiano, Sara, Coppola, Annapaola, Borriello, Margherita, Ingrosso, Diego, Perna, Alessandra, Zacchia, Miriam, Trepiccione, Francesco, Capasso, Giovambattista, Amruthraj Nagoth, Joseph, Perna, Alessandra F., and Capasso., Francesco Trepiccione and Giovambattista

Subjects
Transplantation, Nephrology, Thick Ascending Limb, high sodium, miRNA-23a, miRNA pro ling, NHE1, thick ascending limb, miRNA-23a, NHE1, miRNA profiling, high sodium
Abstract

Background The kidney is the main organ in the pathophysiology of essential hypertension. Although most bicarbonate reabsorption occurs in the proximal tubule, the medullary thick ascending limb (mTAL) of the nephron also maintains acid–base balance by contributing to 25% of bicarbonate reabsorption. A crucial element in this regulation is the sodium-hydrogen exchanger 1 (NHE1), a ubiquitous membrane protein controlling intracellular pH, where proton extrusion is driven by the inward sodium flux. MicroRNA (miRNA) expression of hypertensive patients significantly differs from that of normotensive subjects. The aim of this study was to determine the functional role of miRNA alterations at the mTAL level. Methods By miRNA microarray analysis, we identified miRNA expression profiles in isolated mTALs from high sodium intake–induced hypertensive rats (HSD) versus their normotensive counterparts (NSD). In vitro validation was carried out in rat mTAL cells. Results Five miRNAs involved in the onset of salt-sensitive hypertension were identified, including miR-23a, which was bioinformatically predicted to target NHE1 mRNA. Data demonstrated that miRNA-23a is downregulated in the mTAL of HSD rats while NHE1 is upregulated. Consistently, transfection of an miRNA-23a mimic in an mTAL cell line, using a viral vector, resulted in NHE1 downregulation. Conclusion NHE1, a protein involved in sodium reabsorption at the mTAL level and blood pressure regulation, is upregulated in our model. This was due to a downregulation of miRNA-23a. Expression levels of this miRNA are influenced by high sodium intake in the mTALs of rats. The downregulation of miRNA-23a in humans affected by essential hypertension corroborate our data and point to the potential role of miRNA-23a in the regulation of mTAL function following high salt intake.

Published
2022
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5. Intraclass Switching among IL17 Inhibitors in Psoriasis: A Real-Life, Long-Term Single-Center Experience

Author

Francesco Cavallo, Silvia Borriello, Luca Mastorino, Paolo Dapavo, Pietro Quaglino, and Simone Ribero

Subjects
Article Subject, Dermatology, General Medicine
Abstract

Interleukin 17 (IL-17) inhibitors such as secukinumab, ixekizumab, and IL17 receptor (IL17RA) inhibitor brodalumab have proved to be highly effective and safe in psoriasis treatment. Still, a substantial proportion of patients show a primary or secondary inefficacy. When this happens, the clinician can change the therapeutical axis (swap) or perform an intraclass switch among IL-17 inhibitors. The latter option could allow us to address some comorbidity better, spare the other axis in case of the future inefficacy, and avoid interacting with other molecules with a different safety profile. To date, no sufficient data are available on the efficacy of a second IL-17 inhibitor therapy. Our study included 29 patients with moderate to severe psoriasis undergoing an intraclass switch among IL-17 inhibitors. The mean PASI dropped from 11.1 ± 6.1 to 5.2 ± 6.6 at week 16, with response maintained at week 28 and week 52 (3.4 ± 4.2 and 3.0 ± 4.3, respectively) with no occurrence of serious adverse events. Our data support the evidence that intraclass switch among IL-17 inhibitors is a safe and effective therapeutic option in these patients. This trial is registered with SS_DERMO_20.

Published
2023
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6. Persistence of protection against SARS-CoV-2 clinical outcomes up to 9 months since vaccine completion: a retrospective observational analysis in Lombardy, Italy

Author

Giovanni Corrao, Matteo Franchi, Danilo Cereda, Francesco Bortolan, Alberto Zoli, Olivia Leoni, Catia Rosanna Borriello, Giulia Petra Della Valle, Marcello Tirani, Giovanni Pavesi, Antonio Barone, Michele Ercolanoni, Jose Jara, Massimo Galli, Guido Bertolaso, Giuseppe Mancia, Corrao, G, Franchi, M, Cereda, D, Bortolan, F, Zoli, A, Leoni, O, Borriello, C, Valle, G, Tirani, M, Pavesi, G, Barone, A, Ercolanoni, M, Jara, J, Galli, M, Bertolaso, G, and Mancia, G

Subjects
COVID-19 Vaccines, Infectious Diseases, SARS-CoV-2, COVID-19, Humans, persistence, Articles, COVID-19 vaccine, effectivene
Abstract

Background: Scarce information is available on the duration of the protective effect of COVID-19 vaccination against the risk of SARS-CoV-2 infection and its severe clinical consequences. We investigated the effect of time since vaccine completion on the SARS-CoV-2 infection and its severe forms. Methods: In this retrospective observational analysis using the vaccination campaign integrated platform of the Italian region of Lombardy, 5 351 085 individuals aged 12 years or older who received complete vaccination from Jan 17 to July 31, 2021, were followed up from 14 days after vaccine completion until Oct 20, 2021. Changes over time in outcome rates (ie, SARS-CoV-2 infection and severe illness among vaccinated individuals) were analysed with age-period-cohort models. Trends in vaccine effectiveness (ie, outcomes comparison in vaccinated and unvaccinated individuals) were also measured. Findings: Overall, 14 140 infections and 2450 severe illnesses were documented, corresponding to incidence rates of 6·7 (95% CI 6·6–6·8) and 1·2 (1·1–1·2) cases per 10 000 person-months, respectively. From the first to the ninth month since vaccine completion, rates increased from 4·6 to 10·2 infections, and from 1·0 to 1·7 severe illnesses every 10 000 person-months. These figures correspond to relative reduction of vaccine effectiveness of 54·9% (95% CI 48·3–60·6) for infection and of 40·0% (16·2–57·0) for severe illness. The increasing infection rate was greater for individuals aged 60 years or older who received adenovirus-vectored vaccines (from 4·0 to 23·5 cases every 10 000 person-months). The increasing severe illness rates were similar for individuals receiving mRNA-based vaccines (from 1·1 to 1·5 every 10 000 person-months) and adenovirus-vectored vaccines (from 0·5 to 0·9 every 10 000 person-months). Interpretation: Although the risk of infection after vaccination, and even more of severe illness, remains low, the gradual increase in clinical outcomes related to SARS-CoV-2 infection suggests that the booster campaign should be accelerated and that social and individual protection measures against COVID-19 spread should not be abandoned. Funding: None.

Published
2022
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7. Normal B-cell ranges in infants: A systematic review and meta-analysis

Author

Francesco Borriello, Noemi Pasquarelli, Lisa Law, Kim Rand, Catarina Raposo, Wei Wei, Licinio Craveiro, and Tobias Derfuss

Subjects
B-Lymphocytes, Reference Values, Antigens, CD19, Immunology, Infant, Humans, Immunology and Allergy, Flow Cytometry
Abstract

During the first year of life, B-cell level is a valuable indicator of whether external factors, such as exposure to B-cell-depleting therapies, have an adverse impact on immune system development. However, there are no standard reference ranges of B-cell levels in healthy infants by age.Our aim was to estimate the normal range of B-cell levels in infants, by age, during the first year of life by pooling data from published studies.Studies reporting B-cell levels measured by using flow cytometry and CD19 markers in healthy infants were identified via a systematic literature review. Quality and feasibility assessments determined suitability for inclusion in meta-analyses by age group and/or continuous age. Means and normal ranges (2.5th-97.5th percentile) were estimated for absolute and percentage B-cell levels. Sensitivity analyses assessed the impact of various assumptions.Of the 37 relevant studies identified, 28 were included in at least 1 meta-analysis. The means and normal ranges of B-cell levels were found to be 707 cells/μL in cord blood (range 123-2324 cells/μL), 508 cells/μL in infants aged 0 to 1 month (range 132-1369 cells/μL), 1493 cells/μL in infants aged 1 to 6 months (range 416-3877 cells/μL), and 1474 cells/μL in infants older than 6 months (range 416-3805 cells/μL). The continuous age model showed that B-cell levels peaked at week 26. Trends were similar for the percentage B-cell estimates and in sensitivity analyses.These meta-analyses provide the first normal reference ranges for B-cell levels in infants, by week of age, during the first year of life.

Published
2022
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8. Signs and symptoms of COVID-19 in patients with multiple sclerosis

Author

Schiavetti I., Carmisciano L., Ponzano M., Cordioli C., Cocco E., Marfia G. A., Inglese M., Filippi M., Radaelli M., Bergamaschi R., Immovilli P., Capobianco M., De Rossi N., Brichetto G., Scandellari C., Cavalla P., Pesci I., Confalonieri P., Perini P., Trojano M., Lanzillo R., Tedeschi G., Comi G., Battaglia M. A., Patti F., Salvetti M., Sormani M. P., Abbadessa G., Aguglia U., Allegorico L., Rossi Allegri B. M., Alteno A., Amato M. P., Annovazzi P., Antozzi C., Appendino L., Arena S., Baione V., Balgera R., Barcella V., Baroncini D., Barrila C., Bellacosa A., Bellucci G., Bergamaschi V., Bezzini D., Biolzi B., Bisecco A., Bonavita S., Borriello G., Bosa C., Bosco A., Bovis F., Bozzali M., Brambilla L., Brescia Morra V., Buccafusca M., Bucciantini E., Bucello S., Buscarinu M. C., Cabboi M. P., Calabrese M., Calabria F., Caleri F., Camilli F., Caniatti L. M., Cantello R., Capra R., Capuano R., Carta P., Celani M. G., Cellerino M., Cerqua R., Chisari C., Clerici R., Clerico M., Cola G., Conte A., Conti M. Z., Cordano C., Cordera S., Corea F., Correale C., Cottone S., Crescenzo F., Curti E., d'Ambrosio A., D'Amico E., Danni M. C., d'Arma A., Dattola V., de Biase S., De Luca G., De Mercanti S. F., De Mitri P., De Stefano N., Della Cava F. M., Cava M. D., Di Lemme S., di Napoli M., Di Sapio A., Docimo R., Dutto A., Evangelista L., Fanara S., Fantozzi R., Ferraro D., Ferro M. T., Fioretti C., Fratta M., Frau J., Fronza M., Furlan R., Gajofatto A., Gallo A., Gallo P., Gasperini C., Ghazaryan A., Giometto B., Gobbin F., Govone F., Granella F., Grange E., Grasso M. G., Grimaldi L. M. E., Guareschi A., Guaschino C., Guerrieri S., Guidetti D., Juergenson I. B., Iaffaldano P., Ianniello A., Iasevoli L., Imperiale D., Infante M. T., Iodice R., Iovino A., Konrad G., Landi D., Lapucci C., Lavorgna L., L'Episcopo M. R., Leva S., Liberatore G., Lo Re M., Longoni M., Lopiano L., Lorefice L., Lucchini M., Lus G., Maimone D., Malentacchi M., Mallucci G., Malucchi S., Mancinelli C. R., Mancinelli L., Manganotti P., Maniscalco G. T., Mantero V., Marangoni S., Marastoni D., Marinelli F., Marti A., Boneschi Martinelli F., Masserano Z. F., Matta F., Mendozzi L., Meucci G., Miante S., Miele G., Milano E., Mirabella M., Missione R., Moccia M., Moiola L., Montepietra S., MontiBragadin M., Montini F., Motta R., Nardone R., Gabri Nicoletti C., Nobile-Orazio E., Nozzolillo A., Onofrj M., Orlandi R., Palmieri A., Paolicelli D., Pasquali L., Pasto L., Pedrazzoli E., Petracca M., Petrone A., Piantadosi C., Pietroboni A. M., Pinardi F., Portaccio E., Pozzato M., Pozzilli C., Prosperini L., Protti A., Ragonese P., Rasia S., Realmuto S., Repice A., Rigoni E., Rilla M. T., Rinaldi F., Romano C. M., Ronzoni M., Rovaris M., Ruscica F., Sabattini L., Salemi G., Saraceno L., Sartori A., Sbragia E., Scarano G. I., Scarano V., Sessa M., Sgarito C., Sibilia G., Siciliano G., Signori A., Signoriello E., Sinisi L., Sireci F., Sola P., Solaro C., Sotgiu S., Sparaco M., Stromillo M. L., Strumia S., Susani E. L., Tabiadon G., Teatini F., Tomassini V., Tonietti S., Torri V., Tortorella C., Toscano S., Totaro R., Trotta M., Turano G., Ulivelli M., Valentino M., Vaula G., Vecchio D., Vercellino M., Verrengia E. P., Vianello M., Virgilio E., Vitetta F., Vollaro S., Zaffaroni M., Zampolini M., Zarbo I. R., Zito A., Zuliani L., Schiavetti, Irene, Carmisciano, Luca, Ponzano, Marta, Cordioli, Cinzia, Cocco, Eleonora, Marfia, Girolama Alessandra, Inglese, Matilde, Filippi, Massimo, Radaelli, Marta, Bergamaschi, Roberto, Immovilli, Paolo, Capobianco, Marco, De Rossi, Nicola, Brichetto, Giampaolo, Scandellari, Cinzia, Cavalla, Paola, Pesci, Ilaria, Confalonieri, Paolo, Perini, Paola, Trojano, Maria, Lanzillo, Roberta, Tedeschi, Gioacchino, Comi, Giancarlo, Battaglia, Mario Alberto, Patti, Francesco, Salvetti, Marco, Sormani, Maria Pia, Gianmarco, Abbadessa, Umberto, Aguglia, Allegorico, Lia, Beatrice Maria Rossi Allegri, Anastasia, Alteno, Amato, MARIA PIA, Pietro, Annovazzi, Carlo, Antozzi, Lucia, Appendino, Sebastiano, Arena, Viola, Baione, Roberto, Balgera, Valeria, Barcella, Damiano, Baroncini, Caterina, Barrilà, Alessandra, Bellacosa, Gianmarco, Bellucci, Valeria, Bergamaschi, Daiana, Bezzini, Beatrice, Biolzi, Bisecco, Alvino, Simona, Bonavita, Giovanna, Borriello, Chiara, Bosa, Antonio, Bosco, Francesca, Bovi, Marco, Bozzali, Laura, Brambilla, BRESCIA MORRA, Vincenzo, Maria, Buccafusca, Elisabetta, Bucciantini, Sebastiano, Bucello, Maria Chiara Buscarinu, Maria Paola Cabboi, Massimiliano, Calabrese, Francesca, Calabria, Francesca, Caleri, Federico, Camilli, Luisa Maria Caniatti, Roberto, Cantello, Ruggero, Capra, Rocco, Capuano, Patrizia, Carta, Maria Grazia Celani, Maria, Cellerino, Raffaella, Cerqua, Clara, Chisari, Raffaella, Clerici, Marinella, Clerico, Gaia, Cola, Antonella, Conte, Marta Zaffira Conti, Christian, Cordano, Susanna, Cordera, Francesco, Corea, Claudio, Correale, Salvatore, Cottone, Francesco, Crescenzo, Erica, Curti, Alessandro, D’Ambrosio, Emanuele, D’Amico, Maura Chiara Danni, Alessia, D’Arma, Vincenzo, Dattola, Stefano de Biase, Giovanna De Luca, Stefania Federica De Mercanti, Paolo De Mitri, Nicola De Stefano, Fabio Maria Della Cava, Marco Della Cava, Sonia Di Lemme, Mario di Napoli, Alessia Di Sapio, Renato, Docimo, Anna, Dutto, Luana, Evangelista, Salvatore, Fanara, Roberta, Fantozzi, Diana, Ferraro, Maria Teresa Ferrò, Cristina, Fioretti, Mario, Fratta, Jessica, Frau, Marzia, Fronza, Roberto, Furlan, Alberto, Gajofatto, Gallo, Antonio, Paolo, Gallo, Claudio, Gasperini, Anna, Ghazaryan, Bruno, Giometto, Francesca, Gobbin, Flora, Govone, Franco, Granella, Erica, Grange, Grasso, MARIA GRAZIA, Grimaldi, Luigi M. E., Angelica, Guareschi, Clara, Guaschino, Simone, Guerrieri, Donata, Guidetti, Ina Barbara Juergenson, Pietro, Iaffaldano, Ianniello, Antonio, Luigi, Iasevoli, Daniele, Imperiale, Maria Teresa Infante, Iodice, Rosa, Iovino, Aniello, Giovanna, Konrad, Doriana, Landi, Caterina, Lapucci, Luigi, Lavorgna, Maria Rita L’Episcopo, Serena, Leva, Giuseppe, Liberatore, Marianna Lo Re, Marco, Longoni, Leonardo, Lopiano, Lorena, Lorefice, Matteo, Lucchini, Lus, Giacomo, Maimone, Davide, Maria, Malentacchi, Giulia, Mallucci, Simona, Malucchi, Chiara Rosa Mancinelli, Luca, Mancinelli, Paolo, Manganotti, Giorgia Teresa Maniscalco, Vittorio, Mantero, Sabrina, Marangoni, Damiano, Marastoni, Fabiana, Marinelli, Marti, NICOLA ALESSANDRO, Filippo Boneschi Martinelli, Zoli Federco Masserano, Francesca, Matta, Laura, Mendozzi, Giuseppe, Meucci, Silvia, Miante, Giuseppina, Miele, Eva, Milano, Massimiliano, Mirabella, Rosanna, Missione, Moccia, Marcello, Lucia, Moiola, Sara, Montepietra, Margherita, Montibragadin, Federico, Montini, Roberta, Motta, Raffaele, Nardone, Carolina Gabri Nicoletti, Eduardo, Nobile‐orazio, Nozzolillo, Agostino, Marco, Onofrj, Riccardo, Orlandi, Anna, Palmieri, Damiano, Paolicelli, Livia, Pasquali, Luisa, Pastò, Elisabetta, Pedrazzoli, Petracca, Maria, Alfredo, Petrone, Carlo, Piantadosi, Pietroboni, Anna M., Federica, Pinardi, Emilio, Portaccio, Mattia, Pozzato, Pozzilli, Carlo, Luca, Prosperini, Alessandra, Protti, Paolo, Ragonese, Sarah, Rasia, Sabrina, Realmuto, Anna, Repice, Eleonora, Rigoni, Maria Teresa Rilla, DELLA RATTA RINALDI, Francesca, Calogero Marcello Romano, Marco, Ronzoni, Marco, Rovari, Francesca, Ruscica, Loredana, Sabattini, Giuseppe, Salemi, Lorenzo, Saraceno, Alessia, Sartori, Arianna, Sartori, Elvira, Sbragia, Giuditta Ilaria Scarano, Valentina, Scarano, Maria, Sessa, Caterina, Sgarito, Sibilia, Grazia, Gabriele, Siciliano, Alessio, Signori, Signoriello, Elisabetta, Sinisi, Leonardo, Francesca, Sireci, Patrizia, Sola, Claudio, Solaro, Stefano, Sotgiu, Maddalena, Sparaco, Maria Laura Stromillo, Silvia, Strumia, Emanuela Laura Susani, Giulietta, Tabiadon, Francesco, Teatini, Valentina, Tomassini, Simone, Tonietti, Valentina, Torri, Tortorella, Carla, Simona, Toscano, Rocco, Totaro, Maria, Trotta, Gabriella, Turano, Monica, Ulivelli, Manzo, Valentino, Giovanna, Vaula, Domizia, Vecchio, Marco, Vercellino, Elena Pinuccia Verrengia, Marika, Vianello, Eleonora, Virgilio, Francesca, Vitetta, Vollaro, Stefano, Mauro, Zaffaroni, Mauro, Zampolini, Ignazio Roberto Zarbo, Antonio, Zito, and Luigi Zuliani, Schiavetti, I., Carmisciano, L., Ponzano, M., Cordioli, C., Cocco, E., Marfia, G. A., Inglese, M., Filippi, M., Radaelli, M., Bergamaschi, R., Immovilli, P., Capobianco, M., De Rossi, N., Brichetto, G., Scandellari, C., Cavalla, P., Pesci, I., Confalonieri, P., Perini, P., Trojano, M., Lanzillo, R., Tedeschi, G., Comi, G., Battaglia, M. A., Patti, F., Salvetti, M., Sormani, M. P., Abbadessa, G., Aguglia, U., Allegorico, L., Rossi Allegri, B. M., Alteno, A., Amato, M. P., Annovazzi, P., Antozzi, C., Appendino, L., Arena, S., Baione, V., Balgera, R., Barcella, V., Baroncini, D., Barrila, C., Bellacosa, A., Bellucci, G., Bergamaschi, V., Bezzini, D., Biolzi, B., Bisecco, A., Bonavita, S., Borriello, G., Bosa, C., Bosco, A., Bovis, F., Bozzali, M., Brambilla, L., Brescia Morra, V., Buccafusca, M., Bucciantini, E., Bucello, S., Buscarinu, M. C., Cabboi, M. P., Calabrese, M., Calabria, F., Caleri, F., Camilli, F., Caniatti, L. M., Cantello, R., Capra, R., Capuano, R., Carta, P., Celani, M. G., Cellerino, M., Cerqua, R., Chisari, C., Clerici, R., Clerico, M., Cola, G., Conte, A., Conti, M. Z., Cordano, C., Cordera, S., Corea, F., Correale, C., Cottone, S., Crescenzo, F., Curti, E., D'Ambrosio, A., D'Amico, E., Danni, M. C., D'Arma, A., Dattola, V., de Biase, S., De Luca, G., De Mercanti, S. F., De Mitri, P., De Stefano, N., Della Cava, F. M., Cava, M. D., Di Lemme, S., di Napoli, M., Di Sapio, A., Docimo, R., Dutto, A., Evangelista, L., Fanara, S., Fantozzi, R., Ferraro, D., Ferro, M. T., Fioretti, C., Fratta, M., Frau, J., Fronza, M., Furlan, R., Gajofatto, A., Gallo, A., Gallo, P., Gasperini, C., Ghazaryan, A., Giometto, B., Gobbin, F., Govone, F., Granella, F., Grange, E., Grasso, M. G., Grimaldi, L. M. E., Guareschi, A., Guaschino, C., Guerrieri, S., Guidetti, D., Juergenson, I. B., Iaffaldano, P., Ianniello, A., Iasevoli, L., Imperiale, D., Infante, M. T., Iodice, R., Iovino, A., Konrad, G., Landi, D., Lapucci, C., Lavorgna, L., L'Episcopo, M. R., Leva, S., Liberatore, G., Lo Re, M., Longoni, M., Lopiano, L., Lorefice, L., Lucchini, M., Lus, G., Maimone, D., Malentacchi, M., Mallucci, G., Malucchi, S., Mancinelli, C. R., Mancinelli, L., Manganotti, P., Maniscalco, G. T., Mantero, V., Marangoni, S., Marastoni, D., Marinelli, F., Marti, A., Boneschi Martinelli, F., Masserano, Z. F., Matta, F., Mendozzi, L., Meucci, G., Miante, S., Miele, G., Milano, E., Mirabella, M., Missione, R., Moccia, M., Moiola, L., Montepietra, S., Montibragadin, M., Montini, F., Motta, R., Nardone, R., Gabri Nicoletti, C., Nobile-Orazio, E., Nozzolillo, A., Onofrj, M., Orlandi, R., Palmieri, A., Paolicelli, D., Pasquali, L., Pasto, L., Pedrazzoli, E., Petracca, M., Petrone, A., Piantadosi, C., Pietroboni, A. M., Pinardi, F., Portaccio, E., Pozzato, M., Pozzilli, C., Prosperini, L., Protti, A., Ragonese, P., Rasia, S., Realmuto, S., Repice, A., Rigoni, E., Rilla, M. T., Rinaldi, F., Romano, C. M., Ronzoni, M., Rovaris, M., Ruscica, F., Sabattini, L., Salemi, G., Saraceno, L., Sartori, A., Sbragia, E., Scarano, G. I., Scarano, V., Sessa, M., Sgarito, C., Sibilia, G., Siciliano, G., Signori, A., Signoriello, E., Sinisi, L., Sireci, F., Sola, P., Solaro, C., Sotgiu, S., Sparaco, M., Stromillo, M. L., Strumia, S., Susani, E. L., Tabiadon, G., Teatini, F., Tomassini, V., Tonietti, S., Torri, V., Tortorella, C., Toscano, S., Totaro, R., Trotta, M., Turano, G., Ulivelli, M., Valentino, M., Vaula, G., Vecchio, D., Vercellino, M., Verrengia, E. P., Vianello, M., Virgilio, E., Vitetta, F., Vollaro, S., Zaffaroni, M., Zampolini, M., Zarbo, I. R., Zito, A., and Zuliani, L.

Subjects
Multiple Sclerosis, Anosmia, Clinical Sciences, neurological disorders, Neurodegenerative, Settore MED/26, demyelinating disease, COVID-19, demyelinating diseases, disease-modifying treatment, multiple sclerosis, Humans, neurological disorder, Aged, Neurology & Neurosurgery, SARS-CoV-2, Pain Research, Neurosciences, Brain Disorders, Settore MED/26 - NEUROLOGIA, Good Health and Well Being, Neurology, multiple sclerosi, Neurology (clinical), MuSC-19 Study Group, Ageusia, Human
Abstract

Background and purpose: Clinical outcomes of multiple sclerosis (MS) patients affected by coronavirus disease 2019 (COVID-19) have been thoroughly investigated, but a further analysis on main signs and symptoms and their risk factors still needs attention. The objective of this study was to group together and describe based on similarity the most common signs and symptoms of COVID-19 in MS patients and identify all factors associated with their manifestation. Method: Logistic and linear regression models were run to recognize factors associated with each pooled group of symptoms and their total number. Results: From March 2020 to November 2021, data were collected from 1354 MS patients with confirmed infection of COVID-19. Ageusia and anosmia was less frequent in older people (odds ratio [OR] 0.98; p=0.005) and more in smoker patients (OR 1.39; p=0.049). Smoke was also associated with an incremental number of symptoms (OR 1.24; p=0.031), substance abuse (drugs or alcohol), conjunctivitis and rash (OR 5.20; p=0.042) and the presence of at least one comorbidity with shortness of breath, tachycardia or chest pain (OR 1.24; p=0.008). Some disease-modifying therapies were associated with greater frequencies of certain COVID-19 symptoms (association between anti-CD20 therapies and increment in the number of concomitant symptoms: OR 1.29; p=0.05). Differences in frequencies between the three waves were found for flu-like symptoms (G1, p=0.024), joint or muscle pain (G2, p=0.013) and ageusia and anosmia (G5, p < 0.001). All cases should be referred to variants up to Delta. Conclusion: Several factors along with the choice of specific therapeutic approaches might have a different impact on the occurrence of some COVID-19 symptoms.

Published
2022

9. Effect of Hydrogen Sulfide on Essential Functions of Polymorphonuclear Leukocytes

Author

Sarah Farahat, Salome Kherkheulidze, Stephan Nopp, Alexander Kainz, Margherita Borriello, Alessandra F. Perna, Gerald Cohen, Farahat, Sarah, Kherkheulidze, Salome, Nopp, Stephan, Kainz, Alexander, Borriello, Margherita, Perna, Alessandra, and Cohen, Gerald

Subjects
immunology, inflammation, polymorphonuclear leukocytes, Health, Toxicology and Mutagenesis, uremic toxins, hydrogen sulfide, apoptosis, Toxicology, signal transduction, chronic kidney disease
Abstract

Impaired polymorphonuclear leukocyte (PMNL) functions contribute to increased infections and cardiovascular diseases in chronic kidney disease (CKD). Uremic toxins reduce hydrogen sulfide (H2S) levels and the anti-oxidant and anti-inflammatory effects of H2S. Its biosynthesis occurs as a side process of transsulfuration and in the disposal of adenosylhomocysteine, a transmethylation inhibitor and proposed uremic toxin. PMNL chemotaxis was measured by the under-agarose method, phagocytosis, and oxidative burst by flow cytometry in whole blood and apoptosis by determining DNA content by flow cytometry and morphological features by fluorescence microscopy. Sodium hydrogen sulfide (NaHS), diallyl trisulphide (DATS) and diallyl disulphide (DADS), cysteine, and GYY4137 were used as H2S-producing substances. Increased H2S concentrations did not affect chemotaxis and phagocytosis. NaHS primed PMNL oxidative burst activated by phorbol 12-myristate 13-acetate (PMA) or E. coli. Both DATS and cysteine significantly decreased E. coli-activated oxidative burst but had no effect on PMA stimulation. While NaHS, DADS, and cysteine attenuated PMNL apoptosis, GYY4137 decreased their viability. Experiments with signal transduction inhibitors suggest that the intrinsic apoptosis pathway is mainly involved in GYY4137-induced PMNL apoptosis and that GYY4137 and cysteine target signaling downstream of phosphoinositide 3-kinase.

Published
2023

11. A Comprehensive Analysis of AISI 316L Samples Printed via FDM: Structural and Mechanical Characterization

Author

Carminati, Mattia, Quarto, Mariangela, D'Urso, Gianluca Danilo, Giardini, Claudio, and Borriello, Carmela

Subjects
porosity, density evaluation, XRD, Mechanics of Materials, Mechanical Engineering, AISI 316L, Metal FDM, mechanical properties, Settore ING-IND/16 - Tecnologie e Sistemi di Lavorazione, General Materials Science
Abstract

Metal Fused Deposition Modelling is a promising multi-step process able to manufacture metal parts by means of a low-cost additive technique. In this study, a metal-polymer composite filament characterized by homogenous mixture of AISI 316L sinterable metal powders and a multi-component polymeric matrix was used to fabricate samples by means of a FDM printer. A 24 full factorial design of experiments was elaborated to define the possible influence of the relevant printing parameters on dimensional shrinkage, bulk density and overall porosity of printed samples. In addition, the mechanical properties of printed AISI 316L samples were investigated by performing tensile tests, compression tests, Charpy impact tests, Rockwell B and Vickers hardness tests. An X-ray diffraction analysis was conducted to assess the crystallographic structure of the FDM AISI 316L samples.

Published
2022
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13. The effect of air pollution on COVID‐19 severity in a sample of patients with multiple sclerosis

Author

Bergamaschi, Roberto, Ponzano, Marta, Schiavetti, Irene, Carmisciano, Luca, Cordioli, Cinzia, Filippi, Massimo, Radaelli, Marta, Immovilli, Paolo, Capobianco, Marco, De Rossi, Nicola, Brichetto, Giampaolo, Cocco, Eleonora, Scandellari, Cinzia, Cavalla, Paola, Pesci, Ilaria, Zito, Antonio, Confalonieri, Paolo, Marfia, Girolama Alessandra, Perini, Paola, Inglese, Matilde, Trojano, Maria, Brescia Morra, Vincenzo, Pisoni, Enrico, Tedeschi, Gioacchino, Comi, Giancarlo, Battaglia, Mario Alberto, Patti, Francesco, Salvetti, Marco, Sormani, Maria Pia, Gianmarco Abbadessa, Umberto Aguglia, Lia Allegorico, Rossi Beatrice Maria Allegri, Anastasia Alteno, Maria Pia Amato, Pietro Annovazzi, Carlo Antozzi, Lucia Appendino, Sebastiano Arena, Viola Baione, Roberto Balgera, Valeria Barcella, Damiano Baroncini, Caterina Barrilà, Mario A Battaglia, Alessandra Bellacosa, Gianmarco Bellucci, Roberto Bergamaschi, Valeria Bergamaschi, Daiana Bezzini, Beatrice Biolzi, Alvino Bisecco, Simona Bonavita, Giovanna Borriello, Chiara Bosa, Antonio Bosco, Francesca Bovis, Marco Bozzali, Laura Brambilla, Morra Vincenzo Brescia, Giampaolo Brichetto, Maria Buccafusca, Elisabetta Bucciantini, Sebastiano Bucello, Maria Chiara Buscarinu, Maria Paola Cabboi, Massimiliano Calabrese, Francesca Calabria, Francesca Caleri, Federico Camilli, Luisa Maria Caniatti, Roberto Cantello, Marco Capobianco, Ruggero Capra, Rocco Capuano, Luca Carmisciano, Patrizia Carta, Paola Cavalla, Maria Grazia Celani, Maria Cellerino, Raffaella Cerqua, Clara Chisari, Raffaella Clerici, Marinella Clerico, Eleonora Cocco, Gaia Cola, Giancarlo Comi, Paolo Confalonieri, Antonella Conte, Marta Zaffira Conti, Christian Cordano, Susanna Cordera, Cinzia Cordioli, Francesco Corea, Claudio Correale, Salvatore Cottone, Francesco Crescenzo, Erica Curti, Alessandro d'Ambrosio, Emanuele D'Amico, Maura Chiara Danni, Alessia d'Arma, Vincenzo Dattola, Stefano de Biase, Giovanna De Luca, Stefania Federica De Mercanti, Paolo De Mitri, Nicola De Rossi, Nicola De Stefano, Cava Marco Della, Mario di Napoli, Alessia Di Sapio, Renato Docimo, Anna Dutto, Luana Evangelista, Salvatore Fanara, Diana Ferraro, Maria Teresa Ferrò, Massimo Filippi, Cristina Fioretti, Mario Fratta, Jessica Frau, Marzia Fronza, Roberto Furlan, Alberto Gajofatto, Antonio Gallo, Paolo Gallo, Claudio Gasperini, Anna Ghazaryan, Bruno Giometto, Francesca Gobbin, Flora Govone, Franco Granella, Erica Grange, Maria Grazia Grasso, Angelica Guareschi, Clara Guaschino, Simone Guerrieri, Donata Guidetti, Pietro Iaffaldano, Antonio Ianniello, Luigi Iasevoli, Paolo Immovilli, Daniele Imperiale, Maria Teresa Infante, Matilde Inglese, Rosa Iodice, Aniello Iovino, Giovanna Konrad, Doriana Landi, Roberta Lanzillo, Caterina Lapucci, Luigi Lavorgna, Maria Rita L'Episcopo, Serena Leva, Giuseppe Liberatore, Re Marianna Lo, Marco Longoni, Leonardo Lopiano, Lorena Lorefice, Matteo Lucchini, Giacomo Lus, Davide Maimone, Maria Malentacchi, Giulia Mallucci, Simona Malucchi, Chiara Rosa Mancinelli, Luca Mancinelli, Paolo Manganotti, Giorgia Teresa Maniscalco, Vittorio Mantero, Sabrina Marangoni, Damiano Marastoni, Girolama Alessandra Marfia, Fabiana Marinelli, Alessandro Marti, Boneschi Filippo Martinelli, Zoli Federco Masserano, Francesca Matta, Laura Mendozzi, Giuseppe Meucci, Silvia Miante, Giuseppina Miele, Eva Milano, Massimiliano Mirabella, Rosanna Missione, Marcello Moccia, Lucia Moiola, Sara Montepietra, Margherita MontiBragadin, Federico Montini, Roberta Motta, Raffaele Nardone, Carolina Gabri Nicoletti, Eduardo Nobile-Orazio, Agostino Nozzolillo, Marco Onofrj, Riccardo Orlandi, Anna Palmieri, Damiano Paolicelli, Livia Pasquali, Luisa Pastò, Francesco Patti, Elisabetta Pedrazzoli, Paola Perini, Ilaria Pesci, Maria Petracca, Alfredo Petrone, Carlo Piantadosi, Anna M Pietroboni, Federica Pinardi, Marta Ponzano, Emilio Portaccio, Mattia Pozzato, Carlo Pozzilli, Luca Prosperini, Alessandra Protti, Marta Radaelli, Paolo Ragonese, Sarah Rasia, Sabrina Realmuto, Anna Repice, Eleonora Rigoni, Maria Teresa Rilla, Francesca Rinaldi, Calogero Marcello Romano, Marco Ronzoni, Marco Rovaris, Francesca Ruscica, Loredana Sabattini, Giuseppe Salemi, Marco Salvetti, Lorenzo Saraceno, Alessia Sartori, Arianna Sartori, Elvira Sbragia, Cinzia Scandellari, Giuditta Ilaria Scarano, Valentina Scarano, Irene Schiavetti, Maria Sessa, Caterina Sgarito, Grazia Sibilia, Gabriele Siciliano, Alessio Signori, Elisabetta Signoriello, Leonardo Sinisi, Francesca Sireci, Patrizia Sola, Claudio Solaro, Maria Pia Sormani, Stefano Sotgiu, Maddalena Sparaco, Maria Laura Stromillo, Silvia Strumia, Emanuela Laura Susani, Giulietta Tabiadon, Francesco Teatini, Gioacchino Tedeschi, Valentina Tomassini, Simone Tonietti, Clerici Valentina Torri, Carla Tortorella, Simona Toscano, Rocco Totaro, Maria Trojano, Maria Trotta, Gabriella Turano, Monica Ulivelli, Manzo Valentino, Giovanna Vaula, Domizia Vecchio, Marco Vercellino, Elena Pinuccia Verrengia, Marika Vianello, Eleonora Virgilio, Francesca Vitetta, Stefano Vollaro, Mauro Zaffaroni, Mauro Zampolini, Ignazio Roberto Zarbo, Antonio Zito, Luigi Zuliani, Bergamaschi, R, Ponzano, M, Schiavetti, I, Carmisciano, L, Cordioli, C, Filippi, M, Radaelli, M, Immovilli, P, Capobianco, M, De Rossi, N, Brichetto, G, Cocco, E, Scandellari, C, Cavalla, P, Pesci, I, Zito, A, Confalonieri, P, Marfia, Ga, Perini, P, Inglese, M, Trojano, M, Brescia Morra, V, Pisoni, E, Tedeschi, G, Comi, G, Battaglia, Ma, Patti, F, Salvetti, M, Sormani, Mp, Abbadessa, Gianmarco, Umberto, Aguglia, Lia, Allegorico, Rossi Beatrice Maria Allegri, Anastasia, Alteno, Maria Pia Amato, Pietro, Annovazzi, Carlo, Antozzi, Lucia, Appendino, Sebastiano, Arena, Viola, Baione, Roberto, Balgera, Valeria, Barcella, Damiano, Baroncini, Caterina, Barrilà, Mario, A Battaglia, Alessandra, Bellacosa, Gianmarco, Bellucci, Roberto, Bergamaschi, Valeria, Bergamaschi, Daiana, Bezzini, Beatrice, Biolzi, Bisecco, Alvino, Bonavita, Simona, Giovanna, Borriello, Chiara, Bosa, Bosco, Antonio, Francesca, Bovi, Marco, Bozzali, Laura, Brambilla, Morra Vincenzo Brescia, Giampaolo, Brichetto, Maria, Buccafusca, Elisabetta, Bucciantini, Sebastiano, Bucello, Maria Chiara Buscarinu, Maria Paola Cabboi, Massimiliano, Calabrese, Francesca, Calabria, Francesca, Caleri, Federico, Camilli, Luisa Maria Caniatti, Roberto, Cantello, Marco, Capobianco, Ruggero, Capra, Capuano, Rocco, Luca, Carmisciano, Patrizia, Carta, Paola, Cavalla, Maria Grazia Celani, Maria, Cellerino, Raffaella, Cerqua, Clara, Chisari, Raffaella, Clerici, Marinella, Clerico, Eleonora, Cocco, Gaia, Cola, Giancarlo, Comi, Paolo, Confalonieri, Antonella, Conte, Marta Zaffira Conti, Christian, Cordano, Susanna, Cordera, Cinzia, Cordioli, Corea, Francesco, Claudio, Correale, Salvatore, Cottone, Francesco, Crescenzo, Erica, Curti, Alessandro, D'Ambrosio, Emanuele, D'Amico, Maura Chiara Danni, Alessia, D'Arma, Vincenzo, Dattola, Stefano de Biase, Giovanna De Luca, Stefania Federica De Mercanti, Paolo De Mitri, Nicola De Rossi, Nicola De Stefano, Cava Marco Della, Mario di Napoli, Alessia Di Sapio, Docimo, Renato, Anna, Dutto, Luana, Evangelista, Salvatore, Fanara, Diana, Ferraro, Maria Teresa Ferrò, Massimo, Filippi, Cristina, Fioretti, Fratta, Mario, Jessica, Frau, Marzia, Fronza, Roberto, Furlan, Alberto, Gajofatto, Gallo, Antonio, Paolo, Gallo, Claudio, Gasperini, Anna, Ghazaryan, Bruno, Giometto, Francesca, Gobbin, Flora, Govone, Franco, Granella, Erica, Grange, Maria Grazia Grasso, Angelica, Guareschi, Clara, Guaschino, Simone, Guerrieri, Donata, Guidetti, Pietro, Iaffaldano, Antonio, Ianniello, Luigi, Iasevoli, Paolo, Immovilli, Daniele, Imperiale, Maria Teresa Infante, Matilde, Inglese, Rosa, Iodice, Aniello, Iovino, Giovanna, Konrad, Doriana, Landi, Roberta, Lanzillo, Caterina, Lapucci, Luigi, Lavorgna, Maria Rita L'Episcopo, Serena, Leva, Giuseppe, Liberatore, Re Marianna Lo, Marco, Longoni, Leonardo, Lopiano, Lorena, Lorefice, Matteo, Lucchini, Lus, Giacomo, Davide, Maimone, Maria, Malentacchi, Giulia, Mallucci, Simona, Malucchi, Chiara Rosa Mancinelli, Luca, Mancinelli, Paolo, Manganotti, Giorgia Teresa Maniscalco, Vittorio, Mantero, Sabrina, Marangoni, Damiano, Marastoni, Girolama Alessandra Marfia, Fabiana, Marinelli, Alessandro, Marti, Boneschi Filippo Martinelli, Zoli Federco Masserano, Francesca, Matta, Laura, Mendozzi, Giuseppe, Meucci, Silvia, Miante, Miele, Giuseppina, Eva, Milano, Massimiliano, Mirabella, Missione, Rosanna, Marcello, Moccia, Lucia, Moiola, Sara, Montepietra, Margherita, Montibragadin, Federico, Montini, Roberta, Motta, Raffaele, Nardone, Carolina Gabri Nicoletti, Eduardo, Nobile-Orazio, Agostino, Nozzolillo, Marco, Onofrj, Riccardo, Orlandi, Palmieri, Anna, Damiano, Paolicelli, Livia, Pasquali, Luisa, Pastò, Francesco, Patti, Elisabetta, Pedrazzoli, Paola, Perini, Ilaria, Pesci, Maria, Petracca, Alfredo, Petrone, Carlo, Piantadosi, Anna, M Pietroboni, Federica, Pinardi, Marta, Ponzano, Emilio, Portaccio, Mattia, Pozzato, Carlo, Pozzilli, Luca, Prosperini, Alessandra, Protti, Marta, Radaelli, Paolo, Ragonese, Sarah, Rasia, Sabrina, Realmuto, Anna, Repice, Eleonora, Rigoni, Maria Teresa Rilla, Francesca, Rinaldi, Calogero Marcello Romano, Marco, Ronzoni, Marco, Rovari, Francesca, Ruscica, Loredana, Sabattini, Giuseppe, Salemi, Marco, Salvetti, Lorenzo, Saraceno, Alessia, Sartori, Arianna, Sartori, Elvira, Sbragia, Cinzia, Scandellari, Giuditta Ilaria Scarano, Valentina, Scarano, Irene, Schiavetti, Maria, Sessa, Caterina, Sgarito, Grazia, Sibilia, Gabriele, Siciliano, Alessio, Signori, Signoriello, Elisabetta, Leonardo, Sinisi, Francesca, Sireci, Patrizia, Sola, Claudio, Solaro, Maria Pia Sormani, Stefano, Sotgiu, Sparaco, Maddalena, Maria Laura Stromillo, Silvia, Strumia, Emanuela Laura Susani, Giulietta, Tabiadon, Francesco, Teatini, Tedeschi, Gioacchino, Valentina, Tomassini, Simone, Tonietti, Clerici Valentina Torri, Carla, Tortorella, Simona, Toscano, Rocco, Totaro, Maria, Trojano, Trotta, Maria Consiglia, Gabriella, Turano, Monica, Ulivelli, Manzo, Valentino, Giovanna, Vaula, Domizia, Vecchio, Marco, Vercellino, Elena Pinuccia Verrengia, Marika, Vianello, Eleonora, Virgilio, Francesca, Vitetta, Stefano, Vollaro, Mauro, Zaffaroni, Mauro, Zampolini, Ignazio Roberto Zarbo, Zito, Guido Antonio, Bergamaschi, R., Ponzano, M., Schiavetti, I., Carmisciano, L., Cordioli, C., Filippi, M., Radaelli, M., Immovilli, P., Capobianco, M., De Rossi, N., Brichetto, G., Cocco, E., Scandellari, C., Cavalla, P., Pesci, I., Zito, A., Confalonieri, P., Marfia, G. A., Perini, P., Inglese, M., Trojano, M., Brescia Morra, V., Pisoni, E., Tedeschi, G., Comi, G., Battaglia, M. A., Patti, F., Salvetti, M., Sormani, M. P., Bergamaschi, Roberto, Ponzano, Marta, Schiavetti, Irene, Carmisciano, Luca, Cordioli, Cinzia, Filippi, Massimo, Radaelli, Marta, Immovilli, Paolo, Capobianco, Marco, De Rossi, Nicola, Brichetto, Giampaolo, Cocco, Eleonora, Scandellari, Cinzia, Cavalla, Paola, Pesci, Ilaria, Zito, Antonio, Confalonieri, Paolo, Marfia, Girolama Alessandra, Perini, Paola, Inglese, Matilde, Trojano, Maria, Brescia Morra, Vincenzo, Pisoni, Enrico, Comi, Giancarlo, Battaglia, Mario Alberto, Patti, Francesco, Salvetti, Marco, Sormani, Maria, Pia, Gianmarco, Abbadessa, Alvino, Bisecco, Simona, Bonavita, Antonio, Bosco, Rocco, Capuano, Francesco, Corea, Renato, Docimo, Mario, Fratta, Antonio, Gallo, Iodice, Rosa, Iovino, Aniello, Lanzillo, Roberta, Giacomo, Lu, Giuseppina, Miele, Rosanna, Missione, Moccia, Marcello, Anna, Palmieri, Elisabetta, Signoriello, Maddalena, Sparaco, Gioacchino, Tedeschi, Maria, Trotta, Antonio, Zito, and Luigi, Zuliani

Subjects
air pollution, coronavirus, multiple sclerosis, medicine.medical_specialty, Multivariate analysis, Coronavirus disease 2019 (COVID-19), Clinical Sciences, Air pollution, Sample (statistics), Neurodegenerative, Settore MED/26, medicine.disease_cause, Autoimmune Disease, law.invention, Sustainable Cities and Communities, Clinical Research, law, Humans, Medicine, Climate-Related Exposures and Conditions, Neurology & Neurosurgery, MuSC-19 study group, SARS-CoV-2, business.industry, Multiple sclerosis, Neurosciences, COVID-19, Retrospective cohort study, Original Articles, medicine.disease, Intensive care unit, Particulate Matter, Air Pollution, Multiple Sclerosis, Brain Disorders, coronaviru, Settore MED/26 - NEUROLOGIA, Good Health and Well Being, Neurology, multiple sclerosi, Emergency medicine, Original Article, Neurology (clinical), Ordered logit, business, Human
Abstract

Background and purpose Some studies have shown that air pollution, often assessed by thin particulate matter with diameter below 2.5 µg/m3 (PM2.5), may contribute to severe COVID‐19 courses, as well as play a role in the onset and evolution of multiple sclerosis (MS). However, the impact of air pollution on COVID‐19 has never been explored specifically amongst patients with MS (PwMS). This retrospective observational study aims to explore associations between PM2.5 and COVID‐19 severity amongst PwMS. Methods Data were retrieved from an Italian web‐based platform (MuSC‐19) which includes PwMS with COVID‐19. PM2.5 2016–2018 average concentrations were provided by the Copernicus Atmospheric Monitoring Service. Italian patients inserted in the platform from 15 January 2020 to 9 April 2021 with a COVID‐19 positive test were included. Ordered logistic regression models were used to study associations between PM2.5 and COVID‐19 severity. Results In all, 1087 patients, of whom 13% required hospitalization and 2% were admitted to an intensive care unit or died, were included. Based on the multivariate analysis, higher concentrations of PM2.5 increased the risk of worse COVID‐19 course (odds ratio 1.90; p = 0.009). Conclusions Even if several other factors explain the unfavourable course of COVID‐19 in PwMS, the role of air pollutants must be considered and further investigated., Air pollution, often assessed by particulate matter with diameter below 2.5 µg/m3, may contribute to severe COVID‐19 courses. 1087 patients were included, of whom 13% required hospitalization and 2% were admitted to an intensive care unit or died. Even if several other factors explain the unfavourable course of COVID‐19 in patients with multiple sclerosis, the role of air pollutants must be considered and further investigated.

Published
2021
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14. Public health actions implemented by the Lombardy Region to revamp cervical cancer prevention

Author

Silvia Deandrea, Chiara Marrocu, Sudwaric Sharma, Roberta Lattanzio, Giovanni Cicconi, Sara Piccinelli, Danilo Cereda, Catia Borriello, Silvana Castaldi, Riccardo Vecchio, and Gaia Ferraguzzi

Subjects
Health (social science), Epidemiology, Health Policy, Public Health, Environmental and Occupational Health, Medicine (miscellaneous), Health Informatics
Published
2023
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15. Efficacy of COVID-19 vaccination campaign in elderly people residing in long-term care facilities: a retrospective observational study from Lombardy region, Italy

Author

Riccardo Vecchio, Roberta Lattanzio, Chiara Marrocu, Sudwaric Sharma, Giovanni Cicconi, Sara Piccinelli, Gaia Ferraguzzi, Anna Odone, Catia Borriello, and Danilo Cereda

Subjects
Health (social science), Epidemiology, Health Policy, Public Health, Environmental and Occupational Health, Medicine (miscellaneous), Health Informatics
Published
2023
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17. Assessment of the treating physicians’ first-hand experience with handling and satisfaction of ofatumumab therapy: findings from the PERITIA survey conducted in Europe

Author

Daniela Rau, Sara Eichau, Giovanna Borriello, João Cerqueira, and Carola Wagner

Subjects
Neurology (clinical), General Medicine
Abstract

Background Real-world evidence on experience and satisfaction of ofatumumab as a treatment option for relapsing multiple sclerosis (RMS) is limited. Objective To present cumulative responses from a questionnaire related to first-hand experience of treating physicians on handling and convenience of ofatumumab therapy along with concerns related to COVID-19. Methods PERITIA was a multicentre survey conducted to collect responses from the ASCLEPIOS I/II trial investigators from Europe via an online questionnaire. Results Forty-six physicians (Germany, n = 14; Spain, n = 12; Portugal, n = 10; Italy, n = 10) completed the survey. Overall, 43% of the physicians considered the benefit-risk ratio of ofatumumab as very good. Over 93% were in favour of ofatumumab self-administration at home and the majority (83%) believed it to be completely true that self-administration of ofatumumab eases the burden for patients in terms of time. All investigators would like to potentially use anti-CD20 therapy as a long-term strategy. Even during the COVID-19 pandemic, physicians were in favour of a self-administration of MS therapy at home over other anti-CD20 therapy infusions. Conclusion European neurologists who were part of this survey considered the benefit-risk-ratio of ofatumumab as favourable and the monthly self-administered subcutaneous injections offering convenience for patients in the clinical practice.

Published
2023
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18. Data from Sphingosine-1-Phosphate Receptor-1 Promotes Environment-Mediated and Acquired Chemoresistance

Author

Hua Yu, Yves A. DeClerck, Lucia Borriello, Adar Makovski-Silverstein, Heehyoung Lee, Gregory Cherryholmes, Wenzhao Li, Saul J. Priceman, and Veronica Lifshitz

Abstract

Drug resistance is a major barrier for the development of effective and durable cancer therapies. Overcoming this challenge requires further defining the cellular and molecular mechanisms underlying drug resistance, both acquired and environment-mediated drug resistance (EMDR). Here, using neuroblastoma (NB), a childhood cancer with high incidence of recurrence due to resistance to chemotherapy, as a model we show that human bone marrow–mesenchymal stromal cells induce tumor expression of sphingosine-1-phosphate receptor-1 (S1PR1), leading to their resistance to chemotherapy. Targeting S1PR1 by shRNA markedly enhances etoposide-induced apoptosis in NB cells and abrogates EMDR, while overexpression of S1PR1 significantly protects NB cells from multidrug-induced apoptosis via activating JAK–STAT3 signaling. Elevated S1PR1 expression and STAT3 activation are also observed in human NB cells with acquired resistance to etoposide. We show in vitro and in human NB xenograft models that treatment with FTY720, an FDA-approved drug and antagonist of S1PR1, dramatically sensitizes drug-resistant cells to etoposide. In summary, we identify S1PR1 as a critical target for reducing both EMDR and acquired chemoresistance in NB. Mol Cancer Ther; 16(11); 2516–27. ©2017 AACR.

Published
2023
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19. Supplemental figure legends from Sphingosine-1-Phosphate Receptor-1 Promotes Environment-Mediated and Acquired Chemoresistance

Author

Hua Yu, Yves A. DeClerck, Lucia Borriello, Adar Makovski-Silverstein, Heehyoung Lee, Gregory Cherryholmes, Wenzhao Li, Saul J. Priceman, and Veronica Lifshitz

Abstract

Supplemental Figure 1. Bone marrow stromal cells enhance NB resistance to etoposide; Supplemental Figure 2. Overexpression of S1PR1 in CHLA-171 cells activates STAT3 and renders cells resistant to etoposide via JAK2/STAT3 signaling; Supplemental Figure 3. Elevated S1PR1 expression and STAT3 activation in etoposide-resistant CHLA-171 NB cells; Supplemental Figure 4. Taxol and JAK inhibitor effects on NB drug resistance; Supplemental Figure 5. Stattic and W146 inhibit STAT3 phosphorylation in NB drug resistant cells; Supplemental Figure 6. Crosstalk between NB cells and BM-MSC cells upregulates Sphk1.

Published
2023
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20. Figure S1, Figure S2, Figure S3, Figure S4, Figure S5, Figure S6 from Sphingosine-1-Phosphate Receptor-1 Promotes Environment-Mediated and Acquired Chemoresistance

Author

Hua Yu, Yves A. DeClerck, Lucia Borriello, Adar Makovski-Silverstein, Heehyoung Lee, Gregory Cherryholmes, Wenzhao Li, Saul J. Priceman, and Veronica Lifshitz

Abstract

Supplemental Figure 1. Bone marrow stromal cells enhance NB resistance to etoposide; Supplemental Figure 2. Overexpression of S1PR1 in CHLA-171 cells activates STAT3 and renders cells resistant to etoposide via JAK2/STAT3 signaling; Supplemental Figure 3. Elevated S1PR1 expression and STAT3 activation in etoposide-resistant CHLA-171 NB cells; Supplemental Figure 4. Taxol and JAK inhibitor effects on NB drug resistance; Supplemental Figure 5. Stattic and W146 inhibit STAT3 phosphorylation in NB drug resistant cells; Supplemental Figure 6. Crosstalk between NB cells and BM-MSC cells upregulates Sphk1.

Published
2023
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22. Body Image Problems in Individuals with Type 1 Diabetes: A Review of the Literature

Author

Crescenzo Cascella, Dario Iafusco, Alda Troncone, Angela Zanfardino, Antonietta Chianese, Anna Borriello, Troncone, A., Cascella, C., Chianese, A., Zanfardino, A., Borriello, A., and Iafusco, D.

Subjects
Physical development, Type 1 diabetes, Youth, Adolescent, Type 1 diabete, Educational psychology, Body satisfaction, medicine.disease, Psychiatry and Mental health, Body image, Pediatrics, Perinatology and Child Health, Systematic review, Developmental and Educational Psychology, medicine, Psychology, Empirical evidence, Social Sciences (miscellaneous), Body dissatisfaction, Clinical psychology
Abstract

Despite type 1 diabetes' (T1D) potential influence on adolescents' physical development, the occurrence of body image problems of adolescents with diabetes remains unclear. No research synthesis has yet addressed this issue. This study aims to systematically evaluate the empirical evidence concerning body image in individuals with T1D in order to provide an overview of the existing literature. Using PRISMA methodology, 51 relevant studies that fulfilled the eligibility criteria were found, the majority of them (N = 48) involving youth. The findings varied across studies: 17 studies indicated that in youth with T1D, body dissatisfaction was common and that body concerns were generally greater in youth with T1D than in controls; nine studies did not find any differences in body image problems between participants with and without T1D; three studies described higher body satisfaction in youth with diabetes than in controls; and three studies reported mixed results. Body concerns in individuals with T1D were often found to be associated with negative medical and psychological functioning. The variability and limits in assessment tools across studies, the overrepresentation of female subjects, and the fact that most research in this field is based on cross-sectional data are stressed in the interpretation of these mixed findings. Future research directions that could improve the understanding of body image concerns and clinical implications are discussed.

Published
2021
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23. Listening to the neurological teams for multiple sclerosis: the SMART project

Author

M. Rezzonico, Rocco Totaro, S. Bucello, Cinzia Cordioli, Alessandra Lugaresi, Alvino Bisecco, Martina Petruzzo, Paola Cavalla, Luisa Pastò, Eleonora Cocco, Giovanna Borriello, Roberta Fantozzi, S. Marangoni, M. Di Giuseppe, Edoardo Sessa, F. Caleri, Maria Liguori, W. Neri, M. G. Marini, L. Locatelli, G. L. Mancardi, C. Tortorella, K. Plewnia, S. Romano, P. Perini, Lucia Moiola, Francesco Patti, E. Mutta, Paola Chesi, Paola Valentino, A. Repice, Franco Granella, L. Alivernini, Marco Rovaris, M. Gattuso, Chesi P., Marini M.G., Mancardi G.L., Patti F., Alivernini L., Bisecco A., Borriello G., Bucello S., Caleri F., Cavalla P., Cocco E., Cordioli C., Di Giuseppe M., Fantozzi R., Gattuso M., Granella F., Liguori M., Locatelli L., Lugaresi A., Marangoni S., Moiola L., Mutta E., Neri W., Pasto L., Perini P., Petruzzo M., Plewnia K., Repice A.M., Rezzonico M., Romano S., Rovaris M., Sessa E., Tortorella C., Totaro R., Valentino P., Chesi, P., Marini, M. G., Mancardi, G. L., Patti, F., Alivernini, L., Bisecco, A., Borriello, G., Bucello, S., Caleri, F., Cavalla, P., Cocco, E., Cordioli, C., Di Giuseppe, M., Fantozzi, R., Gattuso, M., Granella, F., Liguori, M., Locatelli, L., Lugaresi, A., Marangoni, S., Moiola, L., Mutta, E., Neri, W., Pasto, L., Perini, P., Petruzzo, M., Plewnia, K., Repice, A. M., Rezzonico, M., Romano, S., Rovaris, M., Sessa, E., Tortorella, C., Totaro, R., and Valentino, P.

Subjects
Male, medicine.medical_specialty, Multiple Sclerosis, Neurology, Dermatology, Burnout, Job Satisfaction, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Surveys and Questionnaires, Health care, medicine, Humans, Active listening, 030212 general & internal medicine, Compassion fatigue, Descriptive statistics, business.industry, General Medicine, Middle Aged, Narrative medicine, burnout, compassion fatigue, narrative medicine, Psychiatry and Mental health, Cross-Sectional Studies, Italy, Family medicine, Quality of Life, Anxiety, Original Article, Female, Neurology (clinical), Empathy, medicine.symptom, Psychology, business, 030217 neurology & neurosurgery
Abstract

Objective Aim of the research was to define the quality of life of Italian neurologists and nurses’ professional caring for multiple sclerosis, to understand their living the clinical practice and identify possible signals of compassion fatigue. Material and methods One hundred five neurologists and nurses from 30 Italian multiple sclerosis centres were involved in an online quali-quantitative survey on the organization of care, combined with the Satisfaction and Compassion Fatigue Test and a collection of narratives. Descriptive statistics of the quantitative data were integrated with the results obtained by the narrative medicine methods of analysis. Results Most of the practitioners were neurologists, 46 average years old, 69% women, 43% part time dedicated to multiple sclerosis. An increased number of patients in the last 3 years were referred in 29 centres. Differences were found between neurologists and nurses. Physicians showed higher risks of burnout, reporting intensive working paces, lack of medical personnel, and anxiety caused by the precarious employment conditions. Nurses appeared more satisfied, although the reference to the lack of spaces, and the cross professional roles risk of compassion fatigue. Both positive and negative relationships of care were depicted as influencing the professional quality of life. Conclusion The interviewed neurological teams need to limit the risk of compassion fatigue, which appeared from the first years of the career. The prevalence of the risk among neurologists suggests more awareness among scientific societies and health care managers on the risk for this category, as first step to prevent it. Electronic supplementary material The online version of this article (10.1007/s10072-020-04301-z) contains supplementary material, which is available to authorized users.

Published
2020
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24. Trans-Oral Robotic Surgery: 14 Cases of Pleomorphic Adenoma of the Parapharyngeal Space

Author

Giovanni, Salzano, Giulia, Togo, Fabio, Maglitto, Gerardo, Borriello, Francesco, Perri, Giovanni, Audino, Luigi Angelo, Vaira, Maria Grazia, Maglione, Marzia, Petrocelli, Luigi, Califano, and Franco, Ionna

Subjects
Parapharyngeal Space, Robotic Surgical Procedures, Otorhinolaryngology, Head and Neck Neoplasms, Adenoma, Pleomorphic, Humans, Pharyngeal Neoplasms, Surgery, General Medicine, Salivary Gland Neoplasms, Retrospective Studies
Abstract

The aim of this study has been to describe our experience with pleomorphic adenomas of the parapharyngeal space (PPS) treated with trans-oral robotic surgery (TORS). Tumors arising from the PPS comprise less than 0.5% of all head and neck tumors. Salivary gland tumors account for 40% to 50% of PPS lesions with pleomorphic adenomas representing the most common salivary tumors (80%-90%). Parapharyngeal space tumors cause nonspecific symptoms and may be difficult to diagnose.In our study a preoperative diagnosis was conducted by fine needle aspiration biopsy and magnetic resonance imaging and the results were used to plan the correct surgical approach.In all cases we were able to employ TORS, a minimally invasive procedure that allows us to operate in narrow and anatomically complex spaces that we can only reach thanks to the use of well-articulated hand pieces.This report indicates that TORS is a safe surgical procedure for the excision of benign tumors of the PPS in selected cases.

Published
2022
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27. Supplementary Figure 6 from Cancer-Associated Fibroblasts Share Characteristics and Protumorigenic Activity with Mesenchymal Stromal Cells

Author

Yves A. DeClerck, Robert C. Seeger, Shahab Asgharzadeh, Hiroyuki Shimada, Laurence Blavier, Jemily Malvar, Richard Sposto, G. Esteban Fernandez, Michael A. Sheard, Rie Nakata, and Lucia Borriello

Abstract

Cytokines and chemokines not up-regulated by NB-MSC interaction and lack of inhibition of STAT3 activation by anti-IL-6/IL-6R

Published
2023
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28. Table A and B from Cancer-Associated Fibroblasts Share Characteristics and Protumorigenic Activity with Mesenchymal Stromal Cells

Author

Yves A. DeClerck, Robert C. Seeger, Shahab Asgharzadeh, Hiroyuki Shimada, Laurence Blavier, Jemily Malvar, Richard Sposto, G. Esteban Fernandez, Michael A. Sheard, Rie Nakata, and Lucia Borriello

Abstract

A: List of antibodies used in the study B: Clinical characteristics of patients from which CAF-MSC and BM-MSC were isolated.

Published
2023
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29. Supplementary Figure 4 from Cancer-Associated Fibroblasts Share Characteristics and Protumorigenic Activity with Mesenchymal Stromal Cells

Author

Yves A. DeClerck, Robert C. Seeger, Shahab Asgharzadeh, Hiroyuki Shimada, Laurence Blavier, Jemily Malvar, Richard Sposto, G. Esteban Fernandez, Michael A. Sheard, Rie Nakata, and Lucia Borriello

Abstract

CAF-MSC and BM-MSC enhance cell viability of NB cells in vitro and protect tumor cells from drug-induced apoptosis in vitro.

Published
2023
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32. Data from Cancer-Associated Fibroblasts Share Characteristics and Protumorigenic Activity with Mesenchymal Stromal Cells

Author

Yves A. DeClerck, Robert C. Seeger, Shahab Asgharzadeh, Hiroyuki Shimada, Laurence Blavier, Jemily Malvar, Richard Sposto, G. Esteban Fernandez, Michael A. Sheard, Rie Nakata, and Lucia Borriello

Abstract

Cancer-associated fibroblasts (CAF) have been suggested to originate from mesenchymal stromal cells (MSC), but their relationship with MSCs is not clear. Here, we have isolated from primary human neuroblastoma tumors a population of αFAP- and FSP-1–expressing CAFs that share phenotypic and functional characteristics with bone marrow–derived MSCs (BM-MSC). Analysis of human neuroblastoma tumors also confirmed the presence of αFAP- and FSP-1–positive cells in the tumor stroma, and their presence correlated with that of M2 tumor-associated macrophages. These cells (designated CAF-MSCs) enhanced in vitro neuroblastoma cell proliferation, survival, and resistance to chemotherapy and stimulated neuroblastoma tumor engraftment and growth in immunodeficient mice, indicating an effect independent of the immune system. The protumorigenic activity of MSCs in vitro and in xenografted mice was dependent on the coactivation of JAK2/STAT3 and MEK/ERK1/2 in neuroblastoma cells. In a mouse model of orthotopically implanted neuroblastoma cells, inhibition of JAK2/STAT3 and MEK/ERK/1/2 by ruxolitinib and trametinib potentiated tumor response to etoposide and increased overall survival. These data point to a new type of protumorigenic CAF in the tumor microenvironment of neuroblastoma and to STAT3 and ERK1/2 as mediators of their activity. Cancer Res; 77(18); 5142–57. ©2017 AACR.

Published
2023
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34. Supplementary Figure 7 from Cancer-Associated Fibroblasts Share Characteristics and Protumorigenic Activity with Mesenchymal Stromal Cells

Author

Yves A. DeClerck, Robert C. Seeger, Shahab Asgharzadeh, Hiroyuki Shimada, Laurence Blavier, Jemily Malvar, Richard Sposto, G. Esteban Fernandez, Michael A. Sheard, Rie Nakata, and Lucia Borriello

Abstract

Combination of ruxolitinib and trametinib inhibits the growth of subcutaneous NB tumors, cell proliferation and STAT3 and ERK1/2 activation in vivo.

Published
2023
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35. Data from MYCN-Dependent Expression of Sulfatase-2 Regulates Neuroblastoma Cell Survival

Author

Yves A. DeClerck, Jeremy E. Turnbull, Edwin A. Yates, Shahab Asgharzadeh, G. Esteban Fernandez, Richard Sposto, Hiroyuki Shimada, Gianluca Turcatel, Lucia Borriello, and Valeria Solari

Abstract

Heparan sulfate proteoglycans (HSPG) play a critical role in the interaction of tumor cells and their microenvironment. HSPG activity is dictated by sulfation patterns controlled by sulfotransferases, which add sulfate groups, and sulfatases (Sulf), which remove 6-O-sulfates. Here, we report altered expression of these enzymes in human neuroblastoma cells with higher levels of Sulf-2 expression, a specific feature of MYCN-amplified cells (MYCN-A cells) that represent a particularly aggressive subclass. Sulf-2 overexpression in neuroblastoma cells lacking MYCN amplification (MYCN-NA cells) increased their in vitro survival. Mechanistic investigations revealed evidence of a link between Sulf-2 expression and MYCN pathogenicity in vitro and in vivo. Analysis of Sulf-2 protein expression in 65 human neuroblastoma tumors demonstrated a higher level of Sulf-2 expression in MYCN-A tumors than in MYCN-NA tumors. In two different patient cohorts, we confirmed the association in expression patterns of Sulf-2 and MYCN and determined that Sulf-2 overexpression predicted poor outcomes in a nonindependent manner with MYCN. Our findings define Sulf-2 as a novel positive regulator of neuroblastoma pathogenicity that contributes to MYCN oncogenicity. Cancer Res; 74(21); 5999–6009. ©2014 AACR.

Published
2023
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38. Data from Retinoic Acid Induces p27Kip1 Nuclear Accumulation by Modulating Its Phosphorylation

Author

Fulvio Della Ragione, Vincenzo Zappia, Achille Iolascon, Debora Bencivenga, Alfonso Giovane, Adriana Oliva, Stefania Indaco, Maria Criscuolo, Valeria Cucciolla, and Adriana Borriello

Abstract

All-trans-retinoic acid (ATRA), the most biologically active metabolite of vitamin A, controls cell proliferation, apoptosis, and differentiation depending on the cellular context. These activities point to ATRA as a candidate for cancer therapy. A pivotal effect of the molecule is the modulation of p27Kip1, a cyclin-dependent kinase (CDK) inhibitor (CDKI). Here, we investigate the mechanisms by which ATRA regulates p27Kip1 level in LAN-5, a neuroblastoma cell line. When added to the cells, ATRA causes a rapid nuclear increase of p27Kip1, which clearly precedes growth arrest. The early buildup is not due to impairment of the CDKI degradation, in contrast to previous observations. Particularly, we did not detect the down-regulation of Skp2 and Cks1, two proteins involved in the nuclear ubiquitin-dependent p27Kip1 removal. Moreover, the morphogen does not impair the CDKI nuclear export and does not cause CDK2 relocalization. The characterization of CDKI isoforms by two-dimensional PAGE/immunoblotting showed that ATRA induces an early nuclear up-regulation of monophosphorylated p27Kip1. Immunologic studies established that this isoform corresponds to p27Kip1 phosphorylated on S10. The buildup of phospho(S10)p27Kip1 precedes the CDKI accumulation and increases its half-life. Finally, ATRA-treated nuclear LAN-5 extracts showed an enhanced capability of phosphorylating p27Kip1 on S10, thus explaining the nuclear up-regulation of the isoform. In conclusion, our data suggest a novel mechanism of ATRA antiproliferative activity, in which the morphogen rapidly up-regulates a nuclear kinase activity that phosphorylates p27Kip1 on S10. In turn, this event causes the stabilization of p27Kip1 and its accumulation in the nuclear compartment. (Cancer Res 2006; 66(8): 4240-8)

Published
2023
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41. Publisher Correction: Carbohydrate fatty acid monosulphate: oil-in-water adjuvant enhances SARS-CoV-2 RBD nanoparticle-induced immunogenicity and protection in mice

Author

Etsuro Nanishi, Francesco Borriello, Hyuk-Soo Seo, Timothy R. O’Meara, Marisa E. McGrath, Yoshine Saito, Jing Chen, Joann Diray-Arce, Kijun Song, Andrew Z. Xu, Soumik Barman, Manisha Menon, Danica Dong, Timothy M. Caradonna, Jared Feldman, Blake M. Hauser, Aaron G. Schmidt, Lindsey R. Baden, Robert K. Ernst, Carly Dillen, Jingyou Yu, Aiquan Chang, Luuk Hilgers, Peter Paul Platenburg, Sirano Dhe-Paganon, Dan H. Barouch, Al Ozonoff, Ivan Zanoni, Matthew B. Frieman, David J. Dowling, and Ofer Levy

Subjects
Pharmacology, Infectious Diseases, Immunology, Pharmacology (medical)
Published
2023
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42. Carbohydrate fatty acid monosulphate: oil-in-water adjuvant enhances SARS-CoV-2 RBD nanoparticle-induced immunogenicity and protection in mice

Author

Etsuro Nanishi, Francesco Borriello, Hyuk-Soo Seo, Timothy R. O’Meara, Marisa E. McGrath, Yoshine Saito, Jing Chen, Joann Diray-Arce, Kijun Song, Andrew Z. Xu, Soumik Barman, Manisha Menon, Danica Dong, Timothy M. Caradonna, Jared Feldman, Blake M. Hauser, Aaron G. Schmidt, Lindsey R. Baden, Robert K. Ernst, Carly Dillen, Jingyou Yu, Aiquan Chang, Luuk Hilgers, Peter Paul Platenburg, Sirano Dhe-Paganon, Dan H. Barouch, Al Ozonoff, Ivan Zanoni, Matthew B. Frieman, David J. Dowling, and Ofer Levy

Subjects
Pharmacology, Infectious Diseases, Immunology, Pharmacology (medical)
Abstract

Development of SARS-CoV-2 vaccines that protect vulnerable populations is a public health priority. Here, we took a systematic and iterative approach by testing several adjuvants and SARS-CoV-2 antigens to identify a combination that elicits antibodies and protection in young and aged mice. While demonstrating superior immunogenicity to soluble receptor-binding domain (RBD), RBD displayed as a protein nanoparticle (RBD-NP) generated limited antibody responses. Comparison of multiple adjuvants including AddaVax, AddaS03, and AS01B in young and aged mice demonstrated that an oil-in-water emulsion containing carbohydrate fatty acid monosulphate derivative (CMS:O/W) most effectively enhanced RBD-NP-induced cross-neutralizing antibodies and protection across age groups. CMS:O/W enhanced antigen retention in the draining lymph node, induced injection site, and lymph node cytokines, with CMS inducing MyD88-dependent Th1 cytokine polarization. Furthermore, CMS and O/W synergistically induced chemokine production from human PBMCs. Overall, CMS:O/W adjuvant may enhance immunogenicity and protection of vulnerable populations against SARS-CoV-2 and other infectious pathogens.

Published
2023
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43. The local topology of dynamical network models for biology

Author

Enrico Borriello

Abstract

The search for motifs –recurrent patterns in the topology of a network– has allowed the identification of universal classes of complex systems from very diverse fields, and has been used as a quantitative tool to highlight unifying properties of evolved and designed networks. This work explores if, and to what extent, network superfamilies previously identified through census of triadic motifs, are represented in the largest data set of dynamic, biological network models. This work presents triad significance profiles of 71 existing biological, and experimentally inspired, network models. The data generated is treated agnostically, and consistently clustered to two classes using several unsupervised techniques. The more populated class correlates with the previously identified superfamily of sensory transmission networks, characterized by the feedforward loop motif typical of signal-processing systems. The other class, surprisingly, better correlates to the superfamily of word-adjacency network. The result is analyzed for varying network size thresholds, and connected to the effect of the model building activity. It is shown that the topology of biological subnetworks starts resembling the topology of “sentences” in word-adjacency networks when the model focuses on smaller portions of the network, coarse-graining the boundary dynamics.

Published
2023
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44. The attractor landscape of duplicated networks

Author

Enrico Borriello

Abstract

We study the effect that network duplication has on the topology of the state space of dynamical Boolean networks with thresholds. We show that the problem of finding the attractor dynamics is just as hard as finding the attractors of the unduplicated network. We also show that a reverse algorithm –normally not computationally advantageous in determining the basins of attraction– can now exploit the symmetry of the system and its computational complexity does not scales exponentially anymore with the size of the network. Lastly, we show that when a chain of network duplication events is considered, only the first events change the nature of the attractors, while successive events only affect/reinforce the basins of attraction.

Published
2023
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46. Perceived stress and social support in a large population of people with multiple sclerosis recruited online through the COVID‐19 pandemic

Author

Simona Bonavita, Maddalena Sparaco, Giovanna Borriello, Antonio Russo, Luigi Lavorgna, Bonavita, Simona, Sparaco, Maddalena, Russo, Antonio, Borriello, Giovanna, and Lavorgna, Luigi

Subjects
medicine.medical_specialty, Stress management, Multiple Sclerosis, stress management, Clinical Neurology, Perceived Stress Scale, Social group, 03 medical and health sciences, Social support, 0302 clinical medicine, stre, Multiple Sclerosi, Humans, Medicine, 030212 general & internal medicine, Pandemics, Depression (differential diagnoses), SARS-CoV-2, business.industry, Multiple sclerosis, COVID-19, social support, medicine.disease, Patient Health Questionnaire, Neurology, Migraine, Physical therapy, Neurology (clinical), Neoplasm Recurrence, Local, business, COVID 19, Stress, Psychological, 030217 neurology & neurosurgery
Abstract

BACKGROUND AND PURPOSE: The COVID-19 emergency may cause post-traumatic stress disorder (PTSD), and with regard to people with MS (pwMS) chronic exposure to a wide range of challenging life events has been shown to be correlated with worsening of neurological symptoms, increased lesion burden on brain magnetic resonance imaging and relapses. The aim was to investigate perceived stress, depression, perceived social support, habits and behaviour changes in pwMS through COVID-19 in comparison to a control group. METHODS: A web-based survey was posted on SMsocialnetwork.com to investigate perceived stress (using the Perceived Stress Scale), depression (with Patient Health Questionnaire 2) and perceived social support (using Social Provision Scale 10 item) in pwMS and a control group through the COVID-19 pandemic. A secondary group of people with migraine was investigated. RESULTS: In all, 1286 answers from 612 pwMS and 674 control people were included in the final analysis. The answers from 318 people with migraine were included for a secondary analysis. A higher proportion of pwMS were depressed (43.1% vs. 23.1%; p

Published
2021
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47. Exposure to natalizumab throughout pregnancy: effectiveness and safety in an Italian cohort of women with multiple sclerosis

Author

Doriana Landi, Francesca Bovis, Alfonso Grimaldi, Pietro Osvaldo Annovazzi, Antonio Bertolotto, Alessia Bianchi, Giovanna Borriello, Vincenzo Brescia Morra, Sebastiano Bucello, Maria Chiara Buscarinu, Francesca Caleri, Marco Capobianco, Ruggero Capra, Maria Cellerino, Diego Centonze, Raffaella Cerqua, Clara Grazia Chisari, Marinella Clerico, Eleonora Cocco, Gaia Cola, Cinzia Cordioli, Erica Curti, Alessandro d'Ambrosio, Emanuele D'Amico, Giovanna De Luca, Massimiliano Di Filippo, Sonia Di Lemme, Roberta Fantozzi, Diana Ferraro, Elisabetta Ferraro, Antonio Gallo, Claudio Gasperini, Franco Granella, Matilde Inglese, Roberta Lanzillo, Lorena Lorefice, Giacomo Lus, Simona Malucchi, Monica Margoni, Giorgia Mataluni, Massimiliano Mirabella, Lucia Moiola, Carolina Gabri Nicoletti, Viviana Nociti, Francesco Patti, Federica Pinardi, Emilio Portaccio, Carlo Pozzilli, Paolo Ragonese, Sarah Rasia, Giuseppe Salemi, Elisabetta Signoriello, Francesca Vitetta, Rocco Totaro, Maria Pia Sormani, Maria Pia Amato, Girolama Alessandra Marfia, Landi, Doriana, Bovis, Francesca, Grimaldi, Alfonso, Annovazzi, Pietro Osvaldo, Bertolotto, Antonio, Bianchi, Alessia, Borriello, Giovanna, Brescia Morra, Vincenzo, Bucello, Sebastiano, Buscarinu, Maria Chiara, Caleri, Francesca, Capobianco, Marco, Capra, Ruggero, Cellerino, Maria, Centonze, Diego, Cerqua, Raffaella, Chisari, Clara Grazia, Clerico, Marinella, Cocco, Eleonora, Cola, Gaia, Cordioli, Cinzia, Curti, Erica, d'Ambrosio, Alessandro, D'Amico, Emanuele, De Luca, Giovanna, Di Filippo, Massimiliano, Di Lemme, Sonia, Fantozzi, Roberta, Ferraro, Diana, Ferraro, Elisabetta, Gallo, Antonio, Gasperini, Claudio, Granella, Franco, Inglese, Matilde, Lanzillo, Roberta, Lorefice, Lorena, Lus, Giacomo, Malucchi, Simona, Margoni, Monica, Mataluni, Giorgia, Mirabella, Massimiliano, Moiola, Lucia, Nicoletti, Carolina Gabri, Nociti, Viviana, Patti, Francesco, Pinardi, Federica, Portaccio, Emilio, Pozzilli, Carlo, Ragonese, Paolo, Rasia, Sarah, Salemi, Giuseppe, Signoriello, Elisabetta, Vitetta, Francesca, Totaro, Rocco, Sormani, Maria Pia, Amato, Maria Pia, Marfia, Girolama Alessandra, and D'Ambrosio, Alessandro

Subjects
Psychiatry and Mental health, Settore MED/26 - NEUROLOGIA, obstetrics, multiple sclerosi, obstetric, Surgery, Neurology (clinical), MRI, multiple sclerosis, Settore MED/26
Abstract

ObjectiveAssessing the risk of clinical and radiological reactivation during pregnancy and post partum in women with multiple sclerosis (MS) treated with natalizumab (NTZ) throughout pregnancy (LONG_EXP) compared with women interrupting treatment before (NO_EXP) and within >−30 days and ≤90 days from conception (SHORT_EXP), and describing newborns’ outcomes.MethodsMaternal clinical and radiological outcomes and obstetric and fetal outcomes were retrospectively collected and compared among groups (NO_EXP, SHORT_EXP, LONG_EXP). Predictors of clinical and radiological reactivation were investigated through univariable and multivariable analysis.Results170 eligible pregnancies from 163 women referring to 29 Italian MS centres were included. Annualised relapse rate (ARR) was significantly lower in LONG_EXP (n=66, 0.02 (0.001–0.09)) compared with NO_EXP (n=31, 0.43 (0.21–0.75), p=0.002) and SHORT_EXP (n=73, 0.46 (0.30–0.66), p=0.0004) during pregnancy, and in LONG_EXP (0.12 (0.05–0.24)) compared with SHORT_EXP (0.30 (0.17–0.50), p=0.008) during post partum. Gadolinium-enhancing (Gd+) lesions were less frequent in LONG_EXP (n=6/50, 2.00%) compared with NO_EXP (n=9/21, 42.86%) and SHORT_EXP after delivery (n=17/49, 34.69%, p=0.010).Delaying NTZ resumption after delivery significantly increased the risk of relapses (OR=1.29 (95% CI 1.07 to 1.57), p=0.009) and Gd+ lesions (OR=1.49 (95% CI 1.17 to 1.89, p=0.001). Newborns’ weight, length, head circumference and gestational age did not differ among groups after adjusting for confounders. Anaemia was tracked in 4/69 LONG_EXP newborns. Congenital anomaly rate was within the expected range for the untreated MS population.ConclusionsOur findings indicate that in women with MS treated with NTZ before conception, continuation of NTZ throughout pregnancy and its early resumption after delivery mitigate the risk of clinical and radiological reactivation. This approach has no major impact on newborns’ outcomes.

Published
2022

48. Vulnerability Predictors of Post-Vaccine SARS-CoV-2 Infection and Disease-Empirical Evidence from a Large Population-Based Italian Platform

Author

Giovanni Corrao, Matteo Franchi, Danilo Cereda, Francesco Bortolan, Olivia Leoni, Catia Rosanna Borriello, Petra Giulia Della Valle, Marcello Tirani, Giovanni Pavesi, Antonio Barone, Michele Ercolanoni, Jose Jara, Massimo Galli, Guido Bertolaso, Corrao, G, Franchi, M, Cereda, D, Bortolan, F, Leoni, O, Borriello, C, Della Valle, P, Tirani, M, Pavesi, G, Barone, A, Ercolanoni, M, Jara, J, Galli, M, and Bertolaso, G

Subjects
Pharmacology, Infectious Diseases, SARS-CoV-2, vaccine, vulnerability, Drug Discovery, Immunology, COVID-19, vaccines, predictors, predictor, Pharmacology (medical)
Abstract

We aimed to identify individual features associated with increased risk of post-vaccine SARS-CoV-2 infection and severe COVID-19 illness. We performed a nested case–control study based on 5,350,295 citizens from Lombardy, Italy, aged ≥ 12 years who received a complete anti-COVID-19 vaccination from 17 January 2021 to 31 July 2021, and followed from 14 days after vaccine completion to 11 November 2021. Overall, 17,996 infections and 3023 severe illness cases occurred. For each case, controls were 1:1 (infection cases) or 1:10 (severe illness cases) matched for municipality of residence and date of vaccination completion. The association between selected predictors (sex, age, previous occurrence of SARS-CoV-2 infection, type of vaccine received, number of previous contacts with the Regional Health Service (RHS), and the presence of 59 diseases) and outcomes was assessed by using multivariable conditional logistic regression models. Sex, age, previous SARS-CoV-2 infection, type of vaccine and number of contacts with the RHS were associated with the risk of infection and severe illness. Moreover, higher odds of infection and severe illness were significantly associated with 14 and 34 diseases, respectively, among those investigated. These results can be helpful to clinicians and policy makers for prioritizing interventions.

Published
2022

50. Engaging caregivers and children in picture books: A family-implemented mathematical language intervention

Author

Joyce Lin, Melody Kung, Caroline Byrd Hornburg, David J. Purpura, Yemimah A. King, Sara A. Schmitt, Amy R. Napoli, Lindsey M. Bryant, Laura Y. Anaya, Emily Rolan, Jennifer Dobbs-Oates, Lauren Westerberg, Giulia A. Borriello, and Ellen C. Litkowski

Subjects
Pictorial stimuli, Picture books, Intervention (counseling), Reading (process), media_common.quotation_subject, Developmental and Educational Psychology, Mathematics education, Language of mathematics, Mathematical ability, Psychology, Education, media_common
Published
2021
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