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252. Fixed-dose combination of indacaterol/glycopyrronium/mometasone furoate once-daily versus salmeterol/fluticasone twice-daily plus tiotropium once-daily in patients with uncontrolled asthma: A randomised, Phase IIIb, non-inferiority study (ARGON)

Author

Gessner, Christian, Kornmann, Oliver, Maspero, Jorge, van Zyl-Smit, Richard, Krüll, Matthias, Salina, Anna, Gupta, Pritam, Bostel, Sebastien, Fucile, Sebastian, Conde, Lorena Garcia, and Pfister, Pascal

Published
2020
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253. Effect of fixed-dose subcutaneous reslizumab on asthma exacerbations in patients with severe uncontrolled asthma and corticosteroid sparing in patients with oral corticosteroid-dependent asthma: results from two phase 3, randomised, double-blind, placebo-controlled trials

Author

Bernstein, Jonathan A, Virchow, J Christian, Murphy, Kevin, Maspero, Jorge Fernando, Jacobs, Joshua, Adir, Yochai, Humbert, Marc, Castro, Mario, Marsteller, Douglas A, McElhattan, Jennifer, Hickey, Lisa, Garin, Margaret, Vanlandingham, Rebecca, and Brusselle, Guy

Published
2020
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255. Dupilumab Efficacy in Uncontrolled, Moderate-to-Severe Asthma with Self-Reported Chronic Rhinosinusitis

Author

Maspero, Jorge F., Katelaris, Constance H., Busse, William W., Castro, Mario, Corren, Jonathan, Chipps, Bradley E., Peters, Anju T., Pavord, Ian D., Ford, Linda B., Sher, Lawrence, Rabe, Klaus F., Rice, Megan S., Rowe, Paul, Lu, Yufang, Harel, Sivan, Jagerschmidt, Alexandre, Khan, Asif H., Kamat, Siddhesh, Pirozzi, Gianluca, Amin, Nikhil, Ruddy, Marcella, Graham, Neil M.H., Mannent, Leda P., and Teper, Ariel

Published
2020
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259. International Variation in Exacerbation Rates in Patients With Severe Asthma

Author

Yadav, C.P., primary, Lee, T.Y., additional, Price, D.B., additional, Roy, R., additional, Mien, L.L.H., additional, Wang, E., additional, Wechsler, M.E., additional, Jackson, D.J., additional, Busby, J., additional, Heaney, L.G., additional, Pfeffer, P.E., additional, Mahboub, B., additional, Perng, D.-W., additional, Cosio, B.G., additional, Perez-De-Llano, L., additional, AL Lohebi, R., additional, Linnemann, D.L., additional, Al-Ahmad, M., additional, Rhee, C.K., additional, Iwanaga, T., additional, Heffler, E., additional, Canonica, G.W., additional, Costello, R.W., additional, Papadopoulos, N., additional, Papaioannou, A., additional, Porsbjerg, C.M., additional, Torres-Duque, C.A., additional, Christoff, G.C., additional, Popov, T.A., additional, Hew, M., additional, Peters, M., additional, Gibson, P.G., additional, Maspero, J., additional, Bergeron, C., additional, Cerda, S., additional, Contreras, M.A., additional, Chen, W., additional, and Sadatsafavi, M., additional

Published
2024
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260. Unveiling the Real-World Causal Interaction of Essential Risk Factors in Severe Asthma Exacerbation: A Bayesian Network Analysis

Author

Yadav, C.P., primary, Chakraborty, A., additional, Price, D., additional, Beasley, R., additional, Sadatsafavi, M., additional, Janson, C., additional, Siyue, M.K., additional, Wang, E., additional, Wechsler, M.E., additional, Jackson, D.J., additional, Busby, J., additional, Heaney, L.G., additional, Pfeffer, P.E., additional, Mahboub, B., additional, Perng, D.-W., additional, Cosio, B.G., additional, Perez-De-Llano, L., additional, AL Lohebi, R., additional, Linnemann, D.L., additional, Al-Ahmad, M., additional, Rhee, C.K., additional, Iwanaga, T., additional, Heffler, E., additional, Canonica, G.W., additional, Costello, R.W., additional, Papadopoulos, N., additional, Papaioannou, A., additional, Porsbjerg, C., additional, Torres-Duque, C.A., additional, Christoff, G.C., additional, Popov, T.A., additional, Hew, M., additional, Peters, M., additional, Gibson, P.G., additional, Maspero, J.F., additional, Bergeron, C., additional, Cerda, S., additional, Contreras, M.A., additional, and Chen, W., additional

Published
2024
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261. Age Matters

Author

Wehrle, Chase J, primary, Maspero, Marianna, additional, Pinna, Antonio D, additional, Dutkowski, Philipp, additional, Miller, Charles, additional, Hashimoto, Koji, additional, Claviaen, Pierre-Alain, additional, and Schlegel, Andrea, additional

Published
2024
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263. Reply to “Exploring the long-term effects of biologic initiation in severe asthma: Insights from the International Severe Asthma Registry”

Author

Chen, Wenjia, primary, Tran, Trung N., additional, Sadatsafavi, Mohsen, additional, Murray, Ruth B., additional, Boon Wong, Nigel Chong, additional, Ali, Nasloon, additional, Ariti, Con, additional, Bulathsinhala, Lakmini, additional, Garcia Gil, Esther, additional, FitzGerald, J. Mark, additional, Alacqua, Marianna, additional, Al-Ahmad, Mona, additional, Altraja, Alan, additional, Al-Lehebi, Riyad, additional, Bhutani, Mohit, additional, Bjermer, Leif, additional, Bjerrum, Anne-Sofie, additional, Bourdin, Arnaud, additional, von Bülow, Anna, additional, Busby, John, additional, Canonica, Giorgio Walter, additional, Carter, Victoria, additional, Christoff, George C., additional, Cosio, Borja G., additional, Costello, Richard W., additional, Fonseca, João A., additional, Gibson, Peter G., additional, Yoo, Kwang Ha, additional, Heaney, Liam G., additional, Heffler, Enrico, additional, Hew, Mark, additional, Hilberg, Ole, additional, Hoyte, Flavia, additional, Iwanaga, Takashi, additional, Jackson, David J., additional, Jones, Rupert C., additional, Koh, Mariko Siyue, additional, Kuna, Piotr, additional, Larenas-Linnemann, Désirée, additional, Lehmann, Sverre, additional, Lehtimäki, Lauri, additional, Lyu, Juntao, additional, Mahboub, Bassam, additional, Maspero, Jorge, additional, Menzies-Gow, Andrew N., additional, Newell, Anthony, additional, Sirena, Concetta, additional, Papadopoulos, Nikolaos G., additional, Papaioannou, Andriana I., additional, Perez-de-Llano, Luis, additional, Perng (Steve), Diahn-Warng, additional, Peters, Matthew J., additional, Pfeffer, Paul E., additional, Porsbjerg, Celeste M., additional, Popov, Todor A., additional, Rhee, Chin Kook, additional, Salvi, Sundeep, additional, Taillé, Camille, additional, Taube, Christian, additional, Torres-Duque, Carlos A., additional, Ulrik, Charlotte, additional, Ra, Seung Won, additional, Wang, Eileen, additional, Wechsler, Michael E., additional, and Price, David B., additional

Published
2024
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264. Assessment of long-term safety and efficacy of dupilumab in children with asthma (LIBERTY ASTHMA EXCURSION): an open-label extension study

Author

Bacharier, Leonard B, primary, Maspero, Jorge F, additional, Katelaris, Constance H, additional, Fiocchi, Alessandro G, additional, Gagnon, Remi, additional, de Mir, Ines, additional, Guilbert, Theresa W, additional, Jackson, Daniel J, additional, Staudinger, Heribert W, additional, Laws, Elizabeth, additional, Mannent, Leda P, additional, Akinlade, Bolanle, additional, Maloney, Jennifer, additional, Tawo, Kelsey, additional, Khokhar, Faisal A, additional, Li, Ning, additional, Hardin, Megan, additional, Abdulai, Raolat M, additional, Lederer, David J, additional, Robinson, Lacey B, additional, Bacharier, Leonard B., additional, Maspero, Jorge F., additional, Katelaris, Constance H., additional, Fiocchi, Alessandro G., additional, De Mir, Ines, additional, Guilbert, Theresa W., additional, Jackson, Daniel J., additional, Staudinger, Heribert W., additional, Mannent, Leda P., additional, Khokhar, Faisal A., additional, Abdulai, Raolat M., additional, Lederer, David J., additional, and Robinson, Lacey B., additional

Published
2023
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266. One smoothing property of the scattering map of the KdV on $\mathbb R$

Author

Maspero, Alberto and Schaad, Beat

Subjects
Mathematics - Analysis of PDEs, 35Q53 (Primary) 35P25, 37K15 (Secondary)
Abstract

In this paper we prove that in appropriate weighted Sobolev spaces, in the case of no bound states, the scattering map of the Korteweg-de Vries (KdV) on $\mathbb R$ is a perturbation of the Fourier transform by a regularizing operator. As an application of this result, we show that the difference of the KdV flow and the corresponding Airy flow is 1-smoothing.

Published
2014
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267. Birkhoff coordinates for the Toda Lattice in the limit of infinitely many particles with an application to FPU

Author

Bambusi, Dario and Maspero, Alberto

Subjects
Mathematical Physics
Abstract

In this paper we study the Birkhoff coordinates (Cartesian action angle coordinates) of the Toda lattice with periodic boundary condition in the limit where the number $N$ of the particles tends to infinity. We prove that the transformation introducing such coordinates maps analytically a complex ball of radius $R/N^\alpha$ (in discrete Sobolev-analytic norms) into a ball of radius $R'/N^\alpha$ (with $R,R'>0$ independent of $N$) if and only if $\alpha\geq2$. Then we consider the problem of equipartition of energy in the spirit of Fermi-Pasta-Ulam. We deduce that corresponding to initial data of size $R/N^2$, $0

Published
2014
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268. Some analytic results on the FPU paradox

Author

Bambusi, Dario, Carati, Andrea, Maiocchi, Alberto, and Maspero, Alberto

Subjects
Mathematical Physics
Abstract

We present some analytic results aiming at explaining the lack of thermalization observed by Fermi Pasta and Ulam in their celebrated numerical experiment. In particular we focus on results which persist as the number $N$ of particles tends to infinity. After recalling the FPU experiment and some classical heuristic ideas that have been used for its explanation, we concentrate on more recent rigorous results which are based on the use of (i) canonical perturbation theory and KdV equation, (ii) Toda lattice, (iii) a new approach based on the construction of functions which are adiabatic invariants with large probability in the Gibbs measure.

Published
2014
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270. Clinical implementation of MRI-based organs-at-risk auto-segmentation with convolutional networks for prostate radiotherapy

Author

Mark H. F. Savenije, Matteo Maspero, Gonda G. Sikkes, Jochem R. N. van der Voort van Zyp, Alexis N. T. J. Kotte, Gijsbert H. Bol, and Cornelis A. T. van den Berg

Subjects
Prostate cancer, Radiotherapy, Magnetic resonance imaging, MR-only treatment planning, Delineation, Contouring, Medical physics. Medical radiology. Nuclear medicine, R895-920, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Structure delineation is a necessary, yet time-consuming manual procedure in radiotherapy. Recently, convolutional neural networks have been proposed to speed-up and automatise this procedure, obtaining promising results. With the advent of magnetic resonance imaging (MRI)-guided radiotherapy, MR-based segmentation is becoming increasingly relevant. However, the majority of the studies investigated automatic contouring based on computed tomography (CT). Purpose In this study, we investigate the feasibility of clinical use of deep learning-based automatic OARs delineation on MRI. Materials and methods We included 150 patients diagnosed with prostate cancer who underwent MR-only radiotherapy. A three-dimensional (3D) T1-weighted dual spoiled gradient-recalled echo sequence was acquired with 3T MRI for the generation of the synthetic-CT. The first 48 patients were included in a feasibility study training two 3D convolutional networks called DeepMedic and dense V-net (dV-net) to segment bladder, rectum and femurs. A research version of an atlas-based software was considered for comparison. Dice similarity coefficient, 95% Hausdorff distances (HD95), and mean distances were calculated against clinical delineations. For eight patients, an expert RTT scored the quality of the contouring for all the three methods. A choice among the three approaches was made, and the chosen approach was retrained on 97 patients and implemented for automatic use in the clinical workflow. For the successive 53 patients, Dice, HD95 and mean distances were calculated against the clinically used delineations. Results DeepMedic, dV-net and the atlas-based software generated contours in 60 s, 4 s and 10-15 min, respectively. Performances were higher for both the networks compared to the atlas-based software. The qualitative analysis demonstrated that delineation from DeepMedic required fewer adaptations, followed by dV-net and the atlas-based software. DeepMedic was clinically implemented. After retraining DeepMedic and testing on the successive patients, the performances slightly improved. Conclusion High conformality for OARs delineation was achieved with two in-house trained networks, obtaining a significant speed-up of the delineation procedure. Comparison of different approaches has been performed leading to the succesful adoption of one of the neural networks, DeepMedic, in the clinical workflow. DeepMedic maintained in a clinical setting the accuracy obtained in the feasibility study.

Published
2020
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272. From Batch to the Semi-Continuous Flow Hydrogenation of pNB, pNZ-Protected Meropenem

Author

Marziale Comito, Riccardo Monguzzi, Silvia Tagliapietra, Angelo Maspero, Giovanni Palmisano, and Giancarlo Cravotto

Subjects
flow chemistry, microwave-assisted, semi-continuous synthesis, meropenem, hydrogenation, drug synthesis, Pharmacy and materia medica, RS1-441
Abstract

Meropenem is currently the most common carbapenem in clinical applications. Industrially, the final synthetic step is characterized by a heterogeneous catalytic hydrogenation in batch mode with hydrogen and Pd/C. The required high-quality standard is very difficult to meet and specific conditions are required to remove both protecting groups [i.e., p-nitrobenzyl (pNB) and p-nitrobenzyloxycarbonyl (pNZ)] simultaneously. The three-phase gas–liquid–solid system makes this step difficult and unsafe. The introduction of new technologies for small-molecule synthesis in recent years has opened up new landscapes in process chemistry. In this context, we have investigated meropenem hydrogenolysis using microwave (MW)-assisted flow chemistry for use as a new technology with industrial prospects. The reaction parameters (catalyst amount, T, P, residence time, flow rate) in the move from the batch process to semi-continuous flow were investigated under mild conditions to determine their influence on the reaction rate. The optimization of the residence time (840 s) and the number of cycles (4) allowed us to develop a novel protocol that halves the reaction time compared to batch production (14 min vs. 30 min) while maintaining the same product quality. The increase in productivity using this semi-continuous flow technique compensates for the slightly lower yield (70% vs. 74%) obtained in batch mode.

Published
2023
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273. Novel Xanomeline-Containing Bitopic Ligands of Muscarinic Acetylcholine Receptors: Design, Synthesis and FRET Investigation

Author

Carlo Matera, Michael Kauk, Davide Cirillo, Marco Maspero, Claudio Papotto, Daniela Volpato, Ulrike Holzgrabe, Marco De Amici, Carsten Hoffmann, and Clelia Dallanoce

Subjects
muscarinic acetylcholine receptors, Xanomeline, 77-LH-28-1, bitopic hybrid ligands, synthesis, fluorescence resonance energy transfer, Organic chemistry, QD241-441
Abstract

In the last few years, fluorescence resonance energy transfer (FRET) receptor sensors have contributed to the understanding of GPCR ligand binding and functional activation. FRET sensors based on muscarinic acetylcholine receptors (mAChRs) have been employed to study dual-steric ligands, allowing for the detection of different kinetics and distinguishing between partial, full, and super agonism. Herein, we report the synthesis of the two series of bitopic ligands, 12-Cn and 13-Cn, and their pharmacological investigation at the M1, M2, M4, and M5 FRET-based receptor sensors. The hybrids were prepared by merging the pharmacophoric moieties of the M1/M4-preferring orthosteric agonist Xanomeline 10 and the M1-selective positive allosteric modulator 77-LH-28-1 (1-[3-(4-butyl-1-piperidinyl)propyl]-3,4-dihydro-2(1H)-quinolinone) 11. The two pharmacophores were connected through alkylene chains of different lengths (C3, C5, C7, and C9). Analyzing the FRET responses, the tertiary amine compounds 12-C5, 12-C7, and 12-C9 evidenced a selective activation of M1 mAChRs, while the methyl tetrahydropyridinium salts 13-C5, 13-C7, and 13-C9 showed a degree of selectivity for M1 and M4 mAChRs. Moreover, whereas hybrids 12-Cn showed an almost linear response at the M1 subtype, hybrids 13-Cn evidenced a bell-shaped activation response. This different activation pattern suggests that the positive charge anchoring the compound 13-Cn to the orthosteric site ensues a degree of receptor activation depending on the linker length, which induces a graded conformational interference with the binding pocket closure. These bitopic derivatives represent novel pharmacological tools for a better understanding of ligand-receptor interactions at a molecular level.

Published
2023
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274. Correlation between Temporo-Mandibular Pain and Gender

Author

Cinzia Maspero, Marzia Segù, Andrea Abate, and Valentina Lanteri

Subjects
n/a, Technology, Engineering (General). Civil engineering (General), TA1-2040, Biology (General), QH301-705.5, Physics, QC1-999, Chemistry, QD1-999
Abstract

The international literature, in restricted contexts but of considerable significance, has begun to highlight this issue, pointing out that in clinical trials of many diseases, there is often a tendency not to take adequate account of the numerical prevalence of the female sex in the general population, in addition to the biological differences between men and women [...]

Published
2023
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275. The Maxilla-Mandibular Discrepancies through Soft-Tissue References: Reliability and Validation of the Anteroposterior Measurement

Author

Cinzia Maspero, Niccolò Cenzato, Francesco Inchingolo, Maria Grazia Cagetti, Gaetano Isola, Davide Sozzi, Massimo Del Fabbro, and Gianluca Martino Tartaglia

Subjects
Wits appraisal, orthodontic discrepancy, Angle’s malocclusions skeletal classification, cephalometric diagnosis, Pediatrics, RJ1-570
Abstract

This research aimed to identify a new measurement to diagnose the sagittal maxillary and mandibular difference that considers the patient’s profile (soft tissue Wits appraisal: obtained by projecting points A and B on the occlusal plane and subsequently measuring the linear distance between the two points). This new measurement was compared to the conventional Wits appraisal obtained to diagnose sagittal jaw discrepancy. In total, 300 subjects (162 males, 138 females) aged between 6 and 50 years requiring orthodontic treatment were analyzed. The cephalometric tracings on the pre-treatment lateral cephalometric radiographs were obtained and the two measurements taken were the Wits appraisal and a new measurement which were both calculated and compared. The analysis of the linear correlations between the conventional Wits value and the measurement obtained on the soft-tissue were undertaken. The relevance was established at 5% (p < 0.05). The mean values were also calculated within sex and age classes, and comparisons between sexes were obtained employing the t test Student’s for independent samples. Subsequently, chi-square analysis was also utilized to verify the sex distributions in the age groups considered. The results obtained suggested that these two measurements were significantly correlated with each other, with no characteristic patterns of sex or age. These data allowed an estimation of the reference values of the new measurement (−1.9 mm and 5.4 mm for patients with Class I molar relationship) showing that the former was more variable than the latter. The new measurement could allow for an accurate evaluation of the jaws sagittal discrepancy from soft tissue analysis.

Published
2023
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282. Generating synthetic computed tomography for radiotherapy: SynthRAD2023 challenge report

Author

Computational Imaging, Cancer, Klinisch Fysici i.o., Huijben, Evi M C, Terpstra, Maarten L, Galapon, Arthur Jr, Pai, Suraj, Thummerer, Adrian, Koopmans, Peter, Afonso, Manya, van Eijnatten, Maureen, Gurney-Champion, Oliver, Chen, Zeli, Zhang, Yiwen, Zheng, Kaiyi, Li, Chuanpu, Pang, Haowen, Ye, Chuyang, Wang, Runqi, Song, Tao, Fan, Fuxin, Qiu, Jingna, Huang, Yixing, Ha, Juhyung, Sung Park, Jong, Alain-Beaudoin, Alexandra, Bériault, Silvain, Yu, Pengxin, Guo, Hongbin, Huang, Zhanyao, Li, Gengwan, Zhang, Xueru, Fan, Yubo, Liu, Han, Xin, Bowen, Nicolson, Aaron, Zhong, Lujia, Deng, Zhiwei, Müller-Franzes, Gustav, Khader, Firas, Li, Xia, Zhang, Ye, Hémon, Cédric, Boussot, Valentin, Zhang, Zhihao, Wang, Long, Bai, Lu, Wang, Shaobin, Mus, Derk, Kooiman, Bram, Sargeant, Chelsea A H, Henderson, Edward G A, Kondo, Satoshi, Kasai, Satoshi, Karimzadeh, Reza, Ibragimov, Bulat, Helfer, Thomas, Dafflon, Jessica, Chen, Zijie, Wang, Enpei, Perko, Zoltan, Maspero, Matteo, Computational Imaging, Cancer, Klinisch Fysici i.o., Huijben, Evi M C, Terpstra, Maarten L, Galapon, Arthur Jr, Pai, Suraj, Thummerer, Adrian, Koopmans, Peter, Afonso, Manya, van Eijnatten, Maureen, Gurney-Champion, Oliver, Chen, Zeli, Zhang, Yiwen, Zheng, Kaiyi, Li, Chuanpu, Pang, Haowen, Ye, Chuyang, Wang, Runqi, Song, Tao, Fan, Fuxin, Qiu, Jingna, Huang, Yixing, Ha, Juhyung, Sung Park, Jong, Alain-Beaudoin, Alexandra, Bériault, Silvain, Yu, Pengxin, Guo, Hongbin, Huang, Zhanyao, Li, Gengwan, Zhang, Xueru, Fan, Yubo, Liu, Han, Xin, Bowen, Nicolson, Aaron, Zhong, Lujia, Deng, Zhiwei, Müller-Franzes, Gustav, Khader, Firas, Li, Xia, Zhang, Ye, Hémon, Cédric, Boussot, Valentin, Zhang, Zhihao, Wang, Long, Bai, Lu, Wang, Shaobin, Mus, Derk, Kooiman, Bram, Sargeant, Chelsea A H, Henderson, Edward G A, Kondo, Satoshi, Kasai, Satoshi, Karimzadeh, Reza, Ibragimov, Bulat, Helfer, Thomas, Dafflon, Jessica, Chen, Zijie, Wang, Enpei, Perko, Zoltan, and Maspero, Matteo

Published
2024

283. Real-world biologics response and super-response in the International Severe Asthma Registry cohort

Author

Denton, Eve, Hew, Mark, Peters, Matthew J., Upham, John W., Bulathsinhala, Lakmini, Tran, Trung N., Martin, Neil, Bergeron, Celine, Al-Ahmad, Mona, Altraja, Alan, Larenas-Linnemann, Desiree, Murray, Ruth, Celis-Preciado, Carlos Andres, Al-Lehebi, Riyad, Belhassen, Manon, Bhutani, Mohit, Bosnic-Anticevich, Sinthia Z., Bourdin, Arnaud, Brusselle, Guy G., Busby, John, Canonica, Giorgio Walter, Heffler, Enrico, Chapman, Kenneth R., Charriot, Jeremy, Christoff, George C., Chung, Li Ping, Cosio, Borja G., Cote, Andreanne, Costello, Richard W., Cushen, Breda, Fingleton, James, Fonseca, Joao A., Gibson, Peter G., Heaney, Liam G., Huang, Erick Wan-Chun, Iwanaga, Takashi, Jackson, David J., Koh, Mariko Siyue, Lehtimaki, Lauri, Maspero, Jorge, Mahboub, Bassam, Menzies-Gow, Andrew N., Mitchell, Patrick D., Papadopoulos, Nikolaos G., Papaioannou, Andriana I., Perez-de-Llano, Luis, Perng, Diahn-Warng, Pfeffer, Paul E., Popov, Todor A., Porsbjerg, Celeste M., Denton, Eve, Hew, Mark, Peters, Matthew J., Upham, John W., Bulathsinhala, Lakmini, Tran, Trung N., Martin, Neil, Bergeron, Celine, Al-Ahmad, Mona, Altraja, Alan, Larenas-Linnemann, Desiree, Murray, Ruth, Celis-Preciado, Carlos Andres, Al-Lehebi, Riyad, Belhassen, Manon, Bhutani, Mohit, Bosnic-Anticevich, Sinthia Z., Bourdin, Arnaud, Brusselle, Guy G., Busby, John, Canonica, Giorgio Walter, Heffler, Enrico, Chapman, Kenneth R., Charriot, Jeremy, Christoff, George C., Chung, Li Ping, Cosio, Borja G., Cote, Andreanne, Costello, Richard W., Cushen, Breda, Fingleton, James, Fonseca, Joao A., Gibson, Peter G., Heaney, Liam G., Huang, Erick Wan-Chun, Iwanaga, Takashi, Jackson, David J., Koh, Mariko Siyue, Lehtimaki, Lauri, Maspero, Jorge, Mahboub, Bassam, Menzies-Gow, Andrew N., Mitchell, Patrick D., Papadopoulos, Nikolaos G., Papaioannou, Andriana I., Perez-de-Llano, Luis, Perng, Diahn-Warng, Pfeffer, Paul E., Popov, Todor A., and Porsbjerg, Celeste M.

Abstract

Background: Biologic asthma therapies reduce exacerbations and long-term oral corticosteroids (LTOCS) use in randomized controlled trials (RCTs); however, there are limited data on outcomes among patients ineligible for RCTs. Hence, we investigated responsiveness to biologics in a real-world population of adults with severe asthma. Methods: Adults in the International Severe Asthma Registry (ISAR) with ≥24 weeks of follow-up were grouped into those who did, or did not, initiate biologics (anti-IgE, anti-IL5/IL5R, anti-IL4/13). Treatment responses were examined across four domains: forced expiratory volume in 1 second (FEV 1) increase by ≥100 mL, improved asthma control, annualized exacerbation rate (AER) reduction ≥50%, and any LTOCS dose reduction. Super-response criteria were: FEV 1 increase by ≥500 mL, new well-controlled asthma, no exacerbations, and LTOCS cessation or tapering to ≤5 mg/day. Results: 5.3% of ISAR patients met basic RCT inclusion criteria; 2116/8451 started biologics. Biologic initiators had worse baseline impairment than non-initiators, despite having similar biomarker levels. Half or more of initiators had treatment responses: 59% AER reduction, 54% FEV 1 increase, 49% improved control, 49% reduced LTOCS, of which 32%, 19%, 30%, and 39%, respectively, were super-responses. Responses/super-responses were more frequent in biologic initiators than in non-initiators; nevertheless, ~40–50% of initiators did not meet response criteria. Conclusions: Most patients with severe asthma are ineligible for RCTs of biologic therapies. Biologics are initiated in patients who have worse baseline impairments than non-initiators despite similar biomarker levels. Although biologic initiators exhibited clinical responses and super-responses in all outcome domains, 40–50% did not meet the response criteria.

Published
2024

284. Association between pre-biologic T2-biomarker combinations and response to biologics in patients with severe asthma

Author

Porsbjerg, Celeste M., Townend, John, Bergeron, Celine, Christoff, George C., Katsoulotos, Gregory P., Larenas-Linnemann, Desiree, Tran, Trung N., Al-Lehebi, Riyad, Bosnic-Anticevich, Sinthia Z., Busby, John, Hew, Mark, Kostikas, Konstantinos, Papadopoulos, Nikolaos G., Pfeffer, Paul E., Popov, Todor A., Rhee, Chin Kook, Sadatsafavi, Mohsen, Tsai, Ming-Ju, Ulrik, Charlotte Suppli, Al-Ahmad, Mona, Altraja, Alan, Beastall, Aaron, Bulathsinhala, Lakmini, Carter, Victoria, Cosio, Borja G., Fletton, Kirsty, Hansen, Susanne, Heaney, Liam G., Hubbard, Richard B., Kuna, Piotr, Murray, Ruth B., Nagano, Tatsuya, Pini, Laura, Rosales, Diana Jimena Cano, Schleich, Florence, Wechsler, Michael E., Amaral, Rita, Bourdin, Arnaud, Brusselle, Guy G., Chen, Wenjia, Chung, Li Ping, Denton, Eve, Fonseca, Joao A., Hoyte, Flavia, Jackson, David J., Katial, Rohit, Kirenga, Bruce J., Koh, Mariko Siyue, Lawkiedraj, Agnieszka, Lehtimaki, Lauri, Liew, Mei Fong, Mahboub, Bassam, Martin, Neil, Menzies-Gow, Andrew N., Pang, Pee Hwee, Papaioannou, Andriana I., Patel, Pujan H., Perez-De-Llano, Luis, Peters, Matthew J., Ricciardi, Luisa, Rodriguez-Caceres, Bellanid, Solarte, Ivan, Tay, Tunn Ren, Torres-Duque, Carlos A., Wang, Eileen, Zappa, Martina, Abisheganaden, John, Assing, Karin Dahl, Costello, Richard W., Gibson, Peter G., Heffler, Enrico, Maspero, Jorge, Nicola, Stefania, Steve, Diahn-Warng Perng, Puggioni, Francesca, Salvi, Sundeep, Sheu, Chau-Chyun, Sirena, Concetta, Taille, Camille, Tan, Tze Lee, Bjermer, Leif, Canonica, Giorgio Walter, Iwanaga, Takashi, Jimenez-Maldonado, Libardo, Taube, Christian, Brussino, Luisa, Price, David B., Porsbjerg, Celeste M., Townend, John, Bergeron, Celine, Christoff, George C., Katsoulotos, Gregory P., Larenas-Linnemann, Desiree, Tran, Trung N., Al-Lehebi, Riyad, Bosnic-Anticevich, Sinthia Z., Busby, John, Hew, Mark, Kostikas, Konstantinos, Papadopoulos, Nikolaos G., Pfeffer, Paul E., Popov, Todor A., Rhee, Chin Kook, Sadatsafavi, Mohsen, Tsai, Ming-Ju, Ulrik, Charlotte Suppli, Al-Ahmad, Mona, Altraja, Alan, Beastall, Aaron, Bulathsinhala, Lakmini, Carter, Victoria, Cosio, Borja G., Fletton, Kirsty, Hansen, Susanne, Heaney, Liam G., Hubbard, Richard B., Kuna, Piotr, Murray, Ruth B., Nagano, Tatsuya, Pini, Laura, Rosales, Diana Jimena Cano, Schleich, Florence, Wechsler, Michael E., Amaral, Rita, Bourdin, Arnaud, Brusselle, Guy G., Chen, Wenjia, Chung, Li Ping, Denton, Eve, Fonseca, Joao A., Hoyte, Flavia, Jackson, David J., Katial, Rohit, Kirenga, Bruce J., Koh, Mariko Siyue, Lawkiedraj, Agnieszka, Lehtimaki, Lauri, Liew, Mei Fong, Mahboub, Bassam, Martin, Neil, Menzies-Gow, Andrew N., Pang, Pee Hwee, Papaioannou, Andriana I., Patel, Pujan H., Perez-De-Llano, Luis, Peters, Matthew J., Ricciardi, Luisa, Rodriguez-Caceres, Bellanid, Solarte, Ivan, Tay, Tunn Ren, Torres-Duque, Carlos A., Wang, Eileen, Zappa, Martina, Abisheganaden, John, Assing, Karin Dahl, Costello, Richard W., Gibson, Peter G., Heffler, Enrico, Maspero, Jorge, Nicola, Stefania, Steve, Diahn-Warng Perng, Puggioni, Francesca, Salvi, Sundeep, Sheu, Chau-Chyun, Sirena, Concetta, Taille, Camille, Tan, Tze Lee, Bjermer, Leif, Canonica, Giorgio Walter, Iwanaga, Takashi, Jimenez-Maldonado, Libardo, Taube, Christian, Brussino, Luisa, and Price, David B.

Abstract

Background: To date, studies investigating the association between pre-biologic biomarker levels and post-biologic outcomes have been limited to single biomarkers and assessment of biologic efficacy from structured clinical trials. Aim: To elucidate the associations of pre-biologic individual biomarker levels or their combinations with pre-to-post biologic changes in asthma outcomes in real-life. Methods: This was a registry-based, cohort study using data from 23 countries, which shared data with the International Severe Asthma Registry (May 2017-February 2023). The investigated biomarkers (highest pre-biologic levels) were immunoglobulin E (IgE), blood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO). Pre- to approximately 12-month post-biologic change for each of three asthma outcome domains (i.e. exacerbation rate, symptom control and lung function), and the association of this change with pre-biologic biomarkers was investigated for individual and combined biomarkers. Results: Overall, 3751 patients initiated biologics and were included in the analysis. No association was found between pre-biologic BEC and pre-to-post biologic change in exacerbation rate for any biologic class. However, higher pre-biologic BEC and FeNO were both associated with greater post-biologic improvement in FEV1 for both anti-IgE and anti-IL5/5R, with a trend for antiI-IL4R alpha. Mean FEV1 improved by 27-178 mL post-anti-IgE as pre-biologic BEC increased (250 to 1000 cells/mu L), and by 43-216 mL and 129-250 mL post-anti-IL5/5R and - anti- IL4R alpha, respectively along the same BEC gradient. Corresponding improvements along a FeNO gradient (25-100 ppb) were 41-274 mL, 69-207 mL and 148-224 mL for anti-IgE, anti-IL5/5R, and anti-IL4R alpha, respectively. Higher baseline BEC was also associated with lower probability of uncontrolled asthma (OR 0.392; p=0.001) post-biologic for anti-IL5/5R. Pre-biologic IgE was a poor predictor of subsequent pre-to-post-biologic change for

Published
2024
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285. Optically Stimulated Luminescence (OSL) Mortar Dating Inter-Comparison Study. The Second Round of Modis, Mortar Dating Inter-Comparison Study

Author

Sanjurjo-Sánchez, Jorge, Urbanová, Petra, Panzeri, Laura, Martini, Marco, Maspero, Francesco, Guibert, Pierre, Galli, Anna, Sanjurjo-Sánchez, Jorge, Urbanová, Petra, Panzeri, Laura, Martini, Marco, Maspero, Francesco, Guibert, Pierre, and Galli, Anna

Abstract

[Abstract] After an intercomparison age experiment carried out in the framework of the first MODIS (MOrtar Dating Inter-comparison Study) project, the results showed general agreement both between optically stimulated luminescence (OSL) dating laboratories and with radiocarbon (14C) dating results. As the needs for the selection of samples convenient for an inter-comparison are not the same between 14C and OSL, for the second running, it has been decided to choose two different sample sets, one to share between the radiocarbon labs and one for the OSL dating ones. The results obtained by applying different experimental protocols (multigrain and single grain techniques) and different statistical models (weighted mean, central age mode, average dose model, minimum age model and exponential exposure dose) are discussed in this work.

Published
2024

286. Deep-learning-based joint rigid and deformable contour propagation for magnetic resonance imaging-guided prostate radiotherapy

Author

Kolenbrander, I.D. (Iris), Maspero, M. (Matteo), Hendriksen, A.A. (Allard), Pollitt, R. (Ryan), Voort van Zyp, J.R.N. (Jochem) van der, Berg, C.A.T. (Cornelis) van den, Pluim, J.P.W. (Josien), Eijnatten, M.A.J.M. (Maureen) van, Kolenbrander, I.D. (Iris), Maspero, M. (Matteo), Hendriksen, A.A. (Allard), Pollitt, R. (Ryan), Voort van Zyp, J.R.N. (Jochem) van der, Berg, C.A.T. (Cornelis) van den, Pluim, J.P.W. (Josien), and Eijnatten, M.A.J.M. (Maureen) van

Abstract

Background: Deep learning-based unsupervised image registration has recently been proposed, promising fast registration. However, it has yet to be adopted in the online adaptive magnetic resonance imaging-guided radiotherapy (MRgRT) workflow. Purpose: In this paper, we design an unsupervised, joint rigid, and deformable registration framework for contour propagation in MRgRT of prostate cancer. Methods: Three-dimensional pelvic T2-weighted MRIs of 143 prostate cancer patients undergoing radiotherapy were collected and divided into 110, 13, and 20 patients for training, validation, and testing. We designed a framework using convolutional neural networks (CNNs) for rigid and deformable registration. We selected the deformable registration network architecture among U-Net, MS-D Net, and LapIRN and optimized the training strategy (end-to-end vs. sequential). The framework was compared against an iterative baseline registration. We evaluated registration accuracy (the Dice and Hausdorff distance of the prostate and bladder contours), structural similarity index, and folding percentage to compare the methods. We also evaluated the framework's robustness to rigid and elastic deformations and bias field perturbations. Results: The end-to-end trained framework comprising LapIRN for the deformable component achieved the best median (interquartile range) prostate and bladder Dice of 0.89 (0.85–0.91) and 0.86 (0.80–0.91), respectively. This accuracy was comparable to the iterative baseline registration: prostate and bladder Dice of 0.91 (0.88–0.93) and 0.86 (0.80–0.92). The best models complete rigid and deformable registration in 0.002 (0.0005) and 0.74 (0.43) s (Nvidia Tesla V100-PCIe 32 GB GPU), respectively. We found that the models are robust to translations up to 52 mm, rotations up to 15 (Formula presented.), elastic deformations up to 40 mm, and bias fields. Conclusions: Our proposed unsupervised, deep learning-based registration framework can perform rigid and deformab

Published
2024
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287. Generalizable synthetic MRI with physics-informed convolutional networks

Author

Radiotherapie, Computational Imaging, Cancer, Circulatory Health, Regenerative Medicine and Stem Cells, Jacobs, Luuk, Mandija, Stefano, Liu, Hongyan, van den Berg, Cornelis A T, Sbrizzi, Alessandro, Maspero, Matteo, Radiotherapie, Computational Imaging, Cancer, Circulatory Health, Regenerative Medicine and Stem Cells, Jacobs, Luuk, Mandija, Stefano, Liu, Hongyan, van den Berg, Cornelis A T, Sbrizzi, Alessandro, and Maspero, Matteo

Published
2024

288. Deep-learning-based joint rigid and deformable contour propagation for magnetic resonance imaging-guided prostate radiotherapy

Author

Computational Imaging, Radiotherapie, MS Radiotherapie, Cancer, Kolenbrander, Iris D, Maspero, Matteo, Hendriksen, Allard A, Pollitt, Ryan, van der Voort van Zyp, Jochem R N, van den Berg, Cornelis A T, Pluim, Josien P W, van Eijnatten, Maureen A J M, Computational Imaging, Radiotherapie, MS Radiotherapie, Cancer, Kolenbrander, Iris D, Maspero, Matteo, Hendriksen, Allard A, Pollitt, Ryan, van der Voort van Zyp, Jochem R N, van den Berg, Cornelis A T, Pluim, Josien P W, and van Eijnatten, Maureen A J M

Published
2024

289. In-vitro dehydration kinetics coefficient of Kalifilcon A and other contact lens materials

Author

Ponzini, E, Maspero, F, Galli, A, Tavazzi, S, Ponzini, E, Maspero, F, Galli, A, and Tavazzi, S

Abstract

In contact lens (CL) wear, dehydration needs to be tailored to avoid dryness and related symptoms. In this view, this work aims to assess and compare the in-vitro dehydration kinetics of five CL materials, including the newly developed Kalifilcon A CL. At 36 °C and 60% relative humidity, the in-vitro dehydration kinetics of the different CLs were compared using a gravimetric method. CLs were analyzed either after a rinse of a few seconds in preservative-free saline solution or after a 24-h incubation in the same solution. A model based on the Fick diffusion equation was employed to deduce a water kinetics coefficient, providing insights into water diffusion within the polymeric matrix. The study reveals that all materials exhibit a non-Fickian dehydration behavior, with significant differences in dehydration kinetics coefficients and dehydration rate slopes. Etafilcon A and Omafilcon A, both hydrogel CLs, exhibit a similar behavior, different compared to the pattern shown by Senofilcon A and Delefilcon A, silicone-hydrogel CLs. Notably, Kalifilcon A, despite being a silicone-hydrogel, displays a hydration behavior reminiscent of hydrogel CLs.

Published
2024

293. Synchronization Effects in a Metabolism-Driven Model of Multi-cellular System

Author

Maspero, Davide, Graudenzi, Alex, Singh, Satwinder, Pescini, Dario, Mauri, Giancarlo, Antoniotti, Marco, Damiani, Chiara, Barbosa, Simone Diniz Junqueira, Editorial Board Member, Filipe, Joaquim, Editorial Board Member, Ghosh, Ashish, Editorial Board Member, Kotenko, Igor, Editorial Board Member, Yuan, Junsong, Editorial Board Member, Zhou, Lizhu, Editorial Board Member, Cagnoni, Stefano, editor, Mordonini, Monica, editor, Pecori, Riccardo, editor, Roli, Andrea, editor, and Villani, Marco, editor

Published
2019
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294. VirMutSig: Discovery and assignment of viral mutational signatures from sequencing data

Author

Davide Maspero, Fabrizio Angaroni, Danilo Porro, Rocco Piazza, Alex Graudenzi, and Daniele Ramazzotti

Subjects
Bioinformatics, Sequence analysis, Genomics, Sequencing, RNAseq, Systems biology, Science (General), Q1-390
Abstract

Summary: We describe the procedures to perform the following: (1) the de novo discovery of mutational signatures from raw sequencing data of viral samples and (2) the association of existing viral mutational signatures to the samples of a given dataset. The goal is to identify and characterize the nucleotide substitution patterns related to the mutational processes that underlie the origination of variants in viral genomes. The VirMutSig protocol is available at this link: https://github.com/BIMIB-DISCo/VirMutSig.For complete information on the theoretical aspects of this protocol, please refer to Graudenzi et al. (2021).

Published
2021
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298. Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials

Author

Bachert, Claus, Han, Joseph K, Desrosiers, Martin, Hellings, Peter W, Amin, Nikhil, Lee, Stella E, Mullol, Joaquim, Greos, Leon S, Bosso, John V, Laidlaw, Tanya M, Cervin, Anders U, Maspero, Jorge F, Hopkins, Claire, Olze, Heidi, Canonica, G Walter, Paggiaro, Pierluigi, Cho, Seong H, Fokkens, Wytske J, Fujieda, Shigeharu, Zhang, Mei, Lu, Xin, Fan, Chunpeng, Draikiwicz, Steven, Kamat, Siddhesh A, Khan, Asif, Pirozzi, Gianluca, Patel, Naimish, Graham, Neil M H, Ruddy, Marcella, Staudinger, Heribert, Weinreich, David, Stahl, Neil, Yancopoulos, George D, and Mannent, Leda P

Published
2019
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