585 results on '"Gianni S"'
Search Results
2. Exploring the short linear motif-mediated protein-protein interactions of CrkL through ProP-PD
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Pagano, L., Simonetti, Leandro, Pennacchietti, V., Toto, A., Malagrino, F., Ivarsson, Ylva, Gianni, S., Pagano, L., Simonetti, Leandro, Pennacchietti, V., Toto, A., Malagrino, F., Ivarsson, Ylva, and Gianni, S.
- Abstract
Adaptor proteins play a pivotal role in cellular signaling mediating a multitude of protein-protein interaction critical for cellular homeostasis. Dysregulation of these interactions has been linked to the onset of various cancer pathologies and exploited by viral pathogens during host cell takeover. CrkL is an adaptor protein composed of an N-terminal SH2 domain followed by two SH3 domains that mediate interactions with diverse partners through the recognition of specific binding motifs. In this study, we employed proteomic peptide-phage display (ProP-PD) to comprehensively explore the short linear motif (SLiM)-based interactions of CrkL. Furthermore, we scrutinized how the binding affinity for selected peptides was influenced in the context of the full-length CrkL versus the isolated N-SH3 domain. Importantly, our results provided insights into SLiM-binding sites within previously reported interactors, as well as revealing novel human and viral ligands, expanding our understanding of the interactions mediated by CrkL and highlighting the significance of SLiM-based interactions in mediating adaptor protein function, with implications for cancer and viral pathologies.
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- 2024
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3. Inhaled nitric oxide (iNO) administration in intubated and nonintubated patients: Delivery systems, interfaces, dose administration, and monitoring techniques
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Morbidelli, L, Muntané, J, Gianni, S, Berra, L, Rezoagli, E, Gianni S., Berra L., Rezoagli E., Morbidelli, L, Muntané, J, Gianni, S, Berra, L, Rezoagli, E, Gianni S., Berra L., and Rezoagli E.
- Abstract
Inhaled nitric oxide (iNO) is a drug used to treat neonates with persistent pulmonary hypertension and as a rescue strategy for the treatment of severe hypoxemia. The clinical administration of iNO is challenging since the patient population is heterogeneous, ranging from critically ill patients intubated and mechanically ventilated to patients with chronic pulmonary hypertension receiving iNO at home [8]. In the intubated mechanically ventilated patients, airways are sealed by a cuffed endotracheal tube. Therefore, it is possible to precisely reach and maintain the target iNO concentration. Conversely, in nonintubated spontaneously breathing patients, the patient airways are not sealed by a cuffed endotracheal tube, so the instantaneous delivered dose cannot be accurately determined. A snug-fitting mask can be used to deliver NO as a patient interface in hospitalized patients with acute bacterial or viral pneumonia. In patients requiring long-term iNO administration, nasal cannula can be a suitable patient interface, which is also often used for long-term oxygen administration. To safely administer iNO, the continuous monitoring of the delivered NO and nitrogen dioxide (NO2) concentrations is recommended to avoid excessive NO2 delivery that is irritant for the airways. Further, blood oxygenation and methemoglobin concentration monitoring have to be considered during iNO administration to ensure an adequate tissue oxygenation.
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- 2023
4. ABCB1 c.-6-180T > G polymorphism and clinical risk factors in a multi-breed cohort of dogs with refractory idiopathic epilepsy
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Gagliardo, T., Gandini, G., Gallucci, A., Menchetti, M., Bianchi, E., Turba, M.E., Cauduro, A., Corlazzoli, D.S., Gianni, S., Baroni, M., Bernardini, M., and Gentilini, F.
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- 2019
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5. An X-ray view of the INTEGRAL/IBIS blazars
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Gianni', S., De Rosa, A., Bassani, L., Bazzano, A., Dean, A. J., and Ubertini, P.
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Astrophysics - Cosmology and Nongalactic Astrophysics - Abstract
Aim of this work is a broad-band study with INTEGRAL, Swift and XMM-Newton satellites of a sample of 9 blazars (7 FSRQ and 2 BL Lac) with redshift up to about 4. The spectral analysis has shown clear evidence of a flattening of the continuum towards the low energies ($E<3$ keV observer frame). This behaviour is well reproduced both with an absorbed power-law model ($N_H\sim10^{20}$-$10^{23}$ cm$^{-2}$ in the rest-frame of the sources) or a broken power-law continuum model (with an energy break below 3 keV in the observer-frame). No Compton reflection features, Fe $K\alpha$ line and hump at high energies, have been detected, with the exception of the source IGR J22517+2218 that shows the presence of a weak iron line. In this work we also investigate a possible correlation between the absorption column density $N_H$ and the red-shift. We confirm the existence of a $N_H$-z trend, with the higher absorption at z$>$2 for a larger sample compared to previous results. The distribution of the $N_H$ and the photon index $\Gamma$ is also presented. The hard X-ray data allow us to detect highly absorbed sources (with $N_H\ge10^{23}$cm$^{-2}$ in rest-frame of the source) characterized by photon index distribution peaked at harder values ($\Gamma\sim1.4$) with respect to that obtained with XMM data only ($\Gamma\sim2$)., Comment: accepted for publication in MNRAS
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- 2010
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6. Monstruos, putas o víctimas. La representación literaria de la mujer criminal en dos autoras mexicanas contemporáneas: Brenda Navarro y Norma Lazo
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Salazar Ugarte, P, Gonzalez Luna Corvera, AM, Raphael De La Madrid, L, Melgar Palacios, L, Monrarrez Fragoso, LE, Gianni, S, Gago, V, Borzacchiello, E, Dova, M, Pecorella, C, Fernandez Chagoya, M, Lima Paiva, L, Brown, J, Gonzalez Barrera, MP, Mendoza Antunez, C, González Luna Corvera, AM, Raphael De la Madrid, L., Gonzalez Luna Corvera, A, Salazar Ugarte, P, Gonzalez Luna Corvera, AM, Raphael De La Madrid, L, Melgar Palacios, L, Monrarrez Fragoso, LE, Gianni, S, Gago, V, Borzacchiello, E, Dova, M, Pecorella, C, Fernandez Chagoya, M, Lima Paiva, L, Brown, J, Gonzalez Barrera, MP, Mendoza Antunez, C, González Luna Corvera, AM, Raphael De la Madrid, L., and Gonzalez Luna Corvera, A
- Abstract
Las distintas representaciones de mujeres delincuentes inscritas en relatos literarios inspirados en un crimen -real o o imaginario - configuran una caracterización tanto del delito como de los sujetos femeninos. En dicha narrativa las mujeres delincuentes suelen ser el revés o la contracara de las víctimas; son percibidas como la cara oscura de la feminidad, reforzando así el arquetipo de la mujer como sujeto pasivo y pacífico. De esta manera se establece un tabú sobre la violencia femenina y se construyen una serie de estereotipos sobre las mujeres violentas que las desnaturaliza y las transforma en la negación del propio género. Este ser 'contro natura' las hace aún más peligrosas, letales y malvadas. La imposibilidad de admitir la potencialidad de las mujeres de ejercer la violencia lleva a la invisibilidad o al sensacionalismo: las mujeres criminales son inexistentes o monstruos deshumanos. Se propone el texto literario como espacio en el que es posible preguntarse sobre el origen de la violencia y cuestionar críticamente el estereotipo social que impone a la mujer pacífica, pasiva y víctima de la violencia masculina. Un espacio en el cual no hay verdades absolutas, pero en el que es posible imaginarnos de otra manera, indagar en los motivos oscuros del acto criminal abriendo pistas interpretativas inéditas, dando voz a personajes olvidados, invisibles.
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- 2023
7. La responsabilidad penal de las mujeres por delitos de empresa o asociacion delictiva: madres, hijas, esposas y novias ante los jueces
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Monarrez Fragoso, J E, Gonzalez Luna, A M, Gianni, S, Gago, V, Borzacchiello, E, Dova, M, Fernandez Chagoya, M, Lima Paiva, L, Brown, J, Gonzalez Barreda, M, Mendoza Antunez, C A., Raphael de la Madrid, L, Melgar Palacios, L, Pecorella, C, Monarrez Fragoso, J E, Gonzalez Luna, A M, Gianni, S, Gago, V, Borzacchiello, E, Dova, M, Fernandez Chagoya, M, Lima Paiva, L, Brown, J, Gonzalez Barreda, M, Mendoza Antunez, C A., Raphael de la Madrid, L, Melgar Palacios, L, and Pecorella, C
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- 2023
8. 377 Sentinel node detection in gynecology oncology: our experience with indocyanine green (ICG)
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Nico, A, Lay, L, Zeff, N, Sanchez, A, Cuellar, S, San Martín, G, Zarlenga, C, Lupo, E, Gianni, S, and Ostojich, M
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- 2019
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9. Sigh in patients with acute hypoxemic respiratory failure and acute respiratory distress syndrome: the PROTECTION pilot randomized clinical trial
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Mauri, T, Foti, G, Fornari, C, Grasselli, G, Pinciroli, R, Lovisari, F, Tubiolo, D, Volta, C, Spadaro, S, Rona, R, Rondelli, E, Navalesi, P, Garofalo, E, Knafelj, R, Gorjup, V, Colombo, R, Cortegiani, A, Zhou, J, D'Andrea, R, Calamai, I, Gonzalez, A, Roca, O, Grieco, D, Jovaisa, T, Bampalis, D, Becher, T, Battaglini, D, Ge, H, Luz, M, Constantin, J, Ranieri, M, Guerin, C, Mancebo, J, Pelosi, P, Fumagalli, R, Brochard, L, Pesenti, A, Papoff, A, Di Fenza, R, Gianni, S, Spinelli, E, Lissoni, A, Abbruzzese, C, Bronco, A, Villa, S, Russotto, V, Iachi, A, Ball, L, Patroniti, N, Spina, R, Giuntini, R, Peruzzi, S, Menga, L, Fossali, T, Castelli, A, Ottolina, D, Garcia-De-Acilu, M, Santafe, M, Schadler, D, Weiler, N, Carvajal, E, Calvo, C, Neou, E, Wang, Y, Zhou, Y, Longhini, F, Bruni, A, Leonardi, M, Gregoretti, C, Ippolito, M, Milazzo, Z, Querci, L, Ranieri, S, Insom, G, Berden, J, Noc, M, Mikuz, U, Arzenton, M, Lazzeri, M, Villa, A, Barreto, B, Rios, M, Gusmao-Flores, D, Phull, M, Barnes, T, Musarat, H, Conti, S, Mauri T., Foti G., Fornari C., Grasselli G., Pinciroli R., Lovisari F., Tubiolo D., Volta C. A., Spadaro S., Rona R., Rondelli E., Navalesi P., Garofalo E., Knafelj R., Gorjup V., Colombo R., Cortegiani A., Zhou J. -X., D'Andrea R., Calamai I., Gonzalez A. V., Roca O., Grieco D. L., Jovaisa T., Bampalis D., Becher T., Battaglini D., Ge H., Luz M., Constantin J. -M., Ranieri M., Guerin C., Mancebo J., Pelosi P., Fumagalli R., Brochard L., Pesenti A., Papoff A., Di Fenza R., Gianni S., Spinelli E., Lissoni A., Abbruzzese C., Bronco A., Villa S., Russotto V., Iachi A., Ball L., Patroniti N., Spina R., Giuntini R., Peruzzi S., Menga L. S., Fossali T., Castelli A., Ottolina D., Garcia-De-Acilu M., Santafe M., Schadler D., Weiler N., Carvajal E. R., Calvo C. P., Neou E., Wang Y. -M., Zhou Y. -M., Longhini F., Bruni A., Leonardi M., Gregoretti C., Ippolito M., Milazzo Z., Querci L., Ranieri S., Insom G., Berden J., Noc M., Mikuz U., Arzenton M., Lazzeri M., Villa A., Barreto B. B., Rios M. N. O., Gusmao-Flores D., Phull M., Barnes T., Musarat H., Conti S., Mauri, T, Foti, G, Fornari, C, Grasselli, G, Pinciroli, R, Lovisari, F, Tubiolo, D, Volta, C, Spadaro, S, Rona, R, Rondelli, E, Navalesi, P, Garofalo, E, Knafelj, R, Gorjup, V, Colombo, R, Cortegiani, A, Zhou, J, D'Andrea, R, Calamai, I, Gonzalez, A, Roca, O, Grieco, D, Jovaisa, T, Bampalis, D, Becher, T, Battaglini, D, Ge, H, Luz, M, Constantin, J, Ranieri, M, Guerin, C, Mancebo, J, Pelosi, P, Fumagalli, R, Brochard, L, Pesenti, A, Papoff, A, Di Fenza, R, Gianni, S, Spinelli, E, Lissoni, A, Abbruzzese, C, Bronco, A, Villa, S, Russotto, V, Iachi, A, Ball, L, Patroniti, N, Spina, R, Giuntini, R, Peruzzi, S, Menga, L, Fossali, T, Castelli, A, Ottolina, D, Garcia-De-Acilu, M, Santafe, M, Schadler, D, Weiler, N, Carvajal, E, Calvo, C, Neou, E, Wang, Y, Zhou, Y, Longhini, F, Bruni, A, Leonardi, M, Gregoretti, C, Ippolito, M, Milazzo, Z, Querci, L, Ranieri, S, Insom, G, Berden, J, Noc, M, Mikuz, U, Arzenton, M, Lazzeri, M, Villa, A, Barreto, B, Rios, M, Gusmao-Flores, D, Phull, M, Barnes, T, Musarat, H, Conti, S, Mauri T., Foti G., Fornari C., Grasselli G., Pinciroli R., Lovisari F., Tubiolo D., Volta C. A., Spadaro S., Rona R., Rondelli E., Navalesi P., Garofalo E., Knafelj R., Gorjup V., Colombo R., Cortegiani A., Zhou J. -X., D'Andrea R., Calamai I., Gonzalez A. V., Roca O., Grieco D. L., Jovaisa T., Bampalis D., Becher T., Battaglini D., Ge H., Luz M., Constantin J. -M., Ranieri M., Guerin C., Mancebo J., Pelosi P., Fumagalli R., Brochard L., Pesenti A., Papoff A., Di Fenza R., Gianni S., Spinelli E., Lissoni A., Abbruzzese C., Bronco A., Villa S., Russotto V., Iachi A., Ball L., Patroniti N., Spina R., Giuntini R., Peruzzi S., Menga L. S., Fossali T., Castelli A., Ottolina D., Garcia-De-Acilu M., Santafe M., Schadler D., Weiler N., Carvajal E. R., Calvo C. P., Neou E., Wang Y. -M., Zhou Y. -M., Longhini F., Bruni A., Leonardi M., Gregoretti C., Ippolito M., Milazzo Z., Querci L., Ranieri S., Insom G., Berden J., Noc M., Mikuz U., Arzenton M., Lazzeri M., Villa A., Barreto B. B., Rios M. N. O., Gusmao-Flores D., Phull M., Barnes T., Musarat H., and Conti S.
- Abstract
Background: Sigh is a cyclic brief recruitment maneuver: previous physiologic studies showed that its use could be an interesting addition to pressure support ventilation to improve lung elastance, decrease regional heterogeneity, and increase release of surfactant. Research Question: Is the clinical application of sigh during pressure support ventilation (PSV) feasible? Study Design and Methods: We conducted a multicenter noninferiority randomized clinical trial on adult intubated patients with acute hypoxemic respiratory failure or ARDS undergoing PSV. Patients were randomized to the no-sigh group and treated by PSV alone, or to the sigh group, treated by PSV plus sigh (increase in airway pressure to 30 cm H2O for 3 s once per minute) until day 28 or death or successful spontaneous breathing trial. The primary end point of the study was feasibility, assessed as noninferiority (5% tolerance) in the proportion of patients failing assisted ventilation. Secondary outcomes included safety, physiologic parameters in the first week from randomization, 28-day mortality, and ventilator-free days. Results: Two-hundred and fifty-eight patients (31% women; median age, 65 [54-75] years) were enrolled. In the sigh group, 23% of patients failed to remain on assisted ventilation vs 30% in the no-sigh group (absolute difference, –7%; 95% CI, –18% to 4%; P =. 015 for noninferiority). Adverse events occurred in 12% vs 13% in the sigh vs no-sigh group (P =. 852). Oxygenation was improved whereas tidal volume, respiratory rate, and corrected minute ventilation were lower over the first 7 days from randomization in the sigh vs no-sigh group. There was no significant difference in terms of mortality (16% vs 21%; P =. 337) and ventilator-free days (22 [7-26] vs 22 [3-25] days; P =. 300) for the sigh vs no-sigh group. Interpretation: Among hypoxemic intubated ICU patients, application of sigh was feasible and without increased risk.
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- 2021
10. SAFETY AND EFFICACY OF INHALED HIGH-DOSE NITRIC OXIDE IN NON-INTUBATED PATIENTS WITH COVID-19 PNEUMONIA
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SAFAEE FAKHR, B., primary, DI FENZA, R., additional, GIANNI, S., additional, WIEGAND, S., additional, MIYAZAKI, Y., additional, ARAUJO MORAIS, C., additional, GIBSON, L., additional, CHANG, M., additional, MUELLER, A., additional, RODRIGUEZ-LOPEZ, J., additional, ACKMAN, J., additional, ARORA, P., additional, SCOTT, L., additional, BLOCH, D., additional, ZAPOL, W., additional, CARROLL, R., additional, ICHINOSE, F., additional, and BERRA, L., additional
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- 2022
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11. High Concentrations of Nitric Oxide Inhalation Therapy in Pregnant Patients With Severe Coronavirus Disease 2019 (COVID-19)
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Safaee Fakhr, B, Wiegand, S, Pinciroli, R, Gianni, S, Morais, C, Ikeda, T, Miyazaki, Y, Marutani, E, Di Fenza, R, Larson, G, Parcha, V, Gibson, L, Chang, M, Arora, P, Carroll, R, Kacmarek, R, Ichinose, F, Barth, W, Kaimal, A, Hohmann, E, Zapol, W, Berra, L, Safaee Fakhr B., Wiegand S. B., Pinciroli R., Gianni S., Morais C. C. A., Ikeda T., Miyazaki Y., Marutani E., Di Fenza R., Larson G. M., Parcha V., Gibson L. E., Chang M. G., Arora P., Carroll R. W., Kacmarek R. M., Ichinose F., Barth W. H., Kaimal A., Hohmann E. L., Zapol W. M., Berra L., Safaee Fakhr, B, Wiegand, S, Pinciroli, R, Gianni, S, Morais, C, Ikeda, T, Miyazaki, Y, Marutani, E, Di Fenza, R, Larson, G, Parcha, V, Gibson, L, Chang, M, Arora, P, Carroll, R, Kacmarek, R, Ichinose, F, Barth, W, Kaimal, A, Hohmann, E, Zapol, W, Berra, L, Safaee Fakhr B., Wiegand S. B., Pinciroli R., Gianni S., Morais C. C. A., Ikeda T., Miyazaki Y., Marutani E., Di Fenza R., Larson G. M., Parcha V., Gibson L. E., Chang M. G., Arora P., Carroll R. W., Kacmarek R. M., Ichinose F., Barth W. H., Kaimal A., Hohmann E. L., Zapol W. M., and Berra L.
- Abstract
BACKGROUND: Rescue therapies to treat or prevent progression of coronavirus disease 2019 (COVID-19) hypoxic respiratory failure in pregnant patients are lacking. METHOD: To treat pregnant patients meeting criteria for severe or critical COVID-19 with high-dose (160-200 ppm) nitric oxide by mask twice daily and report on their clinical response. EXPERIENCE: Six pregnant patients were admitted with severe or critical COVID-19 at Massachusetts General Hospital from April to June 2020 and received inhalational nitric oxide therapy. All patients tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A total of 39 treatments was administered. An improvement in cardiopulmonary function was observed after commencing nitric oxide gas, as evidenced by an increase in systemic oxygenation in each administration session among those with evidence of baseline hypoxemia and reduction of tachypnea in all patients in each session. Three patients delivered a total of four neonates during hospitalization. At 28-day follow-up, all three patients were home and their newborns were in good condition. Three of the six patients remain pregnant after hospital discharge. Five patients had two negative test results on nasopharyngeal swab for SARS-CoV-2 within 28 days from admission. CONCLUSION: Nitric oxide at 160-200 ppm is easy to use, appears to be well tolerated, and might be of benefit in pregnant patients with COVID-19 with hypoxic respiratory failure.
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- 2020
12. Ideation and assessment of a nitric oxide delivery system for spontaneously breathing subjects
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Gianni, S, Morais, C, Larson, G, Pinciroli, R, Carroll, R, Yu, B, Zapol, W, Berra, L, Gianni S., Morais C. C. A., Larson G., Pinciroli R., Carroll R., Yu B., Zapol W. M., Berra L., Gianni, S, Morais, C, Larson, G, Pinciroli, R, Carroll, R, Yu, B, Zapol, W, Berra, L, Gianni S., Morais C. C. A., Larson G., Pinciroli R., Carroll R., Yu B., Zapol W. M., and Berra L.
- Abstract
Background: There is an increasing interest in safely delivering high dose of inhaled nitric oxide (NO) as an antimicrobial and antiviral therapeutics for spontaneously breathing patients. A novel NO delivery system is described. Methods: We developed a gas delivery system that utilizes standard respiratory circuit connectors, a reservoir bag, and a scavenging chamber containing calcium hydroxide. The performance of the system was tested using a mechanical lung, assessing the NO concentration delivered at varying inspiratory flows. Safety was assessed in vitro and in vivo by measuring nitrogen dioxide (NO2) levels in the delivered NO gas. Lastly, we measured the inspired and expired NO and NO2 of this system in 5 healthy subjects during a 15-min administration of high dose NO (160 parts-per-million, ppm) using our delivery system. Results: The system demonstrated stable delivery of prescribed NO levels at various inspiratory flow rates (0–50 L/min). The reservoir bag and a high flow of entering air minimized the oscillation of NO concentrations during inspiration on average 4.6 ppm for each 10 L/min increment in lung inspiratory flow. The calcium hydroxide scavenger reduced the inhaled NO2 concentration on average 0.9 ppm (95% CI -1.58, −0.22; p =.01). We performed 49 NO administrations of 160 ppm in 5 subjects. The average concentration of inspired NO was 164.8±10.74 ppm, with inspired NO2 levels of 0.7±0.13 ppm. The subjects did not experience any adverse events; transcutaneous methemoglobin concentrations increased from 1.05±0.58 to 2.26±0.47%. Conclusions: The system we developed to administer high-dose NO for inhalation is easy to build, reliable, was well tolerated in healthy subjects.
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- 2020
13. Patata Rossa di Colfiorito IGP (Solanum tuberosum, L.) and health-promoting potentialities: Do cooking techniques and storage affect chemical profile and antioxidant activity?
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Mattia Acito, Agnese Santanatoglia, Cristina Fatigoni, Milena Villarini, Giovanni Caprioli, Gianni Sagratini, Iolanda Grappasonni, and Massimo Moretti
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Patata Rossa di Colfiorito ,Potato ,HPLC-ESI-MS/MS ,Antioxidant activity ,Cooking procedures ,Human health ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Acting as ‘antioxidants’, phenolic compounds have been shown to have a potential protective effect against a wide range of noncommunicable diseases. However, their content in plant-based products – and, in turn, their potential benefits – might be affected by the thermal procedures used in food cooking. In light of this, the aim of this work was a characterization of Patata Rossa di Colfiorito (PRC, an Italian PGI red-skinned potato) and an investigation of the impact of cooking and storage on its bioactive compounds, phenolic content, and antioxidant activity. After the harvesting (T0), samples were analyzed using instrumental analysis (e.g., HPLC-ESI-MS/MS) and a set of chemical assays (total phenolic content, 2,2-Diphenyl-1-picrylhydrazyl – DPPH, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) – ABTS, and oxygen radical absorbance capacity – ORAC assays). Analyses were also performed on boiled, pressure-cooked and one-month-stored (T1) products. A commercial red-skinned potato (RSP) was also analyzed.Overall, compared with the raw product, both boiling and pressure-cooking led to a significant increase in bioactive compounds (raw: 168.15 mg kg−1 of fresh matter, FM; boiled: 398.92 mg kg−1 FM; pressure-cooked: 309.24 mg kg−1 FM), total phenolic content and antioxidant activity measured by DPPH and ABTS assays.PRC samples showed higher content in bioactive compounds, TPC values and antioxidant activity compared with commercial RSP (with some sporadic exceptions in ORAC values). Interestingly, one month of domestic storage did not affect the freshly harvested product’s features.In conclusion, these results highlighted the quality of this local product and its property to withstand thermal processing and storage. We believe that the results we have obtained should be taken into consideration by health professionals, at both local and national levels, and that PRC deserves to be further studied to investigate its potential human health benefits, as well.
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- 2024
- Full Text
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14. Folding and Misfolding of a PDZ Tandem Repeat: Folding of a PDZ tandem
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Visconti L., Malagrino Francesca., Troilo F., Pagano L., Toto A., Gianni S., Visconti, L., Malagrino, Francesca., Troilo, F., Pagano, L., Toto, A., and Gianni, S.
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multidomain protein folding ,PDZ Domain ,Tandem Repeat Sequence ,Protein Folding ,Protein Conformation ,kinetic ,folding intermediate ,Amino Acid Sequence ,Whirlin ,Membrane Protein ,Human ,Protein Binding - Abstract
Although the vast majority of the human proteome is represented by multi-domain proteins, the study of multi-domain folding and misfolding is a relatively poorly explored field. The protein Whirlin is a multi-domain scaffolding protein expressed in the inner ear. It is characterized by the presence of tandem repeats of PDZ domains. The first two PDZ domains of Whirlin (PDZ1 and PDZ2 – namely P1P2) are structurally close and separated by a disordered short linker. We recently described the folding mechanism of the P1P2 tandem. The difference in thermodynamic stability of the two domains allowed us to selectively unfold one or both PDZ domains and to pinpoint the accumulation of a misfolded intermediate, which we demonstrated to retain physiological binding activity. In this work, we provide an extensive characterization of the folding and unfolding of P1P2. Based on the observed data, we describe an integrated kinetic analysis that satisfactorily fits the experiments and provides a valuable model to interpret multi-domain folding. The experimental and analytical approaches described in this study may be of general interest for the interpretation of complex multi-domain protein folding kinetics.
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- 2021
15. Comparing the binding properties of peptides mimicking the Envelope protein of SARS-CoV and SARS-CoV-2 to the PDZ domain of the tight junction-associated PALS1 protein
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Toto A., Ma S., Malagrino Francesca., Visconti L., Pagano L., Stromgaard K., Gianni S., Toto, A., Ma, S., Malagrino, Francesca., Visconti, L., Pagano, L., Stromgaard, K., and Gianni, S.
- Subjects
Models, Molecular ,PDZ Domain ,binding ,SARS Viru ,Betacoronaviru ,Pandemic ,PALS1 ,SARS-CoV-2 ,Coronavirus Infection ,Pneumonia, Viral ,kinetic ,Binding Site ,COVID-19 ,Severe Acute Respiratory Syndrome ,envelope protein ,Viral Envelope Proteins ,Peptide ,PDZ ,Coronavirus Envelope Protein ,Amino Acid Sequence ,Nucleoside-Phosphate Kinase ,Membrane Protein ,Human ,Protein Binding - Abstract
The Envelope protein (E) is one of the four structural proteins encoded by the genome of SARS-CoV and SARS-CoV-2 Coronaviruses. It is an integral membrane protein, highly expressed in the host cell, which is known to have an important role in Coronaviruses maturation, assembly and virulence. The E protein presents a PDZ-binding motif at its C-terminus. One of the key interactors of the E protein in the intracellular environment is the PDZ containing protein PALS1. This interaction is known to play a key role in the SARS-CoV pathology and suspected to affect the integrity of the lung epithelia. In this paper we measured and compared the affinity of peptides mimicking the E protein from SARS-CoV and SARS-CoV-2 for the PDZ domain of PALS1, through equilibrium and kinetic binding experiments. Our results support the hypothesis that the increased virulence of SARS-CoV-2 compared to SARS-CoV may rely on the increased affinity of its Envelope protein for PALS1.
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- 2020
16. Sigh in patients with acute hypoxemic respiratory failure and acute respiratory distress syndrome: the PROTECTION pilot randomized clinical trial
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Mauri T., Foti G., Fornari C., Grasselli G., Pinciroli R., Lovisari F., Tubiolo D., Volta C. A., Spadaro S., Rona R., Rondelli E., Navalesi P., Garofalo E., Knafelj R., Gorjup V., Colombo R., Cortegiani A., Zhou J. -X., D'Andrea R., Calamai I., Gonzalez A. V., Roca O., Grieco D. L., Jovaisa T., Bampalis D., Becher T., Battaglini D., Ge H., Luz M., Constantin J. -M., Ranieri M., Guerin C., Mancebo J., Pelosi P., Fumagalli R., Brochard L., Pesenti A., Papoff A., Di Fenza R., Gianni S., Spinelli E., Lissoni A., Abbruzzese C., Bronco A., Villa S., Russotto V., Iachi A., Ball L., Patroniti N., Spina R., Giuntini R., Peruzzi S., Menga L. S., Fossali T., Castelli A., Ottolina D., Garcia-De-Acilu M., Santafe M., Schadler D., Weiler N., Carvajal E. R., Calvo C. P., Neou E., Wang Y. -M., Zhou Y. -M., Longhini F., Bruni A., Leonardi M., Gregoretti C., Ippolito M., Milazzo Z., Querci L., Ranieri S., Insom G., Berden J., Noc M., Mikuz U., Arzenton M., Lazzeri M., Villa A., Barreto B. B., Rios M. N. O., Gusmao-Flores D., Phull M., Barnes T., Musarat H., Conti S., Mauri, Tommaso, Foti, Giuseppe, Fornari, Carla, Grasselli, Giacomo, Pinciroli, Riccardo, Lovisari, Federica, Tubiolo, Daniela, Volta, Carlo Alberto, Spadaro, Savino, Rona, Roberto, Rondelli, Egle, Navalesi, Paolo, Garofalo, Eugenio, Knafelj, Rihard, Gorjup, Vojka, Colombo, Riccardo, Cortegiani, Andrea, Zhou, Jian-Xin, D'Andrea, Rocco, Calamai, Italo, González, Ánxela Vidal, Roca, Oriol, Grieco, Domenico Luca, Jovaisa, Toma, Bampalis, Dimitrio, Becher, Tobia, Battaglini, Denise, Ge, Huiqing, Luz, Mariana, Constantin, Jean-Michel, Ranieri, Marco, Guerin, Claude, Mancebo, Jordi, Pelosi, Paolo, Fumagalli, Roberto, Brochard, Laurent, Pesenti, Antonio, PROTECTION collaborators: Alessandra Papoff, Raffaele Di Fenza, Stefano Gianni, Elena Spinelli, Alfredo Lissoni, Chiara Abbruzzese, Alfio Bronco, Silvia Villa, Vincenzo Russotto, Arianna Iachi, Lorenzo Ball, Nicolò Patroniti, Rosario Spina, Romano Giuntini, Simone Peruzzi, Luca Salvatore Menga, Tommaso Fossali, Antonio Castelli, Davide Ottolina, Marina García-de-Acilu, Manel Santafè, Dirk Schädler, Norbert Weiler, Emilia Rosas Carvajal, César Pérez Calvo, Evangelia Neou, Yu-Mei Wang, Yi-Min Zhou, Federico Longhini, Andrea Bruni, Mariacristina Leonardi, Cesare Gregoretti, Mariachiara Ippolito, Zelia Milazzo, Lorenzo Querci, Serena Ranieri, Giulia Insom, Jernej Berden, Marko Noc, Ursa Mikuz, Matteo Arzenton, Marta Lazzeri, Arianna Villa, Bruna Brandão Barreto, Marcos Nogueira Oliveira Rios, Dimitri Gusmao-Flores, Mandeep Phull, Tom Barnes, Hussain Musarat, Sara Conti, Mauri, T, Foti, G, Fornari, C, Grasselli, G, Pinciroli, R, Lovisari, F, Tubiolo, D, Volta, C, Spadaro, S, Rona, R, Rondelli, E, Navalesi, P, Garofalo, E, Knafelj, R, Gorjup, V, Colombo, R, Cortegiani, A, Zhou, J, D'Andrea, R, Calamai, I, Gonzalez, A, Roca, O, Grieco, D, Jovaisa, T, Bampalis, D, Becher, T, Battaglini, D, Ge, H, Luz, M, Constantin, J, Ranieri, M, Guerin, C, Mancebo, J, Pelosi, P, Fumagalli, R, Brochard, L, Pesenti, A, Papoff, A, Di Fenza, R, Gianni, S, Spinelli, E, Lissoni, A, Abbruzzese, C, Bronco, A, Villa, S, Russotto, V, Iachi, A, Ball, L, Patroniti, N, Spina, R, Giuntini, R, Peruzzi, S, Menga, L, Fossali, T, Castelli, A, Ottolina, D, Garcia-De-Acilu, M, Santafe, M, Schadler, D, Weiler, N, Carvajal, E, Calvo, C, Neou, E, Wang, Y, Zhou, Y, Longhini, F, Bruni, A, Leonardi, M, Gregoretti, C, Ippolito, M, Milazzo, Z, Querci, L, Ranieri, S, Insom, G, Berden, J, Noc, M, Mikuz, U, Arzenton, M, Lazzeri, M, Villa, A, Barreto, B, Rios, M, Gusmao-Flores, D, Phull, M, Barnes, T, Musarat, H, and Conti, S
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pressure support ,ventilation ,sigh ,ARDS ,mechanical ventilation ,feasibility - Abstract
Background: Sigh is a cyclic brief recruitment manoeuvre: previous physiological studies showed that its use could be an interesting addition to pressure support ventilation to improve lung elastance, decrease regional heterogeneity and increase release of surfactant. Research question: Is the clinical application of sigh during pressure support ventilation (PSV) feasible? Study design and methods: We conducted a multi-center non-inferiority randomized clinical trial on adult intubated patients with acute hypoxemic respiratory failure or acute respiratory distress syndrome undergoing PSV. Patients were randomized to the No Sigh group and treated by PSV alone, or to the Sigh group, treated by PSV plus sigh (increase of airway pressure to 30 cmH2Ofor 3 seconds once per minute) until day 28 or death or successful spontaneous breathing trial. The primary endpoint of the study was feasibility, assessed as non-inferiority (5% tolerance) in the proportion of patients failing assisted ventilation. Secondary outcomes included safety, physiological parameters in the first week from randomization, 28-day mortality and ventilator-free days. Results: Two-hundred fifty-eight patients (31% women; median age 65 [54-75] years) were enrolled. In the Sigh group, 23% of patients failed to remain on assisted ventilation vs. 30% in the No Sigh group (absolute difference -7%, 95%CI -18% to 4%; p=0.015 for non-inferiority). Adverse events occurred in 12% vs. 13% in Sigh vs. No Sigh (p=0.852). Oxygenation was improved while tidal volume, respiratory rate and corrected minute ventilation were lower over the first 7 days from randomization in Sigh vs. No Sigh. There was no significant difference in terms of mortality (16% vs. 21%, p=0.342) and ventilator-free days (22 [7-26] vs. 22 [3-25] days, p=0.300) for Sigh vs. No Sigh. Interpretation: Among hypoxemic intubated ICU patients, application of sigh was feasible and without increased risk.
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- 2020
17. Enhancing the sensitivity of 3D printed sensors via ironing and void reduction
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Gianni Stano, Antonio Pavone, Md Abu Jafor, Khaled Matalgah, Gianluca Percoco, and Trevor J. Fleck
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Material extrusion ,3D printed sensors ,voids reduction ,smart structures ,Science ,Manufactures ,TS1-2301 - Abstract
ABSTRACTMaterial Extrusion (MEX) Additive Manufacturing (AM) has risen as a promising technology to monolithically manufacture smart structures with embedded sensors. Despite all the benefits of MEX AM, 3D printed piezoresistive sensors still suffer from low sensitivity, making them unsuitable for the detection of low values of force, displacement and bending angle. In the present paper, a simple, effective, and inexpensive method to increase the sensitivity in 3D printed sensors is proposed, based on the leveraging of the ironing strategy, which resulted in an improvement in the sensitivity of 83% compared to traditional process parameter selection. The ironing strategy reduced intralayer porosity by 59%, as verified by X-Ray CT. Additionally, the ironing strategy involves an increased healing time, which promotes the polymer chain diffusion between layers, which translated into a greater stability of the sensor when cyclically stressed. Smart structures capable of detecting small forces (0.19 N of resolution against 1.96 N for traditional MEX scenario) and smart auxetic devices have been manufactured, demonstrating the potential of the proposed approach. The present research demonstrates the ability to reduce interlayer voids by using an intrinsic feature of the MEX process and consequently improve electrical performance of 3D printed sensors.
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- 2024
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18. Surveillance for hepatocellular carcinoma in cirrhosis: is it cost-effective?
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Farinati, F and Gianni, S
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- 2001
19. HYPOXIA AND BIOMARKERS EXPRESSION IN CERVICAL CANCER (CC) AND HIGH GRADE SQUAMOUS INTRAEPITHELIAL LESIONS (HSIL): IGCS-0037 Cervical Cancer
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Ostojich, M. A., Gianni, S., Marino, L., Lupo, E., De Dios, D., Zeff, N., Lay, L., Damiani, F., Sanchez, A., Gimenez, L., and Jasnis, M. A.
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- 2015
20. Pushing with Soft Robotic Arms via Deep Reinforcement Learning
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Carlo Alessi, Diego Bianchi, Gianni Stano, Matteo Cianchetti, and Egidio Falotico
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dynamic control ,manipulation ,reinforcement learning ,sim‐to‐real ,soft robots ,system modeling ,Computer engineering. Computer hardware ,TK7885-7895 ,Control engineering systems. Automatic machinery (General) ,TJ212-225 - Abstract
Soft robots can adaptively interact with unstructured environments. However, nonlinear soft material properties challenge modeling and control. Learning‐based controllers that leverage efficient mechanical models are promising for solving complex interaction tasks. This article develops a closed‐loop pose/force controller for a dexterous soft manipulator enabling dynamic pushing tasks using deep reinforcement learning. Force tests investigate the mechanical properties of a soft robot module, resulting in orthogonal forces of 9−13 N. Then, the policy is trained in simulation leveraging a dynamic Cosserat rod model of the soft robot. Domain randomization mitigate the sim‐to‐real gap while careful reward engineering induced pose and force control even without explicit force inputs. Despite the approximate simulation, the sim‐to‐real transfer achieved an average reaching distance of 34±14 mm (8.1%L±3.4%L), an average orientation error of 0.40±0.29 rad (23°±17°) and applied pushing forces up to 3 N. Such performance is reasonable for the intended assistive tasks of the manipulator. The experiments uncovered that the soft robot interacting with the environment exhibited torsional and counter‐balancing movements. Although not explicitly enforced, they emerged from the mechanical intelligence of the manipulator. The results demonstrate the potential of soft robotic manipulation via reinforcement learning.
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- 2024
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21. Proteomics and bioinformatics analyses based on two-dimensional electrophoresis and LC-MS/MS for the primary characterization of protein changes in chicken breast meat from divergent farming systems: Organic versus antibiotic-free
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Laura Alessandroni, Gianni Sagratini, and Mohammed Gagaoua
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Chicken meat ,Proteomics ,Meat authenticity ,Meat proteome ,Biomarkers ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Proteomics is a key analytical method in meat research thanks to its potential in investigating the proteins at interplay in post-mortem muscles. This study aimed to characterize for the first time the differences in early post-mortem muscle proteomes of chickens raised under two farming systems: organic versus antibiotic-free. Forty post-mortem Pectoralis major muscle samples from two chicken strains (Ross 308 versus Ranger Classic) reared under organic versus antibiotic-free farming systems were characterized and compared using two-dimensional electrophoresis and LC-MS/MS mass spectrometry. Within antibiotic-free and organic farming systems, 14 and 16 proteins were differentially abundant between Ross 308 and Ranger Classic, respectively. Within Ross 308 and Ranger Classic chicken strains, 12 and 18 proteins were differentially abundant between organic and antibiotic-free, respectively. Bioinformatics was applied to investigate the molecular pathways at interplay, which highlighted the key role of muscle structure and energy metabolism. Antibiotic-free and organic farming systems were found to significantly impact the muscle proteome of chicken breast meat. This paper further proposes a primary list of putative protein biomarkers that can be used for chicken meat or farming system authenticity.
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- 2024
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22. Info-climate
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Folco Soffietti, Lucilla Calogero, Gianni Sinni, and Francesco Musco
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Environmental communication ,Infographics ,Climate change ,Sustainability ,Data ,Architectural drawing and design ,NA2695-2793 - Abstract
La presa di coscienza sui cambiamenti climatici, le politiche dello European Green Deal e il PNRR in Italia, hanno generato, tra il 2017 e il 2021, importanti cambi di paradigma strategico-legislativi. Il presente studio si interroga sulla comunicazione di questi temi tramite l’utilizzo degli strumenti dell’information design. Nello studio sono considerate infografiche prodotte in tre livelli di azione (globale, europeo, nazionale) da quattro istituzioni. L’obiettivo è verificarne la coerenza di contenuto e analizzare le strategie di visualizzazione del dato scientifico.
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- 2024
23. Prognostic analysis and outcomes of metastatic pancreatic cancer patients receiving nab‐paclitaxel plus gemcitabine as second or later‐line treatment
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Guido Giordano, Michele Milella, Matteo Landriscina, Francesca Bergamo, Giuseppe Tirino, Antonio Santaniello, Alberto Zaniboni, Enrico Vasile, Ferdinando De Vita, Giovanni Lo Re, Vanja Vaccaro, Elisa Giommoni, Donato Natale, Raffaele Conca, Daniele Santini, Luigi Maiorino, Gianni Sanna, Vincenzo Ricci, Aldo Iop, Vincenzo Montesarchio, Letizia Procaccio, Silvia Noventa, Roberto Bianco, Antonio Febbraro, Sara Lonardi, Giampaolo Tortora, Isabella Sperduti, and Davide Melisi
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FOLFIRINOX ,gemcitabine ,nab‐paclitaxel ,pancreatic cancer ,prognostic model ,second‐line chemotherapy ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Pancreatic cancer (PC) first‐line therapy often consists of polychemotherapy regimens, but choosing a second‐line therapy after disease progression, especially following first‐line FOLFIRINOX, remains a clinical challenge. This study presents results from a large, multicenter, retrospective analysis of Italian patients with metastatic PC (mPC) treated with Nab‐paclitaxel/Gemcitabine (AG) as second or later line of treatment. Main objective of the study is to identify prognostic factors that could inform treatment decisions. Methods The study included 160 mPC patients treated with AG in 17 Italian institutions. AG was administered according to labelling dose, until disease progression, unacceptable toxicity or patient refusal. Variations in schedules, dose modifications, supportive measures, and response evaluation were determined by individual clinicians' practice. Results AG was well‐tolerated and exhibited promising clinical activity. The overall response rate (ORR) and the disease control rate (DCR) were 22.5% and 45.6%, respectively. Median progression‐free survival (PFS) and overall survival (OS) were 3.9 and 6.8 months, respectively. Among the patients who received AG as a second‐line therapy (n = 111, 66.9%), median PFS and OS were 4.2 and 7.4 months, respectively. Notably, in the 76 patients (68%) receiving AG after first‐line FOLFIRINOX, an ORR of 19.7% and a DCR of 46.0% were observed, resulting in a median PFS of 3.5 and median OS of 5.7 months. The study identified specific clinical or laboratory parameters (LDH, NLR, fasting serum glucose, liver metastases, ECOG PS, and first‐line PFS) as independent prognostic factors at multivariate level. These factors were used to create a prognostic nomogram that divided patients into three risk classes, helping to predict second‐line OS and PFS. Conclusions This study represents the largest real‐world population of mPC patients treated with AG as a second or later line of therapy. It supports the feasibility of this regimen following first‐line FOLFIRINOX, particularly in patients with specific clinical and laboratory characteristics who derived prolonged benefit from first‐line therapy.
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- 2024
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24. Comparing 2-day vs 3-day flu-CY lymphodepleting regimens for CD19 CAR T-cell therapy in patients with non-hodgkin’s lymphoma
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David G. Frame, Marcus Geer, Salena Kasha, Denise Markstrom, Gianni Scappaticci, Tate Feeney, Andrew Hayduk, Hilary M. Mansoor, Avery Oberfeld, Hannah D’Antonio, Sarah Anand, Sung Won Choi, John Maciejewski, Attaphol Pawarode, Mary Mansour Riwes, Muneesh Tewari, John Magenau, and Monalisa Ghosh
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CAR T-cell ,non-hodgkin’s lymphoma ,lymphodepletion ,CRS ,ICANS ,Immunologic diseases. Allergy ,RC581-607 - Abstract
IntroductionLymphodepleting chemotherapy (LDC) is critical to CAR T-cell expansion and efficacy. Despite this, there is not a consensus in the literature regarding the optimal LDC regimen, including dose and frequency.MethodsWe retrospectively reviewed consecutive patients at a single institution that received LDC prior to treatment with the CD19 directed CAR T-cell products axicabtagene ciloleucel and tisagenlecleucel. Patients treated at our center received fludarabine 30 mg/m2 and cyclophosphamide 500 mg/m2 for 3 consecutive days prior to May 2019. After this timepoint patients routinely received fludarabine 40 mg/m2 and cyclophosphamide 500 mg/m2 for 2 consecutive days. Clinical data from each cohort were obtained from the electronic medical record and compared for differences in CAR T-cell efficacy and toxicity.ResultsFrom June 2018 to August 2023, LDC was given to 92 patients prior to CD19 directed CAR T-cell therapy for relapsed non-Hodgkin’s lymphoma. Twenty-eight patients received a 3-day regimen, and 64 patients received a 2-day regimen. In the total cohort, 75% of patients received axicabtagene ciloleucel and 25% received tisagenlecleucel. The overall response rates in both the 2-day regimen group and the 3-day regimen group were similar (69% vs 75%, p= 0.21) as were the complete response rates (50% vs 54%, p=0.82). There were no significant differences between the 2-day and 3-day regimens for grade 2–4 cytokine release syndrome (55% vs 50%, p=0.82), grade 2–4 immune effector cell associated-neurotoxicity syndrome (42% vs 29%, p=0.25), or time to resolution of neutropenia or thrombocytopenia. The rate of prolonged platelet recovery lasting greater than 60 days was higher with the 3-day regimen (9% vs 27%, p=0.026).DiscussionAs the number of patients eligible for CAR T-cell therapy continues to increase, optimizing each component of therapy is necessary. We show that a 2-day regimen of LDC with fludarabine and cyclophosphamide is feasible without significant impact on CAR T-cell efficacy or toxicity. Prospective studies are necessary to further determine the most effective LDC regimen.
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- 2024
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25. From 7-dehydrocholesterol to vitamin D3: Optimization of UV conversion procedures toward the valorization of fish waste matrices
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Yue Sun, Laura Alessandroni, Simone Angeloni, Erika Del Bianco, and Gianni Sagratini
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Vitamin D3 ,Fish waste ,UV conversion ,By-products ,HPLC-DAD ,Nutrition. Foods and food supply ,TX341-641 ,Food processing and manufacture ,TP368-456 - Abstract
Vitamin D, a fat-soluble steroid, has increasingly taken a central role due to its crucial role in human health. It is estimated that about 40% of worldwide population are vitamin D deficient. The fish industry produces significant quantities of waste daily, with consequent high environmental impact. The aim of this work is to place a first brick for the fish waste reuse as a source of vitamin D3 extracts to be used for nutraceutical purposes. For this purpose, an UV conversion method for transforming the 7-dehydrocholesterol, highly present in fish, in vitamin D3 has been optimized. The UV wavelength, exposure time, temperature, stirring, and UV intensity were optimized using a surface response design tool. The optimized treatment was applied to five fish species with different fat percentages and the results were very promising reaching vitamin D3 levels >10 times higher than the pre-treatment ones.
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- 2024
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26. Binding induced folding: Lessons from the kinetics of interaction between NTAIL and XD
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Toto, A., Troilo, F., Visconti, L., Malagrinò, F., Bignon, C., Longhi, Sonia Rachele Agata, Gianni, S., S, Department of Biochemical Sciences 'Rossi Fanelli', Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Università degli Studi di Roma 'La Sapienza' [Rome], Istituto di Biologia e Patologia Molecolari - CNR [Roma, Italy], Università degli Studi di Roma 'La Sapienza' [Rome], Architecture et fonction des macromolécules biologiques (AFMB), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Work partly supported by grants from the Italian Ministero dell’Istruzione dell’Università e della Ricerca (Progetto di Interesse ‘Invecchiamento’ to S.G.), Sapienza University of Rome (C26A155S48, B52F16003410005 and RP11715C34AEAC9B to S.G), the Associazione Italiana per la Ricerca sul Cancro (Individual Grant - MFAG 2016, 18701 to S.G.) the Istituto Pasteur Italia (Teresa Ariaudo Research Project 2018, to A.T.), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), CNR Istituto di Biologia e Patologia Molecolari [Roma] (CNR | IBPM), National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), Toto, A., Troilo, F., Visconti, L., Malagrino, Francesca, Bignon, C., Longhi, S., Gianni, S., Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], and Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)
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0301 basic medicine ,proteome ,Kinetics ,Biophysics ,Templated folding ,Intrinsically disordered proteins ,Biochemistry ,03 medical and health sciences ,Binding induced folding ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM] ,Molecular Biology ,protein disorder ,Kinetic ,030102 biochemistry & molecular biology ,Chemistry ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,Receptor–ligand kinetics ,proteins ,[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM] ,Folding (chemistry) ,[SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics ,030104 developmental biology ,Intrinsically disordered protein ,Function (biology) - Abstract
International audience; Intrinsically Disordered Proteins (IDPs) are a class of protein that exert their function despite lacking a well-defined three-dimensional structure, which is sometimes achieved only upon binding to their natural ligands. This feature implies the folding of IDPs to be generally coupled with a binding event, representing an interesting challenge for kinetic studies. In this review, we recapitulate some of the most important findings of IDPs binding-induced folding mechanisms obtained by analyzing their binding kinetics. Furthermore, by focusing on the interaction between the Measles virus NTAIL protein, a prototypical IDP, and its physiological partner, the X domain, we recapitulate the major theoretical and experimental approaches that were used to describe binding induced folding.
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- 2019
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27. High-Dose Inhaled Nitric Oxide as Adjunct Therapy in Cystic Fibrosis Targeting Burkholderia Multivorans in a Patient Receiving Elexacaftor-Tezacaftor-Ivacaftor
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Gardner, K., primary, Bartley, B., additional, Wiegand, S., additional, Gianni, S., additional, Fakhr Safaee, B., additional, Hurley, B., additional, Berra, L., additional, Yonker, L., additional, and Carroll, R., additional
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- 2021
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28. Breathing Nitric Oxide at High Dose in Severe-Critical COVID-19 During Pregnancy: A Case Series
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Safaee Fakhr, B., primary, Wiegand, S.B., additional, Pinciroli, R., additional, Gianni, S., additional, Morais, C.A., additional, Ikeda, T., additional, Miyazaki, Y., additional, Marutani, E., additional, Di Fenza, R., additional, Larson, G., additional, Parcha, V., additional, Gibson, L.E., additional, Chang, M., additional, Ackman, J.B., additional, Arora, P., additional, Carroll, R.W., additional, Kacmarek, R.M., additional, Ichinose, F., additional, Barth Jr, W.H., additional, Kaimal, A., additional, Hohmann, E.L., additional, Zapol, W.M., additional, and Berra, L., additional
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- 2021
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29. Ideation and Assessment of a Novel Nitric Oxide Delivery System for Spontaneously Breathing Subjects
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Gianni, S., primary, Araujo Morais, C.C., additional, Larson, G., additional, Pinciroli, R., additional, Carroll, R.W., additional, Yu, B., additional, Zapol, W.M., additional, and Berra, L., additional
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- 2021
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30. Titration of Mechanical Ventilation in Supine Compared to Prone Position Reveals Different Respiratory Mechanics Behavior in Covid19 Patients
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Morais, C.A., primary, Alcala, G.C., additional, Santiago, R.R.D.S., additional, Wanderley, H., additional, Diaz Delgado, E., additional, Di Fenza, R., additional, Safaee Fakhr, B., additional, Gianni, S., additional, Kacmarek, R., additional, and Berra, L., additional
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- 2021
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31. A Methodologic Approach to Study Large and Complex Landslides: An Application in Central Apennines
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Massimo Mangifesta, Domenico Aringoli, Gilberto Pambianchi, Leonardo Maria Giannini, Gianni Scalella, and Nicola Sciarra
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complex landslide ,site surveys ,three-dimensional slope stability ,local seismic response ,Geology ,QE1-996.5 - Abstract
The evaluation of landslide hazards in seismic areas is based on a deterministic analysis, which is unable to account for various uncertainties in the analysis process. This paper focuses on the probabilistic local seismic hazard analysis and extends the results to the landslide hazard analysis to consider both the uncertainties of the ground deformations and the strengths. The work studies the areas between Nibbiano and Sant’Erasmo hamlets in the Camerino municipality located in central Italy, where all constructions present evidence of damage caused by both the seismic sequence of 2016–2017 and the slope instability. An exhaustive geological and geophysical investigation has clarified the geological, geomorphological, and hydrogeological characteristics of the area, enabling a new characterization of material stress-strain behaviour. The study reveals that the low stiffness of the debris covers, and their fair degree of permeability contribute to potential instability scenarios triggered by both intense rainfall and the effects of strong earthquakes. The goal was to utilize the results to support local urban planning because in-depth knowledge of the possible evolutionary scenarios of the slopes is fundamental to the management of the degree of danger for structures, especially for people. Moreover, it was shown once again how a multi-source approach, with different investigation techniques, cannot be ignored for the study of the evolution of complex landslides.
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- 2024
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32. Sigh in Patients With Acute Hypoxemic Respiratory Failure and ARDS: The PROTECTION Pilot Randomized Clinical Trial
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Mauri, T., Foti, G., Fornari, C., Grasselli, G., Pinciroli, R., Lovisari, F., Tubiolo, D., Volta, C. A., Spadaro, S., Rona, R., Rondelli, E., Navalesi, P., Garofalo, E., Knafelj, R., Gorjup, V., Colombo, R., Cortegiani, A., Zhou, J. -X., D'Andrea, R., Calamai, I., Gonzalez, A. V., Roca, O., Grieco, D. L., Jovaisa, T., Bampalis, D., Becher, T., Battaglini, D., Ge, H., Luz, M., Constantin, J. -M., Ranieri, M., Guerin, C., Mancebo, J., Pelosi, P., Fumagalli, R., Brochard, L., Pesenti, A., Papoff, A., Di Fenza, R., Gianni, S., Spinelli, E., Lissoni, A., Abbruzzese, C., Bronco, A., Villa, S., Russotto, V., Iachi, A., Ball, L., Patroniti, N., Spina, R., Giuntini, R., Peruzzi, S., Menga, L. S., Fossali, T., Castelli, A., Ottolina, D., Garcia-De-Acilu, M., Santafe, M., Schadler, D., Weiler, N., Carvajal, E. R., Calvo, C. P., Neou, E., Wang, Y. -M., Zhou, Y. -M., Longhini, F., Bruni, A., Leonardi, M., Gregoretti, C., Ippolito, M., Milazzo, Z., Querci, L., Ranieri, S., Insom, G., Berden, J., Noc, M., Mikuz, U., Arzenton, M., Lazzeri, M., Villa, A., Barreto, B. B., Rios, M. N. O., Gusmao-Flores, D., Phull, M., Barnes, T., Musarat, H., and Conti, S.
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Male ,RCT, Randomized Control Trial ,VFDs, Ventilator- free days ,sigh ,PaO2/FiO2 ratio, Arterial Partial Pressure of O2/ Fraction of Inspired Oxygen ,SpO2/FiO2 ratio, Peripheral Oxygen Saturation/ Fraction of Inspired Oxygen ,Pilot Projects ,ESICM, European Society of Intensive Care Medicine ,NO ,Positive-Pressure Respiration ,ICU, Intensive Care Unit ,Vt, Tidal Volume ,SBT, Spontaneous Breathing Trial ,Intubation, Intratracheal ,Humans ,PEEP, Positive End Expiratory Pressure ,RR, Respiratory Rate ,FiO2, Fraction of Inspired Oxygen ,ARDS ,feasibility ,pressure support ,ventilation ,Aged ,Female ,Middle Aged ,Respiratory Distress Syndrome ,Respiratory Insufficiency ,Respiratory Mechanics ,Original Research ,GEE, Generalize Estimate Equation ,RASS, Richmond Agitation- Sedation Scale ,ARDS, Acute Respiratory Distress Syndrome ,P-SILI, Patient - Self Inflicted Lung Injury ,AHRF, Acute Hypoxemic Respiratory Failure ,PBW, Predicted Body Weight ,PSV, Pressure Support Ventilation ,SOFA, Sequence Organ Failure Assessment ,Intratracheal ,SAPS II, Simplified Acute Physiology Score II ,SpO2, Peripheral Oxygen Saturation ,PaCO2, Arterial Partial Pressure of CO2 ,TRALI, Transfusion-Related Acute Lung Injury ,BMI, Body Mass Index ,Intubation ,MV, Mechanical Ventilation - Abstract
BACKGROUND: Sigh is a cyclic brief recruitment maneuver: previous physiologic studies showed that its use could be an interesting addition to pressure support ventilation to improve lung elastance, decrease regional heterogeneity, and increase release of surfactant. RESEARCH QUESTION: Is the clinical application of sigh during pressure support ventilation (PSV) feasible? STUDY DESIGN AND METHODS: We conducted a multicenter noninferiority randomized clinical trial on adult intubated patients with acute hypoxemic respiratory failure or ARDS undergoing PSV. Patients were randomized to the no-sigh group and treated by PSV alone, or to the sigh group, treated by PSV plus sigh (increase in airway pressure to 30 cm H2O for 3 s once per minute) until day 28 or death or successful spontaneous breathing trial. The primary end point of the study was feasibility, assessed as noninferiority (5% tolerance) in the proportion of patients failing assisted ventilation. Secondary outcomes included safety, physiologic parameters in the first week from randomization, 28-day mortality, and ventilator-free days. RESULTS: Two-hundred and fifty-eight patients (31% women; median age, 65 [54-75] years) were enrolled. In the sigh group, 23% of patients failed to remain on assisted ventilation vs 30% in the no-sigh group (absolute difference, -7%; 95% CI, -18% to 4%; P = .015 for noninferiority). Adverse events occurred in 12% vs 13% in the sigh vs no-sigh group (P = .852). Oxygenation was improved whereas tidal volume, respiratory rate, and corrected minute ventilation were lower over the first 7 days from randomization in the sigh vs no-sigh group. There was no significant difference in terms of mortality (16% vs 21%; P = .337) and ventilator-free days (22 [7-26] vs 22 [3-25] days; P = .300) for the sigh vs no-sigh group. INTERPRETATION: Among hypoxemic intubated ICU patients, application of sigh was feasible and without increased risk.
- Published
- 2020
33. PO-2024 Effectiveness of Non-coplanar Monoisocenter Multifraction Radiosurgery for Multiple Brain Metastases
- Author
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Colombo, F., Salaroli, F., Renna, I., Ceccon, G., Lattanzi, E., Gianni, S., Grondelli, C., Bergamini, M., Dell'Anna, C., Galaverni, M., Bozzetti, F., Tortoli, P., Maddalo, M., Mazzilli, A., Benecchi, G., Ghetti, C., D'Abbiero, N., and Simoni, N.
- Published
- 2023
- Full Text
- View/download PDF
34. PO-1597 Stereotactic Arrhythmia Radioablation for Ventricular Tachycardia: Single Center Experience
- Author
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Colombo, F., Salaroli, F., Renna, I., Lattanzi, E., Ceccon, G., Gianni, S., Grondelli, C., Bergamini, M., Dell'Anna, C., Galaverni, M., Benecchi, G., Gonzi, G., Notarangelo, M.F., Palumbo, A., Ghetti, C., D'Abbiero, N., and Simoni, N.
- Published
- 2023
- Full Text
- View/download PDF
35. Le carcinome hépato-cellulaire, prévention et diagnostic précoce: où en sommes-nous?
- Author
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Farinati, F., Gianni, S., and Franco, M.
- Published
- 2001
- Full Text
- View/download PDF
36. DEEP LEARNING FOR CT IMAGES SEGMENTATION
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Gianni Shigeru Setoue Liveraro, Maria Emília Seren Takahashi, Fabiana Lascala, Maria Carolina Santos Mendes, Jun Takahashi, and José Barreto Campello Carvalheira
- Subjects
Automated body composition analysis ,Computed tomography ,Deep learning ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Introduction/Justification: Computed tomography (CT) scans are integral to cancer patient diagnosis, revealing changes in body composition linked to survival progression. The conventional approach to body composition analysis using CT scans is labor-intensive and expensive, demanding skilled professionals and licensed software for manual segmentation of Regions of Interest (ROIs). To address these challenges, we introduce a Deep Learning algorithm designed for automated CT image segmentation, presenting an efficient alternative that overcomes the limitations of the current methodology. Beyond the advantages of speed, automation enhances result uniformity and enables uncertainty estimation. In this presentation, we will show preliminary results from our algorithm, highlighting its potential contributions to survival analysis in cancer patients. Objectives: The primary goal of this study was to develop an automated segmentation algorithm for CT scans using Deep Learning models. Materials and Methods: In developing segmentation algorithms, a dataset of 453 CT slices at the L3 lumbar vertebral level from gastric cancer patients was utilized, with an 80% training and 20% testing partition. Employing the UNET+ResNet18 deep learning architecture, supervised training utilized manually generated segmentation masks as references. Four dedicated UNET+ResNet18 algorithms were trained for distinct ROIs: Skeletal Muscle (SM), Intramuscular Adipose Tissue (IMAT), Visceral Adipose Tissue (VAT), and Subcutaneous Adipose Tissue (SAT). Segmentation performance on the test set was evaluated using the Dice Coefficient, underestimation and overestimation percentages, Bland-Altman analyses, and qualitative visual inspection of segmented images. Results: The UNet+ResNet18 models demonstrated superior segmentation performance for SM, VAT, and SAT, achieving mean Dice scores exceeding 0.95. In comparison to manual segmentation, the Deep Learning algorithm exhibited minor average underestimations and overestimations, both below 5% for these tissues. However, IMAT segmentation exhibited relatively lower performance, with a mean Dice score of approximately 0.86 and underestimation and overestimation percentages around 15% and 13%, respectively. The Bland-Altman analysis revealed mean bias and limits of agreement for mean radiodensities of SM, VAT, SAT, and IMAT as follows: 0.14 [-0.82, 1.10] HU, -0.53 [-2.03, 0.98] HU, -0.18 [-1.70, 1.33] HU, and 0.48 [-3.86, 4.82] HU, respectively. Conclusion: The Deep Learning approach provides a standard and fast solution for CT image segmentation, demonstrating good results for SM, VAT and SAT. For these tissues, derived radiomics features could provide valuable insights into the analysis of cancer patient outcomes. Further studies are necessary for enhancing IMAT segmentation, given its challenging small area. Additionally, future investigations should focus on uncertainty estimation in CT images, exploring its impact on segmentation procedures and radiomic feature extraction.
- Published
- 2024
- Full Text
- View/download PDF
37. Effect of Process Parameters in Additively Manufactured Sensors prepared via Material Extrusion Processes: Correlation among Electrical, Mechanical and Microstructure Properties
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Gianni Stano, Neshat Sayah, Douglas E. Smith, and Trevor J. Fleck
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Material Extrusion Additive Manufacturing ,Microstructure ,Sensors ,Process Parameters ,Industrial engineering. Management engineering ,T55.4-60.8 - Abstract
Fusion-based Material Extrusion (MEX) Additive Manufacturing (AM) processes have been extensively used for the fabrication of smart structures with embedded sensors, proving to have several benefits such as reduction in cost, manufacturing time, and assembly. A major issue negatively affecting 3D printed sensors is related to their poor electrical conductivity, as well as inconsistent electrical performance, which leads to electrical power losses amongst other issues. In the present paper, a set of process parameters (ironing, printing temperature, and infill overlap) has been analyzed by performing a Design of Experiment (DoE) factorial plan to minimize the electrical resistance. The best process parameters configuration involves a remarkable reduction of electrical resistance of 47.9%, as well as an improvement of mechanical properties of 31.9% (ultimate tensile strength), 25.8% (elongation at break) and 28.14% (flexural stress). The microstructure of the obtained results has also been analyzed by employing a high-resolution, X-ray Computed Tomography (X-Ray CT) system showing a reduction of intralayer voids of 19.5%. This work demonstrates a clear correlation between process parameters and the corresponding electrical properties, mechanical properties, and internal microstructure. In the present research, it has been shown that i) it is possible to significantly improve the overall 3D printed sensors performance by process parameter selection, and ii) small changes in the microstructure lead to remarkable improvements in electrical and mechanical performance.
- Published
- 2024
- Full Text
- View/download PDF
38. Comparative Study on the Chemical Profile, Antioxidant Activity, and Enzyme Inhibition Capacity of Red and White Hibiscus sabdariffa Variety Calyces
- Author
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Sakina Yagi, Abdullahi Ibrahim Uba, Kouadio Ibrahime Sinan, Diletta Piatti, Gianni Sagratini, Giovanni Caprioli, Sayadat M. Eltigani, Irina Lazarova, and Gökhan Zengin
- Subjects
Chemistry ,QD1-999 - Published
- 2023
- Full Text
- View/download PDF
39. The value of serum creatinine as biomarker of disease progression in spinal and bulbar muscular atrophy (SBMA)
- Author
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Lorenzo Blasi, Daniele Sabbatini, Andrea Fortuna, Giorgia Querin, Ilaria Martinelli, Sara Vianello, Cinzia Bertolin, Davide Pareyson, Maria Pennuto, Elena Pegoraro, Luca Bello, and Gianni Sorarù
- Subjects
Medicine ,Science - Abstract
Abstract Serum creatinine has been indicated as a potential marker of motor function in SBMA and results form previous longitudinal studies pointed to its decline over time. This is a longitudinal retrospective study investigating creatinine changes over a 36-month-period in 73 patients with SBMA. Severity and progression of the disease was assessed according to serum creatine kinase (CK) values, manual muscle testing (MMT), SBMA functional rating scale (SBMAFRS) score, 6-min-walk test (6MWT) value, and spirometry (forced vital capacity, fVC%) obtained at the baseline and at each of the annual follow-up visits. Baseline serum creatinine concentrations positively correlated with 6MWT, the MMT megascore score of both the upper (ULM) and lower (LLM) limbs and SBMAFRS. No correlation was found with CK or fVC% values. Similar correlation results were achieved at all the subsequent time points. Longitudinal assessments conducted by the generalized estimating equations (GEE) method returned significant changes for SBMAFRS (− 1.41 points per year, p 0.05). We also observed that creatinine levels at baseline did not correlate with changes in the other measures from baseline at each annual visit. Our data do not support a role for serum creatinine as sensitive biomarker of disease progression, and possibily prognosis, in SBMA.
- Published
- 2023
- Full Text
- View/download PDF
40. Presence and Role of Associations of Cancer Patients and Volunteers in Specialist Breast Centres: An Italian National Survey of Breast Centres Associated with Senonetwork
- Author
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Rosanna D’Antona, Silvia Deandrea, Elisabetta Sestini, Loredana Pau, Francesca Ferrè, Catia Angiolini, Marina Bortul, Lauro Bucchi, Francesca Caumo, Lucio Fortunato, Livia Giordano, Monica Giordano, Paola Mantellini, Irene Martelli, Giuseppe Melucci, Carlo Naldoni, Eugenio Paci, Gianni Saguatti, Corrado Tinterri, Milena Vainieri, and Luigi Cataliotti
- Subjects
breast cancer ,breast centre ,associations ,patients ,volunteers ,survey ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
This article aims to present the results of a national, cross-sectional, voluntary, online survey on the presence and roles of associations of breast cancer patients and volunteers in Italian specialist breast centres. The survey was developed according to standard methods. The questionnaire was pre-tested by a random sample of three breast centres, loaded onto the SurveyMonkey platform, and piloted by one volunteer breast centre. The breast centre clinical leads were invited to participate via email. A link to the online instrument was provided. No financial incentives were offered. The results were reported using standard descriptive statistics. The response rate was 82/128 (65%). Members of associations were routinely present in 70% Italian breast centres. Breast centres most often reporting their presence were those certified by the European Society of Breast Cancer Specialists. Patient support (reception and information, listening, identification of needs, and psychological support) was the primary area where associations were reported to offer services. The magnitude of this phenomenon warrants a study to investigate the impact of the activities of associations on the quality of life of patients and on the cost–benefit ratio of the service, and the modes of their interactions with the nursing staff and the medical staff.
- Published
- 2023
- Full Text
- View/download PDF
41. The complete folding pathway of the leukaemiaassociated Nucleophosmin C-terminal domain: YSF-100 (oral presentation)
- Author
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Scaloni, F., Federici, L., Brunori, M., and Gianni, S.
- Published
- 2010
42. MortalitY in caRdIAc surgery (MYRIAD): A randomizeD controlled trial of volatile anesthetics. Rationale and design
- Author
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Landoni, G, Lomivorotov, V, Pisano, A, Nigro Neto, C, Benedetto, U, Biondi Zoccai, G, Gemma, M, Frassoni, S, Agro, F, Baiocchi, M, Barbosa Gomes Galas, F, Bautin, A, Bradic, N, Carollo, C, Crescenzi, G, Elnakera, A, El-Tahan, M, Fominskiy, E, Farag, A, Gazivoda, G, Gianni, S, Grigoryev, E, Guarracino, F, Hanafi, S, Huang, W, Kunst, G, Kunstyr, J, Lei, C, Lembo, R, Li, Z, Likhvantsev, V, Lozovskiy, A, Ma, J, Monaco, F, Navalesi, P, Nazar, B, Pasyuga, V, Porteri, E, Royse, C, Ruggeri, L, Riha, H, Santos Silva, F, Severi, L, Shmyrev, V, Uvaliev, N, Wang, C, Winterton, D, Yong, C, Yu, J, Bellomo, R, Zangrillo, A, Landoni G., Lomivorotov V., Pisano A., Nigro Neto C., Benedetto U., Biondi Zoccai G., Gemma M., Frassoni S., Agro F. E., Baiocchi M., Barbosa Gomes Galas F. R., Bautin A., Bradic N., Carollo C., Crescenzi G., Elnakera A. M., El-Tahan M. R., Fominskiy E., Farag A. G., Gazivoda G., Gianni S., Grigoryev E., Guarracino F., Hanafi S., Huang W., Kunst G., Kunstyr J., Lei C., Lembo R., Li Z. -J., Likhvantsev V., Lozovskiy A., Ma J., Monaco F., Navalesi P., Nazar B., Pasyuga V., Porteri E., Royse C., Ruggeri L., Riha H., Santos Silva F., Severi L., Shmyrev V., Uvaliev N., Wang C. B., Wang C. -Y., Winterton D., Yong C. -Y., Yu J., Bellomo R., Zangrillo A., Landoni, G, Lomivorotov, V, Pisano, A, Nigro Neto, C, Benedetto, U, Biondi Zoccai, G, Gemma, M, Frassoni, S, Agro, F, Baiocchi, M, Barbosa Gomes Galas, F, Bautin, A, Bradic, N, Carollo, C, Crescenzi, G, Elnakera, A, El-Tahan, M, Fominskiy, E, Farag, A, Gazivoda, G, Gianni, S, Grigoryev, E, Guarracino, F, Hanafi, S, Huang, W, Kunst, G, Kunstyr, J, Lei, C, Lembo, R, Li, Z, Likhvantsev, V, Lozovskiy, A, Ma, J, Monaco, F, Navalesi, P, Nazar, B, Pasyuga, V, Porteri, E, Royse, C, Ruggeri, L, Riha, H, Santos Silva, F, Severi, L, Shmyrev, V, Uvaliev, N, Wang, C, Winterton, D, Yong, C, Yu, J, Bellomo, R, Zangrillo, A, Landoni G., Lomivorotov V., Pisano A., Nigro Neto C., Benedetto U., Biondi Zoccai G., Gemma M., Frassoni S., Agro F. E., Baiocchi M., Barbosa Gomes Galas F. R., Bautin A., Bradic N., Carollo C., Crescenzi G., Elnakera A. M., El-Tahan M. R., Fominskiy E., Farag A. G., Gazivoda G., Gianni S., Grigoryev E., Guarracino F., Hanafi S., Huang W., Kunst G., Kunstyr J., Lei C., Lembo R., Li Z. -J., Likhvantsev V., Lozovskiy A., Ma J., Monaco F., Navalesi P., Nazar B., Pasyuga V., Porteri E., Royse C., Ruggeri L., Riha H., Santos Silva F., Severi L., Shmyrev V., Uvaliev N., Wang C. B., Wang C. -Y., Winterton D., Yong C. -Y., Yu J., Bellomo R., and Zangrillo A.
- Abstract
Objective There is initial evidence that the use of volatile anesthetics can reduce the postoperative release of cardiac troponin I, the need for inotropic support, and the number of patients requiring prolonged hospitalization following coronary artery bypass graft (CABG) surgery. Nevertheless, small randomized controlled trials have failed to demonstrate a survival advantage. Thus, whether volatile anesthetics improve the postoperative outcome of cardiac surgical patients remains uncertain. An adequately powered randomized controlled trial appears desirable. Design Single blinded, international, multicenter randomized controlled trial with 1:1 allocation ratio. Setting Tertiary and University hospitals. Interventions Patients (n = 10,600) undergoing coronary artery bypass graft will be randomized to receive either volatile anesthetic as part of the anesthetic plan, or total intravenous anesthesia. Measurements and main results The primary end point of the study will be one-year mortality (any cause). Secondary endpoints will be 30-day mortality; 30-day death or non-fatal myocardial infarction (composite endpoint); cardiac mortality at 30 day and at one year; incidence of hospital re-admission during the one year follow-up period and duration of intensive care unit, and hospital stay. The sample size is based on the hypothesis that volatile anesthetics will reduce 1-year unadjusted mortality from 3% to 2%, using a two-sided alpha error of 0.05, and a power of 0.9. Conclusions The trial will determine whether the simple intervention of adding a volatile anesthetic, an intervention that can be implemented by all anesthesiologists, can improve one-year survival in patients undergoing coronary artery bypass graft surgery.
- Published
- 2017
43. Design, synthesis and biological evaluation of PDZ1 targeting NHERF1 inhibitors as anticancer agents
- Author
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La Regina, G., Naccarato, V., Masci, D., Puxeddu, M., Bufano, M., Nalli, M., Coluccia, A., Orlando, V., Canettieri, G., Gianni, S., and Silvestri, R.
- Subjects
PDZ1 ,NHERF1 ,Small Molecules ,Drug Design ,PDZ1, NHERF1, small molecule, cancer ,small molecule ,Settore CHIM/08 - CHIMICA FARMACEUTICA ,Molecular docking simulation ,Cancer - Published
- 2019
44. Tumour staging, morphology and p53 overexpression concur in predicting survival in hepatocellular carcinoma
- Author
-
GIANNI, S., CECCHETTO, A., ALTAVILLA, G., RAGAZZI, R., BERTAZZO, M., DE GIORGIO, M., BALDAN, A., FAGIUOLI, S., and FARINATI, F.
- Published
- 2005
45. Design, synthesis and biological evaluation of PDZ1 targeting NHERF1 inhibitors as anticancer agents
- Author
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La Regina, Giuseppe, Naccarato, V., Masci, Domiziana, Puxeddu, M., Bufano, Maria Oliva, Nalli, M., Coluccia, A., Orlando, Vittorio, Canettieri, G., Gianni, Silvia Maria, Silvestri, R., La Regina, G., Masci, D. (ORCID:0000-0002-5615-5111), Bufano, M., Orlando, V., Gianni, S., La Regina, Giuseppe, Naccarato, V., Masci, Domiziana, Puxeddu, M., Bufano, Maria Oliva, Nalli, M., Coluccia, A., Orlando, Vittorio, Canettieri, G., Gianni, Silvia Maria, Silvestri, R., La Regina, G., Masci, D. (ORCID:0000-0002-5615-5111), Bufano, M., Orlando, V., and Gianni, S.
- Abstract
NHERF1 (Na+/H+ exchanger 3 regulating factor 1) is an integral membrane adaptor protein carrying two NH2-terminal PDZ (postsynaptic density 95/discs large/zona occludens 1) tandem domains. PDZ1 (11-97 amino acids) and PDZ2 (150-237 amino acids) show 74% identity to each other and bind to specific carboxyl-terminal motifs on target proteins, such as E-catenin and PTEN, that may have a pivotal role in tumorigenesis. Oncogenic activity of NHERF1 is strictly dictated by changes on its subcellular localization. A pharmacophore model was used to filter out an in-house training set of about 6000 compounds, leading to identify a potent inhibitor of NHERF1. We herein reported the design and synthesis of new NHERF1 inhibitors (Figure 1). The new compounds were synthesized by treating the appropriate indole with thionyl chloride and the proper amino derivative in the presence of pyridine in dichloromethane at room temperature for 12 h; alternatively, the coupling reaction was carried out using (benzotriazol-1- yloxy)tripyrrolidinophosphonium hexafluorophosphate and triethylamine in N,N-dimethylformamide at room temperature for 12 h. Compounds 5, 9, 10 and 13 exhibited a remarkable cytotoxicity in Ls174TshE-Cat cells. The binding to NHERF1 PDZ was confirmed by means of a dansylated peptide corresponding to the C-terminal sequence of E2-AR. When used in combination with antagonists of E-catenin, the new derivatives increased the apoptotic death of colorectal cancer cells refractory to currently available Wnt/E-catenintargeted agents.
- Published
- 2019
46. Randomized, double-blind, placebo-controlled trial of rapamycin in amyotrophic lateral sclerosis
- Author
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Jessica Mandrioli, Roberto D’Amico, Elisabetta Zucchi, Sara De Biasi, Federico Banchelli, Ilaria Martinelli, Cecilia Simonini, Domenico Lo Tartaro, Roberto Vicini, Nicola Fini, Giulia Gianferrari, Marcello Pinti, Christian Lunetta, Francesca Gerardi, Claudia Tarlarini, Letizia Mazzini, Fabiola De Marchi, Ada Scognamiglio, Gianni Sorarù, Andrea Fortuna, Giuseppe Lauria, Eleonora Dalla Bella, Claudia Caponnetto, Giuseppe Meo, Adriano Chio, Andrea Calvo, and Andrea Cossarizza
- Subjects
Science - Abstract
Abstract In preclinical studies rapamycin was found to target neuroinflammation, by expanding regulatory T cells, and affecting autophagy, two pillars of amyotrophic lateral sclerosis (ALS) pathogenesis. Herein we report a multicenter, randomized, double-blind trial, in 63 ALS patients who were randomly assigned in a 1:1:1 ratio to receive rapamycin 2 mg/m2/day,1 mg/m2/day or placebo (EUDRACT 2016-002399-28; NCT03359538). The primary outcome, the number of patients exhibiting an increase >30% in regulatory T cells from baseline to treatment end, was not attained. Secondary outcomes were changes from baseline of T, B, NK cell subpopulations, inflammasome mRNA expression and activation status, S6-ribosomal protein phosphorylation, neurofilaments; clinical outcome measures of disease progression; survival; safety and quality of life. Of the secondary outcomes, rapamycin decreased mRNA relative expression of the pro-inflammatory cytokine IL-18, reduced plasmatic IL-18 protein, and increased the percentage of classical monocytes and memory switched B cells, although no corrections were applied for multiple tests. In conclusion, we show that rapamycin treatment is well tolerated and provides reassuring safety findings in ALS patients, but further trials are necessary to understand the biological and clinical effects of this drug in ALS.
- Published
- 2023
- Full Text
- View/download PDF
47. Data-independent acquisition-based SWATH-MS proteomics profiling to decipher the impact of farming system and chicken strain and discovery of biomarkers of authenticity in organic versus antibiotic-free chicken meat
- Author
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Laura Alessandroni, Gianni Sagratini, Susana B. Bravo, and Mohammed Gagaoua
- Subjects
Poultry muscle proteome ,Farming systems ,Gel-based proteomics ,SWATH-MS ,Omics ,Organic meat ,Nutrition. Foods and food supply ,TX341-641 ,Food processing and manufacture ,TP368-456 - Abstract
In the literature, there is a paucity of methods and tools that allow the identification of biomarkers of authenticity to discriminate organic and non-organic chicken meat products. Shotgun proteomics is a powerful tool that allows the investigation of the entire proteome of a muscle and/or meat sample. In this study, a shotgun proteomics approach using Sequential Window Acquisition of All Theoretical Mass Spectra (SWATH-MS) has been applied for the first time to characterize and identify candidate protein biomarkers of authenticity in post-mortem chicken Pectoralis major muscles produced under organic and non-organic farming systems (antibiotic-free). The proteomics characterization was further performed within two chicken strains, these being Ross 308 and Ranger Classic, which differ in their growth rate. From the candidate protein biomarkers, the bioinformatics enrichment analyses revealed significant differences in the muscle proteome between the two chicken strains, which may be related to their genetic background and rearing conditions. The results further provided novel insights on the potential interconnected pathways at interplay that are associated with the differences as a consequence of farming system of chicken strain, such as muscle contraction and energy metabolism. This study could pave the way to more in-depth investigations in proteomics applications to assess chicken meat authenticity and better understand the impact of farming systems on the chicken muscle and meat quality.
- Published
- 2024
- Full Text
- View/download PDF
48. Manufacturing-oriented review on 3D printed lithium-ion batteries fabricated using material extrusion
- Author
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Alexis Maurel, Antonio Pavone, Gianni Stano, Ana C. Martinez, Eric MacDonald, and Gianluca Percoco
- Subjects
battery ,lithium-ion ,electrodes ,material extrusion ,composites ,energy storage ,Science ,Manufactures ,TS1-2301 - Abstract
The advent of conductive extrudable materials has broadened the range of additive manufacturing applications to include smart devices, circuits, actuators and sensors – all requiring electrical power. 3D printing of components dedicated to energy storage has also gained interest, with the goal of the monolithic printing of batteries directly integrated into subsuming smart components. This review focuses on the state of the art of extrusion-based 3D printed batteries, appearing as the most widespread, inexpensive and simple additive process. The paper is intended to introduce the processes and materials of 3D printing batteries, while highlighting the main manufacturing challenges and associated solutions proposed in literature. Particular attention is dedicated to describing the extrusion-based printers being employed and the required modifications, printing parameters and multi-material capabilities, with the aim of highlighting the most promising solutions required to print composite individual components and complete rechargeable batteries in a single non-assembly step.
- Published
- 2023
- Full Text
- View/download PDF
49. Experimental Characterization of Fuzzy Protein Assemblies: Interactions of Paramyxoviral NTAIL Domains With Their Functional Partners
- Author
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Troilo F., Bignon C., Gianni S., Fuxreiter M., and Longhi S.
- Subjects
ESI-MS and IM-MS ,Experimental assessment of fuzziness ,Fuzzy interactions ,Impact of fuzziness on binding ,Kinetics ,Mutagenesis ,NMR ,Protein complementation assays ,SAXS ,SEC ,Site-directed spin-labeling EPR spectroscopy ,Split-GFP reassembly - Abstract
In this chapter we detail various experimental approaches to characterize the fuzziness of complexes made of the C-terminal domain of the nucleoprotein (NTAIL) from three representative paramyxoviruses and of the C-terminal X domain (XD) of the homologous phosphoprotein. We discuss the advantages, the limitations, as well as the caveats of the various methods. We describe experimental data showing that paramyxoviral NTAIL-XD complexes are characterized by a considerable amount of conformational heterogeneity. We also detail recent data that revealed that NTAIL is highly malleable, i.e., it displays a partner-mediated polymorphism. All the results suggest that NTAIL plasticity and fuzziness play a role in the coordination and regulation of the NTAIL interaction network so as to ensure efficient transcription and replication.
- Published
- 2018
- Full Text
- View/download PDF
50. 377 Sentinel node detection in gynecology oncology: our experience with indocyanine green (ICG)
- Author
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Nico, A, primary, Lay, L, additional, Zeff, N, additional, Sanchez, A, additional, Cuellar, S, additional, San Martín, G, additional, Zarlenga, C, additional, Lupo, E, additional, Gianni, S, additional, and Ostojich, M, additional
- Published
- 2019
- Full Text
- View/download PDF
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