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1. Modified Patankar Linear Multistep methods for production-destruction systems

Author

Izzo, Giuseppe, Messina, Eleonora, Pezzella, Mario, and Vecchio, Antonia

Subjects
Mathematics - Numerical Analysis, Mathematics - Dynamical Systems, 65L05 (Primary) 65L06, 34B18 (Secondary)
Abstract

Modified Patankar schemes are linearly implicit time integration methods designed to be unconditionally positive and conservative. In the present work we extend the Patankar-type approach to linear multistep methods and prove that the resulting discretizations retain, with no restrictions on the step size, the positivity of the solution and the linear invariant of the continuous-time system. Moreover, we provide results on arbitrarily high order of convergence and we introduce an embedding technique for the Patankar weight denominators to achieve it.

Published
2024

2. Promelanogenic Effects by an Annurca Apple-Based Natural Formulation in Human Primary Melanocytes

Author

Ferraro MG, Piccolo M, Pezzella A, Guerra F, Maione F, Tenore GC, Santamaria R, Irace C, and Novellino E

Subjects
melanins, skin pigmentation, tyrosinase, skin pigmenting agents, natural bioactive molecules, Dermatology, RL1-803
Abstract

Maria Grazia Ferraro,1 Marialuisa Piccolo,1 Alessandro Pezzella,2 Fabrizia Guerra,1 Francesco Maione,1 Gian Carlo Tenore,1 Rita Santamaria,1 Carlo Irace,1 Ettore Novellino1 1Department of Pharmacy, School of Medicine and Surgery, University of Naples “Federico II”, Naples, 80131, Italy; 2Department of Chemical Sciences, University of Naples “Federico II”, Naples, 80126, ItalyCorrespondence: Carlo Irace;Rita SantamariaDepartment of Pharmacy, School of Medicine and Surgery, University of Naples “Federico II”, Via D. Montesano 49, Naples, 80131, ItalyTel +39 081 678416; +39 081 678421Fax +39 081 678403Email carlo.irace@unina.it; rita.santamaria@unina.itIntroduction: Melanocytes are engaged in synthesis, transport, and release of pigments at the epidermal-melanin units in response to the finely regulated melanogenic pathway. A multifaceted combination of both intrinsic and extrinsic factors – from endocrine and paracrine dynamics to exogenous stimuli such as sunlight and xenobiotics – modulates expression and activity of proteins involved in pigmentation, including the rate-limiting enzyme tyrosinase. As well as playing critical physiological functions comprising skin photoprotection, melanins define hair and skin pigmentation which in turn have impacted considerably to human social communication since time immemorial. Additionally, numerous skin diseases based on pigmentation alterations can have serious public influence. While several melanogenesis inhibitors are already available, the number of melanin activators and tyrosinase stimulators as drug-like agents is still limited.Methods: To explore the biological effects of an Annurca Apple-based nutraceutical preparation (AMS) on melanin production, experiments in cellular models of human skin were performed. Both primary cultures and co-cultures of epidermal melanocytes (HEMa) and follicular keratinocytes (HHFK) were used.Results: We show that AMS, by now branded for its cutaneous beneficial effects, induces in total biocompatibility a significant promelanogenic effect in human primary melanocytes. In line, we found melanin cytosolic accumulation consistent with tyrosinase up-regulation.Conclusion: Disposal of skin pigmenting agents would be attractive for the treatment of hypopigmentation disorders, to postpone skin photoaging or simply for fashion, so that discovery and development of melanogenesis stimulators, especially from natural sources, is nowadays a dynamic area of research.Keywords: melanins, skin pigmentation, tyrosinase, skin pigmenting agents, natural bioactive molecules

Published
2021

3. The 2024 release of the ExoMol database: molecular line lists for exoplanet and other hot atmospheres

Author

Tennyson, Jonathan, Yurchenko, Sergei N., Zhang, Jingxin, Bowesman, Charles A., Brady, Ryan P., Buldyreva, Jeanna, Chubb, Katy L., Gamache, Robert R., Gorman, Maire N., Guest, Elizabeth R., Hill, Christian, Kefala, Kyriaki, Lynas-Gray, A. E., Mellor, Thomas M., McKemmish, Laura K., Mitev, Georgi B., Mizus, Irina I., Owens, Alec, Peng, Zhijian, Perri, Armando N., Pezzella, Marco, Polyansky, Oleg L., Qu, Qianwei, Semenov, Mikhail, Smola, Oleksiy, Solokov, Andrei, Somogyi, Wilfrid, Upadhyay, Apoorva, Wright, Samuel O. M., and Zobov, Nikolai F.

Subjects
Astrophysics - Astrophysics of Galaxies
Abstract

The ExoMol database (www.exomol.com) provides molecular data for spectroscopic studies of hot atmospheres. These data are widely used to model atmospheres of exoplanets, cool stars and other astronomical objects, as well as a variety of terrestrial applications. The 2024 data release reports the current status of the database which contains recommended line lists for 91 molecules and 224 isotopologues giving a total of almost 10$^{12}$ individual transitions. New features of the database include extensive "MARVELization" of line lists to allow them to be used for high resolutions studies, extension of several line lists to ultraviolet wavelengths, provision of photodissociation cross sections and extended provision of broadening parameters. Some of the in-house data specifications have been rewritten in JSON and moved to conformity with other international standards. Data products, including specific heats, a database of lifetimes for plasma studies, and the ExoMolHR web app which allows exclusively high resolution data to be extracted, are discussed.

Published
2024

4. Searching for gravitational wave optical counterparts with the Zwicky Transient Facility: summary of O4a

Author

Ahumada, Tomás, Anand, Shreya, Coughlin, Michael W., Gupta, Vaidehi, Kasliwal, Mansi M., Karambelkar, Viraj R., Stein, Robert D., Waratkar, Gaurav, Swain, Vishwajeet, Laz, Theophile Jegou du, Anumarlapudi, Akash, Andreoni, Igor, Bulla, Mattia, Srinivasaragavan, Gokul P., Toivonen, Andrew, Wold, Avery, Bellm, Eric C., Cenko, S. Bradley, Kaplan, David L., Sollerman, Jesper, Bhalerao, Varun, Perley, Daniel, Salgundi, Anirudh, Suresh, Aswin, Hinds, K-Ryan, Reusch, Simeon, Necker, Jannis, Cook, David O., Pletskova, Natalya, Singer, Leo P., Banerjee, Smaranika, Barna, Tyler, Copperwheat, Christopher M., Healy, Brian, Kiendrebeogo, R. Weizmann, Kumar, Harsh, Kumar, Ravi, Pezzella, Marianna, Sagues-Carracedo, Ana, Sravan, Niharika, Bloom, Joshua S., Chen, Tracy X., Graham, Matthew, Helou, George, Laher, Russ R., Mahabal, Ashish A., Purdum, Josiah, Anupama, G. C., Barway, Sudhanshu, Basu, Judhajeet, Raman, Dhananjay, and Roychowdhury, Tamojeet

Subjects
Astrophysics - High Energy Astrophysical Phenomena, Astrophysics - Solar and Stellar Astrophysics
Abstract

During the first half of the fourth observing run (O4a) of the International Gravitational Wave Network (IGWN), the Zwicky Transient Facility (ZTF) conducted a systematic search for kilonova (KN) counterparts to binary neutron star (BNS) and neutron star-black hole (NSBH) merger candidates. Here, we present a comprehensive study of the five high-significance (FAR < 1 per year) BNS and NSBH candidates in O4a. Our follow-up campaigns relied on both target-of-opportunity observations (ToO) and re-weighting of the nominal survey schedule to maximize coverage. We describe the toolkit we have been developing, Fritz, an instance of SkyPortal, instrumental in coordinating and managing our telescope scheduling, candidate vetting, and follow-up observations through a user-friendly interface. ZTF covered a total of 2841 deg$^2$ within the skymaps of the high-significance GW events, reaching a median depth of g~20.2 mag. We circulated 15 candidates, but found no viable KN counterpart to any of the GW events. Based on the ZTF non-detections of the high-significance events in O4a, we used a Bayesian approach, nimbus, to quantify the posterior probability of KN model parameters that are consistent with our non-detections. Our analysis favors KNe with initial absolute magnitude fainter than -16 mag. The joint posterior probability of a GW170817-like KN associated with all our O4a follow-ups was 64%. Additionally, we use a survey simulation software, simsurvey, to determine that our combined filtered efficiency to detect a GW170817-like KN is 36%, when considering the 5 confirmed astrophysical events in O3 (1 BNS and 4 NSBH), along with our O4a follow-ups. Following Kasliwal et al. (2020), we derived joint constraints on the underlying KN luminosity function based on our O3 and O4a follow-ups, determining that no more than 76% of KNe fading at 1 mag/day can peak at a magnitude brighter than -17.5 mag., Comment: submitted

Published
2024

5. Jacobi Sigma Models and Twisted Jacobi Structures

Author

Bascone, Francesco, Pezzella, Franco, and Vitale, Patrizia

Subjects
High Energy Physics - Theory, Mathematical Physics
Abstract

Jacobi sigma models are two-dimensional topological non-linear field theories which are associated with Jacobi structures. The latter can be considered as a generalization of Poisson structures. After reviewing the main properties and peculiarities of these models, we focus on the twisted version in which a Wess-Zumino term is included. This modification allows for the target space to be a twisted Jacobi manifold. We discuss in particular the model on the sphere $S^5$.

Published
2024

12. Benefits of dark chocolate intake on retinal vessels functionality: a randomized, blind, crossover clinical trial

Author

Riccardo Sacconi, Mario Pezzella, Nicolo’ Ribarich, Matteo Menean, Andrea Servillo, Francesco Bandello, and Giuseppe Querques

Subjects
Medicine, Science
Abstract

Abstract There is a lack of knowledge about the effect of flavanols-rich dark chocolate intake on the anatomy and functionality of retinal vessels. The aim of this study prospective, randomized, blind, crossover clinical trial (ClinicalTrials.gov Identifier: NCT05227248, 07/02/2022) was to evaluate the effect of dark-chocolate intake on the functionality and anatomy of the retinal vessels in healthy subjects using dynamic vessel analyzer (DVA) and optical coherence tomography angiography (OCT-A). Twenty eyes of 20 healthy subjects (mean age, 24.4 ± 1.6 years; 12 females) were enrolled. Participants were randomized to consume 20 g of dark chocolate or 7.5 g of milk chocolate. Visual function, DVA and OCT-A parameters were evaluated before chocolate consumption and two hours later. One week later, the same participants were tested before and after consuming the opposite chocolate. Using OCT-A, no differences were disclosed in terms of perfusion density changes after dark-chocolate and milk-chocolate intake analyzing all chorioretinal plexuses (p > 0.09 in all analyses). Using DVA, a significant increase in the arterial dilation percentage after flicker stimulation was disclosed comparing baseline (2.750 ± 2.054%) with values after the dark chocolate intake (4.145 ± 3.055%, p = 0.016). This difference was not disclosed after the milk chocolate intake (p = 0.465). We disclosed that a reasonable amount of flavanols-rich chocolate in healthy subjects has benefic functional short-term effects in retinal vessels measured with DVA. This suggests a potential role of dark chocolate intake on retinal vessels. Further studies with long-term follow-up are warranted to show if the chronic assumption of dark chocolate could play a favorable role in the prevention of retinal diseases.

Published
2024
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13. ExoMol line lists -- L: High-resolution line lists of H$_3^+$, H$_2$D$^+$, D$_2$H$^+$ and D$_3^+$

Author

Bowesman, Charles A., Mizus, Irina I., Zobov, Nikolay F., Polyansky, Oleg L., Sarka, Janos, Poirier, Bill, Pezzella, Marco, Yurchenko, Sergei N., and Tennyson, Jonathan

Subjects
Astrophysics - Solar and Stellar Astrophysics, Astrophysics - Astrophysics of Galaxies
Abstract

New MiZo line lists are presented for the D$_2$H$^+$ and D$_3^+$ isotopologues of H$_3^+$. These line lists plus the existing H$_3^+$ MiZATeP and the Sochi H$_2$D$^+$ line lists are updated using empirical energy levels generated using the MARVEL procedure for H$_3^+$, H$_2$D$^+$ and D$_2$H$^+$, and effective Hamiltonian energies for D$_3^+$ for which there is significantly less laboratory data available. These updates allow accurate frequencies for far infrared lines for these species to be predicted. Assignments of the energy levels of H$_3^+$ and D$_3^+$ are extended using a combination of high accuracy variational calculations and analysis of transition intensities. All line lists are made available via www.exomol.com.

Published
2023
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14. Data structures for photoabsorption within the ExoMol project

Author

Tennyson, Jonathan, Pezzella, Marco, Zhang, Jingxin, and Yurchenko, Sergei N.

Subjects
Astrophysics - Earth and Planetary Astrophysics, Astrophysics - Instrumentation and Methods for Astrophysics, Physics - Chemical Physics
Abstract

The ExoMol database currently provides comprehensive line lists for modelling the spectroscopic properties of molecules in hot atmospheres. Extending the spectral range of the data provided to ultraviolet (UV) wavelengths brings into play three processes not currently accounted for in the ExoMol data structure, namely photodissociation, which is an important chemical process in its own right,the opacity contribution due to continuum absorption and predissociation which can lead to significant and observable line broadening effects. Data structures are proposed which will allow these processes to be correctly captured and the (strong) temperature-dependent effects predicted for UV molecular photoabsorption in general and photodissociation in particular to be represented., Comment: This version contains some minor corrections compared to the published version

Published
2023
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15. Positivity Conditions for Generalised Schwarzschild Space-Times

Author

D'Alise, A., Fabiano, G., Frattulillo, D., Hohenegger, S., Iacobacci, D., Pezzella, F., and Sannino, F.

Subjects
General Relativity and Quantum Cosmology, High Energy Physics - Theory
Abstract

We analyse the impact of positivity conditions on static spherically symmetric deformations of the Schwarzschild space-time. The metric is taken to satisfy, at least asymptotically, the Einstein equation in the presence of a non-trivial stress-energy tensor, on which we impose various physicality conditions. We systematically study and compare the impact of these conditions on the space-time deformations. The universal nature of our findings applies to both classical and quantum metric deformations with and without event horizons. We further discuss minimal realisations of the asymptotic stress energy tensor in terms of physical fields. Finally, we illustrate our results by discussing concrete models of quantum black holes., Comment: LaTeX, 40 pages, 9 figures

Published
2023

16. Advances in the understanding of the pathophysiology of schizophrenia and bipolar disorder through induced pluripotent stem cell models

Author

Perrottelli, Andrea, Marzocchi, Francesco Flavio, Caporusso, Edoardo, Giordano, Giulia Maria, Giuliani, Luigi, Melillo, Antonio, Pezzella, Pasquale, Bucci, Paola, Mucci, Armida, and Galderisi, Silvana

Subjects
Medical research, Medicine, Experimental, Schizophrenia, Stem cells, GABA, Neurophysiology, Health, Psychology and mental health
Abstract

The pathophysiology of schizophrenia and bipolar disorder involves a complex interaction between genetic and environmental factors that begins in the early stages of neurodevelopment. Recent advancements in the field of induced pluripotent stem cells (iPSCs) offer a promising tool for understanding the neurobiological alterations involved in these disorders and, potentially, for developing new treatment options. In this review, we summarize the results of iPSC-based research on schizophrenia and bipolar disorder, showing disturbances in neurodevelopmental processes, imbalance in glutamatergic-GABAergic transmission and neuromorphological alterations. The limitations of the reviewed literature are also highlighted, particularly the methodological heterogeneity of the studies, the limited number of studies developing iPSC models of both diseases simultaneously, and the lack of in-depth clinical characterization of the included samples. Further studies are needed to advance knowledge on the common and disease-specific pathophysiological features of schizophrenia and bipolar disorder and to promote the development of new treatment options., Introduction Schizophrenia and bipolar disorder are complex and challenging mental disorders, whose etiopathogenesis can be traced back to a complex interaction between genetic and environmental factors that begins at the [...]

Published
2024
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19. Water Dynamics around T0 vs. R4 of Hemoglobin from Local Hydrophobicity Analysis

Author

Salehi, Seyedeh Maryam, Pezzella, Marco, Willard, Adam, Meuwly, Markus, and Karplus, Martin

Subjects
Physics - Chemical Physics, Physics - Biological Physics
Abstract

The local hydration around tetrameric Hb in its T$_0$ and R$_4$ conformational substates is analyzed based on molecular dynamics simulations. Analysis of the local hydrophobicity (LH) for all residues at the $\alpha_1 \beta_2$ and $\alpha_2 \beta_1$ interfaces, responsible for the quaternary T$\rightarrow$R transition, which is encoded in the MWC model, as well as comparison with earlier computations of the solvent accessible surface area (SASA), makes clear that the two quantities measure different aspects of hydration. Local hydrophobicity quantifies the presence and structure of water molecules at the interface whereas ``buried surface'' reports on the available space for solvent. For simulations with Hb frozen in its T$_0$ and R$_4$ states the correlation coefficient between LH and buried surface is 0.36 and 0.44, respectively, but it increases considerably if the 95 \% confidence interval is used. The LH with Hb frozen and flexible changes little for most residues at the interfaces but is significantly altered for a few select ones, which are Thr41$\alpha$, Tyr42$\alpha$, Tyr140$\alpha$, Trp37$\beta$, Glu101$\beta$ (for T$_0$) and Thr38$\alpha$, Tyr42$\alpha$, Tyr140$\alpha$ (for R$_4$). The number of water molecules at the interface is found to increase by $\sim 25$ \% for T$_0$$\rightarrow$R$_4$ which is consistent with earlier measurements. Since hydration is found to be essential to protein function, it is clear that hydration also plays an essential role in allostery.

Published
2022

20. On the classical Integrability of Poisson-Lie T-dual WZW models

Author

Bascone, Francesco, Pezzella, Franco, and Vitale, Patrizia

Subjects
High Energy Physics - Theory, Mathematical Physics
Abstract

We consider the integrability of a two-parameter deformation of the Wess-Zumino-Witten model, previously introduced in relation with Poisson-Lie T-duality. The resulting family of Poisson-Lie dual models is shown to be integrable by using the Maillet r/s formalism., Comment: 20 pages

Published
2022
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21. Illness-related variables and abnormalities of resting-state brain activity in schizophrenia

Author

Luigi Giuliani, Pasquale Pezzella, Giulia Maria Giordano, Leonardo Fazio, Armida Mucci, Andrea Perrottelli, Giuseppe Blasi, Mario Amore, Paola Rocca, Alessandro Rossi, Alessandro Bertolino, Silvana Galderisi, and Mario Maj

Subjects
cognitive impairments, negative symptoms, expressive deficit domain, motivational deficit domain, biomarkers, resting-state fMRI, Psychiatry, RC435-571
Abstract

BackgroundThe development of neuroimaging biomarkers in patients with schizophrenia (SCZ) requires a refined clinical characterization. A limitation of the neuroimaging literature is the partial uptake of progress in characterizing disease-related features, particularly negative symptoms (NS) and cognitive impairment (CI). In the present study, we assessed NS and CI using up-to-date instruments and investigated the associations of abnormalities in brain resting-state (rs)-activity with disease-related features.MethodsSixty-two community-dwelling SCZ subjects participated in the study. Multiple regression analyses were performed with the rs-activity of nine regions of interest as dependent variables and disease-related features as explanatory variables.ResultsAttention/vigilance deficits were negatively associated with dorsal anterior cingulate rs-activity and, together with depression, were positively associated with right dorsolateral prefrontal cortex rs-activity. These deficits and impairment of Reasoning/problem-solving, together with conceptual disorganization, were associated with right inferior parietal lobule and temporal parietal junction rs-activity. Independent of other features, the NS Expressive Deficit domain was associated with the left ventral caudate, while the Motivational Deficit was associated with the dorsal caudate rs-activity.ConclusionNeurocognitive deficits and the two negative symptom domains are associated with different neural markers. Replications of these findings could foster the identification of clinically actionable biomarkers of poor functional outcomes.

Published
2024
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25. ExoMol photodissociation cross sections I: HCl and HF

Author

Pezzella, Marco, Tennyson, Jonathan, and Yurchenko, Sergei N.

Subjects
Physics - Chemical Physics, Astrophysics - Earth and Planetary Astrophysics
Abstract

Photon initiated chemistry, \textit{i.e.} the interaction of light with chemical species, is a key factor in the evolution of the atmosphere of exoplanets. For planets orbiting stars in UV-rich environments, photodissociation induced by high energy photons dominates the atmosphere composition and dynamics. The rate of photodissociation can be highly dependent on atmospheric temperature, as increased temperature leads to increased population of vibrational excited states and the consequent lowering of the photodissociation threshold. This paper inaugurates a new series of papers presenting computed temperature-dependent photodissociation cross sections with rates generated for different stellar fields. Cross sections calculations are performed by solving the time-independent Schr\"{o}dinger equation for each electronic state involved in the process. Here photodissociation cross sections for hydrogen chloride and hydrogen fluoride are computed for a grid of 34 temperatures between 0 and 10~000 K. Use of different radiation fields shows that for the Sun and cooler stars the photodissociation rate can increase exponentially for molecular temperatures above 1000 K; conversely the photodissociation rates in UV rich fields instead are almost insensitive to the temperature of the molecule. Furthermore, these rates show extreme sensitivity to the radiation model used for cool stars, suggesting that further work on these may be required. The provision of an ExoMol database of cross sections is discussed.

Published
2022
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26. Low cytoplasmic NUB1 protein exerts hypoxic cell death with poorer prognosis in oestrogen receptor negative breast cancer patients

Author

Ka-Liong Tan, Syed Haider, Christos E. Zois, Jianting Hu, Helen Turley, Russell Leek, Francesca Buffa, Oreste Acuto, Adrian L. Harris, and Francesco Pezzella

Subjects
NUB1, Oestrogen receptor, Immunohistochemistry, Biomarkers, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Current prognostic biomarkers fall short in stratifying Oestrogen receptor (ER)-negative breast cancer patients regarding tumour progression risk at diagnosis. The role of AIPL1 in activating its tumour suppressor client protein, NEDD8 Ultimate Buster-1 (NUB1) remains unknown in cancer. Our study demonstrated how downregulated AIPL1 results in the deactivated NUB1 protein under hypoxic conditions. We examined the AIPL1-NUB1 pathwayin vitro using cell lines i.e. MCF-7, MDA-MB-231, RCC4 etc. NUB1 expression was assessed using Oncomine, and cBioPortal was performed to assess NUB1′s prognostic significance in human cancers. In the John Radcliffe Hospital cohort (n = 122), immunohistochemistry analysis revealed downregulated AIPL1 (Log2 fold change=-0.28; p < 0.001) and upregulated NUB1 transcripts (Log2 fold change=0.59; p < 0.001) compared to adjacent normal tissues. In severe chronic hypoxia, multimerised AIPL1 localisedin the cytoplasm while NUB1 protein migrated to the nucleus, where the absence of NUB1 nuclear localisation led to cell cycle arrest. Biopsies showed that patients with lower cytoplasmic NUB1 expression (n = 57) had poorer overall survival compared to those with higher cytoplasmic expression (n = 57), HR=1.78; 95 % CI=1.01–3.35, p = 0.048. Low NUB1 protein levels in both normoxic and hypoxic conditions were associated with cell cycle arrest and upregulation ofp21 and p27 in breast cancer cell lines, correlating significantly withpoorer survival outcomes in all breast cancer and ER-negative breast cancer patients.

Published
2024
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27. Comprehensive Observational and Longitudinal study on the Outbreak of Stroke-related Spasticity focusing on the Early Onset management with Botulinum NeuroToxin (COLOSSEO-BoNT): protocol for a real-world prospective observational study on upper limb spasticity

Author

Vincenzo Di Lazzaro, Claudio Gasperini, Diego Centonze, Danilo Toni, Deepak Gupta, Irene Aprile, Fabio Pilato, Marina Diomedi, Massimo Marano, Giovanni Frisullo, Marco Andrighetti, Maria Concetta Altavista, Luigi Polidori, Antonio Suppa, Maria Giuseppina Palmieri, Emanuela Cecconi, Roberta Bovenzi, Vittorio Riso, Alexia Anzini, Marianna Brienza, Sabrina Anticoli, Domenica Crupi, Morena Giovannelli, Andrea Massimiani, Steno Rinalduzzi, Emanuele Morena, Maria Carlotta Massara, Letizia Cupini, Federica Bressi, Loredana Maggi, Donato Sauchelli, Ennio Iezzi, Alessandro Magliozzi, Stefano Toro, Gaia Anzini, Claudia Celletti, Paolo Amisano, Marco Falletti, Pierandrea Rizzo, Grazia Libutti, Marilena Mangiardi, Francesca Romana Pezzella, Silvia La Cesa, Marina Cao, Francesco Asci, Serena Capobianco, Luisella D’Angeli, and Caterina Galluccio

Subjects
Medicine
Abstract

Introduction Poststroke spasticity (PSS) affects up to 40% of patients who had a stroke. Botulinum neurotoxin type A (BoNT-A) has been shown to improve spasticity, but the optimal timing of its application remains unclear. While several predictors of upper limb PSS are known, their utility in clinical practice in relation to BoNT-A treatment has yet to be fully elucidated. The COLOSSEO-BoNT study aims to investigate predictors of PSS and the effects of BoNT-A timing on spasticity-related metrics in a real-world setting.Methods and analysis The recruitment will involve approximately 960 patients who have recently experienced an ischaemic stroke (within 10 days, V0) and will follow them up for 24 months. Parameters will be gathered at specific intervals: (V1) 4, (V2) 8, (V3) 12, (V4) 18 months and (V5) 24 months following enrolment. Patients will be monitored throughout their rehabilitation and outpatient clinic journeys and will be compared based on their BoNT-A treatment status—distinguishing between patients receiving treatment at different timings and those who undergo rehabilitation without treatment. Potential predictors will encompass the Fugl-Meyer assessment, the National Institute of Health Stroke Scale (NIHSS), stroke radiological characteristics, performance status, therapies and access to patient care pathways. Outcomes will evaluate muscle stiffness using the modified Ashworth scale and passive range of motion, along with measures of quality of life, pain, and functionality.Ethics and dissemination This study underwent review and approval by the Ethics Committee of the Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy. Regardless of the outcome, the findings will be disseminated through publication in peer-reviewed journals and presentations at national and international conferences.Trial registration number NCT05379413.

Published
2024
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29. The Effective Theory of Quantum Black Holes

Author

Binetti, Emanuele, Del Piano, Manuel, Hohenegger, Stefan, Pezzella, Franco, and Sannino, Francesco

Subjects
General Relativity and Quantum Cosmology, High Energy Physics - Phenomenology, High Energy Physics - Theory
Abstract

We explore the quantum nature of black holes by introducing an effective framework that takes into account deviations from the classical results. The approach is based on introducing quantum corrections to the classical Schwarzschild geometry in a way that is consistent with the physical scales of the black hole and its classical symmetries. This is achieved by organizing the quantum corrections in inverse powers of a physical distance. By solving the system in a self-consistent way we show that the derived physical quantities, such as event horizons, temperature and entropy can be expressed in a well defined expansion in the inverse powers of the black hole mass. The approach captures the general form of the quantum corrections to black hole physics without requiring to commit to a specific model of quantum gravity., Comment: Revised version matching the published one

Published
2022
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33. Models of care in emergency neurology: from the Neuro Fast Track to the emergency neurologist—a position paper of the Italian Association for Emergency Neurology (ANEU)

Author

Micieli, Giuseppe, Cortelli, Pietro, Del Sette, Massimo, Quatrale, Rocco, Cavallini, Anna, Zedde, Maria Luisa, Zanferrari, Carla, de Falco, Arturo, Guarino, Maria, Cossu, Giovanni, Haggiag, Shalom, Pezzella, Francesca Romana, Porreca, Alessandro, Pistoia, Francesca, Andreone, Vincenzo, Giometto, Bruno, Gasperini, Claudio, Giorli, Elisa, Salmaggi, Andrea, Lattanzi, Simona, Labate, Carmelo Roberto, Rinaldi, Giuseppe, Melis, Maurizio, Caggia, Emanuele, Volpi, Gino, Passadore, Paolo, Corea, Francesco, and Franco, Giovanni Maria

Published
2023
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34. MYOD-SKP2 axis boosts tumorigenesis in fusion negative rhabdomyosarcoma by preventing differentiation through p57Kip2 targeting

Author

Silvia Pomella, Matteo Cassandri, Lucrezia D’Archivio, Antonella Porrazzo, Cristina Cossetti, Doris Phelps, Clara Perrone, Michele Pezzella, Antonella Cardinale, Marco Wachtel, Sara Aloisi, David Milewski, Marta Colletti, Prethish Sreenivas, Zoë S. Walters, Giovanni Barillari, Angela Di Giannatale, Giuseppe Maria Milano, Cristiano De Stefanis, Rita Alaggio, Sonia Rodriguez-Rodriguez, Nadia Carlesso, Christopher R. Vakoc, Enrico Velardi, Beat W. Schafer, Ernesto Guccione, Susanne A. Gatz, Ajla Wasti, Marielle Yohe, Myron Ignatius, Concetta Quintarelli, Janet Shipley, Lucio Miele, Javed Khan, Peter J. Houghton, Francesco Marampon, Berkley E. Gryder, Biagio De Angelis, Franco Locatelli, and Rossella Rota

Subjects
Science
Abstract

Abstract Rhabdomyosarcomas (RMS) are pediatric mesenchymal-derived malignancies encompassing PAX3/7-FOXO1 Fusion Positive (FP)-RMS, and Fusion Negative (FN)-RMS with frequent RAS pathway mutations. RMS express the master myogenic transcription factor MYOD that, whilst essential for survival, cannot support differentiation. Here we discover SKP2, an oncogenic E3-ubiquitin ligase, as a critical pro-tumorigenic driver in FN-RMS. We show that SKP2 is overexpressed in RMS through the binding of MYOD to an intronic enhancer. SKP2 in FN-RMS promotes cell cycle progression and prevents differentiation by directly targeting p27Kip1 and p57Kip2, respectively. SKP2 depletion unlocks a partly MYOD-dependent myogenic transcriptional program and strongly affects stemness and tumorigenic features and prevents in vivo tumor growth. These effects are mirrored by the investigational NEDDylation inhibitor MLN4924. Results demonstrate a crucial crosstalk between transcriptional and post-translational mechanisms through the MYOD-SKP2 axis that contributes to tumorigenesis in FN-RMS. Finally, NEDDylation inhibition is identified as a potential therapeutic vulnerability in FN-RMS.

Published
2023
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35. Association of Radiochemotherapy to Immunotherapy in unresectable locally advanced Oesophageal carciNoma—randomized phase 2 trial ARION UCGI 33/PRODIGE 67: the study protocol

Author

Anouchka Modesto, David Tougeron, Pierre Tremolières, Philippe Ronchin, Ariane Darut Jouve, Delphine Argo Leignel, Véronique Vendrely, Olivier Riou, Jérôme Martin-Babau, Samuel Le Sourd, Xavier Mirabel, Thomas Leroy, Florence Huguet, Lucile Montaigne, Isabelle Baumgaertner, Marion Deslandres, Elizabeth Moyal, Catherine Seva, Janick Selves, Philippe Otal, Veronica Pezzella, Rosine Guimbaud, Thomas Filleron, and Laurent Quéro

Subjects
Esophagus carcinoma, Randomized trial, Phase II, Chemo-radiotherapy, Immunotherapy, Anti-PD-L1, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background In case of locally advanced and/or non-metastatic unresectable esophageal cancer, definitive chemoradiotherapy (CRT) delivering 50 Gy in 25 daily fractions in combination with platinum-based regimen remains the standard of care resulting in a 2-year disease-free survival of 25% which deserves to be associated with new systemic strategies. In recent years, several immune checkpoint inhibitors (anti-PD1/anti-PD-L1, anti-Program-Death 1/anti-Program-Death ligand 1) have been approved for the treatment of various solid malignancies including metastatic esophageal cancer. As such, we hypothesized that the addition of an anti-PD-L1 to CRT would provide clinical benefit for patients with locally advanced oesophageal cancer. To assess the efficacy of the anti-PD-L1 durvalumab in combination with CRT and then as maintenance therapy we designed the randomized phase II ARION (Association of Radiochemotherapy with Immunotherapy in unresectable Oesophageal carciNoma- UCGI 33/PRODIGE 67). Methods ARION is a multicenter, open-label, randomized, comparative phase II trial. Patients are randomly assigned in a 1:1 ratio in each arm with a stratification according to tumor stage, histology and centre. Experimental arm relies on CRT with 50 Gy in 25 daily fractions in combination with FOLFOX regimen administrated during and after radiotherapy every two weeks for a total of 6 cycles and durvalumab starting with CRT for a total of 12 infusions. Standard arm is CRT alone. Use of Intensity Modulated radiotherapy is mandatory. The primary endpoint is to increase progression-free survival at 12 months from 50 to 68% (HR = 0.55) (power 90%; one-sided alpha-risk, 10%). Progression will be defined with central external review of imaging. Ancillary studies are planned PD-L1 Combined Positivity Score on carcinoma cells and stromal immune cells of diagnostic biopsy specimen will be correlated to disease free survival. The study of gut microbiota will aim to determine if baseline intestinal bacteria correlates with tumor response. Proteomic analysis on blood samples will compare long-term responder after CRT with durvalumab to non-responder to identify biomarkers. Conclusion Results of the present study will be of great importance to evaluate the impact of immunotherapy in combination with CRT and decipher immune response in this unmet need clinical situation. Trial registration ClinicalTrials.gov, NCT: 03777813.Trial registration date: 5th December 2018.

Published
2023
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36. Spontaneous Non-Aneurysmal Convexity Subarachnoid Hemorrhage: A Scoping Review of Different Etiologies beyond Cerebral Amyloid Angiopathy

Author

Marialuisa Zedde, Ilaria Grisendi, Federica Assenza, Manuela Napoli, Claudio Moratti, Claudio Pavone, Lara Bonacini, Giovanna Di Cecco, Serena D’Aniello, Francesca Romana Pezzella, Giovanni Merlino, Fabrizio Piazza, Alessandro Pezzini, Andrea Morotti, Enrico Fainardi, Danilo Toni, Franco Valzania, and Rosario Pascarella

Subjects
convexity subarachnoid hemorrhage, MRI, cerebral amyloid angiopathy, CAA-related inflammation, endocarditis, cerebral venous thrombosis, Medicine
Abstract

Spontaneous convexity subarachnoid hemorrhage (cSAH) is a vascular disease different from aneurysmal SAH in neuroimaging pattern, causes, and prognosis. Several causes might be considered in individual patients, with a limited value of the patient’s age for discriminating among these causes. Cerebral amyloid angiopathy (CAA) is the most prevalent cause in people > 60 years, but reversible cerebral vasoconstriction syndrome (RCVS) has to be considered in young people. CAA gained attention in the last years, but the most known manifestation of cSAH in this context is constituted by transient focal neurological episodes (TFNEs). CAA might have an inflammatory side (CAA-related inflammation), whose diagnosis is relevant due to the efficacy of immunosuppression in resolving essudation. Other causes are hemodynamic stenosis or occlusion in extracranial and intracranial arteries, infective endocarditis (with or without intracranial infectious aneurysms), primary central nervous system angiitis, cerebral venous thrombosis, and rarer diseases. The diagnostic work-up is fundamental for an etiological diagnosis and includes neuroimaging techniques, nuclear medicine techniques, and lumbar puncture. The correct diagnosis is the first step for choosing the most effective and appropriate treatment.

Published
2024
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39. Genetic determinants of coping, resilience and self-esteem in schizophrenia suggest a primary role for social factors and hippocampal neurogenesis

Author

Caulo, Chiara, D'Agostino, Giulia, Corrivetti, Giulio, Selvaggi, Pierluigi, D'Ambrosio, Enrico, Di Palo, Piergiuseppe, Atti, Anna Rita, Barlati, Stefano, Ceraso, Anna, Nibbio, Gabriele, Paribello, Pasquale, Marras, Luca, Carpiniello, Bernardo, Piegari, Giuseppe, Giordano, Giulia Maria, Pezzella, Pasquale, Melillo, Antonio, Concerto, Carmen, Mineo, Ludovico, Pettorruso, Mauro, Chiappini, Stefania, Di Carlo, Francesco, Altamura, Mario, Leccisotti, Ivana, De Masi, Laura, Calcagno, Pietro, Serafini, Gianluca, Arzani, Costanza, Di Stefano, Ramona, Pacitti, Francesca, Rossi, Rodolfo, Giusti, Laura, Mammarella, Silvia, Vecchio, Sasha Del, Marcatili, Matteo, Fusi, Oscar, Gramaglia, Carla, Marangon, Debora, Bestagini, Lucia, Meneguzzo, Paolo, Tenconi, Elena, Favaro, Angela, Gerra, Maria Lidia, Borelli, Davide Fausto, Magnani, Francesca, Carpita, Barbara, Cremone, Ivan Mirko, Amatori, Giulia, Buzzanca, Antonino, Frascarelli, Marianna, Accinni, Tommaso, Berardelli, Isabella, Erbuto, Denise, Comparelli, Anna, Cuomo, Alessandro, Goracci, Arianna, Bolognesi, Simone, Niolu, Cinzia, Di Lorenzo, Giorgio, Jannini, Tommaso, Brasso, Claudio, Villari, Vincenzo, Sgro, Rodolfo, Mazzarotto, Francesco, Monteleone, Palmiero, Minelli, Alessandra, Mattevi, Stefania, Cascino, Giammarco, Rocca, Paola, Rossi, Alessandro, Bertolino, Alessandro, Aguglia, Eugenio, Altamura, Carlo, Amore, Mario, Bellomo, Antonello, Bucci, Paola, Collantoni, Enrico, Dell'Osso, Liliana, Di Fabio, Fabio, Fagiolini, Andrea, Giuliani, Luigi, Marchesi, Carlo, Martinotti, Giovanni, Montemagni, Cristiana, Pinna, Federica, Pompili, Maurizio, Rampino, Antonio, Roncone, Rita, Siracusano, Alberto, Vita, Antonio, Zeppegno, Patrizia, Galderisi, Silvana, Gennarelli, Massimo, and Maj, Mario

Published
2024
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40. Effect of the Factor XIa Inhibitor Asundexian According to Baseline Infarct Pattern and on MRI Covert Infarct Outcomes

Author

Smith, Eric E., Shoamanesh, Ashkan, Xu, Lizhen, Heenan, Laura, Saad, Feryal, Colorado, Pablo, Chen, Chih-Hao, Lemmens, Robin, De Marchis, Gian Marco, Caso, Valeria, Masjuan, Jaime, Hirano, Teruyuki, Milanov, Ivan, Campbell, Bruce C.V., Mas, Jean-Louis, Connolly, Stuart J., Mundl, Hardi, Hart, Robert G., Bailey, P., Kleinig, T., Cordato, D., Choi, P., Garcia-Esperon, C., Chew, A., Cloud, G., Stanislaus, V., Krause, M., Priglinger, M., Grimley, R., Ghia, D., Sahathevan, R., Brown, H., Kwan, C., Devlin, M., Greisenegger, S., Bonelli-Nauer, S., Rath, J., Langer, A., Marko, M., Ferrari, J., Bernegger, A., Baumgartinger, M., Vigl, M., Krebs, S., Lang, W., Knoflach, M., Dejakum, B., Kiechl, S., Töll, T., Domig, L., Mutzenbach, J.S., Ganser, B., Hecker, C., Rösler, C., Bubel, N., Pikija, S., Zellner, T., Leitner, U., Berger, O., Surböck, B., Beirer, S., Staykov, D., Schrammel, D., Halilovic, A., Frattner, M., Barmherzigen, D., Lampl, C., Höfer, C., Nagl, S., Bocksrucker, C., Demeestere, J., Desfontaines, P., Ciobanu, C., De Pauw, A., Terwecoren, A., Hasenbroekx, M.C., Clement, F., De Klippel, N., Soors, P., Hermans, S., De Raedt, S., Vandervorst, F., Seynaeve, L., Fockaert, N., Smet, S., Rutgers, M., Del Gaudio, N., Paindeville, P., Staikov, I., Simeonova, A., Stoyanova, I., Cholakova, M., Mihnev, N., Petrova, T., Koralova, A., Dimov, D., Kuzev, Y., Danovska, M., Marinova, D., Marinova-Trifonova, D., Ovcharova, E., Mladenovski, I., Yanakieva, M., Stoev, P., Dimitrova, M., Todorova-Georgieva, S., Haralanov, L., Milkov, B., Solakov, D., Petkova, N., Ignatova-Valkova, V., Karabinov, V., Marinova, V., Miteva, Y., Andonova, V., Kasabova, D., Kostadinova, E., Shopova-Vrabcheva, Y., Gatev, D., Semova, D., Halil, E., Kaprelyan, A., Ivanov, B., Panov, G., Grudkova, M., Syuleyman, N., Kalpachki, R., Alexiev, F., Ivanova, I., Kancheva, K., Sakelarova, T., Maslarov, D., Drenska, D., Georgiev, V., Petrova, K., Petrova, N., Ivanova, I., Semerdjieva, N., Zhelyazkov, P., Spasova-Markova, S., Dong, X., Wang, D., Wang, S., Huang, W., Zhao, H., Wang, C., Jie, L., Xinyang, Y., Ping, Z., Dong, Q., Wang, Y., Fuling, Y., Yue, W., Liu, R., Yang, Y., Stetkarova, I., Mikulenka, P., Vasko, P., Peisker, T., Bar, M., Roubec, M., Mikulik, R., Cabukova, M., Vinklarek, J., Kovar, M., Pansky, M., Mencl, P., Skoda, O., Carek, M., Pernicka, M., Skodova, M., Geier, P., Cepkova, J., Drlik, J., Prax, T., Herzig, R., Krajickova, D., Vitkova, E., Haluskova, S., Vaclavik, D., Martinkova, J., Blejcharova, K., Tkacova, M., Pavlik, O., Nevšímalová, M., Rosol, J., Nevsimalova, M., Hruby, R., Iversen, H., Andersen, A.V., Rahimi, D., Christensen, H., Grundtvig, J., Hjort, N., Andersen, G., Sandal, B., Stilund, M., Modrau, B., Strade, A., Porobic, M., Andersen, S.D., Kruuse, C., Ölmestig, J., Kolmos, M., Parvez, A., Christensen, T., Stokholm, J., Jensen, H.B., Putaala, J., Strbian, D., Sibolt, G., Tiainen, M., Martinez-Majander, N., Curtze, S., Raty, S., Kraemer, Y., Roine, R., Aivo, J., Ruuskanen, J., Ylikotila, P., Roine, S., Hallikainen, M., Jakala, P., Kurl, S., Julkunen, V., Sibon, I., Olindo, S., Richard, S., Larrue, V., Gollion, C., Catala, H., Henon, H., Lucie, D.S., Nelly, D., Calvet, D., Malbranque, A., Mazé, B., Barbieux-Ghitu, C., Rosso, C., Samson, Y., Vannier, S., Moulin, T., Bonnet, L., Reiner, P., Buffon, F., Denier, C., Amri, K., Legris, N., Chassin, O., Selli, N., Mariana, S., Berrouschot, J., Stoll, A., Klunk, D., Keilitz, J., Neustadt, M., Zerrenner, S., Veltkamp, R., Hajjar, K., Heeger, A., Winezki, E., Apel, L., Pompsch, M., Mueller, P., Rappard, P., Auer, R., Ringleb, P.A., Berberich, A., Heyse, M., Mundiyanapurath, S., Reiff, T., Poli, S., Gomez-Exposito, A., Mengel, A., Tünnerhoff, J., Adeyemi, K., Poli, K., Kusch, V., Pelz, J., Michalski, D., Wartenberg, K., Althaus, K., Tavares, F., Mueller, S., Soda, H., Rascher, A., Hiermann, E., Weinhardt, R., Weissenborn, K., Leotescu, A., Grosse, G., Worthmann, H., Ernst, J., Gabriel, M., Schuppner, R., Schäfer, J.H., Charisse, D., Gruber, K., Kurka, N., Reitz, S.C., Pfeilschifter, W., Lee, J.I., Gliem, M., Moll, M., Steiner, T., Segura, L., Szegedi, N., Barandi, D., Uhrinakova, L., Czencz, M., Pasztor, M., Gyuker, N., Bartha, N.E., May, Z., Simony, Z., Szasz, G., Kakuk, I., Pető, N., Panczel, G.F., Olah, A., Racz, O., Balla, T., Horvath, B., Tuba, K., Czinderi, V., Klivenyi, P., Annus, A., Hertelendy, P., Szapary, L., Bosnyak, E., Kalmar, P., Karadi, Z., Cziba, L., Olah, L., Berki, A., Hudak, L., Kozák, M., Babel, S., Nemeth, L., Molnár, B., Simon, Z., Roveri, L., Cerri, F., Giacalone, G., Zini, A., Mauro, G., Asioli, G.M., Forlivesi, S., Arnone, G., Fiaccadori, A., Maria Fontana Francesca, E., Allegra, G., Mosconi, M.G., Longoni, M., Terlizzi, R., Paolucci, M., Tassi, R., Franci, B., Lucani, B., Domenichelli, C., Paoletti, D., Acampa, M., Zedde, M.L., Pezzella, F.R., Mangiardi, M., Galizia, P., Anticoli, S., Scalise, S., Lattanzi, S., Norata, D., Cannuccia, M., Cavallini, A., Federica, F., Denaro, M.F., Tosi, P., Sonoda, K., Kawajiri, M., Kusano, Y., Haraguchi, K., Kawano, H., Terasaki, T., Kaneko, C., Murase, S., Kumagai, M., Murai, N., Miyazaki, Y., Mori, T., Hatano, T., Kawanishi, M., Ochiai, J., Ishihara, S., Uehara, T., Yasaka, M., Nakagawa, H., Makino, M., Yonehara, T., Fukushima, Y., Hirotsune, N., Sakai, N., Yamasaki, M., Coutinho, J., Wouters, A., den Hertog, H., Zwartbol, R., Beumer, D., Kerklaan, J., Hilkens, P., Schreuder, T., Propper, D., Slowik, A., Wlodarczyk, E., Wrona, P., Pulyk, R., Lasek-Bal, A., Kosarz-Lanczek, K., Puz, P., Bilik, M., Magielska, A., Zamiela – Żółciak, A., Ochocinska, L., Bahdasaryan, S., Stępień, A., Dębiec, A., Joanna, K., Pawel, M., Jacek, S., Daniel, P., Marta, S., Rejdak, K., Wojczal, J., Luchowski, P., Fryze, W., Wisniewska, A., Krzyzanowska, M., Skowron, P., Wolosz, A., Galan, A., Grzymala, K., Krajewska, M., Nowak, R., Kłos, M., Cruz, V., Castro, P., Ferro, J., Canhão, P., Gouveia, R., Inácio, N., Rodrigues, M., Rachão, A., Ionel, C., Pereira, L., Viana-Baptista, M., Machado, C., Fernandes, C., Sargento, J., Inácio, N., Timchenko, L., Mironova, J., Zhadan, O., Torgashova, A., Bazhenova, O., Barashenkova, M., Kireeva, M., Romadina, N., Stepanova, I., Lenskaya, L., Lukinykh, L., Vorontsova, T., Agafina, A., Fedorova, A., Yashina, A., Alasheev, A., Smolkin, A., Prazdnichkova, E., Lutskovich, O., Gonysheva, Y., Mordvintseva, E., Nechaev, A., Martynova, E., Fedoraeva, N., Vishnyakova, T., Popov, D., Merzliakova, A., Margarita, K., Rechkalova, L., Ilyina, A., Kurenkova, N., Barbarash, O., Bazdyrev, E., Zvereva, T., Hromova, A., Morkvenas, A., Postnikova, E., Kovalenko, G., Taran, I., Pavlov, L., Ott, M., Chernitsova, N., Vodopyanova, N., Drozdova, E., Korebo, E., Lobanova, M., Lazareva, N., Snegova, N., Nikolaeva, O., Kolesnikov, Y., Kosheleva, Y., Krastev, G., Tomasova, K., Danis, M., Mako, M., Jankovicova, Z., Stevkova, Z., Kovacik, M., Kubikova, T., Jarosova, A., Serdahely, V., Cilingova, I., Pribulova, I., Sedlak, J., Slebodova, K., Paldaufova, M., Risnovsky, R., Berndtova, B., Urbanova, I., Junas, R., Karapetian, S., Gurcik, L., Vantrobova, A., Verbovsky, F., Vanacka, K., Ferenc, M., Galik, P., Bucakova, S., Ferencova, M., Kubalova, P., Boksanska, Z., Zacharova, E., Mahundi, E., Judita, H., Bachnak, M., Turcani, P., Kvasnicova Kamenska, A., Jurik, M., Vestenicka, V., Kycina, M., Sagatova, E., Dvorak, M., Hlubekova, A., Kucera, C., Gernath, L., Ferenc, M., Frimmelova, P., Slebodnikova, J., Aksteinerova, N., Horny, V., Gregova, Z., Segura, T., Romero, C., Ayo, O., Masjuan Vallejo, J., Cruz, A., De felipe, A, Matute, M.C., Garcia, S., Tembl Ferrairo, J., Vielba, I., Morales Caba, L., Molina, C., Garcia-Tornel García-Camba, Á., Requena Ruiz, M., Noelia, R., Rodriguez-Yañez, M., Rodriguez Castro, E., Lopez, I., Santamaria, M., Arias, S., Purroy García, F., Vázquez Justes, D., Mauri Capdevila, G., Vicente Pascual, M., Martí Fabregas, J., Camps Renom, P., Rodríguez Campello, A., Giralt, E., Krupinski, J., Molina, J., Trillo Senin, C. Ramos Martin, S., De La Fuente Sanz, E., Moniche, F., Manuel, M.R., Pardo, B., Martínez, I., Hernández Pérez, M., Arenillas Lara, J.F., De Lera, M., Egido, J.A., Gomez Escalonilla, C., Guillan, M., Martinez, J., Lindgren, A., Andsberg, G., Wictor, L., Leonidou, M., Stenman, M., Dalberg, N., Laska, A.C., Grünfeldt, A., Lundström, A., Nadzjafov, E., Rooth, E., Dalenbring, I., Sandén, P., Johansson, E., Thomas, G., Zietz, A.V., Rudin, S., Dittrich, T.D., Lilian, K., Kägi, G., Vehoff, J., Arnold, M., Scutelnic, A., Clénin, L., Beyeler, M., Madlaine, M., Maamari, B., Siepen, B., Vynckier, J., Tarnutzer, A., Bertschi, D., Luciani, M., Cereda, C., Maulucci, F., Bianco, G., Shairin, S., Pihan, H.A., Salmen, S., Quinn, T., McAlpine, C., Wright, F., Kalladka, D., Taylor, E., Sohaa, J., Brown, Z., Dawson, J., Cameron, A., Muir, S., Dima, S., Khan, U., Zhang, L., Warburton, E., Chatterjee, K., Nallasivan, A., Curran, D., Haider, S., Ghani, U., Kenton, A., Dallol, B., Mirza, M., Menezes, B., Davies, R., Robinson, T.G., Manning, L., Sztriha, L., Phinney, T., Sethi, P., Altafullah, I., Sharaf, A., Ostrander, M., Renati, S., Burgin, W.S., Olds, K., Delio, P., Malek, A., Dissin, J., Khatri, P., Flaherty, M., Demel, S., and Dofitas, S.

Published
2024
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44. Differential alternative splicing analysis links variation in ZRSR2 to a novel type of oral-facial-digital syndrome

Author

Hannes, Laurens, Atzori, Marta, Goldenberg, Alice, Argente, Jesús, Attie-Bitach, Tania, Amiel, Jeanne, Attanasio, Catia, Braslavsky, Débora G., Bruel, Ange-Line, Castanet, Mireille, Dubourg, Christèle, Jacobs, An, Lyonnet, Stanislas, Martinez-Mayer, Julian, Pérez Millán, María Inés, Pezzella, Nunziana, Pelgrims, Elise, Aerden, Mio, Bauters, Marijke, Rochtus, Anne, Scaglia, Paula, Swillen, Ann, Sifrim, Alejandro, Tammaro, Roberta, Mau-Them, Frederic Tran, Odent, Sylvie, Thauvin-Robinet, Christel, Franco, Brunella, and Breckpot, Jeroen

Published
2024
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45. MYOD-SKP2 axis boosts tumorigenesis in fusion negative rhabdomyosarcoma by preventing differentiation through p57Kip2 targeting

Author

Pomella, Silvia, Cassandri, Matteo, D’Archivio, Lucrezia, Porrazzo, Antonella, Cossetti, Cristina, Phelps, Doris, Perrone, Clara, Pezzella, Michele, Cardinale, Antonella, Wachtel, Marco, Aloisi, Sara, Milewski, David, Colletti, Marta, Sreenivas, Prethish, Walters, Zoë S., Barillari, Giovanni, Di Giannatale, Angela, Milano, Giuseppe Maria, De Stefanis, Cristiano, Alaggio, Rita, Rodriguez-Rodriguez, Sonia, Carlesso, Nadia, Vakoc, Christopher R., Velardi, Enrico, Schafer, Beat W., Guccione, Ernesto, Gatz, Susanne A., Wasti, Ajla, Yohe, Marielle, Ignatius, Myron, Quintarelli, Concetta, Shipley, Janet, Miele, Lucio, Khan, Javed, Houghton, Peter J., Marampon, Francesco, Gryder, Berkley E., De Angelis, Biagio, Locatelli, Franco, and Rota, Rossella

Published
2023
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46. Association of Radiochemotherapy to Immunotherapy in unresectable locally advanced Oesophageal carciNoma—randomized phase 2 trial ARION UCGI 33/PRODIGE 67: the study protocol

Author

Modesto, Anouchka, Tougeron, David, Tremolières, Pierre, Ronchin, Philippe, Jouve, Ariane Darut, Leignel, Delphine Argo, Vendrely, Véronique, Riou, Olivier, Martin-Babau, Jérôme, Le Sourd, Samuel, Mirabel, Xavier, Leroy, Thomas, Huguet, Florence, Montaigne, Lucile, Baumgaertner, Isabelle, Deslandres, Marion, Moyal, Elizabeth, Seva, Catherine, Selves, Janick, Otal, Philippe, Pezzella, Veronica, Guimbaud, Rosine, Filleron, Thomas, and Quéro, Laurent

Published
2023
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48. Negative symptoms and social cognition as mediators of the relationship between neurocognition and functional outcome in schizophrenia

Author

Giulia M. Giordano, Pasquale Pezzella, Armida Mucci, Stephen F. Austin, Andreas Erfurth, Birte Glenthøj, Alex Hofer, Jan Hubenak, Jan Libiger, Ingrid Melle, Mette Ø. Nielsen, Janusz K. Rybakowski, Pawel Wojciak, Silvana Galderisi, and Gabriele Sachs

Subjects
schizophrenia, negative symptoms, expressive deficit, motivational deficit, emotion recognition, processing speed, Psychiatry, RC435-571
Abstract

IntroductionIn this study we assessed the contribution of psychopathology, including the two domains of negative symptoms (motivational deficit and expressive deficit), processing speed as an index of neurocognition, and emotion recognition, as an index of social cognition, to poor functional outcomes in people with schizophrenia.MethodsThe Positive and Negative Syndrome Scale was used to evaluate positive symptoms and disorganization and the Brief Negative Symptom Scale to assess negative symptoms. The Symbol Coding and the Trail Making Test A and B were used to rate processing speed and the Facial Emotion Identification Test to assess emotion recognition. Functional outcome was assessed with the Personal and Social Performance Scale (PSP). Regression analyses were performed to identify predictors of functional outcome. Mediation analyses was used to investigate whether social cognition and negative symptom domains fully or partially mediated the impact of processing speed on functional outcome.ResultsOne hundred and fifty subjects from 8 different European centers were recruited. Our data showed that the expressive deficit predicted global functioning and together with motivational deficit fully mediated the effects of neurocognition on it. Motivational deficit was a predictor of personal and social functioning and fully mediated neurocognitive impairment effects on the same outcome. Both motivational deficit and neurocognitive impairment predicted socially useful activities, and the emotion recognition domain of social cognition partially mediated the impact of neurocognitive deficits on this outcome.ConclusionsOur results indicate that pathways to functional outcomes are specific for different domains of real-life functioning and that negative symptoms and social cognition mediate the impact of neurocognitive deficits on different domains of functioning. Our results suggest that both negative symptoms and social cognition should be targeted by psychosocial interventions to enhance the functional impact of neurocognitive remediation.

Published
2024
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49. External validation of the five domains of negative symptoms: Focus on cognition, functional capacity, and real-world functioning

Author

Giulia M. Giordano, Francesco Sanmarchi, Armida Mucci, Paola Rucci, Francesco Brando, Edoardo Caporusso, Luigi Giuliani, Antonio Melillo, Pasquale Pezzella, Paola Bucci, Paola Rocca, Alessandro Rossi, Alessandro Bertolino, Rodolfo Rossi, Giulio Pergola, Silvana Galderisi, and Mario Maj

Subjects
BNSS, cognition, five-factor model, functional capacity, hierarchical model, negative symptoms, Psychiatry, RC435-571
Abstract

Abstract Background The conceptualization of negative symptoms (NS) in schizophrenia is still controversial. Recent confirmatory factor-analytic studies suggested that the bi-dimensional model (motivational deficit [MAP] and expressive deficit [EXP]) may not capture the complexity of NS structure, which could be better defined by a five-factor (five NS domains) or a hierarchical model (five NS domains as first-order factors, and MAP and EXP, as second-order factors). A validation of these models is needed to define the structure of NS. To evaluate the validity and temporal stability of the five-factor or the hierarchical structure of the brief negative symptom scale (BNSS) in individuals with schizophrenia (SCZ), exploring associations between these models with cognition, social cognition, functional capacity, and functioning at baseline and at 4 years follow-up. Methods Clinical variables were assessed using state-of-the-art tools in 612 SCZ at two-time points. The validity of the five-factor and the hierarchical models was analyzed through structural equation models. Results The two models had both a good fit and showed a similar pattern of associations with external validators at the two-time points, with minor variations. The five-factor solution had a slightly better fit. The associations with external validators favored the five-factor structure. Conclusions Our findings suggest that both five-factor and hierarchical models provide a valid conceptualization of NS in relation to external variables and that five-factor solution provides the best balance between parsimony and granularity to summarize the BNSS structure. This finding has important implications for the study of pathophysiological mechanisms and the development of new treatments.

Published
2024
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50. A non-standard numerical scheme for an age-of-infection epidemic model

Author

Messina, Eleonora, Pezzella, Mario, and Vecchio, Antonia

Subjects
Mathematics - Numerical Analysis, G.1.9, G.1.10
Abstract

We propose a numerical method for approximating integro-differential equations arising in age-of-infection epidemic models. The method is based on a non-standard finite differences approximation of the integral term appearing in the equation. The study of convergence properties and the analysis of the qualitative behavior of the numerical solution show that it preserves all the basic properties of the continuous model with no restrictive conditions on the step-length $h$ of integration and that it recovers the continuous dynamic as $h$ tends to zero., Comment: 17 pages, 3 figures

Published
2021
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