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1. Hybrid iterating-averaging low photon budget Gabor holographic microscopy

Author

Rogalski, Mikołaj, Arcab, Piotr, Wdowiak, Emilia, Picazo-Bueno, José Ángel, Micó, Vicente, Józwik, Michał, and Trusiak, Maciej

Subjects
Physics - Optics, Electrical Engineering and Systems Science - Image and Video Processing
Abstract

One of the primary challenges in live cell culture observation is achieving high-contrast imaging with minimal impact on sample behavior. Quantitative phase imaging (QPI) techniques address this by providing label-free, high-contrast images of transparent samples. Measurement system influence may be further reduced by imaging samples under low illumination intensity (low photon budget - LPB), thereby minimizing photostimulation, phototoxicity, and photodamage, and enabling high-speed imaging. LPB imaging is challenging in QPI due to significant camera shot noise and quantification noise. Digital in-line holographic microscopy (DIHM), working with or without lenses, is a QPI technique known for its robustness to quantification noise. However, reducing simultaneously the camera shot noise and the inherent in-line holographic twin image disturbances remain a critical, yet unaddressed, challenge. This study introduces an innovative iterative Gabor averaging (IGA) algorithm designed specifically for filling this important scientific gap in multi-frame DIHM under LPB conditions. We evaluated the performance of the IGA on simulated data showing that it outperformed traditional algorithms in terms of reconstruction accuracy under high noise conditions. Those results were corroborated by experimental validation involving high-speed imaging of dynamic sperm cells and a phase test target under significantly reduced illumination power. Additionally, the IGA algorithm proved successful in reconstructing optically thin samples, which typically produce low signal-to-noise ratio holograms even under high photon budget conditions. These advancements facilitate photostimulation-free and high-speed imaging of dynamic biological samples and enhance the capability to image samples with extremely low optical thickness, potentially transforming various applications in biomedical and environmental imaging.

Published
2024

3. «Quale Europa cristiana e quale Lutero?» A proposito di un recente volume di F. Buzzi

Author

Ľubomír J. Žák and Nico de Mico

Subjects
Christianity, BR1-1725
Abstract

The article aims to draw attention to the book Quale Europa cristiana? La continuità di una presenza (Which Christian Europe? The Continuity of a Presence) by Franco Buzzi, a Milanese theologian and renowned scholar of the Lutheran Reformation. It particularly focuses on Buzzi’s intention to explore the relationship between Western Europe and Christianity, not only regarding the developments stemming from the birth and spread of Luther’s Reformation but also concerning the critique of Luther’s thought and reformist work, which continues to characterise certain strands of Catholic historiography and theology. At the core of this critique lies a twofold conviction: that Luther is the instigator of the division of Christianity and Europe, and that he is the primary cause of the decline of European Christendom. The article explains why Buzzi considers these convictions to be entirely unfounded and unjust. Moreover, it demonstrates that his interpretative stance offers important insights, enabling further progress in exploring the theme of ‘Europe and Christianity’ and examining the interconnection between the unity of Europe and the unity of Christianity.

Published
2024
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4. Physics-driven universal twin-image removal network for digital in-line holographic microscopy

Author

Rogalski, Mikołaj, Arcab, Piotr, Stanaszek, Luiza, Micó, Vicente, Zuo, Chao, and Trusiak, Maciej

Subjects
Electrical Engineering and Systems Science - Image and Video Processing, Physics - Optics
Abstract

Digital in-line holographic microscopy (DIHM) enables efficient and cost-effective computational quantitative phase imaging with a large field of view, making it valuable for studying cell motility, migration, and bio-microfluidics. However, the quality of DIHM reconstructions is compromised by twin-image noise, posing a significant challenge. Conventional methods for mitigating this noise involve complex hardware setups or time-consuming algorithms with often limited effectiveness. In this work, we propose UTIRnet, a deep learning solution for fast, robust, and universally applicable twin-image suppression, trained exclusively on numerically generated datasets. The availability of open-source UTIRnet codes facilitates its implementation in various DIHM systems without the need for extensive experimental training data. Notably, our network ensures the consistency of reconstruction results with input holograms, imparting a physics-based foundation and enhancing reliability compared to conventional deep learning approaches. Experimental verification was conducted among others on live neural glial cell culture migration sensing, which is crucial for neurodegenerative disease research.

Published
2023
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5. Clinical characteristics, racial inequities, and outcomes in patients with breast cancer and COVID-19: A COVID-19 and cancer consortium (CCC19) cohort study

Author

Nagaraj, Gayathri, Vinayak, Shaveta, Khaki, Ali Raza, Sun, Tianyi, Kuderer, Nicole M, Aboulafia, David M, Acoba, Jared D, Awosika, Joy, Bakouny, Ziad, Balmaceda, Nicole B, Bao, Ting, Bashir, Babar, Berg, Stephanie, Bilen, Mehmet A, Bindal, Poorva, Blau, Sibel, Bodin, Brianne E, Borno, Hala T, Castellano, Cecilia, Choi, Horyun, Deeken, John, Desai, Aakash, Edwin, Natasha, Feldman, Lawrence E, Flora, Daniel B, Friese, Christopher R, Galsky, Matthew D, Gonzalez, Cyndi J, Grivas, Petros, Gupta, Shilpa, Haynam, Marcy, Heilman, Hannah, Hershman, Dawn L, Hwang, Clara, Jani, Chinmay, Jhawar, Sachin R, Joshi, Monika, Kaklamani, Virginia, Klein, Elizabeth J, Knox, Natalie, Koshkin, Vadim S, Kulkarni, Amit A, Kwon, Daniel H, Labaki, Chris, Lammers, Philip E, Lathrop, Kate I, Lewis, Mark A, Li, Xuanyi, de Lima Lopes, Gilbert, Lyman, Gary H, Makower, Della F, Mansoor, Abdul-Hai, Markham, Merry-Jennifer, Mashru, Sandeep H, McKay, Rana R, Messing, Ian, Mico, Vasil, Nadkarni, Rajani, Namburi, Swathi, Nguyen, Ryan H, Nonato, Taylor Kristian, O'Connor, Tracey Lynn, Panagiotou, Orestis A, Park, Kyu, Patel, Jaymin M, Patel, Kanishka GopikaBimal, Peppercorn, Jeffrey, Polimera, Hyma, Puc, Matthew, Rao, Yuan James, Razavi, Pedram, Reid, Sonya A, Riess, Jonathan W, Rivera, Donna R, Robson, Mark, Rose, Suzanne J, Russ, Atlantis D, Schapira, Lidia, Shah, Pankil K, Shanahan, M Kelly, Shapiro, Lauren C, Smits, Melissa, Stover, Daniel G, Streckfuss, Mitrianna, Tachiki, Lisa, Thompson, Michael A, Tolaney, Sara M, Weissmann, Lisa B, Wilson, Grace, Wotman, Michael T, Wulff-Burchfield, Elizabeth M, Mishra, Sanjay, French, Benjamin, Warner, Jeremy L, Lustberg, Maryam B, Accordino, Melissa K, and Shah, Dimpy P

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Cancer, Infectious Diseases, Women's Health, Coronaviruses, Lung, Emerging Infectious Diseases, Breast Cancer, Good Health and Well Being, United States, Humans, Female, Middle Aged, COVID-19, SARS-CoV-2, Cohort Studies, Breast Neoplasms, Retrospective Studies, COVID-19 and Cancer Consortium, breast cancer, epidemiology, global health, human, oncology, pandemic, racial inequities, Biochemistry and Cell Biology, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundLimited information is available for patients with breast cancer (BC) and coronavirus disease 2019 (COVID-19), especially among underrepresented racial/ethnic populations.MethodsThis is a COVID-19 and Cancer Consortium (CCC19) registry-based retrospective cohort study of females with active or history of BC and laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection diagnosed between March 2020 and June 2021 in the US. Primary outcome was COVID-19 severity measured on a five-level ordinal scale, including none of the following complications, hospitalization, intensive care unit admission, mechanical ventilation, and all-cause mortality. Multivariable ordinal logistic regression model identified characteristics associated with COVID-19 severity.Results1383 female patient records with BC and COVID-19 were included in the analysis, the median age was 61 years, and median follow-up was 90 days. Multivariable analysis revealed higher odds of COVID-19 severity for older age (aOR per decade, 1.48 [95% CI, 1.32-1.67]); Black patients (aOR 1.74; 95 CI 1.24-2.45), Asian Americans and Pacific Islander patients (aOR 3.40; 95 CI 1.70-6.79) and Other (aOR 2.97; 95 CI 1.71-5.17) racial/ethnic groups; worse ECOG performance status (ECOG PS ≥2: aOR, 7.78 [95% CI, 4.83-12.5]); pre-existing cardiovascular (aOR, 2.26 [95% CI, 1.63-3.15])/pulmonary comorbidities (aOR, 1.65 [95% CI, 1.20-2.29]); diabetes mellitus (aOR, 2.25 [95% CI, 1.66-3.04]); and active and progressing cancer (aOR, 12.5 [95% CI, 6.89-22.6]). Hispanic ethnicity, timing, and type of anti-cancer therapy modalities were not significantly associated with worse COVID-19 outcomes. The total all-cause mortality and hospitalization rate for the entire cohort was 9% and 37%, respectively however, it varied according to the BC disease status.ConclusionsUsing one of the largest registries on cancer and COVID-19, we identified patient and BC-related factors associated with worse COVID-19 outcomes. After adjusting for baseline characteristics, underrepresented racial/ethnic patients experienced worse outcomes compared to non-Hispanic White patients.FundingThis study was partly supported by National Cancer Institute grant number P30 CA068485 to Tianyi Sun, Sanjay Mishra, Benjamin French, Jeremy L Warner; P30-CA046592 to Christopher R Friese; P30 CA023100 for Rana R McKay; P30-CA054174 for Pankil K Shah and Dimpy P Shah; KL2 TR002646 for Pankil Shah and the American Cancer Society and Hope Foundation for Cancer Research (MRSG-16-152-01-CCE) and P30-CA054174 for Dimpy P Shah. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH). The funding sources had no role in the writing of the manuscript or the decision to submit it for publication.Clinical trial numberCCC19 registry is registered on ClinicalTrials.gov, NCT04354701.

Published
2023

6. Hot rings on Io observed by Juno/JIRAM

Author

Mura, Alessandro, Tosi, Federico, Zambon, Francesca, Lopes, Rosaly M. C., Mouginis-Mark, Peter J., Becker, Heidi, Filacchione, Gianrico, Migliorini, Alessandra, Hansen, Candice. J., Adriani, Alberto, Altieri, Francesca, Bolton, Scott, Cicchetti, Andrea, Di Mico, Elisa, Grassi, Davide, Noschese, Raffaella, Moirano, Alessandro, Pettine, Madeline, Piccioni, Giuseppe, Plainaki, Christina, Rathbun, Julie, Sordini, Roberto, and Sindoni, Giuseppe

Published
2024
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9. ECP versus ruxolitinib in steroid-refractory chronic GVHD – a retrospective study by the EBMT transplant complications working party

Author

Penack, Olaf, Peczynski, Christophe, Boreland, William, Lemaitre, Jessica, Reinhardt, H. Christian, Afanasyeva, Ksenia, Avenoso, Daniele, Holderried, Tobias A. W., Kornblit, Brian Thomas, Gavriilaki, Eleni, Martinez, Carmen, Chiusolo, Patrizia, Mico, Maria Caterina, Daguenet, Elisabeth, Wichert, Stina, Ozdogu, Hakan, Piekarska, Agnieszka, Kinsella, Francesca, Basak, Grzegorz W., Schoemans, Hélène, Koenecke, Christian, Moiseev, Ivan, and Peric, Zinaida

Published
2024
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10. Versatile optimization-based speed-up method for autofocusing in digital holographic microscopy

Author

Winnik, Julianna, Suski, Damian, Zdańkowski, Piotr, Stanaszek, Luiza, Micó, Vicente, and Trusiak, Maciej

Subjects
Quantitative Biology - Quantitative Methods, Electrical Engineering and Systems Science - Image and Video Processing, Physics - Optics
Abstract

We propose a speed-up method for the in-focus plane detection in digital holographic microscopy that can be applied to a broad class of autofocusing algorithms that involve repetitive propagation of an object wave to various axial locations to decide the in-focus position. The classical autofocusing algorithms apply a uniform search strategy, i.e., they probe multiple, uniformly distributed axial locations, which leads to heavy computational overhead. Our method substantially reduces the computational load, without sacrificing the accuracy, by skillfully selecting the next location to investigate, which results in a decreased total number of probed propagation distances. This is achieved by applying the golden selection search with parabolic interpolation, which is the gold standard for tackling single-variable optimization problems. The proposed approach is successfully applied to three diverse autofocusing cases, providing up to 136-fold speed-up.

Published
2023

11. Lessons learned after three years of SPIDER operation and the first MITICA integrated tests

Author

Marcuzzi, D., Toigo, V., Boldrin, M., Chitarin, G., Bello, S. Dal, Grando, L., Luchetta, A., Pasqualotto, R., Pavei, M., Serianni, G., Zanotto, L., Agnello, R., Agostinetti, P., Agostini, M., Aprile, D., Barbisan, M., Battistella, M., Berton, G., Bigi, M., Brombin, M., Candela, V., Candeloro, V., Canton, A., Casagrande, R., Cavallini, C., Cavazzana, R., Cordaro, L., Cruz, N., Palma, M. Dalla, Dan, M., De Lorenzi, A., Delogu, R., De Muri, M., De Nardi, M., Denizeau, S., Fadone, M., Fellin, F., Ferro, A., Gaio, E., Gasparrini, C., Gnesotto, F., Jain, P., La Rosa, A., Lopez-Bruna, D., Lorenzini, R., Maistrello, A., Manduchi, G., Manfrin, S., Marconato, N., Mario, I., Martini, G., Milazzo, R., Patton, T., Peruzzo, S., Pilan, N., Pimazzoni, A., Poggi, C., Pomaro, N., Pouradier-Duteil, B., Recchia, M., Rigoni-Garola, A., Rizzetto, D., Rizzolo, A., Santoro, F., Sartori, E., Segalini, B., Shepherd, A., Siragusa, M., Sonato, P., Sottocornola, A., Spada, E., Spagnolo, S., Spolaore, M., Taliercio, C., Tinti, P., Tomsič, P., Trevisan, L., Ugoletti, M., Valente, M., Valisa, M., Veronese, F., Vignando, M., Zaccaria, P., Zagorski, R., Zaniol, B., Zaupa, M., Zuin, M., Cavenago, M., Boilson, D., Rotti, C., Decamps, H., Geli, F., Sharma, A., Veltri, P., Zacks, J., Simon, M., Paolucci, F., Garbuglia, A., Gutierrez, D., Masiello, A., Mico, G., Labate, C., Readman, P., Bragulat, E., Bailly-Maitre, L., Gomez, G., Kouzmenko, G., Albajar, F., Kashiwagi, M., Tobari, H., Kojima, A., Murayama, M., Hatakeyama, S., Oshita, E., Maejima, T., Shibata, N., Yamashita, Y., Watanabe, K., Singh, N. P., Singh, M. J., Dhola, H., Fantz, U., Heinemann, B., Wimmer, C., Wünderlich, D., Tsumori, K., Croci, G., Gorini, G., Muraro, A., Rebai, M., Tardocchi, M., Giacomelli, L., Rigamonti, D., Taccogna, F., Bruno, D., Rutigliano, M., Longo, S., Deambrosis, S., Miorin, E., Montagner, F., Tonti, A., and Panin, F.

Subjects
Physics - Plasma Physics, Physics - Accelerator Physics
Abstract

ITER envisages the use of two heating neutral beam injectors plus an optional one as part of the auxiliary heating and current drive system. The 16.5 MW expected neutral beam power per injector is several notches higher than worldwide existing facilities. A Neutral Beam Test Facility (NBTF) was established at Consorzio RFX, exploiting the synergy of two test beds, SPIDER and MITICA. SPIDER is dedicated to developing and characterizing large efficient negative ion sources at relevant parameters in ITER-like conditions: source and accelerator located in the same vacuum where the beam propagates, immunity to electromagnetic interferences of multiple radio-frequency (RF) antennas, avoidance of RF-induced discharges on the outside of the source. Three years of experiments on SPIDER have addressed to the necessary design modifications to enable full performances. The source is presently under a long shut-down phase to incorporate learnings from the experimental campaign. Parallelly, developments on MITICA, the full-scale prototype of the ITER NBI featuring a 1 MV accelerator and ion neutralization, are underway including manufacturing of in-vessel components, while power supplies and auxiliary plants are already under final testing and commissioning. Integration, commissioning and tests of the 1MV power supplies are essential for this first-of-kind system, unparalleled both in research and industry field. The integrated test to confirm 1MV output by combining invertor systems, DC generators and transmission lines extracted errors/accidents in some components. To realize a concrete system for ITER, solutions for the repair and the improvement of the system were developed. Hence, NBTF is emerging as a necessary facility, due to the large gap with existing injectors, effectively dedicated to identify issues and find solutions to enable successful ITER NBI operations in a time bound fashion.

Published
2023
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12. Hot rings on Io observed by Juno/JIRAM

Author

Alessandro Mura, Federico Tosi, Francesca Zambon, Rosaly M. C. Lopes, Peter J. Mouginis-Mark, Heidi Becker, Gianrico Filacchione, Alessandra Migliorini, Candice. J. Hansen, Alberto Adriani, Francesca Altieri, Scott Bolton, Andrea Cicchetti, Elisa Di Mico, Davide Grassi, Raffaella Noschese, Alessandro Moirano, Madeline Pettine, Giuseppe Piccioni, Christina Plainaki, Julie Rathbun, Roberto Sordini, and Giuseppe Sindoni

Subjects
Geology, QE1-996.5, Environmental sciences, GE1-350
Abstract

Abstract It has been thought that Io’s many paterae may contain lava lakes, but observations by NASA’s Galileo spacecraft at sufficiently high resolution were limited to a few locations, such as Loki Patera. Data acquired by NASA’s Juno mission in May 2023 reveal a common set of thermal characteristics for at least ten paterae on Io, with bright (hot) “thermal rings” around the perimeter of their floors. Loki, Surt, Fuchi, Amaterasu, Mulungu, Chors, and Dazhbog Patera, and four unnamed paterae, all show the same pattern of surface temperature. This new Juno/JIRAM data suggests that hot rings around paterae are a common phenomenon, and that they are indicative of active lava lakes. All the investigated paterae lack recent lava flows on their flanks, suggesting that at the time of observations, the level of the lake was not high enough to overflow the rim. These observations provide insight about the characteristics of paterae’s activity, which may involve either central upwelling of magma, or up-and-down “piston-like” vertical motion of the lake surface. Tidal forces, which are extreme at Io, could play a role as well. Future observations from Juno, particularly during the closest flybys, may indicate which mechanism is more plausible.

Published
2024
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15. Computational Fluid Dynamics (CFD) Modelling of a Full-Scale Oxidation Ditch: Suitable Mesh Selection Method and Hydrodynamic Perfomance Analysis

Author

Vázquez, Carla, del Mar Micó, María, Colprim, Jesús, di Prisco, Marco, Series Editor, Chen, Sheng-Hong, Series Editor, Vayas, Ioannis, Series Editor, Kumar Shukla, Sanjay, Series Editor, Sharma, Anuj, Series Editor, Kumar, Nagesh, Series Editor, Wang, Chien Ming, Series Editor, Cui, Zhen-Dong, Series Editor, Lu, Xinzheng, Series Editor, Mannina, Giorgio, editor, Cosenza, Alida, editor, and Mineo, Antonio, editor

Published
2024
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16. BALANGAY: Navigating Innovation Through Design Thinking Approach for a Boat Reservation and Booking System

Author

Banta, Jules Vincent C., Maaño, Roselyn A., Quinsanos, Mikaela S., Oriola, Mico Jhosua A., Paderez, Osias Robert O., Sinag, John Rover R., Hernandez, Donabell S., Salas, Leah T., Binh, Nguyen Duc, Kacprzyk, Janusz, Series Editor, Gomide, Fernando, Advisory Editor, Kaynak, Okyay, Advisory Editor, Liu, Derong, Advisory Editor, Pedrycz, Witold, Advisory Editor, Polycarpou, Marios M., Advisory Editor, Rudas, Imre J., Advisory Editor, Wang, Jun, Advisory Editor, Nghia, Phung Trung, editor, Thai, Vu Duc, editor, Thuy, Nguyen Thanh, editor, Son, Le Hoang, editor, and Huynh, Van-Nam, editor

Published
2024
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17. Hilbert phase microscopy based on pseudo thermal illumination in Linnik configuration

Author

Rogalski, Mikołaj, Cywińska, Maria, Ahmad, Azeem, Patorski, Krzysztof, Micó, Vicente, Ahluwalia, Balpreet S., and Trusiak, Maciej

Subjects
Physics - Optics, Physics - Biological Physics
Abstract

Quantitative phase microscopy (QPM) is often based on recording an object-reference interference pattern and its further phase demodulation. We propose Pseudo Hilbert Phase Microscopy (PHPM) where we combine pseudo thermal light source illumination and Hilbert spiral transform phase demodulation to achieve hybrid hardware-software-driven noise robustness and increase in resolution of single-shot coherent QPM. Those advantageous features stem from physically altering the laser spatial coherence and numerically restoring spectrally overlapped object spatial frequencies. Capabilities of the PHPM are demonstrated analyzing calibrated phase targets and live HeLa cells in comparison with laser illumination and phase demodulation via temporal phase shifting and Fourier transform techniques. Performed studies verified unique ability of the PHPM to couple single-shot imaging, noise minimization, and preservation of phase details.

Published
2022
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19. Effectiveness of biosimilar pegfilgrastim in patients with lymphoma after high-dose chemotherapy and autologous stem cell transplantation: a real-life study

Author

Barbara Loteta, Annalisa Pitino, Martina Pitea, Caterina Alati, Giovanni Tripepi, Maria Caterina Mico', Maria Pellicano', Francesca Cogliandro, Gaetana Porto, Giorgia Policastro, Giovanna Utano, Ilaria Maria Delfino, Annalisa Sgarlata, Anna Scopelliti, Aurora Idato, Giovanni Laenza, Maria Altomonte, Graziella D'Arrigo, Mercedes Gori, and Massimo Martino

Subjects
lymphoma, biosimilar pegfilgrastim, autologous stem cell transplantation, chemotherapy, BIO-PEG, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

ObjectivesTo evaluate the efficacy of biosimilar (BIO) pegfilgrastim (PEG) in lymphoma patients after autologous stem cell transplantation (ASCT).Methods86 consecutive lymphoma patients who received BIO/PEG after ASCT were assessed. The primary endpoints of this study were the incidence of febrile neutropenia (FN) and time to neutrophil engraftment.ResultsMost patients were males (67.4%) with a median age of 48 years. FN occurred in 66 patients (76.7%), and most of the fever was grade 1-2. The median time to neutrophil engraftment was 9 days. The incidence of FN differs based on lymphoma type (p-value

Published
2024
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20. Omicron SARS-CoV-2 infection management and outcomes in patients with hematologic disease and recipients of cell therapy

Author

José Luis Piñana, Lourdes Vazquez, Inmaculada Heras, Tommaso Francesco Aiello, Lucia López-Corral, Ignacio Arroyo, Eva Soler-Espejo, Irene García-Cadenas, Valentín Garcia-Gutierrez, Cristina Aroca, Pedro Chorao, María T. Olave, Javier Lopez-Jimenez, Marina Acera Gómez, Elena Arellano, Marian Cuesta-Casas, Alejandro Avendaño-Pita, Clara González-Santillana, José Ángel Hernández-Rivas, Alicia Roldán-Pérez, Mireia Mico-Cerdá, Manuel Guerreiro, Julia Morell, Paula Rodriguez-Galvez, Jorge Labrador, Diana Campos, Ángel Cedillo, Carolina Garcia Vidal, Rodrigo Martino, and Carlos Solano

Subjects
SARS-CoV-2, hematologic disease, immunocompromised, risk factors, COVID - 19, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

IntroductionScarce real-life data exists for COVID-19 management in hematologic disease (HD) patients in the Omicron era.PurposeTo assess the current clinical management and outcome of SARS-CoV-2 infection diagnosed, identify the risk factors for severe outcomes according to the HD characteristics and cell therapy procedures in a real-world setting.MethodsA retrospective observational registry led by the Spanish Transplant Group (GETH-TC) with 692 consecutive patients with HD from December 2021 to May 2023 was analyzed.ResultsNearly one-third of patients (31%) remained untreated and presented low COVID-19-related mortality (0.9%). Nirmatrelvir/ritonavir was used mainly in mild COVID-19 cases in the outpatient setting (32%) with a low mortality (1%), while treatment with remdesivir was preferentially administered in moderate-to-severe SARS-CoV-2 infection cases during hospitalization (35%) with a mortality rate of 8.6%. The hospital admission rate was 23%, while 18% developed pneumonia. COVID-19-related mortality in admitted patients was 14%. Older age, autologous hematopoietic stem cell transplantation (SCT), chimeric antigen receptor T-cell therapy, corticosteroids and incomplete vaccination were factors independently associated with COVID-19 severity and significantly related with higher rates of hospital admission and pneumonia. Incomplete vaccination status, treatment with prior anti-CD20 monoclonal antibodies, and comorbid cardiomyopathy were identified as independent risk factors for COVID-19 mortality.ConclusionsThe results support that, albeit to a lower extent, COVID-19 in the Omicron era remains a significant problem in HD patients. Complete vaccination (3 doses) should be prioritized in these immunocompromised patients. The identified risk factors may help to improve COVID-19 management to decrease the rate of severe disease, ICU admissions and mortality.

Published
2024
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21. Scalable switched slab coupler based optical phased array on silicon nitride

Author

Muñoz, Pascual, Pastor, Daniel, Bru, Luis A., Micó, Gloria, Benítez, Jesús, Goodwill, Dominic J., and Bernier, Eric

Subjects
Physics - Optics, Physics - Applied Physics
Abstract

A two-dimensional optical-phased array is demonstrated by using a multiple-input star coupler, compatible with FMCW LiDAR. Previous approach using a single-input design achieves two-dimensional beam-steering by relying on a tunable laser source, taking advantage of grating coupler radiation angle wavelength dependance and variation of the waveguide refractive index. While implementing a convenient way to distribute power in a single step, star coupler architecture is inefficient in terms of employed waveguide length and thus, optical loss and footprint. Multi-input approach partially alleviates this by condensing several single-input devices into one, permitting to reduce the footprint proportionally to the employed number of inputs. We fabricated in silicon nitride technology a proof of concept steerer with beam waist 0.36 deg x 0.175 deg addressing a field of view of 15 deg x 2.8 deg. A new design iteration is also reported with and 0.24 deg x 0.16 deg beam waist and 15 deg x 11.2 deg field of view. Implications of this optical-phased array chips from a LiDAR system perspective are also presented., Comment: Accepted for publication in the IEEE Journal of Selected Topics in Quantum Electronics. Copyright 2022 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses

Published
2022
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33. ctDNA whole exome sequencing in pancreatic ductal adenocarcinoma unveils organ-dependent metastatic mechanisms and identifies actionable alterations in fast progressing patients

Author

Huerta, Marisol, Martín-Arana, Jorge, Gimeno-Valiente, Francisco, Carbonell-Asins, Juan Antonio, García-Micó, Blanca, Martínez-Castedo, Belén, Robledo-Yagüe, Fabián, Camblor, Daniel G., Fleitas, Tania, García Bartolomé, Miguel, Alfaro-Cervelló, Clara, Garcés-Albir, Marina, Dorcaratto, Dimitri, Muñoz-Forner, Elena, Seguí, Víctor, Mora-Oliver, Isabel, Gambardella, Valentina, Roselló, Susana, Sabater, Luis, Roda, Desamparados, Cervantes, Andrés, and Tarazona, Noelia

Published
2024
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34. Real-time imaging of mitochondrial redox reveals increased mitochondrial oxidative stress associated with amyloid β aggregates in vivo in a mouse model of Alzheimer’s disease

Author

Maria Calvo-Rodriguez, Elizabeth K. Kharitonova, Austin C. Snyder, Steven S. Hou, Maria Virtudes Sanchez-Mico, Sudeshna Das, Zhanyun Fan, Hamid Shirani, K. Peter R. Nilsson, Alberto Serrano-Pozo, and Brian J. Bacskai

Subjects
Oxidative stress, ROS, Alzheimer’s disease, Mitochondria, SS31, Neurodegeneration, Neurology. Diseases of the nervous system, RC346-429, Geriatrics, RC952-954.6
Abstract

Abstract Background Reactive oxidative stress is a critical player in the amyloid beta (Aβ) toxicity that contributes to neurodegeneration in Alzheimer’s disease (AD). Damaged mitochondria are one of the main sources of reactive oxygen species and accumulate in Aβ plaque-associated dystrophic neurites in the AD brain. Although Aβ causes neuronal mitochondria reactive oxidative stress in vitro, this has never been directly observed in vivo in the living mouse brain. Here, we tested for the first time whether Aβ plaques and soluble Aβ oligomers induce mitochondrial oxidative stress in surrounding neurons in vivo, and whether this neurotoxic effect can be abrogated using mitochondrial-targeted antioxidants. Methods We expressed a genetically encoded fluorescent ratiometric mitochondria-targeted reporter of oxidative stress in mouse models of the disease and performed intravital multiphoton microscopy of neuronal mitochondria and Aβ plaques. Results For the first time, we demonstrated by direct observation in the living mouse brain exacerbated mitochondrial oxidative stress in neurons after both Aβ plaque deposition and direct application of soluble oligomeric Aβ onto the brain, and determined the most likely pathological sequence of events leading to oxidative stress in vivo. Oxidative stress could be inhibited by both blocking calcium influx into mitochondria and treating with the mitochondria-targeted antioxidant SS31. Remarkably, the latter ameliorated plaque-associated dystrophic neurites without impacting Aβ plaque burden. Conclusions Considering these results, combination of mitochondria-targeted compounds with other anti-amyloid beta or anti-tau therapies hold promise as neuroprotective drugs for the prevention and/or treatment of AD.

Published
2024
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39. Association between use of enhanced recovery after surgery protocols and postoperative complications after gastric surgery for cancer (POWER 4): a nationwide, prospective multicentre study

Author

Farré, Mercè Güell, Font, Roser Farré, del Gobbo, Rafael Diaz, Jimenez, Raquel Sánchez, Reche, Isabel Pérez, Calvo, Belen Gil, García, Jordi Llorca, Sánchez, Laura Carrasco, Llimargas, Cristina Prat, García-Sánchez, Ana María, Martínez-Ragüés, Gema, Gómez-Fernández, María, del-Castillo-Criado, Álvaro, Martínez-Díaz, Ruth, Alegría-Rebollo, Sara, Ferrerode-Paz, Javier, García-Pérez, Cristina, Marcos-Contreras, Sergio, Fernández-García, Diana, Torío-Marcos, Maeva, Fernández, Omar Abdellah, Parreño-Manchado, Felipe Carlos, Martín, María Ángeles, Tena-Guerrero, José María, Palma-González, Estefanía, Flores-Flores, Gustavo, Zugasti-Echarte, Orreaga, Pérez-Bergara, Elena, Hernández-García, Susana, Martín-Vizcaíno, Marta, Yoldi-Murillo, Francisco Javier, Valencia-Alzueta, Maider, Chaveli-Díaz, Carlos, Miranda-Murua, Coro, Yárnoz-Irazábal, Concepción, Botella-Martínez, Sonsoles, López-Pardo, Rafael, Torres-Montalvo, Marta, Pinilla-Pico, Isabel, del-Cojo-Peces, Enrique, del Pilar Rodríguez-Chaparro, María, Gómez-Ríos, Manuel Ángel, del-Río-Regueira, Sara, Mosquera-Rodríguez, Eva, Hernández-Beslmeisl, Jessica, Perozo-Medina, María Alejandra, Darias-Delbey, Beneharo, del Carmen Martín-Lorenzo, María, González-Fariña, Vanessa, Rodríguez-Domínguez, Montserrat, Fernández-de-la-Vega-Medina, Jaime, Berrotarán-Ayub, Pilar, Valín-Martínez, José, Concepción-Santana, Laura, Cruz-Zorio, Raúl, Betancort-Gutiérrez Rodríguez, Dolores, Gómez-Viana, Leticia, Figueiredo, Olalla, Rodríguez, Ariadna, González, Manuel, Iglesias, David, Domínguez-Carrera, José Manuel, Olmo, Jorgedo, Del-Río-Fernández, Sabela, Dos-Santos-Carregal, Laura, Rodríguez-Forja, María Jesús, Campaña-Figueira, Olga, Álvarez-Escudero, Julián, Lesquereux-Martínez, Lucía, Parada-González, Purificación, Montenegro-Romero, Ricardo, Bustamante-Montalvo, Manuel, García-Placín, Ana Rosa, Carpintero-Rama, Carmen, Brea-Bahamonde, Sergio, Torres-Alfonso, José Ramón, Barragán-Serrano, Cristina, Posada-González, María, Salcedo-Cabañas, Gabriel, Vor-wald-Wolfgang, Peter, Otero-Martínez, Isabel, Jove-Alborés, Patricia, López-Otero, Marta, Pardellas-Rivera, Hermelinda, Maruri-Chimeno, Ignacio, González-Fernández, Sonia, Sánchez-Santos, Raquel, Luna-Mendoza, Luis, Lloria-Pons, Enrique, Gramuntell-Marco, Francisco, Cánovas-de-Lucas, Raúl, Sancho-Moya, Cristina, Risco, Raquel, Fernández-Esmerats, Anna, Sanahuja-Blasco, Josep Martí, López-Baamonde, Manuel, Ubré, Marta, Martínez-Pallí, Graciela, Momblán, Dulce, Rivas-Gallardo, Nuria, Sánchez-Martín, Rubén, Moral, Pedro, Navarro, Rosalía, Santé, Luis, Almenta, Esther, Muñoz-Hernández, Henar, Rodríguez-Jiménez, Rita Pilar, Ruiz, Nuria, Peláez, María Teresa, Rojo, Juan José, Gordaliza, Carlota, Jezieniecki, Carlos, Jimenez-Viñas, Carlos, Brugiotti, Carlo, Onchalos-Lopez, Ulices, Llácer-Pérez, Manuel, Batalla, Astrid, Azparren, Gonzalo, Bastitta, Micaela, Cueva, Luisa, Felipe, Mar, Giné, Marta, Gómez, Ana M., India, Inmaculada, Piñol, Santiago, Gimeno-Campos, Maria José, Moreno-Gázquez, Aurora, Llorens-Herrerías, Julio, Del-Castillo-Rodrigo, Gema, Herrero-Bogajo, María Luz, De Miguel-Cabrera, María Isabel, España-Pamplona, José Miguel, Gellida-Vilarroig, María, Jordá-Sanz, Laura, Gil-Trujillo, Silvia, Calatayud-Gómez, Laura, Valencia-Echeverri, Juan David, Baladrón-González, Víctor, Gil-Rendo, Aurora, Sanchez-García, Susana, García-Santos, Esther, Benito, Carmen, Lisbona, Cristina, Benito, Pilar, Correa-Chacón, Olga Cecilia, Alcázar-Urrea, Alejandro, Fernández-López, Ana Belén, Betancourt-Bastidas, Ramiro, Navarro-García, Inmaculada, Romera-Barba, Elena, Mira-Jovells, Nuria, Estevez-Perez, Liz Karime, Saludes-Serra, Judit, Olona-Casas, Carles, Vadillo-Bargalló, Jordi, Jorba-Martín, Rosa, Mojarro, Irene, Lorente, Juan Victor, Longo-Guridi, Pablo, Quintero-Moreno, Ana Maria, Soriano-López, David, de la Peña Gómez-Dominguez, Maria, Prieto-Candau, Cecilia, Hernández-Castillo, Marisol, Jarana, Irene, García-Andreu, Francisco, González-González, Jose, Díaz-Lara, María Dolores, Añón-Iranzo, Elena, Aguiló-Lucia, Javier, Fernandez-Martin, Maria Teresa, Guerra, Yessica, Gimeno-Fernández, Pablo, Iglesias-Morales, Carla, Villalba, Ana María Ríos, Nespereira-García, Paula, Castro-Neira, María José, Ochoa-Díez, María, García-Orallo, Silvia, Mozo-Segurado, Maialen, Gutiérrez-Cabezas, Jose Manuel, Gonzalo-González, Ruben, García-Álvarez, Raquel, Ramiro-Ruíz, Álvaro, González-Cofrade, María, Carvajal-Revuelta, Estefanía, Bellido-López, Ana, Redondo-Cristóbal, Guillermo, Amoza-Pais, Sonia, Díaz-Vico, Tamara, Moreno-Gijón, María, Sanz-Navarro, Sandra, Sanz-Álvarez, Lourdes M, Turienzo-Santos, Estrella Olga, Rodicio-Miravalles, Jose Luis, Rizzo-Ramos, Amaya, Cuéllar-Martínez, Ana, Álvarez-Fernández, Rosa Ana, Fernández-Seijo, Carmen, Álvarez-Barrial, Amelia, Gónzalez-Ortea, Carmen, Fernández-Rodriguez, Silvia, García-González, Nerea, Varela-Rodriguez, Lorena, Berzal-Canga, Elena, García-Díaz-Negrete, Ángela, García-Sánchez, Helena, Saenz-Abos, Javier, Ayuso-Iñigo, Beatriz, Vega-Colón, María, Palacios-Córdoba, Ángela Catalina, Quel-Collado, María Teresa, Olvera-García, Mercedes, Martinez-Sánchez, Agustina, Serrano-Alvarez, Carmen, Ganuza-Martínez, Eunate, Maroño-Boedo, María Jesús, Sánchez-Campos, Alberto, Escontrela-Rodríguez, Blanca Anuncia, Martínez-Ruiz, Alberto, Errazti-Olartecoechea, Gaizka, Rodeño-Esteban, Iratxe, Moreno-Allende, Tamara, Gutierrez-Grijalba, Oihane, Katary-niuk-Di-Costanzo, Yanina, Alvarez-Abad, Irene, Sendino-Cañizares, Patricia, Mifsut-Porcel, Patricia, Sarriugarte-Lasarte, Aingeru, Guerra-Lerma, Mikel, Logroño-Ejea, Margarita, Iturricastillo-Pérez, María Del Carmen, Gastaca-Abasolo, María, Muñoz-Sanz, María José, Iriarte-Zaranton, Ibai, Olea-De-La-Fuente, Erika, Mendiguren-Murua, Ana, Reka-Mediavilla, Lorena, Gastón-Moreno, Alberto, Martínez-De-Aragón-Remirez-De-Esparza, Gabriel Jesús, Sierra-Esteban, Valentín, Montero-Mejías, Gema, Pardo-Martínez, Claudia, Valadés-Periañez, Teresa, Marín-Moreno, Ana, Caro-González, Juan Ricardo, Rodríguez-Pérez, María José, Herrero-Herrero, José Carlos, Renedo-Corcóstegui, Pablo, Martín-Oliva, Alejandro, Fernández-Herrero, Ana Isabel, Andrieu-Estefanía, Nerea, Albaladejo-Magdalena, Javier, Álvarez-Rodriguez, María, Sosa-Rodríguez, Valentina, Fresnedo-Pérez, Raquel María, Gil-Lapetra, Cristina, Bolzoni-Marciel, Beatriz, Herrera-López, Maria Isabel, Setién-Moreno, Fernando, Castro-Costoya, Ana Zulema, Olarra-Nuel, José, De-Vega-Irañeta, Marta, Ugarte-Sierra, Bakarne, Vicente-Rodríguez, Irune, Fernández-Pablos, Francisco Javier, Abad-Alonso, Rafael Alberto, Maniega-Alba, Roberto, Ibáñez-Aguirre, Francisco Javier, Postigo-Morales, Susana, Intxaurraga-Fernández, Karmelo, Telletxea-Benguria, Sorkunde, Outón-Guerrero, Ángela, Acosta-Mérida, María Asunción, de la Plaza-Llamas, Roberto, García-Gil, José Manuel, Gemio-del-Rey, Ignacio Antonio, Cabellos-Olivares, Mercedes, Fernández-García, Raquel, Freitas, Lidia Castro, Alcorta, Beatriz Nacarino, Ayuso, María Martín, González, María Moral, Teruel, David García, Serrat-Puyol, Jordi, Molinas-Bruguera, Joan, Fernández, Sara, Peris-Tomás, Nuria, Díez-Ares, Jose Ángel, Periáñez-Gómez, Dolores, Gonzálvez-Guardiola, Paula, Trullenque-Juan, Ramón, Martínez-Mas, Ezequiel, Martínez, Estefanía, Martín, Julia, Higueras, Raquel, Cuenca, Sara, Martín-Vaquerizo, Beatriz, Espinosa-Moreno, Alma M., Sánchez-Merchante, Miriam, Alcañiz-Sobrino, Rebeca, Egea-Hita, Guillermo, García-del-Valle-y-Manzano, Santiago, Moreno-Blanco, Virginia, Bruna-Esteban, Marcos, Mingol-Navarro, Fernando, Vaqué-Urbaneja, Javier, Díaz-Cambronero, Óscar, Luján-Sandemetrio, Beatriz, Copariate-Piqueras, Bisila, Giménez-Salcedo, Sonia, Ripolles-Melchor, Javier, Abad-Motos, Ane, Abad-Gurumeta, Alfredo, Aracil-Escoda, Norma, Saez-Ruiz, Elena, Salva-chua-Fernandez, Rut, Paseiro-Crespo, Gloria, García-Nebreda, María, Toribio, Begoña, Ferrero-Celemin, Esther, García-Sancho-Téllez, Luis, Sánchez-López, José Daniel, Núñez O'Sullivan, Sara, Gar-cía-Virosta, Mariana, Rodriguez-Haro, Carmen, Hernández-O’Reilly, María, Suarez-de-la-Rica, Alejandro, Lopez-Martinez, Mercedes, Croes, Bryant, Mujica, Jaime, Maseda, Emilio, Alday-Muñoz, Enrique, Mata-Mena, Esperanza, García-Sanz, Iñigo, Marín, Cristina, Muñoz, Antonio Pedraza, Dominguez, Jorge Puertas, González-López, Rocío, Navarro-Quirós, Gisela, Pérez-Moreiras, M. Isabel, Conde-Rodriguez, María, Muinelo-Lorenzo, Manuel, Díez-Zapirain, Miren Jasone, Tejón-Pérez, Guillermo, Álvarez-Cebrián, María Asunción, Barrero-Ruiz, Eva, Capa-Fuertes, Eva, Carrillo-Rivas, Mariana, Hernandez-Sanchez, Isabel, Monteagudo-Cimiano, Valvanuz, Pascual-Casado, Ángela, Rábago-Morillón, Jose Luis, Martinez-Ubieto, Javier, Pascual-Bellosta, Ana, Ortega-Lucea, Sonia, Perez-Otal, Berta, Tardos-Ascaso, Lucia, Ligorred-Padilla, Luis Antonio, Tur-Martínez, Jaume, Rodríguez-Santiago, Joaquin, Pérez-Romero, Noelia, Puértolas-Rico, Noelia, Hernández-Giménez, Laura, Concepción-Martín, Vanessa, Molnar, Viktoria, Barbero, Macarena, San-Antonio, Belén, Pueyo, Alberto, Mayo-Ossorio, M de los Angeles, Bengoechea-Trujillo, Ander, Pacheco-Garcia, José Manuel, Diez-Remesal, Yolanda, Gonzalo-Millán, Alba, Berruezo-Camacho, Alberto, Alaez-Cortés, Azucena, Ortolá-Rocher, Begoña, Iglesias-Gallego, Berta, Martín-Montero, Eduardo, Arias-Cuesta, Gerardo, de la Hoz-Polo, Inés, Recuero-Torrijos, Isabel, Pereira-Torres, Lucia, Cañamas-Catalá, Maria, Martin-González, Maria C., Zambrana-García, Paloma, Llorente-Damas, Sergio, Aldecoa, Cesar, Perez-Gonzalez, Alba, Bolaño-Perez, Clara, Velasco-Andres, Delia, Aguado-Saster, Esther, Arranz, Irene, Mendez-Torrubiano, Itziar, Vaquero-Perez, Laura, Sanz-de-Leon, Maria Jesus, Rodicio, Pablo, Martin-Alfonso, Silvia, Martin-Tappi, David, Madrid-Tribano, Mario, Rioja-Garrido, Rocio, Morales-Jaquete, Borja, Vicente-Orgaz, Marta, Orozco-Vinasco, Adriana Carolina, Fraga-Casais, Gema, Miyagi-Yonamine, Any Minerva, Ramos-de-Castro, Raquel, Mejía-Arnaud, Rossel Alina, Saz-Castro, Rubén, Díaz-Peña, Patricia, Camps-Cervantes, Angels, Tormos-Perez, M Pilar, Galan-Menendez, Patricia, Esclapez-Sampere, Elena, Villarino-Villa, Laura, Loaiza-Aldeán, Yuri, Chocron-Dapratt, Ivette, Martinez-Silva, Olga, Matarin-Olmo, Silvia, Berges-Gutiérrez, Héctor, Pérez-Serrano, Macarena, Diaz-Castillo, Juan Javier, Sancho-Muñoz-de-Verger, Álvaro, Villanueva-Mena-Bernal, Jesús Alejandro, Gil-Gómez, Maria Lucia, Fernanz-Anton, Jesús, Marmaña-Mezquita, Sandra, Galofré-Pujol, Gonzalo, Jericó, Carlos, Motos-Micó, José Jacob, Orts-Micó, Francisco José, Serra-Díaz, Carlos, Arlandis-Félix, Francisco, Pérez-Climent, Nieves, Blanes-Pastor, Lorena, Jover-Pinillos, Jose Luis, Salvaterra, David, Linero, Manuel, Galipienzo, Javier, Alonso, Óscar, Ortega, Gloria, Gonzalez, Santiago, Lopez-Rojo, Irene, Ripollés-Melchor, Javier, Abdel-lah Fernández, Omar, Tormos-Pérez, María P., A Mayo-Ossorio, María, Gil-Gómez, Lucia, Parreño-Manchado, Felipe C, De-Miguel-Cabrera, María I, García-Erce, José A., Río-Fernández, Sabela del, Herrero-Bogajo, María L., Zorrilla-Vaca, Andrés, Vaquero-Pérez, Laura, Fernández-Martín, María T., Ferrando-Ortolà, Carlos, Ramírez-Rodríguez, José M., and Aldecoa, César

Published
2023
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42. EEG before chimeric antigen receptor T-cell therapy and early after onset of immune effector cell-associated neurotoxicity syndrome

Author

Hernani, Rafael, Aiko, Mika, Victorio, Ruth, Benzaquén, Ana, Pérez, Ariadna, Piñana, José Luis, Hernández-Boluda, Juan Carlos, Amat, Paula, Pastor-Galán, Irene, Remigia, María José, Ferrer-Lores, Blanca, Micó, Mireia, Carbonell, Nieves, Ferreres, José, Blasco-Cortés, María Luisa, Santonja, José Miguel, Dosdá, Rosa, Estellés, Rocío, Campos, Salvador, Martínez-Ciarpaglini, Carolina, Ferrández-Izquierdo, Antonio, Goterris, Rosa, Gómez, Montse, Teruel, Anabel, Saus, Ana, Ortiz, Alfonso, Morello, Daniela, Martí, Edel, Carretero, Carlos, Calabuig, Marisa, Tormo, Mar, Terol, María José, Cases, Paula, and Solano, Carlos

Published
2024
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46. “Proteotranscriptomic analysis of advanced colorectal cancer patient derived organoids for drug sensitivity prediction”

Author

Papaccio, Federica, García-Mico, Blanca, Gimeno-Valiente, Francisco, Cabeza-Segura, Manuel, Gambardella, Valentina, Gutiérrez-Bravo, María Fernanda, Alfaro-Cervelló, Clara, Martinez-Ciarpaglini, Carolina, Rentero-Garrido, Pilar, Zúñiga-Trejos, Sheila, Carbonell-Asins, Juan Antonio, Fleitas, Tania, Roselló, Susana, Huerta, Marisol, Sánchez del Pino, Manuel M., Sabater, Luís, Roda, Desamparados, Tarazona, Noelia, Cervantes, Andrés, and Castillo, Josefa

Published
2023
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47. Monocyte-derived cells invade brain parenchyma and amyloid plaques in human Alzheimer’s disease hippocampus

Author

Muñoz-Castro, Clara, Mejias-Ortega, Marina, Sanchez-Mejias, Elisabeth, Navarro, Victoria, Trujillo-Estrada, Laura, Jimenez, Sebastian, Garcia-Leon, Juan Antonio, Fernandez-Valenzuela, Juan Jose, Sanchez-Mico, Maria Virtudes, Romero-Molina, Carmen, Moreno-Gonzalez, Ines, Baglietto-Vargas, David, Vizuete, Marisa, Gutierrez, Antonia, and Vitorica, Javier

Published
2023
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48. Developmental outcome of electroencephalographic findings in SYNGAP1 encephalopathy

Author

Juliana Ribeiro-Constante, Alba Tristán-Noguero, Fernando Francisco Martínez Calvo, Salvador Ibañez-Mico, José Luis Peña Segura, José Miguel Ramos-Fernández, María del Carmen Moyano Chicano, Rafael Camino León, Víctor Soto Insuga, Elena González Alguacil, Carlos Valera Dávila, Alberto Fernández-Jaén, Laura Plans, Ana Camacho, Nuria Visa-Reñé, María del Pilar Martin-Tamayo Blázquez, Fernando Paredes-Carmona, Itxaso Marti-Carrera, Aránzazu Hernández-Fabián, Meritxell Tomas Davi, Merce Casadesus Sanchez, Laura Cuesta Herraiz, Patricia Fuentes Pita, Teresa Bermejo Gonzalez, Mar O'Callaghan, Federico Felipe Iglesias Santa Polonia, María Rosario Cazorla, María Teresa Ferrando Lucas, Antonio González-Meneses, Júlia Sala-Coromina, Alfons Macaya, Amaia Lasa-Aranzasti, Anna Ma Cueto-González, Francisca Valera Párraga, Jaume Campistol Plana, Mercedes Serrano, Xenia Alonso, Diego Del Castillo-Berges, Marc Schwartz-Palleja, Sofía Illescas, Alia Ramírez Camacho, Oscar Sans Capdevila, Angeles García-Cazorla, Àlex Bayés, and Itziar Alonso-Colmenero

Subjects
SYNGAP1, rare disease, interictal epileptiform discharges, diffuse fast activity, autism spectrum disorder, EEG, Biology (General), QH301-705.5
Abstract

SYNGAP1 haploinsufficiency results in a developmental and epileptic encephalopathy (DEE) causing generalized epilepsies accompanied by a spectrum of neurodevelopmental symptoms. Concerning interictal epileptiform discharges (IEDs) in electroencephalograms (EEG), potential biomarkers have been postulated, including changes in background activity, fixation-off sensitivity (FOS) or eye closure sensitivity (ECS). In this study we clinically evaluate a new cohort of 36 SYNGAP1-DEE individuals. Standardized questionnaires were employed to collect clinical, electroencephalographic and genetic data. We investigated electroencephalographic findings, focusing on the cortical distribution of interictal abnormalities and their changes with age. Among the 36 SYNGAP1-DEE cases 18 presented variants in the SYNGAP1 gene that had never been previously reported. The mean age of diagnosis was 8 years and 8 months, ranging from 2 to 17 years, with 55.9% being male. All subjects had global neurodevelopmental/language delay and behavioral abnormalities; 83.3% had moderate to profound intellectual disability (ID), 91.7% displayed autistic traits, 73% experienced sleep disorders and 86.1% suffered from epileptic seizures, mainly eyelid myoclonia with absences (55.3%). A total of 63 VEEGs were revised, observing a worsening of certain EEG findings with increasing age. A disorganized background was observed in all age ranges, yet this was more common among older cases. The main IEDs were bilateral synchronous and asynchronous posterior discharges, accounting for ≥50% in all age ranges. Generalized alterations with maximum amplitude in the anterior region showed as the second most frequent IED (≥15% in all age ranges) and were also more common with increasing age. Finally, diffuse fast activity was much more prevalent in cases with 6 years or older. To the best of our knowledge, this is the first study to analyze EEG features across different age groups, revealing an increase in interictal abnormalities over infancy and adolescence. Our findings suggest that SYNGAP1 haploinsufficiency has complex effects in human brain development, some of which might unravel at different developmental stages. Furthermore, they highlight the potential of baseline EEG to identify candidate biomarkers and the importance of natural history studies to develop specialized therapies and clinical trials.

Published
2024
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