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1. Heterologous Materials Are Really Better than Autologous in Tympanoplasty Mastoid Obliteration? A Systematic Review with Meta-Analysis

Author

Francesca Viberti, Giovanni Monciatti, Aniello Donniacuo, Fabio Ferretti, Lorenzo Salerni, Andrea De Vito, Daniele Bernardeschi, and Marco Mandalà

Subjects
Otorhinolaryngology, RF1-547
Abstract

Background: The aim is to analyze Literature concerning mastoid obliteration in adults with either autologous or heterologous grafts in the last 10 years. Data Source: Databases such as NIH PubMed, Bookshelf, NLM Catalog, Cochrane Library, and Embase were consulted. Methods: Thirty-seven studies were selected (22 concerning autologous materials, 15 about heterologous ones). Only studies with more than 12 months of follow-up were considered. A statistical analysis with random-effects models was performed to allow the true effect sizes to differ from study to study. Results: The present literature review and meta-analysis does not allow to establish the supremacy of one technique over the other, but underlines the advantages of each reconstructive choice and the importance of mastoid obliteration in cholesteatoma surgery. The total number of obliterated ears was 2882. Overall otorrhea rate was 5% (5.2% for heterologous grafts; 4.9% for autologous materials; P < .05). Recurrent and residual cholesteatoma rate was 4.5% (3.4% in heterologous materials; 5.2% in autologous grafts; P < .05). Recurrent cholesteatoma rate was 1.8% (1.6% when using heterologous grafts, 1.9% with autologous; P < .05). Residual cholesteatoma rate was 1.5% (1.6% with heterologous materials, 1.5% with autologous; P < .05). TM (tympanic membrane) retraction pockets rate was 5.3% (3.6% with heterologous materials; P >.05; 7% with autologous materials; P < .05). TM perforations rate was 2.9% (4.3% with heterologous materials, 2.5% with autologous; P < .05). Infection rate was 2.3% (2.3% with heterologous materials, 2.2% with autologous; P < .05). Conclusion: Heterologous materials are associated with significantly lower rates of recurrent and residual cholesteatoma and retraction pockets development, although they are associated with higher rates of otorrhea and TM perforation.

Published
2024
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2. Multi-Magnet Cochlear Implant Technology and Magnetic Resonance Imaging: The Safety Issue

Author

Pietro Canzi, Elena Carlotto, Elisabetta Zanoletti, Johan H. M. Frijns, Daniele Borsetto, Antonio Caruso, Luisa Chiapparini, Andrea Ciorba, Giorgio Conte, Nathan Creber, Stefania Criscuolo, Filippo Di Lella, Sebastiano Franchella, Erik F. Hensen, Lorenzo Lauda, Stefano Malpede, Marco Mandalà, Liselotte J. C. Rotteveel, Anna Simoncelli, Anna Chiara Stellato, Diego Zanetti, and Marco Benazzo

Subjects
cochlear implants, magnetic resonance imaging, safety, Ultra 3D, magnet, Otorhinolaryngology, RF1-547
Abstract

Despite the spread of novel-generation cochlear-implant (CI) magnetic systems, access to magnetic resonance imaging (MRI) for CI recipients is still limited due to safety concerns. The aim of this study is to assess and record the experiences of Hires Ultra 3D (Advanced Bionics) recipients who underwent an MRI examination. A multicentric European survey about this topic was conducted focusing on safety issues, and the results were compared with the current literature. We collected a total of 65 MRI scans performed in 9 otologic referral centers for a total of 47 Hires Ultra 3D recipients, including, for the first time, 2 children and 3 teenagers. Preventive measures were represented by scanning time and sedation for children. Head wrapping was used in eight cases, and six of the eight cases received local anesthesia, even if both measures were not needed. Only three patients complained of pain (3/65 examinations, 4.6%) due to the tight head bandage, and one of the three cases required MRI scan interruption. No other adverse events were reported. We believe that these results should encourage MRI execution in accordance with manufacturer recommendations for Ultra 3D recipients.

Published
2024
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3. Host genetics and COVID-19 severity: increasing the accuracy of latest severity scores by Boolean quantum features

Author

Gabriele Martelloni, Alessio Turchi, Chiara Fallerini, Andrea Degl’Innocenti, Margherita Baldassarri, Simona Olmi, Simone Furini, Alessandra Renieri, GEN-COVID Multicenter study, Francesca Mari, Sergio Daga, Ilaria Meloni, Mirella Bruttini, Susanna Croci, Mirjam Lista, Debora Maffeo, Elena Pasquinelli, Giulia Brunelli, Kristina Zguro, Viola Bianca Serio, Enrica Antolini, Simona Letizia Basso, Samantha Minetto, Giulia Rollo, Martina Rozza, Angela Rina, Rossella Tita, Maria Antonietta Mencarelli, Caterina Lo Rizzo, Anna Maria Pinto, Francesca Ariani, Francesca Montagnani, Mario Tumbarello, Ilaria Rancan, Massimiliano Fabbiani, Elena Bargagli, Laura Bergantini, Miriana d’Alessandro, Paolo Cameli, David Bennett, Federico Anedda, Simona Marcantonio, Sabino Scolletta, Federico Franchi, Maria Antonietta Mazzei, Susanna Guerrini, Edoardo Conticini, Luca Cantarini, Bruno Frediani, Danilo Tacconi, Chiara Spertilli Raffaelli, Arianna Emiliozzi, Marco Feri, Alice Donati, Raffaele Scala, Luca Guidelli, Genni Spargi, Marta Corridi, Cesira Nencioni, Leonardo Croci, Gian Piero Caldarelli, Davide Romani, Paolo Piacentini, Maria Bandini, Elena Desanctis, Silvia Cappelli, Anna Canaccini, Agnese Verzuri, Valentina Anemoli, Manola Pisani, Agostino Ognibene, Maria Lorubbio, Alessandro Pancrazzi, Massimo Vaghi, Antonella D’Arminio Monforte, Federica Gaia Miraglia, Mario U. Mondelli, Stefania Mantovani, Raffaele Bruno, Marco Vecchia, Marcello Maffezzoni, Enrico Martinelli, Massimo Girardis, Stefano Busani, Sophie Venturelli, Andrea Cossarizza, Andrea Antinori, Alessandra Vergori, Stefano Rusconi, Matteo Siano, Arianna Gabrieli, Agostino Riva, Daniela Francisci, Elisabetta Schiaroli, Carlo Pallotto, Saverio Giuseppe Parisi, Monica Basso, Sandro Panese, Stefano Baratti, Pier Giorgio Scotton, Francesca Andretta, Mario Giobbia, Renzo Scaggiante, Francesca Gatti, Francesco Castelli, Eugenia Quiros-Roldan, Melania Degli Antoni, Isabella Zanella, Matteo della Monica, Carmelo Piscopo, Mario Capasso, Roberta Russo, Immacolata Andolfo, Achille Iolascon, Giuseppe Fiorentino, Massimo Carella, Marco Castori, Giuseppe Merla, Gabriella Maria Squeo, Filippo Aucella, Pamela Raggi, Rita Perna, Matteo Bassetti, Antonio Di Biagio, Maurizio Sanguinetti, Luca Masucci, Alessandra Guarnaccia, Serafina Valente, Alex Di Florio, Marco Mandalà, Alessia Giorli, Lorenzo Salerni, Patrizia Zucchi, Pierpaolo Parravicini, Elisabetta Menatti, Tullio Trotta, Ferdinando Giannattasio, Gabriella Coiro, Fabio Lena, Gianluca Lacerenza, Cristina Mussini, Luisa Tavecchia, Lia Crotti, Gianfranco Parati, Roberto Menè, Maurizio Sanarico, Marco Gori, Francesco Raimondi, Alessandra Stella, Filippo Biscarini, Tiziana Bachetti, Maria Teresa La Rovere, Maurizio Bussotti, Serena Ludovisi, Katia Capitani, Simona Dei, Sabrina Ravaglia, Annarita Giliberti, Giulia Gori, Rosangela Artuso, Elena Andreucci, Angelica Pagliazzi, Erika Fiorentini, Antonio Perrella, Francesco Bianchi, Paola Bergomi, Emanuele Catena, Riccardo Colombo, Sauro Luchi, Giovanna Morelli, Paola Petrocelli, Sarah Iacopini, Sara Modica, Silvia Baroni, Giulia Micheli, Marco Falcone, Donato Urso, Giusy Tiseo, Tommaso Matucci, Davide Grassi, Claudio Ferri, Franco Marinangeli, Francesco Brancati, Antonella Vincenti, Valentina Borgo, Stefania Lombardi, Mirco Lenzi, Massimo Antonio Di Pietro, Francesca Vichi, Benedetta Romanin, Letizia Attala, Cecilia Costa, Andrea Gabbuti, Alessio Bellucci, Marta Colaneri, Patrizia Casprini, Cristoforo Pomara, Massimiliano Esposito, Roberto Leoncini, Michele Cirianni, Lucrezia Galasso, Marco Antonio Bellini, Chiara Gabbi, and Nicola Picchiotti

Subjects
COVID-19, host genetics, integrated polygenic score, genetic algorithm, logistic regression, genetic science modeling, Genetics, QH426-470
Abstract

The impact of common and rare variants in COVID-19 host genetics has been widely studied. In particular, in Fallerini et al. (Human genetics, 2022, 141, 147–173), common and rare variants were used to define an interpretable machine learning model for predicting COVID-19 severity. First, variants were converted into sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. After that, the Boolean features, selected by these logistic models, were combined into an Integrated PolyGenic Score (IPGS), which offers a very simple description of the contribution of host genetics in COVID-19 severity.. IPGS leads to an accuracy of 55%–60% on different cohorts, and, after a logistic regression with both IPGS and age as inputs, it leads to an accuracy of 75%. The goal of this paper is to improve the previous results, using not only the most informative Boolean features with respect to the genetic bases of severity but also the information on host organs involved in the disease. In this study, we generalize the IPGS adding a statistical weight for each organ, through the transformation of Boolean features into “Boolean quantum features,” inspired by quantum mechanics. The organ coefficients were set via the application of the genetic algorithm PyGAD, and, after that, we defined two new integrated polygenic scores (IPGSph1 and IPGSph2). By applying a logistic regression with both IPGS, (IPGSph2 (or indifferently IPGSph1) and age as inputs, we reached an accuracy of 84%–86%, thus improving the results previously shown in Fallerini et al. (Human genetics, 2022, 141, 147–173) by a factor of 10%.

Published
2024
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4. A case of metastic melanoma of IACs with a rapidly decay of auditory and vestibular function

Author

Aniello Donniacuo, Ludovica Livi, Francesca Viberti, Lorenzo Salerni, and Marco Mandalà

Subjects
Melanoma, IACs, Cerebellopontine, Otology, Vestibular disorders, Otorhinolaryngology, RF1-547
Abstract

Melanoma is one of the tumours whose incidence has increased the most in recent decades.Metastasis of the inner ear and cerebellopontine angle from melanoma are rare and only few cases of melanoma metastases with simultaneous bilateral involvement of the inner ear have been reported.We report the case of DM, a 52 years old man, who was admitted to our department for a rapidly worsening sensorineural hearing loss with bilateral tinnitus and postural instability. Seven years before, the patient was diagnosed with a stage III-B melanoma of the trunk treated with surgical excision and axillary lymph-nodes dissection. The following oncological follow-up resulted negative. Vestibular evaluation excluded vestibular neuritis, revealing instead an horizontal nystagmus on the left side, alteration of the right orbicularis oculi muscle with minimal lagophthalmos and gait anomalies. The CT-scan excluded a stroke. The MRI showed bilateral enhancing lesions at IACs, thickened appearance at the right VIII cranial nerve level with hyperintensity of the signal and a similar lesion at D1 spine level. A debulking surgery and biopsy with translabyrinthine access were planned.The histological report showed a BRAF mutated melanoma and for that reason the patient was referred to the oncology department to start immunotherapy treatment.

Published
2023
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6. The incidence of vestibular neuritis in Italy

Author

Marco Mandalà, Lorenzo Salerni, Fabio Ferretti, Ilaria Bindi, Giacomo Gualtieri, Giulia Corallo, Francesca Viberti, Roberto Gusinu, Claudio Fantino, Silvia Ponzo, Serena Astore, Simone Boccuzzi, and Daniele Nuti

Subjects
acute vestibular neuronitis, dizziness, prospective study, epidemiology, incidence, Neurology. Diseases of the nervous system, RC346-429
Abstract

ObjectiveThis study aims to estimate the incidence of Vestibular neuritis (VN) in three different districts in Italy, its epidemiological features, and the prevalence of comorbidities associated with it.MethodsAn observational prospective study of 198 patients referred to ENT departments in Siena, Grosseto, and Cuneo was carried out over a 2-year period. Each patient underwent a complete otoneurologic examination in the first 48 h from the onset of symptoms and a brain MRI in the early stages of the disease. The follow-up lasted for 1 year.ResultsThe total VN incidence rate of the three municipalities was 48.497 (95% CI: 48.395–48.598) and its standardized value was 53.564 (95% CI: 53.463–53.666). The total VN incidence rate for the whole sample (municipality and district of the three centers) was 18.218 (95% CI: 18.164–18.272), and its standardized value was 20.185 (95% CI: 20.129–20.241). A significant difference was highlighted between patients living in the city compared to those living in the surrounding area (p < 0.000), this may be due to the ease of reaching the otoneurological referral center.ConclusionThe total incidence rate for the three municipalities was 48.497. This result is higher than previously reported studies.

Published
2023
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7. Treating benign paroxysmal positional vertigo of the lateral semicircular canal with a shortened forced position

Author

Beatrice Giannoni, Rudi Pecci, Federica Pollastri, Sebastiano Mininni, Giuseppe Licci, Rossana Santimone, Fabio Di Giustino, and Marco Mandalà

Subjects
forced prolonged position, forced position, benign paroxysmal positional vertigo, lateral semicircular canal, canalithiasis, cupulolithisias, Neurology. Diseases of the nervous system, RC346-429
Abstract

Benign paroxysmal positional vertigo (BPPV) is the peripheral vestibular disorder that is most frequently encountered in routine neuro-otological practice. Among the three semicircular canals, the lateral semicircular canal (LSC) is the second most frequently interested in the pathological process. In most cases, LSC BPPV is attributable to a canalithiasis or cupulolithiasis mechanism. The clinical picture of LSC BPPV is that of positional nystagmus and vertigo evoked by turning the head from the supine to the side lateral position. With such a movement, a horizontal positional (and often also paroxysmal) direction-changing nystagmus is generated. Depending on whether the pathogenetic mechanism is that of canalithiasis or cupulolithiasis and depending on where the dense particles are located, LSC BPPV direction-changing positional nystagmus is geotropic or apogeotropic on both lateral sides. Due to its mechanical nature, BPPV is effectively treated by means of physical therapy. In the case of a LSC BPPV, one of the most effective therapies is the forced prolonged position (FPP), in which the patient is invited to lie for 12 h on the lateral side on which vertigo and nystagmus are less intense, to move the canaliths out from the canal (or to shift them inside of the canal from one tract to another) exploiting the force of gravity. Despite its efficacy, FPP is not always well tolerated by every patient, and it cannot be done during the diagnostic session because of its duration. The present study aimed to verify the efficacy of a different forced position, shortened forced position (SFP), with respect to the original FPP. SFP treatment would allow patients to more easily bear the forced position and physicians to control the outcome almost immediately, possibly enabling them to dismiss patients without vertigo. After 1 h of lying on the side where vertigo and nystagmus are the less intense, 38 out of 53 (71.7%) patients treated with SFP were either healed or improved. Although the outcomes are not as satisfying as those of the original FPP, SFP should be considered as a therapeutic prospect, especially by those physicians who work in collaboration with emergency departments or otherwise encounter acute patients to cure them of vertigo as soon as possible.

Published
2023
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9. Development of a Magnetoresistive-Based Wearable Eye-Tracking System for Oculomotor Assessment in Neurological and Otoneurological Research—Preliminary In Vivo Tests

Author

Aniello Donniacuo, Francesca Viberti, Mario Carucci, Valerio Biancalana, Lorenzo Bellizzi, and Marco Mandalà

Subjects
eye tracker, vHIT, eye movements, search coil, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Over the past 20 years, several eye-tracking technologies have been developed. This article aims to present a new type of eye tracker capable of producing detailed information on eye and head movements using an array of magnetoresistive detectors fixed on the patient’s head and a small magnet inserted into a contact lens, adapted to the curvature of the cornea of the subject. The software used for data analysis can combine or compare eye and head movements and can represent them as 2D or 3D images. Preliminary data involve an initial patient who was asked to perform several tasks to establish the accuracy, reliability, and tolerance of the magnetic eye tracker and software. The tasks included assessment of saccadic eye movements and pursuit, “drawing” alphabetic shapes or letters, and reading. Finally, a Head Impulse Test (HIT) was performed to estimate the VOR gain, comparing the standard deviation established via vHIT with that established via this magnetic eye tracker (mHIT). This prototypical device is minimally invasive, lightweight, relatively cheap, and tolerable, with a high degree of reliability and precision. All these characteristics could lead to the future use of the magnetic eye tracker in neurological and otoneurological fields.

Published
2023
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10. Speech perception improvement through rTMS in hearing loss

Author

Francesco Neri, Chiara CAppello, Maria Luigia Tomai Pitinca, Sabrina Taddei, Francesca Viberti, Alessandra Cinti, Alberto Benelli, Emiliano Santarnecchi, Marco Mandalà, and Simone Rossi

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Published
2023
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12. Risk of falls, vestibular multimodal processing, and multisensory integration decline in the elderly–Predictive role of the functional head impulse test

Author

Leandro Politi, Lorenzo Salerni, Luciano Bubbico, Fabio Ferretti, Mario Carucci, Giovanni Rubegni, and Marco Mandalà

Subjects
elderly, falls, presbyastasis, cognitive decline, functional head impulse test, Neurology. Diseases of the nervous system, RC346-429
Abstract

Age-related degeneration of the vestibular system, also known as presbyastasis, leads to unstable gait and higher risk of falls. These conditions affect lifestyle and may have non-negligible social repercussions due to fear-related states of anxiety and depression. In order to develop a model for predicting risk of falls, we assessed vestibulo-ocular function by video and functional Head Impulse Tests (vHIT and fHIT) and their possible correlations with Tinetti Balance Test score. Thirty-one patients over 65 years of age admitted with trauma due to falls were recruited. Vestibular evaluation (complete otoneurological assessment, vHIT, fHIT), cognitive tests (Mini Mental State Examination), anxiety and depression evaluation and Tinetti Balance Test were performed. The possibility of a correlation between the head impulse tests (vHIT, fHIT) and the Tinetti Balance Test was investigated by logistic regression analysis (Nagelkerke r2 and Wald test). A linear correlation was found between the Tinetti Balance Test score and fHIT, whereas no correlation was found for vHIT. Functional HIT is an effective test for predicting the risk of falls in elderly patients.

Published
2022
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13. rTMS increases speech perception ability in deaf patients

Author

Francesco Neri, Chiara Cappello, Francesca Viberti, Aniello Donniacuo, Lucia Burzi, Alessandra Cinti, Alberto Benelli, Carmelo Luca Smeralda, Sara Romanella, Emiliano Santarnecchi, Marco Mandalà, and Simone Rossi

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Published
2023
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15. Two‐point‐NGS analysis of cancer genes in cell‐free DNA of metastatic cancer patients

Author

Maria Palmieri, Margherita Baldassarri, Francesca Fava, Alessandra Fabbiani, Elisa Gelli, Rossella Tita, Pamela Torre, Roberto Petrioli, Theodora Hadijstilianou, Daniela Galimberti, Elisa Cinotti, Carmelo Bengala, Marco Mandalà, Pietro Piu, Salvatora Tindara Miano, Ignazio Martellucci, Agnese Vannini, Anna Maria Pinto, Maria Antonietta Mencarelli, Stefania Marsili, Alessandra Renieri, and Elisa Frullanti

Subjects
cell‐free DNA, liquid biopsy, next‐generation sequencing, solid tumors, targeted‐therapy, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Although the efficacy of molecularly target agents in vitro, their use in routine setting is limited mainly to the use of anti‐HER2 and antiEGFR agents in vivo. Moreover, core biopsy of a single cancer site may not be representative of the whole expanding clones and cancer molecular profile at relapse may differ with respect to the primary tumor. Methods We assessed the status of a large panel of cancer driver genes by cell‐free DNA (cfDNA) analysis in a cohort of 68 patients with 13 different solid tumors at disease progression. Whenever possible, a second cfDNA analysis was performed after a mean of 2.5 months, in order to confirm the identified clone(s) and to check the correlation with clinical evolution. Results The approach was able to identify clones plausibly involved in the disease progression mechanism in about 65% of cases. A mean of 1.4 mutated genes (range 1‐3) for each tumor was found. Point mutations in TP53, PIK3CA, and KRAS and copy number variations in FGFR3 were the gene alterations more commonly observed, with a rate of 48%, 20%, 16%, and 20%, respectively. Two‐points‐Next‐Generation Sequencing (NGS) analysis demonstrated statistically significant correlation between allele frequency variation and clinical outcome (P = .026). Conclusions Irrespective of the primary tumor mutational burden, few mutated genes are present at disease progression. Clinical outcome is consistent with variation of allele frequency of specific clones indicating that cfDNA two‐point‐NGS analysis of cancer driver genes could be an efficacy tool for precision oncology.

Published
2020
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16. Care Gaps and Recommendations in Vestibular Migraine: An Expert Panel Summit

Author

Monica P. Mallampalli, Habib G. Rizk, Amir Kheradmand, Shin C. Beh, Mehdi Abouzari, Alaina M. Bassett, James Buskirk, Claire E. J. Ceriani, Matthew G. Crowson, Hamid Djalilian, Joel A. Goebel, Jeffery J. Kuhn, Anne E. Luebke, Marco Mandalà, Magdalena Nowaczewska, Nicole Spare, Roberto Teggi, Maurizio Versino, Hsiangkuo Yuan, Ashley Zaleski-King, Michael Teixido, and Frederick Godley

Subjects
vestibular migraine, chronic migraine (CM), trigemino-vascular pathway, vertigo-pathophysiology, vestibular disorders, Neurology. Diseases of the nervous system, RC346-429
Abstract

Vestibular migraine (VM) is an increasingly recognized pathology yet remains as an underdiagnosed cause of vestibular disorders. While current diagnostic criteria are codified in the 2012 Barany Society document and included in the third edition of the international classification of headache disorders, the pathophysiology of this disorder is still elusive. The Association for Migraine Disorders hosted a multidisciplinary, international expert workshop in October 2020 and identified seven current care gaps that the scientific community needs to resolve, including a better understanding of the range of symptoms and phenotypes of VM, the lack of a diagnostic marker, a better understanding of pathophysiologic mechanisms, as well as the lack of clear recommendations for interventions (nonpharmacologic and pharmacologic) and finally, the need for specific outcome measures that will guide clinicians as well as research into the efficacy of interventions. The expert group issued several recommendations to address those areas including establishing a global VM registry, creating an improved diagnostic algorithm using available vestibular tests as well as others that are in development, conducting appropriate trials of high quality to validate current clinically available treatment and fostering collaborative efforts to elucidate the pathophysiologic mechanisms underlying VM, specifically the role of the trigemino-vascular pathways.

Published
2022
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17. A Retrospective Evaluation to Assess Reliability of Electrophysiological Methods for Diagnosis of Hearing Loss in Infants

Author

Marco Mandalà, Luca Mazzocchin, Bryan Kevin Ward, Francesca Viberti, Ilaria Bindi, Lorenzo Salerni, Giacomo Colletti, Liliana Colletti, and Vittorio Colletti

Subjects
infants, auditory electrophysiological investigation, cochlear implant, auditory brainstem implant, reliability, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Background: An electrophysiological investigation with auditory brainstem response (ABR), round window electrocochleography (RW-ECoG), and electrical-ABR (E-ABR) was performed in children with suspected hearing loss with the purpose of early diagnosis and treatment. The effectiveness of the electrophysiological measures as diagnostic tools was assessed in this study. Methods: In this retrospective case series with chart review, 790 children below 3 years of age with suspected profound hearing loss were tested with impedance audiometry and underwent electrophysiological investigation (ABR, RW-ECoG, and E-ABR). All implanted cases underwent pure-tone audiometry (PTA) of the non-implanted ear at least 5 years after surgery for a long-term assessment of the reliability of the protocol. Results: Two hundred and fourteen children showed bilateral severe-to-profound hearing loss. In 56 children with either ABR thresholds between 70 and 90 dB nHL or no response, RW-ECoG showed thresholds below 70 dB nHL. In the 21 infants with bilateral profound sensorineural hearing loss receiving a unilateral cochlear implant, no statistically significant differences were found in auditory thresholds in the non-implanted ear between electrophysiological measures and PTA at the last follow-up (p > 0.05). Eight implanted children showed residual hearing below 2000 Hz worse than 100 dB nHL and 2 children showed pantonal residual hearing worse than 100 dB nHL (p > 0.05). Conclusion: The audiological evaluation of infants with a comprehensive protocol is highly reliable. RW-ECoG provided a better definition of hearing thresholds, while E-ABR added useful information in cases of auditory nerve deficiency.

Published
2022
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18. BPPV: Comparison of the SémontPLUS With the Sémont Maneuver: A Prospective Randomized Trial

Author

Michael Strupp, Nicolina Goldschagg, Anne-Sophie Vinck, Otmar Bayer, Sebastian Vandenbroeck, Lorenzo Salerni, Anita Hennig, Dominik Obrist, and Marco Mandalà

Subjects
BPPV [2,182], Sémont maneuver [143], Epley maneuver [477], vertigo [18,284], dizziness [35,838], Neurology. Diseases of the nervous system, RC346-429
Abstract

Objective: To compare the efficacy of the Sémont maneuver (SM) with the new “SémontPLUS maneuver” (SM+) in patients with posterior canal BPPV canalolithiasis (pcBPPVcan).Methods and Patients: In a prospective trinational (Germany, Italy, and Belgium) randomized trial, patients with pcBPPVcan were randomly assigned to SM or SM+; SM+ means overextension of the head by 60+° below earth horizontal line during the movement of the patient toward the affected side. The first maneuver was done by the physician, and the subsequent maneuvers by the patients 9 times/day on their own. Each morning the patient documented whether vertigo could be induced. The primary endpoints were: “How long (in days) does it take until no attacks can be induced?” and “What is the efficacy of a single SM/SM+?”Results: In the 194 patients analyzed (96 SM, 98 SM+), it took 2 days (median, range 1–21 days, mean 3.6 days) for recovery with SM and 1 day (median, range 1-8 days, mean 1.8 days) with SM+ (p = 0.001, Mann-Whitney U-test). There was no difference in the second primary endpoint (chi2-test, p = 0.39).Interpretation: This prospective trial shows that SM+ is more effective than SM when repeated therapeutic maneuvers are performed but not when a single maneuver is performed. It also supports the hypothesis of the biophysical model: overextension of the head during step 2 brings the clot of otoconia beyond the vertex of the canal, which increases the effectivity.Classification of Evidence: This study provides Class I evidence that SM+ is superior to SM for multiple treatment maneuvers of pcBPPVcan.

Published
2021
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19. Case Report: Local Anesthesia Round Window Plugging and Simultaneous Vibrant Soundbridge Implant for Superior Semicircular Canal Dehiscence

Author

Giulia Mignacco, Lorenzo Salerni, Ilaria Bindi, Giovanni Monciatti, Alfonso Cerase, and Marco Mandalà

Subjects
superior semicircular canal dehiscence, round window plugging, round window reinforcement, middle ear implant, canal dehiscence syndrome, Neurology. Diseases of the nervous system, RC346-429
Abstract

The aim of the present study is to report the outcomes of round window reinforcement surgery performed with the application of a Vibrant Soundbridge middle ear implant (VSB; MED-EL) in a patient with superior semicircular canal dehiscence (SSCD) who presented with recurrent vertigo, Tullio phenomenon, Hennebert's sign, bone conduction hypersensitivity, and bilateral moderate to severe mixed hearing loss. Vestibular evoked myogenic potentials (VEMPs) and high-resolution computed tomography (HRCT) confirmed bilateral superior semicircular canal dehiscence while this was not seen in magnetic resonance imaging. The surgical procedure was performed in the right ear as it had worse vestibular and auditory symptoms, a poorer hearing threshold, and greatly altered HRCT and VEMPs findings. With local-assisted anesthesia, round window reinforcement surgery (plugging) with perichondrium was performed with simultaneous positioning of a VSB on the round window niche. At the one and 3 months follow-up after surgery, VSB-aided hearing threshold in the right ear improved to mild, and loud sounds did not elicit either dizziness or pain in the patient.

Published
2020
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20. Clinical and molecular characterization of COVID-19 hospitalized patients.

Author

Elisa Benetti, Annarita Giliberti, Arianna Emiliozzi, Floriana Valentino, Laura Bergantini, Chiara Fallerini, Federico Anedda, Sara Amitrano, Edoardo Conticini, Rossella Tita, Miriana d'Alessandro, Francesca Fava, Simona Marcantonio, Margherita Baldassarri, Mirella Bruttini, Maria Antonietta Mazzei, Francesca Montagnani, Marco Mandalà, Elena Bargagli, Simone Furini, GEN-COVID Multicenter Study, Alessandra Renieri, and Francesca Mari

Subjects
Medicine, Science
Abstract

Clinical and molecular characterization by Whole Exome Sequencing (WES) is reported in 35 COVID-19 patients attending the University Hospital in Siena, Italy, from April 7 to May 7, 2020. Eighty percent of patients required respiratory assistance, half of them being on mechanical ventilation. Fiftyone percent had hepatic involvement and hyposmia was ascertained in 3 patients. Searching for common genes by collapsing methods against 150 WES of controls of the Italian population failed to give straightforward statistically significant results with the exception of two genes. This result is not unexpected since we are facing the most challenging common disorder triggered by environmental factors with a strong underlying heritability (50%). The lesson learned from Autism-Spectrum-Disorders prompted us to re-analyse the cohort treating each patient as an independent case, following a Mendelian-like model. We identified for each patient an average of 2.5 pathogenic mutations involved in virus infection susceptibility and pinpointing to one or more rare disorder(s). To our knowledge, this is the first report on WES and COVID-19. Our results suggest a combined model for COVID-19 susceptibility with a number of common susceptibility genes which represent the favorite background in which additional host private mutations may determine disease progression.

Published
2020
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21. Corrigendum: Clinical Features of Headache in Patients With Diagnosis of Definite Vestibular Migraine: The VM-Phenotypes Projects

Author

Roberto Teggi, Bruno Colombo, Roberto Albera, Giacinto Asprella Libonati, Cristiano Balzanelli, Angel Batuecas Caletrio, Augusto P. Casani, Juan Manuel Espinosa-Sanchez, Paolo Gamba, Jose A. Lopez-Escamez, Sergio Lucisano, Marco Mandalà, Giampiero Neri, Daniele Nuti, Rudi Pecci, Antonio Russo, Eduardo Martin-Sanz, Ricardo Sanz, Gioacchino Tedeschi, Paola Torelli, Paolo Vannucchi, Giancarlo Comi, and Mario Bussi

Subjects
Vestibular Migraine, vertigo, headache, migraine, clinical diagnosis, vestibular disorders, Neurology. Diseases of the nervous system, RC346-429
Published
2020
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22. Validation of a Fast and Accurate Magnetic Tracker Operating in the Environmental Field

Author

Valerio Biancalana, Roberto Cecchi, Piero Chessa, Marco Mandalà, Giuseppe Bevilacqua, Yordanka Dancheva, and Antonio Vigilante

Subjects
tracking, magnetic tracking, eye tracking, sensor array, eye motion, Physics, QC1-999, Nuclear and particle physics. Atomic energy. Radioactivity, QC770-798
Abstract

We characterize the performance of a system based on a magnetoresistor array. This instrument is developed to map the magnetic field, and to track a dipolar magnetic source in the presence of a static homogeneous field. The position and orientation of the magnetic source with respect to the sensor frame is retrieved together with the orientation of the frame with respect to the environmental field. A nonlinear best-fit procedure is used, and its precision, time performance, and reliability are analyzed. This analysis is performed in view of the practical application for which the system is designed that is an eye-tracking diagnostics and rehabilitative tool for medical purposes, which require high speed (≥100 Sa/s) and sub-millimetric spatial resolution. A throughout investigation on the results makes it possible to list several observations, suggestions, and hints, which will be useful in the design of similar setups.

Published
2021
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23. Clinical Features of Headache in Patients With Diagnosis of Definite Vestibular Migraine: The VM-Phenotypes Projects

Author

Roberto Teggi, Bruno Colombo, Roberto Albera, Giacinto Asprella Libonati, Cristiano Balzanelli, Angel Batuecas Caletrio, Augusto P. Casani, Juan Manuel Espinosa-Sanchez, Paolo Gamba, Jose A. Lopez-Escamez, Sergio Lucisano, Marco Mandalà, Giampiero Neri, Daniele Nuti, Rudi Pecci, Antonio Russo, Eduardo Martin-Sanz, Ricardo Sanz, Gioacchino Tedeschi, Paola Torelli, Paolo Vannucchi, Giancarlo Comi, and Mario Bussi

Subjects
Vestibular Migraine, vertigo, headache, migraine, clinical diagnosis, vestibular disorders, Neurology. Diseases of the nervous system, RC346-429
Abstract

Migraine is a common neurological disorder characterized by episodic headaches with specific features, presenting familial aggregation. Migraine is associated with episodic vertigo, named Vestibular Migraine (VM) whose diagnosis mainly rely on clinical history showing a temporary association of symptoms. Some patient refers symptoms occurring in pediatric age, defined “episodic symptoms which may be associated with migraine.” The aim of this cross sectional observational study was to assess migraine-related clinical features in VM subjects. For the purpose, 279 patients were recruited in different centers in Europe; data were collected by a senior neurologist or ENT specialist through a structured questionnaire. The age of onset of migraine was 21.8 ± 9. The duration of headaches was lower than 24 h in 79.1% of cases. Symptoms accompanying migrainous headaches were, in order of frequency, nausea (79.9%), phonophobia (54.5%), photophobia (53.8%), vomiting (29%), lightheadedness (21.1%). Visual or other auras were reported by 25.4% of subjects. A familial aggregation was referred by 67.4%, while migraine precursors were reported by 52.3% of subjects. Patients reporting nausea and vomiting during headaches more frequently experienced the same symptoms during vertigo. Comparing our results in VM subjects with previously published papers in migraine sufferers, our patients presented a lower duration of headaches and a higher rate of familial aggregation; moreover some common characters were observed in headache and vertigo attacks for accompanying symptoms like nausea and vomiting and clustering of attacks.

Published
2018
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24. Validation of the Italian Version of the Dizziness Handicap Inventory, the Situational Vertigo Questionnaire, and the Activity-Specific Balance Confidence Scale for Peripheral and Central Vestibular Symptoms

Author

Silvia Colnaghi, Cristiana Rezzani, Marco Gnesi, Marco Manfrin, Silvia Quaglieri, Daniele Nuti, Marco Mandalà, Maria Cristina Monti, and Maurizio Versino

Subjects
Dizziness Handicap Inventory, Situational Vertigo Questionnaire, Activity-specific Balance Confidence scale, vertigo, vestibular, questionnaires, Neurology. Diseases of the nervous system, RC346-429
Abstract

Neurophysiological measurements of the vestibular function for diagnosis and follow-up evaluations provide an objective assessment, which, unfortunately, does not necessarily correlate with the patients’ self-feeling. The literature provides many questionnaires to assess the outcome of rehabilitation programs for disequilibrium, but only for the Dizziness Handicap Inventory (DHI) is an Italian translation available, validated on a small group of patients suffering from a peripheral acute vertigo. We translated and validated the reliability and validity of the DHI, the Situational Vertigo Questionnaire (SVQ), and the Activities-Specific Balance Confidence Scale (ABC) in 316 Italian patients complaining of dizziness due either to a peripheral or to a central vestibular deficit, or in whom vestibular signs were undetectable by means of instrumental testing or clinical evaluation. Cronbach’s coefficient alpha, the homogeneity index, and test–retest reproducibility, confirmed reliability of the Italian version of the three questionnaires. Validity was confirmed by correlation test between questionnaire scores. Correlations with clinical variables suggested that they can be used as a complementary tool for the assessment of vestibular symptoms. In conclusion, the Italian versions of DHI, SVQ, and ABC are reliable and valid questionnaires for assessing the impact of dizziness on the quality of life of Italian patients with peripheral or central vestibular deficit.

Published
2017
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26. Current trends on subtotal petrosectomy with cochlear implantation in recalcitrant chronic middle ear disorders

Author

Pietro Canzi, Stefano Berrettini, Andrea Albera, Maurizio Barbara, Luca Bruschini, Andrea Canale, Elena Carlotto, Edoardo Covelli, Domenico Cuda, Francesco Dispenza, Maurizio Falcioni, Francesca Forli, Sebastiano Franchella, Lorenzo Gaini, Salvatore Gallina, Andrea Laborai, Ruggero Lapenna, Francesco Lazzerini, Stefano Malpede, Marco Mandalà, Domenico Minervini, Enrico Pasanisi, Giampietro Ricci, Francesca Viberti, Diego Zanetti, Elisabetta Zanoletti, and Marco Benazzo

Subjects
General Energy, Otorhinolaryngology
Published
2023

27. A Wearable Wireless Magnetic Eye-Tracker, in-vitro and in-vivo Tests

Author

francesca viberti, Leonardo Stiaccini, Marco Mandalà, Aniello Donniacuo, Piero Chessa, Roberto Cecchi, Mario Carucci, Valerio Biancalana, and Giuseppe Bevilacqua

Subjects
Magnetoresistor, Physics - Instrumentation and Detectors, Sensor Array, Eye Tracking, Magnetic field measurement, FOS: Physical sciences, Applied Physics (physics.app-ph), Instrumentation and Detectors (physics.ins-det), Physics - Applied Physics, Magnetometers, Physics - Medical Physics, Magnetic heads, Calibration, Eye Motion, Head, Magnetic Sensor, Magnetic tracker, Sensor arrays, Visualization, Medical Physics (physics.med-ph)
Abstract

A wireless, wearable magnetic eye tracker is described and characterized. The proposed instrumentation enables simultaneous evaluation of eye and head angular displacements. Such a system can be used to determine the absolute gaze direction as well as to analyze spontaneous eye re-orientation in response to stimuli consisting in head rotations. The latter feature has implications to analyze the vestibulo-ocular reflex and constitutes an interesting opportunity to develop medical (oto-neurological) diagnostics. Details of data analysis are reported together with some results obtained in-vivo or with simple mechanical simulators that enable measurements under controlled conditions., 11 pages, 7 figures, 46 references

Published
2023

29. A Wearable Wireless Magnetic Eye-Tracker

Author

francesca viberti, Leonardo Stiaccini, Marco Mandalà, Aniello Donniacuo, Piero Chessa, Roberto Cecchi, Mario Carucci, Valerio Biancalana, and Giuseppe Bevilacqua

Abstract

A wireless, wearable magnetic eye tracker is described and characterized. The proposed instrumentation enables simultaneous evaluation of eye and head angular displacements. Such a system can be used to determine the absolute gaze direction as well as to analyze spontaneous eye re-orientation in response to stimuli consisting in head rotations. The latter feature has implications to analyze the vestibulo-ocular reflex and constitutes an interesting opportunity to develop medical (oto-neurological) diagnostics. Details of data analysis are reported together with some results obtained in-vivo or with simple mechanical simulators that enable measurements under controlled conditions.

Published
2023

31. Ultra-rare RTEL1 gene variants associate with acute severity of COVID-19 and evolution to pulmonary fibrosis as a specific long COVID disorder

Author

Bergantini, Laura, Baldassarri, Margherita, D'Alessandro, Miriana, Brunelli, Giulia, Fabbri, Gaia, Zguro, Kristina, Degl'Innocenti, Andrea, Fallerini, Chiara, Bargagli, Elena, Renieri, Alessandra GEN-COVID Multicenter study: Francesca Mari, Sergio, Daga, Ilaria, Meloni, Mirella, Bruttini, Susanna, Croci, Mirjam, Lista, Debora, Maffeo, Elena, Pasquinelli, Viola Bianca Serio, Enrica, Antolini, Simona Letizia Basso, Samantha, Minetto, Rossella, Tita, Maria Antonietta Mencarelli, Caterina Lo Rizzo, Anna Maria Pinto, Francesca, Ariani, Francesca, Montagnani, Mario, Tumbarello, Ilaria, Rancan, Massimiliano, Fabbiani, Paolo, Cameli, David, Bennett, Federico, Anedda, Simona, Marcantonio, Sabino, Scolletta, Federico, Franchi, Maria Antonietta Mazzei, Susanna, Guerrini, Edoardo, Conticini, Luca, Cantarini, Bruno, Frediani, Danilo, Tacconi, Chiara Spertilli Raffaelli, Arianna, Emiliozzi, Marco, Feri, Alice, Donati, Raffaele, Scala, Luca, Guidelli, Genni, Spargi, Marta, Corridi, Cesira, Nencioni, Leonardo, Croci, Gian Piero Caldarelli, Davide, Romani, Paolo, Piacentini, Maria, Bandini, Elena, Desanctis, Silvia, Cappelli, Anna, Canaccini, Agnese, Verzuri, Valentina, Anemoli, Manola, Pisani, Agostino, Ognibene, Maria, Lorubbio, Alessandro, Pancrazzi, Massimo, Vaghi, Antonella, D 'Arminio Monforte, Federica Gaia Miraglia, Mario, U Mondelli, Stefania, Mantovani, Raffaele, Bruno, Marco, Vecchia, Marcello, Maffezzoni, Enrico, Martinelli, Massimo, Girardis, Stefano, Busani, Sophie, Venturelli, Andrea, Cossarizza, Andrea, Antinori, Alessandra, Vergori, Stefano, Rusconi, Matteo, Siano, Arianna, Gabrieli, Agostino, Riva, Daniela, Francisci, Elisabetta, Schiaroli, Carlo, Pallotto, Saverio Giuseppe Parisi, Monica, Basso, Sandro, Panese, Stefano, Baratti, Pier Giorgio Scotton, Francesca, Andretta, Mario, Giobbia, Renzo, Scaggiante, Francesca, Gatti, Francesco, Castelli, Eugenia, Quiros-Roldan, Melania Degli Antoni, Isabella, Zanella, Matteo Della Monica, Carmelo, Piscopo, Mario, Capasso, Roberta, Russo, Immacolata, Andolfo, Achille, Iolascon, Giuseppe, Fiorentino, Massimo, Carella, Marco, Castori, Giuseppe, Merla, Gabriella Maria Squeo, Filippo, Aucella, Pamela, Raggi, Rita, Perna, Matteo, Bassetti, Antonio Di Biagio, Maurizio, Sanguinetti, Luca, Masucci, Alessandra, Guarnaccia, Serafina, Valente, Alex Di Florio, Marco, Mandalà, Alessia, Giorli, Lorenzo, Salerni, Patrizia, Zucchi, Pierpaolo, Parravicini, Elisabetta, Menatti, Tullio, Trotta, Ferdinando, Giannattasio, Gabriella, Coiro, Fabio, Lena, Gianluca, Lacerenza, Cristina, Mussini, Luisa, Tavecchia, Lia, Crotti, Gianfranco, Parati, Roberto, Menè, Maurizio, Sanarico, Marco, Gori, Francesco, Raimondi, Alessandra, Stella, Filippo, Biscarini, Tiziana, Bachetti, Maria Teresa La Rovere, Maurizio, Bussotti, Serena, Ludovisi, Katia, Capitani, Simona, Dei, Sabrina, Ravaglia, Annarita, Giliberti, Giulia, Gori, Rosangela, Artuso, Elena, Andreucci, Angelica, Pagliazzi, Erika, Fiorentini, Antonio, Perrella, Francesco, Bianchi, Paola, Bergomi, Emanuele, Catena, Riccardo, Colombo, Sauro, Luchi, Giovanna, Morelli, Paola, Petrocelli, Sarah, Iacopini, Sara, Modica, Silvia, Baroni, Micheli, Giulia, Marco, Falcone, Donato, Urso, Giusy, Tiseo, Tommaso, Matucci, Grassi, Davide, Ferri, Claudio, Marinangeli, Franco, Brancati, Francesco, Antonella, Vincenti, Valentina, Borgo, Lombardi, Stefania, Mirco, Lenzi, Massimo Antonio Di Pietro, Francesca, Vichi, Benedetta, Romanin, Letizia, Attala, Cecilia, Costa, Andrea, Gabbuti, Alessio, Bellucci, Marta, Colaneri, Patrizia, Casprini, Cristoforo, Pomara, Massimiliano, Esposito, Roberto, Leoncini, Michele, Cirianni, Lucrezia, Galasso, Marco Antonio Bellini, Chiara, Gabbi, Nicola, Picchiotti, and Simone, Furini

Subjects
COVID-19, Long COVID, Pulmonary fibrosis, RTEL1
Published
2023

32. The impact of the COVID-19 pandemic on the quality of life of head and neck cancer survivors

Author

Francesca Viberti, Pierguido Ciabatti, Giuseppe Fancello, Pietro Orlando, Federica Martelli, S. Boccuzzi, Luca Giovanni Locatello, Oreste Gallo, Giandomenico Maggiore, Marco Mandalà, Maria Cilona, and Chiara Bruno

Subjects
medicine.medical_specialty, Total laryngectomy, medicine.medical_treatment, Population, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Surveys and Questionnaires, Internal medicine, Lockdown, Pandemic, medicine, Humans, Survivors, Head and neck cancer, 030223 otorhinolaryngology, education, Pandemics, education.field_of_study, SARS-CoV-2, business.industry, Social distance, COVID-19, medicine.disease, humanities, Laryngectomy, Oncology, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, Communicable Disease Control, Cohort, Quality of Life, Original Article, business, Psychosocial
Abstract

Background Head and neck cancer (HNC) survivors are particularly vulnerable to the deleterious consequences of lockdown and social distancing. The psychosocial effects of the COVID-19 pandemic on this group are still unknown, and we want to explore how their quality of life (QoL) has changed in this unique situation. Materials and methods An online survey, composed of pandemic-specific items, plus the EORTC QLQ-C30, was administered to a cohort of HNC survivors. Using previously published reference values as a control group, we have evaluated the impact of the pandemic on their QoL. We have also explored the differences between those who had received a total laryngectomy (LP, laryngectomized population) vs other HNC patients, in order to assess the role of tracheostomy in this regard. Results One hundred and twenty-one HNC patients completed the survey. The scores of the physical (80.5 vs 85, p = 0.028), role (78 vs 84, p = 0.030), and emotional functioning (76 vs 81, p = 0.041) were significantly different in the two groups, with worse functioning in our patients. Comparing LP with the other HNC patients, social (76.6 vs 88.9, p = 0.008) and physical functioning (75.5 vs 86.1, p = 0.006) were significantly worse in the former group. LP also reported a greater perception that others are afraid to be close to them (1.67 vs 1.32, p = 0.020). No differences were found between LP with and without voice prosthesis. Conclusions Our results show how HNC patients are at high risk for a worsening in QoL because of the ongoing COVID-19 global pandemic.

Published
2021

33. An explainable model of host genetic interactions linked to COVID-19 severity

Author

Anthony, O, Nicola, P, Chiara, F, Margherita, B, Francesca, F, Francesca, C, Alessandra, R, Simone, F, Francesco, R, Mari, F, Daga, S, Benetti, E, Bruttini, M, Palmieri, M, Croci, S, Amitrano, S, Meloni, I, Frullanti, E, Doddato, G, Lista, M, Beligni, G, Valentino, F, Zguro, K, Tita, R, Giliberti, A, Antonietta Mencarelli, M, Lo Rizzo, C, Maria Pinto, A, Ariani, F, Di Sarno, L, Montagnani, F, Tumbarello, M, Rancan, I, Fabbiani, M, Rossetti, B, Bergantini, L, D’Alessandro, M, Cameli, P, Bennett, D, Anedda, F, Marcantonio, S, Scolletta, S, Franchi, F, Antonietta Mazzei, M, Guerrini, S, Conticini, E, Cantarini, L, Frediani, B, Tacconi, D, Spertilli Raffaelli, C, Feri, M, Donati, A, Scala, R, Guidelli, L, Spargi, G, Corridi, M, Nencioni, C, Croci, L, Piero Caldarelli, G, Romani, D, Piacentini, P, Bandini, M, Desanctis, E, Cappelli, S, Canaccini, A, Verzuri, A, Anemoli, V, Pisani, M, Ognibene, A, Pancrazzi, A, Lorubbio, M, Vaghi, M, D’Arminio Monforte, A, Gaia Miraglia, F, Bruno, R, Vecchia, M, Girardis, M, Venturelli, S, Busani, S, Cossarizza, A, Antinori, A, Vergori, A, Emiliozzi, A, Rusconi, S, Siano, M, Gabrieli, A, Riva, A, Francisci, D, Schiaroli, E, Paciosi, F, Tommasi, A, Zuccon, U, Vietri, L, Giorgio Scotton, P, Andretta, F, Panese, S, Baratti, S, Scaggiante, R, Gatti, F, Giuseppe Parisi, S, Castelli, F, Quiros-Roldan, E, Degli Antoni, M, Zanella, I, Della Monica, M, Piscopo, C, Capasso, M, Russo, R, Andolfo, I, Iolascon, A, Fiorentino, G, Carella, M, Castori, M, Aucella, F, Raggi, P, Perna, R, Bassetti, M, Di Biagio, A, Sanguinetti, M, Masucci, L, Guarnaccia, A, Valente, S, De Vivo, O, Bargagli, E, Mandalà, M, Giorli, A, Salerni, L, Zucchi, P, Parravicini, P, Menatti, E, Trotta, T, Giannattasio, F, Coiro, G, Lena, F, Lacerenza, G, Coviello, D, Mussini, C, Martinelli, E, Tavecchia, L, Ann Belli, M, Crotti, L, Parati, G, Sanarico, M, Biscarini, F, Stella, A, Rizzi, M, Maggiolo, F, Ripamonti, D, Suardi, C, Bachetti, T, Teresa La Rovere, M, Sarzi-Braga, S, Bussotti, M, Capitani, K, Dei, S, Ravaglia, S, Artuso, R, Andreucci, E, Gori, G, Pagliazzi, A, Fiorentini, E, Perrella, A, Bianchi, F, Bergomi, P, Catena, E, Colombo, R, Luchi, S, Morelli, G, Petrocelli, P, Iacopini, S, Modica, S, Baroni, S, Vladimiro Segala, F, Menichetti, F, Falcone, M, Tiseo, G, Barbieri, C, Matucci, T, Grassi, D, Ferri, C, Marinangeli, F, Brancati, F, Vincenti, A, Borgo, V, Lombardi, S, Lenzi, M, Antonio Di Pietro, M, Vichi, F, Romanin, B, Attala, L, Costa, C, Gabbuti, A, Menè, R, Colaneri, M, Casprini, P, Merla, G, Maria Squeo, G, Maffezzoni, M, Mantovani, S, Mondelli &amp, M, Ludovisi, S, Onoja, Anthony, Picchiotti, Nicola, Fallerini, Chiara, Baldassarri, Margherita, Fava, Francesca, Colombo, Francesca, Chiaromonte, Francesca, Renieri, Alessandra, Furini, Simone, Raimondi Francesco, Francesca Mari, Sergio Daga, Elisa Benetti, Mirella Bruttini, Maria Palmieri, Susanna Croci, Sara Amitrano, Ilaria Meloni, Elisa Frullanti, Gabriella Doddato, Mirjam Lista, Giada Beligni, Floriana Valentino, Kristina Zguro, Rossella Tita, Annarita Giliberti, Maria Antonietta Mencarelli, Caterina Lo Rizzo, Anna Maria Pinto, Francesca Ariani, Laura Di Sarno, Francesca Montagnani, Mario Tumbarello, Ilaria Rancan, Massimiliano Fabbiani, Barbara Rossetti, Laura Bergantini, Miriana D’Alessandro, Paolo Cameli, David Bennett, Federico Anedda, Simona Marcantonio, Sabino Scolletta, Federico Franchi, Maria Antonietta Mazzei, Susanna Guerrini, Edoardo Conticini, Luca Cantarini, Bruno Frediani, Danilo Tacconi, Chiara Spertilli Raffaelli, Marco Feri, Alice Donati, Raffaele Scala, Luca Guidelli, Genni Spargi, Marta Corridi, Cesira Nencioni, Leonardo Croci, Gian Piero Caldarelli, Davide Romani, Paolo Piacentini, Maria Bandini, Elena Desanctis, Silvia Cappelli, Anna Canaccini, Agnese Verzuri, Valentina Anemoli, Manola Pisani, Agostino Ognibene, Alessandro Pancrazzi, Maria Lorubbio, Massimo Vaghi, Antonella D’Arminio Monforte, Federica Gaia Miraglia, Raffaele Bruno, Marco Vecchia, Massimo Girardis, Sophie Venturelli, Stefano Busani, Andrea Cossarizza, Andrea Antinori, Alessandra Vergori, Arianna Emiliozzi, Stefano Rusconi, Matteo Siano, Arianna Gabrieli, Agostino Riva, Daniela Francisci, Elisabetta Schiaroli, Francesco Paciosi, Andrea Tommasi, Umberto Zuccon, Lucia Vietri, Pier Giorgio Scotton, Francesca Andretta, Sandro Panese, Stefano Baratti, Renzo Scaggiante, Francesca Gatti, Saverio Giuseppe Parisi, Francesco Castelli, Eugenia Quiros-Roldan, Melania Degli Antoni, Isabella Zanella, Matteo Della Monica, Carmelo Piscopo, Mario Capasso, Roberta Russo, Immacolata Andolfo, Achille Iolascon, Giuseppe Fiorentino, Massimo Carella, Marco Castori, Filippo Aucella, Pamela Raggi, Rita Perna, Matteo Bassetti, Antonio Di Biagio, Maurizio Sanguinetti, Luca Masucci, Alessandra Guarnaccia, Serafina Valente, Oreste De Vivo, Elena Bargagli, Marco Mandalà, Alessia Giorli, Lorenzo Salerni, Patrizia Zucchi, Pierpaolo Parravicini, Elisabetta Menatti, Tullio Trotta, Ferdinando Giannattasio, Gabriella Coiro, Fabio Lena, Gianluca Lacerenza, Domenico A. Coviello, Cristina Mussini, Enrico Martinelli, Luisa Tavecchia, Mary Ann Belli, Lia Crotti, Gianfranco Parati, Maurizio Sanarico, Filippo Biscarini, Alessandra Stella, Marco Rizzi, Franco Maggiolo, Diego Ripamonti, Claudia Suardi, Tiziana Bachetti, Maria Teresa La Rovere, Simona Sarzi-Braga, Maurizio Bussotti, Katia Capitani, Simona Dei, Sabrina Ravaglia, Rosangela Artuso, Elena Andreucci, Giulia Gori, Angelica Pagliazzi, Erika Fiorentini, Antonio Perrella, Francesco Bianchi, Paola Bergomi, Emanuele Catena, Riccardo Colombo, Sauro Luchi, Giovanna Morelli, Paola Petrocelli, Sarah Iacopini, Sara Modica, Silvia Baroni, Francesco Vladimiro Segala, Francesco Menichetti, Marco Falcone, Giusy Tiseo, Chiara Barbieri, Tommaso Matucci, Davide Grassi, Claudio Ferri, Franco Marinangeli, Francesco Brancati, Antonella Vincenti, Valentina Borgo, Stefania Lombardi, Mirco Lenzi, Massimo Antonio Di Pietro, Francesca Vichi, Benedetta Romanin, Letizia Attala, Cecilia Costa, Andrea Gabbuti, Roberto Menè, Marta Colaneri, Patrizia Casprini, Giuseppe Merla, Gabriella Maria Squeo, Marcello Maffezzoni, Stefania Mantovani, Mario U. Mondelli &, Serena Ludovisi, Anthony, O, Nicola, P, Chiara, F, Margherita, B, Francesca, F, Francesca, C, Alessandra, R, Simone, F, Francesco, R, Mari, F, Daga, S, Benetti, E, Bruttini, M, Palmieri, M, Croci, S, Amitrano, S, Meloni, I, Frullanti, E, Doddato, G, Lista, M, Beligni, G, Valentino, F, Zguro, K, Tita, R, Giliberti, A, Antonietta Mencarelli, M, Lo Rizzo, C, Maria Pinto, A, Ariani, F, Di Sarno, L, Montagnani, F, Tumbarello, M, Rancan, I, Fabbiani, M, Rossetti, B, Bergantini, L, D’Alessandro, M, Cameli, P, Bennett, D, Anedda, F, Marcantonio, S, Scolletta, S, Franchi, F, Antonietta Mazzei, M, Guerrini, S, Conticini, E, Cantarini, L, Frediani, B, Tacconi, D, Spertilli Raffaelli, C, Feri, M, Donati, A, Scala, R, Guidelli, L, Spargi, G, Corridi, M, Nencioni, C, Croci, L, Piero Caldarelli, G, Romani, D, Piacentini, P, Bandini, M, Desanctis, E, Cappelli, S, Canaccini, A, Verzuri, A, Anemoli, V, Pisani, M, Ognibene, A, Pancrazzi, A, Lorubbio, M, Vaghi, M, D’Arminio Monforte, A, Gaia Miraglia, F, Bruno, R, Vecchia, M, Girardis, M, Venturelli, S, Busani, S, Cossarizza, A, Antinori, A, Vergori, A, Emiliozzi, A, Rusconi, S, Siano, M, Gabrieli, A, Riva, A, Francisci, D, Schiaroli, E, Paciosi, F, Tommasi, A, Zuccon, U, Vietri, L, Giorgio Scotton, P, Andretta, F, Panese, S, Baratti, S, Scaggiante, R, Gatti, F, Giuseppe Parisi, S, Castelli, F, Quiros-Roldan, E, Degli Antoni, M, Zanella, I, Della Monica, M, Piscopo, C, Capasso, M, Russo, R, Andolfo, I, Iolascon, A, Fiorentino, G, Carella, M, Castori, M, Aucella, F, Raggi, P, Perna, R, Bassetti, M, Di Biagio, A, Sanguinetti, M, Masucci, L, Guarnaccia, A, Valente, S, De Vivo, O, Bargagli, E, Mandalà, M, Giorli, A, Salerni, L, Zucchi, P, Parravicini, P, Menatti, E, Trotta, T, Giannattasio, F, Coiro, G, Lena, F, Lacerenza, G, Coviello, D, Mussini, C, Martinelli, E, Tavecchia, L, Ann Belli, M, Crotti, L, Parati, G, Sanarico, M, Biscarini, F, Stella, A, Rizzi, M, Maggiolo, F, Ripamonti, D, Suardi, C, Bachetti, T, Teresa La Rovere, M, Sarzi-Braga, S, Bussotti, M, Capitani, K, Dei, S, Ravaglia, S, Artuso, R, Andreucci, E, Gori, G, Pagliazzi, A, Fiorentini, E, Perrella, A, Bianchi, F, Bergomi, P, Catena, E, Colombo, R, Luchi, S, Morelli, G, Petrocelli, P, Iacopini, S, Modica, S, Baroni, S, Vladimiro Segala, F, Menichetti, F, Falcone, M, Tiseo, G, Barbieri, C, Matucci, T, Grassi, D, Ferri, C, Marinangeli, F, Brancati, F, Vincenti, A, Borgo, V, Lombardi, S, Lenzi, M, Antonio Di Pietro, M, Vichi, F, Romanin, B, Attala, L, Costa, C, Gabbuti, A, Menè, R, Colaneri, M, Casprini, P, Merla, G, Maria Squeo, G, Maffezzoni, M, Mantovani, S, Mondelli &amp, M, Ludovisi, S, Onoja, Anthony, Picchiotti, Nicola, Fallerini, Chiara, Baldassarri, Margherita, Fava, Francesca, Colombo, Francesca, Chiaromonte, Francesca, Renieri, Alessandra, Furini, Simone, Raimondi Francesco, Francesca Mari, Sergio Daga, Elisa Benetti, Mirella Bruttini, Maria Palmieri, Susanna Croci, Sara Amitrano, Ilaria Meloni, Elisa Frullanti, Gabriella Doddato, Mirjam Lista, Giada Beligni, Floriana Valentino, Kristina Zguro, Rossella Tita, Annarita Giliberti, Maria Antonietta Mencarelli, Caterina Lo Rizzo, Anna Maria Pinto, Francesca Ariani, Laura Di Sarno, Francesca Montagnani, Mario Tumbarello, Ilaria Rancan, Massimiliano Fabbiani, Barbara Rossetti, Laura Bergantini, Miriana D’Alessandro, Paolo Cameli, David Bennett, Federico Anedda, Simona Marcantonio, Sabino Scolletta, Federico Franchi, Maria Antonietta Mazzei, Susanna Guerrini, Edoardo Conticini, Luca Cantarini, Bruno Frediani, Danilo Tacconi, Chiara Spertilli Raffaelli, Marco Feri, Alice Donati, Raffaele Scala, Luca Guidelli, Genni Spargi, Marta Corridi, Cesira Nencioni, Leonardo Croci, Gian Piero Caldarelli, Davide Romani, Paolo Piacentini, Maria Bandini, Elena Desanctis, Silvia Cappelli, Anna Canaccini, Agnese Verzuri, Valentina Anemoli, Manola Pisani, Agostino Ognibene, Alessandro Pancrazzi, Maria Lorubbio, Massimo Vaghi, Antonella D’Arminio Monforte, Federica Gaia Miraglia, Raffaele Bruno, Marco Vecchia, Massimo Girardis, Sophie Venturelli, Stefano Busani, Andrea Cossarizza, Andrea Antinori, Alessandra Vergori, Arianna Emiliozzi, Stefano Rusconi, Matteo Siano, Arianna Gabrieli, Agostino Riva, Daniela Francisci, Elisabetta Schiaroli, Francesco Paciosi, Andrea Tommasi, Umberto Zuccon, Lucia Vietri, Pier Giorgio Scotton, Francesca Andretta, Sandro Panese, Stefano Baratti, Renzo Scaggiante, Francesca Gatti, Saverio Giuseppe Parisi, Francesco Castelli, Eugenia Quiros-Roldan, Melania Degli Antoni, Isabella Zanella, Matteo Della Monica, Carmelo Piscopo, Mario Capasso, Roberta Russo, Immacolata Andolfo, Achille Iolascon, Giuseppe Fiorentino, Massimo Carella, Marco Castori, Filippo Aucella, Pamela Raggi, Rita Perna, Matteo Bassetti, Antonio Di Biagio, Maurizio Sanguinetti, Luca Masucci, Alessandra Guarnaccia, Serafina Valente, Oreste De Vivo, Elena Bargagli, Marco Mandalà, Alessia Giorli, Lorenzo Salerni, Patrizia Zucchi, Pierpaolo Parravicini, Elisabetta Menatti, Tullio Trotta, Ferdinando Giannattasio, Gabriella Coiro, Fabio Lena, Gianluca Lacerenza, Domenico A. Coviello, Cristina Mussini, Enrico Martinelli, Luisa Tavecchia, Mary Ann Belli, Lia Crotti, Gianfranco Parati, Maurizio Sanarico, Filippo Biscarini, Alessandra Stella, Marco Rizzi, Franco Maggiolo, Diego Ripamonti, Claudia Suardi, Tiziana Bachetti, Maria Teresa La Rovere, Simona Sarzi-Braga, Maurizio Bussotti, Katia Capitani, Simona Dei, Sabrina Ravaglia, Rosangela Artuso, Elena Andreucci, Giulia Gori, Angelica Pagliazzi, Erika Fiorentini, Antonio Perrella, Francesco Bianchi, Paola Bergomi, Emanuele Catena, Riccardo Colombo, Sauro Luchi, Giovanna Morelli, Paola Petrocelli, Sarah Iacopini, Sara Modica, Silvia Baroni, Francesco Vladimiro Segala, Francesco Menichetti, Marco Falcone, Giusy Tiseo, Chiara Barbieri, Tommaso Matucci, Davide Grassi, Claudio Ferri, Franco Marinangeli, Francesco Brancati, Antonella Vincenti, Valentina Borgo, Stefania Lombardi, Mirco Lenzi, Massimo Antonio Di Pietro, Francesca Vichi, Benedetta Romanin, Letizia Attala, Cecilia Costa, Andrea Gabbuti, Roberto Menè, Marta Colaneri, Patrizia Casprini, Giuseppe Merla, Gabriella Maria Squeo, Marcello Maffezzoni, Stefania Mantovani, Mario U. Mondelli &, and Serena Ludovisi

Abstract

We employed a multifaceted computational strategy to identify the genetic factors contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing (WES) dataset of a cohort of 2000 Italian patients. We coupled a stratified k-fold screening, to rank variants more associated with severity, with the training of multiple supervised classifiers, to predict severity based on screened features. Feature importance analysis from tree-based models allowed us to identify 16 variants with the highest support which, together with age and gender covariates, were found to be most predictive of COVID-19 severity. When tested on a follow-up cohort, our ensemble of models predicted severity with high accuracy (ACC = 81.88%; AUCROC = 96%; MCC = 61.55%). Our model recapitulated a vast literature of emerging molecular mechanisms and genetic factors linked to COVID-19 response and extends previous landmark Genome-Wide Association Studies (GWAS). It revealed a network of interplaying genetic signatures converging on established immune system and inflammatory processes linked to viral infection response. It also identified additional processes cross-talking with immune pathways, such as GPCR signaling, which might offer additional opportunities for therapeutic intervention and patient stratification. Publicly available PheWAS datasets revealed that several variants were significantly associated with phenotypic traits such as “Respiratory or thoracic disease”, supporting their link with COVID-19 severity outcome.

Published
2022

34. Two‐point‐NGS analysis of cancer genes in cell‐free DNA of metastatic cancer patients

Author

Pietro Piu, Elisa Gelli, Margherita Baldassarri, Elisa Frullanti, Marco Mandalà, Elisa Cinotti, Alessandra Fabbiani, Maria Palmieri, Francesca Fava, Anna Maria Pinto, Roberto Petrioli, Pamela Torre, Maria Antonietta Mencarelli, Alessandra Renieri, Carmelo Bengala, Agnese Vannini, Stefania Marsili, Salvatora Tindara Miano, Daniela Galimberti, Theodora Hadijstilianou, Ignazio Martellucci, and Rossella Tita

Subjects
Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_treatment, DNA Mutational Analysis, targeted-therapy, next‐generation sequencing, medicine.disease_cause, Circulating Tumor DNA, Targeted therapy, 0302 clinical medicine, Neoplasms, Prospective Studies, Copy-number variation, Precision Medicine, Child, cell‐free DNA, Original Research, Aged, 80 and over, targeted‐therapy, High-Throughput Nucleotide Sequencing, Middle Aged, solid tumors, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Primary tumor, Cell-free fetal DNA, Child, Preschool, 030220 oncology & carcinogenesis, Disease Progression, Female, KRAS, Adult, medicine.medical_specialty, Adolescent, DNA Copy Number Variations, cell-free DNA, liquid biopsy, next-generation sequencing, lcsh:RC254-282, Clonal Evolution, Young Adult, 03 medical and health sciences, Internal medicine, Biomarkers, Tumor, medicine, Humans, Point Mutation, Radiology, Nuclear Medicine and imaging, Liquid biopsy, Allele frequency, Aged, business.industry, Infant, Clinical Cancer Research, Cancer, medicine.disease, 030104 developmental biology, Mutation, Feasibility Studies, business, Follow-Up Studies
Abstract

Background Although the efficacy of molecularly target agents in vitro, their use in routine setting is limited mainly to the use of anti‐HER2 and antiEGFR agents in vivo. Moreover, core biopsy of a single cancer site may not be representative of the whole expanding clones and cancer molecular profile at relapse may differ with respect to the primary tumor. Methods We assessed the status of a large panel of cancer driver genes by cell‐free DNA (cfDNA) analysis in a cohort of 68 patients with 13 different solid tumors at disease progression. Whenever possible, a second cfDNA analysis was performed after a mean of 2.5 months, in order to confirm the identified clone(s) and to check the correlation with clinical evolution. Results The approach was able to identify clones plausibly involved in the disease progression mechanism in about 65% of cases. A mean of 1.4 mutated genes (range 1‐3) for each tumor was found. Point mutations in TP53, PIK3CA, and KRAS and copy number variations in FGFR3 were the gene alterations more commonly observed, with a rate of 48%, 20%, 16%, and 20%, respectively. Two‐points‐Next‐Generation Sequencing (NGS) analysis demonstrated statistically significant correlation between allele frequency variation and clinical outcome (P = .026). Conclusions Irrespective of the primary tumor mutational burden, few mutated genes are present at disease progression. Clinical outcome is consistent with variation of allele frequency of specific clones indicating that cfDNA two‐point‐NGS analysis of cancer driver genes could be an efficacy tool for precision oncology., Core biopsy of a single cancer site may not be representative of the whole expanding clones and cancer molecular profile at relapse may differ with respect to the primary tumor. In this study, we performed a first and whenever possible, a second NGS liquid biopsy analysis after a mean of 2.5 months in advanced cancer patients. The approach was able to identify clones plausibly involved in the disease progression mechanism in about 65% of cases. Clinical outcome is consistent with variation of allele frequency of specific clones indicating that cfDNA two point‐NGS analysis of cancer driver genes could be an efficacy tool for precision oncology.

Published
2020

35. An explainable model of host genetic interactions linked to COVID-19 severity

Author

Onoja, Anthony, Picchiotti, Nicola, Fallerini, Chiara, Baldassarri, Margherita, Fava, Francesca, Colombo, Francesca, Chiaromonte, Francesca, Renieri, Alessandra, Furini, Simone, Raimondi, Francesco GEN-COVID Multicenter Study: Francesca Mari, Sergio, Daga, Elisa, Benetti, Mirella, Bruttini, Maria, Palmieri, Susanna, Croci, Sara, Amitrano, Ilaria, Meloni, Elisa, Frullanti, Gabriella, Doddato, Mirjam, Lista, Giada, Beligni, Floriana, Valentino, Kristina, Zguro, Rossella, Tita, Annarita, Giliberti, Maria Antonietta Mencarelli, Caterina Lo Rizzo, Anna Maria Pinto, Francesca, Ariani, Laura Di Sarno, Francesca, Montagnani, Mario, Tumbarello, Ilaria, Rancan, Massimiliano, Fabbiani, Barbara, Rossetti, Laura, Bergantini, Miriana, D'Alessandro, Paolo, Cameli, David, Bennett, Federico, Anedda, Simona, Marcantonio, Sabino, Scolletta, Federico, Franchi, Maria Antonietta Mazzei, Susanna, Guerrini, Edoardo, Conticini, Luca, Cantarini, Bruno, Frediani, Danilo, Tacconi, Chiara Spertilli Raffaelli, Marco, Feri, Alice, Donati, Raffaele, Scala, Luca, Guidelli, Genni, Spargi, Marta, Corridi, Cesira, Nencioni, Leonardo, Croci, Gian Piero Caldarelli, Davide, Romani, Paolo, Piacentini, Maria, Bandini, Elena, Desanctis, Silvia, Cappelli, Anna, Canaccini, Agnese, Verzuri, Valentina, Anemoli, Manola, Pisani, Agostino, Ognibene, Alessandro, Pancrazzi, Maria, Lorubbio, Massimo, Vaghi, Antonella D'Arminio Monforte, Federica Gaia Miraglia, Raffaele, Bruno, Marco, Vecchia, Massimo, Girardis, Sophie, Venturelli, Stefano, Busani, Andrea, Cossarizza, Andrea, Antinori, Alessandra, Vergori, Arianna, Emiliozzi, Stefano, Rusconi, Matteo, Siano, Arianna, Gabrieli, Agostino, Riva, Daniela, Francisci, Elisabetta, Schiaroli, Francesco, Paciosi, Andrea, Tommasi, Umberto, Zuccon, Lucia, Vietri, Pier Giorgio Scotton, Francesca, Andretta, Sandro, Panese, Stefano, Baratti, Renzo, Scaggiante, Francesca, Gatti, Saverio Giuseppe Parisi, Francesco, Castelli, Eugenia, Quiros-Roldan, Melania Degli Antoni, Isabella, Zanella, Matteo Della Monica, Carmelo, Piscopo, Mario, Capasso, Roberta, Russo, Immacolata, Andolfo, Achille, Iolascon, Giuseppe, Fiorentino, Massimo, Carella, Marco, Castori, Filippo, Aucella, Pamela, Raggi, Rita, Perna, Matteo, Bassetti, Antonio Di Biagio, Maurizio, Sanguinetti, Luca, Masucci, Alessandra, Guarnaccia, Serafina, Valente, Oreste De Vivo, Elena, Bargagli, Marco, Mandalà, Alessia, Giorli, Lorenzo, Salerni, Patrizia, Zucchi, Pierpaolo, Parravicini, Elisabetta, Menatti, Tullio, Trotta, Ferdinando, Giannattasio, Gabriella, Coiro, Fabio, Lena, Gianluca, Lacerenza, Domenico, A Coviello, Cristina, Mussini, Enrico, Martinelli, Luisa, Tavecchia, Mary Ann Belli, Lia, Crotti, Gianfranco, Parati, Maurizio, Sanarico, Filippo, Biscarini, Alessandra, Stella, Marco, Rizzi, Franco, Maggiolo, Diego, Ripamonti, Claudia, Suardi, Tiziana, Bachetti, Maria Teresa La Rovere, Simona, Sarzi-Braga, Maurizio, Bussotti, Katia, Capitani, Simona, Dei, Sabrina, Ravaglia, Rosangela, Artuso, Elena, Andreucci, Giulia, Gori, Angelica, Pagliazzi, Erika, Fiorentini, Antonio, Perrella, Francesco, Bianchi, Paola, Bergomi, Emanuele, Catena, Riccardo, Colombo, Sauro, Luchi, Giovanna, Morelli, Paola, Petrocelli, Sarah, Iacopini, Sara, Modica, Silvia, Baroni, Francesco Vladimiro Segala, Francesco, Menichetti, Marco, Falcone, Giusy, Tiseo, Chiara, Barbieri, Tommaso, Matucci, Grassi, Davide, Ferri, Claudio, Marinangeli, Franco, Brancati, Francesco, Antonella, Vincenti, Valentina, Borgo, Lombardi, Stefania, Mirco, Lenzi, Massimo Antonio Di Pietro, Francesca, Vichi, Benedetta, Romanin, Letizia, Attala, Cecilia, Costa, Andrea, Gabbuti, Roberto, Menè, Marta, Colaneri, Patrizia, Casprini, Giuseppe, Merla, Gabriella Maria Squeo, Marcello, Maffezzoni, Stefania, Mantovani, Mario, U Mondelli, Serena, Ludovisi, Onoja, Anthony, Picchiotti, Nicola, Fallerini, Chiara, Baldassarri, Margherita, Fava, Francesca, nbsp, Multicenter Study, GEN-COVID, Colombo, Francesca, Chiaromonte, Francesca, Renieri, Alessandra, Furini, Simone, Raimondi, Francesco, Anthony, O, Nicola, P, Chiara, F, Margherita, B, Francesca, F, Francesca, C, Alessandra, R, Simone, F, Francesco, R, Mari, F, Daga, S, Benetti, E, Bruttini, M, Palmieri, M, Croci, S, Amitrano, S, Meloni, I, Frullanti, E, Doddato, G, Lista, M, Beligni, G, Valentino, F, Zguro, K, Tita, R, Giliberti, A, Antonietta Mencarelli, M, Lo Rizzo, C, Maria Pinto, A, Ariani, F, Di Sarno, L, Montagnani, F, Tumbarello, M, Rancan, I, Fabbiani, M, Rossetti, B, Bergantini, L, D’Alessandro, M, Cameli, P, Bennett, D, Anedda, F, Marcantonio, S, Scolletta, S, Franchi, F, Antonietta Mazzei, M, Guerrini, S, Conticini, E, Cantarini, L, Frediani, B, Tacconi, D, Spertilli Raffaelli, C, Feri, M, Donati, A, Scala, R, Guidelli, L, Spargi, G, Corridi, M, Nencioni, C, Croci, L, Piero Caldarelli, G, Romani, D, Piacentini, P, Bandini, M, Desanctis, E, Cappelli, S, Canaccini, A, Verzuri, A, Anemoli, V, Pisani, M, Ognibene, A, Pancrazzi, A, Lorubbio, M, Vaghi, M, D’Arminio Monforte, A, Gaia Miraglia, F, Bruno, R, Vecchia, M, Girardis, M, Venturelli, S, Busani, S, Cossarizza, A, Antinori, A, Vergori, A, Emiliozzi, A, Rusconi, S, Siano, M, Gabrieli, A, Riva, A, Francisci, D, Schiaroli, E, Paciosi, F, Tommasi, A, Zuccon, U, Vietri, L, Giorgio Scotton, P, Andretta, F, Panese, S, Baratti, S, Scaggiante, R, Gatti, F, Giuseppe Parisi, S, Castelli, F, Quiros-Roldan, E, Degli Antoni, M, Zanella, I, Della Monica, M, Piscopo, C, Capasso, M, Russo, R, Andolfo, I, Iolascon, A, Fiorentino, G, Carella, M, Castori, M, Aucella, F, Raggi, P, Perna, R, Bassetti, M, Di Biagio, A, Sanguinetti, M, Masucci, L, Guarnaccia, A, Valente, S, De Vivo, O, Bargagli, E, Mandalà, M, Giorli, A, Salerni, L, Zucchi, P, Parravicini, P, Menatti, E, Trotta, T, Giannattasio, F, Coiro, G, Lena, F, Lacerenza, G, Coviello, D, Mussini, C, Martinelli, E, Tavecchia, L, Ann Belli, M, Crotti, L, Parati, G, Sanarico, M, Biscarini, F, Stella, A, Rizzi, M, Maggiolo, F, Ripamonti, D, Suardi, C, Bachetti, T, Teresa La Rovere, M, Sarzi-Braga, S, Bussotti, M, Capitani, K, Dei, S, Ravaglia, S, Artuso, R, Andreucci, E, Gori, G, Pagliazzi, A, Fiorentini, E, Perrella, A, Bianchi, F, Bergomi, P, Catena, E, Colombo, R, Luchi, S, Morelli, G, Petrocelli, P, Iacopini, S, Modica, S, Baroni, S, Vladimiro Segala, F, Menichetti, F, Falcone, M, Tiseo, G, Barbieri, C, Matucci, T, Grassi, D, Ferri, C, Marinangeli, F, Brancati, F, Vincenti, A, Borgo, V, Lombardi, S, Lenzi, M, Antonio Di Pietro, M, Vichi, F, Romanin, B, Attala, L, Costa, C, Gabbuti, A, Menè, R, Colaneri, M, Casprini, P, Merla, G, Maria Squeo, G, Maffezzoni, M, Mantovani, S, Mondelli &amp, M, and Ludovisi, S

Subjects
Genetics, Coronavirus disease 2019 (COVID-19), Host (biology), COVID-19, Medicine (miscellaneous), Settore BIO/11 - Biologia Molecolare, Biology, Settore MED/07 - MICROBIOLOGIA E MICROBIOLOGIA CLINICA, Whole Exome Sequencing, General Biochemistry, Genetics and Molecular Biology, machine learning, Phenotype, Exome Sequencing, Humans, Genetic Predisposition to Disease, Genome-Wide Association Study, General Agricultural and Biological Sciences, COVID, Human
Abstract

We employed a multifaceted computational strategy to identify the genetic factors contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing (WES) dataset of a cohort of 2000 Italian patients. We coupled a stratified k-fold screening, to rank variants more associated with severity, with training of multiple supervised classifiers, to predict severity on the basis of screened features. Feature importance analysis from tree-based models allowed to identify a handful of 16 variants with highest support which, together with age and gender covariates, were found to be most predictive of COVID-19 severity. When tested on a follow-up cohort, our ensemble of models predicted severity with good accuracy (ACC=81.88%; ROC_AUC=96%; MCC=61.55%). Principal Component Analysis (PCA) and clustering of patients on important variants orthogonally identified two groups of individuals with a higher fraction of severe cases. Our model recapitulated a vast literature of emerging molecular mechanisms and genetic factors linked to COVID-19 response and extends previous landmark Genome Wide Association Studies (GWAS). It revealed a network of interplaying genetic signatures converging on established immune system and inflammatory processes linked to viral infection response, such as JAK-STAT, Cytokine, Interleukin, and C-type lectin receptor signaling. It also identified additional processes cross-talking with immune pathways, such as GPCR signalling, which might offer additional opportunities for therapeutic intervention and patient stratification. Publicly available PheWAS datasets revealed that several variants were significantly associated with phenotypic traits such as “Respiratory or thoracic disease”, confirming their link with COVID-19 severity outcome. Taken together, our analysis suggests that curated genetic information can be effectively integrated along with other patient clinical covariates to forecast COVID-19 disease severity and dissect the underlying host genetic mechanisms for personalized medicine treatments.

Published
2022

36. Novel retinal finding in a patient with 4q12 deletion

Author

Alessandra Renieri, Theodora Hadjistilianou, Mario Fruschelli, Nicola Lorusso, Mirella Bruttini, Alessandro Di Maggio, Marco Mandalà, and Maria Antonietta Mencarelli

Subjects
hypoacusia, Adult, medicine.medical_specialty, Visual acuity, Posterior pole, Visual Acuity, Retinal Pigment Epithelium, Multimodal Imaging, Retina, chemistry.chemical_compound, Young Adult, Depigmentation, Ophthalmology, medicine, Blue sclerae, Humans, 4q12 deletion, RPE detachment, piebaldism, Fluorescein Angiography, Genetics (clinical), Retinal pigment epithelium, business.industry, Piebaldism, Retinal, medicine.disease, eye diseases, medicine.anatomical_structure, chemistry, Pediatrics, Perinatology and Child Health, Female, sense organs, medicine.symptom, Chromosome Deletion, business, Poliosis, Tomography, Optical Coherence
Abstract

Background Chromosome 4q deletions are rare disorders phenotypically characterized by several features. The most commonly described ocular abnormalities include unilateral microphthalmia with bilateral colobomata, blue sclerae with pigmented retinal clumps, hypermetropia, and a divergent squint. Purpose To report a case of 4q12 deletion with a singular retinal feature. Materials and methods Case report. Results A 20-year-old Caucasian female with a history of poliosis, progressive appearance of small areas of skin depigmentation along trunk and limbs since birth and diagnosis of learning deficit was referred for a complete ocular examination. The genetic counseling showed microdeletion in the 4q12 region. An audiometric test was performed, showing a progressive bilateral neurosensorial hypoacusia. Ocular examination showed the presence of multifocal, tiny, whitish deposits in the posterior pole. Multimodal imaging defined the lesions as small elevations of the retinal pigment epithelium with slight hyper-autofluorescence and staining in the late phase of fluoresceine angiography (FA). Visual acuity was 20/20. The retinal findings did not change during the three-month follow-up. Conclusions Although the findings herein reported have never been described before in patients affected by 4q12 mutations, we do not exclude that they could represent a manifestation of the peculiar genetic asset of the patient, related to dysfunction in pigment epithelium/neuroretinal metabolic activity.

Published
2021

37. Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

Author

Fallerini, Chiara, Picchiotti, Nicola, Baldassarri, Margherita, Zguro, Kristina, Daga, Sergio, Fava, Francesca, Benetti, Elisa, Amitrano, Sara, Bruttini, Mirella, Palmieri, Maria, Croci, Susanna, Lista, Mirjam, Beligni, Giada, Valentino, Floriana, Meloni, Ilaria, Tanfoni, Marco, Minnai, Francesca, Colombo, Francesca, Cabri, Enrico, Fratelli, Maddalena, Gabbi, Chiara, Mantovani, Stefania, Frullanti, Elisa, Gori, Marco, Crawley, Francis P, Butler-Laporte, Guillaume, Richards, Brent, Zeberg, Hugo, Lipcsey, Miklos, Hultström, Michael, Ludwig, Kerstin U, Schulte, Eva C, Pairo-Castineira, Erola, Baillie, John Kenneth, Schmidt, Axel, Frithiof, Robert, Mari, Francesca, Renieri, Alessandra, Furini, Simone Simone Furini, Francesca, Montagnani, Mario, Tumbarello, Ilaria, Rancan, Massimiliano, Fabbiani, Barbara, Rossetti, Laura, Bergantini, Miriana, D'Alessandro, Paolo, Cameli, David, Bennett, Federico, Anedda, Simona, Marcantonio, Sabino, Scolletta, Federico, Franchi, Maria Antonietta Mazzei, Susanna, Guerrini, Edoardo, Conticini, Luca, Cantarini, Bruno, Frediani, Danilo, Tacconi, Chiara Spertilli Raffaelli, Marco, Feri, Alice, Donati, Raffaele, Scala, Luca, Guidelli, Genni, Spargi, Marta, Corridi, Cesira, Nencioni, Leonardo, Croci, Gian Piero Caldarelli, Maurizio, Spagnesi, Davide, Romani, Paolo, Piacentini, Maria, Bandini, Elena, Desanctis, Silvia, Cappelli, Anna, Canaccini, Agnese, Verzuri, Valentina, Anemoli, Manola, Pisani, Agostino, Ognibene, Alessandro, Pancrazzi, Maria, Lorubbio, Massimo, Vaghi, Antonella, D 'Arminio Monforte, Federica Gaia Miraglia, Mario, U Mondelli, Massimo, Girardis, Sophie, Venturelli, Stefano, Busani, Andrea, Cossarizza, Andrea, Antinori, Alessandra, Vergori, Arianna, Emiliozzi, Stefano, Rusconi, Matteo, Siano, Arianna, Gabrieli, Agostino, Riva, Daniela, Francisci, Elisabetta, Schiaroli, Francesco, Paciosi, Andrea, Tommasi, Pier Giorgio Scotton, Francesca, Andretta, Sandro, Panese, Stefano, Baratti, Renzo, Scaggiante, Francesca, Gatti, Saverio Giuseppe Parisi, Francesco, Castelli, Eugenia, Quiros-Roldan, Melania Degli Antoni, Isabella, Zanella, Matteo Della Monica, Carmelo, Piscopo, Mario, Capasso, Roberta, Russo, Immacolata, Andolfo, Achille, Iolascon, Giuseppe, Fiorentino, Massimo, Carella, Marco, Castori, Filippo, Aucella, Pamela, Raggi, Rita, Perna, Matteo, Bassetti, Antonio Di Biagio, Maurizio, Sanguinetti, Luca, Masucci, Alessandra, Guarnaccia, Serafina, Valente, Oreste De Vivo, Gabriella, Doddato, Rossella, Tita, Annarita, Giliberti, Maria Antonietta Mencarelli, Caterina Lo Rizzo, Anna Maria Pinto, Valentina, Perticaroli, Francesca, Ariani, Miriam Lucia Carriero, Laura Di Sarno, Diana, Alaverdian, Elena, Bargagli, Marco, Mandalà, Alessia, Giorli, Lorenzo, Salerni, Patrizia, Zucchi, Pierpaolo, Parravicini, Elisabetta, Menatti, Tullio, Trotta, Ferdinando, Giannattasio, Gabriella, Coiro, Fabio, Lena, Leonardo Gianluca Lacerenza, Domenico, A Coviello, Cristina, Mussini, Enrico, Martinelli, Sandro, Mancarella, Luisa, Tavecchia, Mary Ann Belli, Lia, Crotti, Gianfranco, Parati, Maurizio, Sanarico, Francesco, Raimondi, Filippo, Biscarini, Alessandra, Stella, Marco, Rizzi, Franco, Maggiolo, Diego, Ripamonti, Claudia, Suardi, Tiziana, Bachetti, Maria Teresa La Rovere, Simona, Sarzi-Braga, Maurizio, Bussotti, Katia, Capitani, Simona, Dei, Sabrina, Ravaglia, Rosangela, Artuso, Elena, Andreucci, Giulia, Gori, Angelica, Pagliazzi, Erika, Fiorentini, Antonio, Perrella, Francesco, Bianchi, Paola, Bergomi, Emanuele, Catena, Riccardo, Colombo, Sauro, Luchi, Giovanna, Morelli, Paola, Petrocelli, Sarah, Iacopini, Sara, Modica, Silvia, Baroni, Francesco Vladimiro Segala, Francesco, Menichetti, Marco, Falcone, Giusy, Tiseo, Chiara, Barbieri, Tommaso, Matucci, Grassi, Davide, Ferri, Claudio, Marinangeli, Franco, Brancati, Francesco, Antonella, Vincenti, Valentina, Borgo, Lombardi, Stefania, Mirco, Lenzi, Massimo Antonio Di Pietro, Francesca, Vichi, Benedetta, Romanin, Letizia, Attala, Cecilia, Costa, Andrea, Gabbuti, Menè, Roberto, Umberto, Zuccon, Lucia, Vietri, Stefano, Ceri, Pietro, Pinoli, Patrizia, Casprini, Giuseppe, Merla, Gabriella Maria Squeo, Marcello, Maffezzoni, Raffaele, Bruno, Marco, Vecchia, Marta, Colaneri, Serena, Ludovisi, Yanara, Marincevic-Zuniga, Jessica, Nordlund, Tomas, Luther, Anders, Larsson, Katja Hanslin Anna Gradin, Sarah, Galien, Sara Bulow Anderberg, Jacob, Rosén, Sten, Rubertsson, Hugo, Zeberg, Robert, Frithiof, Miklós, Lipcsey, Michael, Hultström, Sara Clohisey Peter Horby, Johnny, Millar, Julian, Knight, Hugh, Montgomery, David, Maslove, Lowell, Ling, Alistair, Nichol, Charlotte, Summers, Tim, Walsh, Charles, Hinds, Malcolm, G Semple, Peter J, M Openshaw, Manu, Shankar-Hari, Antonia, Ho, Danny, Mcauley, Chris, Ponting, Kathy, Rowan, J Kenneth Baillie, Fiona, Griffiths, Wilna, Oosthuyzen, Jen, Meikle, Paul, Finernan, James, Furniss, Ellie, Mcmaster, Andy, Law, Sara, Clohisey, Trevor, Paterson, Tony, Wackett, Ruth, Armstrong, Lee, Murphy, Angie, Fawkes, Richard, Clark, Audrey, Coutts, Lorna, Donnelly, Tammy, Gilchrist, Katarzyna, Hafezi, Louise, Macgillivray, Alan, Maclean, Sarah, Mccafferty, Kirstie, Morrice, Jane, Weaver, Ceilia, Boz, Ailsa, Golightly, Mari, Ward, Hanning, Mal, Helen, Szoor-McElhinney, Adam, Brown, Ross, Hendry, Andrew, Stenhouse, Louise, Cullum, Dawn, Law, Sarah, Law, Rachel, Law, Max Head Fourman, Maaike, Swets, Nicky, Day, Filip, Taneski, Esther, Duncan, Marie, Zechner, Nicholas, Parkinson, Erola, Pairo-Castineira, Lucija, Klaric, Andrew, D Bretherick, Konrad, Rawlik, Dorota, Pasko, Susan, Walker, Nick, Parkinson, Clark, D Russell, Anne, Richmond, Elvina, Gountouna, David, Harrison, Wang, Bo, Yang, Wu, Alison, Meynert, Athanasios, Kousathanas, Loukas, Moutsianas, Zhijian, Yang, Ranran, Zhai, Chenqing, Zheng, Graeme, Grimes, Jonathan, Millar, Barbara, Shih, Jian, Yang, Xia, Shen, Chris, P Ponting, Albert, Tenesa, Andrew, Law, Veronique, Vitart, James, F Wilson, Collier, D, Wood, S, Zak, A, Borra, C, Matharu, M, May, P, Alldis, Z, Mitchelmore, O, Bowles, R, Easthorpe, A, Bibi, F, Lancoma-Malcolm, I, Gurasashvili, J, Pheby, J, Shiel, J, Bolton, M, Patel, M, Taylor, M, Zongo, O, Ebano, P, Harding, P, Astin-Chamberlain, R, Choudhury, Y, Cox, A, Kallon, D, Burton, M, Hall, R, Blowes, S, Prime, Z, Biddle, J, Prysyazhna, O, Newman, T, Tierney, C, Kassam, J, Shankar-Hari, M, Ostermann, M, Campos, S, Bociek, A, Lim, R, Grau, N, O Jones, T, Whitton, C, Marotti, M, Arbane, G, Bonner, S, Hugill, K, Reid, J, Welters, I, Waugh, V, Williams, K, Shaw, D, J Fernandez Roman, M Lopez Martinez, Johnson, E, Waite, A, Johnson, B, Hamilton, O, Mulla, S, Mcphail, M, Smith, J, K Baillie, J, Barclay, L, Hope, D, Mcculloch, C, Mcquillan, L, Clark, S, Singleton, J, Priestley, K, Rea, N, Callaghan, M, Campbell, R, Andrew, G, Marshall, L, Mckechnie, S, Hutton, P, Bashyal, A, Davidson, N, Summers, C, Polgarova, P, Stroud, K, Pathan, N, Elston, K, Agrawal, S, Battle, C, Newey, L, Rees, T, Harford, R, Brinkworth, E, Williams, M, Murphy, C, White, I, Croft, M, Bandla, N, Gellamucho, M, Tomlinson, J, Turner, H, Davies, M, Quinn, A, Hussain, I, Thompson, C, Parker, H, Bradley, R, Griffiths, R, Scriven, J, Gill, J, Puxty, A, Cathcart, S, Salutous, D, Turner, L, Duffy, K, Puxty, K, Joseph, A, Herdman-Grant, R, Simms, R, Swain, A, Naranjo, A, Crowe, R, Sollesta, K, Loveridge, A, Baptista, D, Morino, E, Davey, M, Golden, D, Jones, J, J Moreno Cuesta, Haldeos, A, Bakthavatsalam, D, Vincent, R, Elhassan, M, Xavier, K, Ganesan, A, Purohit, D, Abdelrazik, M, Morgan, J, Akeroyd, L, Bano, S, Warren, D, Bromley, M, Sellick, K, Gurr, L, Wilkinson, B, Nagarajan, V, Szedlak, P, Cupitt, J, Stoddard, E, Benham, L, Preston, S, Slawson, N, Bradshaw, Z, Brown, J, Caswell, M, Smelling, Bamford, P, Faulkner, M, Cawley, K, Jeffrey, H, London, E, Sainsbury, H, Nagra, I, Nasir, F, Dunmore, Ce, Jones, R, Abraheem, A, Al-Moasseb, M, Girach, R, Brantwood, C, Alexander, P, Bradley-Potts, J, Allen, S, Felton, T, Manna, S, Farnell-Ward, S, Leaver, S, Queiroz, J, Maccacari, E, Dawson, D, C Castro Delgado, R Pepermans Saluzzio, Ezeobu, O, Ding, L, Sicat, C, Kanu, R, Durrant, G, Texeira, J, Harrison, A, Samakomva, T, Willis, H, Hopkins, B, Thrasyvoulou, L, Jackson, M, Zaki, A, Tibke, C, Bennett, S, Woodyatt, W, Kent, A, Goodwin, E, Brandwood, C, Clark, R, Smith, L, Rooney, K, Thomson, N, Rodden, N, Hughes, E, Mcglynn, D, Clark, C, Clark, P, Abel, L, Sundaram, R, Gemmell, L, Brett, M, Hornsby, J, Macgoey, P, Price, R, Digby, B, O'Neil, P, Mcconnell, P, Henderson, P, Henderson, S, Sim, M, Kennedy-Hay, S, Mcparland, C, Rooney, L, Baxter, N, Pogson, D, Rose, S, Daly, Z, Brimfield, L, K Phull, M, Hussain, M, Pogreban, T, Rosaroso, L, E Salciute, L Grauslyte, Brealey, D, Wraith, E, Maccallum, N, Bercades, G, Hass, I, Smyth, D, Reyes, A, Martir, G, D Clement, I, Webster, K, Hays, C, Gulati, A, Hodgson, L, Margarson, M, Gomez, R, Baird, Y, Thirlwall, Y, Folkes, L, Butler, A, Meadows, E, Moore, S, Raynard, D, Fox, H, Riddles, L, King, K, Kimber, S, Hobden, G, Mccarthy, A, Cannons, V, Balagosa, I, Chadbourn, I, Gardner, A, Horner, D, Mclaughlanv, D, Charles, B, Proudfoot, N, Marsden, T, L Mc Morrow, Blackledge, B, Pendlebury, J, Harvey, A, Apetri, E, Basikolo, C, Catlow, L, Doonan, R, Knowles, K, Lee, S, Lomas, D, Lyons, C, Perez, J, Poulaka, M, Slaughter, M, Slevin, K, Thomas, V, Walker, D, Harris, J, Drummond, A, Tully, R, Dearden, J, Philbin, J, Munt, S, Rishton, C, O'Connor, G, Mulcahy, M, Dobson, E, Cuttler, J, Edward, M, Rose, A, Sloan, B, Buckley, S, Brooke, H, Smithson, E, Charlesworth, R, Sandu, R, Thirumaran, M, Wagstaff, V, J Cebrian Suarez, Kaliappan, A, Vertue, M, Nicholson, A, Riches, J, Solesbury, A, Kittridge, L, Forsey, M, Maloney, G, Cole, J, Davies, R, Hill, H, Thomas, E, Williams, A, Duffin, D, Player, B, Radhakrishnan, J, Gibson, S, Lyle, A, Mcneela, F, Patel, B, Gummadi, M, Sloane, G, Dormand, N, Salmi, S, Farzad, Z, Cristiano, D, Liyanage, K, Thwaites, V, Varghese, M, Meredith, M, Mills, G, Willson, J, Harrington, K, Lenagh, B, Cawthron, K, Masuko, S, Raithatha, A, Bauchmuller, K, Ahmad, N, Barker, J, Jackson, Y, Kibutu, F, Bird, S, Watson, G, Martin, J, Bevan, E, C Wrey Brown, Trodd, D, English, K, Bell, G, Wilcox, L, Katary, A, Gopal, S, Lake, V, Harris, N, Metherell, S, Radford, E, Moore, F, Bancroft, H, Daglish, J, Sangombe, M, Carmody, M, Rhodes, J, Bellamy, M, Garg, A, Kuravi, A, Virgilio, E, Ranga, P, Butler, J, Botfield, L, Dexter, C, Fletcher, J, Shanmugasundaram, P, Hambrook, G, Burn, I, Manso, K, Thornton, D, Tebbutt, J, Penn, R, Hulme, J, Hussain, S, Maqsood, Z, Joseph, S, Colley, J, Hayes, A, Ahmed, C, Haque, R, Clamp, S, Kumar, R, Purewal, M, Baines, B, Frise, M, Jacques, N, Coles, H, Caterson, J, S Gurung Rai, Brunton, M, Tilney, E, Keating, L, Walden, A, Antcliffe, D, Gordon, A, Templeton, M, Rojo, R, Banach, D, S Sousa Arias, Fernandez, Z, Coghlan, P, Williams, D, Jardine, C, Bewley, J, Sweet, K, Grimmer, L, Johnson, R, Garland, Z, Gumbrill, B, Phillips, C, L Ortiz-Ruiz de Gordoa, Peasgood, E, Tridente, A, K Shuker, S Greer, Lynch, C, Pothecary, C, Roche, L, Deacon, B, Turner, K, Singh, J, G Sera Howe, Paul, P, Gill, M, Wynter, I, Ratnam, V, Shelton, S, Naisbitt, J, Melville, J, Baruah, R, Morrison, S, Mcgregor, A, Parris, V, Mpelembue, M, Srikaran, S, Dennis, C, Sukha, A, Verlande, M, Holding, K, Riches, K, Downes, C, Swan, C, Rostron, A, Roy, A, Woods, L, Cornell, S, Wakinshaw, F, Creagh-Brown, B, Blackman, H, Salberg, A, Smith, E, Donlon, S, Mtuwa, S, Michalak-Glinska, N, Stone, S, Beazley, C, Pristopan, V, Nikitas, N, Lankester, L, Wells, C, S Raj, A, Fletcher, K, Khade, R, Tsinaslanidis, G, Mcmahon, M, Fowler, S, Coventry, T, Stewart, R, Wren, L, Mwaura, E, Mew, L, Scaletta, D, Williams, F, Inweregbu, K, Lancaster, N, Cunningham, M, Daniels, A, Harrison, L, Hope, S, Jones, S, Crew, A, Wray, G, Matthews, J, Crawley, R, Carter, J, Birkinshaw, I, Ingham, J, Scott, Z, Howard, K, Joy, R, Roche, S, Clark, M, Purvis, S, Morrison, A, Strachan, D, Clements, S, Black, K, Parmar, C, Altabaibeh, A, Simpson, K, Mostoles, L, Gilbert, K, L, Ma, Alvaro, A, Thomas, M, Faulkner, B, Worner, R, Hayes, K, Gendall, E, Blakemore, H, Borislavova, B, Goff, E, Vuylsteke, A, Mwaura, L, Zamikula, J, Garner, L, Mitchell, A, Mepham, S, Cagova, L, Fofano, A, Holcombe, H, Praman, K, Szakmany, T, E Heron, A, Cherian, S, Cutler, S, Roynon-Reed, A, Randell, G, Convery, K, K Stammers, D Fottrell-Gould, Hudig, L, Keshet-Price, J, Peters, M, O'Neill, L, Ray, S, Belfield, H, Mchugh, T, Jones, G, Akinkugbe, O, Tomas, A, Abaleke, E, Beech, E, Meghari, H, Yussuf, S, Bamford, A, Hairsine, B, Dooks, E, Farquhar, F, Packham, S, Bates, H, Armstrong, L, Kaye, C, Allan, A, Medhora, J, Liew, J, Botello, A, Anderson, F, Cusack, R, Golding, H, Prager, K, Williams, T, Leggett, S, Golder, K, Male, M, Jones, O, Criste, K, Marani, M, Anumakonda, V, Amin, V, Karthik, K, Kausar, R, Anastasescu, E, Reid, K, Jacqui, M, Hormis, A, Walker, R, Duncan, T, Uriel, A, Ustianowski, A, T-Michael, H, Bruce, M, Connolly, K, Smith, K, Partridge, R, Griffin, D, Mcdonald, M, Muchenje, N, Martin, D, Filipe, H, Eastgate, C, Jackson, C, Gratrix, A, Foster, L, Martinson, V, Stones, E, Caroline, Abernathy, Parkinson, P, Reed, A, Prendergast, C, Rogers, P, Woodruff, M, Shokkar, R, Kaul, S, Barron, A, Collins, C, Beavis, S, Whileman, A, Dale, K, Hawes, J, Pritchard, K, Gascoyne, R, Stevenson, L, Jha, R, Lim, L, Krishnamurthy, V, Parker, R, Turner-Bone, I, Wilding, L, Reddy, A, Whiteley, S, Wilby, E, Howcroft, C, Aspinwall, A, Charlton, S, Ogg, B, Menzies, D, Pugh, R, Allan, E, Lean, R, Davies, F, Easton, J, Qiu, X, Kumar, S, Darlington, K, Houston, G, O'Brien, P, Geary, T, Allan, J, Meikle, A, Hughes, G, Balasubramaniam, M, Latham, S, Mckenna, E, Flanagan, R, Sathe, S, Davies, E, Chablani, M, Kirkby, A, Netherton, K, Archer, S, Yates, B, Ashbrook-Raby, C, Cole, S, Casey, M, Cabrelli, L, Chapman, S, Austin, P, Hutcheon, A, Whyte, C, Almaden-Boyle, C, Pattison, N, Cruz, C, Vochin, A, Kent, H, Thomas, A, Murdoch, S, David, B, Penacerrada, M, Lubimbi, G, Bastion, V, Wulandari, R, Valentine, J, Clarke, D, Serrano-Ruiz, A, Hierons, S, Ramos, L, Demetriou, C, Mitchard, S, White, K, White, N, Pitts, S, Branney, D, Frankham, J, Watters, M, Langton, H, Prout, R, Page, V, Varghes, T, Cowton, A, Kay, A, Potts, K, Birt, M, Kent, M, Wilkinson, A, Jude, E, Turner, V, Savill, H, Mccormick, J, Coulding, M, Siddiqui, S, Mercer, O, Rehman, H, Potla, D, Capps, N, Donaldson, D, Button, H, Martin, T, Hard, K, Agasou, A, Tonks, L, Arden, T, Boyle, P, Carnahan, M, Strickley, J, Adams, C, Childs, D, Rikunenko, R, Leigh, M, Breekes, M, Wilcox, R, Bowes, A, Tiveran, H, Hurford, F, Summers, J, Carter, A, Hussain, Y, Ting, L, Javaid, A, Motherwell, N, Moore, H, Millward, H, Jose, S, Schunki, N, Noakes, A, Clulow, C, Sadera, G, Jacob, R, Jones, C, Blunt, M, Coton, Z, Curgenven, H, S Mohamed Ally, Beaumont, K, Elsaadany, M, Fernandes, K, I Ali Mohamed Ali, Rangarajan, H, Sarathy, V, Selvanayagam, S, Vedage, D, White, M, Smith, M, Truman, N, Chukkambotla, S, Keith, S, Cockerill-Taylor, J, Ryan-Smith, J, Bolton, R, Springle, P, Dykes, J, Thomas, J, Khan, M, T Hijazi, M, Massey, E, Croston, G, Reschreiter, H, Camsooksai, J, Patch, S, Jenkins, S, Humphrey, C, Wadams, B, Bhatia, N, Msiska, M, Adanini, O, Attwood, B, Parsons, P, Tatham, K, Jhanji, S, Black, E, A Dela Rosa, Howle, R, Thomas, B, Bemand, T, Raobaikady, R, Saha, R, Staines, N, Daniel, A, Finn, J, Hutter, J, Doble, P, Shovelton, C, Pawley, C, Kannan, T, Hill, M, Combes, E, Monnery, S, Joefield, T, Popescu, M, Thankachen, M, Oblak, M, Little, J, Mcivor, S, Brady, A, Whittle, H, Prady, H, Chan, R, Ahmed, A, Morris, A, Gibson, C, Gordon, E, Keenan, S, Quinn, H, Benyon, S, Marriott, S, Zitter, L, Park, L, Baines, K, Lyons, M, Holland, M, Keenan, N, Young, M, Garrioch, S, Dawson, J, Tolson, M, Scholefield, B, R, Bi, Richardson, N, Schumacher, N, Cosier, T, Millen, G, Higham, A, Turki, S, Allen, L, Crisp, N, Hazleton, T, Knight, A, Deery, J, Price, C, Turney, S, Tilbey, S, Beranova, E, Wright, D, Georg, L, Twiss, S, Wadd, S, Postlethwaite, K, Gondo, P, Masunda, B, Kayani, A, Hadebe, B, Whiteside, J, Clarke, N, Donnison, P, Trim, F, Leadbitter, I, Butcher, D, O'Sullivan, S, Purewal, B, Bell, S, Rivers', V, O'Leary, R, Birch, J, Collins, E, Anderson, S, Hammerton, K, Andrews, E, Burns, K, Edmond, I, Todd, A, Donnachie, J, Turner, P, Prentice, L, Symon, L, Runciman, N, Auld, F, Halkes, M, Mercer, P, Thornton, L, Debreceni, G, Wilkins, J, Brown, A, Crickmore, V, Subramanian, G, Marshall, R, Jennings, C, Latif, M, Bunni, L, Spivey, M, Bean, S, Burt, K, Linnett, V, Ritzema, J, Sanderson, A, Mccormick, W, Bokhari, M, Kapoor, R, Loader, D, Ayers, A, Harrison, W, North, J, Belagodu, Z, Parasomthy, R, Olufuwa, O, Gherman, A, Fuller, B, Stuart, C, Kelsall, O, Davis, C, Wild, L, Wood, H, Thrush, J, Durie, A, Austin', K, Archer, K, Anderson, P, Vigurs, C, Thorpe, C, Knights, E, Boyle, N, Price, A, Kubisz-Pudelko, A, Wood, D, Lewis, A, Board, S, Pippard, L, Perry, J, Beesley, K, Rattray, A, Lee, E, Lennon, L, Douglas, K, Bell, D, Boyle, R, Glass, L, M Nauman Akhtar, Dent, K, Potoczna, D, Pearson, S, Horsley, E, Spencer, S, Mullan, D, Skinner, D, Gaylard, J, Ortiz-Ruizdegordoa, L, Barber, R, Hewitt, C, Hilldrith, A, Shepardson, S, Wills, M, Jackson-Lawrence, K, Gupta, A, Easthope, A, Timlick, E, Gorman, C, Otaha, I, Gales, A, Coetzee, S, Raj, M, Peiu, M, Quaid, S, Watson, E, Elliott, K, Mallinson, J, Chandler, B, Turnbull, A, Finch, C, Holl, C, Cooper, J, Evans, A, Khaliq, W, Collins, A, E Treus Gude, Love, N, L van Koutrik, Hunt, J, Kaye, D, Fisher, E, Brayne, A, Tuckey, V, Jackson, P, Parkin, J, Raith, E, Tariq, A, Houlden, H, Tucci, A, Hardy, J, Moncur, E, Highgate, J, Cowley, A, Mitra, A, Stead, R, Behan, T, Burnett, C, Newton, M, Heeney, E, Pollard, R, Hatton, J, Patel, A, Kasipandian, V, Allibone, S, M Genetu, R, Otahal, I, O'Brien, L, Omar, Z, Perkins, E, Davies, K, Tetla, D, Shelley, B, Irvine, V, Williams, S, Williams, P, Goodsell, J, Tutton, R, Bough, L, Winter-Goodwin, B, Kitson, R, Pinnell, J, Wilson, A, Nortcliffe, T, Wood, T, Home, M, Holdroyd, K, Robinson, M, Shaw, R, Greig, J, Brady, M, Haigh, A, Matupe, L, Usher, M, Mellor, S, Dale, S, Gledhill, L, Shaw, L, Turner, G, Kelly, D, Anwar, B, Riley, H, Sturgeon, H, Ali, A, Thomis, L, Melia, D, Dance, A, Hanson, K, Humphreys, S, Frost, I, Gopal, V, Godden, J, Holden, A, Swann, S, Smith, T, Clapham, M, Poultney, U, Harper, R, Rice, P, Reece-Anthony, R, Gurung, B, Moultrie, S, Odam, M, Mayer, A, Bellini, A, Pickard, A, Bryant, J, Roe, N, Sowter, J, Lang, K, Taylor, J, Barry, P, Hobrok, M, Tench, H, Wolf-Roberts, R, Mcguinness, H, Loosley, R, Hawcutt, D, Rad, L, O'Malley, L, Saunderson, P, Seddon, G, Anderson, T, Rogers, N, Ruddy, J, Harkins, M, Beith, C, Mcalpine, A, Ferguson, L, Grant, P, Macfadyen, S, Mclaughlin, M, Baird, T, Rundell, S, Welsh, B, Hamill, R, Fisher, F, Gregory, J, Axel, Schmidt, Kerstin, U Ludwig, Selina, Rolker, Markus, M Nöthen, Julia, Fazaal, Verena, Keitel, Björn, Jensen, Torsten, Feldt, Lisa, Knopp, Julia, Schröder, Carlo, Maj, Fabian, Brand, Marc, M Berger, Thorsten, Brenner, Anke, Hinney, Oliver, Witzke, Robert, Bals, Christian, Herr, Nicole, Ludwig, Jörn, Walter, Jochen, Schneider, Johanna, Erber, Christoph, D Spinner, Clemens, M Wendtner, Christof, Winter, Ulrike, Protzer, Nicolas, Casadei, Stephan, Ossowski, Olaf, H Riess, Eva, C Schulte, J Brent Richards, Guillaume, Butler-Laporte, Mirosław, Kwasniewski, Urszula, Korotko, Karolina, Chwialkowska, Magdalena, Niemira, Jerzy, Jaroszewicz, Barbara, Sobala-Szczygiel, Beata, Puzanowska, Anna, Parfieniuk-Kowerda, Diana, Martonik, Anna, Moniuszko-Malinowska, Sławomir, Pancewicz, Dorota, Zarębska-Michaluk, Krzysztof, Simon, Monika, Pazgan-Simon, Iwona, Mozer-Lisewska, Maciej, Bura, Agnieszka, Adamek, Krzysztof Tomasiewicz Małgorzata Pawłowska, Anna, Piekarska, Aleksandra, Berkan-Kawinska, Andrzej, Horban, Justyna, Kowalska, Regina, Podlasin, Piotr, Wasilewski, Arsalin, Azzadin, Miroslaw, Czuczwar, Slawomir, Czaban, Paweł, Olszewski, Jacek, Bogocz, Magdalena, Ochab, Anna, Kruk, Sandra, Uszok, Agnieszka, Bielska, Anna, Szałkowska, Justyna, Raczkowska, Gabriela, Sokołowska, Joanna, Chorostowska-Wynimko, Aleksandra, Jezela-Stanek, Adriana, Roży, Urszula, Lechowicz, Urszula, Polowianiuk, Kamil, Grubczak, Aleksandra, Starosz, Andrzej, Eljaszewicz, Wiktoria, Izdebska, Adam, Krętowski, Robert, Flisiak, Marcin Moniuszko Malak Abedalthagafi Manal Alaamery, Salam, Massadeh, Mohamed, Fawzy, Hadeel, Albardis, Nora, Aljawini, Moneera, Alsuwailm, Faisal, Almalki, Serghei, Mangul, Junghyun, Jung, Hamdi, Mbarek, Chadi, Saad, Yaser, Al-Sarraj, Wadha, Al-Muftah, Radja, Badji, Asma Al Thani, Said, I Ismail, HGI, WES/WGS Working Group Within the, Consortium, GenOMICC, Study, GEN-COVID Multicenter, Renieri, Alessandra [0000-0002-0846-9220], Apollo - University of Cambridge Repository, NIHR, Fallerini, C, Picchiotti, N, Baldassarri, M, Zguro, K, Daga, S, Fava, F, Benetti, E, Amitrano, S, Bruttini, M, Palmieri, M, Croci, S, Lista, M, Beligni, G, Valentino, F, Meloni, I, Tanfoni, M, Minnai, F, Colombo, F, Cabri, E, Fratelli, M, Gabbi, C, Mantovani, S, Frullanti, E, Gori, M, Crawley, F, Butler-Laporte, G, Richards, B, Zeberg, H, Lipcsey, M, Hultström, M, Ludwig, K, Schulte, E, Pairo-Castineira, E, Baillie, J, Schmidt, A, Frithiof, R, Mari, F, Renieri, A, Furini, S, and Crotti, L

Subjects
Male, Medicin och hälsovetenskap, Linkage disequilibrium, Medizin, severity, Genome-wide association study, Disease, WES/WGS Working Group Within the HGI, Logistic regression, Severity of Illness Index, Medical and Health Sciences, Whole Exome Sequencing, Cohort Studies, 0302 clinical medicine, Lasso (statistics), GEN-COVID Multicenter Study, Germany, 80 and over, Genetics (clinical), Exome sequencing, Original Investigation, Genetics & Heredity, Aged, 80 and over, 0303 health sciences, Adult, Aged, COVID-19, Female, Humans, Italy, Middle Aged, Polymorphism, Single Nucleotide, Quebec, SARS-CoV-2, Sweden, United Kingdom, Genetic Predisposition to Disease, Phenotype, Single Nucleotide, covid-19, 1104 Complementary and Alternative Medicine, GenOMICC Consortium, Human, coding variants, Computational biology, Biology, 03 medical and health sciences, Exome Sequencing, Genetics, Polymorphism, Gene, 030304 developmental biology, 0604 Genetics, 1114 Paediatrics and Reproductive Medicine, Cohort Studie, 030217 neurology & neurosurgery, Coding (social sciences)
Abstract

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. Supplementary Information The online version contains supplementary material available at 10.1007/s00439-021-02397-7.

Published
2021

38. Alexander Crum Brown: A Forgotten Pioneer in Vestibular Sciences

Author

Enis Alpin Güneri, Soumit Dasgupta, and Marco Mandalà

Subjects
Vestibular system, Deaf mutes, Semicircular canal, business.industry, The Renaissance, Vestibular pathway, History, 19th Century, Anatomy, History, 20th Century, Otolaryngology, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Scotland, Vestibular Diseases, Otorhinolaryngology, 030220 oncology & carcinogenesis, Humans, Medicine, Surgery, 030223 otorhinolaryngology, business
Abstract

Although vestibular anatomy was described in the Renaissance period, research in vestibular physiology began in the 1820s and was spearheaded by Purkinje and Flourens. This was subsequently expanded by Meniere, Helmholtz, Goltz, Mach, Breuer, Ewald, and Hogyes, who are regarded as the early pioneers in research on vestibular physiology in the 19th century. The relationship of endolymphatic flow and semicircular canal function is termed the Mach-Breuer hypothesis. What is less well known is that a Scottish chemist, Alexander Crum Brown, arrived at similar conclusions as Mach and Breuer at the same time quite independently. In fact, he pioneered several concepts in vestibular physiology that included pairing of semicircular canals for function, the vestibular pathway, optic fixation elimination in vestibular experimentation, the theory of motion intolerance, and study in deaf mutes for insights into vestibular pathology and vestibular compensation. This article is a tribute to this forgotten pioneer in vestibular research.

Published
2020

39. Patient Perceptions of Effectiveness in Treatments for Menière's Disease: a National Survey in Italy

Author

Giulia Corallo, John F. Golding, Franco Trabalzini, Marco Mandalà, Bryan K. Ward, Daniele Nuti, Vincent G. Wettstein, University of Zurich, and Mandala, Marco

Subjects
Male, Injection, Dizziness, Sensorineural hearing loss, Social impact, Absenteeism, Anti-Bacterial Agents, Betahistine, Cross-Sectional Studies, Diet Therapy, Diuretics, Female, Gentamicins, Histamine Agonists, Humans, Injection, Intratympanic, Italy, Meniere Disease, Middle Aged, Self Concept, Surveys and Questionnaires, Treatment Outcome, Vertigo, Cross-sectional study, 10045 Clinic for Otorhinolaryngology, Disease, 0302 clinical medicine, 030223 otorhinolaryngology, biology, General Medicine, lcsh:Otorhinolaryngology, lcsh:RF1-547, Family life, 2733 Otorhinolaryngology, Original Article, medicine.drug, medicine.medical_specialty, 610 Medicine & health, Placebo, 03 medical and health sciences, Internal medicine, medicine, Intratympanic, business.industry, biology.organism_classification, medicine.disease, Otorhinolaryngology, business, 030217 neurology & neurosurgery, Meniere's disease
Abstract

OBJECTIVES: The aim of the present study was to investigate current treatment practices and self-reported effectiveness in Meniere’s disease. MATERIALS and METHODS: Members of two Italian Meniere’s disease support (n=170) with ≥6-month history of Meniere’s disease were administered an online survey about recent treatments. Vertigo episode count, work absenteeism, and limitations in family life, social life, work, or travel as included in the Social Life and Work Impact of Dizziness Questionnaire before and after recent treatments were queried. RESULTS: Twenty-four different treatments were reported for Meniere’s disease, with dietary modifications (55%), diuretics (47%), and betahistine (41%) being the most common. The majority (71%) received multiple simultaneous treatments. Prior to the most recent treatments, 78%-89% of respondents indicated limitations in family or social life, work, or traveling. After their most recent treatment, respondents reported improvements in mean vertigo episode counts (5.7±7.6 vs. 2.6±4.6, p

Published
2019

40. SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Author

Matteo D’Antonio, Jennifer P. Nguyen, Timothy D. Arthur, Hiroko Matsui, Agnieszka D’Antonio-Chronowska, Kelly A. Frazer, Benjamin M. Neale, Mark Daly, Andrea Ganna, Christine Stevens, Gita A. Pathak, Shea J. Andrews, Masahiro Kanai, Mattia Cordioli, Juha Karjalainen, Renato Polimanti, Matti Pirinen, Nadia Harerimana, Kumar Veerapen, Brooke Wolford, Huy Nguyen, Matthew Solomonson, Rachel G. Liao, Karolina Chwialkowska, Amy Trankiem, Mary K. Balaconis, Caroline Hayward, Anne Richmond, Archie Campbell, Marcela Morris, Chloe Fawns-Ritchie, Joseph T. Glessner, Douglas M. Shaw, Xiao Chang, Hannah Polikowski, Petty E. Lauren, Hung-Hsin Chen, Zhu Wanying, Hakon Hakonarson, David J. Porteous, Jennifer Below, Kari North, Joseph B. McCormick, Paul R.H.J. Timmers, James F. Wilson, Albert Tenesa, Kenton D’Mellow, Shona M. Kerr, Mari E.K. Niemi, Lindokuhle Nkambul, Kathrin Aprile von Hohenstaufen, Ali Sobh, Madonna M. Eltoukhy, Amr M. Yassen, Mohamed A.F. Hegazy, Kamal Okasha, Mohammed A. Eid, Hanteera S. Moahmed, Doaa Shahin, Yasser M. El-Sherbiny, Tamer A. Elhadidy, Mohamed S. Abd Elghafar, Jehan J. El-Jawhari, Attia A.S. Mohamed, Marwa H. Elnagdy, Amr Samir, Mahmoud Abdel-Aziz, Walid T. Khafaga, Walaa M. El-Lawaty, Mohamed S. Torky, Mohamed R. El-shanshory, Chiara Batini, Paul H. Lee, Nick Shrine, Alexander T. Williams, Martin D. Tobin, Anna L. Guyatt, Catherine John, Richard J. Packer, Altaf Ali, Robert C. Free, Xueyang Wang, Louise V. Wain, Edward J. Hollox, Laura D. Venn, Catherine E. Bee, Emma L. Adams, Ahmadreza Niavarani, Bahareh Sharififard, Rasoul Aliannejad, Ali Amirsavadkouhi, Zeinab Naderpour, Hengameh Ansari Tadi, Afshar Etemadi Aleagha, Saeideh Ahmadi, Seyed Behrooz Mohseni Moghaddam, Alireza Adamsara, Morteza Saeedi, Hamed Abdollahi, Abdolmajid Hosseini, Pajaree Chariyavilaskul, Monpat Chamnanphon, Thitima B. Suttichet, Vorasuk Shotelersuk, Monnat Pongpanich, Chureerat Phokaew, Wanna Chetruengchai, Watsamon Jantarabenjakul, Opass Putchareon, Pattama Torvorapanit, Thanyawee Puthanakit, Pintip Suchartlikitwong, Nattiya Hirankarn, Voraphoj Nilaratanakul, Pimpayao Sodsai, Ben M. Brumpton, Kristian Hveem, Cristen Willer, Wei Zhou, Tormod Rogne, Erik Solligard, Bjørn Olav Åsvold, Malak Abedalthagafi, Manal Alaamery, Saleh Alqahtani, Dona Baraka, Fawz Al Harthi, Ebtehal Alsolm, Leen Abu Safieh, Albandary M. Alowayn, Fatimah Alqubaishi, Amal Al Mutairi, Serghei Mangul, Abdulraheem Alshareef, Mona Sawaji, Mansour Almutairi, Nora Aljawini, Nour Albesher, Yaseen M. Arabi, Ebrahim S. Mahmoud, Amin K. Khattab, Roaa T. Halawani, Ziab Z. Alahmadey, Jehad K. Albakri, Walaa A. Felemban, Bandar A. Suliman, Rana Hasanato, Laila Al-Awdah, Jahad Alghamdi, Deema AlZahrani, Sameera AlJohani, Hani Al-Afghani, May Alrashed, Nouf AlDhawi, Hadeel AlBardis, Sarah Alkwai, Moneera Alswailm, Faisal Almalki, Maha Albeladi, Iman Almohammed, Eman Barhoush, Anoud Albader, Salam Massadeh, Abdulaziz AlMalik, Sara Alotaibi, Bader Alghamdi, Junghyun Jung, Mohammad S. Fawzy, Yunsung Lee, Per Magnus, Lill-Iren S. Trogstad, Øyvind Helgeland, Jennifer R. Harris, Massimo Mangino, Tim D. Spector, Duncan Emma, Sandra P. Smieszek, Bartlomiej P. Przychodzen, Christos Polymeropoulos, Vasilios Polymeropoulos, Mihael H. Polymeropoulos, Israel Fernandez-Cadenas, Jordi Perez-Tur, Laia Llucià-Carol, Natalia Cullell, Elena Muiño, Jara Cárcel-Márquez, Marta L. DeDiego, Lara Lloret Iglesias, Anna M. Planas, Alex Soriano, Veronica Rico, Daiana Agüero, Josep L. Bedini, Francisco Lozano, Carlos Domingo, Veronica Robles, Francisca Ruiz-Jaén, Leonardo Márquez, Juan Gomez, Eliecer Coto, Guillermo M. Albaiceta, Marta García-Clemente, David Dalmau, Maria J. Arranz, Beatriz Dietl, Alex Serra-Llovich, Pere Soler, Roger Colobrán, Andrea Martín-Nalda, Alba Parra Martínez, David Bernardo, Silvia Rojo, Aida Fiz-López, Elisa Arribas, Paloma de la Cal-Sabater, Tomás Segura, Esther González-Villa, Gemma Serrano-Heras, Joan Martí-Fàbregas, Elena Jiménez-Xarrié, Alicia de Felipe Mimbrera, Jaime Masjuan, Sebastian García-Madrona, Anna Domínguez-Mayoral, Joan Montaner Villalonga, Paloma Menéndez-Valladares, Daniel I. Chasman, Julie E. Buring, Paul M. Ridker, Giulianini Franco, Howard D. Sesso, JoAnn E. Manson, Joseph R. Glessner, Carolina Medina-Gomez, Andre G. Uitterlinden, M. Arfan Ikram, Kati Kristiansson, Sami Koskelainen, Markus Perola, Kati Donner, Katja Kivinen, Aarno Palotie, Samuli Ripatti, Sanni Ruotsalainen, Mari Kaunisto, null FinnGen, Tomoko Nakanishi, Guillaume Butler-Laporte, Vincenzo Forgetta, David R. Morrison, Biswarup Ghosh, Laetitia Laurent, Alexandre Belisle, Danielle Henry, Tala Abdullah, Olumide Adeleye, Noor Mamlouk, Nofar Kimchi, Zaman Afrasiabi, Nardin Rezk Branka Vulesevic, Meriem Bouab, Charlotte Guzman, Louis Petitjean, Chris Tselios, Xiaoqing Xue, Erwin Schurr, Jonathan Afilalo, Marc Afilalo, Maureen Oliveira, Bluma Brenner, Pierre Lepage, Jiannis Ragoussis, Daniel Auld, Nathalie Brassard, Madeleine Durand, Michaël Chassé, Daniel E. Kaufmann, G. Mark Lathrop, Vincent Mooser, J. Brent Richards, Rui Li, Darin Adra, Souad Rahmouni, Michel Georges, Michel Moutschen, Benoit Misset, Gilles Darcis, Julien Guiot, Julien Guntz, Samira Azarzar, Stéphanie Gofflot, Yves Beguin, Sabine Claassen, Olivier Malaise, Pascale Huynen, Christelle Meuris, Marie Thys, Jessica Jacques, Philippe Léonard, Frederic Frippiat, Jean-Baptiste Giot, Anne-Sophie Sauvage, Christian Von Frenckell, Yasmine Belhaj, Bernard Lambermont, Sara Pigazzini, Lindokuhle Nkambule, Michelle Daya, Jonathan Shortt, Nicholas Rafaels, Stephen J. Wicks, Kristy Crooks, Kathleen C. Barnes, Christopher R. Gignoux, Sameer Chavan, Triin Laisk, Kristi Läll, Maarja Lepamets, Reedik Mägi, Tõnu Esko, Ene Reimann, Lili Milani, Helene Alavere, Kristjan Metsalu, Mairo Puusepp, Andres Metspalu, Paul Naaber, Edward Laane, Jaana Pesukova, Pärt Peterson, Kai Kisand, Jekaterina Tabri, Raili Allos, Kati Hensen, Joel Starkopf, Inge Ringmets, Anu Tamm, Anne Kallaste, Pierre-Yves Bochud, Carlo Rivolta, Stéphanie Bibert, Mathieu Quinodoz, Dhryata Kamdar, Noémie Boillat, Semira Gonseth Nussle, Werner Albrich, Noémie Suh, Dionysios Neofytos, Véronique Erard, Cathy Voide, null FHoGID, null RegCOVID, null P-PredictUs, null SeroCOVID, null CRiPSI, Rafael de Cid, Iván Galván-Femenía, Natalia Blay, Anna Carreras, Beatriz Cortés, Xavier Farré, Lauro Sumoy, Victor Moreno, Josep Maria Mercader, Marta Guindo-Martinez, David Torrents, Manolis Kogevinas, Judith Garcia-Aymerich, Gemma Castaño-Vinyals, Carlota Dobaño, Alessandra Renieri, Francesca Mari, Chiara Fallerini, Sergio Daga, Elisa Benetti, Margherita Baldassarri, Francesca Fava, Elisa Frullanti, Floriana Valentino, Gabriella Doddato, Annarita Giliberti, Rossella Tita, Sara Amitrano, Mirella Bruttini, Susanna Croci, Ilaria Meloni, Maria Antonietta Mencarelli, Caterina Lo Rizzo, Anna Maria Pinto, Giada Beligni, Andrea Tommasi, Laura Di Sarno, Maria Palmieri, Miriam Lucia Carriero, Diana Alaverdian, Stefano Busani, Raffaele Bruno, Marco Vecchia, Mary Ann Belli, Nicola Picchiotti, Maurizio Sanarico, Marco Gori, Simone Furini, Stefania Mantovani, Serena Ludovisi, Mario Umberto Mondelli, Francesco Castelli, Eugenia Quiros-Roldan, Melania Degli Antoni, Isabella Zanella, Massimo Vaghi, Stefano Rusconi, Matteo Siano, Francesca Montagnani, Arianna Emiliozzi, Massimiliano Fabbiani, Barbara Rossetti, Elena Bargagli, Laura Bergantini, Miriana D’Alessandro, Paolo Cameli, David Bennett, Federico Anedda, Simona Marcantonio, Sabino Scolletta, Federico Franchi, Maria Antonietta Mazzei, Susanna Guerrini, Edoardo Conticini, Luca Cantarini, Bruno Frediani, Danilo Tacconi, Chiara Spertilli, Marco Feri, Alice Donati, Raffaele Scala, Luca Guidelli, Genni Spargi, Marta Corridi, Cesira Nencioni, Leonardo Croci, Maria Bandini, Gian Piero Caldarelli, Paolo Piacentini, Elena Desanctis, Silvia Cappelli, Anna Canaccini, Agnese Verzuri, Valentina Anemoli, Agostino Ognibene, Alessandro Pancrazzi, Maria Lorubbio, Antonella D’Arminio Monforte, Federica Gaia Miraglia, Massimo Girardis, Sophie Venturelli, Andrea Cossarizza, Andrea Antinori, Alessandra Vergori, Arianna Gabrieli, Agostino Riva, Daniela Francisci, Elisabetta Schiaroli, Francesco Paciosi, Pier Giorgio Scotton, Francesca Andretta, Sandro Panese, Renzo Scaggiante, Francesca Gatti, Saverio Giuseppe Parisi, Stefano Baratti, Matteo Della Monica, Carmelo Piscopo, Mario Capasso, Roberta Russo, Immacolata Andolfo, Achille Iolascon, Giuseppe Fiorentino, Massimo Carella, Marco Castori, Giuseppe Merla, Gabriella Maria Squeo, Filippo Aucella, Pamela Raggi, Carmen Marciano, Rita Perna, Matteo Bassetti, Antonio Di Biagio, Maurizio Sanguinetti, Luca Masucci, Serafina Valente, Marco Mandalà, Alessia Giorli, Lorenzo Salerni, Patrizia Zucchi, Pierpaolo Parravicini, Elisabetta Menatti, Tullio Trotta, Ferdinando Giannattasio, Gabriella Coiro, Fabio Lena, Domenico A. Coviello, Cristina Mussini, Enrico Martinelli, Sandro Mancarella, Luisa Tavecchia, Lia Crotti, Chiara Gabbi, Marco Rizzi, Franco Maggiolo, Diego Ripamonti, Tiziana Bachetti, Maria Teresa La Rovere, Simona Sarzi-Braga, Maurizio Bussotti, Stefano Ceri, Pietro Pinoli, Francesco Raimondi, Filippo Biscarini, Alessandra Stella, Kristina Zguro, Katia Capitani, Claudia Suardi, Simona Dei, Gianfranco Parati, Sabrina Ravaglia, Rosangela Artuso, Giordano Bottà, Paolo Di Domenico, Ilaria Rancan, Antonio Perrella Francesco Bianchi, Davide Romani, Paola Bergomi, Emanuele Catena, Riccardo Colombo, Marco Tanfoni, Antonella Vincenti, Claudio Ferri, Davide Grassi, Gloria Pessina, Mario Tumbarello, Massimo Di Pietro, Ravaglia Sabrina, Sauro Luchi, Chiara Barbieri, Donatella Acquilini, Elena Andreucci, Francesco Vladimiro Segala, Giusy Tiseo, Marco Falcone, Mirjam Lista, Monica Poscente, Oreste De Vivo, Paola Petrocelli, Alessandra Guarnaccia, Silvia Baroni, Albert V. Smith, Andrew P. Boughton, Kevin W. Li, Jonathon LeFaive, Aubrey Annis, Anne E. Justice, Tooraj Mirshahi, Geetha Chittoor, Navya Shilpa Josyula, Jack A. Kosmicki, Manuel A.R. Ferreira, Joseph B. Leader, Dave J. Carey, Matthew C. Gass, Julie E. Horowitz, Michael N. Cantor, Ashish Yadav, Aris Baras, Goncalo R. Abecasis, David A. van Heel, Karen A. Hunt, Dan Mason, Qin Qin Huang, Sarah Finer, null Genes & Health Research Team, Bhavi Trivedi, Christopher J. Griffiths, Hilary C. Martin, John Wright, Richard C. Trembath, Nicole Soranzo, Jing Hua Zhao, Adam S. Butterworth, John Danesh, Emanuele Di Angelantonio, Lude Franke Marike Boezen, Patrick Deelen, Annique Claringbould, Esteban Lopera, Robert Warmerdam, Judith.M. Vonk, Irene van Blokland, Pauline Lanting, Anil P.S. Ori, Brooke Wolford Sebastian Zöllner, Jiongming Wang, Andrew Beck, Gina Peloso, Yuk-Lam Ho, Yan V. Sun, Jennifer E. Huffman, Christopher J. O’Donnell, Kelly Cho, Phil Tsao, J. Michael Gaziano, Michel (M.G.) Nivard, Eco (E.J.C.) de geus, Meike Bartels, Jouke Jan Hottenga, Scott T. Weiss, Elizabeth W. Karlson, Jordan W. Smoller, Robert C. Green, Yen-Chen Anne Feng, Josep Mercader, Shawn N. Murphy, James B. Meigs, Ann E. Woolley, Emma F. Perez, Daniel Rader, Anurag Verma, Marylyn D. Ritchie, Binglan Li, Shefali S. Verma, Anastasia Lucas, Yuki Bradford, Hugo Zeberg, Robert Frithiof, Michael Hultström, Miklos Lipcsey, Lindo Nkambul, Nicolas Tardif, Olav Rooyackers, Jonathan Grip, Tomislav Maricic, Konrad J. Karczewski, Elizabeth G. Atkinson, Kristin Tsuo, Nikolas Baya, Patrick Turley, Rahul Gupta, Shawneequa Callier, Raymond K. Walters, Duncan S. Palmer, Gopal Sarma, Nathan Cheng, Wenhan Lu, Sam Bryant, Claire Churchhouse, Caroline Cusick, Jacqueline I. Goldstein, Daniel King, Cotton Seed, Hilary Finucane, Alicia R. Martin, F. Kyle Satterstrom, Daniel J. Wilson, Jacob Armstrong, Justine K. Rudkin, Gavin Band, Sarah G. Earle, Shang-Kuan Lin, Nicolas Arning, Derrick W. Crook, David H. Wyllie, Anne Marie O’Connell, Chris C.A. Spencer, Nils Koelling, Mark J. Caulfield, Richard H. Scott, Tom Fowler, Loukas Moutsianas, Athanasios Kousathanas, Dorota Pasko, Susan Walker, Augusto Rendon, Alex Stuckey, Christopher A. Odhams, Daniel Rhodes, Georgia Chan, Prabhu Arumugam, Catherine A. Ball, Eurie L. Hong, Kristin Rand, Ahna Girshick, Harendra Guturu, Asher Haug Baltzell, Genevieve Roberts, Danny Park, Marie Coignet, Shannon McCurdy, Spencer Knight, Raghavendran Partha, Brooke Rhead, Miao Zhang, Nathan Berkowitz, Michael Gaddis, Keith Noto, Luong Ruiz, Milos Pavlovic, Laura G. Sloofman, Alexander W. Charney, Noam D. Beckmann, Eric E. Schadt, Daniel M. Jordan, Ryan C. Thompson, Kyle Gettler, Noura S. Abul-Husn, Steven Ascolillo, Joseph D. Buxbaum, Kumardeep Chaudhary, Judy H. Cho, Yuval Itan, Eimear E. Kenny, Gillian M. Belbin, Stuart C. Sealfon, Robert P. Sebra, Irene Salib, Brett L. Collins, Tess Levy, Bari Britvan, Katherine Keller, Lara Tang, Michael Peruggia, Liam L. Hiester, Kristi Niblo, Alexandra Aksentijevich, Alexander Labkowsky, Avromie Karp, Menachem Zlatopolsky, Michael Preuss, Ruth J.F. Loos, Girish N. Nadkarni, Ron Do, Clive Hoggart, Sam Choi, Slayton J. Underwood, Paul O’Reilly, Laura M. Huckins, Marissa Zyndorf, AII - Infectious diseases, Amsterdam Neuroscience - Neuroinfection & -inflammation, and Neurology

Subjects
Medical Physiology, Gene Expression, Genome-wide association study, Genome, Severity of Illness Index, colocalization, Gene expression, Databases, Genetic, Ethnicity, 2.1 Biological and endogenous factors, GWAS, Aetiology, Biology (General), Lung, Genetics, Chromosome Mapping, Single Nucleotide, Organ Specificity, Biotechnology, Cell type, QH301-705.5, Quantitative Trait Loci, Single-nucleotide polymorphism, Biology, eQTL, Polymorphism, Single Nucleotide, Article, General Biochemistry, Genetics and Molecular Biology, Databases, Genetic, SNP, Humans, Genetic Predisposition to Disease, COVID-19 Host Genetics Initiative, Polymorphism, Gene, COVID-19, SARS-CoV-2, Gene Expression Profiling, Prevention, Human Genome, Computational Biology, Genetic Variation, Good Health and Well Being, Expression quantitative trait loci, Biochemistry and Cell Biology, Transcriptome, Genome-Wide Association Study
Abstract

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types., Graphical abstract, D’Antonio et al. characterize associations between GWAS signals for COVID-19 disease and eQTLs in 69 human tissues to identify causal variants and their underlying molecular mechanisms. They show that diverse symptoms and disease severity of COVID-19 are associated with variants affecting gene expression in a wide variety of tissues.

Published
2022

41. Conventional approaches versus laser CO2 surgery in stapes surgery: a multicentre retrospective study

Author

Francesco Soprani, Antonino Maniaci, Giannicola Iannella, Andrea De Vito, Ludovica Livi, Marco Mandalà, Claudio Vicini, Salvatore Cocuzza, Gloria Napoli, Francesca Viberti, Valeria Roustan, and Stefano Pelucchi

Subjects
medicine.medical_specialty, Statistical difference, Stapes surgery · Otosclerosis · Stapes · Stapedotomy · Laser stapedotomy · Laser stapes surgery, Stapes Surgery, 03 medical and health sciences, 0302 clinical medicine, laser stapedotomy, laser stapes surgery, otosclerosis, stapedotomy, stapes, stapes surgery, carbon dioxide, humans, middle aged, retrospective studies, treatment outcome, lasers, gas, gas, medicine, Humans, 030223 otorhinolaryngology, Stapes, Retrospective Studies, Co2 laser, business.industry, Retrospective cohort study, General Medicine, Carbon Dioxide, Middle Aged, medicine.disease, Stapes surgery, Surgery, Otosclerosis, Treatment Outcome, Otorhinolaryngology, 030220 oncology & carcinogenesis, Lasers, Gas, Neurosurgery, business, lasers
Abstract

To analyze and compare surgical and audiological outcomes of conventional approaches versus laser CO2 surgery in stapes surgery. 333 patients who underwent stapes surgery were enrolled in the study; the patient population was divided into three groups: group 1: 170 patients treated with conventional stapedotomy with manual microdrill (average age 49.13 years); group 2: 119 patients treated with conventional stapedotomy with electrical microdrill (average age 51.06 years); group 3: 44 patients (average age 50.4 years) who underwent CO2 laser stapedotomy. Intra-operative, postoperative outcomes and audiological results were investigated. The average surgical time of laser CO2 surgery was longer than for other surgical procedures. No statistical differences emerged in post-operative abnormal taste sensation. There was also no difference in postoperative dizziness. Air-bone gap (ABG) went down from 29.7 ± 10 dB (group 1) and 27.32 ± 9.20 (group 2) to 10 ± 6.9 dB (group 1) and 10.7 ± 6.03 dB (group 2). In group 3 the preoperative ABG was lowered from 28.3 ± 10.1 to 11.8 ± 10.9, with a statistical difference in auditory recovery (p = 0.0001); The group of patients treated with laser CO2 showed a percentage of patients with an ABG closure of between 0 and 10 dB higher than in the group treated with manual microdrills (77.2% vs. 60%, respectively; p = 0.03). Overall surgical results of CO2 laser and conventional stapedotomy are comparable without any significant difference; however, the group treated with CO2 laser appears to have a percentage of patients with an ABG closure 0–10 dB higher than the group treated using the conventional technique.

Published
2021

42. Author response: Association of Toll-like receptor 7 variants with life-threatening COVID-19 disease in males: findings from a nested case-control study

Author

Diego Ripamonti, Sandro Panese, Agnese Verzuri, Giancarlo Bosio, Francesco Castelli, Leonardo Croci, Maurizio Spagnesi, Sergio Daga, Massimiliano Fabbiani, Barbara Rossetti, Silvia Cappelli, Giada Beligni, Gabriella Coiro, Antonio Di Biagio, Domenico A Coviello, Massimo Girardis, Pamela Raggi, Roberta Russo, Federico Franchi, Matteo Bassetti, Stefano Baratti, Gianfranco Parati, Francesca Montagnani, Marco Rizzi, Eugenia Quiros-Roldan, Francesca Fava, Tiziana Bachetti, Agostino Riva, Filippo Aucella, Francesca Gatti, Anna Canaccini, Anna Maria Pinto, Sandro Mancarella, Alessandra Renieri, Arianna Gabrieli, Mario Chiariello, Rossella Tita, Luca Guidelli, Sophie Venturelli, Ilaria Meloni, Luisa Tavecchia, Marta Corridi, Susanna Croci, Francesca Mari, Pierpaolo Parravicini, Andrea Tommasi, Carmelo Piscopo, Tullio Trotta, Miriana d'Alessandro, Maria Antonietta Mencarelli, Cristina Mussini, Simone Furini, Alessandra Vergori, Gen-Covid Multicenter Study, Margherita Baldassarri, Daniela Francisci, Giuseppe Fiorentino, Simona Sarzi-Braga, Mirella Bruttini, Sabino Scolletta, Mario Capasso, Melania Degli Antoni, Serafina Valente, Alice Donati, Maria Antonietta Mazzei, Maurizio Bussotti, Chiara Fallerini, Laura Di Sarno, Federico Anedda, Davide Romani, Katia Capitani, Gian Piero Caldarelli, Elisa Frullanti, Caterina Lo Rizzo, Bruno Frediani, Marco Castori, Arianna Emiliozzi, Andrea Cossarizza, Elena Desanctis, Luca Cantarini, Cesira Nencioni, Ottavia Spiga, Fabio Lena, Isabella Zanella, Genni Spargi, Francesco Paciosi, Pier Giorgio Scotton, Simona Dei, Marco Mandalà, Giacomo Zanelli, Alessia Giorli, Elena Bargagli, Maria Palmieri, Stefano Rusconi, Laura Bergantini, Ferdinando Giannattasio, David Bennett, Carmen Marciano, Chiara Spertilli, Maria Bandini, Serena Ludovisi, Enrico Martinelli, Edoardo Conticini, Valentina Anemoli, Nicola Iuso, Elisa Benetti, Matteo Siano, Achille Iolascon, Danilo Tacconi, Mario U. Mondelli, Sara Amitrano, Raffaele Scala, Paolo Piacentini, Lia Crotti, Maria Teresa La Rovere, Nicola Picchiotti, Patrizia Zucchi, Elisabetta Schiaroli, Immacolata Andolfo, Francesca Andretta, Gabriella Doddato, Annarita Giliberti, Stefano Busani, Simona Marcantonio, Antonella d'Arminio Monforte, Mary Ann Belli, Luca Masucci, Rita Perna, Chiara Gabbi, Gabriella Maria Squeo, Franco Maggiolo, Marco Feri, Susanna Guerrini, Paolo Cameli, Elisabetta Menatti, Maurizio Sanguinetti, Andrea Antinori, Lorenzo Salerni, Saverio Giuseppe Parisi, Stefania Mantovani, Floriana Valentino, Federica Gaia Miraglia, Agostino Ognibene, Marco Gori, Renzo Scaggiante, Matteo Della Monica, Giuseppe Merla, Massimo Vaghi, and Massimo Carella

Subjects
Toll-like receptor, Coronavirus disease 2019 (COVID-19), business.industry, Association (object-oriented programming), Nested case-control study, Immunology, Medicine, Disease, business
Published
2021

43. An innovative eye-tracker. Main features and demonstrative tests

Author

Lorenzo Bellizzi, Giuseppe Bevilacqua, Valerio Biancalana, Mario Carucci, Roberto Cecchi, Piero Chessa, Aniello Donniacuo, Marco Mandalà, and Leonardo Stiaccini

Subjects
Physics - Instrumentation and Detectors, Eye Movements, Magnetoresistance, Magnetic tracking, Eye Tracking, FOS: Physical sciences, Physics - Applied Physics, Applied Physics (physics.app-ph), Instrumentation and Detectors (physics.ins-det), Physics - Medical Physics, Magnetic tracking, Eye Tracking, Magnetoresistance, Sensor array, Magnetics, Medical Physics (physics.med-ph), Instrumentation, Sensor array
Abstract

We present a set of results obtained with an innovative eye-tracker based on magnetic dipole localization by means of an array of magnetoresistive sensors. The system tracks both head and eye movements with a high rate (100-200 Sa/s) and in real time. A simple setup is arranged to simulate head and eye motions and to test the tracker performance under realistic conditions. Multimedia material is provided to substantiate and exemplify the results. A comparison with other available technologies for eye tracking is drawn, discussing advantages (e.g. precision) and disadvantages (e.g. invasivity) of the diverse approaches, the presented method standing out for low cost, robustness and relatively low invasivity., Comment: 7 pages, 5 figures, 6 links to multimedia (video), 26 refs

Published
2021
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44. Feasibility of TMS in patients with new generation cochlear implants

Author

Domenico Prattichizzo, Emiliano Santarnecchi, Tommaso Lisini Baldi, Lucia Mencarelli, Simone Rossi, Sara M. Romanella, Monica Ulivelli, Francesco Neri, and Marco Mandalà

Subjects
Materials science, Speech perception, medicine.medical_treatment, 050105 experimental psychology, Cochlear implant, rTMS, Safety, TMS, Transcranial Magnetic Stimulation, 03 medical and health sciences, 0302 clinical medicine, Physiology (medical), medicine, Humans, 0501 psychology and cognitive sciences, In patient, Hearing Loss, Neuronal Plasticity, medicine.diagnostic_test, 05 social sciences, Magnetic resonance imaging, Equipment Design, Cochlear Implantation, Sensory Systems, Intensity (physics), Transcranial magnetic stimulation, Cochlear Implants, Neurology, Electromagnetic coil, Feasibility Studies, Neurology (clinical), Implant, human activities, 030217 neurology & neurosurgery, Biomedical engineering
Abstract

Objective The presence of a cochlear implant is being considered an absolute contraindication for experiments and/or treatments. We aimed to verify TMS (Transcranial Magnetic Stimulation) compatibility of a new generation of cochlear implants. Methods In a series of experiments, we test if MED-EL cochlear implants -compatible with stable fields of magnetic resonance imaging scanning- are fully resistant even to rapidly varying magnetic fields as those generated by single pulses and low and high-frequency trains of repetitive TMS (rTMS) applied with a figure of eight coil and different magnetic stimulators. Results With a TMS intensity equal or below 2.2 Tesla (T) the cochlear implant and all its electronic components remain fully functional, even when the combination of frequency, intensity and number of pulses exceeds the currently available safety guidelines. Induced forces on the implant are negligible. With higher magnetic fields (i.e., 3.2 T), one device was corrupted. Conclusions Results exclude the risk of electronic damaging, demagnetizing or displacements of the studied cochlear implants when exposed to magnetic fields of up to 2.2 T delivered through a focal coil. Significance They open the way to use focal rTMS protocols with the aim of promoting neural plasticity in auditory networks, possibly helping the post-implant recovery of speech perception performance.

Published
2021

45. Genetic mechanisms of critical illness in COVID-19

Author

Pairo-Castineira, Erola, Clohisey, Sara, Klaric, Lucija, Bretherick, Andrew D, Rawlik, Konrad, Pasko, Dorota, Walker, Susan, Parkinson, Nick, Fourman, Max Head, Russell, Clark D, Furniss, James, Richmond, Anne, Gountouna, Elvina, Wrobel, Nicola, Harrison, David, Wang, Bo, Yang, Wu, Meynert, Alison, Griffiths, Fiona, Oosthuyzen, Wilna, Kousathanas, Athanasios, Moutsianas, Loukas, Yang, Zhijian, Zhai, Ranran, Zheng, Chenqing, Grimes, Graeme, Beale, Rupert, Millar, Jonathan, Shih, Barbara, Keating, Sean, Zechner, Marie, Haley, Chris, Porteous, David J, Hayward, Caroline, Yang, Jian, Knight, Julian, Summers, Charlotte, Shankar-Hari, Manu, Klenerman, Paul, Turtle, Lance, Antonia, Ho, Moore, Shona C, Hinds, Charles, Horby, Peter, Nichol, Alistair, Maslove, David, Ling, Lowell, Mcauley, Danny, Montgomery, Hugh, Walsh, Timothy, Pereira, Alexandre C, Renieri, Johnny, Millar, Alistair, Nichol, Tim, Walsh, Manu, Shankar-Hari, Chris, Ponting, Jen, Meikle, Paul, Finernan, Ellie, Mcmaster, Andy, Law, J Kenneth Baillie, Trevor, Paterson, Tony, Wackett, Ruth, Armstrong, Richard, Clark, Audrey, Coutts, Lorna, Donnelly, Tammy, Gilchrist, Katarzyna, Hafezi, Louise, Macgillivray, Alan, Maclean, Sarah, Mccafferty, Kirstie, Morrice, Jane, Weaver, Ceilia, Boz, Ailsa, Golightly, Mari, Ward, Hanning, Mal, Helen, Szoor-McElhinney, Adam, Brown, Ross, Hendry, Andrew, Stenhouse, Louise, Cullum, Dawn, Law, Sarah, Law, Rachel, Law, Maaike, Swets, Nicky, Day, Filip, Taneski, Esther, Duncan, Nicholas, Parkinson, Collier, D, Wood, S, Zak, A, Borra, C, Matharu, M, May, P, Alldis, Z, Mitchelmore, O, Bowles, R, Easthope, A, Bibi, F, Lancoma-Malcolm, I, Gurasashvili, J, Pheby, J, Shiel, J, Bolton, M, Patel, M, Taylor, M, Zongo, O, Ebano, P, Harding, P, Astin-Chamberlain, R, Choudhury, Y, Cox, A, Kallon, D, Burton, M, Hall, R, Blowes, S, Prime, Z, Biddle, J, Prysyazhna, O, Newman, T, Tierney, C, Kassam, J, Shankar-Hari, M, Ostermann, M, Campos, S, Bociek, A, Lim, R, Grau, N, O Jones, T, Whitton, C, Marotti, M, Arbane, G, Bonner, S, Hugill, K, Reid, J, Welters, I, Waugh, V, Williams, K, Shaw, D, J Fernandez Roman, M Lopez Martinez, Johnson, E, Waite, A, Johnston, B, Hamilton, D, Mulla, S, Mcphail, M, Smith, J, K Baillie, J, Barclay, L, Hope, D, Mcculloch, C, Mcquillan, L, Clark, S, Singleton, J, Priestley, K, Rea, N, Callaghan, M, Campbell, R, Andrew, G, Marshall, L, Mckechnie, S, Hutton, P, Bashyal, A, Davidson, N, Summers, C, Polgarova, P, Stroud, K, Pathan, N, Elston, K, Agrawal, S, Battle, C, Newey, L, Rees, T, Harford, R, Brinkworth, E, Williams, M, Murphy, C, White, I, Croft, M, Bandla, N, Gellamucho, M, Tomlinson, J, Turner, H, Davies, M, Quinn, A, Hussain, I, Thompson, C, Parker, H, Bradley, R, Griffiths, R, Scriven, J, Nilsson, A, Bates, M, Dasgin, J, Gill, J, Puxty, A, Cathcart, S, Salutous, D, Turner, L, Duffy, K, Puxty, K, Joseph, A, Herdman-Grant, R, Simms, R, Swain, A, Naranjo, A, Crowe, R, Sollesta, K, Loveridge, A, Baptista, D, Morino, E, Davey, M, Golden, D, Jones, J, J Moreno Cuesta, Haldeos, A, Bakthavatsalam, D, Vincent, R, Elhassan, M, Xavier, K, Ganesan, A, Purohit, D, Abdelrazik, M, Morgan, J, Akeroyd, L, Bano, S, Lawton, T, Warren, D, Bromley, M, Sellick, K, Gurr, L, Wilkinson, B, Nagarajan, V, Szedlak, P, Cupitt, J, Stoddard, E, Benham, L, Preston, S, Laha, S, Slawson, N, Bradshaw, Z, Brown, J, Caswell, M, Melling, S, Bamford, P, Faulkner, M, Cawley, K, Jeffrey, H, London, E, Sainsbury, H, Nagra, I, Nasir, F, Dunmore, C, Jones, R, Abraheem, A, Al-Moasseb, M, Girach, R, Padden, G, Egan, J, Brantwood, C, Alexander, P, Bradley-Potts, J, Allen, S, Felton, T, Manna, S, Farnell-Ward, S, Leaver, S, Queiroz, J, Maccacari, E, Dawson, D, C Castro Delgado, R Pepermans Saluzzio, Ezeobu, O, Ding, L, Sicat, C, Kanu, R, Durrant, G, Texeira, J, Harrison, A, Samakomva, T, Willis, H, Hopkins, B, Thrasyvoulou, L, Jackson, M, Zaki, A, Tibke, C, Bennett, S, Woodyatt, W, Kent, A, Goodwin, E, Brandwood, C, Clark, R, Smith, L, Rooney, K, Thomson, N, Rodden, N, Hughes, E, Mcglynn, D, Clark, C, Clark, P, Abel, L, Sundaram, R, Gemmell, L, Brett, M, Hornsby, J, Macgoey, P, Price, R, Digby, B, O'Neil, P, Mcconnell, P, Henderson, P, Henderson, S, Sim, M, Kennedy-Hay, S, Mcparland, C, Rooney, L, Baxter, N, Pogson, D, Rose, S, Daly, Z, Brimfield, L, K Phull, M, Hussain, M, Pogreban, T, Rosaroso, L, Salciute, E, Grauslyte, L, Brealey, D, Raith, E, Maccallum, N, Bercades, G, Hass, I, Smyth, D, Reyes, A, Martir, G, D Clement, I, Webster, K, Hays, C, Gulati, A, Hodgson, L, Margarson, M, Gomez, R, Baird, Y, Thirlwall, Y, Folkes, L, Butler, A, Meadows, E, Moore, S, Raynard, D, Fox, H, Riddles, L, King, K, Kimber, S, Hobden, G, Mccarthy, A, Cannons, V, Balagosa, I, Chadbourn, I, Gardner, A, Horner, D, Mclaughlanv, D, Charles, B, Proudfoot, N, Marsden, T, Mcmorrow, L, Blackledge, B, Pendlebury, J, Harvey, A, Apetri, E, Basikolo, C, Catlow, L, Doonan, R, Knowles, K, Lee, S, Lomas, D, Lyons, C, Perez, J, Poulaka, M, Slaughter, M, Slevin, K, Thomas, V, Walker, D, Harris, J, Drummond, A, Tully, R, Dearden, J, Philbin, J, Munt, S, Rishton, C, O'Connor, G, Mulcahy, M, Dobson, E, Cuttler, J, Edward, M, Norris, J, Hanson, K, Poole, A, Rose, A, Sloan, B, Buckley, S, Brooke, H, Smithson, E, Charlesworth, R, Sandhu, R, Thirumaran, M, Wagstaff, V, J Cebrian Suarez, Kaliappan, A, Vertue, M, Nicholson, A, Riches, J, Solesbury, A, Kittridge, L, Forsey, M, Maloney, G, Cole, J, Davies, R, Hill, H, Thomas, E, Williams, A, Duffin, D, Player, B, Radhakrishnan, J, Gibson, S, Lyle, A, Mcneela, F, Patel, B, Gummadi, M, Sloane, G, Dormand, N, Salmi, S, Farzad, Z, Cristiano, D, Liyanage, K, Thwaites, V, Varghese, M, Meredith, M, Mills, G, Willson, J, Harrington, K, Lenagh, B, Cawthron, K, Masuko, S, Raithatha, A, Bauchmuller, K, Wiles, M, Ahmad, N, Barker, J, Jackson, Y, Kibutu, F, Bird, S, Watson, G, Martin, J, Bevan, E, C Wrey Brown, Trodd, D, English, K, Bell, G, Wilcox, L, Katary, A, Gopal, S, Lake, V, Harris, N, Metherell, S, Radford, E, Moore, F, Bancroft, H, Daglish, J, Sangombe, M, Carmody, M, Rhodes, J, Bellamy, M, Garg, A, Kuravi, A, Virgilio, E, Ranga, P, Butler, J, Botfield, L, Dexter, C, Fletcher, J, Shanmugasundaram, P, Hambrook, G, Burn, I, Manso, K, Thornton, D, Tebbutt, J, Penn, R, Hulme, J, Hussain, S, Maqsood, Z, Joseph, S, Colley, J, Hayes, A, Ahmed, C, Haq, R, Clamp, S, Kumar, R, Purewal, M, Baines, B, Frise, M, Jacques, N, Coles, H, Caterson, J, S Gurung Rai, Brunton, M, Tilney, E, Keating, L, Walden, A, Antcliffe, D, Brett, S, Gordon, A, Templeton, M, Rojo, R, Banach, D, S Sousa Arias, Fernandez, Z, Coghlan, P, Williams, D, Jardine, C, Bewley, J, Sweet, K, Grimmer, L, Johnson, R, Garland, Z, Gumbrill, B, Phillips, C, L Ortiz-Ruiz de Gordoa, Peasgood, E, Tridente, A, Shuker, K, Greer, S, Lynch, C, Pothecary, C, Roche, L, Deacon, B, Turner, K, Singh, J, G Sera Howe, Paul, P, Gill, M, Wynter, I, Ratnam, V, Shelton, S, Naisbitt, J, Melville, J, Baruah, R, Morrison, S, Mcgregor, A, Parris, V, Mpelembue, M, Srikaran, S, Dennis, C, Sukha, A, Verlander, M, Holding, K, Riches, K, Downes, C, Swan, C, Rostron, A, Roy, A, Woods, L, Cornell, S, Wakinshaw, F, Creagh-Brown, B, Blackman, H, Salberg, A, Smith, E, Donlon, S, Mtuwa, S, Michalak-Glinska, N, Stone, S, Beazley, C, Pristopan, V, Nikitas, N, Lankester, L, Wells, C, S Raj, A, Fletcher, K, Khade, R, Tsinaslanidis, G, Macmahon, M, Fowler, S, Coventry, T, Stewart, R, Wren, L, Mwaura, E, Mew, L, Scaletta, D, Williams, F, Inweregbu, K, Lancaster, N, Cunningham, M, Daniels, A, Harrison, L, Hope, S, Jones, S, Crew, A, Wray, G, Matthews, J, Crawley, R, Carter, J, Birkinshaw, I, Ingham, J, Scott, Z, Pearson, H, Howard, K, Joy, R, Roche, S, Clark, M, Purvis, S, Morrison, A, Strachan, D, Clements, S, Black, K, Parmar, C, Altabaibeh, A, Simpson, K, Mostoles, L, Gilbert, K, L, Ma, Alvaro, A, Thomas, M, Faulkner, B, Worner, R, Hayes, K, Gendall, E, Blakemore, H, Borislavova, B, Goff, E, Vuylsteke, A, Mwaura, L, Zamikula, J, Garner, L, Mitchell, A, Mepham, S, 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C., Kaliappan, A., Vertue, M., Nicholson, A., Riches, J., Solesbury, A., Kittridge, L., Forsey, M., Maloney, G., Cole, J., Davies, R., Hill, H., Thomas, E., Williams, A., Duffin, D., Player, B., Radhakrishnan, J., Gibson, S., Lyle, A., Mcneela, F., Patel, B., Gummadi, M., Sloane, G., Dormand, N., Salmi, S., Farzad, Z., Cristiano, D., Liyanage, K., Thwaites, V., Varghese, M., Meredith, M., Mills, G., Willson, J., Harrington, K., Lenagh, B., Cawthron, K., Masuko, S., Raithatha, A., Bauchmuller, K., Wiles, M., Ahmad, N., Barker, J., Jackson, Y., Kibutu, F., Bird, S., Watson, G., Martin, J., Bevan, E., Brown, C. W., Trodd, D., English, K., Bell, G., Wilcox, L., Katary, A., Gopal, S., Lake, V., Harris, N., Metherell, S., Radford, E., Moore, F., Bancroft, H., Daglish, J., Sangombe, M., Carmody, M., Rhodes, J., Bellamy, M., Garg, A., Kuravi, A., Virgilio, E., Ranga, P., Butler, J., Botfield, L., Dexter, C., Fletcher, J., Shanmugasundaram, P., Hambrook, G., Burn, I., Manso, K., Thornton, D., Tebbutt, J., Penn, R., Hulme, J., Hussain, S., Maqsood, Z., Joseph, S., Colley, J., Hayes, A., Ahmed, C., Haq, R., Clamp, S., Kumar, R., Purewal, M., Baines, B., Frise, M., Jacques, N., Coles, H., Caterson, J., Rai, S. G., Brunton, M., Tilney, E., Keating, L., Walden, A., Antcliffe, D., Brett, S., Gordon, A., Templeton, M., Rojo, R., Banach, D., Arias, S. S., Fernandez, Z., Coghlan, P., Williams, D., Jardine, C., Bewley, J., Sweet, K., Grimmer, L., Johnson, R., Garland, Z., Gumbrill, B., Phillips, C., Ortiz-Ruiz de Gordoa, L., Peasgood, E., Tridente, A., Shuker, K., Greer, S., Lynch, C., Pothecary, C., Roche, L., Deacon, B., Turner, K., Singh, J., Howe, G. S., Paul, P., Gill, M., Wynter, I., Ratnam, V., Shelton, S., Naisbitt, J., Melville, J., Baruah, R., Morrison, S., Mcgregor, A., Parris, V., Mpelembue, M., Srikaran, S., Dennis, C., Sukha, A., Verlander, M., Holding, K., Riches, K., Downes, C., Swan, C., Rostron, A., Roy, A., Woods, L., Cornell, S., Wakinshaw, F., Creagh-Brown, B., Blackman, H., Salberg, A., Smith, E., Donlon, S., Mtuwa, S., Michalak-Glinska, N., Stone, S., Beazley, C., Pristopan, V., Nikitas, N., Lankester, L., Wells, C., Raj, A. S., Fletcher, K., Khade, R., Tsinaslanidis, G., Macmahon, M., Fowler, S., Coventry, T., Stewart, R., Wren, L., Mwaura, E., Mew, L., Scaletta, D., Williams, F., Inweregbu, K., Lancaster, N., Cunningham, M., Daniels, A., Harrison, L., Hope, S., Jones, S., Crew, A., Wray, G., Matthews, J., Crawley, R., Carter, J., Birkinshaw, I., Ingham, J., Scott, Z., Pearson, H., Howard, K., Joy, R., Roche, S., Clark, M., Purvis, S., Morrison, A., Strachan, D., Clements, S., Black, K., Parmar, C., Altabaibeh, A., Simpson, K., Mostoles, L., Gilbert, K., Ma, L., Alvaro, A., Thomas, M., Faulkner, B., Worner, R., Hayes, K., Gendall, E., Blakemore, H., Borislavova, B., Goff, E., Vuylsteke, A., Mwaura, L., Zamikula, J., Garner, L., Mitchell, A., Mepham, S., Cagova, L., Fofano, A., Holcombe, H., Praman, K., Szakmany, T., Heron, A. E., Cherian, S., Cutler, S., Roynon-Reed, A., Randell, G., Convery, K., Stammers, K., Fottrell-Gould, D., Hudig, L., Keshet-Price, J., Peters, M., O'Neill, L., Ray, S., Belfield, H., Mchugh, T., Jones, G., Akinkugbe, O., Tomas, A., Abaleke, E., Beech, E., Meghari, H., Yussuf, S., Bamford, A., Hairsine, B., Dooks, E., Farquhar, F., Packham, S., Bates, H., Armstrong, L., Kaye, C., Allan, A., Medhora, J., Liew, J., Botello, A., Anderson, F., Cusack, R., Golding, H., Prager, K., Williams, T., Leggett, S., Golder, K., Male, M., Jones, O., Criste, K., Marani, M., Anumakonda, V., Amin, V., Karthik, K., Kausar, R., Anastasescu, E., Reid, K., Smith, M., Hormis, A., Walker, R., Duncan, T., Uriel, A., Ustianowski, A., T-Michael, H., Bruce, M., Connolly, K., Smith, K., Partridge, R., Griffin, D., Mupudzi, M., Muchenje, N., Martin, D., Filipe, H., Eastgate, C., Jackson, C., Gratrix, A., Foster, L., Martinson, V., Stones, E., Abernathy, C., Parkinson, P., Reed, A., Prendergast, C., Rogers, P., Woodruff, M., Shokkar, R., Kaul, S., Barron, A., Collins, C., Beavis, S., Whileman, A., Dale, K., Hawes, J., Pritchard, K., Gascoyne, R., Stevenson, L., Jha, R., Lim, L., Krishnamurthy, V., Parker, R., Turner-Bone, I., Wilding, L., Reddy, A., Whiteley, S., Wilby, E., Howcroft, C., Aspinwall, A., Charlton, S., Ogg, B., Menzies, D., Pugh, R., Allan, E., Lean, R., Davies, F., Easton, J., Qiu, X., Kumar, S., Darlington, K., Houston, G., O'Brien, P., Geary, T., Allan, J., Meikle, A., Hughes, G., Balasubramaniam, M., Latham, S., Mckenna, E., Flanagan, R., Sathe, S., Davies, E., Chablani, M., Kirkby, A., Netherton, K., Archer, S., Yates, B., Ashbrook-Raby, C., Cole, S., Casey, M., Cabrelli, L., Chapman, S., Hutcheon, A., Whyte, C., Almaden-Boyle, C., Pattison, N., Cruz, C., Vochin, A., Kent, H., Thomas, A., Murdoch, S., David, B., Penacerrada, M., Lubimbi, G., Bastion, V., Wulandari, R., Lorusso, R., Valentine, J., Clarke, D., Serrano-Ruiz, A., Hierons, S., Eckbad, C., Ramos, L., Demetriou, C., Mitchard, S., White, K., White, N., Pitts, S., Branney, D., Frankham, J., Watters, M., Langton, H., Prout, R., Page, V., Varghes, T., Cowton, A., Kay, A., Potts, K., Birt, M., Kent, M., Wilkinson, A., Jude, E. B., Turner, V., Savill, H., Mccormick, J., Coulding, M., Siddiqui, S., Mercer, O., Rehman, H., Potla, D., Capps, N., Donaldson, D., Button, H., Martin, T., Hard, K., Agasou, A., Tonks, L., Arden, T., Boyle, P., Carnahan, M., Strickley, J., Adams, C., Childs, D., Rikunenko, R., Leigh, M., Breekes, M., Wilcox, R., Bowes, A., Tiveran, H., Hurford, F., Summers, J., Carter, A., Hussain, Y., Ting, L., Javaid, A., Motherwell, N., Moore, H., Millward, H., Jose, S., Schunki, N., Noakes, A., Clulow, C., Sadera, G., Jacob, R., Jones, C., Blunt, M., Coton, Z., Curgenven, H., Ally, S. M., Beaumont, K., Elsaadany, M., Fernandes, K., Ali Mohamed Ali, I., Rangarajan, H., Sarathy, V., Selvanayagam, S., Vedage, D., White, M., Truman, N., Chukkambotla, S., Keith, S., Cockerill-Taylor, J., Ryan-Smith, J., Bolton, R., Springle, P., Dykes, J., Thomas, J., Khan, M., Hijazi, M. T., Massey, E., Croston, G., Reschreiter, H., Camsooksai, J., Patch, S., Jenkins, S., Humphrey, C., Wadams, B., Msiska, M., Adanini, O., Attwood, B., Parsons, P., Tatham, K., Jhanji, S., Black, E., Dela Rosa, A., Howle, R., Thomas, B., Bemand, T., Raobaikady, R., Saha, R., Staines, N., Daniel, A., Finn, J., Hutter, J., Doble, P., Shovelton, C., Pawley, C., Kannan, T., Hill, M., Combes, E., Monnery, S., Joefield, T., Popescu, M., Thankachen, M., Oblak, M., Little, J., Mcivor, S., Brady, A., Whittle, H., Prady, H., Chan, R., Ahmed, A., Morris, A., Gibson, C., Gordon, E., Keenan, S., Quinn, H., Benyon, S., Marriott, S., Zitter, L., Park, L., Baines, K., Lyons, M., Holland, M., Keenan, N., Young, M., Garrioch, S., Dawson, J., Tolson, M., Scholefield, B., Bi, R., Richardson, N., Schumacher, N., Cosier, T., Millen, G., Higham, A., Turki, S., Allen, L., Crisp, N., Hazleton, T., Knight, A., Deery, J., Price, C., Turney, S., Tilbey, S., Beranova, E., Wright, D., George, L., Twiss, S., Wadd, S., Postlethwaite, K., Gondo, P., Masunda, B., Kayani, A., Hadebe, B., Whiteside, J., Clarke, N., Donnison, P., Trim, F., Leadbitter, I., Butcher, D., O'Sullivan, S., Purewal, B., Bell, S., Rivers, V., O'Leary, R., Birch, J., Collins, E., Anderson, S., Hammerton, K., Andrews, E., Burns, K., Edmond, I., Todd, A., Donnachie, J., Turner, P., Prentice, L., Symon, L., Runciman, N., Auld, F., Halkes, M., Mercer, P., Thornton, L., Debreceni, G., Wilkins, J., Crickmore, V., Subramanian, G., Marshall, R., Jennings, C., Latif, M., Bunni, L., Spivey, M., Bean, S., Burt, K., Linnett, V., Ritzema, J., Sanderson, A., Mccormick, W., Bokhari, M., Kapoor, R., Loader, D., Ayers, A., Harrison, W., North, J., Belagodu, Z., Paramsothy, R., Olufuwa, O., Gherman, A., Fuller, B., Stuart, C., Kelsall, O., Davis, C., Wild, L., Wood, H., Thrush, J., Durie, A., Austin, K., Archer, K., Anderson, P., Vigurs, C., Thorpe, C., Knights, E., Boyle, N., Price, A., Kubisz-Pudelko, A., Wood, D., Lewis, A., Board, S., Pippard, L., Perry, J., Beesley, K., Rattray, A., Lee, E., Lennon, L., Douglas, K., Bell, D., Boyle, R., Glass, L., Nauman Akhtar, M., Dent, K., Potoczna, D., Pearson, S., Horsley, E., Spencer, S., Mullan, D., Skinner, D., Gaylard, J., Barber, R., Hewitt, C., Hilldrith, A., Shepardson, S., Wills, M., Jackson-Lawrence, K., Gupta, A., Timlick, E., Gorman, C., Otahal, I., Gales, A., Coetzee, S., Sell, C., Raj, M., Peiu, M., Quaid, S., Watson, E., Elliott, K., Mallinson, J., Chandler, B., Turnbull, A., Finch, C., Holl, C., Cooper, J., Evans, A., Khaliq, W., Collins, A., Gude, E. T., Love, N., van Koutrik, L., Hunt, J., Kaye, D., Fisher, E., Brayne, A., Tuckey, V., Jackson, P., Parkin, J., Tariq, A., Houlden, H., Tucci, A., Hardy, J., Moncur, E., Highgate, J., Cowley, A., Mitra, A., Stead, R., Behan, T., Burnett, C., Newton, M., Heeney, E., Pollard, R., Hatton, J., Patel, A., Kasipandian, V., Allibone, S., Genetu, R. M., O'Brien, L., Omar, Z., Perkins, E., Davies, K., Tetla, D., Shelley, B., Irvine, V., Williams, S., Williams, P., Goodsell, J., Tutton, R., Bough, L., Winter-Goodwin, B., Kitson, R., Pinnell, J., Wilson, A., Nortcliffe, T., Wood, T., Home, M., Holdroyd, K., Robinson, M., Shaw, R., Greig, J., Brady, M., Haigh, A., Matupe, L., Usher, M., Mellor, S., Dale, S., Gledhill, L., Shaw, L., Turner, G., Kelly, D., Anwar, B., Riley, H., Sturgeon, H., Ali, A., Thomis, L., Melia, D., Dance, A., Humphreys, S., Frost, I., Gopal, V., Godden, J., Holden, A., Swann, S., Smith, T., Clapham, M., Poultney, U., Harper, R., Rice, P., Reece-Anthony, R., Gurung, B., Moultrie, S., Odam, M., Mayer, A., Bellini, A., Pickard, A., Bryant, J., Roe, N., Sowter, J., Lang, K., Taylor, J., Barry, P., Hobrok, M., Tench, H., Wolf-Roberts, R., Mcguinness, H., Loosley, R., Hawcutt, D., Rad, L., O'Malley, L., Saunderson, P., Seddon, G., Anderson, T., Rogers, N., Ruddy, J., Harkins, M., Beith, C., Mcalpine, A., Ferguson, L., Grant, P., Macfadyen, S., Mclaughlin, M., Baird, T., Rundell, S., Welsh, B., Hamill, R., Fisher, F., Gregory, J., Campbell, A., Smuts, S., Kenneth Baillie, J., Carson, G., Alex, B., Bach, B., Barclay, W. S., Bogaert, D., Chand, M., Cooke, G. S., Docherty, A. B., Dunning, J., da Silva Filipe, A., Fletcher, T., Green, C. A., Harrison, E. M., Hiscox, J. A., Ho, A. Y. W., Horby, P. W., Ijaz, S., Khoo, S., Lim, W. S., Mentzer, A. J., Merson, L., Meynert, A. M., Noursadeghi, M., Palmarini, M., Paxton, W. A., Pollakis, G., Price, N., Rambaut, A., Robertson, D. L., Sancho-Shimizu, V., Scott, J. T., de Silva, T., Sigfrid, L., Solomon, T., Sriskandan, S., Stuart, D., Tedder, R. S., Thomson, E. C., Thompson, A. A. R., Thwaites, R. S., Turtle, L. C. W., Zambon, M., Hardwick, H., Donohue, C., Lyons, R., Norman, L., Pius, R., Drake, T. M., Fairfield, C. J., Knight, S. R., Mclean, K. A., Murphy, D., Shaw, C. A., Dalton, J., Girvan, M., Saviciute, E., Roberts, S., Harrison, J., Marsh, L., Connor, M., Halpin, S., Gamble, C., Leeming, G., Wham, M., Greenhalf, W., Shaw, V., Mcdonald, S., Ganna, A., Sulem, P., van Heel, D. A., Cordioli, M., Sveinbjornsson, G., Niemi, M. E. K., Shelton, J. F., Shastri, A. J., Ye, C., Weldon, C. H., Filshtein-Sonmez, T., Coker, D., Symons, A., Esparza-Gordillo, J., Aslibekyan, S., Auton, A., Krieger, J. E., Marques, E., Jannes, C. E., Mari, F., Daga, S., Baldassarri, M., Benetti, E., Furini, S., Fallerini, C., Fava, F., Valentino, F., Doddato, G., Giliberti, A., Tita, R., Amitrano, S., Bruttini, M., Croci, S., Meloni, I., Pinto, A. M., Frullanti, E., Mencarelli, M. A., Rizzo, C. L., Montagnani, F., Di Sarno, L., Tommasi, A., Palmieri, M., Emiliozzi, A., Fabbiani, M., Rossetti, B., Zanelli, G., Bargagli, E., Bergantini, L., D'Alessandro, M., Cameli, P., Bennet, D., Anedda, F., Marcantonio, S., Scolletta, S., Franchi, F., Mazzei, M. A., Guerrini, S., Conticini, E., Cantarini, L., Frediani, B., Tacconi, D., Spertilli, C., Feri, M., Donati, A., Scala, R., Guidelli, L., Spargi, G., Corridi, M., Nencioni, C., Croci, L., Caldarelli, G. P., Spagnesi, M., Piacentini, P., Bandini, M., Desanctis, E., Cappelli, S., Canaccini, A., Verzuri, A., Anemoli, V., Ognibene, A., Vaghi, M., D'Arminio Monforte, A., Merlini, E., Mondelli, M. U., Mantovani, S., Ludovisi, S., Girardis, M., Venturelli, S., Sita, M., Cossarizza, A., Antinori, A., Vergori, A., Rusconi, S., Siano, M., Gabrieli, A., Riva, A., Francisci, D., Schiaroli, E., Scotton, P. G., Andretta, F., Panese, S., Scaggiante, R., Gatti, F., Parisi, S. G., Castelli, F., Quiros-Roldan, M. E., Magro, P., Zanella, I., Della Monica, M., Piscopo, C., Capasso, M., Russo, R., Andolfo, I., Iolascon, A., Fiorentino, G., Carella, M., Castori, M., Merla, G., Aucella, F., Raggi, P., Marciano, C., Perna, R., Bassetti, M., Di Biagio, A., Sanguinetti, M., Masucci, L., Valente, S., Mandala, M., Giorli, A., Salerni, L., Zucchi, P., Parravicini, P., Menatti, E., Baratti, S., Trotta, T., Giannattasio, F., Coiro, G., Lena, F., Coviello, D. A., Mussini, C., Bosio, G., Martinelli, E., Mancarella, S., Tavecchia, L., Crotti, L., Picchiotti, N., Gori, M., Gabbi, C., Sanarico, M., Ceri, S., Pinoli, P., Raimondi, F., Biscarini, F., Stella, A., Shen, X., Ponting, C. P., Fawkes, A., Tenesa, A., Caulfield, M., Scott, R., Rowan, K., Murphy, L., Openshaw, P. J. M., Semple, M. G., Vitart, V., and Wilson, J. F.

Subjects
0301 basic medicine, Male, CCR2, Chromosomes, Human, Pair 21, Genome-wide association study, Receptor, Interferon alpha-beta, Disease, Bioinformatics, Genome-wide association studies, 23andMe Investigators, Interferon alpha-beta, 0302 clinical medicine, Receptors, 2',5'-Oligoadenylate Synthetase, Pair 12, genetics, Lung, BRACOVID Investigators, Multidisciplinary, GenOMICC Investigators, Tyrosine kinase 2, 030220 oncology & carcinogenesis, Multigene Family, Medical genetics, Female, Dipeptidyl-Peptidases and Tripeptidyl-Peptidase, 5'-Oligoadenylate Synthetase, Human, Receptor, medicine.medical_specialty, Critical Care, Receptors, CCR2, General Science & Technology, Critical Illness, Chromosomes, 03 medical and health sciences, Intensive care, Mendelian randomization, Immunogenetics, medicine, Humans, Dipeptidyl-Peptidases and Tripeptidyl-Peptidases, Gen-COVID Investigators, Inflammation, TYK2 Kinase, Chromosomes, Human, Pair 12, Pair 19, SARS-CoV-2, business.industry, Drug Repositioning, COVID-19, United Kingdom, COVID-19 Human Genetics Initiative, 030104 developmental biology, Viral infection, Chromosomes, Human, Pair 19, Genome-Wide Association Study, Pharmacogenomics, ISARICC Investigators, Pair 21, 2', business
Abstract

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079,P=1.65×10−8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1,OAS2andOAS3); on chromosome 19p13.2 (rs74956615,P=2.3×10−8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069,P=3.98× 10−12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757,P=4.99×10−8) in the interferon receptor geneIFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression ofIFNAR2, or high expression ofTYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte–macrophage chemotactic receptorCCR2is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice.

Published
2020
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46. Instrumenting Hand-held Surgical Drills With a Pneumatic Sensing Cover for Haptic Feedback

Author

Tommaso Lisini Baldi, Chiara Gaudeni, Marco Mandalà, Domenico Prattichizzo, Gabriele Maria Achilli, Università degli Studi di Siena = University of Siena (UNISI), and Università degli Studi di Perugia (UNIPG)

Subjects
0209 industrial biotechnology, Cover (telecommunications), Computer science, Hand held, 02 engineering and technology, 021001 nanoscience & nanotechnology, Contact force, Haptic display, Task (computing), 020901 industrial engineering & automation, Drill bit, [INFO.INFO-RB]Computer Science [cs]/Robotics [cs.RO], 0210 nano-technology, Reliability (statistics), Simulation, Haptic technology
Abstract

International audience; Despite the recent achievements in the development of open surgery tools, preserving the haptic capabilities during drilling tasks is still an open issue. In this paper, we propose a novel tool for hand-held drills composed of a cover for force sensing and a haptic display for force feedback. A pneumatic device has been developed to estimate the contact force occurring during the interaction between drill bit and bones. A performance comparison with a precise commercial force sensor proved the reliability of the measurements. A haptic ring is in charge of providing cutaneous sensations helping the surgeon in performing the task. The effectiveness of our method has been confirmed by experimental results and supported by statistical analysis.

Published
2020

47. A Literature Systematic Review with Meta-Analysis of Symptoms Prevalence in Covid-19: the Relevance of Olfactory Symptoms in Infection Not Requiring Hospitalization

Author

Giacomo Gualtieri, Marco Mandalà, Fabio Ferretti, Soumit Dasgupta, Ilaria Bindi, Anna Coluccia, A. Giorli, C. Biagini, Lorenzo Salerni, R. Gusinu, and Andrea Pozza

Subjects
medicine.medical_specialty, Sars-CoV-2, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Anosmia, New onset, 03 medical and health sciences, 0302 clinical medicine, Rate difference, Internal medicine, Diabetes mellitus, medicine, Quality assessment, business.industry, COVID-19, Reflections from the COVID Pandemic (A Iranzo and M Rosenfeld, Section Editor), medicine.disease, Hospitalization, Meta-analysis, 030220 oncology & carcinogenesis, Olfactory disorders, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

Purpose of review To investigate the association between the olfactory dysfunction and the more typical symptoms (fever, cough, dyspnoea) within the Sars-CoV-2 infection (COVID-19) in hospitalized and non-hospitalized patients. Recent findings PubMed, Scopus and Web of Science databases were reviewed from May 5, 2020, to June 1, 2020. Inclusion criteria included English, French, German, Spanish or Italian language studies containing original data related to COVID19, anosmia, fever, cough, and dyspnoea, in both hospital and non-hospital settings. Two investigators independently reviewed all manuscripts and performed quality assessment and quantitative meta-analysis using validated tools. A third author arbitrated full-text disagreements. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), 11 of 135 studies fulfilled eligibility. Anosmia was estimated less prevalent than fever and cough (respectively rate difference = − 0.316, 95% CI: − 0.574 to − 0.058, Z = − 2.404, p k = 11 and rate difference = − 0.249, 95% CI: − 0.402 to − 0.096, Z = − 3.185, p k = 11); the analysis between anosmia and dyspnoea was not significant (rate difference = − 0.008, 95% CI: − 0.166 to 0.150, Z = − 0.099, p k = 8). The typical symptoms were significantly more frequent than anosmia in hospitalized more critical patients than in non-hospitalized ones (respectively [Q(1) = 50.638 p Q(1) = 52.520 p Q(1) = 100.734 p Summary Patient with new onset olfactory dysfunction should be investigated for COVID-19. Anosmia is more frequent in non-hospitalized COVID-19 patients than in hospitalized ones.

Published
2020

48. Dizziness and Balance Problems in Children

Author

Marco Mandalà, Lorenzo Salerni, Soumit Dasgupta, Sudhira Ratnayake, and Rosa Crunkhorn

Subjects
Balance, medicine.medical_specialty, Neurology, medicine.medical_treatment, Dizziness, 03 medical and health sciences, 0302 clinical medicine, Multidisciplinary approach, Epidemiology, Medicine, Children, Balance (ability), Rehabilitation, Vestibular, business.industry, food and beverages, Cognition, Natural history, 030220 oncology & carcinogenesis, Physical therapy, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery, Balance problems
Abstract

Dizziness and balance problems in children can be multifactorial. Awareness regarding these disorders is limited. This paper reviews the existing literature in this field to raise the awareness of the discipline that can generate significant morbidity in children. It looks in detail into epidemiology, the aetiology, the diagnostic algorithm and the management of dizziness and balance problems in children. An accurate history followed by the latest diagnostic algorithm with the latest vestibular test battery that are utilised in adults can be used in children that lead to the diagnosis. The aetiological profile and natural history of different pathologies can be different from that in adults. Most cases can be managed successfully with multidisciplinary cognitive and customised rehabilitation approach. Diagnosis and management of dizziness and balance disorders in children require experience and skill to yield the best outcome. Research is needed to study application of individual tests for diagnosis in children and the behaviour of vestibular and central disorders in children.

Published
2020

49. Benign Paroxysmal Positional Vertigo: What We Do and Do Not Know

Author

Marco Mandalà, Daniele Nuti, and David S. Zee

Subjects
Pediatrics, medicine.medical_specialty, Benign paroxysmal positional vertigo, business.industry, Positional Nystagmus, Disease, 030204 cardiovascular system & hematology, medicine.disease, Review article, 03 medical and health sciences, 0302 clinical medicine, Neurology, Positional vertigo, otorhinolaryngologic diseases, Medicine, Humans, sense organs, Neurology (clinical), Benign Paroxysmal Positional Vertigo, business, 030217 neurology & neurosurgery
Abstract

Benign paroxysmal positional vertigo (BPPV) is common, sometimes terrifying, but rarely portends serious disease. It is usually easily diagnosed and treated, and both the patient and the physician are immediately gratified. While much has been learned about the pathogenesis of BPPV in the past decades, many of its features remain mysterious, and one must still be wary of the rare times it mimics a dangerous brain disorder. Here we review common, relatively well understood clinical features of BPPV but also emphasize what we do not know and when the physician must look deeper for a more ominous cause.

Published
2020

50. Double-Blind Randomized Trial on the Efficacy of the Forced Prolonged Position for Treatment of Lateral Canal Benign Paroxysmal Positional Vertigo

Author

Daniele Nuti, Giampiero Neri, Paolo Vannucchi, Soumit Dasgupta, Augusto Pietro Casani, Vincenzo Marcelli, Luigi Califano, Lorenzo Salerni, Rudi Pecci, Ilaria Bindi, Marco Mandalà, Felice Scasso, Beatrice Giannoni, Mario Faralli, and Leonardo Scotto di Santillo

Subjects
Adult, Male, Benign paroxysmal positional vertigo, Supine position, Adolescent, Lateral canal, law.invention, Double blind, evidence based, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Double-Blind Method, law, semicircular canals, Medicine, Humans, Sham treatment, 030223 otorhinolaryngology, double-blind randomized trial, forced prolonged position maneuver, lateral canal, vestibular, Physical Therapy Modalities, Aged, Vestibular system, Aged, 80 and over, business.industry, Middle Aged, medicine.disease, Otorhinolaryngology, Anesthesia, Female, business, 030217 neurology & neurosurgery
Abstract

OBJECTIVES/HYPOTHESIS The need for class I and II studies on the efficacy of liberatory maneuvers in the treatment of lateral canal benign paroxysmal positional vertigo (LC-BPPV) motivated the present double-blind randomized trial on the short-term efficacy of the forced prolonged position (FPP). STUDY DESIGN Double-blind, randomized controlled trial. METHODS Two hundred twenty-one patients with unilateral LC-BPPV met the inclusion criteria for a multicentric study. Patients were randomly assigned to treatment by FPP (116 subjects) or sham treatment (105 subjects). Subjects were followed up at 24 hours with the supine roll test by blinded examiners. RESULTS Among the sample, 67.4% and 32.6% of the patients showed respectively geotropic and apogeotropic variant of LC-BPPV. At the 24-hour follow-up, the effectiveness of FFP compared to the sham maneuver was, respectively, 57.8% versus 12.4% (P

Published
2020

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