Author: "Bombaci A." / Publication Type: Electronic Resources - Searchworks@Jio Institute Digital Library Search Results

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184 results on '"Bombaci A."'

1. Neurological Consequences of COVID-19: A Systematic Review of the Pandemic’s Impact on Neurology Training

Author: Ercoli, T, Barbato, F, Bombaci, A, Cuffaro, L, Di Lorenzo, F, Iodice, F, Romoli, M, Solla, P, Defazio, G, Ercoli T., Barbato F., Bombaci A., Cuffaro L., Di Lorenzo F., Iodice F., Romoli M., Solla P., Defazio G., Ercoli, T, Barbato, F, Bombaci, A, Cuffaro, L, Di Lorenzo, F, Iodice, F, Romoli, M, Solla, P, Defazio, G, Ercoli T., Barbato F., Bombaci A., Cuffaro L., Di Lorenzo F., Iodice F., Romoli M., Solla P., and Defazio G.
Abstract: The COVID-19 pandemic had a significant impact on neurology training programs, leading to disruptions and changes that may have long-term implications for neurological education. The objective of this study was to investigate the impact of COVID-19 on neurological training programs, collecting available data relating to residents’ experience worldwide. We performed a systematic search of the literature published on PubMed from January 2020 to March 2023, including studies referring to quantitative analysis of residents’/trainees’ perspectives. Specifically, we included studies that examined how the pandemic has affected clinical and research activities, the use of telemedicine, the delivery of education and the psychological status of residents. Of the 95460 studies identified through database searching, 12 studies met the full criteria and underwent data extraction. In conclusion, the COVID-19 pandemic has had significant impacts on neurology training programs, highlighting the need for resilience and flexibility in medical education. Future research should focus on the long-term outcomes of these adaptations in the quality of neurology education and patient care.
Published: 2023

2. Chronic cholesterol administration to the brain supports complete and long-lasting cognitive and motor amelioration in Huntington's disease

Author: Birolini, G, Valenza, M, Ottonelli, I, Talpo, F, Minoli, L, Cappelleri, A, Bombaci, M, Caccia, C, Canevari, C, Trucco, A, Leoni, V, Passoni, A, Favagrossa, M, Nucera, M, Colombo, L, Paltrinieri, S, Bagnati, R, Duskey, J, Caraffi, R, Vandelli, M, Taroni, F, Salmona, M, Scanziani, E, Biella, G, Ruozi, B, Tosi, G, Cattaneo, E, Birolini G., Valenza M., Ottonelli I., Talpo F., Minoli L., Cappelleri A., Bombaci M., Caccia C., Canevari C., Trucco A., Leoni V., Passoni A., Favagrossa M., Nucera M. R., Colombo L., Paltrinieri S., Bagnati R., Duskey J. T., Caraffi R., Vandelli M. A., Taroni F., Salmona M., Scanziani E., Biella G., Ruozi B., Tosi G., Cattaneo E., Birolini, G, Valenza, M, Ottonelli, I, Talpo, F, Minoli, L, Cappelleri, A, Bombaci, M, Caccia, C, Canevari, C, Trucco, A, Leoni, V, Passoni, A, Favagrossa, M, Nucera, M, Colombo, L, Paltrinieri, S, Bagnati, R, Duskey, J, Caraffi, R, Vandelli, M, Taroni, F, Salmona, M, Scanziani, E, Biella, G, Ruozi, B, Tosi, G, Cattaneo, E, Birolini G., Valenza M., Ottonelli I., Talpo F., Minoli L., Cappelleri A., Bombaci M., Caccia C., Canevari C., Trucco A., Leoni V., Passoni A., Favagrossa M., Nucera M. R., Colombo L., Paltrinieri S., Bagnati R., Duskey J. T., Caraffi R., Vandelli M. A., Taroni F., Salmona M., Scanziani E., Biella G., Ruozi B., Tosi G., and Cattaneo E.
Abstract: Evidence that Huntington's disease (HD) is characterized by impaired cholesterol biosynthesis in the brain has led to strategies to increase its level in the brain of the rapidly progressing R6/2 mouse model, with a positive therapeutic outcome. Here we tested the long-term efficacy of chronic administration of cholesterol to the brain of the slowly progressing zQ175DN knock-in HD mice in preventing (“early treatment”) or reversing (“late treatment”) HD symptoms. To do this we used the most advanced formulation of cholesterol loaded brain-permeable nanoparticles (NPs), termed hybrid-g7-NPs-chol, which were injected intraperitoneally. We show that one cycle of treatment with hybrid-g7-NPs-chol, administered in the presymptomatic (“early treatment”) or symptomatic (“late treatment”) stages is sufficient to normalize cognitive defects up to 5 months, as well as to improve other behavioral and neuropathological parameters. A multiple cycle treatment combining both early and late treatments (“2 cycle treatment”) lasting 6 months generates therapeutic effects for more than 11 months, without severe adverse reactions. Sustained cholesterol delivery to the brain of zQ175DN mice also reduces mutant Huntingtin aggregates in both the striatum and cortex and completely normalizes synaptic communication in the striatal medium spiny neurons compared to saline-treated HD mice. Furthermore, through a meta-analysis of published and current data, we demonstrated the power of hybrid-g7-NPs-chol and other strategies able to increase brain cholesterol biosynthesis, to reverse cognitive decline and counteract the formation of mutant Huntingtin aggregates. These results demonstrate that cholesterol delivery via brain-permeable NPs is a therapeutic option to sustainably reverse HD-related behavioral decline and neuropathological signs over time, highlighting the therapeutic potential of cholesterol-based strategies in HD patients. Data availability: This study does not include data deposit
Published: 2023

3. The future of neurology after the COVID-19 pandemic according to neurology residents

Author: Ercoli, T, Barbato, F, Cuffaro, L, Iodice, F, Romoli, M, Tedeschi, G, Berardelli, A, Di Lorenzo, F, Bombaci, A, Ercoli T., Barbato F., Cuffaro L., Iodice F., Romoli M., Tedeschi G., Berardelli A., Di Lorenzo F., Bombaci A., Ercoli, T, Barbato, F, Cuffaro, L, Iodice, F, Romoli, M, Tedeschi, G, Berardelli, A, Di Lorenzo, F, Bombaci, A, Ercoli T., Barbato F., Cuffaro L., Iodice F., Romoli M., Tedeschi G., Berardelli A., Di Lorenzo F., and Bombaci A.
Abstract: Background: The ongoing COVID-19 pandemic has resulted in significant changes in the delivery of neurological disease care and in neurology training in academic departments. Objective: We aimed to investigate how neurology residents viewed the future of neurology after the COVID-19 pandemic with regard to three main aspects: (i) organization of neurological activity, (ii) patient care, and (iii) funding availability for neurological diseases. Methods: We surveyed Italian neurology residents in order to investigate how they viewed the future of neurology after the COVID-19 pandemic. Results: Responses were collected from 254 residents who reported: a high risk of reduction of hospital neurological beds, of worsening of the quality of neurological patient management, and of lack of funding for neurological care and research. Conclusion: The survey results demonstrate the views of future neurologists regarding the direction of neurology after the COVID-19 emergency. It is important to focus on these aspects in order to adapt neurology training to the societal changes introduced by the pandemic, and to safeguard the essential role of neurology in the management and prevention of chronic degenerative illnesses and emergencies.
Published: 2023

4. Immunosuppressant Treatment in Rheumatic Musculoskeletal Diseases Does Not Inhibit Elicitation of Humoral Response to SARS-CoV-2 Infection and Preserves Effector Immune Cell Populations

Author: Favalli, A, Favalli, E, Gobbini, A, Zagato, E, Bombaci, M, Maioli, G, Pesce, E, Donnici, L, Gruarin, P, Biggioggero, M, Curti, S, Manganaro, L, Marchisio, E, Bevilacqua, V, Martinovic, M, Fabbris, T, Sarnicola, M, Crosti, M, Marongiu, L, Granucci, F, Notarbartolo, S, Bandera, A, Gori, A, De Francesco, R, Abrignani, S, Caporali, R, Grifantini, R, Favalli A., Favalli E. G., Gobbini A., Zagato E., Bombaci M., Maioli G., Pesce E., Donnici L., Gruarin P., Biggioggero M., Curti S., Manganaro L., Marchisio E., Bevilacqua V., Martinovic M., Fabbris T., Sarnicola M. L., Crosti M., Marongiu L., Granucci F., Notarbartolo S., Bandera A., Gori A., De Francesco R., Abrignani S., Caporali R., Grifantini R., Favalli, A, Favalli, E, Gobbini, A, Zagato, E, Bombaci, M, Maioli, G, Pesce, E, Donnici, L, Gruarin, P, Biggioggero, M, Curti, S, Manganaro, L, Marchisio, E, Bevilacqua, V, Martinovic, M, Fabbris, T, Sarnicola, M, Crosti, M, Marongiu, L, Granucci, F, Notarbartolo, S, Bandera, A, Gori, A, De Francesco, R, Abrignani, S, Caporali, R, Grifantini, R, Favalli A., Favalli E. G., Gobbini A., Zagato E., Bombaci M., Maioli G., Pesce E., Donnici L., Gruarin P., Biggioggero M., Curti S., Manganaro L., Marchisio E., Bevilacqua V., Martinovic M., Fabbris T., Sarnicola M. L., Crosti M., Marongiu L., Granucci F., Notarbartolo S., Bandera A., Gori A., De Francesco R., Abrignani S., Caporali R., and Grifantini R.
Published: 2022

5. Corrigendum: The Impact of Anti-rheumatic Drugs on the Seroprevalence of Anti-SARS-CoV-2 Antibodies in a Cohort of Patients With Inflammatory Arthritis: The MAINSTREAM Study(Front. Med., (2022), 9, (850858), 10.3389/fmed.2022.850858)

Author: Favalli E. G., Favalli, E, Gobbini, A, Bombaci, M, Maioli, G, Biggioggero, M, Pesce, E, Favalli, A, Martinovic, M, Fabbris, T, Marchisio, E, Bandera, A, Gori, A, Abrignani, S, Grifantini, R, Caporali, R, Favalli E. G., Gobbini A., Bombaci M., Maioli G., Biggioggero M., Pesce E., Favalli A., Martinovic M., Fabbris T., Marchisio E., Bandera A., Gori A., Abrignani S., Grifantini R., Caporali R., Favalli E. G., Favalli, E, Gobbini, A, Bombaci, M, Maioli, G, Biggioggero, M, Pesce, E, Favalli, A, Martinovic, M, Fabbris, T, Marchisio, E, Bandera, A, Gori, A, Abrignani, S, Grifantini, R, Caporali, R, Favalli E. G., Gobbini A., Bombaci M., Maioli G., Biggioggero M., Pesce E., Favalli A., Martinovic M., Fabbris T., Marchisio E., Bandera A., Gori A., Abrignani S., Grifantini R., and Caporali R.
Abstract: [This corrects the article DOI: 10.3389/fmed.2022.850858.]
Published: 2022

6. Author Correction: Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology (Nature Genetics, (2021), 53, 12, (1636-1648), 10.1038/s41588-021-00973-1)

Author: van Rheenen W., van Rheenen, W, van der Spek, R, Bakker, M, van Vugt, J, Hop, P, Zwamborn, R, de Klein, N, Westra, H, Bakker, O, Deelen, P, Shireby, G, Hannon, E, Moisse, M, Baird, D, Restuadi, R, Dolzhenko, E, Dekker, A, Gawor, K, Westeneng, H, Tazelaar, G, van Eijk, K, Kooyman, M, Byrne, R, Doherty, M, Heverin, M, Al Khleifat, A, Iacoangeli, A, Shatunov, A, Ticozzi, N, Cooper-Knock, J, Smith, B, Gromicho, M, Chandran, S, Pal, S, Morrison, K, Shaw, P, Hardy, J, Orrell, R, Sendtner, M, Meyer, T, Basak, N, van der Kooi, A, Ratti, A, Fogh, I, Gellera, C, Lauria, G, Corti, S, Cereda, C, Sproviero, D, D'Alfonso, S, Soraru, G, Siciliano, G, Filosto, M, Padovani, A, Chio, A, Calvo, A, Moglia, C, Brunetti, M, Canosa, A, Grassano, M, Beghi, E, Pupillo, E, Logroscino, G, Nefussy, B, Osmanovic, A, Nordin, A, Lerner, Y, Zabari, M, Gotkine, M, Baloh, R, Bell, S, Vourc'H, P, Corcia, P, Couratier, P, Millecamps, S, Meininger, V, Salachas, F, Mora Pardina, J, Assialioui, A, Rojas-Garcia, R, Dion, P, Ross, J, Ludolph, A, Weishaupt, J, Brenner, D, Freischmidt, A, Bensimon, G, Brice, A, Durr, A, Payan, C, Saker-Delye, S, Wood, N, Topp, S, Rademakers, R, Tittmann, L, Lieb, W, Franke, A, Ripke, S, Braun, A, Kraft, J, Whiteman, D, Olsen, C, Uitterlinden, A, Hofman, A, Rietschel, M, Cichon, S, Nothen, M, Amouyel, P, Comi, G, Riva, N, Lunetta, C, Gerardi, F, Cotelli, M, Rinaldi, F, Chiveri, L, Guaita, M, Perrone, P, Ceroni, M, Diamanti, L, Ferrarese, C, Tremolizzo, L, Delodovici, M, Bono, G, Manera, U, Vasta, R, Bombaci, A, Casale, F, Fuda, G, Salamone, P, Iazzolino, B, Peotta, L, Cugnasco, P, De Marco, G, Torrieri, M, Palumbo, F, Gallone, S, Barberis, M, Sbaiz, L, Gentile, S, Mauro, A, Mazzini, L, De Marchi, F, Corrado, L, Bertolotto, A, Gionco, M, Leotta, D, Odddenino, E, Imperiale, D, Cavallo, R, Pignatta, P, De Mattei, M, Geda, C, Papurello, D, Gusmaroli, G, Comi, C, Labate, C, Ruiz, L, Ferrandi, D, Rota, E, Aguggia, M, Di Vito, N, Meineri, P, Ghiglione, P, Launaro, N, Dotta, M, Di Sapio, A, Giardini, G, Tiloca, C, Peverelli, S, Taroni, F, Pensato, V, Castellotti, B, Del Bo, R, Gagliardi, S, Raggi, F, Simoncini, C, Lo Gerfo, A, Inghilleri, M, Ferlini, A, Simone, I, Passarella, B, Guerra, V, Zoccolella, S, Nozzoli, C, Mundi, C, Leone, M, Zarrelli, M, Tamma, F, Valluzzi, F, Calabrese, G, Boero, G, Rini, A, Traynor, B, Singleton, A, Mitne Neto, M, Cauchi, R, Ophoff, R, Wiedau-Pazos, M, Lomen-Hoerth, C, van Deerlin, V, Grosskreutz, J, Roediger, A, Gaur, N, Jork, A, Barthel, T, Theele, E, Ilse, B, Stubendorff, B, Witte, O, Steinbach, R, Hubner, C, Graff, C, Brylev, L, Fominykh, V, Demeshonok, V, Ataulina, A, Rogelj, B, Koritnik, B, Zidar, J, Ravnik-Glavac, M, Glavac, D, Stevic, Z, Drory, V, Povedano, M, Blair, I, Kiernan, M, Benyamin, B, Henderson, R, Furlong, S, Mathers, S, Mccombe, P, Needham, M, Ngo, S, Nicholson, G, Pamphlett, R, Rowe, D, Steyn, F, Williams, K, Mather, K, Sachdev, P, Henders, A, Wallace, L, de Carvalho, M, Pinto, S, Petri, S, Weber, M, Rouleau, G, Silani, V, Curtis, C, Breen, G, Glass, J, Brown, R, Landers, J, Shaw, C, Andersen, P, Groen, E, van Es, M, Pasterkamp, R, Fan, D, Garton, F, Mcrae, A, Davey Smith, G, Gaunt, T, Eberle, M, Mill, J, Mclaughlin, R, Hardiman, O, Kenna, K, Wray, N, Tsai, E, Runz, H, Franke, L, Al-Chalabi, A, Van Damme, P, van den Berg, L, Veldink, J, van Rheenen W., van der Spek R. A. A., Bakker M. K., van Vugt J. J. F. A., Hop P. J., Zwamborn R. A. J., de Klein N., Westra H. -J., Bakker O. B., Deelen P., Shireby G., Hannon E., Moisse M., Baird D., Restuadi R., Dolzhenko E., Dekker A. M., Gawor K., Westeneng H. -J., Tazelaar G. H. P., van Eijk K. R., Kooyman M., Byrne R. P., Doherty M., Heverin M., Al Khleifat A., Iacoangeli A., Shatunov A., Ticozzi N., Cooper-Knock J., Smith B. N., Gromicho M., Chandran S., Pal S., Morrison K. E., Shaw P. J., Hardy J., Orrell R. W., Sendtner M., Meyer T., Basak N., van der Kooi A. J., Ratti A., Fogh I., Gellera C., Lauria G., Corti S., Cereda C., Sproviero D., D'Alfonso S., Soraru G., Siciliano G., Filosto M., Padovani A., Chio A., Calvo A., Moglia C., Brunetti M., Canosa A., Grassano M., Beghi E., Pupillo E., Logroscino G., Nefussy B., Osmanovic A., Nordin A., Lerner Y., Zabari M., Gotkine M., Baloh R. H., Bell S., Vourc'h P., Corcia P., Couratier P., Millecamps S., Meininger V., Salachas F., Mora Pardina J. S., Assialioui A., Rojas-Garcia R., Dion P. A., Ross J. P., Ludolph A. C., Weishaupt J. H., Brenner D., Freischmidt A., Bensimon G., Brice A., Durr A., Payan C. A. M., Saker-Delye S., Wood N. W., Topp S., Rademakers R., Tittmann L., Lieb W., Franke A., Ripke S., Braun A., Kraft J., Whiteman D. C., Olsen C. M., Uitterlinden A. G., Hofman A., Rietschel M., Cichon S., Nothen M. M., Amouyel P., Comi G., Riva N., Lunetta C., Gerardi F., Cotelli M. S., Rinaldi F., Chiveri L., Guaita M. C., Perrone P., Ceroni M., Diamanti L., Ferrarese C., Tremolizzo L., Delodovici M. L., Bono G., Manera U., Vasta R., Bombaci A., Casale F., Fuda G., Salamone P., Iazzolino B., Peotta L., Cugnasco P., De Marco G., Torrieri M. C., Palumbo F., Gallone S., Barberis M., Sbaiz L., Gentile S., Mauro A., Mazzini L., De Marchi F., Corrado L., Bertolotto A., Gionco M., Leotta D., Odddenino E., Imperiale D., Cavallo R., Pignatta P., De Mattei M., Geda C., Papurello D. M., Gusmaroli G., Comi C., Labate C., Ruiz L., Ferrandi D., Rota E., Aguggia M., Di Vito N., Meineri P., Ghiglione P., Launaro N., Dotta M., Di Sapio A., Giardini G., Tiloca C., Peverelli S., Taroni F., Pensato V., Castellotti B., Comi G. P., Del Bo R., Gagliardi S., Raggi F., Simoncini C., Lo Gerfo A., Inghilleri M., Ferlini A., Simone I. L., Passarella B., Guerra V., Zoccolella S., Nozzoli C., Mundi C., Leone M., Zarrelli M., Tamma F., Valluzzi F., Calabrese G., Boero G., Rini A., Traynor B. J., Singleton A. B., Mitne Neto M., Cauchi R. J., Ophoff R. A., Wiedau-Pazos M., Lomen-Hoerth C., van Deerlin V. M., Grosskreutz J., Roediger A., Gaur N., Jork A., Barthel T., Theele E., Ilse B., Stubendorff B., Witte O. W., Steinbach R., Hubner C. A., Graff C., Brylev L., Fominykh V., Demeshonok V., Ataulina A., Rogelj B., Koritnik B., Zidar J., Ravnik-Glavac M., Glavac D., Stevic Z., Drory V., Povedano M., Blair I. P., Kiernan M. C., Benyamin B., Henderson R. D., Furlong S., Mathers S., McCombe P. A., Needham M., Ngo S. T., Nicholson G. A., Pamphlett R., Rowe D. B., Steyn F. J., Williams K. L., Mather K. A., Sachdev P. S., Henders A. K., Wallace L., de Carvalho M., Pinto S., Petri S., Weber M., Rouleau G. A., Silani V., Curtis C. J., Breen G., Glass J. D., Brown R. H., Landers J. E., Shaw C. E., Andersen P. M., Groen E. J. N., van Es M. A., Pasterkamp R. J., Fan D., Garton F. C., McRae A. F., Davey Smith G., Gaunt T. R., Eberle M. A., Mill J., McLaughlin R. L., Hardiman O., Kenna K. P., Wray N. R., Tsai E., Runz H., Franke L., Al-Chalabi A., Van Damme P., van den Berg L. H., Veldink J. H., van Rheenen W., van Rheenen, W, van der Spek, R, Bakker, M, van Vugt, J, Hop, P, Zwamborn, R, de Klein, N, Westra, H, Bakker, O, Deelen, P, Shireby, G, Hannon, E, Moisse, M, Baird, D, Restuadi, R, Dolzhenko, E, Dekker, A, Gawor, K, Westeneng, H, Tazelaar, G, van Eijk, K, Kooyman, M, Byrne, R, Doherty, M, Heverin, M, Al Khleifat, A, Iacoangeli, A, Shatunov, A, Ticozzi, N, Cooper-Knock, J, Smith, B, Gromicho, M, Chandran, S, Pal, S, Morrison, K, Shaw, P, Hardy, J, Orrell, R, Sendtner, M, Meyer, T, Basak, N, van der Kooi, A, Ratti, A, Fogh, I, Gellera, C, Lauria, G, Corti, S, Cereda, C, Sproviero, D, D'Alfonso, S, Soraru, G, Siciliano, G, Filosto, M, Padovani, A, Chio, A, Calvo, A, Moglia, C, Brunetti, M, Canosa, A, Grassano, M, Beghi, E, Pupillo, E, Logroscino, G, Nefussy, B, Osmanovic, A, Nordin, A, Lerner, Y, Zabari, M, Gotkine, M, Baloh, R, Bell, S, Vourc'H, P, Corcia, P, Couratier, P, Millecamps, S, Meininger, V, Salachas, F, Mora Pardina, J, Assialioui, A, Rojas-Garcia, R, Dion, P, Ross, J, Ludolph, A, Weishaupt, J, Brenner, D, Freischmidt, A, Bensimon, G, Brice, A, Durr, A, Payan, C, Saker-Delye, S, Wood, N, Topp, S, Rademakers, R, Tittmann, L, Lieb, W, Franke, A, Ripke, S, Braun, A, Kraft, J, Whiteman, D, Olsen, C, Uitterlinden, A, Hofman, A, Rietschel, M, Cichon, S, Nothen, M, Amouyel, P, Comi, G, Riva, N, Lunetta, C, Gerardi, F, Cotelli, M, Rinaldi, F, Chiveri, L, Guaita, M, Perrone, P, Ceroni, M, Diamanti, L, Ferrarese, C, Tremolizzo, L, Delodovici, M, Bono, G, Manera, U, Vasta, R, Bombaci, A, Casale, F, Fuda, G, Salamone, P, Iazzolino, B, Peotta, L, Cugnasco, P, De Marco, G, Torrieri, M, Palumbo, F, Gallone, S, Barberis, M, Sbaiz, L, Gentile, S, Mauro, A, Mazzini, L, De Marchi, F, Corrado, L, Bertolotto, A, Gionco, M, Leotta, D, Odddenino, E, Imperiale, D, Cavallo, R, Pignatta, P, De Mattei, M, Geda, C, Papurello, D, Gusmaroli, G, Comi, C, Labate, C, Ruiz, L, Ferrandi, D, Rota, E, Aguggia, M, Di Vito, N, Meineri, P, Ghiglione, P, Launaro, N, Dotta, M, Di Sapio, A, Giardini, G, Tiloca, C, Peverelli, S, Taroni, F, Pensato, V, Castellotti, B, Del Bo, R, Gagliardi, S, Raggi, F, Simoncini, C, Lo Gerfo, A, Inghilleri, M, Ferlini, A, Simone, I, Passarella, B, Guerra, V, Zoccolella, S, Nozzoli, C, Mundi, C, Leone, M, Zarrelli, M, Tamma, F, Valluzzi, F, Calabrese, G, Boero, G, Rini, A, Traynor, B, Singleton, A, Mitne Neto, M, Cauchi, R, Ophoff, R, Wiedau-Pazos, M, Lomen-Hoerth, C, van Deerlin, V, Grosskreutz, J, Roediger, A, Gaur, N, Jork, A, Barthel, T, Theele, E, Ilse, B, Stubendorff, B, Witte, O, Steinbach, R, Hubner, C, Graff, C, Brylev, L, Fominykh, V, Demeshonok, V, Ataulina, A, Rogelj, B, Koritnik, B, Zidar, J, Ravnik-Glavac, M, Glavac, D, Stevic, Z, Drory, V, Povedano, M, Blair, I, Kiernan, M, Benyamin, B, Henderson, R, Furlong, S, Mathers, S, Mccombe, P, Needham, M, Ngo, S, Nicholson, G, Pamphlett, R, Rowe, D, Steyn, F, Williams, K, Mather, K, Sachdev, P, Henders, A, Wallace, L, de Carvalho, M, Pinto, S, Petri, S, Weber, M, Rouleau, G, Silani, V, Curtis, C, Breen, G, Glass, J, Brown, R, Landers, J, Shaw, C, Andersen, P, Groen, E, van Es, M, Pasterkamp, R, Fan, D, Garton, F, Mcrae, A, Davey Smith, G, Gaunt, T, Eberle, M, Mill, J, Mclaughlin, R, Hardiman, O, Kenna, K, Wray, N, Tsai, E, Runz, H, Franke, L, Al-Chalabi, A, Van Damme, P, van den Berg, L, Veldink, J, van Rheenen W., van der Spek R. A. A., Bakker M. K., van Vugt J. J. F. A., Hop P. J., Zwamborn R. A. J., de Klein N., Westra H. -J., Bakker O. B., Deelen P., Shireby G., Hannon E., Moisse M., Baird D., Restuadi R., Dolzhenko E., Dekker A. M., Gawor K., Westeneng H. -J., Tazelaar G. H. P., van Eijk K. R., Kooyman M., Byrne R. P., Doherty M., Heverin M., Al Khleifat A., Iacoangeli A., Shatunov A., Ticozzi N., Cooper-Knock J., Smith B. N., Gromicho M., Chandran S., Pal S., Morrison K. E., Shaw P. J., Hardy J., Orrell R. W., Sendtner M., Meyer T., Basak N., van der Kooi A. J., Ratti A., Fogh I., Gellera C., Lauria G., Corti S., Cereda C., Sproviero D., D'Alfonso S., Soraru G., Siciliano G., Filosto M., Padovani A., Chio A., Calvo A., Moglia C., Brunetti M., Canosa A., Grassano M., Beghi E., Pupillo E., Logroscino G., Nefussy B., Osmanovic A., Nordin A., Lerner Y., Zabari M., Gotkine M., Baloh R. H., Bell S., Vourc'h P., Corcia P., Couratier P., Millecamps S., Meininger V., Salachas F., Mora Pardina J. S., Assialioui A., Rojas-Garcia R., Dion P. A., Ross J. P., Ludolph A. C., Weishaupt J. H., Brenner D., Freischmidt A., Bensimon G., Brice A., Durr A., Payan C. A. M., Saker-Delye S., Wood N. W., Topp S., Rademakers R., Tittmann L., Lieb W., Franke A., Ripke S., Braun A., Kraft J., Whiteman D. C., Olsen C. M., Uitterlinden A. G., Hofman A., Rietschel M., Cichon S., Nothen M. M., Amouyel P., Comi G., Riva N., Lunetta C., Gerardi F., Cotelli M. S., Rinaldi F., Chiveri L., Guaita M. C., Perrone P., Ceroni M., Diamanti L., Ferrarese C., Tremolizzo L., Delodovici M. L., Bono G., Manera U., Vasta R., Bombaci A., Casale F., Fuda G., Salamone P., Iazzolino B., Peotta L., Cugnasco P., De Marco G., Torrieri M. C., Palumbo F., Gallone S., Barberis M., Sbaiz L., Gentile S., Mauro A., Mazzini L., De Marchi F., Corrado L., Bertolotto A., Gionco M., Leotta D., Odddenino E., Imperiale D., Cavallo R., Pignatta P., De Mattei M., Geda C., Papurello D. M., Gusmaroli G., Comi C., Labate C., Ruiz L., Ferrandi D., Rota E., Aguggia M., Di Vito N., Meineri P., Ghiglione P., Launaro N., Dotta M., Di Sapio A., Giardini G., Tiloca C., Peverelli S., Taroni F., Pensato V., Castellotti B., Comi G. P., Del Bo R., Gagliardi S., Raggi F., Simoncini C., Lo Gerfo A., Inghilleri M., Ferlini A., Simone I. L., Passarella B., Guerra V., Zoccolella S., Nozzoli C., Mundi C., Leone M., Zarrelli M., Tamma F., Valluzzi F., Calabrese G., Boero G., Rini A., Traynor B. J., Singleton A. B., Mitne Neto M., Cauchi R. J., Ophoff R. A., Wiedau-Pazos M., Lomen-Hoerth C., van Deerlin V. M., Grosskreutz J., Roediger A., Gaur N., Jork A., Barthel T., Theele E., Ilse B., Stubendorff B., Witte O. W., Steinbach R., Hubner C. A., Graff C., Brylev L., Fominykh V., Demeshonok V., Ataulina A., Rogelj B., Koritnik B., Zidar J., Ravnik-Glavac M., Glavac D., Stevic Z., Drory V., Povedano M., Blair I. P., Kiernan M. C., Benyamin B., Henderson R. D., Furlong S., Mathers S., McCombe P. A., Needham M., Ngo S. T., Nicholson G. A., Pamphlett R., Rowe D. B., Steyn F. J., Williams K. L., Mather K. A., Sachdev P. S., Henders A. K., Wallace L., de Carvalho M., Pinto S., Petri S., Weber M., Rouleau G. A., Silani V., Curtis C. J., Breen G., Glass J. D., Brown R. H., Landers J. E., Shaw C. E., Andersen P. M., Groen E. J. N., van Es M. A., Pasterkamp R. J., Fan D., Garton F. C., McRae A. F., Davey Smith G., Gaunt T. R., Eberle M. A., Mill J., McLaughlin R. L., Hardiman O., Kenna K. P., Wray N. R., Tsai E., Runz H., Franke L., Al-Chalabi A., Van Damme P., van den Berg L. H., and Veldink J. H.
Abstract: In the version of this article initially published, the affiliation for Nazli Başak appeared incorrectly. Nazli Başak is at Koç University, School of Medicine, KUTTAM-NDAL, Istanbul, Turkey, and not Bogazici University. The error has been corrected in the HTML and PDF versions of the article.
Published: 2022

7. Telemedicine for management of patients with amyotrophic lateral sclerosis through COVID-19 tail

Author: Bombaci, A, Abbadessa, G, Trojsi, F, Leocani, L, Bonavita, S, Lavorgna, L, Tedeschi, G, Mancardi, G, Padovani, A, Clerico, M, Brigo, F, Lanzillo, R, Russo, A, Giometto, B, Straccia, G, Iodice, R, Bucello, S, Annovazzi, P, Moccia, M, Prosperini, L, Stromillo, M, Repice, A, Miele, G, Lerario, A, De Martino, A, Iodice, F, Di Lorenzo, F, Cuffaro, L, Romoli, M, Silvestro, M, Artusi, C, Bombaci A., Abbadessa G., Trojsi F., Leocani L., Bonavita S., Lavorgna L., Tedeschi G., Mancardi G., Padovani A., Clerico M., Brigo F., Lanzillo R., Russo A., Giometto B., Straccia G., Iodice R., Bucello S., Annovazzi P., Moccia M., Prosperini L., Stromillo M. L., Repice A. M., Miele G., Lerario A., De Martino A., Iodice F., Di Lorenzo F., Cuffaro L., Romoli M., Silvestro M., Artusi C. A., Bombaci, A, Abbadessa, G, Trojsi, F, Leocani, L, Bonavita, S, Lavorgna, L, Tedeschi, G, Mancardi, G, Padovani, A, Clerico, M, Brigo, F, Lanzillo, R, Russo, A, Giometto, B, Straccia, G, Iodice, R, Bucello, S, Annovazzi, P, Moccia, M, Prosperini, L, Stromillo, M, Repice, A, Miele, G, Lerario, A, De Martino, A, Iodice, F, Di Lorenzo, F, Cuffaro, L, Romoli, M, Silvestro, M, Artusi, C, Bombaci A., Abbadessa G., Trojsi F., Leocani L., Bonavita S., Lavorgna L., Tedeschi G., Mancardi G., Padovani A., Clerico M., Brigo F., Lanzillo R., Russo A., Giometto B., Straccia G., Iodice R., Bucello S., Annovazzi P., Moccia M., Prosperini L., Stromillo M. L., Repice A. M., Miele G., Lerario A., De Martino A., Iodice F., Di Lorenzo F., Cuffaro L., Romoli M., Silvestro M., and Artusi C. A.
Abstract: Over the last months, due to coronavirus disease (COVID-19) pandemic, containment measures have led to important social restriction. Healthcare systems have faced a complete rearrangement of resources and spaces, with the creation of wards devoted to COVID-19 patients. In this context, patients affected by chronic neurological diseases, such as amyotrophic lateral sclerosis (ALS), are at risk to be lost at follow-up, leading to a higher risk of morbidity and mortality. Telemedicine may allow meet the needs of these patients. In this commentary, we briefly discuss the digital tools to remotely monitor and manage ALS patients. Focusing on detecting disease progression and preventing life-threatening conditions, we propose a toolset able to improve ALS management during this unprecedented situation.
Published: 2021

8. COVID-19 impact on neurology training program in Italy

Author: Di Lorenzo, F, Ercoli, T, Cuffaro, L, Barbato, F, Iodice, F, Tedeschi, G, Bombaci, A, Di Lorenzo F., Ercoli T., Cuffaro L., Barbato F., Iodice F., Tedeschi G., Bombaci A., Di Lorenzo, F, Ercoli, T, Cuffaro, L, Barbato, F, Iodice, F, Tedeschi, G, Bombaci, A, Di Lorenzo F., Ercoli T., Cuffaro L., Barbato F., Iodice F., Tedeschi G., and Bombaci A.
Abstract: The ongoing COVID-19 pandemic is having a huge impact on clinical activity of all hospitals, including the ones involved in training of residents. In addition, neurology residents underwent substantial modifications of their training program. Aim of our investigation was to evaluate the impact of COVID-19 pandemic on the educational activities of Italian neurology residents through an online questionnaire delivered to neurology residents. The results obtained showed that almost 30% of the respondents were redistributed to COVID-19 units. Neurology departments underwent substantial modifications of their organization influencing clinical educational activities; lessons and seminars were rescheduled online and research protocols were stopped and transferred to remote working, when feasible. There was a relevant use of telemedicine approach even if most of the respondents had never been trained before. Some of the changes had a North-South gradient, following the epidemiology of the pandemic. The data obtained from our survey highlight those points to address to be prepared for possible future emergencies.
Published: 2021

9. Integrated longitudinal immunophenotypic, transcriptional and repertoire analyses delineate immune responses in COVID-19 patients

Author: Notarbartolo, S, Ranzani, V, Bandera, A, Gruarin, P, Bevilacqua, V, Putignano, A, Gobbini, A, Galeota, E, Manara, C, Bombaci, M, Pesce, E, Zagato, E, Favalli, A, Sarnicola, M, Curti, S, Crosti, M, Martinovic, M, Fabbris, T, Marini, F, Donnici, L, Lorenzo, M, Mancino, M, Ungaro, R, Lombardi, A, Mangioni, D, Muscatello, A, Aliberti, S, Blasi, F, De Feo, T, Prati, D, Manganaro, L, Granucci, F, Lanzavecchia, A, De Francesco, R, Gori, A, Grifantini, R, Abrignani, S, Notarbartolo S., Ranzani V., Bandera A., Gruarin P., Bevilacqua V., Putignano A. R., Gobbini A., Galeota E., Manara C., Bombaci M., Pesce E., Zagato E., Favalli A., Sarnicola M. L., Curti S., Crosti M., Martinovic M., Fabbris T., Marini F., Donnici L., Lorenzo M., Mancino M., Ungaro R., Lombardi A., Mangioni D., Muscatello A., Aliberti S., Blasi F., De Feo T., Prati D., Manganaro L., Granucci F., Lanzavecchia A., De Francesco R., Gori A., Grifantini R., Abrignani S., Notarbartolo, S, Ranzani, V, Bandera, A, Gruarin, P, Bevilacqua, V, Putignano, A, Gobbini, A, Galeota, E, Manara, C, Bombaci, M, Pesce, E, Zagato, E, Favalli, A, Sarnicola, M, Curti, S, Crosti, M, Martinovic, M, Fabbris, T, Marini, F, Donnici, L, Lorenzo, M, Mancino, M, Ungaro, R, Lombardi, A, Mangioni, D, Muscatello, A, Aliberti, S, Blasi, F, De Feo, T, Prati, D, Manganaro, L, Granucci, F, Lanzavecchia, A, De Francesco, R, Gori, A, Grifantini, R, Abrignani, S, Notarbartolo S., Ranzani V., Bandera A., Gruarin P., Bevilacqua V., Putignano A. R., Gobbini A., Galeota E., Manara C., Bombaci M., Pesce E., Zagato E., Favalli A., Sarnicola M. L., Curti S., Crosti M., Martinovic M., Fabbris T., Marini F., Donnici L., Lorenzo M., Mancino M., Ungaro R., Lombardi A., Mangioni D., Muscatello A., Aliberti S., Blasi F., De Feo T., Prati D., Manganaro L., Granucci F., Lanzavecchia A., De Francesco R., Gori A., Grifantini R., and Abrignani S.
Abstract: To understand how a protective immune response against SARS-CoV-2 develops over time, we integrated phenotypic, transcriptional and repertoire analyses on PBMCs from mild and severe COVID-19 patients during and after infection, and compared them to healthy donors (HD). A type I IFN-response signature marked all the immune populations from severe patients during the infection. Humoral immunity was dominated by IgG production primarily against the RBD and N proteins, with neutralizing antibody titers increasing post infection and with disease severity. Memory B cells, including an atypical FCRL5+ T-BET+ memory subset, increased during the infection, especially in patients with mild disease. A significant reduction of effector memory, CD8+T cells frequency characterized patients with severe disease. Despite such impairment, we observed robust clonal expansion of CD8+T lymphocytes, while CD4+T cells were less expanded and skewed toward TCMand TH2-like phenotypes. MAIT cells were also expanded, but only in patients with mild disease. Terminally differentiated CD8+GZMB+effector cells were clonally expanded both during the infection and post-infection, while CD8+GZMK+lymphocytes were more expanded post-infection and represented bona fide memory precursor effector cells. TCR repertoire analysis revealed that only highly proliferating T cell clonotypes, which included SARS-CoV-2-specific cells, were maintained post-infection and shared between the CD8+GZMB+and GZMK+subsets. Overall, this study describes the development of immunity against SARS-CoV-2 and identifies an effector CD8+T cell population with memory precursor-like features.
Published: 2021

10. Insights into kinetics, release, and behavioral effects of brain-targeted hybrid nanoparticles for cholesterol delivery in Huntington's disease

Author: Birolini, G, Valenza, M, Ottonelli, I, Passoni, A, Favagrossa, M, Duskey, J, Bombaci, M, Vandelli, M, Colombo, L, Bagnati, R, Caccia, C, Leoni, V, Taroni, F, Forni, F, Ruozi, B, Salmona, M, Tosi, G, Cattaneo, E, Birolini G., Valenza M., Ottonelli I., Passoni A., Favagrossa M., Duskey J. T., Bombaci M., Vandelli M. A., Colombo L., Bagnati R., Caccia C., Leoni V., Taroni F., Forni F., Ruozi B., Salmona M., Tosi G., Cattaneo E., Birolini, G, Valenza, M, Ottonelli, I, Passoni, A, Favagrossa, M, Duskey, J, Bombaci, M, Vandelli, M, Colombo, L, Bagnati, R, Caccia, C, Leoni, V, Taroni, F, Forni, F, Ruozi, B, Salmona, M, Tosi, G, Cattaneo, E, Birolini G., Valenza M., Ottonelli I., Passoni A., Favagrossa M., Duskey J. T., Bombaci M., Vandelli M. A., Colombo L., Bagnati R., Caccia C., Leoni V., Taroni F., Forni F., Ruozi B., Salmona M., Tosi G., and Cattaneo E.
Abstract: Supplementing brain cholesterol is emerging as a potential treatment for Huntington's disease (HD), a genetic neurodegenerative disorder characterized, among other abnormalities, by inefficient brain cholesterol biosynthesis. However, delivering cholesterol to the brain is challenging due to the blood-brain barrier (BBB), which prevents it from reaching the striatum, especially, with therapeutically relevant doses. Here we describe the distribution, kinetics, release, and safety of novel hybrid polymeric nanoparticles made of PLGA and cholesterol which were modified with an heptapeptide (g7) for BBB transit (hybrid-g7-NPs-chol). We show that these NPs rapidly reach the brain and target neural cells. Moreover, deuterium-labeled cholesterol from hybrid-g7-NPs-chol is released in a controlled manner within the brain and accumulates over time, while being rapidly removed from peripheral tissues and plasma. We confirm that systemic and repeated injections of the new hybrid-g7-NPs-chol enhanced endogenous cholesterol biosynthesis, prevented cognitive decline, and ameliorated motor defects in HD animals, without any inflammatory reaction. In summary, this study provides insights about the benefits and safety of cholesterol delivery through advanced brain-permeable nanoparticles for HD treatment.
Published: 2021

11. Benchmark calculations of infinite neutron matter with realistic two- and three-nucleon potentials

Author: Lovato, A., Bombaci, I., Logoteta, D., Piarulli, M., Wiringa, R. B., Lovato, A., Bombaci, I., Logoteta, D., Piarulli, M., and Wiringa, R. B.
Abstract: We present the equation of state of infinite neutron matter as obtained from highly-realistic Hamiltonians that include nucleon-nucleon and three-nucleon coordinate-space potentials. We benchmark three independent many-body methods: Brueckner-Bethe-Goldstone (BBG), Fermi hypernetted chain/single-operator chain (FHNC/SOC), and auxiliary-field diffusion Monte Carlo (AFDMC). We find them to provide similar equations of state when the Argonne $v_{18}$ and the Argonne $v_{6}^\prime$ nucleon-nucleon potentials are used in combination with the Urbana IX three-body force. Only at densities larger than about 1.5 the nuclear saturation density ($\rho_0 = 0.16\,\rm{fm}^{-3}$) the FHNC/SOC energies are appreciably lower than the other two approaches. The AFDMC calculations carried out with all of the Norfolk potentials fitted to reproduce the experimental trinucleon ground-state energies and $nd$ doublet scattering length yield unphysically bound neutron matter, associated with the formation of neutron droplets. Including tritium $\beta$-decay in the fitting procedure, as in the second family of Norfolk potentials, mitigates but does not completely resolve this problem. An excellent agreement between the BBG and AFDMC results is found for the subset of Norfolk interactions that do not make neutron-matter collapse, while the FHNC/SOC equations of state are moderately softer., Comment: 15 pages, 3 figures. arXiv admin note: text overlap with arXiv:1908.04426
Published: 2022

12. Author Correction: Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Author: van Rheenen, W., van der Spek, R.A.A., Bakker, M.K., van Vugt, J.J.F.A., Hop, P.J., Zwamborn, R.A.J., de Klein, N., Westra, H-J, Bakker, O.B., Deelen, P., Shireby, G., Hannon, E., Moisse, M., Baird, D., Restuadi, R., Dolzhenko, E., Dekker, A.M., Gawor, K., Westeneng, H-J, Tazelaar, G.H.P., van Eijk, K.R., Kooyman, M., Byrne, R.P., Doherty, M., Heverin, M., Al Khleifat, A., Iacoangeli, A., Shatunov, A., Ticozzi, N., Cooper-Knock, J., Smith, B.N., Gromicho, M., Chandran, S., Pal, S., Morrison, K.E., Shaw, P.J., Hardy, J., Orrell, R.W., Sendtner, M., Meyer, T., Başak, N., van der Kooi, A.J., Ratti, A., Fogh, I., Gellera, C., Lauria, G., Corti, S., Cereda, C., Sproviero, D., D’alfonso, S., Sorarù, G., Siciliano, G., Filosto, M., Padovani, A., Chiò, A., Calvo, A., Moglia, C., Brunetti, M., Canosa, A., Grassano, M., Beghi, E., Pupillo, E., Logroscino, G., Nefussy, B., Osmanovic, A., Nordin, A., Lerner, Y., Zabari, M., Gotkine, M., Baloh, R.H., Bell, S., Vourc’h, P., Corcia, P., Couratier, P., Millecamps, S., Meininger, V., Salachas, F., Mora Pardina, J.S., Assialioui, A., Rojas-García, R., Dion, P.A., Ross, J.P., Ludolph, A.C., Weishaupt, J.H., Brenner, D., Freischmidt, A., Bensimon, G., Brice, A., Durr, A., Payan, C.A.M., Saker-Delye, S., Wood, N.W., Topp, S., Rademakers, R., Tittmann, L., Lieb, W., Franke, A., Ripke, S., Braun, A., Kraft, J., Whiteman, D.C., Olsen, C.M., Uitterlinden, A.G., Hofman, A., Rietschel, M., Cichon, S., Nöthen, M.M., Amouyel, P., Comi, G., Riva, N., Lunetta, C., Gerardi, F., Cotelli, M.S., Rinaldi, F., Chiveri, L., Guaita, M.C., Perrone, P., Ceroni, M., Diamanti, L., Ferrarese, C., Tremolizzo, L., Delodovici, M.L., Bono, G., Manera, U., Vasta, R., Bombaci, A., Casale, F., Fuda, G., Salamone, P., Iazzolino, B., Peotta, L., Cugnasco, P., De Marco, G., Torrieri, M.C., Palumbo, F., Gallone, S., Barberis, M., Sbaiz, L., Gentile, S., Mauro, A., Mazzini, L., De Marchi, F., Corrado, L., D’Alfonso, S., Bertolotto, A., Gionco, M., Leotta, D., Odddenino, E., Imperiale, D., Cavallo, R., Pignatta, P., De Mattei, M., Geda, C., Papurello, D.M., Gusmaroli, G., Comi, C., Labate, C., Ruiz, L., Ferrandi, D., Rota, E., Aguggia, M., Di Vito, N., Meineri, P., Ghiglione, P., Launaro, N., Dotta, M., Di Sapio, A., Giardini, G., Tiloca, C., Peverelli, S., Taroni, F., Pensato, V., Castellotti, B., Comi, G.P., Del Bo, R., Gagliardi, S., Raggi, F., Simoncini, C., Lo Gerfo, A., Inghilleri, M., Ferlini, A., Simone, I.L., Passarella, B., Guerra, V., Zoccolella, S., Nozzoli, C., Mundi, C., Leone, M., Zarrelli, M., Tamma, F., Valluzzi, F., Calabrese, G., Boero, G., Rini, A., Traynor, B.J., Singleton, A.B., Mitne Neto, M., Cauchi, R.J., Ophoff, R.A., Wiedau-Pazos, M., Lomen-Hoerth, C., van Deerlin, V.M., Grosskreutz, J., Roediger, A., Gaur, N., Jörk, A., Barthel, T., Theele, E., Ilse, B., Stubendorff, B., Witte, O.W., Steinbach, R., Hübner, C.A., Graff, C., Brylev, L., Fominykh, V., Demeshonok, V., Ataulina, A., Rogelj, B., Koritnik, B., Zidar, J., Ravnik-Glavač, M., Glavač, D., Stević, Z., Drory, V., Povedano, M., Blair, I.P., Kiernan, M.C., Benyamin, B., Henderson, R.D., Furlong, S., Mathers, S., McCombe, P.A., Needham, M., Ngo, S.T., Nicholson, G.A., Pamphlett, R., Rowe, D.B., Steyn, F.J., Williams, K.L., Mather, K.A., Sachdev, P.S., Henders, A.K., Wallace, L., de Carvalho, M., Pinto, S., Petri, S., Weber, M., Rouleau, G.A., Silani, V., Curtis, C.J., Breen, G., Glass, J.D., Brown, R.H., Landers, J.E., Shaw, C.E., Andersen, P.M., Groen, E.J.N., van Es, M.A., Pasterkamp, R.J., Fan, D., Garton, F.C., McRae, A.F., Davey Smith, G., Gaunt, T.R., Eberle, M.A., Mill, J., McLaughlin, R.L., Hardiman, O., Kenna, K.P., Wray, N.R., Tsai, E., Runz, H., Franke, L., Al-Chalabi, A., Van Damme, P., van den Berg, L.H., Veldink, J.H., van Rheenen, W., van der Spek, R.A.A., Bakker, M.K., van Vugt, J.J.F.A., Hop, P.J., Zwamborn, R.A.J., de Klein, N., Westra, H-J, Bakker, O.B., Deelen, P., Shireby, G., Hannon, E., Moisse, M., Baird, D., Restuadi, R., Dolzhenko, E., Dekker, A.M., Gawor, K., Westeneng, H-J, Tazelaar, G.H.P., van Eijk, K.R., Kooyman, M., Byrne, R.P., Doherty, M., Heverin, M., Al Khleifat, A., Iacoangeli, A., Shatunov, A., Ticozzi, N., Cooper-Knock, J., Smith, B.N., Gromicho, M., Chandran, S., Pal, S., Morrison, K.E., Shaw, P.J., Hardy, J., Orrell, R.W., Sendtner, M., Meyer, T., Başak, N., van der Kooi, A.J., Ratti, A., Fogh, I., Gellera, C., Lauria, G., Corti, S., Cereda, C., Sproviero, D., D’alfonso, S., Sorarù, G., Siciliano, G., Filosto, M., Padovani, A., Chiò, A., Calvo, A., Moglia, C., Brunetti, M., Canosa, A., Grassano, M., Beghi, E., Pupillo, E., Logroscino, G., Nefussy, B., Osmanovic, A., Nordin, A., Lerner, Y., Zabari, M., Gotkine, M., Baloh, R.H., Bell, S., Vourc’h, P., Corcia, P., Couratier, P., Millecamps, S., Meininger, V., Salachas, F., Mora Pardina, J.S., Assialioui, A., Rojas-García, R., Dion, P.A., Ross, J.P., Ludolph, A.C., Weishaupt, J.H., Brenner, D., Freischmidt, A., Bensimon, G., Brice, A., Durr, A., Payan, C.A.M., Saker-Delye, S., Wood, N.W., Topp, S., Rademakers, R., Tittmann, L., Lieb, W., Franke, A., Ripke, S., Braun, A., Kraft, J., Whiteman, D.C., Olsen, C.M., Uitterlinden, A.G., Hofman, A., Rietschel, M., Cichon, S., Nöthen, M.M., Amouyel, P., Comi, G., Riva, N., Lunetta, C., Gerardi, F., Cotelli, M.S., Rinaldi, F., Chiveri, L., Guaita, M.C., Perrone, P., Ceroni, M., Diamanti, L., Ferrarese, C., Tremolizzo, L., Delodovici, M.L., Bono, G., Manera, U., Vasta, R., Bombaci, A., Casale, F., Fuda, G., Salamone, P., Iazzolino, B., Peotta, L., Cugnasco, P., De Marco, G., Torrieri, M.C., Palumbo, F., Gallone, S., Barberis, M., Sbaiz, L., Gentile, S., Mauro, A., Mazzini, L., De Marchi, F., Corrado, L., D’Alfonso, S., Bertolotto, A., Gionco, M., Leotta, D., Odddenino, E., Imperiale, D., Cavallo, R., Pignatta, P., De Mattei, M., Geda, C., Papurello, D.M., Gusmaroli, G., Comi, C., Labate, C., Ruiz, L., Ferrandi, D., Rota, E., Aguggia, M., Di Vito, N., Meineri, P., Ghiglione, P., Launaro, N., Dotta, M., Di Sapio, A., Giardini, G., Tiloca, C., Peverelli, S., Taroni, F., Pensato, V., Castellotti, B., Comi, G.P., Del Bo, R., Gagliardi, S., Raggi, F., Simoncini, C., Lo Gerfo, A., Inghilleri, M., Ferlini, A., Simone, I.L., Passarella, B., Guerra, V., Zoccolella, S., Nozzoli, C., Mundi, C., Leone, M., Zarrelli, M., Tamma, F., Valluzzi, F., Calabrese, G., Boero, G., Rini, A., Traynor, B.J., Singleton, A.B., Mitne Neto, M., Cauchi, R.J., Ophoff, R.A., Wiedau-Pazos, M., Lomen-Hoerth, C., van Deerlin, V.M., Grosskreutz, J., Roediger, A., Gaur, N., Jörk, A., Barthel, T., Theele, E., Ilse, B., Stubendorff, B., Witte, O.W., Steinbach, R., Hübner, C.A., Graff, C., Brylev, L., Fominykh, V., Demeshonok, V., Ataulina, A., Rogelj, B., Koritnik, B., Zidar, J., Ravnik-Glavač, M., Glavač, D., Stević, Z., Drory, V., Povedano, M., Blair, I.P., Kiernan, M.C., Benyamin, B., Henderson, R.D., Furlong, S., Mathers, S., McCombe, P.A., Needham, M., Ngo, S.T., Nicholson, G.A., Pamphlett, R., Rowe, D.B., Steyn, F.J., Williams, K.L., Mather, K.A., Sachdev, P.S., Henders, A.K., Wallace, L., de Carvalho, M., Pinto, S., Petri, S., Weber, M., Rouleau, G.A., Silani, V., Curtis, C.J., Breen, G., Glass, J.D., Brown, R.H., Landers, J.E., Shaw, C.E., Andersen, P.M., Groen, E.J.N., van Es, M.A., Pasterkamp, R.J., Fan, D., Garton, F.C., McRae, A.F., Davey Smith, G., Gaunt, T.R., Eberle, M.A., Mill, J., McLaughlin, R.L., Hardiman, O., Kenna, K.P., Wray, N.R., Tsai, E., Runz, H., Franke, L., Al-Chalabi, A., Van Damme, P., van den Berg, L.H., and Veldink, J.H.
Abstract: Correction to: Nature Genetics https://doi.org/10.1038/s41588-021-00973-1, published online 6 December 2021. In the version of this article initially published, the affiliation for Nazli Başak appeared incorrectly. Nazli Başak is at Koç University, School of Medicine, KUTTAM-NDAL, Istanbul, Turkey, and not Bogazici University. The error has been corrected in the HTML and PDF versions of the article.
Published: 2022

13. Author Correction: Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Author: van Rheenen, W., van der Spek, R.A.A., Bakker, M.K., van Vugt, J.J.F.A., Hop, P.J., Zwamborn, R.A.J., de Klein, N., Westra, H-J, Bakker, O.B., Deelen, P., Shireby, G., Hannon, E., Moisse, M., Baird, D., Restuadi, R., Dolzhenko, E., Dekker, A.M., Gawor, K., Westeneng, H-J, Tazelaar, G.H.P., van Eijk, K.R., Kooyman, M., Byrne, R.P., Doherty, M., Heverin, M., Al Khleifat, A., Iacoangeli, A., Shatunov, A., Ticozzi, N., Cooper-Knock, J., Smith, B.N., Gromicho, M., Chandran, S., Pal, S., Morrison, K.E., Shaw, P.J., Hardy, J., Orrell, R.W., Sendtner, M., Meyer, T., Başak, N., van der Kooi, A.J., Ratti, A., Fogh, I., Gellera, C., Lauria, G., Corti, S., Cereda, C., Sproviero, D., D’alfonso, S., Sorarù, G., Siciliano, G., Filosto, M., Padovani, A., Chiò, A., Calvo, A., Moglia, C., Brunetti, M., Canosa, A., Grassano, M., Beghi, E., Pupillo, E., Logroscino, G., Nefussy, B., Osmanovic, A., Nordin, A., Lerner, Y., Zabari, M., Gotkine, M., Baloh, R.H., Bell, S., Vourc’h, P., Corcia, P., Couratier, P., Millecamps, S., Meininger, V., Salachas, F., Mora Pardina, J.S., Assialioui, A., Rojas-García, R., Dion, P.A., Ross, J.P., Ludolph, A.C., Weishaupt, J.H., Brenner, D., Freischmidt, A., Bensimon, G., Brice, A., Durr, A., Payan, C.A.M., Saker-Delye, S., Wood, N.W., Topp, S., Rademakers, R., Tittmann, L., Lieb, W., Franke, A., Ripke, S., Braun, A., Kraft, J., Whiteman, D.C., Olsen, C.M., Uitterlinden, A.G., Hofman, A., Rietschel, M., Cichon, S., Nöthen, M.M., Amouyel, P., Comi, G., Riva, N., Lunetta, C., Gerardi, F., Cotelli, M.S., Rinaldi, F., Chiveri, L., Guaita, M.C., Perrone, P., Ceroni, M., Diamanti, L., Ferrarese, C., Tremolizzo, L., Delodovici, M.L., Bono, G., Manera, U., Vasta, R., Bombaci, A., Casale, F., Fuda, G., Salamone, P., Iazzolino, B., Peotta, L., Cugnasco, P., De Marco, G., Torrieri, M.C., Palumbo, F., Gallone, S., Barberis, M., Sbaiz, L., Gentile, S., Mauro, A., Mazzini, L., De Marchi, F., Corrado, L., D’Alfonso, S., Bertolotto, A., Gionco, M., Leotta, D., Odddenino, E., Imperiale, D., Cavallo, R., Pignatta, P., De Mattei, M., Geda, C., Papurello, D.M., Gusmaroli, G., Comi, C., Labate, C., Ruiz, L., Ferrandi, D., Rota, E., Aguggia, M., Di Vito, N., Meineri, P., Ghiglione, P., Launaro, N., Dotta, M., Di Sapio, A., Giardini, G., Tiloca, C., Peverelli, S., Taroni, F., Pensato, V., Castellotti, B., Comi, G.P., Del Bo, R., Gagliardi, S., Raggi, F., Simoncini, C., Lo Gerfo, A., Inghilleri, M., Ferlini, A., Simone, I.L., Passarella, B., Guerra, V., Zoccolella, S., Nozzoli, C., Mundi, C., Leone, M., Zarrelli, M., Tamma, F., Valluzzi, F., Calabrese, G., Boero, G., Rini, A., Traynor, B.J., Singleton, A.B., Mitne Neto, M., Cauchi, R.J., Ophoff, R.A., Wiedau-Pazos, M., Lomen-Hoerth, C., van Deerlin, V.M., Grosskreutz, J., Roediger, A., Gaur, N., Jörk, A., Barthel, T., Theele, E., Ilse, B., Stubendorff, B., Witte, O.W., Steinbach, R., Hübner, C.A., Graff, C., Brylev, L., Fominykh, V., Demeshonok, V., Ataulina, A., Rogelj, B., Koritnik, B., Zidar, J., Ravnik-Glavač, M., Glavač, D., Stević, Z., Drory, V., Povedano, M., Blair, I.P., Kiernan, M.C., Benyamin, B., Henderson, R.D., Furlong, S., Mathers, S., McCombe, P.A., Needham, M., Ngo, S.T., Nicholson, G.A., Pamphlett, R., Rowe, D.B., Steyn, F.J., Williams, K.L., Mather, K.A., Sachdev, P.S., Henders, A.K., Wallace, L., de Carvalho, M., Pinto, S., Petri, S., Weber, M., Rouleau, G.A., Silani, V., Curtis, C.J., Breen, G., Glass, J.D., Brown, R.H., Landers, J.E., Shaw, C.E., Andersen, P.M., Groen, E.J.N., van Es, M.A., Pasterkamp, R.J., Fan, D., Garton, F.C., McRae, A.F., Davey Smith, G., Gaunt, T.R., Eberle, M.A., Mill, J., McLaughlin, R.L., Hardiman, O., Kenna, K.P., Wray, N.R., Tsai, E., Runz, H., Franke, L., Al-Chalabi, A., Van Damme, P., van den Berg, L.H., Veldink, J.H., van Rheenen, W., van der Spek, R.A.A., Bakker, M.K., van Vugt, J.J.F.A., Hop, P.J., Zwamborn, R.A.J., de Klein, N., Westra, H-J, Bakker, O.B., Deelen, P., Shireby, G., Hannon, E., Moisse, M., Baird, D., Restuadi, R., Dolzhenko, E., Dekker, A.M., Gawor, K., Westeneng, H-J, Tazelaar, G.H.P., van Eijk, K.R., Kooyman, M., Byrne, R.P., Doherty, M., Heverin, M., Al Khleifat, A., Iacoangeli, A., Shatunov, A., Ticozzi, N., Cooper-Knock, J., Smith, B.N., Gromicho, M., Chandran, S., Pal, S., Morrison, K.E., Shaw, P.J., Hardy, J., Orrell, R.W., Sendtner, M., Meyer, T., Başak, N., van der Kooi, A.J., Ratti, A., Fogh, I., Gellera, C., Lauria, G., Corti, S., Cereda, C., Sproviero, D., D’alfonso, S., Sorarù, G., Siciliano, G., Filosto, M., Padovani, A., Chiò, A., Calvo, A., Moglia, C., Brunetti, M., Canosa, A., Grassano, M., Beghi, E., Pupillo, E., Logroscino, G., Nefussy, B., Osmanovic, A., Nordin, A., Lerner, Y., Zabari, M., Gotkine, M., Baloh, R.H., Bell, S., Vourc’h, P., Corcia, P., Couratier, P., Millecamps, S., Meininger, V., Salachas, F., Mora Pardina, J.S., Assialioui, A., Rojas-García, R., Dion, P.A., Ross, J.P., Ludolph, A.C., Weishaupt, J.H., Brenner, D., Freischmidt, A., Bensimon, G., Brice, A., Durr, A., Payan, C.A.M., Saker-Delye, S., Wood, N.W., Topp, S., Rademakers, R., Tittmann, L., Lieb, W., Franke, A., Ripke, S., Braun, A., Kraft, J., Whiteman, D.C., Olsen, C.M., Uitterlinden, A.G., Hofman, A., Rietschel, M., Cichon, S., Nöthen, M.M., Amouyel, P., Comi, G., Riva, N., Lunetta, C., Gerardi, F., Cotelli, M.S., Rinaldi, F., Chiveri, L., Guaita, M.C., Perrone, P., Ceroni, M., Diamanti, L., Ferrarese, C., Tremolizzo, L., Delodovici, M.L., Bono, G., Manera, U., Vasta, R., Bombaci, A., Casale, F., Fuda, G., Salamone, P., Iazzolino, B., Peotta, L., Cugnasco, P., De Marco, G., Torrieri, M.C., Palumbo, F., Gallone, S., Barberis, M., Sbaiz, L., Gentile, S., Mauro, A., Mazzini, L., De Marchi, F., Corrado, L., D’Alfonso, S., Bertolotto, A., Gionco, M., Leotta, D., Odddenino, E., Imperiale, D., Cavallo, R., Pignatta, P., De Mattei, M., Geda, C., Papurello, D.M., Gusmaroli, G., Comi, C., Labate, C., Ruiz, L., Ferrandi, D., Rota, E., Aguggia, M., Di Vito, N., Meineri, P., Ghiglione, P., Launaro, N., Dotta, M., Di Sapio, A., Giardini, G., Tiloca, C., Peverelli, S., Taroni, F., Pensato, V., Castellotti, B., Comi, G.P., Del Bo, R., Gagliardi, S., Raggi, F., Simoncini, C., Lo Gerfo, A., Inghilleri, M., Ferlini, A., Simone, I.L., Passarella, B., Guerra, V., Zoccolella, S., Nozzoli, C., Mundi, C., Leone, M., Zarrelli, M., Tamma, F., Valluzzi, F., Calabrese, G., Boero, G., Rini, A., Traynor, B.J., Singleton, A.B., Mitne Neto, M., Cauchi, R.J., Ophoff, R.A., Wiedau-Pazos, M., Lomen-Hoerth, C., van Deerlin, V.M., Grosskreutz, J., Roediger, A., Gaur, N., Jörk, A., Barthel, T., Theele, E., Ilse, B., Stubendorff, B., Witte, O.W., Steinbach, R., Hübner, C.A., Graff, C., Brylev, L., Fominykh, V., Demeshonok, V., Ataulina, A., Rogelj, B., Koritnik, B., Zidar, J., Ravnik-Glavač, M., Glavač, D., Stević, Z., Drory, V., Povedano, M., Blair, I.P., Kiernan, M.C., Benyamin, B., Henderson, R.D., Furlong, S., Mathers, S., McCombe, P.A., Needham, M., Ngo, S.T., Nicholson, G.A., Pamphlett, R., Rowe, D.B., Steyn, F.J., Williams, K.L., Mather, K.A., Sachdev, P.S., Henders, A.K., Wallace, L., de Carvalho, M., Pinto, S., Petri, S., Weber, M., Rouleau, G.A., Silani, V., Curtis, C.J., Breen, G., Glass, J.D., Brown, R.H., Landers, J.E., Shaw, C.E., Andersen, P.M., Groen, E.J.N., van Es, M.A., Pasterkamp, R.J., Fan, D., Garton, F.C., McRae, A.F., Davey Smith, G., Gaunt, T.R., Eberle, M.A., Mill, J., McLaughlin, R.L., Hardiman, O., Kenna, K.P., Wray, N.R., Tsai, E., Runz, H., Franke, L., Al-Chalabi, A., Van Damme, P., van den Berg, L.H., and Veldink, J.H.
Abstract: Correction to: Nature Genetics https://doi.org/10.1038/s41588-021-00973-1, published online 6 December 2021. In the version of this article initially published, the affiliation for Nazli Başak appeared incorrectly. Nazli Başak is at Koç University, School of Medicine, KUTTAM-NDAL, Istanbul, Turkey, and not Bogazici University. The error has been corrected in the HTML and PDF versions of the article.
Published: 2022

14. Benchmark calculations of infinite neutron matter with realistic two- and three-nucleon potentials

Author: Lovato, A., Bombaci, I., Logoteta, D., Piarulli, M., Wiringa, R. B., Lovato, A., Bombaci, I., Logoteta, D., Piarulli, M., and Wiringa, R. B.
Abstract: We present the equation of state of infinite neutron matter as obtained from highly-realistic Hamiltonians that include nucleon-nucleon and three-nucleon coordinate-space potentials. We benchmark three independent many-body methods: Brueckner-Bethe-Goldstone (BBG), Fermi hypernetted chain/single-operator chain (FHNC/SOC), and auxiliary-field diffusion Monte Carlo (AFDMC). We find them to provide similar equations of state when the Argonne $v_{18}$ and the Argonne $v_{6}^\prime$ nucleon-nucleon potentials are used in combination with the Urbana IX three-body force. Only at densities larger than about 1.5 the nuclear saturation density ($\rho_0 = 0.16\,\rm{fm}^{-3}$) the FHNC/SOC energies are appreciably lower than the other two approaches. The AFDMC calculations carried out with all of the Norfolk potentials fitted to reproduce the experimental trinucleon ground-state energies and $nd$ doublet scattering length yield unphysically bound neutron matter, associated with the formation of neutron droplets. Including tritium $\beta$-decay in the fitting procedure, as in the second family of Norfolk potentials, mitigates but does not completely resolve this problem. An excellent agreement between the BBG and AFDMC results is found for the subset of Norfolk interactions that do not make neutron-matter collapse, while the FHNC/SOC equations of state are moderately softer., Comment: 15 pages, 3 figures. arXiv admin note: text overlap with arXiv:1908.04426
Published: 2022
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15. Evidence for a pathogenic role of extrafollicular, IL-10-producing CCR6+B helper T cells in systemic lupus erythematosus

Author: Facciotti, F, Larghi, P, Bosotti, R, Vasco, C, Gagliani, N, Cordiglieri, C, Mazzara, S, Ranzani, V, Rottoli, E, Curti, S, Penatti, A, Karnani, B, Kobayashi, Y, Crosti, M, Bombaci, M, van Hamburg, J, Rossetti, G, Gualtierotti, R, Gerosa, M, Gatti, S, Torretta, S, Pignataro, L, Tas, S, Abrignani, S, Pagani, M, Grassi, F, Meroni, P, Flavell, R, Geginat, J, Facciotti F, Larghi P, Bosotti R, Vasco C, Gagliani N, Cordiglieri C, Mazzara S, Ranzani V, Rottoli E, Curti S, Penatti A, Karnani B, Kobayashi Y, Crosti M, Bombaci M, van Hamburg JP, Rossetti G, Gualtierotti R, Gerosa M, Gatti S, Torretta S, Pignataro L, Tas SW, Abrignani S, Pagani M, Grassi F, Meroni PL, Flavell RA, Geginat J, Facciotti, F, Larghi, P, Bosotti, R, Vasco, C, Gagliani, N, Cordiglieri, C, Mazzara, S, Ranzani, V, Rottoli, E, Curti, S, Penatti, A, Karnani, B, Kobayashi, Y, Crosti, M, Bombaci, M, van Hamburg, J, Rossetti, G, Gualtierotti, R, Gerosa, M, Gatti, S, Torretta, S, Pignataro, L, Tas, S, Abrignani, S, Pagani, M, Grassi, F, Meroni, P, Flavell, R, Geginat, J, Facciotti F, Larghi P, Bosotti R, Vasco C, Gagliani N, Cordiglieri C, Mazzara S, Ranzani V, Rottoli E, Curti S, Penatti A, Karnani B, Kobayashi Y, Crosti M, Bombaci M, van Hamburg JP, Rossetti G, Gualtierotti R, Gerosa M, Gatti S, Torretta S, Pignataro L, Tas SW, Abrignani S, Pagani M, Grassi F, Meroni PL, Flavell RA, and Geginat J
Abstract: Interleukin 10 (IL-10) is an antiinflammatory cytokine, but also promotes B cell responses and plays a pathogenic role in systemic lupus erythematosus (SLE). CD4+CCR6+IL-7R+T cells from human tonsils produced IL-10 following stimulation by naïve B cells, which promoted B cell immunoglobulin G (IgG) production. These tonsillar CCR6+B helper T cells were phenotypically distinct from follicular helper T (TFH) cells and lacked BCL6 expression. In peripheral blood, a CCR6+T cell population with similar characteristics was identified, which lacked Th17- and TFH-associated gene signatures and differentiation-associated surface markers. CD4+CCR6+T cells expressing IL-10, but not IL-17, were also detectable in the spleens of cytokine reporter mice. They provided help for IgG production in vivo, and expanded systemically in pristane-induced lupus-like disease. In SLE patients, CD4+CCR6+IL-7R+T cells were associated with the presence of pathogenic anti-dsDNA (doublestranded DNA) antibodies, and provided spontaneous help for autoantibody production ex vivo. Strikingly, IL-10-producing CCR6+T cells were highly abundant in lymph nodes of SLE patients, and colocalized with B cells at the margins of follicles. In conclusion, we identified a previously uncharacterized population of extrafollicular B helper T cells, which produced IL-10 and could play a prominent pathogenic role in SLE.
Published: 2020

16. Effect modification of the association between total cigarette smoking and ALS risk by intensity, duration and time-since-quitting: Euro-MOTOR

Author: Peters, S, Vlaanderen, J, Portengen, L, Vermeulen, R, Visser, A, Veldink, J, Van Den Berg, L, D'Ovidio, F, Chio, A, Beghi, E, Pupillo, E, Logroscino, G, Hardiman, O, Van Der Kooi, A, Raaphorst, J, Calvo, A, Moglia, C, Casale, F, Fuda, G, Canosa, A, Manera, U, Bombaci, A, Grassano, M, Vasta, R, Salamone, P, Marrali, G, Iazzolino, B, Mazzini, L, Rooney, J, Heverin, M, Vajda, A, Comi, G, Riva, N, Lunetta, C, Gerardi, F, Filosto, M, Cotelli, M, Rinaldi, F, Chiveri, L, Guaita, M, Perrone, P, Mauro, C, Diamanti, L, Ferrarese, C, Tremolizzo, L, Delodovici, M, Bono, G, Tortelli, R, Zecca, C, Peters S., Vlaanderen J., Portengen L., Vermeulen R., Visser A. E., Veldink J. H., Van Den Berg L. H., D'Ovidio F., Chio A., Beghi E., Pupillo E., Logroscino G., Hardiman O., Van Der Kooi A. J., Raaphorst J., Calvo A., Moglia C., Casale F., Fuda G., Canosa A., Manera U., Bombaci A., Grassano M., Vasta R., Salamone P., Marrali G., Iazzolino B., Mazzini L., Rooney J., Heverin M., Vajda A., Comi G., Riva N., Lunetta C., Gerardi F., Filosto M., Cotelli M. S., Rinaldi F., Chiveri L., Guaita M. C., Perrone P., Mauro C., Diamanti L., Ferrarese C., Tremolizzo L., Delodovici M. L., Bono G., Tortelli R., Zecca C., Peters, S, Vlaanderen, J, Portengen, L, Vermeulen, R, Visser, A, Veldink, J, Van Den Berg, L, D'Ovidio, F, Chio, A, Beghi, E, Pupillo, E, Logroscino, G, Hardiman, O, Van Der Kooi, A, Raaphorst, J, Calvo, A, Moglia, C, Casale, F, Fuda, G, Canosa, A, Manera, U, Bombaci, A, Grassano, M, Vasta, R, Salamone, P, Marrali, G, Iazzolino, B, Mazzini, L, Rooney, J, Heverin, M, Vajda, A, Comi, G, Riva, N, Lunetta, C, Gerardi, F, Filosto, M, Cotelli, M, Rinaldi, F, Chiveri, L, Guaita, M, Perrone, P, Mauro, C, Diamanti, L, Ferrarese, C, Tremolizzo, L, Delodovici, M, Bono, G, Tortelli, R, Zecca, C, Peters S., Vlaanderen J., Portengen L., Vermeulen R., Visser A. E., Veldink J. H., Van Den Berg L. H., D'Ovidio F., Chio A., Beghi E., Pupillo E., Logroscino G., Hardiman O., Van Der Kooi A. J., Raaphorst J., Calvo A., Moglia C., Casale F., Fuda G., Canosa A., Manera U., Bombaci A., Grassano M., Vasta R., Salamone P., Marrali G., Iazzolino B., Mazzini L., Rooney J., Heverin M., Vajda A., Comi G., Riva N., Lunetta C., Gerardi F., Filosto M., Cotelli M. S., Rinaldi F., Chiveri L., Guaita M. C., Perrone P., Mauro C., Diamanti L., Ferrarese C., Tremolizzo L., Delodovici M. L., Bono G., Tortelli R., and Zecca C.
Abstract: Background We investigated the association between cigarette smoking and risk of amyotrophic lateral sclerosis (ALS) in a pooled analysis of population-based case-control studies and explored the independent effects of intensity, duration and time-since-quitting. Methods ALS cases and controls, matched by age, sex and region, were recruited in the Netherlands, Italy and Ireland (∗Euro-MOTOR project). Demographics and detailed lifetime smoking histories were collected through questionnaires. Effects of smoking status, intensity (cigarettes/day), duration (years), pack-years and time-since-quitting (years) on ALS risk were estimated using logistic regression models, adjusting for age, sex, alcohol, education and centre. We further investigated effect modification of the linear effects of pack-years by intensity, duration and time-since-quitting using excess OR (eOR) models. Results Analyses were performed on 1410 cases and 2616 controls. Pack-years were positively associated with ALS risk; OR=1.26 (95%CI: 1.03 to 1.54) for the highest quartile compared with never smokers. This association appeared to be predominantly driven by smoking duration (p trend=0.001) rather than intensity (p trend=0.86), although the trend for duration disappeared after adjustment for time-since-quitting. Time-since-quitting was inversely related to ALS (p trend <0.0001). The eOR decreased with time-since-quitting smoking, until about 10 years prior to disease onset. High intensity smoking with shorter duration appeared more deleterious than lower intensity for a longer duration. Conclusions Our findings provide further support for the association between smoking and ALS. Pack-years alone may be insufficient to capture effects of different smoking patterns. Time-since-quitting appeared to be an important factor, suggesting that smoking may be an early disease trigger.
Published: 2020

17. Novel biomarkers for primary biliary cholangitis to improve diagnosis and understand underlying regulatory mechanisms

Author: Bombaci, M, Pesce, E, Torri, A, Carpi, D, Crosti, M, Lanzafame, M, Cordiglieri, C, Sinisi, A, DEL MORO, L, Bernuzzi, F, Gerussi, A, Geginat, J, Muratori, L, Terracciano, L, Invernizzi, P, Abrignani, S, Grifantini, R, Bombaci M., Pesce E., Torri A., Carpi D., Crosti M., Lanzafame M., Cordiglieri C., Sinisi A., DEL MORO, LILIA ANNA PAOLA MARIA, Bernuzzi F., Gerussi A., Geginat J., Muratori L., Terracciano L. M., Invernizzi P., Abrignani S., Grifantini R., Bombaci, M, Pesce, E, Torri, A, Carpi, D, Crosti, M, Lanzafame, M, Cordiglieri, C, Sinisi, A, DEL MORO, L, Bernuzzi, F, Gerussi, A, Geginat, J, Muratori, L, Terracciano, L, Invernizzi, P, Abrignani, S, Grifantini, R, Bombaci M., Pesce E., Torri A., Carpi D., Crosti M., Lanzafame M., Cordiglieri C., Sinisi A., DEL MORO, LILIA ANNA PAOLA MARIA, Bernuzzi F., Gerussi A., Geginat J., Muratori L., Terracciano L. M., Invernizzi P., Abrignani S., and Grifantini R.
Abstract: Background and aims: Primary biliary cholangitis is an autoimmune biliary disease characterized by injury of bile ducts, eventually leading to cirrhosis and death. In most cases, anti-mitochondrial antibodies and persistently elevated serum alkaline phosphatase are the basis for the serological diagnosis. Anti-nuclear antibodies are also useful and may indicate a more aggressive diseases course. In patients in which anti-mitochondrial antibodies are not detected, an accurate diagnosis requires liver histology. This study aims at identifying specific biomarkers for the serological diagnosis of primary biliary cholangitis. Methods: Sera from patients affected by primary biliary cholangitis, primary sclerosing cholangitis, hepatitis C virus (with and without cryoglobulinemia), hepatocarcinoma and healthy donors were tested on a protein array representing 1658 human proteins. The most reactive autoantigens were confirmed by DELFIA analysis on expanded cohorts of the same mentioned serum classes, and on autoimmune hepatitis sera, using anti-PDC-E2 as reference biomarker. Results: Two autoantigens, SPATA31A3 and GARP, showed high reactivity with primary biliary cholangitis sera, containing or not anti-mitochondrial antibodies. Their combination with PDC-E2 allowed to discriminate primary biliary cholangitis from all tested control classes with high sensitivity and specificity. We found that GARP expression is upregulated upon exposure to biliary salts in human cholangiocytes, an event involving EGFR and insulin pathways. GARP expression was also detected in biliary duct cells of PBC patients. Conclusions: This study highlighted SPATA31A3 and GARP as new biomarkers for primary biliary cholangitis and unravelled molecular stimuli underlying GARP expression in human cholangiocytes
Published: 2019

18. Numerical relativity simulations of prompt collapse mergers: threshold mass and phenomenological constraints on neutron star properties after GW170817

Author: Kashyap, Rahul, Das, Abhishek, Radice, David, Padamata, Surendra, Prakash, Aviral, Logoteta, Domenico, Perego, Albino, Godzieba, Daniel A., Bernuzzi, Sebastiano, Bombaci, Ignazio, Fattoyev, Farrukh J., Reed, Brendan T., Schneider, André da Silva, Kashyap, Rahul, Das, Abhishek, Radice, David, Padamata, Surendra, Prakash, Aviral, Logoteta, Domenico, Perego, Albino, Godzieba, Daniel A., Bernuzzi, Sebastiano, Bombaci, Ignazio, Fattoyev, Farrukh J., Reed, Brendan T., and Schneider, André da Silva
Abstract: We determine the threshold mass for prompt (no bounce) black hole formation in equal-mass neutron star (NS) mergers using a new set of 227 numerical relativity simulations. We consider 23 phenomenological and microphysical finite temperature equations of state (EOS), including models with hyperons and first-order phase transitions to deconfined quarks. We confirm the existence of EOS-insensitive relations between the threshold mass, the binary tidal parameter at the threshold ($\Lambda_{th}$), the maximum mass of nonrotating NSs, and the radii of reference mass NSs. We correct the systematic errors in previously reported fitting coefficients that were obtained with approximate general-relativity simulations. We combine the EOS-insensitive relations, phenomenological constraints on NS properties and observational data from GW170817 to derive an improved lower limit on radii of maximum mass and 1.6 M$_\odot$ NS of 9.81 km and 10.90 km, respectively. We also constrain the radius and quadrupolar tidal deformability ($\Lambda$) of a 1.4 $M_\odot$ NS to be larger than 10.74 km and 172, respectively. We consider uncertainties in all independent parameters -- fitting coefficients as well as GW170817 masses while reporting the range of radii constraints. We introduce new methods to constrain the upper as well as lower limit of NS maximum mass using future BNS detections and their identification as prompt or delayed collapse. With future observations it will be possible to derive even tighter constraints on the properties of matter at and above nuclear density using the method proposed in this work., Comment: Accepted for publication in Physical Review D
Published: 2021

19. Signatures of deconfined quark phases in binary neutron star mergers

Author: Prakash, Aviral, Radice, David, Logoteta, Domenico, Perego, Albino, Nedora, Vsevolod, Bombaci, Ignazio, Kashyap, Rahul, Bernuzzi, Sebastiano, Endrizzi, Andrea, Prakash, Aviral, Radice, David, Logoteta, Domenico, Perego, Albino, Nedora, Vsevolod, Bombaci, Ignazio, Kashyap, Rahul, Bernuzzi, Sebastiano, and Endrizzi, Andrea
Abstract: (abridged) We investigate the quark deconfinement phase transition in the context of binary neutron star (BNS) mergers. We employ a new finite-temperature composition-dependent equation of state (EOS) with a first order phase transition between hadrons and deconfined quarks to perform numerical relativity simulations of BNS mergers. The softening of the EOS due to the phase transition causes the merger remnants to be more compact and to collapse to a black hole (BH) at earlier times. The phase transition is imprinted on the postmerger gravitational wave (GW) signal duration, amplitude, and peak frequency. However, this imprint is only detectable for binaries with sufficiently long-lived remnants. Moreover, the phase transition does not result in significant deviations from quasi-universal relations for the postmerger GW peak frequency. We also study the impact of the phase transition on dynamical ejecta, remnant accretion disk masses, r-process nucleosynthetic yields and associated electromagnetic (EM) counterparts. While there are differences in the EM counterparts and nucleosynthesis yields between the purely hadronic models and the models with phase transitions, these can be primarily ascribed to the difference in remnant collapse time between the two. An exception is the non-thermal afterglow caused by the interaction of the fastest component of the dynamical ejecta and the interstellar medium, which is systematically boosted in the binaries with phase transition as a consequence of the more violent merger they experience., Comment: 28 pages and 16 figures
Published: 2021
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20. Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Author: van Rheenen, Wouter, van der Spek, Rick A. A., Bakker, Mark K., van Vugt, Joke J. F. A., Hop, Paul J., Zwamborn, Ramona A. J., de Klein, Niek, Westra, Harm-Jan, Bakker, Olivier B., Deelen, Patrick, Shireby, Gemma, Hannon, Eilis, Moisse, Matthieu, Baird, Denis, Restuadi, Restuadi, Dolzhenko, Egor, Dekker, Annelot M., Gawor, Klara, Westeneng, Henk-Jan, Tazelaar, Gijs H. P., van Eijk, Kristel R., Kooyman, Maarten, Byrne, Ross P., Doherty, Mark, Heverin, Mark, Al Khleifat, Ahmad, Iacoangeli, Alfredo, Shatunov, Aleksey, Ticozzi, Nicola, Cooper-Knock, Johnathan, Smith, Bradley N., Gromicho, Marta, Chandran, Siddharthan, Pal, Suvankar, Morrison, Karen E., Shaw, Pamela J., Hardy, John, Orrell, Richard W., Sendtner, Michael, Meyer, Thomas, Basak, Nazli, van der Kooi, Anneke J., Ratti, Antonia, Fogh, Isabella, Gellera, Cinzia, Lauria, Giuseppe, Corti, Stefania, Cereda, Cristina, Sproviero, Daisy, D'Alfonso, Sandra, Soraru, Gianni, Siciliano, Gabriele, Filosto, Massimiliano, Padovani, Alessandro, Chio, Adriano, Calvo, Andrea, Moglia, Cristina, Brunetti, Maura, Canosa, Antonio, Grassano, Maurizio, Beghi, Ettore, Pupillo, Elisabetta, Logroscino, Giancarlo, Nefussy, Beatrice, Osmanovic, Alma, Nordin, Angelica, Lerner, Yossef, Zabari, Michal, Gotkine, Marc, Baloh, Robert H., Bell, Shaughn, Vourc'h, Patrick, Corcia, Philippe, Couratier, Philippe, Millecamps, Stephanie, Meininger, Vincent, Salachas, Francois, Mora Pardina, Jesus S., Assialioui, Abdelilah, Rojas-Garcia, Ricardo, Dion, Patrick A., Ross, Jay P., Ludolph, Albert C., Weishaupt, Jochen H., Brenner, David, Freischmidt, Axel, Bensimon, Gilbert, Brice, Alexis, Durr, Alexandra, Payan, Christine A. M., Saker-Delye, Safa, Wood, Nicholas W., Topp, Simon, Rademakers, Rosa, Tittmann, Lukas, Lieb, Wolfgang, Franke, Andre, Ripke, Stephan, Braun, Alice, Kraft, Julia, Whiteman, David C., Olsen, Catherine M., Uitterlinden, Andre G., Hofman, Albert, Rietschel, Marcella, Cichon, Sven, Nothen, Markus M., Amouyel, Philippe, Comi, Giancarlo, Riva, Nilo, Lunetta, Christian, Gerardi, Francesca, Cotelli, Maria Sofia, Rinaldi, Fabrizio, Chiveri, Luca, Guaita, Maria Cristina, Perrone, Patrizia, Ceroni, Mauro, Diamanti, Luca, Ferrarese, Carlo, Tremolizzo, Lucio, Delodovici, Maria Luisa, Bono, Giorgio, Manera, Umberto, Vasta, Rosario, Bombaci, Alessandro, Casale, Federico, Fuda, Giuseppe, Salamone, Paolina, Iazzolino, Barbara, Peotta, Laura, Cugnasco, Paolo, De Marco, Giovanni, Torrieri, Maria Claudia, Palumbo, Francesca, Gallone, Salvatore, Barberis, Marco, Sbaiz, Luca, Gentile, Salvatore, Mauro, Alessandro, Mazzini, Letizia, De Marchi, Fabiola, Corrado, Lucia, Bertolotto, Antonio, Gionco, Maurizio, Leotta, Daniela, Odddenino, Enrico, Imperiale, Daniele, Cavallo, Roberto, Pignatta, Pietro, De Mattei, Marco, Geda, Claudio, Papurello, Diego Maria, Gusmaroli, Graziano, Comi, Cristoforo, Labate, Carmelo, Ruiz, Luigi, Ferrandi, Delfina, Rota, Eugenia, Aguggia, Marco, Di Vito, Nicoletta, Meineri, Piero, Ghiglione, Paolo, Launaro, Nicola, Dotta, Michele, Di Sapio, Alessia, Giardini, Guido, Tiloca, Cinzia, Peverelli, Silvia, Taroni, Franco, Pensato, Viviana, Castellotti, Barbara, Comi, Giacomo P., Del Bo, Roberto, Gagliardi, Stella, Raggi, Flavia, Simoncini, Costanza, Lo Gerfo, Annalisa, Inghilleri, Maurizio, Ferlini, Alessandra, Simone, Isabella L., Passarella, Bruno, Guerra, Vito, Zoccolella, Stefano, Nozzoli, Cecilia, Mundi, Ciro, Leone, Maurizio, Zarrelli, Michele, Tamma, Filippo, Valluzzi, Francesco, Calabrese, Gianluigi, Boero, Giovanni, Rini, Augusto, Traynor, Bryan J., Singleton, Andrew B., Mitne Neto, Miguel, Cauchi, Ruben J., Ophoff, Roel A., Wiedau-Pazos, Martina, Lomen-Hoerth, Catherine, van Deerlin, Vivianna M., Grosskreutz, Julian, Roediger, Annekathrin, Gaur, Nayana, Joerk, Alexander, Barthel, Tabea, Theele, Erik, Ilse, Benjamin, Stubendorff, Beatrice, Witte, Otto W., Steinbach, Robert, Huebner, Christian A., Graff, Caroline, Brylev, Lev, Fominykh, Vera, Demeshonok, Vera, Ataulina, Anastasia, Rogelj, Boris, Koritnik, Blaz, Zidar, Janez, Ravnik-Glavac, Metka, Glavac, Damjan, Stevic, Zorica, Drory, Vivian, Povedano, Monica, Blair, Ian P., Kiernan, Matthew C., Benyamin, Beben, Henderson, Robert D., Furlong, Sarah, Mathers, Susan, McCombe, Pamela A., Needham, Merrilee, Ngo, Shyuan T., Nicholson, Garth A., Pamphlett, Roger, Rowe, Dominic B., Steyn, Frederik J., Williams, Kelly L., Mather, Karen A., Sachdev, Perminder S., Henders, Anjali K., Wallace, Leanne, de Carvalho, Mamede, Pinto, Susana, Petri, Susanne, Weber, Markus, Rouleau, Guy A., Silani, Vincenzo, Curtis, Charles J., Breen, Gerome, Glass, Jonathan D., Brown, Robert H., Jr., Landers, John E., Shaw, Christopher E., Andersen, Peter M., Groen, Ewout J. N., van Es, Michael A., Pasterkamp, R. Jeroen, Fan, Dongsheng, Garton, Fleur C., McRae, Allan F., Davey Smith, George, Gaunt, Tom R., Eberle, Michael A., Mill, Jonathan, McLaughlin, Russell L., Hardiman, Orla, Kenna, Kevin P., Wray, Naomi R., Tsai, Ellen, Runz, Heiko, Franke, Lude, Al-Chalabi, Ammar, Van Damme, Philip, van den Berg, Leonard H., Veldink, Jan H., van Rheenen, Wouter, van der Spek, Rick A. A., Bakker, Mark K., van Vugt, Joke J. F. A., Hop, Paul J., Zwamborn, Ramona A. J., de Klein, Niek, Westra, Harm-Jan, Bakker, Olivier B., Deelen, Patrick, Shireby, Gemma, Hannon, Eilis, Moisse, Matthieu, Baird, Denis, Restuadi, Restuadi, Dolzhenko, Egor, Dekker, Annelot M., Gawor, Klara, Westeneng, Henk-Jan, Tazelaar, Gijs H. P., van Eijk, Kristel R., Kooyman, Maarten, Byrne, Ross P., Doherty, Mark, Heverin, Mark, Al Khleifat, Ahmad, Iacoangeli, Alfredo, Shatunov, Aleksey, Ticozzi, Nicola, Cooper-Knock, Johnathan, Smith, Bradley N., Gromicho, Marta, Chandran, Siddharthan, Pal, Suvankar, Morrison, Karen E., Shaw, Pamela J., Hardy, John, Orrell, Richard W., Sendtner, Michael, Meyer, Thomas, Basak, Nazli, van der Kooi, Anneke J., Ratti, Antonia, Fogh, Isabella, Gellera, Cinzia, Lauria, Giuseppe, Corti, Stefania, Cereda, Cristina, Sproviero, Daisy, D'Alfonso, Sandra, Soraru, Gianni, Siciliano, Gabriele, Filosto, Massimiliano, Padovani, Alessandro, Chio, Adriano, Calvo, Andrea, Moglia, Cristina, Brunetti, Maura, Canosa, Antonio, Grassano, Maurizio, Beghi, Ettore, Pupillo, Elisabetta, Logroscino, Giancarlo, Nefussy, Beatrice, Osmanovic, Alma, Nordin, Angelica, Lerner, Yossef, Zabari, Michal, Gotkine, Marc, Baloh, Robert H., Bell, Shaughn, Vourc'h, Patrick, Corcia, Philippe, Couratier, Philippe, Millecamps, Stephanie, Meininger, Vincent, Salachas, Francois, Mora Pardina, Jesus S., Assialioui, Abdelilah, Rojas-Garcia, Ricardo, Dion, Patrick A., Ross, Jay P., Ludolph, Albert C., Weishaupt, Jochen H., Brenner, David, Freischmidt, Axel, Bensimon, Gilbert, Brice, Alexis, Durr, Alexandra, Payan, Christine A. M., Saker-Delye, Safa, Wood, Nicholas W., Topp, Simon, Rademakers, Rosa, Tittmann, Lukas, Lieb, Wolfgang, Franke, Andre, Ripke, Stephan, Braun, Alice, Kraft, Julia, Whiteman, David C., Olsen, Catherine M., Uitterlinden, Andre G., Hofman, Albert, Rietschel, Marcella, Cichon, Sven, Nothen, Markus M., Amouyel, Philippe, Comi, Giancarlo, Riva, Nilo, Lunetta, Christian, Gerardi, Francesca, Cotelli, Maria Sofia, Rinaldi, Fabrizio, Chiveri, Luca, Guaita, Maria Cristina, Perrone, Patrizia, Ceroni, Mauro, Diamanti, Luca, Ferrarese, Carlo, Tremolizzo, Lucio, Delodovici, Maria Luisa, Bono, Giorgio, Manera, Umberto, Vasta, Rosario, Bombaci, Alessandro, Casale, Federico, Fuda, Giuseppe, Salamone, Paolina, Iazzolino, Barbara, Peotta, Laura, Cugnasco, Paolo, De Marco, Giovanni, Torrieri, Maria Claudia, Palumbo, Francesca, Gallone, Salvatore, Barberis, Marco, Sbaiz, Luca, Gentile, Salvatore, Mauro, Alessandro, Mazzini, Letizia, De Marchi, Fabiola, Corrado, Lucia, Bertolotto, Antonio, Gionco, Maurizio, Leotta, Daniela, Odddenino, Enrico, Imperiale, Daniele, Cavallo, Roberto, Pignatta, Pietro, De Mattei, Marco, Geda, Claudio, Papurello, Diego Maria, Gusmaroli, Graziano, Comi, Cristoforo, Labate, Carmelo, Ruiz, Luigi, Ferrandi, Delfina, Rota, Eugenia, Aguggia, Marco, Di Vito, Nicoletta, Meineri, Piero, Ghiglione, Paolo, Launaro, Nicola, Dotta, Michele, Di Sapio, Alessia, Giardini, Guido, Tiloca, Cinzia, Peverelli, Silvia, Taroni, Franco, Pensato, Viviana, Castellotti, Barbara, Comi, Giacomo P., Del Bo, Roberto, Gagliardi, Stella, Raggi, Flavia, Simoncini, Costanza, Lo Gerfo, Annalisa, Inghilleri, Maurizio, Ferlini, Alessandra, Simone, Isabella L., Passarella, Bruno, Guerra, Vito, Zoccolella, Stefano, Nozzoli, Cecilia, Mundi, Ciro, Leone, Maurizio, Zarrelli, Michele, Tamma, Filippo, Valluzzi, Francesco, Calabrese, Gianluigi, Boero, Giovanni, Rini, Augusto, Traynor, Bryan J., Singleton, Andrew B., Mitne Neto, Miguel, Cauchi, Ruben J., Ophoff, Roel A., Wiedau-Pazos, Martina, Lomen-Hoerth, Catherine, van Deerlin, Vivianna M., Grosskreutz, Julian, Roediger, Annekathrin, Gaur, Nayana, Joerk, Alexander, Barthel, Tabea, Theele, Erik, Ilse, Benjamin, Stubendorff, Beatrice, Witte, Otto W., Steinbach, Robert, Huebner, Christian A., Graff, Caroline, Brylev, Lev, Fominykh, Vera, Demeshonok, Vera, Ataulina, Anastasia, Rogelj, Boris, Koritnik, Blaz, Zidar, Janez, Ravnik-Glavac, Metka, Glavac, Damjan, Stevic, Zorica, Drory, Vivian, Povedano, Monica, Blair, Ian P., Kiernan, Matthew C., Benyamin, Beben, Henderson, Robert D., Furlong, Sarah, Mathers, Susan, McCombe, Pamela A., Needham, Merrilee, Ngo, Shyuan T., Nicholson, Garth A., Pamphlett, Roger, Rowe, Dominic B., Steyn, Frederik J., Williams, Kelly L., Mather, Karen A., Sachdev, Perminder S., Henders, Anjali K., Wallace, Leanne, de Carvalho, Mamede, Pinto, Susana, Petri, Susanne, Weber, Markus, Rouleau, Guy A., Silani, Vincenzo, Curtis, Charles J., Breen, Gerome, Glass, Jonathan D., Brown, Robert H., Jr., Landers, John E., Shaw, Christopher E., Andersen, Peter M., Groen, Ewout J. N., van Es, Michael A., Pasterkamp, R. Jeroen, Fan, Dongsheng, Garton, Fleur C., McRae, Allan F., Davey Smith, George, Gaunt, Tom R., Eberle, Michael A., Mill, Jonathan, McLaughlin, Russell L., Hardiman, Orla, Kenna, Kevin P., Wray, Naomi R., Tsai, Ellen, Runz, Heiko, Franke, Lude, Al-Chalabi, Ammar, Van Damme, Philip, van den Berg, Leonard H., and Veldink, Jan H.
Abstract: A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons.
Published: 2021
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21. Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Author: van Rheenen, Wouter, van der Spek, Rick A. A., Bakker, Mark K., van Vugt, Joke J. F. A., Hop, Paul J., Zwamborn, Ramona A. J., de Klein, Niek, Westra, Harm-Jan, Bakker, Olivier B., Deelen, Patrick, Shireby, Gemma, Hannon, Eilis, Moisse, Matthieu, Baird, Denis, Restuadi, Restuadi, Dolzhenko, Egor, Dekker, Annelot M., Gawor, Klara, Westeneng, Henk-Jan, Tazelaar, Gijs H. P., van Eijk, Kristel R., Kooyman, Maarten, Byrne, Ross P., Doherty, Mark, Heverin, Mark, Al Khleifat, Ahmad, Iacoangeli, Alfredo, Shatunov, Aleksey, Ticozzi, Nicola, Cooper-Knock, Johnathan, Smith, Bradley N., Gromicho, Marta, Chandran, Siddharthan, Pal, Suvankar, Morrison, Karen E., Shaw, Pamela J., Hardy, John, Orrell, Richard W., Sendtner, Michael, Meyer, Thomas, Basak, Nazli, van der Kooi, Anneke J., Ratti, Antonia, Fogh, Isabella, Gellera, Cinzia, Lauria, Giuseppe, Corti, Stefania, Cereda, Cristina, Sproviero, Daisy, D'Alfonso, Sandra, Soraru, Gianni, Siciliano, Gabriele, Filosto, Massimiliano, Padovani, Alessandro, Chio, Adriano, Calvo, Andrea, Moglia, Cristina, Brunetti, Maura, Canosa, Antonio, Grassano, Maurizio, Beghi, Ettore, Pupillo, Elisabetta, Logroscino, Giancarlo, Nefussy, Beatrice, Osmanovic, Alma, Nordin, Angelica, Lerner, Yossef, Zabari, Michal, Gotkine, Marc, Baloh, Robert H., Bell, Shaughn, Vourc'h, Patrick, Corcia, Philippe, Couratier, Philippe, Millecamps, Stephanie, Meininger, Vincent, Salachas, Francois, Mora Pardina, Jesus S., Assialioui, Abdelilah, Rojas-Garcia, Ricardo, Dion, Patrick A., Ross, Jay P., Ludolph, Albert C., Weishaupt, Jochen H., Brenner, David, Freischmidt, Axel, Bensimon, Gilbert, Brice, Alexis, Durr, Alexandra, Payan, Christine A. M., Saker-Delye, Safa, Wood, Nicholas W., Topp, Simon, Rademakers, Rosa, Tittmann, Lukas, Lieb, Wolfgang, Franke, Andre, Ripke, Stephan, Braun, Alice, Kraft, Julia, Whiteman, David C., Olsen, Catherine M., Uitterlinden, Andre G., Hofman, Albert, Rietschel, Marcella, Cichon, Sven, Nothen, Markus M., Amouyel, Philippe, Comi, Giancarlo, Riva, Nilo, Lunetta, Christian, Gerardi, Francesca, Cotelli, Maria Sofia, Rinaldi, Fabrizio, Chiveri, Luca, Guaita, Maria Cristina, Perrone, Patrizia, Ceroni, Mauro, Diamanti, Luca, Ferrarese, Carlo, Tremolizzo, Lucio, Delodovici, Maria Luisa, Bono, Giorgio, Manera, Umberto, Vasta, Rosario, Bombaci, Alessandro, Casale, Federico, Fuda, Giuseppe, Salamone, Paolina, Iazzolino, Barbara, Peotta, Laura, Cugnasco, Paolo, De Marco, Giovanni, Torrieri, Maria Claudia, Palumbo, Francesca, Gallone, Salvatore, Barberis, Marco, Sbaiz, Luca, Gentile, Salvatore, Mauro, Alessandro, Mazzini, Letizia, De Marchi, Fabiola, Corrado, Lucia, Bertolotto, Antonio, Gionco, Maurizio, Leotta, Daniela, Odddenino, Enrico, Imperiale, Daniele, Cavallo, Roberto, Pignatta, Pietro, De Mattei, Marco, Geda, Claudio, Papurello, Diego Maria, Gusmaroli, Graziano, Comi, Cristoforo, Labate, Carmelo, Ruiz, Luigi, Ferrandi, Delfina, Rota, Eugenia, Aguggia, Marco, Di Vito, Nicoletta, Meineri, Piero, Ghiglione, Paolo, Launaro, Nicola, Dotta, Michele, Di Sapio, Alessia, Giardini, Guido, Tiloca, Cinzia, Peverelli, Silvia, Taroni, Franco, Pensato, Viviana, Castellotti, Barbara, Comi, Giacomo P., Del Bo, Roberto, Gagliardi, Stella, Raggi, Flavia, Simoncini, Costanza, Lo Gerfo, Annalisa, Inghilleri, Maurizio, Ferlini, Alessandra, Simone, Isabella L., Passarella, Bruno, Guerra, Vito, Zoccolella, Stefano, Nozzoli, Cecilia, Mundi, Ciro, Leone, Maurizio, Zarrelli, Michele, Tamma, Filippo, Valluzzi, Francesco, Calabrese, Gianluigi, Boero, Giovanni, Rini, Augusto, Traynor, Bryan J., Singleton, Andrew B., Mitne Neto, Miguel, Cauchi, Ruben J., Ophoff, Roel A., Wiedau-Pazos, Martina, Lomen-Hoerth, Catherine, van Deerlin, Vivianna M., Grosskreutz, Julian, Roediger, Annekathrin, Gaur, Nayana, Joerk, Alexander, Barthel, Tabea, Theele, Erik, Ilse, Benjamin, Stubendorff, Beatrice, Witte, Otto W., Steinbach, Robert, Huebner, Christian A., Graff, Caroline, Brylev, Lev, Fominykh, Vera, Demeshonok, Vera, Ataulina, Anastasia, Rogelj, Boris, Koritnik, Blaz, Zidar, Janez, Ravnik-Glavac, Metka, Glavac, Damjan, Stevic, Zorica, Drory, Vivian, Povedano, Monica, Blair, Ian P., Kiernan, Matthew C., Benyamin, Beben, Henderson, Robert D., Furlong, Sarah, Mathers, Susan, McCombe, Pamela A., Needham, Merrilee, Ngo, Shyuan T., Nicholson, Garth A., Pamphlett, Roger, Rowe, Dominic B., Steyn, Frederik J., Williams, Kelly L., Mather, Karen A., Sachdev, Perminder S., Henders, Anjali K., Wallace, Leanne, de Carvalho, Mamede, Pinto, Susana, Petri, Susanne, Weber, Markus, Rouleau, Guy A., Silani, Vincenzo, Curtis, Charles J., Breen, Gerome, Glass, Jonathan D., Brown, Robert H., Jr., Landers, John E., Shaw, Christopher E., Andersen, Peter M., Groen, Ewout J. N., van Es, Michael A., Pasterkamp, R. Jeroen, Fan, Dongsheng, Garton, Fleur C., McRae, Allan F., Davey Smith, George, Gaunt, Tom R., Eberle, Michael A., Mill, Jonathan, McLaughlin, Russell L., Hardiman, Orla, Kenna, Kevin P., Wray, Naomi R., Tsai, Ellen, Runz, Heiko, Franke, Lude, Al-Chalabi, Ammar, Van Damme, Philip, van den Berg, Leonard H., Veldink, Jan H., van Rheenen, Wouter, van der Spek, Rick A. A., Bakker, Mark K., van Vugt, Joke J. F. A., Hop, Paul J., Zwamborn, Ramona A. J., de Klein, Niek, Westra, Harm-Jan, Bakker, Olivier B., Deelen, Patrick, Shireby, Gemma, Hannon, Eilis, Moisse, Matthieu, Baird, Denis, Restuadi, Restuadi, Dolzhenko, Egor, Dekker, Annelot M., Gawor, Klara, Westeneng, Henk-Jan, Tazelaar, Gijs H. P., van Eijk, Kristel R., Kooyman, Maarten, Byrne, Ross P., Doherty, Mark, Heverin, Mark, Al Khleifat, Ahmad, Iacoangeli, Alfredo, Shatunov, Aleksey, Ticozzi, Nicola, Cooper-Knock, Johnathan, Smith, Bradley N., Gromicho, Marta, Chandran, Siddharthan, Pal, Suvankar, Morrison, Karen E., Shaw, Pamela J., Hardy, John, Orrell, Richard W., Sendtner, Michael, Meyer, Thomas, Basak, Nazli, van der Kooi, Anneke J., Ratti, Antonia, Fogh, Isabella, Gellera, Cinzia, Lauria, Giuseppe, Corti, Stefania, Cereda, Cristina, Sproviero, Daisy, D'Alfonso, Sandra, Soraru, Gianni, Siciliano, Gabriele, Filosto, Massimiliano, Padovani, Alessandro, Chio, Adriano, Calvo, Andrea, Moglia, Cristina, Brunetti, Maura, Canosa, Antonio, Grassano, Maurizio, Beghi, Ettore, Pupillo, Elisabetta, Logroscino, Giancarlo, Nefussy, Beatrice, Osmanovic, Alma, Nordin, Angelica, Lerner, Yossef, Zabari, Michal, Gotkine, Marc, Baloh, Robert H., Bell, Shaughn, Vourc'h, Patrick, Corcia, Philippe, Couratier, Philippe, Millecamps, Stephanie, Meininger, Vincent, Salachas, Francois, Mora Pardina, Jesus S., Assialioui, Abdelilah, Rojas-Garcia, Ricardo, Dion, Patrick A., Ross, Jay P., Ludolph, Albert C., Weishaupt, Jochen H., Brenner, David, Freischmidt, Axel, Bensimon, Gilbert, Brice, Alexis, Durr, Alexandra, Payan, Christine A. M., Saker-Delye, Safa, Wood, Nicholas W., Topp, Simon, Rademakers, Rosa, Tittmann, Lukas, Lieb, Wolfgang, Franke, Andre, Ripke, Stephan, Braun, Alice, Kraft, Julia, Whiteman, David C., Olsen, Catherine M., Uitterlinden, Andre G., Hofman, Albert, Rietschel, Marcella, Cichon, Sven, Nothen, Markus M., Amouyel, Philippe, Comi, Giancarlo, Riva, Nilo, Lunetta, Christian, Gerardi, Francesca, Cotelli, Maria Sofia, Rinaldi, Fabrizio, Chiveri, Luca, Guaita, Maria Cristina, Perrone, Patrizia, Ceroni, Mauro, Diamanti, Luca, Ferrarese, Carlo, Tremolizzo, Lucio, Delodovici, Maria Luisa, Bono, Giorgio, Manera, Umberto, Vasta, Rosario, Bombaci, Alessandro, Casale, Federico, Fuda, Giuseppe, Salamone, Paolina, Iazzolino, Barbara, Peotta, Laura, Cugnasco, Paolo, De Marco, Giovanni, Torrieri, Maria Claudia, Palumbo, Francesca, Gallone, Salvatore, Barberis, Marco, Sbaiz, Luca, Gentile, Salvatore, Mauro, Alessandro, Mazzini, Letizia, De Marchi, Fabiola, Corrado, Lucia, Bertolotto, Antonio, Gionco, Maurizio, Leotta, Daniela, Odddenino, Enrico, Imperiale, Daniele, Cavallo, Roberto, Pignatta, Pietro, De Mattei, Marco, Geda, Claudio, Papurello, Diego Maria, Gusmaroli, Graziano, Comi, Cristoforo, Labate, Carmelo, Ruiz, Luigi, Ferrandi, Delfina, Rota, Eugenia, Aguggia, Marco, Di Vito, Nicoletta, Meineri, Piero, Ghiglione, Paolo, Launaro, Nicola, Dotta, Michele, Di Sapio, Alessia, Giardini, Guido, Tiloca, Cinzia, Peverelli, Silvia, Taroni, Franco, Pensato, Viviana, Castellotti, Barbara, Comi, Giacomo P., Del Bo, Roberto, Gagliardi, Stella, Raggi, Flavia, Simoncini, Costanza, Lo Gerfo, Annalisa, Inghilleri, Maurizio, Ferlini, Alessandra, Simone, Isabella L., Passarella, Bruno, Guerra, Vito, Zoccolella, Stefano, Nozzoli, Cecilia, Mundi, Ciro, Leone, Maurizio, Zarrelli, Michele, Tamma, Filippo, Valluzzi, Francesco, Calabrese, Gianluigi, Boero, Giovanni, Rini, Augusto, Traynor, Bryan J., Singleton, Andrew B., Mitne Neto, Miguel, Cauchi, Ruben J., Ophoff, Roel A., Wiedau-Pazos, Martina, Lomen-Hoerth, Catherine, van Deerlin, Vivianna M., Grosskreutz, Julian, Roediger, Annekathrin, Gaur, Nayana, Joerk, Alexander, Barthel, Tabea, Theele, Erik, Ilse, Benjamin, Stubendorff, Beatrice, Witte, Otto W., Steinbach, Robert, Huebner, Christian A., Graff, Caroline, Brylev, Lev, Fominykh, Vera, Demeshonok, Vera, Ataulina, Anastasia, Rogelj, Boris, Koritnik, Blaz, Zidar, Janez, Ravnik-Glavac, Metka, Glavac, Damjan, Stevic, Zorica, Drory, Vivian, Povedano, Monica, Blair, Ian P., Kiernan, Matthew C., Benyamin, Beben, Henderson, Robert D., Furlong, Sarah, Mathers, Susan, McCombe, Pamela A., Needham, Merrilee, Ngo, Shyuan T., Nicholson, Garth A., Pamphlett, Roger, Rowe, Dominic B., Steyn, Frederik J., Williams, Kelly L., Mather, Karen A., Sachdev, Perminder S., Henders, Anjali K., Wallace, Leanne, de Carvalho, Mamede, Pinto, Susana, Petri, Susanne, Weber, Markus, Rouleau, Guy A., Silani, Vincenzo, Curtis, Charles J., Breen, Gerome, Glass, Jonathan D., Brown, Robert H., Jr., Landers, John E., Shaw, Christopher E., Andersen, Peter M., Groen, Ewout J. N., van Es, Michael A., Pasterkamp, R. Jeroen, Fan, Dongsheng, Garton, Fleur C., McRae, Allan F., Davey Smith, George, Gaunt, Tom R., Eberle, Michael A., Mill, Jonathan, McLaughlin, Russell L., Hardiman, Orla, Kenna, Kevin P., Wray, Naomi R., Tsai, Ellen, Runz, Heiko, Franke, Lude, Al-Chalabi, Ammar, Van Damme, Philip, van den Berg, Leonard H., and Veldink, Jan H.
Abstract: A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons.
Published: 2021
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22. Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Author: van Rheenen, Wouter, van der Spek, Rick A. A., Bakker, Mark K., van Vugt, Joke J. F. A., Hop, Paul J., Zwamborn, Ramona A. J., de Klein, Niek, Westra, Harm-Jan, Bakker, Olivier B., Deelen, Patrick, Shireby, Gemma, Hannon, Eilis, Moisse, Matthieu, Baird, Denis, Restuadi, Restuadi, Dolzhenko, Egor, Dekker, Annelot M., Gawor, Klara, Westeneng, Henk-Jan, Tazelaar, Gijs H. P., van Eijk, Kristel R., Kooyman, Maarten, Byrne, Ross P., Doherty, Mark, Heverin, Mark, Al Khleifat, Ahmad, Iacoangeli, Alfredo, Shatunov, Aleksey, Ticozzi, Nicola, Cooper-Knock, Johnathan, Smith, Bradley N., Gromicho, Marta, Chandran, Siddharthan, Pal, Suvankar, Morrison, Karen E., Shaw, Pamela J., Hardy, John, Orrell, Richard W., Sendtner, Michael, Meyer, Thomas, Basak, Nazli, van der Kooi, Anneke J., Ratti, Antonia, Fogh, Isabella, Gellera, Cinzia, Lauria, Giuseppe, Corti, Stefania, Cereda, Cristina, Sproviero, Daisy, D'Alfonso, Sandra, Soraru, Gianni, Siciliano, Gabriele, Filosto, Massimiliano, Padovani, Alessandro, Chio, Adriano, Calvo, Andrea, Moglia, Cristina, Brunetti, Maura, Canosa, Antonio, Grassano, Maurizio, Beghi, Ettore, Pupillo, Elisabetta, Logroscino, Giancarlo, Nefussy, Beatrice, Osmanovic, Alma, Nordin, Angelica, Lerner, Yossef, Zabari, Michal, Gotkine, Marc, Baloh, Robert H., Bell, Shaughn, Vourc'h, Patrick, Corcia, Philippe, Couratier, Philippe, Millecamps, Stephanie, Meininger, Vincent, Salachas, Francois, Mora Pardina, Jesus S., Assialioui, Abdelilah, Rojas-Garcia, Ricardo, Dion, Patrick A., Ross, Jay P., Ludolph, Albert C., Weishaupt, Jochen H., Brenner, David, Freischmidt, Axel, Bensimon, Gilbert, Brice, Alexis, Durr, Alexandra, Payan, Christine A. M., Saker-Delye, Safa, Wood, Nicholas W., Topp, Simon, Rademakers, Rosa, Tittmann, Lukas, Lieb, Wolfgang, Franke, Andre, Ripke, Stephan, Braun, Alice, Kraft, Julia, Whiteman, David C., Olsen, Catherine M., Uitterlinden, Andre G., Hofman, Albert, Rietschel, Marcella, Cichon, Sven, Nothen, Markus M., Amouyel, Philippe, Comi, Giancarlo, Riva, Nilo, Lunetta, Christian, Gerardi, Francesca, Cotelli, Maria Sofia, Rinaldi, Fabrizio, Chiveri, Luca, Guaita, Maria Cristina, Perrone, Patrizia, Ceroni, Mauro, Diamanti, Luca, Ferrarese, Carlo, Tremolizzo, Lucio, Delodovici, Maria Luisa, Bono, Giorgio, Manera, Umberto, Vasta, Rosario, Bombaci, Alessandro, Casale, Federico, Fuda, Giuseppe, Salamone, Paolina, Iazzolino, Barbara, Peotta, Laura, Cugnasco, Paolo, De Marco, Giovanni, Torrieri, Maria Claudia, Palumbo, Francesca, Gallone, Salvatore, Barberis, Marco, Sbaiz, Luca, Gentile, Salvatore, Mauro, Alessandro, Mazzini, Letizia, De Marchi, Fabiola, Corrado, Lucia, Bertolotto, Antonio, Gionco, Maurizio, Leotta, Daniela, Odddenino, Enrico, Imperiale, Daniele, Cavallo, Roberto, Pignatta, Pietro, De Mattei, Marco, Geda, Claudio, Papurello, Diego Maria, Gusmaroli, Graziano, Comi, Cristoforo, Labate, Carmelo, Ruiz, Luigi, Ferrandi, Delfina, Rota, Eugenia, Aguggia, Marco, Di Vito, Nicoletta, Meineri, Piero, Ghiglione, Paolo, Launaro, Nicola, Dotta, Michele, Di Sapio, Alessia, Giardini, Guido, Tiloca, Cinzia, Peverelli, Silvia, Taroni, Franco, Pensato, Viviana, Castellotti, Barbara, Comi, Giacomo P., Del Bo, Roberto, Gagliardi, Stella, Raggi, Flavia, Simoncini, Costanza, Lo Gerfo, Annalisa, Inghilleri, Maurizio, Ferlini, Alessandra, Simone, Isabella L., Passarella, Bruno, Guerra, Vito, Zoccolella, Stefano, Nozzoli, Cecilia, Mundi, Ciro, Leone, Maurizio, Zarrelli, Michele, Tamma, Filippo, Valluzzi, Francesco, Calabrese, Gianluigi, Boero, Giovanni, Rini, Augusto, Traynor, Bryan J., Singleton, Andrew B., Mitne Neto, Miguel, Cauchi, Ruben J., Ophoff, Roel A., Wiedau-Pazos, Martina, Lomen-Hoerth, Catherine, van Deerlin, Vivianna M., Grosskreutz, Julian, Roediger, Annekathrin, Gaur, Nayana, Joerk, Alexander, Barthel, Tabea, Theele, Erik, Ilse, Benjamin, Stubendorff, Beatrice, Witte, Otto W., Steinbach, Robert, Huebner, Christian A., Graff, Caroline, Brylev, Lev, Fominykh, Vera, Demeshonok, Vera, Ataulina, Anastasia, Rogelj, Boris, Koritnik, Blaz, Zidar, Janez, Ravnik-Glavac, Metka, Glavac, Damjan, Stevic, Zorica, Drory, Vivian, Povedano, Monica, Blair, Ian P., Kiernan, Matthew C., Benyamin, Beben, Henderson, Robert D., Furlong, Sarah, Mathers, Susan, McCombe, Pamela A., Needham, Merrilee, Ngo, Shyuan T., Nicholson, Garth A., Pamphlett, Roger, Rowe, Dominic B., Steyn, Frederik J., Williams, Kelly L., Mather, Karen A., Sachdev, Perminder S., Henders, Anjali K., Wallace, Leanne, de Carvalho, Mamede, Pinto, Susana, Petri, Susanne, Weber, Markus, Rouleau, Guy A., Silani, Vincenzo, Curtis, Charles J., Breen, Gerome, Glass, Jonathan D., Brown, Robert H., Jr., Landers, John E., Shaw, Christopher E., Andersen, Peter M., Groen, Ewout J. N., van Es, Michael A., Pasterkamp, R. Jeroen, Fan, Dongsheng, Garton, Fleur C., McRae, Allan F., Davey Smith, George, Gaunt, Tom R., Eberle, Michael A., Mill, Jonathan, McLaughlin, Russell L., Hardiman, Orla, Kenna, Kevin P., Wray, Naomi R., Tsai, Ellen, Runz, Heiko, Franke, Lude, Al-Chalabi, Ammar, Van Damme, Philip, van den Berg, Leonard H., Veldink, Jan H., van Rheenen, Wouter, van der Spek, Rick A. A., Bakker, Mark K., van Vugt, Joke J. F. A., Hop, Paul J., Zwamborn, Ramona A. J., de Klein, Niek, Westra, Harm-Jan, Bakker, Olivier B., Deelen, Patrick, Shireby, Gemma, Hannon, Eilis, Moisse, Matthieu, Baird, Denis, Restuadi, Restuadi, Dolzhenko, Egor, Dekker, Annelot M., Gawor, Klara, Westeneng, Henk-Jan, Tazelaar, Gijs H. P., van Eijk, Kristel R., Kooyman, Maarten, Byrne, Ross P., Doherty, Mark, Heverin, Mark, Al Khleifat, Ahmad, Iacoangeli, Alfredo, Shatunov, Aleksey, Ticozzi, Nicola, Cooper-Knock, Johnathan, Smith, Bradley N., Gromicho, Marta, Chandran, Siddharthan, Pal, Suvankar, Morrison, Karen E., Shaw, Pamela J., Hardy, John, Orrell, Richard W., Sendtner, Michael, Meyer, Thomas, Basak, Nazli, van der Kooi, Anneke J., Ratti, Antonia, Fogh, Isabella, Gellera, Cinzia, Lauria, Giuseppe, Corti, Stefania, Cereda, Cristina, Sproviero, Daisy, D'Alfonso, Sandra, Soraru, Gianni, Siciliano, Gabriele, Filosto, Massimiliano, Padovani, Alessandro, Chio, Adriano, Calvo, Andrea, Moglia, Cristina, Brunetti, Maura, Canosa, Antonio, Grassano, Maurizio, Beghi, Ettore, Pupillo, Elisabetta, Logroscino, Giancarlo, Nefussy, Beatrice, Osmanovic, Alma, Nordin, Angelica, Lerner, Yossef, Zabari, Michal, Gotkine, Marc, Baloh, Robert H., Bell, Shaughn, Vourc'h, Patrick, Corcia, Philippe, Couratier, Philippe, Millecamps, Stephanie, Meininger, Vincent, Salachas, Francois, Mora Pardina, Jesus S., Assialioui, Abdelilah, Rojas-Garcia, Ricardo, Dion, Patrick A., Ross, Jay P., Ludolph, Albert C., Weishaupt, Jochen H., Brenner, David, Freischmidt, Axel, Bensimon, Gilbert, Brice, Alexis, Durr, Alexandra, Payan, Christine A. M., Saker-Delye, Safa, Wood, Nicholas W., Topp, Simon, Rademakers, Rosa, Tittmann, Lukas, Lieb, Wolfgang, Franke, Andre, Ripke, Stephan, Braun, Alice, Kraft, Julia, Whiteman, David C., Olsen, Catherine M., Uitterlinden, Andre G., Hofman, Albert, Rietschel, Marcella, Cichon, Sven, Nothen, Markus M., Amouyel, Philippe, Comi, Giancarlo, Riva, Nilo, Lunetta, Christian, Gerardi, Francesca, Cotelli, Maria Sofia, Rinaldi, Fabrizio, Chiveri, Luca, Guaita, Maria Cristina, Perrone, Patrizia, Ceroni, Mauro, Diamanti, Luca, Ferrarese, Carlo, Tremolizzo, Lucio, Delodovici, Maria Luisa, Bono, Giorgio, Manera, Umberto, Vasta, Rosario, Bombaci, Alessandro, Casale, Federico, Fuda, Giuseppe, Salamone, Paolina, Iazzolino, Barbara, Peotta, Laura, Cugnasco, Paolo, De Marco, Giovanni, Torrieri, Maria Claudia, Palumbo, Francesca, Gallone, Salvatore, Barberis, Marco, Sbaiz, Luca, Gentile, Salvatore, Mauro, Alessandro, Mazzini, Letizia, De Marchi, Fabiola, Corrado, Lucia, Bertolotto, Antonio, Gionco, Maurizio, Leotta, Daniela, Odddenino, Enrico, Imperiale, Daniele, Cavallo, Roberto, Pignatta, Pietro, De Mattei, Marco, Geda, Claudio, Papurello, Diego Maria, Gusmaroli, Graziano, Comi, Cristoforo, Labate, Carmelo, Ruiz, Luigi, Ferrandi, Delfina, Rota, Eugenia, Aguggia, Marco, Di Vito, Nicoletta, Meineri, Piero, Ghiglione, Paolo, Launaro, Nicola, Dotta, Michele, Di Sapio, Alessia, Giardini, Guido, Tiloca, Cinzia, Peverelli, Silvia, Taroni, Franco, Pensato, Viviana, Castellotti, Barbara, Comi, Giacomo P., Del Bo, Roberto, Gagliardi, Stella, Raggi, Flavia, Simoncini, Costanza, Lo Gerfo, Annalisa, Inghilleri, Maurizio, Ferlini, Alessandra, Simone, Isabella L., Passarella, Bruno, Guerra, Vito, Zoccolella, Stefano, Nozzoli, Cecilia, Mundi, Ciro, Leone, Maurizio, Zarrelli, Michele, Tamma, Filippo, Valluzzi, Francesco, Calabrese, Gianluigi, Boero, Giovanni, Rini, Augusto, Traynor, Bryan J., Singleton, Andrew B., Mitne Neto, Miguel, Cauchi, Ruben J., Ophoff, Roel A., Wiedau-Pazos, Martina, Lomen-Hoerth, Catherine, van Deerlin, Vivianna M., Grosskreutz, Julian, Roediger, Annekathrin, Gaur, Nayana, Joerk, Alexander, Barthel, Tabea, Theele, Erik, Ilse, Benjamin, Stubendorff, Beatrice, Witte, Otto W., Steinbach, Robert, Huebner, Christian A., Graff, Caroline, Brylev, Lev, Fominykh, Vera, Demeshonok, Vera, Ataulina, Anastasia, Rogelj, Boris, Koritnik, Blaz, Zidar, Janez, Ravnik-Glavac, Metka, Glavac, Damjan, Stevic, Zorica, Drory, Vivian, Povedano, Monica, Blair, Ian P., Kiernan, Matthew C., Benyamin, Beben, Henderson, Robert D., Furlong, Sarah, Mathers, Susan, McCombe, Pamela A., Needham, Merrilee, Ngo, Shyuan T., Nicholson, Garth A., Pamphlett, Roger, Rowe, Dominic B., Steyn, Frederik J., Williams, Kelly L., Mather, Karen A., Sachdev, Perminder S., Henders, Anjali K., Wallace, Leanne, de Carvalho, Mamede, Pinto, Susana, Petri, Susanne, Weber, Markus, Rouleau, Guy A., Silani, Vincenzo, Curtis, Charles J., Breen, Gerome, Glass, Jonathan D., Brown, Robert H., Jr., Landers, John E., Shaw, Christopher E., Andersen, Peter M., Groen, Ewout J. N., van Es, Michael A., Pasterkamp, R. Jeroen, Fan, Dongsheng, Garton, Fleur C., McRae, Allan F., Davey Smith, George, Gaunt, Tom R., Eberle, Michael A., Mill, Jonathan, McLaughlin, Russell L., Hardiman, Orla, Kenna, Kevin P., Wray, Naomi R., Tsai, Ellen, Runz, Heiko, Franke, Lude, Al-Chalabi, Ammar, Van Damme, Philip, van den Berg, Leonard H., and Veldink, Jan H.
Abstract: A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons.
Published: 2021
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23. Context dependency of disease-mediated competitive release in bat assemblages following white-nose syndrome

Author: Bombaci, Sara P., Russell, Robin E., St Germain, Michael J., Dobony, Christopher A., Ford, W. Mark, Loeb, Susan C., Jachowski, David S., Bombaci, Sara P., Russell, Robin E., St Germain, Michael J., Dobony, Christopher A., Ford, W. Mark, Loeb, Susan C., and Jachowski, David S.
Abstract: White-nose syndrome (WNS) has caused dramatic declines of several cave-hibernating bat species in North America since 2006, which has increased the activity of non-susceptible species in some geographic areas or during times of night formerly occupied by susceptible species-indicative of disease-mediated competitive release (DMCR). Yet, this pattern has not been evaluated across multiple bat assemblages simultaneously or across multiple years since WNS onset. We evaluated whether WNS altered spatial and temporal niche partitioning in bat assemblages at four locations in the eastern United States using long-term datasets of bat acoustic activity collected before and after WNS arrival. Activity of WNS-susceptible bat species decreased by 79-98% from pre-WNS levels across the four study locations, but only one of our four study sites provided strong evidence supporting the DMCR hypothesis in bats post-WNS. These results suggest that DMCR is likely dependent on the relative difference in activity by susceptible and non-susceptible species groups pre-WNS and the relative decline of susceptible species post-WNS allowing for competitive release, as well as the amount of time that had elapsed post-WNS. Our findings challenge the generality of WNS-mediated competitive release between susceptible and non-susceptible species and further highlight declining activity of some non-susceptible species, especially Lasiurus borealis, across three of four locations in the eastern United States. These results underscore the broader need for conservation efforts to address the multiple potential interacting drivers of bat declines on both WNS-susceptible and non-susceptible species.
Published: 2021
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24. Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Author: van Rheenen, W., van der Spek, R.A.A., Bakker, M.K., van Vugt, J.J.F.A., Hop, P.J., Zwamborn, R.A.J., de Klein, N., Westra, H-J, Bakker, O.B., Deelen, P., Shireby, G., Hannon, E., Moisse, M., Baird, D., Restuadi, R., Dolzhenko, E., Dekker, A.M., Gawor, K., Westeneng, H-J, Tazelaar, G.H.P., van Eijk, K.R., Kooyman, M., Byrne, R.P., Doherty, M., Heverin, M., Al Khleifat, A., Iacoangeli, A., Shatunov, A., Ticozzi, N., Cooper-Knock, J., Smith, B.N., Gromicho, M., Chandran, S., Pal, S., Morrison, K.E., Shaw, P.J., Hardy, J., Orrell, R.W., Sendtner, M., Meyer, T., Başak, N., van der Kooi, A.J., Ratti, A., Fogh, I., Gellera, C., Lauria, G., Corti, S., Cereda, C., Sproviero, D., D’alfonso, S., Sorarù, G., Siciliano, G., Filosto, M., Padovani, A., Chio, A., Calvo, A., Moglia, C., Brunetti, M., Canosa, A., Grassano, M., Beghi, E., Pupillo, E., Logroscino, G., Nefussy, B., Osmanovic, A., Nordin, A., Lerner, Y., Zabari, M., Gotkine, M., Baloh, R.H., Bell, S., Vourc’h, P., Corcia, P., Couratier, P., Millecamps, S., Meininger, V., Salachas, F., Mora Pardina, J.S., Assialioui, A., Rojas-García, R., Dion, P.A., Ross, J.P., Ludolph, A.C., Weishaupt, J.H., Brenner, D., Freischmidt, A., Bensimon, G., Brice, A., Durr, A., Payan, C.A.M., Saker-Delye, S., Wood, N.W., Topp, S., Rademakers, R., Tittmann, L., Lieb, W., Franke, A., Ripke, S., Braun, A., Kraft, J., Whiteman, D.C., Olsen, C.M., Uitterlinden, A.G., Hofman, A., Rietschel, M., Cichon, S., Nöthen, M.M., Amouyel, P., Comi, G., Riva, N., Lunetta, C., Gerardi, F., Cotelli, M.S., Rinaldi, F., Chiveri, L., Guaita, M.C., Perrone, P., Ceroni, M., Diamanti, L., Ferrarese, C., Tremolizzo, L., Delodovici, M.L., Bono, G., Manera, U., Vasta, R., Bombaci, A., Casale, F., Fuda, G., Salamone, P., Iazzolino, B., Peotta, L., Cugnasco, P., De Marco, G., Torrieri, M.C., Palumbo, F., Gallone, S., Barberis, M., Sbaiz, L., Gentile, S., Mauro, A., Mazzini, L., De Marchi, F., Corrado, L., D’Alfonso, S., Bertolotto, A., Gionco, M., Leotta, D., Odddenino, E., Imperiale, D., Cavallo, R., Pignatta, P., De Mattei, M., Geda, C., Papurello, D.M., Gusmaroli, G., Comi, C., Labate, C., Ruiz, L., Ferrandi, D., Rota, E., Aguggia, M., Di Vito, N., Meineri, P., Ghiglione, P., Launaro, N., Dotta, M., di Sapio, A., Giardini, G., Tiloca, C., Peverelli, S., Taroni, F., Pensato, V., Castellotti, B., Comi, G.P., Del Bo, R., Gagliardi, S., Raggi, F., Simoncini, C., Lo Gerfo, A., Inghilleri, M., Ferlini, A., Simone, I.L., Passarella, B., Guerra, V., Zoccolella, S., Nozzoli, C., Mundi, C., Leone, M., Zarrelli, M., Tamma, F., Valluzzi, F., Calabrese, G., Boero, G., Rini, A., Traynor, B.J., Singleton, A.B., Mitne Neto, M., Cauchi, R.J., Ophoff, R.A., Wiedau-Pazos, M., Lomen-Hoerth, C., van Deerlin, V.M., Grosskreutz, J., Roediger, A., Gaur, N., Jörk, A., Barthel, T., Theele, E., Ilse, B., Stubendorff, B., Witte, O.W., Steinbach, R., Hübner, C.A., Graff, C., Brylev, L., Fominykh, V., Demeshonok, V., Ataulina, A., Rogelj, B., Koritnik, B., Zidar, J., Ravnik-Glavač, M., Glavač, D., Stević, Z., Drory, V., Povedano, M., Blair, I.P., Kiernan, M.C., Benyamin, B., Henderson, R.D., Furlong, S., Mathers, S., McCombe, P.A., Needham, M., Ngo, S.T., Nicholson, G.A., Pamphlett, R., Rowe, D.B., Steyn, F.J., Williams, K.L., Mather, K.A., Sachdev, P.S., Henders, A.K., Wallace, L., de Carvalho, M., Pinto, S., Petri, S., Weber, M., Rouleau, G.A., Silani, V., Curtis, C.J., Breen, G., Glass, J.D., Brown, R.H., Landers, J.E., Shaw, C.E., Andersen, P.M., Groen, E.J.N., van Es, M.A., Pasterkamp, R.J., Fan, D., Garton, F.C., McRae, A.F., Davey Smith, G., Gaunt, T.R., Eberle, M.A., Mill, J., McLaughlin, R.L., Hardiman, O., Kenna, K.P., Wray, N.R., Tsai, E., Runz, H., Franke, L., Al-Chalabi, A., Van Damme, P., van den Berg, L.H., Veldink, J.H., van Rheenen, W., van der Spek, R.A.A., Bakker, M.K., van Vugt, J.J.F.A., Hop, P.J., Zwamborn, R.A.J., de Klein, N., Westra, H-J, Bakker, O.B., Deelen, P., Shireby, G., Hannon, E., Moisse, M., Baird, D., Restuadi, R., Dolzhenko, E., Dekker, A.M., Gawor, K., Westeneng, H-J, Tazelaar, G.H.P., van Eijk, K.R., Kooyman, M., Byrne, R.P., Doherty, M., Heverin, M., Al Khleifat, A., Iacoangeli, A., Shatunov, A., Ticozzi, N., Cooper-Knock, J., Smith, B.N., Gromicho, M., Chandran, S., Pal, S., Morrison, K.E., Shaw, P.J., Hardy, J., Orrell, R.W., Sendtner, M., Meyer, T., Başak, N., van der Kooi, A.J., Ratti, A., Fogh, I., Gellera, C., Lauria, G., Corti, S., Cereda, C., Sproviero, D., D’alfonso, S., Sorarù, G., Siciliano, G., Filosto, M., Padovani, A., Chio, A., Calvo, A., Moglia, C., Brunetti, M., Canosa, A., Grassano, M., Beghi, E., Pupillo, E., Logroscino, G., Nefussy, B., Osmanovic, A., Nordin, A., Lerner, Y., Zabari, M., Gotkine, M., Baloh, R.H., Bell, S., Vourc’h, P., Corcia, P., Couratier, P., Millecamps, S., Meininger, V., Salachas, F., Mora Pardina, J.S., Assialioui, A., Rojas-García, R., Dion, P.A., Ross, J.P., Ludolph, A.C., Weishaupt, J.H., Brenner, D., Freischmidt, A., Bensimon, G., Brice, A., Durr, A., Payan, C.A.M., Saker-Delye, S., Wood, N.W., Topp, S., Rademakers, R., Tittmann, L., Lieb, W., Franke, A., Ripke, S., Braun, A., Kraft, J., Whiteman, D.C., Olsen, C.M., Uitterlinden, A.G., Hofman, A., Rietschel, M., Cichon, S., Nöthen, M.M., Amouyel, P., Comi, G., Riva, N., Lunetta, C., Gerardi, F., Cotelli, M.S., Rinaldi, F., Chiveri, L., Guaita, M.C., Perrone, P., Ceroni, M., Diamanti, L., Ferrarese, C., Tremolizzo, L., Delodovici, M.L., Bono, G., Manera, U., Vasta, R., Bombaci, A., Casale, F., Fuda, G., Salamone, P., Iazzolino, B., Peotta, L., Cugnasco, P., De Marco, G., Torrieri, M.C., Palumbo, F., Gallone, S., Barberis, M., Sbaiz, L., Gentile, S., Mauro, A., Mazzini, L., De Marchi, F., Corrado, L., D’Alfonso, S., Bertolotto, A., Gionco, M., Leotta, D., Odddenino, E., Imperiale, D., Cavallo, R., Pignatta, P., De Mattei, M., Geda, C., Papurello, D.M., Gusmaroli, G., Comi, C., Labate, C., Ruiz, L., Ferrandi, D., Rota, E., Aguggia, M., Di Vito, N., Meineri, P., Ghiglione, P., Launaro, N., Dotta, M., di Sapio, A., Giardini, G., Tiloca, C., Peverelli, S., Taroni, F., Pensato, V., Castellotti, B., Comi, G.P., Del Bo, R., Gagliardi, S., Raggi, F., Simoncini, C., Lo Gerfo, A., Inghilleri, M., Ferlini, A., Simone, I.L., Passarella, B., Guerra, V., Zoccolella, S., Nozzoli, C., Mundi, C., Leone, M., Zarrelli, M., Tamma, F., Valluzzi, F., Calabrese, G., Boero, G., Rini, A., Traynor, B.J., Singleton, A.B., Mitne Neto, M., Cauchi, R.J., Ophoff, R.A., Wiedau-Pazos, M., Lomen-Hoerth, C., van Deerlin, V.M., Grosskreutz, J., Roediger, A., Gaur, N., Jörk, A., Barthel, T., Theele, E., Ilse, B., Stubendorff, B., Witte, O.W., Steinbach, R., Hübner, C.A., Graff, C., Brylev, L., Fominykh, V., Demeshonok, V., Ataulina, A., Rogelj, B., Koritnik, B., Zidar, J., Ravnik-Glavač, M., Glavač, D., Stević, Z., Drory, V., Povedano, M., Blair, I.P., Kiernan, M.C., Benyamin, B., Henderson, R.D., Furlong, S., Mathers, S., McCombe, P.A., Needham, M., Ngo, S.T., Nicholson, G.A., Pamphlett, R., Rowe, D.B., Steyn, F.J., Williams, K.L., Mather, K.A., Sachdev, P.S., Henders, A.K., Wallace, L., de Carvalho, M., Pinto, S., Petri, S., Weber, M., Rouleau, G.A., Silani, V., Curtis, C.J., Breen, G., Glass, J.D., Brown, R.H., Landers, J.E., Shaw, C.E., Andersen, P.M., Groen, E.J.N., van Es, M.A., Pasterkamp, R.J., Fan, D., Garton, F.C., McRae, A.F., Davey Smith, G., Gaunt, T.R., Eberle, M.A., Mill, J., McLaughlin, R.L., Hardiman, O., Kenna, K.P., Wray, N.R., Tsai, E., Runz, H., Franke, L., Al-Chalabi, A., Van Damme, P., van den Berg, L.H., and Veldink, J.H.
Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons.
Published: 2021

25. Harnessing the NEON data revolution to advance open environmental science with a diverse and data-capable community

Author: Nagy, RC, Nagy, RC, Balch, JK, Bissell, EK, Cattau, ME, Glenn, NF, Halpern, BS, Ilangakoon, N, Johnson, B, Joseph, MB, Marconi, S, O’Riordan, C, Sanovia, J, Swetnam, TL, Travis, WR, Wasser, LA, Woolner, E, Zarnetske, P, Abdulrahim, M, Adler, J, Barnes, G, Bartowitz, KJ, Blake, RE, Bombaci, SP, Brun, J, Buchanan, JD, Chadwick, KD, Chapman, MS, Chong, SS, Chung, YA, Corman, JR, Couret, J, Crispo, E, Doak, TG, Donnelly, A, Duffy, KA, Dunning, KH, Duran, SM, Edmonds, JW, Fairbanks, DE, Felton, AJ, Florian, CR, Gann, D, Gebhardt, M, Gill, NS, Gram, WK, Guo, JS, Harvey, BJ, Hayes, KR, Helmus, MR, Hensley, RT, Hondula, KL, Huang, T, Hundertmark, WJ, Iglesias, V, Jacinthe, PA, Jansen, LS, Jarzyna, MA, Johnson, TM, Jones, KD, Jones, MA, Just, MG, Kaddoura, YO, Kagawa-Vivani, AK, Kaushik, A, Keller, AB, King, KBS, Kitzes, J, Koontz, MJ, Kouba, PV, Kwan, WY, LaMontagne, JM, LaRue, EA, Li, D, Li, B, Lin, Y, Liptzin, D, Long, WA, Mahood, AL, Malloy, SS, Malone, SL, McGlinchy, JM, Meier, CL, Melbourne, BA, Mietkiewicz, N, Morisette, JT, Moustapha, M, Muscarella, C, Musinsky, J, Muthukrishnan, R, Naithani, K, Neely, M, Norman, K, Parker, SM, Perez Rocha, M, Petri, L, Ramey, CA, Record, S, Rossi, MW, SanClements, M, Scholl, VM, Nagy, RC, Nagy, RC, Balch, JK, Bissell, EK, Cattau, ME, Glenn, NF, Halpern, BS, Ilangakoon, N, Johnson, B, Joseph, MB, Marconi, S, O’Riordan, C, Sanovia, J, Swetnam, TL, Travis, WR, Wasser, LA, Woolner, E, Zarnetske, P, Abdulrahim, M, Adler, J, Barnes, G, Bartowitz, KJ, Blake, RE, Bombaci, SP, Brun, J, Buchanan, JD, Chadwick, KD, Chapman, MS, Chong, SS, Chung, YA, Corman, JR, Couret, J, Crispo, E, Doak, TG, Donnelly, A, Duffy, KA, Dunning, KH, Duran, SM, Edmonds, JW, Fairbanks, DE, Felton, AJ, Florian, CR, Gann, D, Gebhardt, M, Gill, NS, Gram, WK, Guo, JS, Harvey, BJ, Hayes, KR, Helmus, MR, Hensley, RT, Hondula, KL, Huang, T, Hundertmark, WJ, Iglesias, V, Jacinthe, PA, Jansen, LS, Jarzyna, MA, Johnson, TM, Jones, KD, Jones, MA, Just, MG, Kaddoura, YO, Kagawa-Vivani, AK, Kaushik, A, Keller, AB, King, KBS, Kitzes, J, Koontz, MJ, Kouba, PV, Kwan, WY, LaMontagne, JM, LaRue, EA, Li, D, Li, B, Lin, Y, Liptzin, D, Long, WA, Mahood, AL, Malloy, SS, Malone, SL, McGlinchy, JM, Meier, CL, Melbourne, BA, Mietkiewicz, N, Morisette, JT, Moustapha, M, Muscarella, C, Musinsky, J, Muthukrishnan, R, Naithani, K, Neely, M, Norman, K, Parker, SM, Perez Rocha, M, Petri, L, Ramey, CA, Record, S, Rossi, MW, SanClements, M, and Scholl, VM
Abstract: It is a critical time to reflect on the National Ecological Observatory Network (NEON) science to date as well as envision what research can be done right now with NEON (and other) data and what training is needed to enable a diverse user community. NEON became fully operational in May 2019 and has pivoted from planning and construction to operation and maintenance. In this overview, the history of and foundational thinking around NEON are discussed. A framework of open science is described with a discussion of how NEON can be situated as part of a larger data constellation—across existing networks and different suites of ecological measurements and sensors. Next, a synthesis of early NEON science, based on >100 existing publications, funded proposal efforts, and emergent science at the very first NEON Science Summit (hosted by Earth Lab at the University of Colorado Boulder in October 2019) is provided. Key questions that the ecology community will address with NEON data in the next 10 yr are outlined, from understanding drivers of biodiversity across spatial and temporal scales to defining complex feedback mechanisms in human–environmental systems. Last, the essential elements needed to engage and support a diverse and inclusive NEON user community are highlighted: training resources and tools that are openly available, funding for broad community engagement initiatives, and a mechanism to share and advertise those opportunities. NEON users require both the skills to work with NEON data and the ecological or environmental science domain knowledge to understand and interpret them. This paper synthesizes early directions in the community’s use of NEON data, and opportunities for the next 10 yr of NEON operations in emergent science themes, open science best practices, education and training, and community building.
Published: 2021

26. Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Author: Başak, Ayşe Nazlı (ORCID 0000-0001-9257-3540 & YÖK ID 1512), van Rheenen, W.; Van der Spek, R.A.A.; Bakker, M.K.; van Vugt, J.J.F.A.; Hop, P.J.; Zwamborn, R.A.J.; de Klein, N.; Westra, H.J.; Bakker, O.B.; Deelen, P.; Shireby, G.; Hannon, E.; Moisse, M.; Baird, D.; Restuadi, R.; Dolzhenko, E.; Dekker, A.M.; Gawor, K.; Westeneng, H.J.; Tazelaar, G.H.P.; van Eijk, K.R.; Kooyman, M.; Byrne, R.P.; Doherty, M.; Heverin, M.; Al Khleifat, A.; Iacoangeli, A.; Shatunov, A.; Ticozzi, N.; Cooper-Knock, J.; Smith, B.N.; Gromicho, M.; Chandran, S.; Pal, S.; Morrison, K.E.; Shaw, P.J.; Hardy, J.; Orrell, R.W.; Sendtner, M.; Meyer, T.; van der Kooi, A.J.; Ratti, A.; Fogh, I.; Gellera, C.; Lauria, G.; Corti, S.; Cereda, C.; Sproviero, D.; D'Alfonso, S.; Sorarù, G.; Siciliano, G.; Filosto, M.; Padovani, A.; Chiò, A.; Calvo, A.; Moglia, C.; Brunetti, M.; Canosa, A.; Grassano, M.; Beghi, E.; Pupillo, E.; Logroscino, G.; Nefussy, B.; Osmanovic, A.; Nordin, A.; Lerner, Y.; Zabari, M.; Gotkine, M.; Baloh, R.H.; Bell, S.; Vourc'h, P.; Corcia, P.; Couratier, P.; Millecamps, S.; Meininger, V.; Salachas, F.; Mora Pardina, J.S.; Assialioui, A.; Rojas-García, R.; Dion, P.A.; Ross, J.P.; Ludolph, A.C.; Weishaupt, J.H.; Brenner, D.; Freischmidt, A.; Bensimon, G.; Brice, A.; Durr, A.; Payan, C.A.M.; Saker-Delye, S.; Wood, N.W.; Topp, S.; Rademakers, R.; Tittmann, L.; Lieb, W.; Franke, A.; Ripke, S.; Braun, A; Kraft, J.,Whiteman, David C.; Olsen, Catherine M.; Uitterlinden, A.G.; Hofman, A.; Rietschel, M.; Cichon, S.; Nothen, M.M.; Amouyel, P.; Comi, G.; Riva, N.; Lunetta, C.; Gerardi, F.; Cotelli, M.S.; Rinaldi, F.; Chiveri, L.; Guaita, M.C.; Perrone, P.; Ceroni, M.; Diamanti, L.; Ferrarese, C.; Tremolizzo, L.; Delodovici, M.L.; Bono, G.; Manera, U.; Vasta, R.; Bombaci, A.; Casale, F.; Fuda, G.; Salamone, P.; Iazzolino, B.; Peotta, L.; Cugnasco, P.; De Marco, G.; Torrieri, M.C.; Palumbo, F.; Gallone, S.; Barberis, M.; Sbaiz, L.; Gentile, S.; Mauro, A.; Mazzini, L.; De Marchi, F.; Corrado, L.; D'Alfonso, S.; Bertolotto, A.; Gionco, M.; Leotta, D.; Odddenino, Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), School of Medicine, Başak, Ayşe Nazlı (ORCID 0000-0001-9257-3540 & YÖK ID 1512), van Rheenen, W.; Van der Spek, R.A.A.; Bakker, M.K.; van Vugt, J.J.F.A.; Hop, P.J.; Zwamborn, R.A.J.; de Klein, N.; Westra, H.J.; Bakker, O.B.; Deelen, P.; Shireby, G.; Hannon, E.; Moisse, M.; Baird, D.; Restuadi, R.; Dolzhenko, E.; Dekker, A.M.; Gawor, K.; Westeneng, H.J.; Tazelaar, G.H.P.; van Eijk, K.R.; Kooyman, M.; Byrne, R.P.; Doherty, M.; Heverin, M.; Al Khleifat, A.; Iacoangeli, A.; Shatunov, A.; Ticozzi, N.; Cooper-Knock, J.; Smith, B.N.; Gromicho, M.; Chandran, S.; Pal, S.; Morrison, K.E.; Shaw, P.J.; Hardy, J.; Orrell, R.W.; Sendtner, M.; Meyer, T.; van der Kooi, A.J.; Ratti, A.; Fogh, I.; Gellera, C.; Lauria, G.; Corti, S.; Cereda, C.; Sproviero, D.; D'Alfonso, S.; Sorarù, G.; Siciliano, G.; Filosto, M.; Padovani, A.; Chiò, A.; Calvo, A.; Moglia, C.; Brunetti, M.; Canosa, A.; Grassano, M.; Beghi, E.; Pupillo, E.; Logroscino, G.; Nefussy, B.; Osmanovic, A.; Nordin, A.; Lerner, Y.; Zabari, M.; Gotkine, M.; Baloh, R.H.; Bell, S.; Vourc'h, P.; Corcia, P.; Couratier, P.; Millecamps, S.; Meininger, V.; Salachas, F.; Mora Pardina, J.S.; Assialioui, A.; Rojas-García, R.; Dion, P.A.; Ross, J.P.; Ludolph, A.C.; Weishaupt, J.H.; Brenner, D.; Freischmidt, A.; Bensimon, G.; Brice, A.; Durr, A.; Payan, C.A.M.; Saker-Delye, S.; Wood, N.W.; Topp, S.; Rademakers, R.; Tittmann, L.; Lieb, W.; Franke, A.; Ripke, S.; Braun, A; Kraft, J.,Whiteman, David C.; Olsen, Catherine M.; Uitterlinden, A.G.; Hofman, A.; Rietschel, M.; Cichon, S.; Nothen, M.M.; Amouyel, P.; Comi, G.; Riva, N.; Lunetta, C.; Gerardi, F.; Cotelli, M.S.; Rinaldi, F.; Chiveri, L.; Guaita, M.C.; Perrone, P.; Ceroni, M.; Diamanti, L.; Ferrarese, C.; Tremolizzo, L.; Delodovici, M.L.; Bono, G.; Manera, U.; Vasta, R.; Bombaci, A.; Casale, F.; Fuda, G.; Salamone, P.; Iazzolino, B.; Peotta, L.; Cugnasco, P.; De Marco, G.; Torrieri, M.C.; Palumbo, F.; Gallone, S.; Barberis, M.; Sbaiz, L.; Gentile, S.; Mauro, A.; Mazzini, L.; De Marchi, F.; Corrado, L.; D'Alfonso, S.; Bertolotto, A.; Gionco, M.; Leotta, D.; Odddenino, Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), and School of Medicine
Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons., Dutch Research Council (NWO); VENI Scheme Grant; VIDI Grant; Prinses Beatrix Spierfonds; Neuromuscular Fellowship Grant; Medical Research Council (MRC); Clinical Infrastructure Award; Epidemiology Unit; Integrative Epidemiology Unit; Canadian Institutes of Health Research; IWT; National Institute on Aging; National Health and Medical Research Council (NHMRC); Enabling Grant; NHMRC/Australian Research Council Strategic Award; NHMRC; NHMRC Centre of Research Excellence Grant; National Health and Medical Research Council of Australia (NHMRC) Research Fellowship; United Kingdom, Medical Research Council; Economic and Social Research Council; European Union (EU); Horizon 2020; European Community's Health Seventh Framework Programme; EuroMOTOR; European Research Council (ERC); Research and Innovation Programme; EScORIAL; ALS Foundation Netherlands; Alzheimer’s Society PhD Studentship; ARSla Funding; Biogen; University of Bristol; Motor Neurone Disease Association (MNDA); NIHR Maudsley Biomedical Research Centre; Dutch Ministry of Education, Culture, and Science; Netherlands Organization for Scientific Research (NWO; BRAINSCAPES); Gravitation Program; ALS Liga België; National Lottery of Belgium; KU Leuven Opening the Future Fund; KU Leuven Funds, “Een Hart voor ALS”, “Laeversfonds voor ALS Onderzoek” and the “Valéry Perrier Race against ALS Fund”; E. von Behring Chair for Neuromuscular and Neurodegenerative Disorders; ALS Liga België; “Live now” Charity Foundation; Moscow ALS palliative Care Service; Canadian Institutes of Health; Research Australia; Ice Bucket Challenge Grant; NIH Intramural Research Programs; FightMND Mid-Career Fellowship; NIHR Senior Investigator; Sheffield NIHR Biomedical Research Centre; Motor Neurone Disease Association; National Institute for Health Research (NIHR) Biomedical Research Centre; Maudsley NHS Foundation Trust; King’s College London; NIHR Senior Investigator Award; Netherlands Organization for Health Research and Development; Vici Sche
Published: 2021

27. Context dependency of disease-mediated competitive release in bat assemblages following white-nose syndrome

Author: Bombaci, Sara P., Russell, Robin E., St Germain, Michael J., Dobony, Christopher A., Ford, W. Mark, Loeb, Susan C., Jachowski, David S., Bombaci, Sara P., Russell, Robin E., St Germain, Michael J., Dobony, Christopher A., Ford, W. Mark, Loeb, Susan C., and Jachowski, David S.
Abstract: White-nose syndrome (WNS) has caused dramatic declines of several cave-hibernating bat species in North America since 2006, which has increased the activity of non-susceptible species in some geographic areas or during times of night formerly occupied by susceptible species-indicative of disease-mediated competitive release (DMCR). Yet, this pattern has not been evaluated across multiple bat assemblages simultaneously or across multiple years since WNS onset. We evaluated whether WNS altered spatial and temporal niche partitioning in bat assemblages at four locations in the eastern United States using long-term datasets of bat acoustic activity collected before and after WNS arrival. Activity of WNS-susceptible bat species decreased by 79-98% from pre-WNS levels across the four study locations, but only one of our four study sites provided strong evidence supporting the DMCR hypothesis in bats post-WNS. These results suggest that DMCR is likely dependent on the relative difference in activity by susceptible and non-susceptible species groups pre-WNS and the relative decline of susceptible species post-WNS allowing for competitive release, as well as the amount of time that had elapsed post-WNS. Our findings challenge the generality of WNS-mediated competitive release between susceptible and non-susceptible species and further highlight declining activity of some non-susceptible species, especially Lasiurus borealis, across three of four locations in the eastern United States. These results underscore the broader need for conservation efforts to address the multiple potential interacting drivers of bat declines on both WNS-susceptible and non-susceptible species.
Published: 2021

28. Boris: a Spoken Conversational Agent for Music Production for People with Motor Disabilities

Author: Catania, F, Crovari, P, Beccaluva, E, De Luca, G, Colombo, E, Bombaci, N, Garzotto, F, Catania, F, Crovari, P, Beccaluva, E, De Luca, G, Colombo, E, Bombaci, N, and Garzotto, F
Abstract: Previous studies suggest that engagement in musical activities may enhance well-being and impact social inclusion. However, unfortunately, people with physical disabilities cannot often use musical instruments or music production software due to accessibility issues. We propose Boris, an original conversational agent specific for people with a physical disability, to entertain, stimulate expressiveness, and promote communication. Boris enables (even inexperienced) users to compose songs through hands-free interaction by analyzing their vocalizations to obtain more than just their transcription: the system listens to the user even while humming a song and generates a melody by learning and reproducing their human voice patterns. Indeed, it exploits an artificial musical intelligence that can imitate the typically human cognitive skills to produce music using an advanced technique called abstract melody.
Published: 2021

29. Numerical relativity simulations of prompt collapse mergers: threshold mass and phenomenological constraints on neutron star properties after GW170817

Author: Kashyap, Rahul, Das, Abhishek, Radice, David, Padamata, Surendra, Prakash, Aviral, Logoteta, Domenico, Perego, Albino, Godzieba, Daniel A., Bernuzzi, Sebastiano, Bombaci, Ignazio, Fattoyev, Farrukh J., Reed, Brendan T., Schneider, André da Silva, Kashyap, Rahul, Das, Abhishek, Radice, David, Padamata, Surendra, Prakash, Aviral, Logoteta, Domenico, Perego, Albino, Godzieba, Daniel A., Bernuzzi, Sebastiano, Bombaci, Ignazio, Fattoyev, Farrukh J., Reed, Brendan T., and Schneider, André da Silva
Abstract: We determine the threshold mass for prompt (no bounce) black hole formation in equal-mass neutron star (NS) mergers using a new set of 227 numerical relativity simulations. We consider 23 phenomenological and microphysical finite temperature equations of state (EOS), including models with hyperons and first-order phase transitions to deconfined quarks. We confirm the existence of EOS-insensitive relations between the threshold mass, the binary tidal parameter at the threshold ($\Lambda_{th}$), the maximum mass of nonrotating NSs, and the radii of reference mass NSs. We correct the systematic errors in previously reported fitting coefficients that were obtained with approximate general-relativity simulations. We combine the EOS-insensitive relations, phenomenological constraints on NS properties and observational data from GW170817 to derive an improved lower limit on radii of maximum mass and 1.6 M$_\odot$ NS of 9.81 km and 10.90 km, respectively. We also constrain the radius and quadrupolar tidal deformability ($\Lambda$) of a 1.4 $M_\odot$ NS to be larger than 10.74 km and 172, respectively. We consider uncertainties in all independent parameters -- fitting coefficients as well as GW170817 masses while reporting the range of radii constraints. We introduce new methods to constrain the upper as well as lower limit of NS maximum mass using future BNS detections and their identification as prompt or delayed collapse. With future observations it will be possible to derive even tighter constraints on the properties of matter at and above nuclear density using the method proposed in this work., Comment: Accepted for publication in Physical Review D
Published: 2021
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30. Signatures of deconfined quark phases in binary neutron star mergers

Author: Prakash, Aviral, Radice, David, Logoteta, Domenico, Perego, Albino, Nedora, Vsevolod, Bombaci, Ignazio, Kashyap, Rahul, Bernuzzi, Sebastiano, Endrizzi, Andrea, Prakash, Aviral, Radice, David, Logoteta, Domenico, Perego, Albino, Nedora, Vsevolod, Bombaci, Ignazio, Kashyap, Rahul, Bernuzzi, Sebastiano, and Endrizzi, Andrea
Abstract: (abridged) We investigate the quark deconfinement phase transition in the context of binary neutron star (BNS) mergers. We employ a new finite-temperature composition-dependent equation of state (EOS) with a first order phase transition between hadrons and deconfined quarks to perform numerical relativity simulations of BNS mergers. The softening of the EOS due to the phase transition causes the merger remnants to be more compact and to collapse to a black hole (BH) at earlier times. The phase transition is imprinted on the postmerger gravitational wave (GW) signal duration, amplitude, and peak frequency. However, this imprint is only detectable for binaries with sufficiently long-lived remnants. Moreover, the phase transition does not result in significant deviations from quasi-universal relations for the postmerger GW peak frequency. We also study the impact of the phase transition on dynamical ejecta, remnant accretion disk masses, r-process nucleosynthetic yields and associated electromagnetic (EM) counterparts. While there are differences in the EM counterparts and nucleosynthesis yields between the purely hadronic models and the models with phase transitions, these can be primarily ascribed to the difference in remnant collapse time between the two. An exception is the non-thermal afterglow caused by the interaction of the fastest component of the dynamical ejecta and the interstellar medium, which is systematically boosted in the binaries with phase transition as a consequence of the more violent merger they experience., Comment: 28 pages and 16 figures
Published: 2021
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31. Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Author: van Rheenen, Wouter, van der Spek, Rick A. A., Bakker, Mark K., van Vugt, Joke J. F. A., Hop, Paul J., Zwamborn, Ramona A. J., de Klein, Niek, Westra, Harm-Jan, Bakker, Olivier B., Deelen, Patrick, Shireby, Gemma, Hannon, Eilis, Moisse, Matthieu, Baird, Denis, Restuadi, Restuadi, Dolzhenko, Egor, Dekker, Annelot M., Gawor, Klara, Westeneng, Henk-Jan, Tazelaar, Gijs H. P., van Eijk, Kristel R., Kooyman, Maarten, Byrne, Ross P., Doherty, Mark, Heverin, Mark, Al Khleifat, Ahmad, Iacoangeli, Alfredo, Shatunov, Aleksey, Ticozzi, Nicola, Cooper-Knock, Johnathan, Smith, Bradley N., Gromicho, Marta, Chandran, Siddharthan, Pal, Suvankar, Morrison, Karen E., Shaw, Pamela J., Hardy, John, Orrell, Richard W., Sendtner, Michael, Meyer, Thomas, Basak, Nazli, van der Kooi, Anneke J., Ratti, Antonia, Fogh, Isabella, Gellera, Cinzia, Lauria, Giuseppe, Corti, Stefania, Cereda, Cristina, Sproviero, Daisy, D'Alfonso, Sandra, Soraru, Gianni, Siciliano, Gabriele, Filosto, Massimiliano, Padovani, Alessandro, Chio, Adriano, Calvo, Andrea, Moglia, Cristina, Brunetti, Maura, Canosa, Antonio, Grassano, Maurizio, Beghi, Ettore, Pupillo, Elisabetta, Logroscino, Giancarlo, Nefussy, Beatrice, Osmanovic, Alma, Nordin, Angelica, Lerner, Yossef, Zabari, Michal, Gotkine, Marc, Baloh, Robert H., Bell, Shaughn, Vourc'h, Patrick, Corcia, Philippe, Couratier, Philippe, Millecamps, Stephanie, Meininger, Vincent, Salachas, Francois, Mora Pardina, Jesus S., Assialioui, Abdelilah, Rojas-Garcia, Ricardo, Dion, Patrick A., Ross, Jay P., Ludolph, Albert C., Weishaupt, Jochen H., Brenner, David, Freischmidt, Axel, Bensimon, Gilbert, Brice, Alexis, Durr, Alexandra, Payan, Christine A. M., Saker-Delye, Safa, Wood, Nicholas W., Topp, Simon, Rademakers, Rosa, Tittmann, Lukas, Lieb, Wolfgang, Franke, Andre, Ripke, Stephan, Braun, Alice, Kraft, Julia, Whiteman, David C., Olsen, Catherine M., Uitterlinden, Andre G., Hofman, Albert, Rietschel, Marcella, Cichon, Sven, Nothen, Markus M., Amouyel, Philippe, Comi, Giancarlo, Riva, Nilo, Lunetta, Christian, Gerardi, Francesca, Cotelli, Maria Sofia, Rinaldi, Fabrizio, Chiveri, Luca, Guaita, Maria Cristina, Perrone, Patrizia, Ceroni, Mauro, Diamanti, Luca, Ferrarese, Carlo, Tremolizzo, Lucio, Delodovici, Maria Luisa, Bono, Giorgio, Manera, Umberto, Vasta, Rosario, Bombaci, Alessandro, Casale, Federico, Fuda, Giuseppe, Salamone, Paolina, Iazzolino, Barbara, Peotta, Laura, Cugnasco, Paolo, De Marco, Giovanni, Torrieri, Maria Claudia, Palumbo, Francesca, Gallone, Salvatore, Barberis, Marco, Sbaiz, Luca, Gentile, Salvatore, Mauro, Alessandro, Mazzini, Letizia, De Marchi, Fabiola, Corrado, Lucia, Bertolotto, Antonio, Gionco, Maurizio, Leotta, Daniela, Odddenino, Enrico, Imperiale, Daniele, Cavallo, Roberto, Pignatta, Pietro, De Mattei, Marco, Geda, Claudio, Papurello, Diego Maria, Gusmaroli, Graziano, Comi, Cristoforo, Labate, Carmelo, Ruiz, Luigi, Ferrandi, Delfina, Rota, Eugenia, Aguggia, Marco, Di Vito, Nicoletta, Meineri, Piero, Ghiglione, Paolo, Launaro, Nicola, Dotta, Michele, Di Sapio, Alessia, Giardini, Guido, Tiloca, Cinzia, Peverelli, Silvia, Taroni, Franco, Pensato, Viviana, Castellotti, Barbara, Comi, Giacomo P., Del Bo, Roberto, Gagliardi, Stella, Raggi, Flavia, Simoncini, Costanza, Lo Gerfo, Annalisa, Inghilleri, Maurizio, Ferlini, Alessandra, Simone, Isabella L., Passarella, Bruno, Guerra, Vito, Zoccolella, Stefano, Nozzoli, Cecilia, Mundi, Ciro, Leone, Maurizio, Zarrelli, Michele, Tamma, Filippo, Valluzzi, Francesco, Calabrese, Gianluigi, Boero, Giovanni, Rini, Augusto, Traynor, Bryan J., Singleton, Andrew B., Mitne Neto, Miguel, Cauchi, Ruben J., Ophoff, Roel A., Wiedau-Pazos, Martina, Lomen-Hoerth, Catherine, van Deerlin, Vivianna M., Grosskreutz, Julian, Roediger, Annekathrin, Gaur, Nayana, Joerk, Alexander, Barthel, Tabea, Theele, Erik, Ilse, Benjamin, Stubendorff, Beatrice, Witte, Otto W., Steinbach, Robert, Huebner, Christian A., Graff, Caroline, Brylev, Lev, Fominykh, Vera, Demeshonok, Vera, Ataulina, Anastasia, Rogelj, Boris, Koritnik, Blaz, Zidar, Janez, Ravnik-Glavac, Metka, Glavac, Damjan, Stevic, Zorica, Drory, Vivian, Povedano, Monica, Blair, Ian P., Kiernan, Matthew C., Benyamin, Beben, Henderson, Robert D., Furlong, Sarah, Mathers, Susan, McCombe, Pamela A., Needham, Merrilee, Ngo, Shyuan T., Nicholson, Garth A., Pamphlett, Roger, Rowe, Dominic B., Steyn, Frederik J., Williams, Kelly L., Mather, Karen A., Sachdev, Perminder S., Henders, Anjali K., Wallace, Leanne, de Carvalho, Mamede, Pinto, Susana, Petri, Susanne, Weber, Markus, Rouleau, Guy A., Silani, Vincenzo, Curtis, Charles J., Breen, Gerome, Glass, Jonathan D., Brown, Robert H., Jr., Landers, John E., Shaw, Christopher E., Andersen, Peter M., Groen, Ewout J. N., van Es, Michael A., Pasterkamp, R. Jeroen, Fan, Dongsheng, Garton, Fleur C., McRae, Allan F., Davey Smith, George, Gaunt, Tom R., Eberle, Michael A., Mill, Jonathan, McLaughlin, Russell L., Hardiman, Orla, Kenna, Kevin P., Wray, Naomi R., Tsai, Ellen, Runz, Heiko, Franke, Lude, Al-Chalabi, Ammar, Van Damme, Philip, van den Berg, Leonard H., Veldink, Jan H., van Rheenen, Wouter, van der Spek, Rick A. A., Bakker, Mark K., van Vugt, Joke J. F. A., Hop, Paul J., Zwamborn, Ramona A. J., de Klein, Niek, Westra, Harm-Jan, Bakker, Olivier B., Deelen, Patrick, Shireby, Gemma, Hannon, Eilis, Moisse, Matthieu, Baird, Denis, Restuadi, Restuadi, Dolzhenko, Egor, Dekker, Annelot M., Gawor, Klara, Westeneng, Henk-Jan, Tazelaar, Gijs H. P., van Eijk, Kristel R., Kooyman, Maarten, Byrne, Ross P., Doherty, Mark, Heverin, Mark, Al Khleifat, Ahmad, Iacoangeli, Alfredo, Shatunov, Aleksey, Ticozzi, Nicola, Cooper-Knock, Johnathan, Smith, Bradley N., Gromicho, Marta, Chandran, Siddharthan, Pal, Suvankar, Morrison, Karen E., Shaw, Pamela J., Hardy, John, Orrell, Richard W., Sendtner, Michael, Meyer, Thomas, Basak, Nazli, van der Kooi, Anneke J., Ratti, Antonia, Fogh, Isabella, Gellera, Cinzia, Lauria, Giuseppe, Corti, Stefania, Cereda, Cristina, Sproviero, Daisy, D'Alfonso, Sandra, Soraru, Gianni, Siciliano, Gabriele, Filosto, Massimiliano, Padovani, Alessandro, Chio, Adriano, Calvo, Andrea, Moglia, Cristina, Brunetti, Maura, Canosa, Antonio, Grassano, Maurizio, Beghi, Ettore, Pupillo, Elisabetta, Logroscino, Giancarlo, Nefussy, Beatrice, Osmanovic, Alma, Nordin, Angelica, Lerner, Yossef, Zabari, Michal, Gotkine, Marc, Baloh, Robert H., Bell, Shaughn, Vourc'h, Patrick, Corcia, Philippe, Couratier, Philippe, Millecamps, Stephanie, Meininger, Vincent, Salachas, Francois, Mora Pardina, Jesus S., Assialioui, Abdelilah, Rojas-Garcia, Ricardo, Dion, Patrick A., Ross, Jay P., Ludolph, Albert C., Weishaupt, Jochen H., Brenner, David, Freischmidt, Axel, Bensimon, Gilbert, Brice, Alexis, Durr, Alexandra, Payan, Christine A. M., Saker-Delye, Safa, Wood, Nicholas W., Topp, Simon, Rademakers, Rosa, Tittmann, Lukas, Lieb, Wolfgang, Franke, Andre, Ripke, Stephan, Braun, Alice, Kraft, Julia, Whiteman, David C., Olsen, Catherine M., Uitterlinden, Andre G., Hofman, Albert, Rietschel, Marcella, Cichon, Sven, Nothen, Markus M., Amouyel, Philippe, Comi, Giancarlo, Riva, Nilo, Lunetta, Christian, Gerardi, Francesca, Cotelli, Maria Sofia, Rinaldi, Fabrizio, Chiveri, Luca, Guaita, Maria Cristina, Perrone, Patrizia, Ceroni, Mauro, Diamanti, Luca, Ferrarese, Carlo, Tremolizzo, Lucio, Delodovici, Maria Luisa, Bono, Giorgio, Manera, Umberto, Vasta, Rosario, Bombaci, Alessandro, Casale, Federico, Fuda, Giuseppe, Salamone, Paolina, Iazzolino, Barbara, Peotta, Laura, Cugnasco, Paolo, De Marco, Giovanni, Torrieri, Maria Claudia, Palumbo, Francesca, Gallone, Salvatore, Barberis, Marco, Sbaiz, Luca, Gentile, Salvatore, Mauro, Alessandro, Mazzini, Letizia, De Marchi, Fabiola, Corrado, Lucia, Bertolotto, Antonio, Gionco, Maurizio, Leotta, Daniela, Odddenino, Enrico, Imperiale, Daniele, Cavallo, Roberto, Pignatta, Pietro, De Mattei, Marco, Geda, Claudio, Papurello, Diego Maria, Gusmaroli, Graziano, Comi, Cristoforo, Labate, Carmelo, Ruiz, Luigi, Ferrandi, Delfina, Rota, Eugenia, Aguggia, Marco, Di Vito, Nicoletta, Meineri, Piero, Ghiglione, Paolo, Launaro, Nicola, Dotta, Michele, Di Sapio, Alessia, Giardini, Guido, Tiloca, Cinzia, Peverelli, Silvia, Taroni, Franco, Pensato, Viviana, Castellotti, Barbara, Comi, Giacomo P., Del Bo, Roberto, Gagliardi, Stella, Raggi, Flavia, Simoncini, Costanza, Lo Gerfo, Annalisa, Inghilleri, Maurizio, Ferlini, Alessandra, Simone, Isabella L., Passarella, Bruno, Guerra, Vito, Zoccolella, Stefano, Nozzoli, Cecilia, Mundi, Ciro, Leone, Maurizio, Zarrelli, Michele, Tamma, Filippo, Valluzzi, Francesco, Calabrese, Gianluigi, Boero, Giovanni, Rini, Augusto, Traynor, Bryan J., Singleton, Andrew B., Mitne Neto, Miguel, Cauchi, Ruben J., Ophoff, Roel A., Wiedau-Pazos, Martina, Lomen-Hoerth, Catherine, van Deerlin, Vivianna M., Grosskreutz, Julian, Roediger, Annekathrin, Gaur, Nayana, Joerk, Alexander, Barthel, Tabea, Theele, Erik, Ilse, Benjamin, Stubendorff, Beatrice, Witte, Otto W., Steinbach, Robert, Huebner, Christian A., Graff, Caroline, Brylev, Lev, Fominykh, Vera, Demeshonok, Vera, Ataulina, Anastasia, Rogelj, Boris, Koritnik, Blaz, Zidar, Janez, Ravnik-Glavac, Metka, Glavac, Damjan, Stevic, Zorica, Drory, Vivian, Povedano, Monica, Blair, Ian P., Kiernan, Matthew C., Benyamin, Beben, Henderson, Robert D., Furlong, Sarah, Mathers, Susan, McCombe, Pamela A., Needham, Merrilee, Ngo, Shyuan T., Nicholson, Garth A., Pamphlett, Roger, Rowe, Dominic B., Steyn, Frederik J., Williams, Kelly L., Mather, Karen A., Sachdev, Perminder S., Henders, Anjali K., Wallace, Leanne, de Carvalho, Mamede, Pinto, Susana, Petri, Susanne, Weber, Markus, Rouleau, Guy A., Silani, Vincenzo, Curtis, Charles J., Breen, Gerome, Glass, Jonathan D., Brown, Robert H., Jr., Landers, John E., Shaw, Christopher E., Andersen, Peter M., Groen, Ewout J. N., van Es, Michael A., Pasterkamp, R. Jeroen, Fan, Dongsheng, Garton, Fleur C., McRae, Allan F., Davey Smith, George, Gaunt, Tom R., Eberle, Michael A., Mill, Jonathan, McLaughlin, Russell L., Hardiman, Orla, Kenna, Kevin P., Wray, Naomi R., Tsai, Ellen, Runz, Heiko, Franke, Lude, Al-Chalabi, Ammar, Van Damme, Philip, van den Berg, Leonard H., and Veldink, Jan H.
Abstract: A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons.
Published: 2021
Full Text: View/download PDF

32. Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Author: van Rheenen, Wouter, van der Spek, Rick A. A., Bakker, Mark K., van Vugt, Joke J. F. A., Hop, Paul J., Zwamborn, Ramona A. J., de Klein, Niek, Westra, Harm-Jan, Bakker, Olivier B., Deelen, Patrick, Shireby, Gemma, Hannon, Eilis, Moisse, Matthieu, Baird, Denis, Restuadi, Restuadi, Dolzhenko, Egor, Dekker, Annelot M., Gawor, Klara, Westeneng, Henk-Jan, Tazelaar, Gijs H. P., van Eijk, Kristel R., Kooyman, Maarten, Byrne, Ross P., Doherty, Mark, Heverin, Mark, Al Khleifat, Ahmad, Iacoangeli, Alfredo, Shatunov, Aleksey, Ticozzi, Nicola, Cooper-Knock, Johnathan, Smith, Bradley N., Gromicho, Marta, Chandran, Siddharthan, Pal, Suvankar, Morrison, Karen E., Shaw, Pamela J., Hardy, John, Orrell, Richard W., Sendtner, Michael, Meyer, Thomas, Basak, Nazli, van der Kooi, Anneke J., Ratti, Antonia, Fogh, Isabella, Gellera, Cinzia, Lauria, Giuseppe, Corti, Stefania, Cereda, Cristina, Sproviero, Daisy, D'Alfonso, Sandra, Soraru, Gianni, Siciliano, Gabriele, Filosto, Massimiliano, Padovani, Alessandro, Chio, Adriano, Calvo, Andrea, Moglia, Cristina, Brunetti, Maura, Canosa, Antonio, Grassano, Maurizio, Beghi, Ettore, Pupillo, Elisabetta, Logroscino, Giancarlo, Nefussy, Beatrice, Osmanovic, Alma, Nordin, Angelica, Lerner, Yossef, Zabari, Michal, Gotkine, Marc, Baloh, Robert H., Bell, Shaughn, Vourc'h, Patrick, Corcia, Philippe, Couratier, Philippe, Millecamps, Stephanie, Meininger, Vincent, Salachas, Francois, Mora Pardina, Jesus S., Assialioui, Abdelilah, Rojas-Garcia, Ricardo, Dion, Patrick A., Ross, Jay P., Ludolph, Albert C., Weishaupt, Jochen H., Brenner, David, Freischmidt, Axel, Bensimon, Gilbert, Brice, Alexis, Durr, Alexandra, Payan, Christine A. M., Saker-Delye, Safa, Wood, Nicholas W., Topp, Simon, Rademakers, Rosa, Tittmann, Lukas, Lieb, Wolfgang, Franke, Andre, Ripke, Stephan, Braun, Alice, Kraft, Julia, Whiteman, David C., Olsen, Catherine M., Uitterlinden, Andre G., Hofman, Albert, Rietschel, Marcella, Cichon, Sven, Nothen, Markus M., Amouyel, Philippe, Comi, Giancarlo, Riva, Nilo, Lunetta, Christian, Gerardi, Francesca, Cotelli, Maria Sofia, Rinaldi, Fabrizio, Chiveri, Luca, Guaita, Maria Cristina, Perrone, Patrizia, Ceroni, Mauro, Diamanti, Luca, Ferrarese, Carlo, Tremolizzo, Lucio, Delodovici, Maria Luisa, Bono, Giorgio, Manera, Umberto, Vasta, Rosario, Bombaci, Alessandro, Casale, Federico, Fuda, Giuseppe, Salamone, Paolina, Iazzolino, Barbara, Peotta, Laura, Cugnasco, Paolo, De Marco, Giovanni, Torrieri, Maria Claudia, Palumbo, Francesca, Gallone, Salvatore, Barberis, Marco, Sbaiz, Luca, Gentile, Salvatore, Mauro, Alessandro, Mazzini, Letizia, De Marchi, Fabiola, Corrado, Lucia, Bertolotto, Antonio, Gionco, Maurizio, Leotta, Daniela, Odddenino, Enrico, Imperiale, Daniele, Cavallo, Roberto, Pignatta, Pietro, De Mattei, Marco, Geda, Claudio, Papurello, Diego Maria, Gusmaroli, Graziano, Comi, Cristoforo, Labate, Carmelo, Ruiz, Luigi, Ferrandi, Delfina, Rota, Eugenia, Aguggia, Marco, Di Vito, Nicoletta, Meineri, Piero, Ghiglione, Paolo, Launaro, Nicola, Dotta, Michele, Di Sapio, Alessia, Giardini, Guido, Tiloca, Cinzia, Peverelli, Silvia, Taroni, Franco, Pensato, Viviana, Castellotti, Barbara, Comi, Giacomo P., Del Bo, Roberto, Gagliardi, Stella, Raggi, Flavia, Simoncini, Costanza, Lo Gerfo, Annalisa, Inghilleri, Maurizio, Ferlini, Alessandra, Simone, Isabella L., Passarella, Bruno, Guerra, Vito, Zoccolella, Stefano, Nozzoli, Cecilia, Mundi, Ciro, Leone, Maurizio, Zarrelli, Michele, Tamma, Filippo, Valluzzi, Francesco, Calabrese, Gianluigi, Boero, Giovanni, Rini, Augusto, Traynor, Bryan J., Singleton, Andrew B., Mitne Neto, Miguel, Cauchi, Ruben J., Ophoff, Roel A., Wiedau-Pazos, Martina, Lomen-Hoerth, Catherine, van Deerlin, Vivianna M., Grosskreutz, Julian, Roediger, Annekathrin, Gaur, Nayana, Joerk, Alexander, Barthel, Tabea, Theele, Erik, Ilse, Benjamin, Stubendorff, Beatrice, Witte, Otto W., Steinbach, Robert, Huebner, Christian A., Graff, Caroline, Brylev, Lev, Fominykh, Vera, Demeshonok, Vera, Ataulina, Anastasia, Rogelj, Boris, Koritnik, Blaz, Zidar, Janez, Ravnik-Glavac, Metka, Glavac, Damjan, Stevic, Zorica, Drory, Vivian, Povedano, Monica, Blair, Ian P., Kiernan, Matthew C., Benyamin, Beben, Henderson, Robert D., Furlong, Sarah, Mathers, Susan, McCombe, Pamela A., Needham, Merrilee, Ngo, Shyuan T., Nicholson, Garth A., Pamphlett, Roger, Rowe, Dominic B., Steyn, Frederik J., Williams, Kelly L., Mather, Karen A., Sachdev, Perminder S., Henders, Anjali K., Wallace, Leanne, de Carvalho, Mamede, Pinto, Susana, Petri, Susanne, Weber, Markus, Rouleau, Guy A., Silani, Vincenzo, Curtis, Charles J., Breen, Gerome, Glass, Jonathan D., Brown, Robert H., Jr., Landers, John E., Shaw, Christopher E., Andersen, Peter M., Groen, Ewout J. N., van Es, Michael A., Pasterkamp, R. Jeroen, Fan, Dongsheng, Garton, Fleur C., McRae, Allan F., Davey Smith, George, Gaunt, Tom R., Eberle, Michael A., Mill, Jonathan, McLaughlin, Russell L., Hardiman, Orla, Kenna, Kevin P., Wray, Naomi R., Tsai, Ellen, Runz, Heiko, Franke, Lude, Al-Chalabi, Ammar, Van Damme, Philip, van den Berg, Leonard H., Veldink, Jan H., van Rheenen, Wouter, van der Spek, Rick A. A., Bakker, Mark K., van Vugt, Joke J. F. A., Hop, Paul J., Zwamborn, Ramona A. J., de Klein, Niek, Westra, Harm-Jan, Bakker, Olivier B., Deelen, Patrick, Shireby, Gemma, Hannon, Eilis, Moisse, Matthieu, Baird, Denis, Restuadi, Restuadi, Dolzhenko, Egor, Dekker, Annelot M., Gawor, Klara, Westeneng, Henk-Jan, Tazelaar, Gijs H. P., van Eijk, Kristel R., Kooyman, Maarten, Byrne, Ross P., Doherty, Mark, Heverin, Mark, Al Khleifat, Ahmad, Iacoangeli, Alfredo, Shatunov, Aleksey, Ticozzi, Nicola, Cooper-Knock, Johnathan, Smith, Bradley N., Gromicho, Marta, Chandran, Siddharthan, Pal, Suvankar, Morrison, Karen E., Shaw, Pamela J., Hardy, John, Orrell, Richard W., Sendtner, Michael, Meyer, Thomas, Basak, Nazli, van der Kooi, Anneke J., Ratti, Antonia, Fogh, Isabella, Gellera, Cinzia, Lauria, Giuseppe, Corti, Stefania, Cereda, Cristina, Sproviero, Daisy, D'Alfonso, Sandra, Soraru, Gianni, Siciliano, Gabriele, Filosto, Massimiliano, Padovani, Alessandro, Chio, Adriano, Calvo, Andrea, Moglia, Cristina, Brunetti, Maura, Canosa, Antonio, Grassano, Maurizio, Beghi, Ettore, Pupillo, Elisabetta, Logroscino, Giancarlo, Nefussy, Beatrice, Osmanovic, Alma, Nordin, Angelica, Lerner, Yossef, Zabari, Michal, Gotkine, Marc, Baloh, Robert H., Bell, Shaughn, Vourc'h, Patrick, Corcia, Philippe, Couratier, Philippe, Millecamps, Stephanie, Meininger, Vincent, Salachas, Francois, Mora Pardina, Jesus S., Assialioui, Abdelilah, Rojas-Garcia, Ricardo, Dion, Patrick A., Ross, Jay P., Ludolph, Albert C., Weishaupt, Jochen H., Brenner, David, Freischmidt, Axel, Bensimon, Gilbert, Brice, Alexis, Durr, Alexandra, Payan, Christine A. M., Saker-Delye, Safa, Wood, Nicholas W., Topp, Simon, Rademakers, Rosa, Tittmann, Lukas, Lieb, Wolfgang, Franke, Andre, Ripke, Stephan, Braun, Alice, Kraft, Julia, Whiteman, David C., Olsen, Catherine M., Uitterlinden, Andre G., Hofman, Albert, Rietschel, Marcella, Cichon, Sven, Nothen, Markus M., Amouyel, Philippe, Comi, Giancarlo, Riva, Nilo, Lunetta, Christian, Gerardi, Francesca, Cotelli, Maria Sofia, Rinaldi, Fabrizio, Chiveri, Luca, Guaita, Maria Cristina, Perrone, Patrizia, Ceroni, Mauro, Diamanti, Luca, Ferrarese, Carlo, Tremolizzo, Lucio, Delodovici, Maria Luisa, Bono, Giorgio, Manera, Umberto, Vasta, Rosario, Bombaci, Alessandro, Casale, Federico, Fuda, Giuseppe, Salamone, Paolina, Iazzolino, Barbara, Peotta, Laura, Cugnasco, Paolo, De Marco, Giovanni, Torrieri, Maria Claudia, Palumbo, Francesca, Gallone, Salvatore, Barberis, Marco, Sbaiz, Luca, Gentile, Salvatore, Mauro, Alessandro, Mazzini, Letizia, De Marchi, Fabiola, Corrado, Lucia, Bertolotto, Antonio, Gionco, Maurizio, Leotta, Daniela, Odddenino, Enrico, Imperiale, Daniele, Cavallo, Roberto, Pignatta, Pietro, De Mattei, Marco, Geda, Claudio, Papurello, Diego Maria, Gusmaroli, Graziano, Comi, Cristoforo, Labate, Carmelo, Ruiz, Luigi, Ferrandi, Delfina, Rota, Eugenia, Aguggia, Marco, Di Vito, Nicoletta, Meineri, Piero, Ghiglione, Paolo, Launaro, Nicola, Dotta, Michele, Di Sapio, Alessia, Giardini, Guido, Tiloca, Cinzia, Peverelli, Silvia, Taroni, Franco, Pensato, Viviana, Castellotti, Barbara, Comi, Giacomo P., Del Bo, Roberto, Gagliardi, Stella, Raggi, Flavia, Simoncini, Costanza, Lo Gerfo, Annalisa, Inghilleri, Maurizio, Ferlini, Alessandra, Simone, Isabella L., Passarella, Bruno, Guerra, Vito, Zoccolella, Stefano, Nozzoli, Cecilia, Mundi, Ciro, Leone, Maurizio, Zarrelli, Michele, Tamma, Filippo, Valluzzi, Francesco, Calabrese, Gianluigi, Boero, Giovanni, Rini, Augusto, Traynor, Bryan J., Singleton, Andrew B., Mitne Neto, Miguel, Cauchi, Ruben J., Ophoff, Roel A., Wiedau-Pazos, Martina, Lomen-Hoerth, Catherine, van Deerlin, Vivianna M., Grosskreutz, Julian, Roediger, Annekathrin, Gaur, Nayana, Joerk, Alexander, Barthel, Tabea, Theele, Erik, Ilse, Benjamin, Stubendorff, Beatrice, Witte, Otto W., Steinbach, Robert, Huebner, Christian A., Graff, Caroline, Brylev, Lev, Fominykh, Vera, Demeshonok, Vera, Ataulina, Anastasia, Rogelj, Boris, Koritnik, Blaz, Zidar, Janez, Ravnik-Glavac, Metka, Glavac, Damjan, Stevic, Zorica, Drory, Vivian, Povedano, Monica, Blair, Ian P., Kiernan, Matthew C., Benyamin, Beben, Henderson, Robert D., Furlong, Sarah, Mathers, Susan, McCombe, Pamela A., Needham, Merrilee, Ngo, Shyuan T., Nicholson, Garth A., Pamphlett, Roger, Rowe, Dominic B., Steyn, Frederik J., Williams, Kelly L., Mather, Karen A., Sachdev, Perminder S., Henders, Anjali K., Wallace, Leanne, de Carvalho, Mamede, Pinto, Susana, Petri, Susanne, Weber, Markus, Rouleau, Guy A., Silani, Vincenzo, Curtis, Charles J., Breen, Gerome, Glass, Jonathan D., Brown, Robert H., Jr., Landers, John E., Shaw, Christopher E., Andersen, Peter M., Groen, Ewout J. N., van Es, Michael A., Pasterkamp, R. Jeroen, Fan, Dongsheng, Garton, Fleur C., McRae, Allan F., Davey Smith, George, Gaunt, Tom R., Eberle, Michael A., Mill, Jonathan, McLaughlin, Russell L., Hardiman, Orla, Kenna, Kevin P., Wray, Naomi R., Tsai, Ellen, Runz, Heiko, Franke, Lude, Al-Chalabi, Ammar, Van Damme, Philip, van den Berg, Leonard H., and Veldink, Jan H.
Abstract: A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons.
Published: 2021
Full Text: View/download PDF

33. Harnessing the NEON data revolution to advance open environmental science with a diverse and data‐capable community

Author: Nagy, R Chelsea; https://orcid.org/0000-0002-7168-3289, Balch, Jennifer K, Bissell, Erin K, Cattau, Megan E; https://orcid.org/0000-0003-2164-3809, Glenn, Nancy F; https://orcid.org/0000-0003-2124-7654, Halpern, Benjamin S, Ilangakoon, Nayani, Johnson, Brian, Joseph, Maxwell B; https://orcid.org/0000-0002-7745-9990, Marconi, Sergio; https://orcid.org/0000-0002-8096-754X, O’Riordan, Catherine, Sanovia, James, Swetnam, Tyson L, Travis, William R, Wasser, Leah A, Woolner, Elizabeth, Zarnetske, Phoebe, Abdulrahim, Mujahid, Adler, John, Barnes, Grenville, Bartowitz, Kristina J, Blake, Rachael E, Bombaci, Sara P, Brun, Julien, Buchanan, Jacob D, Chadwick, K Dana; https://orcid.org/0000-0002-5633-4865, Chapman, Melissa S, Chong, Steven S, Chung, Y Anny; https://orcid.org/0000-0001-5207-2872, Corman, Jessica R; https://orcid.org/0000-0002-2633-8080, Schweiger, Anna K; https://orcid.org/0000-0002-5567-4200, et al, Nagy, R Chelsea; https://orcid.org/0000-0002-7168-3289, Balch, Jennifer K, Bissell, Erin K, Cattau, Megan E; https://orcid.org/0000-0003-2164-3809, Glenn, Nancy F; https://orcid.org/0000-0003-2124-7654, Halpern, Benjamin S, Ilangakoon, Nayani, Johnson, Brian, Joseph, Maxwell B; https://orcid.org/0000-0002-7745-9990, Marconi, Sergio; https://orcid.org/0000-0002-8096-754X, O’Riordan, Catherine, Sanovia, James, Swetnam, Tyson L, Travis, William R, Wasser, Leah A, Woolner, Elizabeth, Zarnetske, Phoebe, Abdulrahim, Mujahid, Adler, John, Barnes, Grenville, Bartowitz, Kristina J, Blake, Rachael E, Bombaci, Sara P, Brun, Julien, Buchanan, Jacob D, Chadwick, K Dana; https://orcid.org/0000-0002-5633-4865, Chapman, Melissa S, Chong, Steven S, Chung, Y Anny; https://orcid.org/0000-0001-5207-2872, Corman, Jessica R; https://orcid.org/0000-0002-2633-8080, Schweiger, Anna K; https://orcid.org/0000-0002-5567-4200, and et al
Abstract: It is a critical time to reflect on the National Ecological Observatory Network (NEON) science to date as well as envision what research can be done right now with NEON (and other) data and what training is needed to enable a diverse user community. NEON became fully operational in May 2019 and has pivoted from planning and construction to operation and maintenance. In this overview, the history of and foundational thinking around NEON are discussed. A framework of open science is described with a discussion of how NEON can be situated as part of a larger data constellation — across existing networks and different suites of ecological measurements and sensors. Next, a synthesis of early NEON science, based on >100 existing publications, funded proposal efforts, and emergent science at the very first NEON Science Summit (hosted by Earth Lab at the University of Colorado Boulder in October 2019) is provided. Key questions that the ecology community will address with NEON data in the next 10 yr are outlined, from understanding drivers of biodiversity across spatial and temporal scales to defining complex feedback mechanisms in human–environmental systems. Last, the essential elements needed to engage and support a diverse and inclusive NEON user community are highlighted: training resources and tools that are openly available, funding for broad community engagement initiatives, and a mechanism to share and advertise those opportunities. NEON users require both the skills to work with NEON data and the ecological or environmental science domain knowledge to understand and interpret them. This paper synthesizes early directions in the community’s use of NEON data, and opportunities for the next 10 yr of NEON operations in emergent science themes, open science best practices, education and training, and community building.
Published: 2021

34. Expanding NEON biodiversity surveys with new instrumentation and machine learning approaches

Author: Kitzes, Justin; https://orcid.org/0000-0001-7839-3594, Blake, Rachael; https://orcid.org/0000-0003-0847-9100, Bombaci, Sara, Chapman, Melissa, Duran, Sandra M, Huang, Tao, Joseph, Maxwell B; https://orcid.org/0000-0002-7745-9990, Lapp, Samuel, Marconi, Sergio; https://orcid.org/0000-0002-8096-754X, Oestreich, William K; https://orcid.org/0000-0002-0137-5053, Rhinehart, Tessa A; https://orcid.org/0000-0002-4352-3464, Schweiger, Anna K; https://orcid.org/0000-0002-5567-4200, Song, Yiluan; https://orcid.org/0000-0003-3660-3797, Surasinghe, Thilina, Yang, Di; https://orcid.org/0000-0002-4010-6163, Yule, Kelsey; https://orcid.org/0000-0002-1447-849X, Kitzes, Justin; https://orcid.org/0000-0001-7839-3594, Blake, Rachael; https://orcid.org/0000-0003-0847-9100, Bombaci, Sara, Chapman, Melissa, Duran, Sandra M, Huang, Tao, Joseph, Maxwell B; https://orcid.org/0000-0002-7745-9990, Lapp, Samuel, Marconi, Sergio; https://orcid.org/0000-0002-8096-754X, Oestreich, William K; https://orcid.org/0000-0002-0137-5053, Rhinehart, Tessa A; https://orcid.org/0000-0002-4352-3464, Schweiger, Anna K; https://orcid.org/0000-0002-5567-4200, Song, Yiluan; https://orcid.org/0000-0003-3660-3797, Surasinghe, Thilina, Yang, Di; https://orcid.org/0000-0002-4010-6163, and Yule, Kelsey; https://orcid.org/0000-0002-1447-849X
Abstract: A core goal of the National Ecological Observatory Network (NEON) is to measure changes in biodiversity across the 30-yr horizon of the network. In contrast to NEON’s extensive use of automated instruments to collect environmental data, NEON’s biodiversity surveys are almost entirely conducted using traditional human-centric field methods. We believe that the combination of instrumentation for remote data collection and machine learning models to process such data represents an important opportunity for NEON to expand the scope, scale, and usability of its biodiversity data collection while potentially reducing long-term costs. In this manuscript, we first review the current status of instrument-based biodiversity surveys within the NEON project and previous research at the intersection of biodiversity, instrumentation, and machine learning at NEON sites. We then survey methods that have been developed at other locations but could potentially be employed at NEON sites in future. Finally, we expand on these ideas in five case studies that we believe suggest particularly fruitful future paths for automated biodiversity measurement at NEON sites: acoustic recorders for sound-producing taxa, camera traps for medium and large mammals, hydroacoustic and remote imagery for aquatic diversity, expanded remote and ground-based measurements for plant biodiversity, and laboratory-based imaging for physical specimens and samples in the NEON biorepository. Through its data science-literate staff and user community, NEON has a unique role to play in supporting the growth of such automated biodiversity survey methods, as well as demonstrating their ability to help answer key ecological questions that cannot be answered at the more limited spatiotemporal scales of human-driven surveys.
Published: 2021

35. Effects of chiral effective field theory equation of state on binary neutron star mergers

Author: Endrizzi, A, Logoteta, D, Giacomazzo, B, Bombaci, I, Kastaun, W, Ciolfi, R, Endrizzi, Andrea, Logoteta, Domenico, Giacomazzo, Bruno, Bombaci, Ignazio, Kastaun, Wolfgang, Ciolfi, Riccardo, Endrizzi, A, Logoteta, D, Giacomazzo, B, Bombaci, I, Kastaun, W, Ciolfi, R, Endrizzi, Andrea, Logoteta, Domenico, Giacomazzo, Bruno, Bombaci, Ignazio, Kastaun, Wolfgang, and Ciolfi, Riccardo
Abstract: We present fully general relativistic simulations of binary neutron star mergers, employing a new zero-temperature chiral effective field theory equation of state (EOS), the BL EOS. We offer a comparison with respect to the older GM3 EOS, which is based on standard relativistic mean-field theory, and separately determine the impact of the mass. We provide a detailed analysis of the dynamics, with focus on the postmerger phase. For all models, we extract the gravitational wave strain and the postmerger frequency spectrum. Further, we determine the amount, velocity, and polar distribution of ejected matter and provide estimates for the resulting kilonova signals. We also study the evolution of the disk while it is interacting with the hypermassive remnant and discuss the merits of different disk mass definitions applicable before collapse, with regard to the mass remaining after black hole formation. Finally, we investigate the radial mass distribution and rotation profile of the remnants, which validate previous results and also corroborate a recently proposed stability criterion.
Published: 2018

36. Effects of chiral effective field theory equation of state on binary neutron star mergers

Author: Endrizzi, A, Logoteta, D, Giacomazzo, B, Bombaci, I, Kastaun, W, Ciolfi, R, Endrizzi, Andrea, Logoteta, Domenico, Giacomazzo, Bruno, Bombaci, Ignazio, Kastaun, Wolfgang, Ciolfi, Riccardo, Endrizzi, A, Logoteta, D, Giacomazzo, B, Bombaci, I, Kastaun, W, Ciolfi, R, Endrizzi, Andrea, Logoteta, Domenico, Giacomazzo, Bruno, Bombaci, Ignazio, Kastaun, Wolfgang, and Ciolfi, Riccardo
Abstract: We present fully general relativistic simulations of binary neutron star mergers, employing a new zero-temperature chiral effective field theory equation of state (EOS), the BL EOS. We offer a comparison with respect to the older GM3 EOS, which is based on standard relativistic mean-field theory, and separately determine the impact of the mass. We provide a detailed analysis of the dynamics, with focus on the postmerger phase. For all models, we extract the gravitational wave strain and the postmerger frequency spectrum. Further, we determine the amount, velocity, and polar distribution of ejected matter and provide estimates for the resulting kilonova signals. We also study the evolution of the disk while it is interacting with the hypermassive remnant and discuss the merits of different disk mass definitions applicable before collapse, with regard to the mass remaining after black hole formation. Finally, we investigate the radial mass distribution and rotation profile of the remnants, which validate previous results and also corroborate a recently proposed stability criterion.
Published: 2018

37. Accretion-induced prompt black hole formation in asymmetric neutron star mergers, dynamical ejecta and kilonova signals

Author: Bernuzzi, Sebastiano, Breschi, Matteo, Daszuta, Boris, Endrizzi, Andrea, Logoteta, Domenico, Nedora, Vsevolod, Perego, Albino, Schianchi, Federico, Radice, David, Zappa, Francesco, Bombaci, Ignazio, Ortiz, Nestor, Bernuzzi, Sebastiano, Breschi, Matteo, Daszuta, Boris, Endrizzi, Andrea, Logoteta, Domenico, Nedora, Vsevolod, Perego, Albino, Schianchi, Federico, Radice, David, Zappa, Francesco, Bombaci, Ignazio, and Ortiz, Nestor
Abstract: We present new numerical relativity results of neutron star mergers with chirp mass $1.188M_\odot$ and mass ratios $q=1.67$ and $q=1.8$ using finite-temperature equations of state (EOS), approximate neutrino transport and a subgrid model for magnetohydrodynamics-induced turbulent viscosity. The EOS are compatible with nuclear and astrophysical constraints and include a new microphysical model derived from ab-initio calculations based on the Brueckner-Hartree-Fock approach. We report for the first time evidence for accretion-induced prompt collapse in high-mass-ratio mergers, in which the tidal disruption of the companion and its accretion onto the primary star determine prompt black hole formation. As a result of the tidal disruption, an accretion disc of neutron-rich and cold matter forms with baryon masses ${\sim}0.15M_\odot$, and it is significantly heavier than the remnant discs in equal-masses prompt collapse mergers. Massive dynamical ejecta of order ${\sim}0.01M_\odot$ also originate from the tidal disruption. They are neutron rich and expand from the orbital plane with a crescent-like geometry. Consequently, bright, red and temporally extended kilonova emission is predicted from these mergers. Our results show that prompt black hole mergers can power bright electromagnetic counterparts for high-mass-ratio binaries, and that the binary mass ratio can be in principle constrained from multimessenger observations., Comment: 20 pages, 21 figures, 4 tables
Published: 2020
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38. Musical and Conversational Artificial Intelligence

Author: Catania, F, De Luca, G, Bombaci, N, Colombo, E, Crovari, P, Beccaluva, E, Garzotto, F, Catania, F, De Luca, G, Bombaci, N, Colombo, E, Crovari, P, Beccaluva, E, and Garzotto, F
Abstract: Music production software often has complex interfaces and needs the user to know the basic musical know-how. In this paper, we present a conversational agent that allows creating music in a simplified way through voice-based interaction. Indeed, our agent can be configured and customized with simple and natural voice commands. In addition, it has some typically human cognitive skills to produce music: it listens to the user while singing a song and generates a melody by discovering and copying the patterns of her/his human voice. Technologically, the system is empowered by Google Dialogflow for conversation management and uses an advanced technique called abstract melody for music production. This Musical and Conversational Artificial Intelligence is an actual innovation since it does not require any preliminary knowledge about music and, consequently, includes professionals, but also children, beginners, and people with physical disease.
Published: 2020

39. Microscopic equation of state of hot nuclear matter for numerical relativity simulations

Author: Logoteta, Domenico, Perego, Albino, Bombaci, Ignazio, Logoteta, Domenico, Perego, Albino, and Bombaci, Ignazio
Abstract: A precise understanding of the equation of state (EOS) of dense and hot matter is key to modeling relativistic astrophysical environments, including core-collapse supernovae (CCSNe), protoneutron star (PNSs) evolution, and compact binary mergers. In this paper, we extend the microscopic zero-temperature BL (Bombaci and Logoteta) %nuclear equation of state nuclear EOS %derived by Bombaci and Logoteta to finite temperature and arbitrary nuclear composition. We employ this new EOS to describe hot $\beta$-stable nuclear matter and to compute various structural properties of nonrotating PNS. %protoneutron stars. We also apply the EOS to perform dynamical simulations of a spherically symmetric CCSN. The EOS is derived using the finite temperature extension of the Brueckner--Bethe--Goldstone quantum many-body theory in the Brueckner--Hartree--Fock approximation. Neutron star properties are computed by solving the Tolman--Oppenheimer--Volkoff structure equations numerically. The sperically symmetric CCSN simulations are performed using the AGILE-IDSA code. Our EOS models are able to reproduce typical features of both PNS and spherically symmetric CCSN simulations. In addition, our EOS model is consistent with present measured neutron star masses and particularly with the masses: $M = 2.01 \pm 0.04 \, M_{\odot}$ and $M = 2.14^{+0.20}_{-0.18} \, M_{\odot}$ of the neutron stars in PSR~J0348+0432 and PSR J0740+6620 respectively. Finally, we suggest a feasible mechanism to produce low-mass black holes ($M \sim 2M_{\odot}$) that could have far-reaching consequences for interpreting the gravitational wave event GW190814 as a BH--BH merger., Comment: Accepted for publication in A&A
Published: 2020
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40. Was GW190814 a black hole -- strange quark star system?

Author: Bombaci, I., Drago, A., Logoteta, D., Pagliara, G., Vidana, I., Bombaci, I., Drago, A., Logoteta, D., Pagliara, G., and Vidana, I.
Abstract: We investigate the possibility that the low mass companion of the black hole in the source of GW190814 was a strange quark star. This possibility is viable within the so-called two-families scenario in which neutron stars and strange quark stars coexist. Strange quark stars can reach the mass range indicated by GW190814, $M\sim (2.5-2.67) M_\odot$ due to a large value of the adiabatic index, without the need for a velocity of sound close to the causal limit. Neutron stars (actually hyperonic stars in the two-families scenario) can instead fulfill the presently available astrophysical and nuclear physics constraints which require a softer equation of state. In this scheme it is possible to satisfy both the request of very large stellar masses and of small radii while using totally realistic and physically motivated equations of state. Moreover it is possible to get a radius for a 1.4 $M_\odot$ star of the order or less than 11 km, which is impossible if only one family of compact stars exists., Comment: 6 pages, 3 figures. Accepted on Phys. Rev. Letters
Published: 2020
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41. Accretion-induced prompt black hole formation in asymmetric neutron star mergers, dynamical ejecta and kilonova signals

Author: Bernuzzi, Sebastiano, Breschi, Matteo, Daszuta, Boris, Endrizzi, Andrea, Logoteta, Domenico, Nedora, Vsevolod, Perego, Albino, Schianchi, Federico, Radice, David, Zappa, Francesco, Bombaci, Ignazio, Ortiz, Nestor, Bernuzzi, Sebastiano, Breschi, Matteo, Daszuta, Boris, Endrizzi, Andrea, Logoteta, Domenico, Nedora, Vsevolod, Perego, Albino, Schianchi, Federico, Radice, David, Zappa, Francesco, Bombaci, Ignazio, and Ortiz, Nestor
Abstract: We present new numerical relativity results of neutron star mergers with chirp mass $1.188M_\odot$ and mass ratios $q=1.67$ and $q=1.8$ using finite-temperature equations of state (EOS), approximate neutrino transport and a subgrid model for magnetohydrodynamics-induced turbulent viscosity. The EOS are compatible with nuclear and astrophysical constraints and include a new microphysical model derived from ab-initio calculations based on the Brueckner-Hartree-Fock approach. We report for the first time evidence for accretion-induced prompt collapse in high-mass-ratio mergers, in which the tidal disruption of the companion and its accretion onto the primary star determine prompt black hole formation. As a result of the tidal disruption, an accretion disc of neutron-rich and cold matter forms with baryon masses ${\sim}0.15M_\odot$, and it is significantly heavier than the remnant discs in equal-masses prompt collapse mergers. Massive dynamical ejecta of order ${\sim}0.01M_\odot$ also originate from the tidal disruption. They are neutron rich and expand from the orbital plane with a crescent-like geometry. Consequently, bright, red and temporally extended kilonova emission is predicted from these mergers. Our results show that prompt black hole mergers can power bright electromagnetic counterparts for high-mass-ratio binaries, and that the binary mass ratio can be in principle constrained from multimessenger observations., Comment: 20 pages, 21 figures, 4 tables
Published: 2020
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42. Dense matter with eXTP

Author: Watts, Anna L., Yu, WenFei, Poutanen, Juri, Zhang, Shu, Bhattacharyya, Sudip, Bogdanov, Slavko, Ji, Long, Patruno, Alessandro, Riley, Thomas E., Bakala, Pavel, Baykal, Altan, Bernardini, Federico, Bombaci, Ignazio, Brown, Edward, Cavecchi, Yuri, Chakrabarty, Deepto, Chenevez, Jerome, Degenaar, Nathalie, Del Santo, Melania, Di Salvo, Tiziana, Doroshenko, Victor, Falanga, Maurizio, Ferdman, Robert D., Feroci, Marco, Gambino, Angelo F., Ge, MingYu, Greif, Svenja K., Guillot, Sebastien, Gungor, Can, Hartmann, Dieter H., Hebeler, Kai, Heger, Alexander, Homan, Jeroen, Iaria, Rosario, in 't Zand, Jean, Kargaltsev, Oleg, Kurkela, Aleksi, Lai, XiaoYu, Li, Ang, Li, XiangDong, Li, ZhaoSheng, Linares, Manuel, Lu, FangJun, Mahmoodifar, Simin, Mendez, Mariano, Miller, M. Coleman, Morsink, Sharon, Nattila, Joonas, Possenti, Andrea, Prescod-Weinstein, Chanda, Qu, JinLu, Riggio, Alessandro, Salmi, Tuomo, Sanna, Andrea, Santangelo, Andrea, Schatz, Hendrik, Schwenk, Achim, Song, LiMing, Sramkova, Eva, Stappers, Benjamin, Stiele, Holger, Strohmayer, Tod, Tews, Ingo, Tolos, Laura, Torok, Gabriel, Tsang, David, Urbanec, Martin, Vacchi, Andrea, Xu, RenXin, Xu, YuPeng, Zane, Silvia, Zhang, GuoBao, Zhang, ShuangNan, Zhang, WenDa, Zheng, ShiJie, Zhou, Xia, Watts, Anna L., Yu, WenFei, Poutanen, Juri, Zhang, Shu, Bhattacharyya, Sudip, Bogdanov, Slavko, Ji, Long, Patruno, Alessandro, Riley, Thomas E., Bakala, Pavel, Baykal, Altan, Bernardini, Federico, Bombaci, Ignazio, Brown, Edward, Cavecchi, Yuri, Chakrabarty, Deepto, Chenevez, Jerome, Degenaar, Nathalie, Del Santo, Melania, Di Salvo, Tiziana, Doroshenko, Victor, Falanga, Maurizio, Ferdman, Robert D., Feroci, Marco, Gambino, Angelo F., Ge, MingYu, Greif, Svenja K., Guillot, Sebastien, Gungor, Can, Hartmann, Dieter H., Hebeler, Kai, Heger, Alexander, Homan, Jeroen, Iaria, Rosario, in 't Zand, Jean, Kargaltsev, Oleg, Kurkela, Aleksi, Lai, XiaoYu, Li, Ang, Li, XiangDong, Li, ZhaoSheng, Linares, Manuel, Lu, FangJun, Mahmoodifar, Simin, Mendez, Mariano, Miller, M. Coleman, Morsink, Sharon, Nattila, Joonas, Possenti, Andrea, Prescod-Weinstein, Chanda, Qu, JinLu, Riggio, Alessandro, Salmi, Tuomo, Sanna, Andrea, Santangelo, Andrea, Schatz, Hendrik, Schwenk, Achim, Song, LiMing, Sramkova, Eva, Stappers, Benjamin, Stiele, Holger, Strohmayer, Tod, Tews, Ingo, Tolos, Laura, Torok, Gabriel, Tsang, David, Urbanec, Martin, Vacchi, Andrea, Xu, RenXin, Xu, YuPeng, Zane, Silvia, Zhang, GuoBao, Zhang, ShuangNan, Zhang, WenDa, Zheng, ShiJie, and Zhou, Xia
Abstract: In this White Paper we present the potential of the Enhanced X-ray Timing and Polarimetry (eXTP) mission for determining the nature of dense matter; neutron star cores host an extreme density regime which cannot be replicated in a terrestrial laboratory. The tightest statistical constraints on the dense matter equation of state will come from pulse profile modelling of accretion-powered pulsars, burst oscillation sources, and rotation-powered pulsars. Additional constraints will derive from spin measurements, burst spectra, and properties of the accretion flows in the vicinity of the neutron star. Under development by an international Consortium led by the Institute of High Energy Physics of the Chinese Academy of Sciences, the eXTP mission is expected to be launched in the mid 2020s., QC 20200313
Published: 2019
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43. Dense matter with eXTP

Author: Watts, Anna L., Yu, WenFei, Poutanen, Juri, Zhang, Shu, Bhattacharyya, Sudip, Bogdanov, Slavko, Ji, Long, Patruno, Alessandro, Riley, Thomas E., Bakala, Pavel, Baykal, Altan, Bernardini, Federico, Bombaci, Ignazio, Brown, Edward, Cavecchi, Yuri, Chakrabarty, Deepto, Chenevez, Jerome, Degenaar, Nathalie, Del Santo, Melania, Di Salvo, Tiziana, Doroshenko, Victor, Falanga, Maurizio, Ferdman, Robert D., Feroci, Marco, Gambino, Angelo F., Ge, MingYu, Greif, Svenja K., Guillot, Sebastien, Gungor, Can, Hartmann, Dieter H., Hebeler, Kai, Heger, Alexander, Homan, Jeroen, Iaria, Rosario, in 't Zand, Jean, Kargaltsev, Oleg, Kurkela, Aleksi, Lai, XiaoYu, Li, Ang, Li, XiangDong, Li, ZhaoSheng, Linares, Manuel, Lu, FangJun, Mahmoodifar, Simin, Mendez, Mariano, Miller, M. Coleman, Morsink, Sharon, Nättilä, Joonas, Possenti, Andrea, Prescod-Weinstein, Chanda, Qu, JinLu, Riggio, Alessandro, Salmi, Tuomo, Sanna, Andrea, Santangelo, Andrea, Schatz, Hendrik, Schwenk, Achim, Song, LiMing, Sramkova, Eva, Stappers, Benjamin, Stiele, Holger, Strohmayer, Tod, Tews, Ingo, Tolos, Laura, Torok, Gabriel, Tsang, David, Urbanec, Martin, Vacchi, Andrea, Xu, RenXin, Xu, YuPeng, Zane, Silvia, Zhang, GuoBao, Zhang, ShuangNan, Zhang, WenDa, Zheng, ShiJie, Zhou, Xia, Watts, Anna L., Yu, WenFei, Poutanen, Juri, Zhang, Shu, Bhattacharyya, Sudip, Bogdanov, Slavko, Ji, Long, Patruno, Alessandro, Riley, Thomas E., Bakala, Pavel, Baykal, Altan, Bernardini, Federico, Bombaci, Ignazio, Brown, Edward, Cavecchi, Yuri, Chakrabarty, Deepto, Chenevez, Jerome, Degenaar, Nathalie, Del Santo, Melania, Di Salvo, Tiziana, Doroshenko, Victor, Falanga, Maurizio, Ferdman, Robert D., Feroci, Marco, Gambino, Angelo F., Ge, MingYu, Greif, Svenja K., Guillot, Sebastien, Gungor, Can, Hartmann, Dieter H., Hebeler, Kai, Heger, Alexander, Homan, Jeroen, Iaria, Rosario, in 't Zand, Jean, Kargaltsev, Oleg, Kurkela, Aleksi, Lai, XiaoYu, Li, Ang, Li, XiangDong, Li, ZhaoSheng, Linares, Manuel, Lu, FangJun, Mahmoodifar, Simin, Mendez, Mariano, Miller, M. Coleman, Morsink, Sharon, Nättilä, Joonas, Possenti, Andrea, Prescod-Weinstein, Chanda, Qu, JinLu, Riggio, Alessandro, Salmi, Tuomo, Sanna, Andrea, Santangelo, Andrea, Schatz, Hendrik, Schwenk, Achim, Song, LiMing, Sramkova, Eva, Stappers, Benjamin, Stiele, Holger, Strohmayer, Tod, Tews, Ingo, Tolos, Laura, Torok, Gabriel, Tsang, David, Urbanec, Martin, Vacchi, Andrea, Xu, RenXin, Xu, YuPeng, Zane, Silvia, Zhang, GuoBao, Zhang, ShuangNan, Zhang, WenDa, Zheng, ShiJie, and Zhou, Xia
Abstract: In this White Paper we present the potential of the Enhanced X-ray Timing and Polarimetry (eXTP) mission for determining the nature of dense matter; neutron star cores host an extreme density regime which cannot be replicated in a terrestrial laboratory. The tightest statistical constraints on the dense matter equation of state will come from pulse profile modelling of accretion-powered pulsars, burst oscillation sources, and rotation-powered pulsars. Additional constraints will derive from spin measurements, burst spectra, and properties of the accretion flows in the vicinity of the neutron star. Under development by an international Consortium led by the Institute of High Energy Physics of the Chinese Academy of Sciences, the eXTP mission is expected to be launched in the mid 2020s.
Published: 2019
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44. Benchmark calculations of pure neutron matter with realistic nucleon-nucleon interactions

Author: Piarulli, M., Bombaci, I., Logoteta, D., Lovato, A., Wiringa, R. B., Piarulli, M., Bombaci, I., Logoteta, D., Lovato, A., and Wiringa, R. B.
Abstract: We report benchmark calculations of the energy per particle of pure neutron matter as a function of the baryon density using three independent many-body methods: Brueckner-Bethe-Goldstone, Fermi hypernetted chain/single-operator chain, and auxiliary-field diffusion Monte Carlo. Significant technical improvements are implemented in the latter two methods. The calculations are made for two distinct families of realistic coordinate-space nucleon-nucleon potentials fit to scattering data, including the standard Argonne $v_{18}$ interaction and two of its simplified versions, and four of the new Norfolk $\Delta$-full chiral effective field theory potentials. The results up to twice nuclear matter saturation density show some divergence among the methods, but improved agreement compared to earlier work. We find that the potentials fit to higher-energy nucleon-nucleon scattering data exhibit a much smaller spread of energies., Comment: 16 pages, 7 figures
Published: 2019
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45. Benchmark calculations of pure neutron matter with realistic nucleon-nucleon interactions

Author: Piarulli, M., Bombaci, I., Logoteta, D., Lovato, A., Wiringa, R. B., Piarulli, M., Bombaci, I., Logoteta, D., Lovato, A., and Wiringa, R. B.
Abstract: We report benchmark calculations of the energy per particle of pure neutron matter as a function of the baryon density using three independent many-body methods: Brueckner-Bethe-Goldstone, Fermi hypernetted chain/single-operator chain, and auxiliary-field diffusion Monte Carlo. Significant technical improvements are implemented in the latter two methods. The calculations are made for two distinct families of realistic coordinate-space nucleon-nucleon potentials fit to scattering data, including the standard Argonne $v_{18}$ interaction and two of its simplified versions, and four of the new Norfolk $\Delta$-full chiral effective field theory potentials. The results up to twice nuclear matter saturation density show some divergence among the methods, but improved agreement compared to earlier work. We find that the potentials fit to higher-energy nucleon-nucleon scattering data exhibit a much smaller spread of energies., Comment: 16 pages, 7 figures
Published: 2019
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46. Accretion in strong field gravity with eXTP

Author: Polish Academy of Sciences, Istituto Nazionale di Astrofisica, Chinese Academy of Sciences, De Rosa, Alessandra, Uttley, P., Gou, L. J., Liu, Y., Bambi, C., Barret, Didier, Belloni, T., Berti, E., Bianchi, Stefano, Caiazzo, I., Casella, P., Feroci, M., Ferrari, V., Gualtieri, L., Heyl, J., Ingram, A., Karas, V., Lu, F.J., Luo, B., Matt, G., Motta, S., Neilsen, J., Pani, P., Santangelo, Andrea, Shu, X. W., Wang, J. F., Wang, J. M., Xue, Y. Q., Xu, Y. P., Yuan, W. M., Yuan, Y. F., Zhang, S. N., Zhang, S., Agudo, Iván, Amati, L., Andersson, N., Baglio, C., Bakala, P., Baykal, A., Bhattacharyya, S., Bombaci, I., Bucciantini, N., Capitanio, F., Ciolfi, Riccardo, Cui, W. K., D'Ammando, F., Dauser, T., Del Santo, M., De Marco, B., Linares, Manuel, Migliari, S., Miniutti, Giovanni, Polish Academy of Sciences, Istituto Nazionale di Astrofisica, Chinese Academy of Sciences, De Rosa, Alessandra, Uttley, P., Gou, L. J., Liu, Y., Bambi, C., Barret, Didier, Belloni, T., Berti, E., Bianchi, Stefano, Caiazzo, I., Casella, P., Feroci, M., Ferrari, V., Gualtieri, L., Heyl, J., Ingram, A., Karas, V., Lu, F.J., Luo, B., Matt, G., Motta, S., Neilsen, J., Pani, P., Santangelo, Andrea, Shu, X. W., Wang, J. F., Wang, J. M., Xue, Y. Q., Xu, Y. P., Yuan, W. M., Yuan, Y. F., Zhang, S. N., Zhang, S., Agudo, Iván, Amati, L., Andersson, N., Baglio, C., Bakala, P., Baykal, A., Bhattacharyya, S., Bombaci, I., Bucciantini, N., Capitanio, F., Ciolfi, Riccardo, Cui, W. K., D'Ammando, F., Dauser, T., Del Santo, M., De Marco, B., Linares, Manuel, Migliari, S., and Miniutti, Giovanni
Abstract: In this paper we describe the potential of the enhanced X-ray Timing and Polarimetry (eXTP) mission for studies related to accretion flows in the strong field gravity regime around both stellar-mass and supermassive black-holes. eXTP has the unique capability of using advanced “spectral-timing-polarimetry” techniques to analyze the rapid variations with three orthogonal diagnostics of the flow and its geometry, yielding unprecedented insight into the inner accreting regions, the effects of strong field gravity on the material within them and the powerful outflows which are driven by the accretion process. X-spinmeasurements.© 2018, Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature.
Published: 2019

47. Dense matter with eXTP

Author: Watts, Anna L., Yu, Wenfei, Poutanen, Juri, Zhang, Shu, Bhattacharyya, Sudip, Bogdanov, Slavko, Ji, Long, Patruno, Alessandro, Riley, Thomas E., Bakala, Pavel, Baykal, Altan, Bernardini, Federico, Bombaci, Ignazio, Brown, Edward, Cavecchi, Yuri, Chakrabarty, Deepto, Chenevez, Jérôme, Degenaar, Nathalie, Del Santo, Melania, Di Salvo, Tiziana, Doroshenko, Victor, Falanga, Maurizio, Ferdman, Robert D., Feroci, Marco, Gambino, Angelo F., Ge, MingYu, Greif, Svenja K., Guillot, Sebastien, Gungor, Can, Hartmann, Dieter H., Hebeler, Kai, Heger, Alexander, Homan, Jeroen, Iaria, Rosario, Zand, Jean in 't, Kargaltsev, Oleg, Kurkela, Aleksi, Lai, Xiaoyu, Li, Ang, Li, XiangDong, Li, Zhaosheng, Linares, Manuel, Lu, FangJun, Mahmoodifar, Simin, Méndez, Mariano, Miller, M. Coleman, Morsink, Sharon, Nättilä, Joonas, Possenti, Andrea, Prescod-Weinstein, Chanda, Qu, JinLu, Riggio, Alessandro, Salmi, Tuomo, Sanna, Andrea, Santangelo, Andrea, Schatz, Hendrik, Schwenk, Achim, Song, LiMing, Šrámková, Eva, Stappers, Benjamin, Stiele, Holger, Strohmayer, Tod, Tews, Ingo, Tolos, Laura, Török, Gabriel, Tsang, David, Urbanec, Martin, Vacchi, Andrea, Xu, RenXin, Xu, Ypeng, Zane, Silvia, Zhang, Guobao, Zhang, ShuangNan, Zhang, Wenda, Zheng, ShiJie, Zhou, Xia, Watts, Anna L., Yu, Wenfei, Poutanen, Juri, Zhang, Shu, Bhattacharyya, Sudip, Bogdanov, Slavko, Ji, Long, Patruno, Alessandro, Riley, Thomas E., Bakala, Pavel, Baykal, Altan, Bernardini, Federico, Bombaci, Ignazio, Brown, Edward, Cavecchi, Yuri, Chakrabarty, Deepto, Chenevez, Jérôme, Degenaar, Nathalie, Del Santo, Melania, Di Salvo, Tiziana, Doroshenko, Victor, Falanga, Maurizio, Ferdman, Robert D., Feroci, Marco, Gambino, Angelo F., Ge, MingYu, Greif, Svenja K., Guillot, Sebastien, Gungor, Can, Hartmann, Dieter H., Hebeler, Kai, Heger, Alexander, Homan, Jeroen, Iaria, Rosario, Zand, Jean in 't, Kargaltsev, Oleg, Kurkela, Aleksi, Lai, Xiaoyu, Li, Ang, Li, XiangDong, Li, Zhaosheng, Linares, Manuel, Lu, FangJun, Mahmoodifar, Simin, Méndez, Mariano, Miller, M. Coleman, Morsink, Sharon, Nättilä, Joonas, Possenti, Andrea, Prescod-Weinstein, Chanda, Qu, JinLu, Riggio, Alessandro, Salmi, Tuomo, Sanna, Andrea, Santangelo, Andrea, Schatz, Hendrik, Schwenk, Achim, Song, LiMing, Šrámková, Eva, Stappers, Benjamin, Stiele, Holger, Strohmayer, Tod, Tews, Ingo, Tolos, Laura, Török, Gabriel, Tsang, David, Urbanec, Martin, Vacchi, Andrea, Xu, RenXin, Xu, Ypeng, Zane, Silvia, Zhang, Guobao, Zhang, ShuangNan, Zhang, Wenda, Zheng, ShiJie, and Zhou, Xia
Abstract: In this White Paper we present the potential of the Enhanced X-ray Timing and Polarimetry (eXTP) mission for determining the nature of dense matter; neutron star cores host an extreme density regime which cannot be replicated in a terrestrial laboratory. The tightest statistical constraints on the dense matter equation of state will come from pulse profile modelling of accretion-powered pulsars, burst oscillation sources, and rotation-powered pulsars. Additional constraints will derive from spin measurements, burst spectra, and properties of the accretion flows in the vicinity of the neutron star. Under development by an international Consortium led by the Institute of High Energy Physics of the Chinese Academy of Science, the eXTP mission is expected to be launched in the mid 2020s., Comment: Accepted for publication on Sci. China Phys. Mech. Astron. (2019)
Published: 2018
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48. Accretion in Strong Field Gravity with eXTP

Author: De Rosa, Alessandra, Uttley, Phil, Gou, Lijun, Liu, Yuan, Bambi, Cosimo, Barret, Didier, Belloni, Tomaso, Berti, Emanuele, Bianchi, Stefano, Caiazzo, Ilaria, Casella, Piergiorgio, Feroci, Marco, Ferrari, Valeria, Gualtieri, Leonardo, Heyl, Jeremy, Ingram, Adam, Karas, Vladimir, Lu, Fangjun, Luo, Bin, Matt, Giorgio, Motta, Sara, Neilsen, Joseph, Pani, Paolo, Santangelo, Andrea, Shu, Xinwen, Wang, Junfeng, Wang, Jian-Min, Xue, Yongquan, Xu, Yupeng, Yuan, Weimin, Yuan, Yefei, Zhang, Shuang-Nan, Zhang, Shu, Agudo, Ivan, Amati, Lorenzo, Andersson, Nils, Baglio, Cristina, Bakala, Pavel, Baykal, Altan, Bhattacharyya, Sudip, Bombaci, Ignazio, Bucciantini, Niccoló, Capitanio, Fiamma, Ciolfi, Riccardo, Cui, Wei K., D'Ammando, Filippo, Dauser, Thomas, Del Santo, Melania, De Marco, Barbara, Di Salvo, Tiziana, Done, Chris, Dovčiak, Michal, Fabian, Andrew C., Falanga, Maurizio, Gambino, Angelo Francesco, Gendre, Bruce, Grinberg, Victoria, Heger, Alexander, Homan, Jeroen, Iaria, Rosario, Jiang, Jiachen, Jin, Chichuan, Koerding, Elmar, Linares, Manu, Liu, Zhu, Maccarone, Thomas J., Malzac, Julien, Manousakis, Antonios, Marin, Frédéric, Marinucci, Andrea, Mehdipour, Missagh, Méndez, Mariano, Migliari, Simone, Miller, Cole, Miniutti, Giovanni, Nardin, Emanuele, O'Brien, Paul T., Osborne, Julian P., Petrucci, Pierre Olivier, Possenti, Andrea, Riggio, Alessandro, Rodriguez, Jerome, Sanna, Andrea, Shao, Lijing, Sobolewska, Malgosia, Sramkova, Eva, Stevens, Abigail L., Stiele, Holger, Stratta, Giulia, Stuchlik, Zdenek, Svoboda, Jiri, Tamburini, Fabrizio, Tauris, Thomas M., Tombesi, Francesco, Tor, Gabriel, Urbanec, Martin, Vincent, Frederic, Wu, Qingwen, Yuan, Feng, Zand, Jean J. M. in 't, Zdziarski, Andrzej A., Zhou, Xinlin, De Rosa, Alessandra, Uttley, Phil, Gou, Lijun, Liu, Yuan, Bambi, Cosimo, Barret, Didier, Belloni, Tomaso, Berti, Emanuele, Bianchi, Stefano, Caiazzo, Ilaria, Casella, Piergiorgio, Feroci, Marco, Ferrari, Valeria, Gualtieri, Leonardo, Heyl, Jeremy, Ingram, Adam, Karas, Vladimir, Lu, Fangjun, Luo, Bin, Matt, Giorgio, Motta, Sara, Neilsen, Joseph, Pani, Paolo, Santangelo, Andrea, Shu, Xinwen, Wang, Junfeng, Wang, Jian-Min, Xue, Yongquan, Xu, Yupeng, Yuan, Weimin, Yuan, Yefei, Zhang, Shuang-Nan, Zhang, Shu, Agudo, Ivan, Amati, Lorenzo, Andersson, Nils, Baglio, Cristina, Bakala, Pavel, Baykal, Altan, Bhattacharyya, Sudip, Bombaci, Ignazio, Bucciantini, Niccoló, Capitanio, Fiamma, Ciolfi, Riccardo, Cui, Wei K., D'Ammando, Filippo, Dauser, Thomas, Del Santo, Melania, De Marco, Barbara, Di Salvo, Tiziana, Done, Chris, Dovčiak, Michal, Fabian, Andrew C., Falanga, Maurizio, Gambino, Angelo Francesco, Gendre, Bruce, Grinberg, Victoria, Heger, Alexander, Homan, Jeroen, Iaria, Rosario, Jiang, Jiachen, Jin, Chichuan, Koerding, Elmar, Linares, Manu, Liu, Zhu, Maccarone, Thomas J., Malzac, Julien, Manousakis, Antonios, Marin, Frédéric, Marinucci, Andrea, Mehdipour, Missagh, Méndez, Mariano, Migliari, Simone, Miller, Cole, Miniutti, Giovanni, Nardin, Emanuele, O'Brien, Paul T., Osborne, Julian P., Petrucci, Pierre Olivier, Possenti, Andrea, Riggio, Alessandro, Rodriguez, Jerome, Sanna, Andrea, Shao, Lijing, Sobolewska, Malgosia, Sramkova, Eva, Stevens, Abigail L., Stiele, Holger, Stratta, Giulia, Stuchlik, Zdenek, Svoboda, Jiri, Tamburini, Fabrizio, Tauris, Thomas M., Tombesi, Francesco, Tor, Gabriel, Urbanec, Martin, Vincent, Frederic, Wu, Qingwen, Yuan, Feng, Zand, Jean J. M. in 't, Zdziarski, Andrzej A., and Zhou, Xinlin
Abstract: In this paper we describe the potential of the enhanced X-ray Timing and Polarimetry (eXTP) mission for studies related to accretion flows in the strong field gravity regime around both stellar-mass and supermassive black-holes. eXTP has the unique capability of using advanced 'spectral-timing-polarimetry' techniques to analyze the rapid variations with three orthogonal diagnostics of the flow and its geometry, yielding unprecedented insight into the inner accreting regions, the effects of strong field gravity on the material within them and the powerful outflows which are driven by the accretion process., Comment: Accepted for publication on Sci. China Phys. Mech. Astron. (2019)
Published: 2018
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49. Effects of Chiral Effective Field Theory Equation of State on Binary Neutron Star Mergers

Author: Endrizzi, Andrea, Logoteta, Domenico, Giacomazzo, Bruno, Bombaci, Ignazio, Kastaun, Wolfgang, Ciolfi, Riccardo, Endrizzi, Andrea, Logoteta, Domenico, Giacomazzo, Bruno, Bombaci, Ignazio, Kastaun, Wolfgang, and Ciolfi, Riccardo
Abstract: We present fully general relativistic simulations of binary neutron star mergers, employing a new zero- temperature chiral effective field theory equation of state, the BL EOS. We offer a comparison with respect to the older GM3 EOS, which is based on standard relativistic mean field theory, and separately determine the impact of the mass. We provide a detailed analysis of the dynamics, with focus on the post-merger phase. For all models, we extract the gravitational wave strain and the post-merger frequency spectrum. Further, we determine the amount, velocity, and polar distribution of ejected matter, and provide estimates for the resulting kilonova signals. We also study the evolution of the disk while it is interacting with the hypermassive remnant, and dis- cuss the merits of different disk mass definitions applicable before collapse, with regard to the mass remaining after BH formation. Finally, we investigate the radial mass distribution and rotation profile of the remnants, which validate previous results and also corroborate a recently proposed stability criterion., Comment: 17 pages, 16 figures
Published: 2018
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50. Neutron star properties from optimized chiral nuclear interactions

Author: Logoteta, Domenico, Bombaci, Ignazio, Logoteta, Domenico, and Bombaci, Ignazio
Abstract: We adopt two- and three-body nuclear forces derived at the next-to-next-to-leading-order (N2LO) in the framework of effective chiral perturbation theory (ChPT) to calculate the equation of state (EOS) of $\beta$-stable neutron star matter using the Brueckner--Hartree--Fock many-body approach. We use the recent optimized chiral two-body nuclear interaction at N2LO derived by \cite{ekstrom1} and two different parametrizations of the three-body N2LO interaction: the first one is fixed to reproduce the saturation point of symmetric nuclear matter while the second one is fixed to reproduce the binding energies of light atomic nuclei. We show that in the second case the properties of nuclear matter are not well determined whereas in the first case various empirical nuclear matter properties around the saturation density are well reproduced. We also calculate the nuclear symmetry energy $E_{sym}$ as a function of the nucleonic density and compare our results with the empirical constraints obtained using the excitation energies of isobaric analog states in nuclei and the experimental data on the neutron skin thickness of heavy nuclei. We next calculate various neutron star properties and in particular the mass-radius and mass-central density relations. We find that the adopted interactions based on a fully microscopic framework, are able to provide an EOS which is consistent with the present data of measured neutron star masses and in particular with the mass $M=2.01\pm0.04 M_\odot$ of the neutron star in PSR J0348+0432. We finally consider the possible presence of hyperons in the stellar core and we find a softening of the EOS and a substantial reduction of the stellar maximum mass in agreement with similar calculations present in the literature., Comment: Accepted for publication in PASA
Published: 2018

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