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1. Continuing benefits of the Montreal Protocol and protection of the stratospheric ozone layer for human health and the environment

Author

Madronich, S., Bernhard, G. H., Neale, P. J., Heikkilä, A., Andersen, M. P. Sulbæk, Andrady, A. L., Aucamp, P. J., Bais, A. F., Banaszak, A. T., Barnes, P. J., Bornman, J. F., Bruckman, L. S., Busquets, R., Chiodo, G., Häder, D.-P., Hanson, M. L., Hylander, S., Jansen, M. A. K., Lingham, G., Lucas, R. M., Calderon, R. Mackenzie, Olsen, C., Ossola, R., Pandey, K. K., Petropavlovskikh, I., Revell, L. E., Rhodes, L. E., Robinson, S. A., Robson, T. M., Rose, K. C., Schikowski, T., Solomon, K. R., Sulzberger, B., Wallington, T. J., Wang, Q.-W., Wängberg, S.-Å., White, C. C., Wilson, S. R., Zhu, L., and Neale, R. E.

Published
2024
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4. Environmental effects of stratospheric ozone depletion, UV radiation, and interactions with climate change: UNEP Environmental Effects Assessment Panel, Update 2021

Author

Barnes, P. W., Robson, T. M., Neale, P. J., Williamson, C. E., Zepp, R. G., Madronich, S., Wilson, S. R., Andrady, A. L., Heikkilä, A. M., Bernhard, G. H., Bais, A. F., Neale, R. E., Bornman, J. F., Jansen, M. A. K., Klekociuk, A. R., Martinez-Abaigar, J., Robinson, S. A., Wang, Q.-W., Banaszak, A. T., Häder, D.-P., Hylander, S., Rose, K. C., Wängberg, S.-Å., Foereid, B., Hou, W.-C., Ossola, R., Paul, N. D., Ukpebor, J. E., Andersen, M. P. S., Longstreth, J., Schikowski, T., Solomon, K. R., Sulzberger, B., Bruckman, L. S., Pandey, K. K., White, C. C., Zhu, L., Zhu, M., Aucamp, P. J., Liley, J. B., McKenzie, R. L., Berwick, M., Byrne, S. N., Hollestein, L. M., Lucas, R. M., Olsen, C. M., Rhodes, L. E., Yazar, S., and Young, A. R.

Published
2022
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5. Evaluating the association of allergies with multiple sclerosis susceptibility risk and disease activity in a pediatric population.

Author

Bourne, Theresa, Waltz, Michael, Casper, T, Kavak, K, Aaen, G, Belman, A, Benson, L, Candee, M, Chitnis, T, Graves, J, Greenberg, B, Gorman, M, Harris, Y, Krupp, L, Lotze, T, Mar, S, Ness, J, Olsen, C, Roalstad, S, Rodriguez, M, Rose, J, Rubin, J, Schreiner, T, Tillema, J, Kahn, I, Waldman, A, Barcellos, L, Waubant, E, and Weinstock-Guttman, B

Subjects
Allergies, Multiple sclerosis, Pediatric, Adolescent, Asthma, Case-Control Studies, Cohort Studies, Disease Susceptibility, Female, Humans, Hypersensitivity, Male, Multiple Sclerosis, Risk Factors
Abstract

BACKGROUND: Multiple sclerosis (MS) and allergies are both considered to be related to imbalanced Th1 and Th2 immune responses. Previous studies evaluating the relationship between MS and allergies provide conflicting results. OBJECTIVE: To assess allergies and asthma as risk factors for MS and as predictors of MS relapses in a pediatric cohort. METHODS: The environment and genetic risk factors for pediatric MS study is a national case-control project with 16 participating US sites. An environmental questionnaire is used that includes history of allergies in the first five years of life. Case-control data are entered in the pediatric MS Network database and cases at 12 of the 16 sites enter relapse data prospectively. Annualized relapse rate was calculated for patients with follow-up and adjusted for age at disease onset, gender, race, ethnicity, and use of disease-modifying therapy (DMT). RESULTS: We included 271 cases (mean age at disease onset of 15.7years and 62% female) and 418 controls. Relapse data were available for 193 cases. There was no difference in prevalence of allergies or asthma between cases and controls. Patients with food allergies had fewer relapses compared to patients without food allergies (0.14 vs 0.48, p=0.01). CONCLUSIONS: While allergies and asthma are not associated with pediatric MS, cases with food allergies have fewer relapses compared to those without food allergies.

Published
2017

6. Environmental effects of stratospheric ozone depletion, UV radiation, and interactions with climate change: UNEP Environmental Effects Assessment Panel, Update 2020

Author

Neale, R. E., Barnes, P. W., Robson, T. M., Neale, P. J., Williamson, C. E., Zepp, R. G., Wilson, S. R., Madronich, S., Andrady, A. L., Heikkilä, A. M., Bernhard, G. H., Bais, A. F., Aucamp, P. J., Banaszak, A. T., Bornman, J. F., Bruckman, L. S., Byrne, S. N., Foereid, B., Häder, D.-P., Hollestein, L. M., Hou, W.-C., Hylander, S., Jansen, M. A. K., Klekociuk, A. R., Liley, J. B., Longstreth, J., Lucas, R. M., Martinez-Abaigar, J., McNeill, K., Olsen, C. M., Pandey, K. K., Rhodes, L. E., Robinson, S. A., Rose, K. C., Schikowski, T., Solomon, K. R., Sulzberger, B., Ukpebor, J. E., Wang, Q.-W., Wängberg, S.-Å., White, C. C., Yazar, S., Young, A. R., Young, P. J., Zhu, L., and Zhu, M.

Published
2021
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7. Environmental effects of stratospheric ozone depletion, UV radiation and interactions with climate change: UNEP Environmental Effects Assessment Panel, update 2019

Author

Bernhard, G. H., Neale, R. E., Barnes, P. W., Neale, P. J., Zepp, R. G., Wilson, S. R., Andrady, A. L., Bais, A. F., McKenzie, R. L., Aucamp, P. J., Young, P. J., Liley, J. B., Lucas, R. M., Yazar, S., Rhodes, L. E., Byrne, S. N., Hollestein, L. M., Olsen, C. M., Young, A. R., Robson, T. M., Bornman, J. F., Jansen, M. A. K., Robinson, S. A., Ballaré, C. L., Williamson, C. E., Rose, K. C., Banaszak, A. T., Häder, D. -P., Hylander, S., Wängberg, S. -Å., Austin, A. T., Hou, W. -C., Paul, N. D., Madronich, S., Sulzberger, B., Solomon, K. R., Li, H., Schikowski, T., Longstreth, J., Pandey, K. K., Heikkilä, A. M., and White, C. C.

Published
2020
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8. Oral dydrogesterone versus micronized vaginal progesterone for luteal phase support: a double-blind crossover study investigating pharmacokinetics and impact on the endometrium.

Author

Loreti, S, Thiele, K, Brucker, M De, Olsen, C, Centelles-Lodeiro, J, Bourgain, C, Waelput, W, Tournaye, H, Griesinger, G, Raes, J, Vieira-Silva, S, Arck, P, Blockeel, C, and Mackens, S

Subjects
LUTEAL phase, OVUM donation, INDUCED ovulation, INTRACYTOPLASMIC sperm injection, GENITALIA, CLOMIPHENE
Abstract

STUDY QUESTION How do plasma progesterone (P) and dydrogesterone (D) concentrations together with endometrial histology, transcriptomic signatures, and immune cell composition differ when oral dydrogesterone (O-DYD) or micronized vaginal progesterone (MVP) is used for luteal phase support (LPS)? SUMMARY ANSWER Although after O-DYD intake, even at steady-state, plasma D and 20αdihydrodydrogesterone (DHD) concentrations spiked in comparison to P concentrations, a similar endometrial signature was observed by histological and transcriptomic analysis of the endometrium. WHAT IS KNOWN ALREADY O-DYD for LPS has been proven to be noninferior compared to MVP in two phase III randomized controlled trials. Additionally, a combined individual participant data and aggregate data meta-analysis indicated that a higher pregnancy rate and live birth rate may be obtained in women receiving O-DYD versus MVP for LPS in fresh IVF/ICSI cycles. Little data are available on the pharmacokinetic (PK) profiles of O-DYD versus MVP and their potential molecular differences at the level of the reproductive organs, particularly at the endometrial level. STUDY DESIGN, SIZE, DURATION Thirty oocyte donors were planned to undergo two ovarian stimulation (OS) cycles with dual triggering (1.000 IU hCG + 0.2 mg triptorelin), each followed by 1 week of LPS: O-DYD or MVP, in a randomized, cross-over, double-blind, double-dummy fashion. On both the first and eighth days of LPS, serial blood samples upon first dosing were harvested for plasma D, DHD, and P concentration analyses. On Day 8 of LPS, an endometrial biopsy was collected for histologic examination, transcriptomics, and immune cell analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS All oocyte donors were <35 years old, had regular menstrual cycles, no intrauterine contraceptive device, anti-Müllerian hormone within normal range and a BMI ≤29 kg/m2. OS was performed on a GnRH antagonist protocol followed by dual triggering (1.000 IU hCG + 0.2 mg triptorelin) as soon as ≥3 follicles of 20 mm were present. Following oocyte retrieval, subjects initiated LPS consisting of MVP 200 mg or O-DYD 10 mg, both three times daily. D, DHD, and P plasma levels were measured using liquid chromatography–tandem mass spectrometry. Histological assessment was carried out using the Noyes criteria. Endometrial RNA-sequencing was performed for individual biopsies and differential gene expression was analyzed. Endometrial single-cell suspensions were created followed by flow cytometry for immune cell typing. MAIN RESULTS AND THE ROLE OF CHANCE A total of 21 women completed the entire study protocol. Subjects and stimulation characteristics were found to be similar between groups. Following the first dose of O-DYD, the average observed maximal plasma concentrations (C max) for D and DHD were 2.9 and 77 ng/ml, respectively. The C max for D and DHD was reached after 1.5 and 1.6 h (= T max), respectively. On the eighth day of LPS, the first administration of that day gave rise to a C max of 3.6 and 88 ng/ml for D and DHD, respectively. For both, the observed T max was 1.5 h. Following the first dose of MVP, the C max for P was 16 ng/ml with a T max of 4.2 h. On the eighth day of LPS, the first administration of that day showed a C max for P of 21 ng/ml with a T max of 7.3 h. All 42 biopsies showed endometrium in the secretory phase. The mean cycle day was 23.9 (±1.2) in the O-DYD group versus 24.0 (±1.3) in the MVP group. RNA-sequencing did not reveal significantly differentially expressed genes between samples of both study groups. The average Euclidean distance between samples following O-DYD was significantly lower than following MVP (respectively 12.1 versus 18.8, Mann–Whitney P  = 6.98e−14). Immune cell profiling showed a decrease of CD3 T-cell, γδ T-cell, and B-cell frequencies after MVP treatment compared to O-DYD, while the frequency of natural killer (NK) cells was significantly increased. LIMITATIONS, REASONS FOR CAUTION The main reason for caution is the small sample size, given the basic research nature of the project. The plasma concentrations are best estimates as this was not a formal PK study. Whole tissue bulk RNA-sequencing has been performed not correcting for bias caused by different tissue compositions across biopsies. WIDER IMPLICATIONS OF THE FINDINGS This is the first study comparing O-DYD/MVP, head-to-head, in a randomized design on a molecular level in IVF/ICSI. Plasma serum concentrations suggest that administration frequency is important, in addition to dose, specifically for O-DYD showing a rapid clearance. The molecular endometrial data are overall comparable and thus support the previously reported noninferior reproductive outcomes for O-DYD as compared to MVP. Further research is needed to explore the smaller intersample distance following O-DYD and the subtle changes detected in endometrial immune cells. STUDY FUNDING/COMPETING INTEREST(S) Not related to this work, C.Bl. has received honoraria for lectures, presentations, manuscript writing, educational events, or scientific advice from Abbott, Ferring, Organon, Cooper Surgical, Gedeon-Richter, IBSA, and Merck. H.T. has received honoraria for lectures, presentations, manuscript writing, educational events, or scientific advice from Abbott, Ferring, Cooper Surgical, Gedeon-Richter, Cook, and Goodlife. S.M. has received honoraria for lectures, presentations, educational events, or scientific advice from Abbott, Cooper Surgical, Gedeon-Richter, IBSA, and Merck and Oxolife. G.G. has received honoraria for lectures, presentations, educational events, or scientific advice from Merck, MSD, Organon, Ferring, Theramex, Gedeon-Richter, Abbott, Biosilu, ReprodWissen, Obseva, PregLem, Guerbet, Cooper, Igyxos, and OxoLife. S.V.-S. is listed as inventor on two patents (WO2019115755A1 and WO2022073973A1), which are not related to this work. TRIAL REGISTRATION NUMBER EUDRACT 2018-000105-23 [ABSTRACT FROM AUTHOR]

Published
2024
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9. 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

13. 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, 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, 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, Ferrarese, C, 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., 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., Ferrarese C., 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, 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, Ferrarese, C, 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., 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., and Ferrarese C.

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

21. Environmental effects of stratospheric ozone depletion, UV radiation, and interactions with climate change:UNEP Environmental Effects Assessment Panel, Update 2021

Author

Barnes, P. W., Robson, T. M., Neale, P. J., Williamson, C. E., Zepp, R. G., Madronich, S., Wilson, S. R., Andrady, A. L., Heikkilä, A. M., Bernhard, G. H., Bais, A. F., Neale, R. E., Bornman, J. F., Jansen, M. A. K., Klekociuk, A. R., Martinez-Abaigar, J., Robinson, S. A., Wang, Q.-W., Banaszak, A. T., Häder, D.-P., Hylander, S., Rose, K. C., Wängberg, S.-Å., Foereid, B., Hou, W.-C., Ossola, R., Paul, N. D., Ukpebor, J. E., Andersen, M. P. S., Longstreth, J., Schikowski, T., Solomon, K. R., Sulzberger, B., Bruckman, L. S., Pandey, K. K., White, C. C., Zhu, L., Zhu, M., Aucamp, P. J., Liley, J. B., McKenzie, R. L., Berwick, M., Byrne, S. N., Hollestein, L. M., Lucas, R. M., Olsen, C. M., Rhodes, L. E., Yazar, S., Young, A. R., Barnes, P. W., Robson, T. M., Neale, P. J., Williamson, C. E., Zepp, R. G., Madronich, S., Wilson, S. R., Andrady, A. L., Heikkilä, A. M., Bernhard, G. H., Bais, A. F., Neale, R. E., Bornman, J. F., Jansen, M. A. K., Klekociuk, A. R., Martinez-Abaigar, J., Robinson, S. A., Wang, Q.-W., Banaszak, A. T., Häder, D.-P., Hylander, S., Rose, K. C., Wängberg, S.-Å., Foereid, B., Hou, W.-C., Ossola, R., Paul, N. D., Ukpebor, J. E., Andersen, M. P. S., Longstreth, J., Schikowski, T., Solomon, K. R., Sulzberger, B., Bruckman, L. S., Pandey, K. K., White, C. C., Zhu, L., Zhu, M., Aucamp, P. J., Liley, J. B., McKenzie, R. L., Berwick, M., Byrne, S. N., Hollestein, L. M., Lucas, R. M., Olsen, C. M., Rhodes, L. E., Yazar, S., and Young, A. R.

Abstract

The Environmental Effects Assessment Panel of the Montreal Protocol under the United Nations Environment Programme evaluates effects on the environment and human health that arise from changes in the stratospheric ozone layer and concomitant variations in ultraviolet (UV) radiation at the Earth’s surface. The current update is based on scientific advances that have accumulated since our last assessment (Photochem and Photobiol Sci 20(1):1–67, 2021). We also discuss how climate change affects stratospheric ozone depletion and ultraviolet radiation, and how stratospheric ozone depletion affects climate change. The resulting interlinking effects of stratospheric ozone depletion, UV radiation, and climate change are assessed in terms of air quality, carbon sinks, ecosystems, human health, and natural and synthetic materials. We further highlight potential impacts on the biosphere from extreme climate events that are occurring with increasing frequency as a consequence of climate change. These and other interactive effects are examined with respect to the benefits that the Montreal Protocol and its Amendments are providing to life on Earth by controlling the production of various substances that contribute to both stratospheric ozone depletion and climate change.

Published
2022

22. Conjunctivitis in adult patients with moderate-to-severe atopic dermatitis:results from five tralokinumab clinical trials

Author

Wollenberg, A., Beck, L. A., de Bruin Weller, M., Simpson, E. L., Imafuku, S., Boguniewicz, M., Zachariae, R., Olsen, C. K., Thyssen, J. P., Wollenberg, A., Beck, L. A., de Bruin Weller, M., Simpson, E. L., Imafuku, S., Boguniewicz, M., Zachariae, R., Olsen, C. K., and Thyssen, J. P.

Abstract

Background: Tralokinumab, a fully human IgG4 monoclonal antibody that specifically binds with high affinity to interleukin-13, effectively reduces moderate-to-severe atopic dermatitis (AD) when given every 2 weeks. The incidence of conjunctivitis is elevated vs. placebo, but severity and aetiology have not been examined. Objective: To analyse conjunctivitis data recorded in five randomized, placebo-controlled trials of tralokinumab in adult patients with moderate-to-severe AD. Methods: Overall, 2285 adults with AD were studied up to 16 weeks. Cochran–Mantel–Haenszel weights were applied to calculate the adjusted incidence of adverse events. Results: The incidence of conjunctivitis was higher (7·5%) with tralokinumab than with placebo (3·2%). Most events were mild or moderate in severity, and 78·6% and 73·9% of events resolved during the trial in the tralokinumab and placebo groups, respectively. Two (1·4%) events led to the permanent discontinuation of tralokinumab. An increased incidence of conjunctivitis, regardless of treatment group, was associated with more severe baseline AD, and history of allergic conjunctivitis/atopic keratoconjunctivitis, as well as the number of atopic comorbidities. Limitations: This analysis reports events up to week 16 only, with limited confirmation of conjunctivitis and its aetiology by an ophthalmologist, and insufficient reporting of ophthalmic treatments. Conclusions: Treatment with tralokinumab was associated with an increased incidence of conjunctivitis vs. placebo, but these cases were mostly mild and transient.

Published
2022

23. Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen

Author

Menden M, Wang D, Mason M, Szalai B, Bulusu K, Guan Y, Yu T, Kang J, Jeon M, Wolfinger R, Nguyen T, Zaslavskiy M, Jang I, Ghazoui Z, Ahsen M, Vogel R, Neto E, Norman T, Tang E, Garnett M, Di Veroli G, Fawell S, Stolovitzky G, Guinney J, Dry J, Saez-Rodriguez J, Abante J, Abecassis B, Aben N, Aghamirzaie D, Aittokallio T, Akhtari F, Al-lazikani B, Alam T, Allam A, Allen C, de Almeida M, Altarawy D, Alves V, Amadoz A, Anchang B, Antolin A, Ash J, Aznar V, Ba-alawi W, Bagheri M, Bajic V, Ball G, Ballester P, Baptista D, Bare C, Bateson M, Bender A, Bertrand D, Wijayawardena B, Boroevich K, Bosdriesz E, Bougouffa S, Bounova G, Brouwer T, Bryant B, Calaza M, Calderone A, Calza S, Capuzzi S, Carbonell-Caballero J, Carlin D, Carter H, Castagnoli L, Celebi R, Cesareni G, Chang H, Chen G, Chen H, Cheng L, Chernomoretz A, Chicco D, Cho K, Cho S, Choi D, Choi J, Choi K, Choi M, De Cock M, Coker E, Cortes-Ciriano I, Cserzo M, Cubuk C, Curtis C, Van Daele D, Dang C, Dijkstra T, Dopazo J, Draghici S, Drosou A, Dumontier M, Ehrhart F, Eid F, ElHefnawi M, Elmarakeby H, van Engelen B, Engin H, de Esch I, Evelo C, Falcao A, Farag S, Fernandez-Lozano C, Fisch K, Flobak A, Fornari C, Foroushani A, Fotso D, Fourches D, Friend S, Frigessi A, Gao F, Gao X, Gerold J, Gestraud P, Ghosh S, Gillberg J, Godoy-Lorite A, Godynyuk L, Godzik A, Goldenberg A, Gomez-Cabrero D, Gonen M, de Graaf C, Gray H, Grechkin M, Guimera R, Guney E, Haibe-Kains B, Han Y, Hase T, He D, He L, Heath L, Hellton K, Helmer-Citterich M, Hidalgo M, Hidru D, Hill S, Hochreiter S, Hong S, Hovig E, Hsueh Y, Hu Z, Huang J, Huang R, Hunyady L, Hwang J, Hwang T, Hwang W, Hwang Y, Isayev O, Walk O, Jack J, Jahandideh S, Ji J, Jo Y, Kamola P, Kanev G, Karacosta L, Karimi M, Kaski S, Kazanov M, Khamis A, Khan S, Kiani N, Kim A, Kim J, Kim K, Kim S, Kim Y, Kirk P, Kitano H, Klambauer G, Knowles D, Ko M, Kohn-Luque A, Kooistra A, Kuenemann M, Kuiper M, Kurz C, Kwon M, van Laarhoven T, Laegreid A, Lederer S, Lee H, Lee J, Lee Y, Leppaho E, Lewis R, Li J, Li L, Liley J, Lim W, Lin C, Liu Y, Lopez Y, Low J, Lysenko A, Machado D, Madhukar N, De Maeyer D, Malpartida A, Mamitsuka H, Marabita F, Marchal K, Marttinen P, Mason D, Mazaheri A, Mehmood A, Mehreen A, Michaut M, Miller R, Mitsopoulos C, Modos D, Van Moerbeke M, Moo K, Motsinger-Reif A, Movva R, Muraru S, Muratov E, Mushthofa M, Nagarajan N, Nakken S, Nath A, Neuvial P, Newton R, Ning Z, De Niz C, Oliva B, Olsen C, Palmeri A, Panesar B, Papadopoulos S, Park J, Park S, Pawitan Y, Peluso D, Pendyala S, Peng J, Perfetto L, Pirro S, Plevritis S, Politi R, Poon H, Porta E, Prellner I, Preuer K, Pujana M, Ramnarine R, Reid J, Reyal F, Richardson S, Ricketts C, Rieswijk L, Rocha M, Rodriguez-Gonzalvez C, Roell K, Rotroff D, de Ruiter J, Rukawa P, Sadacca B, Safikhani Z, Safitri F, Sales-Pardo M, Sauer S, Schlichting M, Seoane J, Serra J, Shang M, Sharma A, Sharma H, Shen Y, Shiga M, Shin M, Shkedy Z, Shopsowitz K, Sinai S, Skola D, Smirnov P, Soerensen I, Soerensen P, Song J, Song S, Soufan O, Spitzmueller A, Steipe B, Suphavilai C, Tamayo S, Tamborero D, Tang J, Tanoli Z, Tarres-Deulofeu M, Tegner J, Thommesen L, Tonekaboni S, Tran H, De Troyer E, Truong A, Tsunoda T, Turu G, Tzeng G, Verbeke L, Videla S, Vis D, Voronkov A, Votis K, Wang A, Wang H, Wang P, Wang S, Wang W, Wang X, Wennerberg K, Wernisch L, Wessels L, van Westen G, Westerman B, White S, Willighagen E, Wurdinger T, Xie L, Xie S, Xu H, Yadav B, Yau C, Yeerna H, Yin J, Yu M, Yun S, Zakharov A, Zamichos A, Zanin M, Zeng L, Zenil H, Zhang F, Zhang P, Zhang W, Zhao H, Zhao L, Zheng W, Zoufir A, Zucknick M, AstraZeneca-Sanger Drug Combinatio, Ege Üniversitesi, Gönen, Mehmet (ORCID 0000-0002-2483-075X & YÖK ID 237468), Menden, Michael P., Wang, Dennis, Mason, Mike J., Szalai, Bence, Bulusu, Krishna C., Guan, Yuanfang, Yu, Thomas, Kang, Jaewoo, Jeon, Minji, Wolfinger, Russ, Nguyen, Tin, Zaslavskiy, Mikhail, Jang, In Sock, Ghazoui, Zara, Ahsen, Mehmet Eren, Vogel, Robert, Neto, Elias Chaibub, Norman, Thea, Tang, Eric K. Y., Garnett, Mathew J., Di Veroli, Giovanni Y., Fawell, Stephen, Stolovitzky, Gustavo, Guinney, Justin, Dry, Jonathan R., Saez-Rodriguez, Julio, Abante, Jordi, Abecassis, Barbara Schmitz, Aben, Nanne, Aghamirzaie, Delasa, Aittokallio, Tero, Akhtari, Farida S., Al-lazikani, Bissan, Alam, Tanvir, Allam, Amin, Allen, Chad, de Almeida, Mariana Pelicano, Altarawy, Doaa, Alves, Vinicius, Amadoz, Alicia, Anchang, Benedict, Antolin, Albert A., Ash, Jeremy R., Romeo Aznar, Victoria, Ba-alawi, Wail, Bagheri, Moeen, Bajic, Vladimir, Ball, Gordon, Ballester, Pedro J., Baptista, Delora, Bare, Christopher, Bateson, Mathilde, Bender, Andreas, Bertrand, Denis, Wijayawardena, Bhagya, Boroevich, Keith A., Bosdriesz, Evert, Bougouffa, Salim, Bounova, Gergana, Brouwer, Thomas, Bryant, Barbara, Calaza, Manuel, Calderone, Alberto, Calza, Stefano, Capuzzi, Stephen, Carbonell-Caballero, Jose, Carlin, Daniel, Carter, Hannah, Castagnoli, Luisa, Celebi, Remzi, Cesareni, Gianni, Chang, Hyeokyoon, Chen, Guocai, Chen, Haoran, Chen, Huiyuan, Cheng, Lijun, Chernomoretz, Ariel, Chicco, Davide, Cho, Kwang-Hyun, Cho, Sunghwan, Choi, Daeseon, Choi, Jaejoon, Choi, Kwanghun, Choi, Minsoo, De Cock, Martine, Coker, Elizabeth, Cortes-Ciriano, Isidro, Cserzo, Miklos, Cubuk, Cankut, Curtis, Christina, Van Daele, Dries, Dang, Cuong C., Dijkstra, Tjeerd, Dopazo, Joaquin, Draghici, Sorin, Drosou, Anastasios, Dumontier, Michel, Ehrhart, Friederike, Eid, Fatma-Elzahraa, ElHefnawi, Mahmoud, Elmarakeby, Haitham, van Engelen, Bo, Engin, Hatice Billur, de Esch, Iwan, Evelo, Chris, Falcao, Andre O., Farag, Sherif, Fernandez-Lozano, Carlos, Fisch, Kathleen, Flobak, Asmund, Fornari, Chiara, Foroushani, Amir B. K., Fotso, Donatien Chedom, Fourches, Denis, Friend, Stephen, Frigessi, Arnoldo, Gao, Feng, Gao, Xiaoting, Gerold, Jeffrey M., Gestraud, Pierre, Ghosh, Samik, Gillberg, Jussi, Godoy-Lorite, Antonia, Godynyuk, Lizzy, Godzik, Adam, Goldenberg, Anna, Gomez-Cabrero, David, de Graaf, Chris, Gray, Harry, Grechkin, Maxim, Guimera, Roger, Guney, Emre, Haibe-Kains, Benjamin, Han, Younghyun, Hase, Takeshi, He, Di, He, Liye, Heath, Lenwood S., Hellton, Kristoffer H., Helmer-Citterich, Manuela, Hidalgo, Marta R., Hidru, Daniel, Hill, Steven M., Hochreiter, Sepp, Hong, Seungpyo, Hovig, Eivind, Hsueh, Ya-Chih, Hu, Zhiyuan, Huang, Justin K., Huang, R. Stephanie, Hunyady, Laszlo, Hwang, Jinseub, Hwang, Tae Hyun, Hwang, Woochang, Hwang, Yongdeuk, Isayev, Olexandr, Walk, Oliver Bear Don't, Jack, John, Jahandideh, Samad, Ji, Jiadong, Jo, Yousang, Kamola, Piotr J., Kanev, Georgi K., Karacosta, Loukia, Karimi, Mostafa, Kaski, Samuel, Kazanov, Marat, Khamis, Abdullah M., Khan, Suleiman Ali, Kiani, Narsis A., Kim, Allen, Kim, Jinhan, Kim, Juntae, Kim, Kiseong, Kim, Kyung, Kim, Sunkyu, Kim, Yongsoo, Kim, Yunseong, Kirk, Paul D. W., Kitano, Hiroaki, Klambauer, Gunter, Knowles, David, Ko, Melissa, Kohn-Luque, Alvaro, Kooistra, Albert J., Kuenemann, Melaine A., Kuiper, Martin, Kurz, Christoph, Kwon, Mijin, van Laarhoven, Twan, Laegreid, Astrid, Lederer, Simone, Lee, Heewon, Lee, Jeon, Lee, Yun Woo, Leppaho, Eemeli, Lewis, Richard, Li, Jing, Li, Lang, Liley, James, Lim, Weng Khong, Lin, Chieh, Liu, Yiyi, Lopez, Yosvany, Low, Joshua, Lysenko, Artem, Machado, Daniel, Madhukar, Neel, De Maeyer, Dries, Malpartida, Ana Belen, Mamitsuka, Hiroshi, Marabita, Francesco, Marchal, Kathleen, Marttinen, Pekka, Mason, Daniel, Mazaheri, Alireza, Mehmood, Arfa, Mehreen, Ali, Michaut, Magali, Miller, Ryan A., Mitsopoulos, Costas, Modos, Dezso, Van Moerbeke, Marijke, Moo, Keagan, Motsinger-Reif, Alison, Movva, Rajiv, Muraru, Sebastian, Muratov, Eugene, Mushthofa, Mushthofa, Nagarajan, Niranjan, Nakken, Sigve, Nath, Aritro, Neuvial, Pierre, Newton, Richard, Ning, Zheng, De Niz, Carlos, Oliva, Baldo, Olsen, Catharina, Palmeri, Antonio, Panesar, Bhawan, Papadopoulos, Stavros, Park, Jaesub, Park, Seonyeong, Park, Sungjoon, Pawitan, Yudi, Peluso, Daniele, Pendyala, Sriram, Peng, Jian, Perfetto, Livia, Pirro, Stefano, Plevritis, Sylvia, Politi, Regina, Poon, Hoifung, Porta, Eduard, Prellner, Isak, Preuer, Kristina, Angel Pujana, Miguel, Ramnarine, Ricardo, Reid, John E., Reyal, Fabien, Richardson, Sylvia, Ricketts, Camir, Rieswijk, Linda, Rocha, Miguel, Rodriguez-Gonzalvez, Carmen, Roell, Kyle, Rotroff, Daniel, de Ruiter, Julian R., Rukawa, Ploy, Sadacca, Benjamin, Safikhani, Zhaleh, Safitri, Fita, Sales-Pardo, Marta, Sauer, Sebastian, Schlichting, Moritz, Seoane, Jose A., Serra, Jordi, Shang, Ming-Mei, Sharma, Alok, Sharma, Hari, Shen, Yang, Shiga, Motoki, Shin, Moonshik, Shkedy, Ziv, Shopsowitz, Kevin, Sinai, Sam, Skola, Dylan, Smirnov, Petr, Soerensen, Izel Fourie, Soerensen, Peter, Song, Je-Hoon, Song, Sang Ok, Soufan, Othman, Spitzmueller, Andreas, Steipe, Boris, Suphavilai, Chayaporn, Tamayo, Sergio Pulido, Tamborero, David, Tang, Jing, Tanoli, Zia-ur-Rehman, Tarres-Deulofeu, Marc, Tegner, Jesper, Thommesen, Liv, Tonekaboni, Seyed Ali Madani, Tran, Hong, De Troyer, Ewoud, Truong, Amy, Tsunoda, Tatsuhiko, Turu, Gabor, Tzeng, Guang-Yo, Verbeke, Lieven, Videla, Santiago, Vis, Daniel, Voronkov, Andrey, Votis, Konstantinos, Wang, Ashley, Wang, Hong-Qiang Horace, Wang, Po-Wei, Wang, Sheng, Wang, Wei, Wang, Xiaochen, Wang, Xin, Wennerberg, Krister, Wernisch, Lorenz, Wessels, Lodewyk, van Westen, Gerard J. P., Westerman, Bart A., White, Simon Richard, Willighagen, Egon, Wurdinger, Tom, Xie, Lei, Xie, Shuilian, Xu, Hua, Yadav, Bhagwan, Yau, Christopher, Yeerna, Huwate, Yin, Jia Wei, Yu, Michael, Yu, MinHwan, Yun, So Jeong, Zakharov, Alexey, Zamichos, Alexandros, Zanin, Massimiliano, Zeng, Li, Zenil, Hector, Zhang, Frederick, Zhang, Pengyue, Zhang, Wei, Zhao, Hongyu, Zhao, Lan, Zheng, Wenjin, Zoufir, Azedine, Zucknick, Manuela, College of Engineering, Department of Industrial Engineering, Institute of Data Science, RS: FSE DACS IDS, Bioinformatica, RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health, RS: FHML MaCSBio, Promovendi NTM, Tero Aittokallio / Principal Investigator, Bioinformatics, Institute for Molecular Medicine Finland, Hu, Z, Fotso, DC, Menden, M, Wang, D, Mason, M, Szalai, B, Bulusu, K, Guan, Y, Yu, T, Kang, J, Jeon, M, Wolfinger, R, Nguyen, T, Zaslavskiy, M, Abante, J, Abecassis, B, Aben, N, Aghamirzaie, D, Aittokallio, T, Akhtari, F, Al-lazikani, B, Alam, T, Allam, A, Allen, C, de Almeida, M, Altarawy, D, Alves, V, Amadoz, A, Anchang, B, Antolin, A, Ash, J, Aznar, V, Ba-alawi, W, Bagheri, M, Bajic, V, Ball, G, Ballester, P, Baptista, D, Bare, C, Bateson, M, Bender, A, Bertrand, D, Wijayawardena, B, Boroevich, K, Bosdriesz, E, Bougouffa, S, Bounova, G, Brouwer, T, Bryant, B, Calaza, M, Calderone, A, Calza, S, Capuzzi, S, Carbonell-Caballero, J, Carlin, D, Carter, H, Castagnoli, L, Celebi, R, Cesareni, G, Chang, H, Chen, G, Chen, H, Cheng, L, Chernomoretz, A, Chicco, D, Cho, K, Cho, S, Choi, D, Choi, J, Choi, K, Choi, M, Cock, M, Coker, E, Cortes-Ciriano, I, Cserzo, M, Cubuk, C, Curtis, C, Daele, D, Dang, C, Dijkstra, T, Dopazo, J, Draghici, S, Drosou, A, Dumontier, M, Ehrhart, F, Eid, F, Elhefnawi, M, Elmarakeby, H, van Engelen, B, Engin, H, de Esch, I, Evelo, C, Falcao, A, Farag, S, Fernandez-Lozano, C, Fisch, K, Flobak, A, Fornari, C, Foroushani, A, Fotso, D, Fourches, D, Friend, S, Frigessi, A, Gao, F, Gao, X, Gerold, J, Gestraud, P, Ghosh, S, Gillberg, J, Godoy-Lorite, A, Godynyuk, L, Godzik, A, Goldenberg, A, Gomez-Cabrero, D, Gonen, M, de Graaf, C, Gray, H, Grechkin, M, Guimera, R, Guney, E, Haibe-Kains, B, Han, Y, Hase, T, He, D, He, L, Heath, L, Hellton, K, Helmer-Citterich, M, Hidalgo, M, Hidru, D, Hill, S, Hochreiter, S, Hong, S, Hovig, E, Hsueh, Y, Huang, J, Huang, R, Hunyady, L, Hwang, J, Hwang, T, Hwang, W, Hwang, Y, Isayev, O, Don't Walk, O, Jack, J, Jahandideh, S, Ji, J, Jo, Y, Kamola, P, Kanev, G, Karacosta, L, Karimi, M, Kaski, S, Kazanov, M, Khamis, A, Khan, S, Kiani, N, Kim, A, Kim, J, Kim, K, Kim, S, Kim, Y, Kirk, P, Kitano, H, Klambauer, G, Knowles, D, Ko, M, Kohn-Luque, A, Kooistra, A, Kuenemann, M, Kuiper, M, Kurz, C, Kwon, M, van Laarhoven, T, Laegreid, A, Lederer, S, Lee, H, Lee, J, Lee, Y, Lepp_aho, E, Lewis, R, Li, J, Li, L, Liley, J, Lim, W, Lin, C, Liu, Y, Lopez, Y, Low, J, Lysenko, A, Machado, D, Madhukar, N, Maeyer, D, Malpartida, A, Mamitsuka, H, Marabita, F, Marchal, K, Marttinen, P, Mason, D, Mazaheri, A, Mehmood, A, Mehreen, A, Michaut, M, Miller, R, Mitsopoulos, C, Modos, D, Moerbeke, M, Moo, K, Motsinger-Reif, A, Movva, R, Muraru, S, Muratov, E, Mushthofa, M, Nagarajan, N, Nakken, S, Nath, A, Neuvial, P, Newton, R, Ning, Z, Niz, C, Oliva, B, Olsen, C, Palmeri, A, Panesar, B, Papadopoulos, S, Park, J, Park, S, Pawitan, Y, Peluso, D, Pendyala, S, Peng, J, Perfetto, L, Pirro, S, Plevritis, S, Politi, R, Poon, H, Porta, E, Prellner, I, Preuer, K, Pujana, M, Ramnarine, R, Reid, J, Reyal, F, Richardson, S, Ricketts, C, Rieswijk, L, Rocha, M, Rodriguez-Gonzalvez, C, Roell, K, Rotroff, D, de Ruiter, J, Rukawa, P, Sadacca, B, Safikhani, Z, Safitri, F, Sales-Pardo, M, Sauer, S, Schlichting, M, Seoane, J, Serra, J, Shang, M, Sharma, A, Sharma, H, Shen, Y, Shiga, M, Shin, M, Shkedy, Z, Shopsowitz, K, Sinai, S, Skola, D, Smirnov, P, Soerensen, I, Soerensen, P, Song, J, Song, S, Soufan, O, Spitzmueller, A, Steipe, B, Suphavilai, C, Tamayo, S, Tamborero, D, Tang, J, Tanoli, Z, Tarres-Deulofeu, M, Tegner, J, Thommesen, L, Tonekaboni, S, Tran, H, Troyer, E, Truong, A, Tsunoda, T, Turu, G, Tzeng, G, Verbeke, L, Videla, S, Vis, D, Voronkov, A, Votis, K, Wang, A, Wang, H, Wang, P, Wang, S, Wang, W, Wang, X, Wennerberg, K, Wernisch, L, Wessels, L, van Westen, G, Westerman, B, White, S, Willighagen, E, Wurdinger, T, Xie, L, Xie, S, Xu, H, Yadav, B, Yau, C, Yeerna, H, Yin, J, Yu, M, Yun, S, Zakharov, A, Zamichos, A, Zanin, M, Zeng, L, Zenil, H, Zhang, F, Zhang, P, Zhang, W, Zhao, H, Zhao, L, Zheng, W, Zoufir, A, Zucknick, M, Jang, I, Ghazoui, Z, Ahsen, M, Vogel, R, Neto, E, Norman, T, Tang, E, Garnett, M, Veroli, G, Fawell, S, Stolovitzky, G, Guinney, J, Dry, J, Saez-Rodriguez, J, Menden, Michael P. [0000-0003-0267-5792], Mason, Mike J. [0000-0002-5652-7739], Yu, Thomas [0000-0002-5841-0198], Kang, Jaewoo [0000-0001-6798-9106], Nguyen, Tin [0000-0001-8001-9470], Ahsen, Mehmet Eren [0000-0002-4907-0427], Stolovitzky, Gustavo [0000-0002-9618-2819], Guinney, Justin [0000-0003-1477-1888], Saez-Rodriguez, Julio [0000-0002-8552-8976], Apollo - University of Cambridge Repository, Menden, Michael P [0000-0003-0267-5792], Mason, Mike J [0000-0002-5652-7739], Pathology, CCA - Cancer biology and immunology, Medical oncology laboratory, Neurosurgery, Chemistry and Pharmaceutical Sciences, AIMMS, Medicinal chemistry, Universidade do Minho, Department of Computer Science, Professorship Marttinen P., Aalto-yliopisto, and Aalto University

Subjects
Drug Resistance, 02 engineering and technology, 13, PATHWAY, Antineoplastic Combined Chemotherapy Protocols, Molecular Targeted Therapy, Càncer, lcsh:Science, media_common, Cancer, Tumor, Settore BIO/18, Settore BIO/11, Drug combinations, High-throughput screening, Drug Synergism, purl.org/becyt/ford/1.2 [https], Genomics, Machine Learning, predictions, 3. Good health, ddc, Technologie de l'environnement, contrôle de la pollution, Benchmarking, 5.1 Pharmaceuticals, Cancer treatment, Farmacogenètica, Science & Technology - Other Topics, Development of treatments and therapeutic interventions, 0210 nano-technology, Human, Drug, media_common.quotation_subject, Science, 49/23, ADAM17 Protein, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, SDG 3 - Good Health and Well-being, RESOURCE, Machine learning, Genetics, Chimie, Humans, BREAST-CANCER, CELL, 49/98, Science & Technology, Antineoplastic Combined Chemotherapy Protocol, 45, MUTATIONS, Computational Biology, Androgen receptor, Breast-cancer, Gene, Cell, Inhibition, Resistance, Pathway, Mutations, Landscape, Resource, 631/114/1305, medicine.disease, Drug synergy, 49, 030104 developmental biology, Pharmacogenetics, Mutation, Ciências Médicas::Biotecnologia Médica, lcsh:Q, 631/154/1435/2163, Biomarkers, RESISTANCE, 0301 basic medicine, ING-INF/06 - BIOINGEGNERIA ELETTRONICA E INFORMATICA, Statistical methods, Computer science, General Physics and Astronomy, Datasets as Topic, Drug resistance, purl.org/becyt/ford/1 [https], Phosphatidylinositol 3-Kinases, Biotecnologia Médica [Ciências Médicas], Neoplasms, Science and technology, Phosphoinositide-3 Kinase Inhibitors, Multidisciplinary, Biomarkers, Tumor, Cell Line, Tumor, Drug Antagonism, Drug Resistance, Neoplasm, Treatment Outcome, Pharmacogenetic, article, ANDROGEN RECEPTOR, 49/39, 631/114/2415, 021001 nanoscience & nanotechnology, 692/4028/67, Multidisciplinary Sciences, 317 Pharmacy, Patient Safety, Systems biology, 3122 Cancers, INHIBITION, Computational biology, Cell Line, medicine, LANDSCAPE, Physique, Human Genome, Data Science, General Chemistry, AstraZeneca-Sanger Drug Combination DREAM Consortium, Astronomie, GENE, Good Health and Well Being, Pharmacogenomics, Genomic, Neoplasm, 631/553, Phosphatidylinositol 3-Kinase
Abstract

PubMed: 31209238, The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells. © 2019, The Author(s)., National Institute for Health Research, NIHR Wellcome Trust, WT: 102696, 206194 Magyar Tudományos Akadémia, MTA Bayer 668858 PrECISE AstraZeneca, We thank the Genomics of Drug Sensitivity in Cancer and COSMIC teams at the Wellcome Trust Sanger Institute for help with the preparation of the molecular data, Denes Turei for help with Omnipath, and Katjusa Koler for help with matching drug names across combination screens. We thank AstraZeneca for funding and provision of data to the DREAM Consortium to run the challenge, and funding from the European Union Horizon 2020 research (under grant agreement No 668858 PrECISE to J.S.R.), the Joint Research Center for Computational Biomedicine (which is partially funded by Bayer AG) to J.S.R., National Institute for Health Research (NIHR) Sheffield Biomedical Research Center, Premium Postdoctoral Fellowship Program of the Hungarian Academy of Sciences. M.G lab is supported by Wellcome Trust (102696 and 206194)., Competing interests: K.C.B., Z.G., G.Y.D., E.K.Y.T., S.F., and J.R.D. are AstraZeneca employees. K.C.B., Z.G., E.K.Y.T., S.F., and J.R.D. are AstraZeneca shareholders. Y.G. receives personal compensation from Eli Lilly and Company, is a shareholder of Cleerly, Inc., and Ann Arbor Algorithms, Inc. M.G. receives research funding from AstraZeneca and has performed consultancy for Sanofi. The remaining authors declare no competing interests.

Published
2019

25. 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 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.

Published
2022

27. Female Sex and Angiotensin-Converting Enzyme (ACE) Insertion/Deletion Polymorphism Amplify the Effects of Adiposity on Blood Pressure

Author

Chiriacò, Martina, primary, Tricò, Domenico, additional, Leonetti, Simone, additional, Petrie, John R., additional, Balkau, Beverley, additional, Højlund, Kurt, additional, Pataky, Zoltan, additional, Nilsson, Peter M, additional, Natali, Andrea, additional, Heine, R.J., additional, Dekker, J., additional, de Rooij, S., additional, Nijpels, G., additional, Boorsma, W., additional, Mitrakou, A., additional, Tournis, S., additional, Kyriakopoulou, K., additional, Thomakos, P., additional, Lalic, N., additional, Lalic, K., additional, Jotic, A., additional, Lukic, L., additional, Civcic, M., additional, Nolan, J., additional, Yeow, T.P., additional, Murphy, M., additional, DeLong, C., additional, Neary, G., additional, Colgan, M.P., additional, Hatunic, M., additional, Konrad, T., additional, Böhles, H., additional, Fuellert, S., additional, Baer, F., additional, Zuchhold, H., additional, Golay, A., additional, Harsch Bobbioni, E., additional, Barthassat, V., additional, Makoundou, V., additional, Lehmann, T.N.O., additional, Merminod, T., additional, Perry, C., additional, Neary, F., additional, MacDougall, C., additional, Shields, K., additional, Malcolm, L., additional, Laakso, M., additional, Salmenniemi, U., additional, Aura, A., additional, Raisanen, R., additional, Ruotsalainen, U., additional, Sistonen, T., additional, Laitinen, M., additional, Saloranta, H., additional, Coppack, S.W., additional, McIntosh, N., additional, Ross, J., additional, Pettersson, L., additional, Khadobaksh, P., additional, Laville, M., additional, Bonnet, F., additional, Brac de la Perriere, A., additional, Louche-Pelissier, C., additional, Maitrepierre, C., additional, Peyrat, J., additional, Beltran, S., additional, Serusclat, A., additional, Gabriel, R., additional, Sánchez, E.M., additional, Carraro, R., additional, Friera, A., additional, Novella, B., additional, Nilsson, P., additional, Persson, M., additional, Östling, G., additional, Melander, O., additional, Burri, P., additional, Piatti, P.M., additional, Monti, L.D., additional, Setola, E., additional, Galluccio, E., additional, Minicucci, F., additional, Colleluori, A., additional, Walker, M., additional, Ibrahim, I.M., additional, Jayapaul, M., additional, Carman, D., additional, Ryan, C., additional, Short, K., additional, McGrady, Y., additional, Richardson, D., additional, Beck-Nielsen, H., additional, Staehr, P., additional, Vestergaard, V., additional, Olsen, C., additional, Hansen, L., additional, Bolli, G.B., additional, Porcellati, F., additional, Fanelli, C., additional, Lucidi, P., additional, Calcinaro, F., additional, Saturni, A., additional, Ferrannini, E., additional, Muscelli, E., additional, Pinnola, S., additional, Kozakova, M., additional, Casolaro, A., additional, Astiarraga, B.D., additional, Mingrone, G., additional, Guidone, C., additional, Favuzzi, A., additional, Di Rocco, P., additional, Anderwald, C., additional, Bischof, M., additional, Promintzer, M., additional, Krebs, M., additional, Mandl, M., additional, Hofer, A., additional, Luger, A., additional, Waldhäusl, W., additional, Roden, M., additional, Dekker, J.M., additional, Mari, A., additional, Petrie, J., additional, Gaffney, P., additional, Boran, G., additional, Kok, A., additional, Patel, S., additional, Gastaldelli, A., additional, Ciociaro, D., additional, Guillanneuf, M.T., additional, Mhamdi, L., additional, Landucci, L., additional, Hills, S., additional, Mota, L., additional, Pacini, G., additional, Cavaggion, C., additional, Tura, A., additional, and Hills, S.A., additional

Published
2022
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30. Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen

Author

Menden, M, Wang, D, Mason, M, Szalai, B, Bulusu, K, Guan, Y, Yu, T, Kang, J, Jeon, M, Wolfinger, R, Nguyen, T, Zaslavskiy, M, Abante, J, Abecassis, B, Aben, N, Aghamirzaie, D, Aittokallio, T, Akhtari, F, Al-lazikani, B, Alam, T, Allam, A, Allen, C, de Almeida, M, Altarawy, D, Alves, V, Amadoz, A, Anchang, B, Antolin, A, Ash, J, Aznar, V, Ba-alawi, W, Bagheri, M, Bajic, V, Ball, G, Ballester, P, Baptista, D, Bare, C, Bateson, M, Bender, A, Bertrand, D, Wijayawardena, B, Boroevich, K, Bosdriesz, E, Bougouffa, S, Bounova, G, Brouwer, T, Bryant, B, Calaza, M, Calderone, A, Calza, S, Capuzzi, S, Carbonell-Caballero, J, Carlin, D, Carter, H, Castagnoli, L, Celebi, R, Cesareni, G, Chang, H, Chen, G, Chen, H, Cheng, L, Chernomoretz, A, Chicco, D, Cho, K, Cho, S, Choi, D, Choi, J, Choi, K, Choi, M, Cock, M, Coker, E, Cortes-Ciriano, I, Cserzo, M, Cubuk, C, Curtis, C, Daele, D, Dang, C, Dijkstra, T, Dopazo, J, Draghici, S, Drosou, A, Dumontier, M, Ehrhart, F, Eid, F, Elhefnawi, M, Elmarakeby, H, van Engelen, B, Engin, H, de Esch, I, Evelo, C, Falcao, A, Farag, S, Fernandez-Lozano, C, Fisch, K, Flobak, A, Fornari, C, Foroushani, A, Fotso, D, Fourches, D, Friend, S, Frigessi, A, Gao, F, Gao, X, Gerold, J, Gestraud, P, Ghosh, S, Gillberg, J, Godoy-Lorite, A, Godynyuk, L, Godzik, A, Goldenberg, A, Gomez-Cabrero, D, Gonen, M, de Graaf, C, Gray, H, Grechkin, M, Guimera, R, Guney, E, Haibe-Kains, B, Han, Y, Hase, T, He, D, He, L, Heath, L, Hellton, K, Helmer-Citterich, M, Hidalgo, M, Hidru, D, Hill, S, Hochreiter, S, Hong, S, Hovig, E, Hsueh, Y, Hu, Z, Huang, J, Huang, R, Hunyady, L, Hwang, J, Hwang, T, Hwang, W, Hwang, Y, Isayev, O, Don't Walk, O, Jack, J, Jahandideh, S, Ji, J, Jo, Y, Kamola, P, Kanev, G, Karacosta, L, Karimi, M, Kaski, S, Kazanov, M, Khamis, A, Khan, S, Kiani, N, Kim, A, Kim, J, Kim, K, Kim, S, Kim, Y, Kirk, P, Kitano, H, Klambauer, G, Knowles, D, Ko, M, Kohn-Luque, A, Kooistra, A, Kuenemann, M, Kuiper, M, Kurz, C, Kwon, M, van Laarhoven, T, Laegreid, A, Lederer, S, Lee, H, Lee, J, Lee, Y, Lepp_aho, E, Lewis, R, Li, J, Li, L, Liley, J, Lim, W, Lin, C, Liu, Y, Lopez, Y, Low, J, Lysenko, A, Machado, D, Madhukar, N, Maeyer, D, Malpartida, A, Mamitsuka, H, Marabita, F, Marchal, K, Marttinen, P, Mason, D, Mazaheri, A, Mehmood, A, Mehreen, A, Michaut, M, Miller, R, Mitsopoulos, C, Modos, D, Moerbeke, M, Moo, K, Motsinger-Reif, A, Movva, R, Muraru, S, Muratov, E, Mushthofa, M, Nagarajan, N, Nakken, S, Nath, A, Neuvial, P, Newton, R, Ning, Z, Niz, C, Oliva, B, Olsen, C, Palmeri, A, Panesar, B, Papadopoulos, S, Park, J, Park, S, Pawitan, Y, Peluso, D, Pendyala, S, Peng, J, Perfetto, L, Pirro, S, Plevritis, S, Politi, R, Poon, H, Porta, E, Prellner, I, Preuer, K, Pujana, M, Ramnarine, R, Reid, J, Reyal, F, Richardson, S, Ricketts, C, Rieswijk, L, Rocha, M, Rodriguez-Gonzalvez, C, Roell, K, Rotroff, D, de Ruiter, J, Rukawa, P, Sadacca, B, Safikhani, Z, Safitri, F, Sales-Pardo, M, Sauer, S, Schlichting, M, Seoane, J, Serra, J, Shang, M, Sharma, A, Sharma, H, Shen, Y, Shiga, M, Shin, M, Shkedy, Z, Shopsowitz, K, Sinai, S, Skola, D, Smirnov, P, Soerensen, I, Soerensen, P, Song, J, Song, S, Soufan, O, Spitzmueller, A, Steipe, B, Suphavilai, C, Tamayo, S, Tamborero, D, Tang, J, Tanoli, Z, Tarres-Deulofeu, M, Tegner, J, Thommesen, L, Tonekaboni, S, Tran, H, Troyer, E, Truong, A, Tsunoda, T, Turu, G, Tzeng, G, Verbeke, L, Videla, S, Vis, D, Voronkov, A, Votis, K, Wang, A, Wang, H, Wang, P, Wang, S, Wang, W, Wang, X, Wennerberg, K, Wernisch, L, Wessels, L, van Westen, G, Westerman, B, White, S, Willighagen, E, Wurdinger, T, Xie, L, Xie, S, Xu, H, Yadav, B, Yau, C, Yeerna, H, Yin, J, Yu, M, Yun, S, Zakharov, A, Zamichos, A, Zanin, M, Zeng, L, Zenil, H, Zhang, F, Zhang, P, Zhang, W, Zhao, H, Zhao, L, Zheng, W, Zoufir, A, Zucknick, M, Jang, I, Ghazoui, Z, Ahsen, M, Vogel, R, Neto, E, Norman, T, Tang, E, Garnett, M, Veroli, G, Fawell, S, Stolovitzky, G, Guinney, J, Dry, J, Saez-Rodriguez, J, Menden M. P., Wang D., Mason M. J., Szalai B., Bulusu K. C., Guan Y., Yu T., Kang J., Jeon M., Wolfinger R., Nguyen T., Zaslavskiy M., Abante J., Abecassis B. S., Aben N., Aghamirzaie D., Aittokallio T., Akhtari F. S., Al-lazikani B., Alam T., Allam A., Allen C., de Almeida M. P., Altarawy D., Alves V., Amadoz A., Anchang B., Antolin A. A., Ash J. R., Aznar V. R., Ba-alawi W., Bagheri M., Bajic V., Ball G., Ballester P. J., Baptista D., Bare C., Bateson M., Bender A., Bertrand D., Wijayawardena B., Boroevich K. A., Bosdriesz E., Bougouffa S., Bounova G., Brouwer T., Bryant B., Calaza M., Calderone A., Calza S., Capuzzi S., Carbonell-Caballero J., Carlin D., Carter H., Castagnoli L., Celebi R., Cesareni G., Chang H., Chen G., Chen H., Cheng L., Chernomoretz A., Chicco D., Cho K. -H., Cho S., Choi D., Choi J., Choi K., Choi M., Cock M. D., Coker E., Cortes-Ciriano I., Cserzo M., Cubuk C., Curtis C., Daele D. V., Dang C. C., Dijkstra T., Dopazo J., Draghici S., Drosou A., Dumontier M., Ehrhart F., Eid F. -E., ElHefnawi M., Elmarakeby H., van Engelen B., Engin H. B., de Esch I., Evelo C., Falcao A. O., Farag S., Fernandez-Lozano C., Fisch K., Flobak A., Fornari C., Foroushani A. B. K., Fotso D. C., Fourches D., Friend S., Frigessi A., Gao F., Gao X., Gerold J. M., Gestraud P., Ghosh S., Gillberg J., Godoy-Lorite A., Godynyuk L., Godzik A., Goldenberg A., Gomez-Cabrero D., Gonen M., de Graaf C., Gray H., Grechkin M., Guimera R., Guney E., Haibe-Kains B., Han Y., Hase T., He D., He L., Heath L. S., Hellton K. H., Helmer-Citterich M., Hidalgo M. R., Hidru D., Hill S. M., Hochreiter S., Hong S., Hovig E., Hsueh Y. -C., Hu Z., Huang J. K., Huang R. S., Hunyady L., Hwang J., Hwang T. H., Hwang W., Hwang Y., Isayev O., Don't Walk O. B., Jack J., Jahandideh S., Ji J., Jo Y., Kamola P. J., Kanev G. K., Karacosta L., Karimi M., Kaski S., Kazanov M., Khamis A. M., Khan S. A., Kiani N. A., Kim A., Kim J., Kim K., Kim S., Kim Y., Kirk P. D. W., Kitano H., Klambauer G., Knowles D., Ko M., Kohn-Luque A., Kooistra A. J., Kuenemann M. A., Kuiper M., Kurz C., Kwon M., van Laarhoven T., Laegreid A., Lederer S., Lee H., Lee J., Lee Y. W., Lepp_aho E., Lewis R., Li J., Li L., Liley J., Lim W. K., Lin C., Liu Y., Lopez Y., Low J., Lysenko A., Machado D., Madhukar N., Maeyer D. D., Malpartida A. B., Mamitsuka H., Marabita F., Marchal K., Marttinen P., Mason D., Mazaheri A., Mehmood A., Mehreen A., Michaut M., Miller R. A., Mitsopoulos C., Modos D., Moerbeke M. V., Moo K., Motsinger-Reif A., Movva R., Muraru S., Muratov E., Mushthofa M., Nagarajan N., Nakken S., Nath A., Neuvial P., Newton R., Ning Z., Niz C. D., Oliva B., Olsen C., Palmeri A., Panesar B., Papadopoulos S., Park J., Park S., Pawitan Y., Peluso D., Pendyala S., Peng J., Perfetto L., Pirro S., Plevritis S., Politi R., Poon H., Porta E., Prellner I., Preuer K., Pujana M. A., Ramnarine R., Reid J. E., Reyal F., Richardson S., Ricketts C., Rieswijk L., Rocha M., Rodriguez-Gonzalvez C., Roell K., Rotroff D., de Ruiter J. R., Rukawa P., Sadacca B., Safikhani Z., Safitri F., Sales-Pardo M., Sauer S., Schlichting M., Seoane J. A., Serra J., Shang M. -M., Sharma A., Sharma H., Shen Y., Shiga M., Shin M., Shkedy Z., Shopsowitz K., Sinai S., Skola D., Smirnov P., Soerensen I. F., Soerensen P., Song J. -H., Song S. O., Soufan O., Spitzmueller A., Steipe B., Suphavilai C., Tamayo S. P., Tamborero D., Tang J., Tanoli Z. -U. -R., Tarres-Deulofeu M., Tegner J., Thommesen L., Tonekaboni S. A. M., Tran H., Troyer E. D., Truong A., Tsunoda T., Turu G., Tzeng G. -Y., Verbeke L., Videla S., Vis D., Voronkov A., Votis K., Wang A., Wang H. -Q. H., Wang P. -W., Wang S., Wang W., Wang X., Wennerberg K., Wernisch L., Wessels L., van Westen G. J. P., Westerman B. A., White S. R., Willighagen E., Wurdinger T., Xie L., Xie S., Xu H., Yadav B., Yau C., Yeerna H., Yin J. W., Yu M., Yu M. H., Yun S. J., Zakharov A., Zamichos A., Zanin M., Zeng L., Zenil H., Zhang F., Zhang P., Zhang W., Zhao H., Zhao L., Zheng W., Zoufir A., Zucknick M., Jang I. S., Ghazoui Z., Ahsen M. E., Vogel R., Neto E. C., Norman T., Tang E. K. Y., Garnett M. J., Veroli G. Y. D., Fawell S., Stolovitzky G., Guinney J., Dry J. R., Saez-Rodriguez J., Menden, M, Wang, D, Mason, M, Szalai, B, Bulusu, K, Guan, Y, Yu, T, Kang, J, Jeon, M, Wolfinger, R, Nguyen, T, Zaslavskiy, M, Abante, J, Abecassis, B, Aben, N, Aghamirzaie, D, Aittokallio, T, Akhtari, F, Al-lazikani, B, Alam, T, Allam, A, Allen, C, de Almeida, M, Altarawy, D, Alves, V, Amadoz, A, Anchang, B, Antolin, A, Ash, J, Aznar, V, Ba-alawi, W, Bagheri, M, Bajic, V, Ball, G, Ballester, P, Baptista, D, Bare, C, Bateson, M, Bender, A, Bertrand, D, Wijayawardena, B, Boroevich, K, Bosdriesz, E, Bougouffa, S, Bounova, G, Brouwer, T, Bryant, B, Calaza, M, Calderone, A, Calza, S, Capuzzi, S, Carbonell-Caballero, J, Carlin, D, Carter, H, Castagnoli, L, Celebi, R, Cesareni, G, Chang, H, Chen, G, Chen, H, Cheng, L, Chernomoretz, A, Chicco, D, Cho, K, Cho, S, Choi, D, Choi, J, Choi, K, Choi, M, Cock, M, Coker, E, Cortes-Ciriano, I, Cserzo, M, Cubuk, C, Curtis, C, Daele, D, Dang, C, Dijkstra, T, Dopazo, J, Draghici, S, Drosou, A, Dumontier, M, Ehrhart, F, Eid, F, Elhefnawi, M, Elmarakeby, H, van Engelen, B, Engin, H, de Esch, I, Evelo, C, Falcao, A, Farag, S, Fernandez-Lozano, C, Fisch, K, Flobak, A, Fornari, C, Foroushani, A, Fotso, D, Fourches, D, Friend, S, Frigessi, A, Gao, F, Gao, X, Gerold, J, Gestraud, P, Ghosh, S, Gillberg, J, Godoy-Lorite, A, Godynyuk, L, Godzik, A, Goldenberg, A, Gomez-Cabrero, D, Gonen, M, de Graaf, C, Gray, H, Grechkin, M, Guimera, R, Guney, E, Haibe-Kains, B, Han, Y, Hase, T, He, D, He, L, Heath, L, Hellton, K, Helmer-Citterich, M, Hidalgo, M, Hidru, D, Hill, S, Hochreiter, S, Hong, S, Hovig, E, Hsueh, Y, Hu, Z, Huang, J, Huang, R, Hunyady, L, Hwang, J, Hwang, T, Hwang, W, Hwang, Y, Isayev, O, Don't Walk, O, Jack, J, Jahandideh, S, Ji, J, Jo, Y, Kamola, P, Kanev, G, Karacosta, L, Karimi, M, Kaski, S, Kazanov, M, Khamis, A, Khan, S, Kiani, N, Kim, A, Kim, J, Kim, K, Kim, S, Kim, Y, Kirk, P, Kitano, H, Klambauer, G, Knowles, D, Ko, M, Kohn-Luque, A, Kooistra, A, Kuenemann, M, Kuiper, M, Kurz, C, Kwon, M, van Laarhoven, T, Laegreid, A, Lederer, S, Lee, H, Lee, J, Lee, Y, Lepp_aho, E, Lewis, R, Li, J, Li, L, Liley, J, Lim, W, Lin, C, Liu, Y, Lopez, Y, Low, J, Lysenko, A, Machado, D, Madhukar, N, Maeyer, D, Malpartida, A, Mamitsuka, H, Marabita, F, Marchal, K, Marttinen, P, Mason, D, Mazaheri, A, Mehmood, A, Mehreen, A, Michaut, M, Miller, R, Mitsopoulos, C, Modos, D, Moerbeke, M, Moo, K, Motsinger-Reif, A, Movva, R, Muraru, S, Muratov, E, Mushthofa, M, Nagarajan, N, Nakken, S, Nath, A, Neuvial, P, Newton, R, Ning, Z, Niz, C, Oliva, B, Olsen, C, Palmeri, A, Panesar, B, Papadopoulos, S, Park, J, Park, S, Pawitan, Y, Peluso, D, Pendyala, S, Peng, J, Perfetto, L, Pirro, S, Plevritis, S, Politi, R, Poon, H, Porta, E, Prellner, I, Preuer, K, Pujana, M, Ramnarine, R, Reid, J, Reyal, F, Richardson, S, Ricketts, C, Rieswijk, L, Rocha, M, Rodriguez-Gonzalvez, C, Roell, K, Rotroff, D, de Ruiter, J, Rukawa, P, Sadacca, B, Safikhani, Z, Safitri, F, Sales-Pardo, M, Sauer, S, Schlichting, M, Seoane, J, Serra, J, Shang, M, Sharma, A, Sharma, H, Shen, Y, Shiga, M, Shin, M, Shkedy, Z, Shopsowitz, K, Sinai, S, Skola, D, Smirnov, P, Soerensen, I, Soerensen, P, Song, J, Song, S, Soufan, O, Spitzmueller, A, Steipe, B, Suphavilai, C, Tamayo, S, Tamborero, D, Tang, J, Tanoli, Z, Tarres-Deulofeu, M, Tegner, J, Thommesen, L, Tonekaboni, S, Tran, H, Troyer, E, Truong, A, Tsunoda, T, Turu, G, Tzeng, G, Verbeke, L, Videla, S, Vis, D, Voronkov, A, Votis, K, Wang, A, Wang, H, Wang, P, Wang, S, Wang, W, Wang, X, Wennerberg, K, Wernisch, L, Wessels, L, van Westen, G, Westerman, B, White, S, Willighagen, E, Wurdinger, T, Xie, L, Xie, S, Xu, H, Yadav, B, Yau, C, Yeerna, H, Yin, J, Yu, M, Yun, S, Zakharov, A, Zamichos, A, Zanin, M, Zeng, L, Zenil, H, Zhang, F, Zhang, P, Zhang, W, Zhao, H, Zhao, L, Zheng, W, Zoufir, A, Zucknick, M, Jang, I, Ghazoui, Z, Ahsen, M, Vogel, R, Neto, E, Norman, T, Tang, E, Garnett, M, Veroli, G, Fawell, S, Stolovitzky, G, Guinney, J, Dry, J, Saez-Rodriguez, J, Menden M. P., Wang D., Mason M. J., Szalai B., Bulusu K. C., Guan Y., Yu T., Kang J., Jeon M., Wolfinger R., Nguyen T., Zaslavskiy M., Abante J., Abecassis B. S., Aben N., Aghamirzaie D., Aittokallio T., Akhtari F. S., Al-lazikani B., Alam T., Allam A., Allen C., de Almeida M. P., Altarawy D., Alves V., Amadoz A., Anchang B., Antolin A. A., Ash J. R., Aznar V. R., Ba-alawi W., Bagheri M., Bajic V., Ball G., Ballester P. J., Baptista D., Bare C., Bateson M., Bender A., Bertrand D., Wijayawardena B., Boroevich K. A., Bosdriesz E., Bougouffa S., Bounova G., Brouwer T., Bryant B., Calaza M., Calderone A., Calza S., Capuzzi S., Carbonell-Caballero J., Carlin D., Carter H., Castagnoli L., Celebi R., Cesareni G., Chang H., Chen G., Chen H., Cheng L., Chernomoretz A., Chicco D., Cho K. -H., Cho S., Choi D., Choi J., Choi K., Choi M., Cock M. D., Coker E., Cortes-Ciriano I., Cserzo M., Cubuk C., Curtis C., Daele D. V., Dang C. C., Dijkstra T., Dopazo J., Draghici S., Drosou A., Dumontier M., Ehrhart F., Eid F. -E., ElHefnawi M., Elmarakeby H., van Engelen B., Engin H. B., de Esch I., Evelo C., Falcao A. O., Farag S., Fernandez-Lozano C., Fisch K., Flobak A., Fornari C., Foroushani A. B. K., Fotso D. C., Fourches D., Friend S., Frigessi A., Gao F., Gao X., Gerold J. M., Gestraud P., Ghosh S., Gillberg J., Godoy-Lorite A., Godynyuk L., Godzik A., Goldenberg A., Gomez-Cabrero D., Gonen M., de Graaf C., Gray H., Grechkin M., Guimera R., Guney E., Haibe-Kains B., Han Y., Hase T., He D., He L., Heath L. S., Hellton K. H., Helmer-Citterich M., Hidalgo M. R., Hidru D., Hill S. M., Hochreiter S., Hong S., Hovig E., Hsueh Y. -C., Hu Z., Huang J. K., Huang R. S., Hunyady L., Hwang J., Hwang T. H., Hwang W., Hwang Y., Isayev O., Don't Walk O. B., Jack J., Jahandideh S., Ji J., Jo Y., Kamola P. J., Kanev G. K., Karacosta L., Karimi M., Kaski S., Kazanov M., Khamis A. M., Khan S. A., Kiani N. A., Kim A., Kim J., Kim K., Kim S., Kim Y., Kirk P. D. W., Kitano H., Klambauer G., Knowles D., Ko M., Kohn-Luque A., Kooistra A. J., Kuenemann M. A., Kuiper M., Kurz C., Kwon M., van Laarhoven T., Laegreid A., Lederer S., Lee H., Lee J., Lee Y. W., Lepp_aho E., Lewis R., Li J., Li L., Liley J., Lim W. K., Lin C., Liu Y., Lopez Y., Low J., Lysenko A., Machado D., Madhukar N., Maeyer D. D., Malpartida A. B., Mamitsuka H., Marabita F., Marchal K., Marttinen P., Mason D., Mazaheri A., Mehmood A., Mehreen A., Michaut M., Miller R. A., Mitsopoulos C., Modos D., Moerbeke M. V., Moo K., Motsinger-Reif A., Movva R., Muraru S., Muratov E., Mushthofa M., Nagarajan N., Nakken S., Nath A., Neuvial P., Newton R., Ning Z., Niz C. D., Oliva B., Olsen C., Palmeri A., Panesar B., Papadopoulos S., Park J., Park S., Pawitan Y., Peluso D., Pendyala S., Peng J., Perfetto L., Pirro S., Plevritis S., Politi R., Poon H., Porta E., Prellner I., Preuer K., Pujana M. A., Ramnarine R., Reid J. E., Reyal F., Richardson S., Ricketts C., Rieswijk L., Rocha M., Rodriguez-Gonzalvez C., Roell K., Rotroff D., de Ruiter J. R., Rukawa P., Sadacca B., Safikhani Z., Safitri F., Sales-Pardo M., Sauer S., Schlichting M., Seoane J. A., Serra J., Shang M. -M., Sharma A., Sharma H., Shen Y., Shiga M., Shin M., Shkedy Z., Shopsowitz K., Sinai S., Skola D., Smirnov P., Soerensen I. F., Soerensen P., Song J. -H., Song S. O., Soufan O., Spitzmueller A., Steipe B., Suphavilai C., Tamayo S. P., Tamborero D., Tang J., Tanoli Z. -U. -R., Tarres-Deulofeu M., Tegner J., Thommesen L., Tonekaboni S. A. M., Tran H., Troyer E. D., Truong A., Tsunoda T., Turu G., Tzeng G. -Y., Verbeke L., Videla S., Vis D., Voronkov A., Votis K., Wang A., Wang H. -Q. H., Wang P. -W., Wang S., Wang W., Wang X., Wennerberg K., Wernisch L., Wessels L., van Westen G. J. P., Westerman B. A., White S. R., Willighagen E., Wurdinger T., Xie L., Xie S., Xu H., Yadav B., Yau C., Yeerna H., Yin J. W., Yu M., Yu M. H., Yun S. J., Zakharov A., Zamichos A., Zanin M., Zeng L., Zenil H., Zhang F., Zhang P., Zhang W., Zhao H., Zhao L., Zheng W., Zoufir A., Zucknick M., Jang I. S., Ghazoui Z., Ahsen M. E., Vogel R., Neto E. C., Norman T., Tang E. K. Y., Garnett M. J., Veroli G. Y. D., Fawell S., Stolovitzky G., Guinney J., Dry J. R., and Saez-Rodriguez J.

Abstract

The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.

Published
2019

34. One hour post-load plasma glucose and 3 year risk of worsening fasting and 2 hour glucose tolerance in the RISC cohort

Author

Manco, Melania, Mari, Andrea, Petrie, John, Mingrone, Geltrude, Balkau, Beverley, Amsterdam, for the EGIR-RISC study group., Heine, Rj, Dekker, J, S de Rooij, Nijpels, G, W Boorsma Athens, Greece:, A Mitrakou, Tournis, S, Kyriakopoulou, K, P Thomakos Belgrade, Serbia:, N Lalic, Lalic, K, Jotic, A, Lukic, L, M Civcic Dublin, Ireland:, J Nolan, Yeow, Tp, Murphy, M, Delong, C, Neary, G, Colgan, Mp, M Hatunic Frankfurt, Germany:, T Konrad, Böhles, H, Fuellert, S, Baer, F, H Zuchhold Geneva, Switzerland:, A Golay, E Harsch Bobbioni, Barthassat, V, Makoundou, V, Tno, Lehmann, T Merminod Glasgow, Scotland, UK: JR Petrie, Perry, C, Neary, F, Macdougall, C, Shields, K, L Malcolm Kuopio, Finland:, M Laakso, Salmenniemi, U, Aura, A, Raisanen, R, Ruotsalainen, U, Sistonen, T, Laitinen, M, H Saloranta London, England, UK: SW Coppack, Mcintosh, N, Ross, J, Pettersson, L, P Khadobaksh Lyon, France:, M Laville, F Bonnet (now Rennes), A Brac de la Perriere, Louche-Pelissier, C, Maitrepierre, C, Peyrat, J, Beltran, S, A Serusclat Madrid, Spain:, R Gabriel, Sánchez, Em, Carraro, R, Friera, A, B Novella Malmö, Sweden (1):, P Nilsson, Persson, M, G Östling (2):, O Melander, P Burri Milan, Italy: PM Piatti, Monti, Ld, Setola, E, Galluccio, E, Minicucci, F, A Colleluori Newcastle-upon-Tyne, Uk:, M Walker, Ibrahim, Im, Jayapaul, M, Carman, D, Ryan, C, Short, K, Mcgrady, Y, D Richardson Odense, Denmark:, H Beck-Nielsen, Staehr, P, Højlund, K, Vestergaard, V, Olsen, C, L Hansen Perugia, Italy: GB Bolli, Porcellati, F, Fanelli, C, Lucidi, P, Calcinaro, F, A Saturni Pisa, Italy:, E Ferrannini, Natali, A, Muscelli, E, Pinnola, S, Kozakova, M, Casolaro, A, BD Astiarraga Rome, Italy:, G Mingrone, Guidone, C, Favuzzi, A, P Di Rocco Vienna, Austria:, C Anderwald, Bischof, M, Promintzer, M, Krebs, M, Mandl, M, Hofer, A, Luger, A, Waldhäusl, W, and Roden, M

Subjects
Post-load glucose, Adult, Male, Blood Glucose, 0301 basic medicine, Diagnostic criteria, Endocrinology, Diabetes and Metabolism, Physiology, 030209 endocrinology & metabolism, Prediabetic State, 03 medical and health sciences, Endocrinology, 0302 clinical medicine, Research Letter, Internal Medicine, medicine, Humans, Prediabetes, Plasma glucose, Glucose tolerance test, Post-challenge glucose, Prediabetes phenotype, Progression, medicine.diagnostic_test, business.industry, Fasting, Female, Glucose Tolerance Test, Middle Aged, Settore MED/13 - ENDOCRINOLOGIA, Human physiology, medicine.disease, Diabetes and Metabolism, 030104 developmental biology, Cohort, business
Abstract

The affiliation details for Geltrude Mingrone are corrected below.

Published
2018

37. Risk Assessment of Ozone Fumigation Under Vacuum to Control Potential Infestation of Coffee Berry Borer and Coffee Leaf Rust in Green Coffee Beans Imported Into Hawaii

Author

Portilla, M, primary, Follett, P A, additional, Armstrong, J W, additional, Leesch, J G, additional, Tebbets, J S, additional, Smilanick, J, additional, McHugh, T H, additional, Olsen, C W, additional, Whitehand, L, additional, Cavaletto, C, additional, Bittenbender, H C S, additional, Bustillo, A E, additional, and Peña, J E, additional

Published
2021
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38. Gamma-glutamyltransferase, arterial remodeling and prehypertension in a healthy population at low cardiometabolic risk

Author

Kozakova, M. Gastaldelli, A. Morizzo, C. Højlund, K. Nilssson, P.M. Ferrannini, E. Heine, R.J. Dekker, J. de Rooij, S. Nijpels, G. Boorsma, W. Kok, A. Mitrakou, A. Tournis, S. Kyriakopoulou, K. Thomakos, P. Lalic, N. Lalic, K. Jotic, A. Lukic, L. Civcic, M. Nolan, J. Yeow, T.P. Murphy, M. DeLong, C. Neary, G. Colgan, M.P. Hatunic, M. Gaffney, P. Boran, G. Konrad, T. Böhles, H. Fuellert, S. Baer, F. Zuchhold, H. Golay, A. Bobbioni, E.H. Barthassat, V. Makoundou, V. Lehmann, T.N.O. Merminod, T. Petrie (now Dundee), J.R. Perry, C. Neary, F. MacDougall, C. Shields, K. Malcolm, L. Laakso, M. Salmenniemi, U. Aura, A. Raisanen, R. Ruotsalainen, U. Sistonen, T. Laitinen, M. Saloranta, H. Coppack, S.W. McIntosh, N. Ross, J. Pettersson, L. Khadobaksh, P. Balkau, B. Mhamdi, L. Guillanneuf, M.T. Laville, M. Bonnet, F. Brac de la Perriere, A. Louche-Pelissier, C. Maitrepierre, C. Peyrat, J. Beltran, S. Serusclat, A. Gabriel, R. Sánchez, E.M. Carraro, R. Friera, A. Novella, B. Nilssone, P. Persson, M. Östling, G. Melander, O. Burri, P. Piatti, P.M. Monti, L.D. Setola, E. Galluccio, E. Minicucci, F. Colleluori, A. Walker, M. Ibrahim, I.M. Jayapaul, M. Carman, D. Ryan, C. Short, K. McGrady, Y. Richardson, D. Patel, S. Beck-Nielsen, H. Staehr, P. Hojlundd, K. Vestergaard, V. Olsen, C. Hansen, L. Bolli, G.B. Porcellati, F. Fanelli, C. Lucidi, P. Calcinaro, F. Saturni, A. Ferranninia, E. Natali, A. Muscelli, E. Pinnola, S. Kozakovaa, M. Hills, S.A. Landucci, L. Mota, L. Gastaldelli, A. Ciociaro, D. Mari, A. Pacini, G. Cavaggion, C. Mingrone, G. Guidone, C. Favuzzi, A. Di Rocco, P. Anderwald, C. Bischof, M. Promintzer, M. Krebs, M. Mandl, M. Hofer, A. Luger, A. Waldhäusl, W. Roden, M. Palombo, C. RISC Investigators

Abstract

Plasma gamma-glutamyltransferase (GGT) was suggested to reflect the level of systemic oxidative stress. Oxidative stress induces changes in arterial structure and function and contributes to the development of hypertension. Therefore, GGT may be associated with arterial remodeling and blood pressure (BP) increment, even in absence of disease. To test this hypothesis, we evaluated, in 825 healthy subjects at low cardiometabolic risk, the associations of plasma GGT with carotid artery intima-media thickness (IMT), luminal diameter and prehypertension; in 154 subjects was evaluated also the association with aortic stiffness (cfPWV). Associations were controlled for insulin sensitivity, C-reactive protein, and life-style habits. In the main population, BP was remeasured after 3 years. Carotid diameter and cfPWV, but not IMT, were directly and independently related to plasma GGT. Subjects with prehypertension (N = 330) had higher GGT as compared with subjects with normal BP (22 [14] vs 17 [11] IU/L; adjusted P = 0.001), and within prehypertensive subjects, those who developed hypertension during 3 years had higher GGT than those without incident hypertension (27 [16] vs 21 [14] IU/L; adjusted P < 0.05). Within subjects with arterial stiffness measurement, those with prehypertension (N = 79) had higher both GGT and arterial stiffness (25 [14] vs 16 [20] IU/L and 9.11 ± 1.24 vs 7.90 ± 0.94 m/s; adjusted P < 0.01 and

Published
2021

39. A comprehensive re-assessment of the association between vitamin D and cancer susceptibility using Mendelian randomization

Author

Ong, JS, Dixon-Suen, Suzanne, Han, X, An, J, Fitzgerald, R, Buas, M, Gammon, MD, Corley, DA, Shaheen, NJ, Hardie, LJ, Bird, NC, Reid, BJ, Chow, WH, Risch, HA, Ye, W, Liu, G, Romero, Y, Bernstein, L, Wu, AH, Whiteman, DE, Vaughan, T, Agee, M, Alipanahi, B, Auton, A, Bell, RK, Bryc, K, Elson, SL, Fontanillas, P, Furlotte, NA, Hinds, DA, Huber, KE, Kleinman, A, Litterman, NK, McIntyre, MH, Mountain, JL, Noblin, ES, Northover, CAM, Pitts, SJ, Sathirapongsasuti, JF, Sazonova, OV, Shelton, JF, Shringarpure, S, Tian, C, Tung, JY, Vacic, V, Wilson, CH, Liyanage, U, Dusingize, JC, Schumacher, J, Gockel, I, Böhmer, A, Jankowski, J, Palles, C, O’Mara, T, Spurdle, A, Law, MH, Iles, MM, Pharoah, P, Berchuck, A, Zheng, W, Thrift, AP, Olsen, C, Neale, RE, Gharahkhani, P, Webb, PM, MacGregor, S, Ong, JS, Dixon-Suen, Suzanne, Han, X, An, J, Fitzgerald, R, Buas, M, Gammon, MD, Corley, DA, Shaheen, NJ, Hardie, LJ, Bird, NC, Reid, BJ, Chow, WH, Risch, HA, Ye, W, Liu, G, Romero, Y, Bernstein, L, Wu, AH, Whiteman, DE, Vaughan, T, Agee, M, Alipanahi, B, Auton, A, Bell, RK, Bryc, K, Elson, SL, Fontanillas, P, Furlotte, NA, Hinds, DA, Huber, KE, Kleinman, A, Litterman, NK, McIntyre, MH, Mountain, JL, Noblin, ES, Northover, CAM, Pitts, SJ, Sathirapongsasuti, JF, Sazonova, OV, Shelton, JF, Shringarpure, S, Tian, C, Tung, JY, Vacic, V, Wilson, CH, Liyanage, U, Dusingize, JC, Schumacher, J, Gockel, I, Böhmer, A, Jankowski, J, Palles, C, O’Mara, T, Spurdle, A, Law, MH, Iles, MM, Pharoah, P, Berchuck, A, Zheng, W, Thrift, AP, Olsen, C, Neale, RE, Gharahkhani, P, Webb, PM, and MacGregor, S

Abstract

Previous Mendelian randomization (MR) studies on 25-hydroxyvitamin D (25(OH)D) and cancer have typically adopted a handful of variants and found no relationship between 25(OH)D and cancer; however, issues of horizontal pleiotropy cannot be reliably addressed. Using a larger set of variants associated with 25(OH)D (74 SNPs, up from 6 previously), we perform a unified MR analysis to re-evaluate the relationship between 25(OH)D and ten cancers. Our findings are broadly consistent with previous MR studies indicating no relationship, apart from ovarian cancers (OR 0.89; 95% C.I: 0.82 to 0.96 per 1 SD change in 25(OH)D concentration) and basal cell carcinoma (OR 1.16; 95% C.I.: 1.04 to 1.28). However, after adjustment for pigmentation related variables in a multivariable MR framework, the BCC findings were attenuated. Here we report that lower 25(OH)D is unlikely to be a causal risk factor for most cancers, with our study providing more precise confidence intervals than previously possible

Published
2021

40. Summary Update 2021 for Policymakers: UNEP Environmental Effects Assessment Panel

Author

Barnes, P W, Bornman, J F, Pandey, K K, Bernhard, G H, Neale, R E, Robinson, Sharon A, Neale, P J, Zepp, R G, Madronich, S, White, C C, Andersen, M P S, Andrady, A L, Aucamp, P J, Bais, A F, Banaszak, A T, Berwick, M, Bruckman, L S, Byrne, S N, Foereid, B, Häder, D-P, Heikkilä, A M, Hollestein, L M, Hou, W-C, Hylander, S, Jansen, M A K, Klekociuk, A R, Liley, J B, Longstreth, J, Lucas, R M, Martinez-Abaigar, J, McKenzie, R L, McNeill, K, Olsen, C M, Ossola, R, Paul, N D, Rhodes, L E, Robson, T M, Rose, K C, Schikowski, T, Solomon, K R, Sulzberger, B, Ukpebor, J E, Wang, Q-W, Wängberg, S-Å, Williamson, C E, Wilson, S. R., Yazar, S, Young, A R, Zhu, L, Zhu, M, Barnes, P W, Bornman, J F, Pandey, K K, Bernhard, G H, Neale, R E, Robinson, Sharon A, Neale, P J, Zepp, R G, Madronich, S, White, C C, Andersen, M P S, Andrady, A L, Aucamp, P J, Bais, A F, Banaszak, A T, Berwick, M, Bruckman, L S, Byrne, S N, Foereid, B, Häder, D-P, Heikkilä, A M, Hollestein, L M, Hou, W-C, Hylander, S, Jansen, M A K, Klekociuk, A R, Liley, J B, Longstreth, J, Lucas, R M, Martinez-Abaigar, J, McKenzie, R L, McNeill, K, Olsen, C M, Ossola, R, Paul, N D, Rhodes, L E, Robson, T M, Rose, K C, Schikowski, T, Solomon, K R, Sulzberger, B, Ukpebor, J E, Wang, Q-W, Wängberg, S-Å, Williamson, C E, Wilson, S. R., Yazar, S, Young, A R, Zhu, L, and Zhu, M

Published
2021

41. Tralokinumab plus topical corticosteroids for the treatment of moderate-to-severe atopic dermatitis:results from the double-blind, randomized, multicentre, placebo-controlled phase III ECZTRA 3 trial

Author

Silverberg, J. I., Toth, D., Bieber, T., Alexis, A. F., Elewski, B. E., Pink, A. E., Hijnen, D., Jensen, T. N., Bang, B., Olsen, C. K., Kurbasic, A., Weidinger, S., Silverberg, J. I., Toth, D., Bieber, T., Alexis, A. F., Elewski, B. E., Pink, A. E., Hijnen, D., Jensen, T. N., Bang, B., Olsen, C. K., Kurbasic, A., and Weidinger, S.

Abstract

Background Tralokinumab is a fully human monoclonal antibody that specifically neutralizes interleukin-13, a key driver of atopic dermatitis (AD).Objectives To evaluate the efficacy and safety of tralokinumab in combination with topical corticosteroids (TCS) in patients with moderate-to-severe AD who were candidates for systemic therapy.Methods This was a double-blind, placebo plus TCS controlled phase III trial. Patients were randomized 2 : 1 to subcutaneous tralokinumab 300 mg or placebo every 2 weeks (Q2W) with TCS as needed over 16 weeks. Patients who achieved an Investigator's Global Assessment (IGA) score of 0/1 and/or 75% improvement in Eczema Area and Severity Index (EASI 75) at week 16 with tralokinumab were rerandomized 1 : 1 to tralokinumab Q2W or every 4 weeks (Q4W), with TCS as needed, for another 16 weeks.Results At week 16, more patients treated with tralokinumab than with placebo achieved IGA 0/1: 38 center dot 9% vs. 26 center dot 2% [difference (95% confidence interval): 12 center dot 4% (2 center dot 9-21 center dot 9); P = 0 center dot 015] and EASI 75: 56 center dot 0% vs. 35 center dot 7% [20 center dot 2% (9 center dot 8-30 center dot 6); P < 0 center dot 001]. Of the patients who were tralokinumab responders at week 16, 89 center dot 6% and 92 center dot 5% of those treated with tralokinumab Q2W and 77 center dot 6% and 90 center dot 8% treated with tralokinumab Q4W maintained an IGA 0/1 and EASI 75 response at week 32, respectively. Among patients who did not achieve IGA 0/1 and EASI 75 with tralokinumab Q2W at 16 weeks, 30 center dot 5% and 55 center dot 8% achieved these endpoints, respectively, at week 32. The overall incidence of adverse events was similar across treatment groups.Conclusions Tralokinumab 300 mg in combination with TCS as needed was effective and well tolerated in patients with moderate-to-severe AD.

Published
2021

43. Study of P/E cycling endurance induced degradation in SANOS memories under NAND (FN/FN) operation

Author

Sandhya, C., Oak, A.B., Chattar, N., Ganguly, U., Olsen, C., Seutter, S.M., Date, L., Hung, R., Vasi, J., and Mahapatra, S.

Subjects
Silicon nitride -- Electric properties, Memory (Computers) -- Innovations, Pulse-duration modulation -- Usage, Mathematical optimization -- Usage, Simulation methods -- Usage, Semiconductor memory, Business, Electronics, Electronics and electrical industries
Published
2010

47. Impact of SiN composition variation on SANOS memory performance and reliability under nand (FN/FN) operation

Author

Sandhya, C., Oak, A. B., Chattar, N., Joshi, A. S., Ganguly, U., Olsen, C., Seutter, S. M., Date, L., Hung, R., Vasi, J., and Mahapatra, S.

Subjects
Memory (Computers) -- Analysis, Holes (Electron deficiencies) -- Analysis, Silicon nitride -- Electric properties, Complementary metal oxide semiconductors -- Usage, Semiconductor memory, Business, Electronics, Electronics and electrical industries
Published
2009

48. Benchmark tests for MOSFET compact models with application to the PSP model

Author

Xin Li, Weimin Wu, Jha, Amit, Gildenblat, Gennady, van Langevelde, Ronald, Smit, Geert D.J., Scholten, Andries J., Klaassen, Dirk B.M., McAndrew, Colin C., Watts, Josef, Olsen, C. Michael, Coram, Geoffrey J., Chaudhry, Samir, and Victory, James

Subjects
Complementary metal oxide semiconductors -- Design and construction, Integrated circuits -- Design and construction, Semiconductor chips -- Design and construction, Metal oxide semiconductor field effect transistors -- Evaluation, Standard IC, Business, Electronics, Electronics and electrical industries
Abstract

The results from several qualitative 'benchmark' tests that are used to verify the physical behavior of the PSP model and its future application in generations of CMOS IC design are presented. The test performed includes new experimental data obtained from low-power, RF, mixed-signal, and analog applications of MOSFETs.

Published
2009

50. Integration of multiple networks and pathways identifies cancer driver genes in pan-cancer analysis

Author

Cava, C, Bertoli, G, Colaprico, A, Olsen, C, Bontempi, G, Castiglioni, I, Cava C, Bertoli G, Colaprico A, Olsen C, Bontempi G, CASTIGLIONI I, Cava, C, Bertoli, G, Colaprico, A, Olsen, C, Bontempi, G, Castiglioni, I, Cava C, Bertoli G, Colaprico A, Olsen C, Bontempi G, and CASTIGLIONI I

Abstract

Background: Modern high-throughput genomic technologies represent a comprehensive hallmark of molecular changes in pan-cancer studies. Although different cancer gene signatures have been revealed, the mechanism of tumourigenesis has yet to be completely understood. Pathways and networks are important tools to explain the role of genes in functional genomic studies. However, few methods consider the functional non-equal roles of genes in pathways and the complex gene-gene interactions in a network. Results: We present a novel method in pan-cancer analysis that identifies de-regulated genes with a functional role by integrating pathway and network data. A pan-cancer analysis of 7158 tumour/normal samples from 16 cancer types identified 895 genes with a central role in pathways and de-regulated in cancer. Comparing our approach with 15 current tools that identify cancer driver genes, we found that 35.6% of the 895 genes identified by our method have been found as cancer driver genes with at least 2/15 tools. Finally, we applied a machine learning algorithm on 16 independent GEO cancer datasets to validate the diagnostic role of cancer driver genes for each cancer. We obtained a list of the top-ten cancer driver genes for each cancer considered in this study. Conclusions: Our analysis 1) confirmed that there are several known cancer driver genes in common among different types of cancer, 2) highlighted that cancer driver genes are able to regulate crucial pathways

Published
2018

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