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351 results on '"Hamilton RL"'

1. BIFoR FACE: Water–soil–vegetation–atmosphere data from a temperate deciduous forest catchment, including under elevated CO2

Author: MacKenzie, AR, Krause, S, Hart, KM, Thomas, RM, Blaen, PJ, Hamilton, RL, Curioni, G, Quick, SE, Kourmouli, A, Hannah, DM, Comer-Warner, SA, Brekenfeld, N, Ullah, S, Press, MC, MacKenzie, AR, Krause, S, Hart, KM, Thomas, RM, Blaen, PJ, Hamilton, RL, Curioni, G, Quick, SE, Kourmouli, A, Hannah, DM, Comer-Warner, SA, Brekenfeld, N, Ullah, S, and Press, MC
Abstract: The ecosystem services provided by forests modulate runoff generation processes, nutrient cycling and water and energy exchange between soils, vegetation and atmosphere. Increasing atmospheric CO2 affects many linked aspects of forest and catchment function in ways we do not adequately understand. Global levels of atmospheric CO2 will be around 40% higher in 2050 than current levels, yet estimates of how water and solute fluxes in forested catchments will respond to increased CO2 are highly uncertain. The Free Air CO2 Enrichment (FACE) facility of the University of Birmingham's Institute of Forest Research (BIFoR) is the only FACE in mature deciduous forest. The site specializes in fundamental studies of the response of whole ecosystem patches of mature, deciduous, temperate woodland to elevated CO2 (eCO2). Here, we describe a dataset of hydrological parameters – seven weather parameters at each of three heights and four locations, shallow soil moisture and temperature, stream hydrology and CO2 enrichment – retrieved at high frequency from the BIFoR FACE catchment.
Published: 2021

2. Pattern of Relapse and Treatment Response in WNT-Activated Medulloblastoma

Author: Nobre, L, Zapotocky, M, Khan, S, Fukuoka, K, Fonseca, A, McKeown, T, Sumerauer, D, Vicha, A, Grajkowska, WA, Trubicka, J, Li, KKW, Ng, H-K, Massimi, L, Lee, JY, Kim, S-K, Zelcer, S, Vasiljevic, A, Faure-Conter, C, Hauser, P, Lach, B, Van Veelen-Vincent, M-L, French, PJ, Van Meir, EG, Weiss, WA, Gupta, N, Pollack, IF, Hamilton, RL, Rao, AAN, Giannini, C, Rubin, JB, Moore, AS, Chambless, LB, Vibhakar, R, Ra, YS, Massimino, M, McLendon, RE, Wheeler, H, Zollo, M, Ferruci, V, Kumabe, T, Faria, CC, Sterba, J, Jung, S, Lopez-Aguilar, E, Mora, J, Carlotti, CG, Olson, JM, Leary, S, Cain, J, Krskova, L, Zamecnik, J, Hawkins, CE, Tabori, U, Huang, A, Bartels, U, Northcott, PA, Taylor, MD, Yip, S, Hansford, JR, Bouffet, E, Ramaswamy, V, Nobre, L, Zapotocky, M, Khan, S, Fukuoka, K, Fonseca, A, McKeown, T, Sumerauer, D, Vicha, A, Grajkowska, WA, Trubicka, J, Li, KKW, Ng, H-K, Massimi, L, Lee, JY, Kim, S-K, Zelcer, S, Vasiljevic, A, Faure-Conter, C, Hauser, P, Lach, B, Van Veelen-Vincent, M-L, French, PJ, Van Meir, EG, Weiss, WA, Gupta, N, Pollack, IF, Hamilton, RL, Rao, AAN, Giannini, C, Rubin, JB, Moore, AS, Chambless, LB, Vibhakar, R, Ra, YS, Massimino, M, McLendon, RE, Wheeler, H, Zollo, M, Ferruci, V, Kumabe, T, Faria, CC, Sterba, J, Jung, S, Lopez-Aguilar, E, Mora, J, Carlotti, CG, Olson, JM, Leary, S, Cain, J, Krskova, L, Zamecnik, J, Hawkins, CE, Tabori, U, Huang, A, Bartels, U, Northcott, PA, Taylor, MD, Yip, S, Hansford, JR, Bouffet, E, and Ramaswamy, V
Abstract: Over the past decade, wingless-activated (WNT) medulloblastoma has been identified as a candidate for therapy de-escalation based on excellent survival; however, a paucity of relapses has precluded additional analyses of markers of relapse. To address this gap in knowledge, an international cohort of 93 molecularly confirmed WNT MB was assembled, where 5-year progression-free survival is 0.84 (95%, 0.763-0.925) with 15 relapsed individuals identified. Maintenance chemotherapy is identified as a strong predictor of relapse, with individuals receiving high doses of cyclophosphamide or ifosphamide having only one very late molecularly confirmed relapse (p = 0.032). The anatomical location of recurrence is metastatic in 12 of 15 relapses, with 8 of 12 metastatic relapses in the lateral ventricles. Maintenance chemotherapy, specifically cumulative cyclophosphamide doses, is a significant predictor of relapse across WNT MB. Future efforts to de-escalate therapy need to carefully consider not only the radiation dose but also the chemotherapy regimen and the propensity for metastatic relapses.
Published: 2020

3. Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates A beta, tau, immunity and lipid processing (vol 51, pg 414, 2019)

Author: Kunkle, BW, Grenier-Boley, B, Sims, R, Bis, JC, Damotte, V, Naj, AC, Boland, A, Vronskaya, M, van der Lee, SJ, Amlie-Wolf, A, Bellenguez, C, Frizatti, A, Chouraki, V, Martin, ER, Sleegers, K, Badarinarayan, N, Jakobsdottir, J, Hamilton-Nelson, KL, Moreno-Grau, S, Olaso, R, Raybould, R, Chen, YN, Kuzma, AB, Hiltunen, M, Morgan, T, Ahmad, S, Vardarajan, BN, Epelbaum, J, Hoffmann, P, Boada, M, Beecham, GW, Garnier, JG, Harold, D, Fitzpatrick, AL, Valladares, O, Moutet, ML, Gerrish, A, Smith, AV, Qu, LM, Bacq, D, Denning, N, Jian, XQ, Zhao, Y, Del Zompo, M, Fox, NC, Choi, SH, Mateo, I, Hughes, JT, Adams, HH, Malamon, J, Sanchez-Garcia, F, Patel, Y, Brody, JA, Dombroski, BA, Naranjo, MCD, Daniilidou, M, Eiriksdottir, G, Mukherjee, S, Wallon, D, Uphill, J, Aspelund, T, Cantwell, LB, Garzia, F, Galimberti, D, Hofer, E, Butkiewicz, M, Fin, B, Scarpini, E, Sarnowski, C, Bush, WS, Meslage, S, Kornhuber, J, White, CC, Song, Y, Barber, RC, Engelborghs, S, Sordon, S, Voijnovic, D, Adams, PM, Vandenberghe, R, Mayhaus, M, Cupples, LA, Albert, MS, De Deyn, PP, Gu, W, Himali, JJ, Beekly, D, Squassina, A, Hartmann, AM, Orellana, A, Blacker, D, Rodriguez-Rodriguez, E, Lovestone, S, Garcia, ME, Doody, RS, Munoz-Fernadez, C, Sussams, R, Lin, HH, Fairchild, TJ, Benito, YA, Holmes, C, Karamujic-Comic, H, Frosch, MP, Thonberg, H, Maier, W, Roshchupkin, G, Ghetti, B, Giedraitis, V, Kawalia, A, Li, S, Huebinger, RM, Kilander, L, Moebus, S, Hernandez, I, Kamboh, MI, Brundin, R, Turton, J, Yang, Q, Katz, MJ, Concari, L, Lord, J, Beiser, AS, Keene, CD, Helisalmi, S, Kloszewska, I, Kukull, WA, Koivisto, AM, Lynch, A, Tarraga, L, Larson, EB, Haapasalo, A, Lawlor, B, Mosley, TH, Lipton, RB, Solfrizzi, V, Gill, M, Longstreth, WT, Montine, TJ, Frisardi, V, Diez-Fairen, M, Rivadeneira, F, Petersen, RC, Deramecourt, V, Alvarez, I, Salani, F, Ciaramella, A, Boerwinkle, E, Reiman, EM, Fievet, N, Rotter, JI, Reisch, JS, Hanon, O, Cupidi, C, Uitterlinden, AGA, Royall, DR, Dufouil, C, Maletta, RG, de Rojas, I, Sano, M, Brice, A, Cecchetti, R, St George-Hyslop, P, Ritchie, K, Tsolaki, M, Tsuang, DW, Dubois, B, Craig, D, Wu, CK, Soininen, H, Avramidou, D, Albin, RL, Fratiglioni, L, Germanou, A, Apostolova, LG, Keller, L, Koutroumani, M, Arnold, SE, Panza, F, Gkatzima, O, Asthana, S, Hannequin, D, Whitehead, P, Atwood, CS, Caffarra, P, Hampel, H, Quintela, I, Carracedo, A, Lannfelt, L, Rubinsztein, DC, Barnes, LL, Pasquier, F, Frolich, L, Barral, S, McGuinness, B, Beach, TG, Johnston, JA, Becker, JT, Passmore, P, Bigio, EH, Schott, JM, Bird, TD, Warren, JD, Boeve, BF, Lupton, MK, Bowen, JD, Proitsi, P, Boxer, A, Powell, JF, Burke, JR, Kauwe, JSK, Burns, JM, Mancuso, M, Buxbaum, JD, Bonuccelli, U, Cairns, NJ, McQuillin, A, Cao, CH, Livingston, G, Carlson, CS, Bass, NJ, Carlsson, CM, Hardy, J, Carney, RM, Bras, J, Carrasquillo, MM, Guerreiro, R, Allen, M, Chui, HC, Fisher, E, Masullo, C, Crocco, EA, DeCarli, C, Bisceglio, G, Dick, M, Ma, L, Duara, R, Graff-Radford, NR, Evans, DA, Hodges, A, Faber, KM, Scherer, M, Fallon, KB, Riemenschneider, M, Fardo, DW, Heun, R, Farlow, MR, Kolsch, H, Ferris, S, Leber, M, Foroud, TM, Heuser, I, Galasko, DR, Giegling, I, Gearing, M, Hull, M, Geschwind, DH, Gilbert, JR, Morris, J, Green, RC, Mayo, K, Growdon, JH, Feulner, T, Hamilton, RL, Harrell, LE, Drichel, D, Honig, LS, Cushion, TD, Huentelman, MJ, Hollingworth, P, Hulette, CM, Hyman, BT, Marshall, R, Jarvik, GP, Meggy, A, Abner, E, Menzies, GE, Jin, LW, Leonenko, G, Real, LM, Jun, GR, Baldwin, CT, Grozeva, D, Karydas, A, Russo, G, Kaye, JA, Kim, R, Jessen, F, Kowall, NW, Vellas, B, Kramer, JH, Vardy, E, LaFerla, FM, Jockel, KH, Lah, JJ, Dichgans, M, Leverenz, JB, Mann, D, Levey, AI, Pickering-Brown, S, Lieberman, AP, Klopp, N, Lunetta, KL, Wichmann, HE, Lyketsos, CG, Morgan, K, Marson, DC, Brown, K, Martiniuk, F, Medway, C, Mash, DC, Nothen, MM, Masliah, E, Hooper, NM, McCormick, WC, Daniele, A, McCurry, SM, Bayer, A, McDavid, AN, Gallacher, J, Mckee, AC, van den Bussche, H, Mesulam, M, Brayne, C, Miller, BL, Riedel-Heller, S, Miller, CA, Miller, JW, Al-Chalabi, A, Morris, JC, Shaw, CE, Myers, AJ, Wiltfang, J, O'Bryant, S, Olichney, JM, Alvarez, V, Parisi, JE, Singleton, AB, Paulson, HL, Collinge, J, Perry, WR, Mead, S, Peskind, E, Cribbs, DH, Rossor, M, Pierce, A, Ryan, NS, Poon, WW, Nacmias, B, Potter, H, Sorbi, S, Quinn, JF, Sacchinelli, E, Raj, A, Spalletta, G, Raskind, M, Caltagirone, C, Bossu, P, Orfei, MD, Reisberg, B, Clarke, R, Reitz, C, Smith, AD, Ringman, JM, Warden, D, Roberson, ED, Wilcock, G, Rogaeva, E, Bruni, AC, Rosen, HJ, Gallo, M, Rosenberg, RN, Ben-Shlomo, Y, Sager, MA, Mecocci, P, Saykin, AJ, Pastor, P, Cuccaro, ML, Vance, JM, Schneider, JA, Schneider, LS, Slifer, S, Seeley, WW, Smith, AG, Sonnen, JA, Spina, S, Stern, RA, Swerdlow, RH, Tang, M, Tanzi, RE, Trojanowski, JQ, Troncoso, JC, Van Deerlin, VM, Van Eldik, LJ, Vinters, HV, Vonsattel, JP, Weintraub, S, Welsh-Bohmer, KA, Wilhelmsen, KC, Williamson, J, Wingo, TS, Woltjer, RL, Wright, CB, Yu, CE, Yu, L, Saba, Y, Pilotto, A, Bullido, MJ, Peters, O, Crane, PK, Bennett, D, Bosco, P, Coto, E, Boccardi, V, De Jager, PL, Lleo, A, Warner, N, Lopez, OL, Ingelsson, M, Deloukas, P, Cruchaga, C, Graff, C, Gwilliam, R, Fornage, M, Goate, AM, Sanchez-Juan, P, Kehoe, PG, Amin, N, Ertekin-Taner, N, Berr, C, Debette, S, Love, S, Launer, LJ, Younkin, SG, Dartigues, JF, Corcoran, C, Ikram, MA, Dickson, DW, Nicolas, G, Campion, D, Tschanz, J, Schmidt, H, Hakonarson, H, Clarimon, J, Munger, R, Schmidt, R, Farrer, LA, Van Broeckhoven, C, O'Donovan, MC, DeStefano, AL, Jones, L, Haines, JL, Deleuze, JF, Owen, MJ, Gudnason, V, Mayeux, R, Escott-Price, V, Psaty, BM, Ramirez, A, Wang, LS, Ruiz, A, van Duijn, CM, Holmans, PA, Seshadri, S, Williams, J, Amouyel, P, Schellenberg, GD, Lambert, JC, Pericak-Vance, MA, ADGC, EADI, Cohorts Heart Aging Res Genomic, and Genetic Environm Risk AD Defining
Published: 2019

4. Meta-analysis of genetic association with diagnosed Alzheimer's disease identifies novel risk loci and implicates Abeta, Tau, immunity and lipid processing

Author: Kunkle, BW, Grenier-Boley, B, Sims, R, Bis, JC, Naj, AC, Boland, A, Vronskaya, M, van der Lee, SJ, Amlie-Wolf, A, Bellenguez, C, Frizatti, A, Chouraki, V, Martin, ER, Sleegers, K, Badarinarayan, N, Jakobsdottir, J, Hamilton-Nelson, KL, Aloso, R, Raybould, R, Chen, Y, Kuzma, AB, Hiltunen, M, Morgan, T, Ahmad, S, Vardarajan, BN, Epelbaum, J, Hoffmann, P, Boada, M, Beecham, GW, Garnier, JG, Harold, D, Fitzpatrick, AL, Valladares, O, Moutet, ML, Gerrish, A, Smith, AV, Qu, L, Bacq, D, Denning, N, Jian, X, Zhao, Y, Zompo, MD, Fox, NC, Grove, ML, Choi, SH, Mateo, I, Hughes, JT, Adams, HH, Malamon, J, Garcia, FS, Patel, Y, Brody, JA, Dombroski, B, Naranjo, MCD, Daniilidou, M, Eiriksdottir, G, Mukherjee, S, Wallon, D, Uphill, J, Aspelund, T, Cantwell, LB, Garzia, F, Galimberti, D, Hofer, E, Butkiewics, M, Fin, B, Scarpini, E, Sarnowski, C, Bush, W, Meslage, S, Kornhuber, J, White, CC, Song, Y, Barber, RC, Engelborghs, S, Pichler, S, Voijnovic, D, Adams, PM, Vandenberghe, R, Mayhaus, M, Cupples, LA, Albert, MS, De Deyn, PP, Gu, W, Himali, JJ, Beekly, D, Squassina, A, Hartmann, AM, Orellana, A, Blacker, D, Rodriguez-Rodriguez, E, Lovestone, S, Garcia, ME, Doody, RS, Fernadez, CM, Sussams, R, Lin, H, Fairchild, TJ, Benito, YA, Holmes, C, Comic, H, Frosch, MP, Thonberg, H, Maier, W, Roschupkin, G, Ghetti, B, Giedraitis, V, Kawalia, A, Li, S, Huebinger, RM, Kilander, L, Moebus, S, Hernández, I, Kamboh, MI, Brundin, R, Turton, J, Yang, Q, Katz, MJ, Concari, L, Lord, J, Beiser, AS, Keene, CD, Helisalmi, S, Kloszewska, I, Kukull, WA, Koivisto, AM, Lynch, A, Tarraga, L, Larson, EB, Haapasalo, A, Lawlor, B, Mosley, TH, Lipton, RB, Solfrizzi, V, Gill, M, Longstreth Jr, WT, Montine, TJ, Frisardi, V, Ortega-Cubero, S, Rivadeneira, F, Petersen, RC, Deramecourt, V, Ciaramella, A, Boerwinkle, E, Reiman, EM, Fievet, N, Caltagirone, C, Rotter, JI, Reisch, JS, Hanon, O, Cupidi, C, Uitterlinden, AG, Royall, DR, Dufouil, C, Maletta, RG, Moreno-Grau, S, Sano, M, Brice, A, Cecchetti, R, St George-Hyslop, P, Ritchie, K, Tsolaki, M, Tsuang, DW, Dubois, B, Craig, D, Wu, CK, Soininen, H, Avramidou, D, Albin, RL, Fratiglioni, L, Germanou, A, Apostolova, LG, Keller, L, Koutroumani, M, Arnold, SE, Panza, F, Gkatzima, O, Asthana, S, Hannequin, D, Whitehead, P, Atwood, CS, Caffarra, P, Hampel, H, Baldwin, CT, Lannfelt, L, Rubinsztein, DC, Barnes, LL, Pasquier, F, Frölich, L, Barral, S, McGuinness, B, Beach, TG, Johnston, JI, Becker, JT, Passmore, P, Bigio, EH, Schott, JM, Bird, TD, Warren, JD, Boeve, BF, Lupton, MK, Bowen, JD, Proitsi, P, Boxer, A, Powell, JF, Burke, JR, Kauwe, JK, Burns, JM, Mancuso, M, Buxbaum, JD, Bonuccelli, U, Cairns, NJ, McQuillin, A, Cao, C, Livingston, G, Carlson, CS, Bass, NJ, Carlsson, CM, Hardy, J, Carney, RM, Bras, J, Carrasquillo, MM, Guerreiro, R, Allen, M, Chui, HC, Fisher, E, Cribbs, DH, Masullo, C, Crocco, EA, DeCarli, C, Bisceglio, G, Dick, M, Ma, L, Duara, R, Graff-Radford, NR, Evans, DA, Hodges, A, Faber, KM, Scherer, M, Fallon, KB, Riemenschneider, M, Fardo, DW, Heun, R, Farlow, MR, Ferris, S, Leber, M, Foroud, TM, Heuser, I, Galasko, DR, Giegling, I, Gearing, M, Hüll, M, Geschwind, DH, Gilbert, JR, Morris, J, Green, RC, Mayo, K, Growdon, JH, Feulner, T, Hamilton, RL, Harrell, LE, Drichel, D, Honig, LS, Cushion, TD, Huentelman, MJ, Hollingworth, P, Hulette, CM, Hyman, BT, Marshall, R, Jarvik, GP, Meggy, A, Abner, E, Menzies, G, Jin, LW, Leonenko, G, Jun, G, Grozeva, D, Karydas, A, Russo, G, Kaye, JA, Kim, R, Jessen, F, Kowall, NW, Vellas, B, Kramer, JH, Vardy, E, LaFerla, FM, Jöckel, KH, Lah, JJ, Dichgans, M, Leverenz, JB, Mann, D, Levey, AI, Pickering-Brown, S, Lieberman, AP, Klopp, N, Lunetta, KL, Wichmann, HE, Lyketsos, CG, Morgan, K, Marson, DC, Brown, K, Martiniuk, F, Medway, C, Mash, DC, Nöthen, MM, Masliah, E, Hooper, NM, McCormick, WC, Daniele, A, McCurry, SM, Bayer, A, McDavid, AN, Gallacher, J, McKee, AC, van den Bussche, H, Mesulam, M, Brayne, C, Miller, BL, Riedel-Heller, S, Miller, CA, Miller, JW, Al-Chalabi, A, Morris, JC, Shaw, CE, Myers, AJ, Wiltfang, J, O’Bryant, S, Coto, E, Olichney, JM, Alvarez, V, Parisi, JE, Singleton, AB, Paulson, HL, Collinge, J, Perry, W, Mead, S, Peskind, E, Rosser, M, Pierce, A, Ryan, N, Poon, WW, Nacmias, B, Potter, H, Sorbi, S, Quinn, JF, Sacchinelli, E, Raj, A, Spalletta, G, Raskind, M, Bossù, P, Reisberg, B, Clarke, R, Reitz, C, Smith, AD, Ringman, JM, Warden, D, Roberson, ED, Wilcock, G, Rogaeva, E, Bruni, AC, Rosen, HJ, Gallo, M, Rosenberg, RN, Ben-Shlomo, Y, Sager, MA, Mecocci, P, Saykin, AJ, Pastor, P, Cuccaro, ML, Vance, JM, Schneider, JA, Schneider, LS, Seeley, WW, Smith, AG, Sonnen, JA, Spina, S, Stern, RA, Swerdlow, RH, Tanzi, RE, Trojanowski, JQ, Troncoso, JC, Van Deerlin, VM, Van Eldik, LJ, Vinters, HV, Vonsattel, JP, Weintraub, S, Welsh-Bohmer, KA, Wilhelmsen, KC, Williamson, J, Wingo, TS, Woltjer, RL, Wright, CB, Yu, CE, Yu, L, Crane, PK, Bennett, DA, Boccardi, V, De Jager, PL, Warner, N, Lopez, OL, McDonough, S, Ingelsson, M, Deloukas, P, Cruchaga, C, Graff, C, Gwilliam, R, Fornage, M, Goate, AM, Sanchez-Juan, P, Kehoe, PG, Amin, N, Ertekin-Taner, N, Berr, C, Debette, S, Love, S, Launer, LJ, Younkin, SG, Dartigues, JF, Corcoran, C, Ikram, MA, Dickson, DW, Campion, D, Tschanz, J, Schmidt, H, Hakonarson, H, Munger, R, Schmidt, R, Farrer, LA, Van Broeckhoven, C, O’Donovan, MC, DeStefano, AL, Jones, L, Haines, JL, Deleuze, JF, Owen, MJ, Gudnason, V, Mayeux, R, Escott-Price, V, Psaty, BM, Ruiz, A, Ramirez, A, Wang, LS, van Duijn, CM, Holmans, PA, Seshadri, S, Williams, J, Amouyel, P, Schellenberg, GD, Lambert, JC, Pericak-Vance, MA, Bis, JC [0000-0002-3409-1110], Garnier, JG [0000-0003-4991-763X], Smith, AV [0000-0001-9088-234X], Denning, N [0000-0001-8467-7382], Vandenberghe, R [0000-0001-6237-2502], Himali, JJ [0000-0003-1391-9481], Rodriguez-Rodriguez, E [0000-0001-7742-677X], Frisardi, V [0000-0003-0764-7387], Ortega-Cubero, S [0000-0003-0520-9439], Hanon, O [0000-0002-4697-122X], Brice, A [0000-0002-0941-3990], Albin, RL [0000-0002-0629-608X], Buxbaum, JD [0000-0001-8898-8313], Bass, NJ [0000-0002-4481-778X], Fisher, E [0000-0003-2850-9936], Bayer, A [0000-0002-7514-248X], Gallacher, J [0000-0002-2394-5299], Brayne, C [0000-0001-5307-663X], Riedel-Heller, S [0000-0003-4321-6090], Al-Chalabi, A [0000-0002-4924-7712], and Apollo - University of Cambridge Repository
Subjects: Aging, 4202 Epidemiology, Genome-wide association study, Disease, Neurodegenerative, Biology, 3101 Biochemistry and Cell Biology, Alzheimer's Disease, 3105 Genetics, 03 medical and health sciences, 0302 clinical medicine, Clinical Research, Acquired Cognitive Impairment, Genetics, medicine, 2.1 Biological and endogenous factors, Dementia, Gene, 030304 developmental biology, Genetic association, 2 Aetiology, 0303 health sciences, Prevention, Human Genome, 42 Health Sciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Lipid metabolism, medicine.disease, Brain Disorders, 3. Good health, Meta-analysis, Neurological, Alzheimer's disease, 030217 neurology & neurosurgery, 31 Biological Sciences
Abstract: IntroductionLate-onset Alzheimer’s disease (LOAD, onset age > 60 years) is the most prevalent dementia in the elderly1, and risk is partially driven by genetics2. Many of the loci responsible for this genetic risk were identified by genome-wide association studies (GWAS)3–8. To identify additional LOAD risk loci, the we performed the largest GWAS to date (89,769 individuals), analyzing both common and rare variants. We confirm 20 previous LOAD risk loci and identify four new genome-wide loci (IQCK, ACE, ADAM10, and ADAMTS1). Pathway analysis of these data implicates the immune system and lipid metabolism, and for the first time tau binding proteins and APP metabolism. These findings show that genetic variants affecting APP and Aβ processing are not only associated with early-onset autosomal dominant AD but also with LOAD. Analysis of AD risk genes and pathways show enrichment for rare variants (P = 1.32 × 10−7) indicating that additional rare variants remain to be identified.
Published: 2018
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5. Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis

Author: Thompson, EM, Hielscher, T, Bouffet, E, Remke, M, Luu, B, Gururangan, S, McLendon, RE, Bigner, DD, Lipp, ES, Perreault, S, Cho, YJ, Grant, G, Kim, SK, Lee, JY, Rao, AAN, Giannini, C, Li, KKW, Ng, HK, Yao, Y, Kumabe, T, Tominaga, T, Grajkowska, WA, Perek-Polnik, M, Low, DCY, Seow, WT, Chang, KTE, Mora, J, Pollack, IF, Hamilton, RL, Leary, S, Moore, AS, Ingram, WJ, Hallahan, AR, Jouvet, A, Fèvre-Montange, M, Vasiljevic, A, Faure-Conter, C, Shofuda, T, Kagawa, N, Hashimoto, N, Jabado, N, Weil, AG, Gayden, T, Wataya, T, Shalaby, T, Grotzer, M, Zitterbart, K, Sterba, J, Kren, L, Hortobágyi, T, Klekner, A, László, B, Pócza, T, Hauser, P, Schüller, U, Jung, S, Jang, WY, French, PJ, Kros, JM, van Veelen, MLC, Massimi, L, Leonard, JR, Rubin, JB, Vibhakar, R, Chambless, LB, Cooper, MK, Thompson, RC, Faria, CC, Carvalho, A, Nunes, S, Pimentel, J, Fan, X, Muraszko, KM, López-Aguilar, E, Lyden, D, Garzia, L, Shih, DJH, Kijima, N, Schneider, C, Adamski, J, Northcott, PA, Kool, M, Jones, DTW, Chan, JA, Nikolic, A, Garre, ML, Van Meir, EG, Osuka, S, Olson, JJ, Jahangiri, A, and Castro, BA
Subjects: Adult, Male, Canada, Brain Neoplasms, Infant, Prognosis, Magnetic Resonance Imaging, Combined Modality Therapy, Disease-Free Survival, Child, Preschool, Disease Progression, Humans, Female, Child, Medulloblastoma, Retrospective Studies
Abstract: © 2016 Elsevier Ltd Background Patients with incomplete surgical resection of medulloblastoma are controversially regarded as having a marker of high-risk disease, which leads to patients undergoing aggressive surgical resections, so-called second-look surgeries, and intensified chemoradiotherapy. All previous studies assessing the clinical importance of extent of resection have not accounted for molecular subgroup. We analysed the prognostic value of extent of resection in a subgroup-specific manner. Methods We retrospectively identified patients who had a histological diagnosis of medulloblastoma and complete data about extent of resection and survival from centres participating in the Medulloblastoma Advanced Genomics International Consortium. We collected from resections done between April, 1997, and February, 2013, at 35 international institutions. We established medulloblastoma subgroup affiliation by gene expression profiling on frozen or formalin-fixed paraffin-embedded tissues. We classified extent of resection on the basis of postoperative imaging as gross total resection (no residual tumour), near-total resection (30 Gy vs no craniospinal irradiation). The primary analysis outcome was the effect of extent of resection by molecular subgroup and the effects of other clinical variables on overall and progression-free survival. Findings We included 787 patients with medulloblastoma (86 with WNT tumours, 242 with SHH tumours, 163 with group 3 tumours, and 296 with group 4 tumours) in our multivariable Cox models of progression-free and overall survival. We found that the prognostic benefit of increased extent of resection for patients with medulloblastoma is attenuated after molecular subgroup affiliation is taken into account. We identified a progression-free survival benefit for gross total resection over sub-total resection (hazard ratio [HR] 1·45, 95% CI 1·07–1·96, p=0·16) but no overall survival benefit (HR 1·23, 0·87–1·72, p=0·24). We saw no progression-free survival or overall survival benefit for gross total resection compared with near-total resection (HR 1·05, 0·71–1·53, p=0·8158 for progression-free survival and HR 1·14, 0·75–1·72, p=0·55 for overall survival). No significant survival benefit existed for greater extent of resection for patients with WNT, SHH, or group 3 tumours (HR 1·03, 0·67–1·58, p=0·89 for sub-total resection vs gross total resection). For patients with group 4 tumours, gross total resection conferred a benefit to progression-free survival compared with sub-total resection (HR 1·97, 1·22–3·17, p=0·0056), especially for those with metastatic disease (HR 2·22, 1·00–4·93, p=0·050). However, gross total resection had no effect on overall survival compared with sub-total resection in patients with group 4 tumours (HR 1·67, 0·93–2·99, p=0·084). Interpretation The prognostic benefit of increased extent of resection for patients with medulloblastoma is attenuated after molecular subgroup affiliation is taken into account. Although maximum safe surgical resection should remain the standard of care, surgical removal of small residual portions of medulloblastoma is not recommended when the likelihood of neurological morbidity is high because there is no definitive benefit to gross total resection compared with near-total resection. Funding Canadian Cancer Society Research Institute, Terry Fox Research Institute, Canadian Institutes of Health Research, National Institutes of Health, Pediatric Brain Tumor Foundation, and the Garron Family Chair in Childhood Cancer Research.
Published: 2016
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6. phenotypic heterogeneity in Creutzfeldt-Jakob disease associated with a new prion protein mutation

Author: PUOTI, Gianfranco, Zou WQ, Nigro M, Cali I, Cracco L, Blevins J, Najjar S, Hamilton RL, Gambetti P., Puoti, Gianfranco, Zou, Wq, Nigro, M, Cali, I, Cracco, L, Blevins, J, Najjar, S, Hamilton, Rl, and Gambetti, P.
Published: 2011

7. Phenotypic Heterogeneity and Type-1/2 PrPSc Co-Occurrence in Creutzfeldt-Jakob Disease Associated With a new Mutation of PRNP

Author: PUOTI, Gianfranco, Nigro M, Chen S, Cali I, Cracco L, Blevins J, Najjar S, Hamilton RL, Gambetti P., Puoti, Gianfranco, Nigro, M, Chen, S, Cali, I, Cracco, L, Blevins, J, Najjar, S, Hamilton, Rl, and Gambetti, P.
Published: 2010

8. Abstract P6-07-07: ESR1 amplification and 5'-3' exon imbalance in metastatic breast cancer

Author: Oesterreich, S, primary, Basudan, A, additional, Preideigkeit, N, additional, Hartmaier, RJ, additional, Bahreini, A, additional, Gyanchandani, R, additional, Leone, JP, additional, Lucas, PC, additional, Hamilton, RL, additional, Brufsky, AM, additional, and Lee, AV, additional
Published: 2017
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9. Abstract PD1-05: Breast cancer brain metastases show limited intrinsic subtype switching, yet exhibit acquired ERBB2 amplifications and activating mutations

Author: Priedigkeit, N, primary, Hartmaier, RJ, additional, Chen, Y, additional, Vareslija, D, additional, Basudan, A, additional, Thomas, R, additional, Leone, JP, additional, Lucas, PC, additional, Bhargava, R, additional, Hamilton, RL, additional, Chmielecki, J, additional, Davidson, NE, additional, Oesterreich, S, additional, Brufsky, AM, additional, Young, L, additional, and Lee, AV, additional
Published: 2017
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10. Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease

Author: Naj, AC, Jun, G, Beecham, GW, Wang, LS, Vardarajan, BN, Buros, J, Gallins, PJ, Buxbaum, JD, Jarvik, GP, Crane, PK, Larson, EB, Bird, TD, Boeve, BF, Graff-Radford, NR, De Jager, PL, Evans, D, Schneider, JA, Carrasquillo, MM, Ertekin-Taner, N, Younkin, SG, Cruchaga, C, Kauwe, JSK, Nowotny, P, Kramer, P, Hardy, J, Huentelman, MJ, Myers, AJ, Barmada, MM, Demirci, FY, Baldwin, CT, Green, RC, Rogaeva, E, George-Hyslop, PS, Arnold, SE, Barber, R, Beach, T, Bigio, EH, Bowen, JD, Boxer, A, Burke, JR, Cairns, NJ, Carlson, CS, Carney, RM, Carroll, SL, Chui, HC, Clark, DG, Corneveaux, J, Cotman, CW, Cummings, JL, Decarli, C, Dekosky, ST, Diaz-Arrastia, R, Dick, M, Dickson, DW, Ellis, WG, Faber, KM, Fallon, KB, Farlow, MR, Ferris, S, Frosch, MP, Galasko, DR, Ganguli, M, Gearing, M, Geschwind, DH, Ghetti, B, Gilbert, JR, Gilman, S, Giordani, B, Glass, JD, Growdon, JH, Hamilton, RL, Harrell, LE, Head, E, Honig, LS, Hulette, CM, Hyman, BT, Jicha, GA, Jin, LW, Johnson, N, Karlawish, J, Karydas, A, Kaye, JA, and Kim, R
Abstract: The Alzheimer Disease Genetics Consortium (ADGC) performed a genome-wide association study of late-onset Alzheimer disease using a three-stage design consisting of a discovery stage (stage 1) and two replication stages (stages 2 and 3). Both joint analysis and meta-analysis approaches were used. We obtained genome-wide significant results at MS4A4A (rs4938933; stages 1 and 2, meta-analysis P (P M) = 1.7 × 10 -9, joint analysis P (P J) = 1.7 × 10 -9; stages 1, 2 and 3, P M = 8.2 × 10 -12), CD2AP (rs9349407; stages 1, 2 and 3, P M = 8.6 × 10 -9), EPHA1 (rs11767557; stages 1, 2 and 3, P M = 6.0 × 10 -10) and CD33 (rs3865444; stages 1, 2 and 3, P M = 1.6 × 10 -9). We also replicated previous associations at CR1 (rs6701713; P M = 4.6 × 10 -10, P J = 5.2 × 10 -11), CLU (rs1532278; P M = 8.3 × 10 -8, P J = 1.9 × 10 -8), BIN1 (rs7561528; P M = 4.0 × 10 -14, P J = 5.2 × 10 -14) and PICALM (rs561655; P M = 7.0 × 10 -11, P J = 1.0 × 10 -10), but not at EXOC3L2, to late-onset Alzheimer's disease susceptibility. © 2011 Nature America, Inc. All rights reserved.
Published: 2011
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11. Coexistence of a ganglioglioma and Rasmussen's encephalitis

Author: Adelson Pd, K S Firlik, and Hamilton Rl
Subjects: Rasmussen's encephalitis, Refractory seizures, Male, Pathology, medicine.medical_specialty, medicine.medical_treatment, Ganglioglioma, Central nervous system disease, Seizures, medicine, Seizure control, Humans, business.industry, Brain Neoplasms, Brain, General Medicine, medicine.disease, Hemispherectomy, Child, Preschool, Pediatrics, Perinatology and Child Health, Chronic Disease, Etiology, Encephalitis, Surgery, Neurology (clinical), business
Abstract: A small number of recent reports have documented coexisting cerebral pathologic entities in patients with Rasmussen’s encephalitis. We report the case of a 4-year-old boy who presented with refractory seizures and was found to have both a ganglioglioma and Rasmussen’s encephalitis of the same hemisphere. The patient ultimately underwent a functional hemispherectomy with excellent seizure control. We also review the clinical and pathologic hallmarks of both gangliogliomas and Rasmussen’s encephalitis. We hope that the addition of this patient to the small but growing literature on dual pathology in Rasmussen’s encephalitis may help shed some light on the etiology of this mysterious disease.
Published: 1999

12. In vivo CHI3L1 (YKL-40) expression in astrocytes in acute and chronic neurological diseases

Author: Bonneh-Barkay, D, Wang, G, Starkey, A, Hamilton, RL, Wiley, CA, Bonneh-Barkay, D, Wang, G, Starkey, A, Hamilton, RL, and Wiley, CA
Abstract: Background: CHI3L1 (YKL-40) is up-regulated in a variety of inflammatory conditions and cancers. We have previously reported elevated CHI3L1 concentration in the cerebrospinal fluid (CSF) of human and non-human primates with lentiviral encephalitis and using immunohistochemistry showed that CHI3L1 was associated with astrocytes.Methods: In the current study CHI3L1 transcription and expression were evaluated in a variety of acute and chronic human neurological diseases.Results: ELISA revealed significant elevation of CHI3L1 in the CSF of multiple sclerosis (MS) patients as well as mild elevation with aging. In situ hybridization (ISH) showed CHI3L1 transcription mostly associated with reactive astrocytes, that was more pronounced in inflammatory conditions like lentiviral encephalitis and MS. Comparison of CHI3L1 expression in different stages of brain infarction showed that YKL40 was abundantly expressed in astrocytes during acute phases and diminished to low levels in chronic infarcts.Conclusions: Taken together, these findings demonstrate that CHI3L1 is induced in astrocytes in a variety of neurological diseases but that it is most abundantly associated with astrocytes in regions of inflammatory cells. © 2010 Bonneh-Barkay et al; licensee BioMed Central Ltd.
Published: 2010

13. Autologous glioma cell vaccine admixed with interleukin-4 gene transfected fibroblasts in the treatment of patients with malignant gliomas

Author: Okada, H, Lieberman, FS, Walter, KA, Lunsford, LD, Kondziolka, DS, Bejjani, GK, Hamilton, RL, Torres-Trejo, A, Kalinski, P, Cai, Q, Mabold, JL, Edington, HD, Butterfield, LH, Whiteside, TL, Potter, DM, Schold, SC, Pollack, IF, Okada, H, Lieberman, FS, Walter, KA, Lunsford, LD, Kondziolka, DS, Bejjani, GK, Hamilton, RL, Torres-Trejo, A, Kalinski, P, Cai, Q, Mabold, JL, Edington, HD, Butterfield, LH, Whiteside, TL, Potter, DM, Schold, SC, and Pollack, IF
Published: 2007

14. A meningeal cyst of the thoracic spine presenting as prolonged paresis after ankle injury: case report

Author: Hamilton Rl, Adelson Pd, Firlik Ad, and Firlik Ks
Subjects: medicine.medical_specialty, Weakness, Adolescent, Spinal Cord Diseases, Central nervous system disease, Diagnosis, Differential, Meninges, Arachnoid cyst, medicine, Humans, Ankle Injuries, Spinal cord injury, Paresis, Neurologic Examination, business.industry, General Medicine, Meningeal cyst, medicine.disease, Spinal cord, Surgery, Arachnoid Cysts, medicine.anatomical_structure, Pediatrics, Perinatology and Child Health, Female, Neurology (clinical), medicine.symptom, Ankle, business
Abstract: A case of a thoracic meningeal cyst causing right lower extremity weakness in a fifteen-year-old girl is presented. The diagnosis was delayed due to a history of ankle injury which was initially used to explain her symptoms. The authors explain the difficulty in diagnosing intraspinal meningeal cysts and stress the importance of surgical excision before spinal cord injury progresses.
Published: 1996

15. NEUROTROPHIC FACTORS IN SIMIAN IMMUNODEFICIENCY VIRUS ENCEPHALITIS

Author: Hamilton Rl, Clayton A. Wiley, Bodnar Ri, Lackner Aa, and Lane Jh
Subjects: Cellular and Molecular Neuroscience, Neurology, Neurotrophic factors, medicine, Neurology (clinical), General Medicine, Simian immunodeficiency virus, Biology, medicine.disease, medicine.disease_cause, Virology, Encephalitis, Pathology and Forensic Medicine
Published: 1997
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16. Two apolipoprotein B gene defects in a kindred with hypobetalipoproteinemia, one of which results in a truncated variant, apoB-61, in VLDL and LDL.

Author: Pullinger, CR, primary, Hillas, E, additional, Hardman, DA, additional, Chen, GC, additional, Naya-Vigne, JM, additional, Iwasa, JA, additional, Hamilton, RL, additional, Lalouel, JM, additional, Williams, RR, additional, and Kane, JP, additional
Published: 1992
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17. HUMAN HERPESVIRUSES AND TEMPORAL ARTERITIS

Author: Clayton A. Wiley, Baldwin Me, and Hamilton Rl
Subjects: Cellular and Molecular Neuroscience, Pathology, medicine.medical_specialty, Neurology, business.industry, medicine, Neurology (clinical), General Medicine, Arteritis, medicine.disease, business, Pathology and Forensic Medicine
Published: 1996
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18. GBA mutations increase risk for Lewy body disease with and without Alzheimer disease pathology.

Author: Tsuang D, Leverenz JB, Lopez OL, Hamilton RL, Bennett DA, Schneider JA, Buchman AS, Larson EB, Crane PK, Kaye JA, Kramer P, Woltjer R, Kukull W, Nelson PT, Jicha GA, Neltner JH, Galasko D, Masliah E, Trojanowski JQ, and Schellenberg GD
Published: 2012
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19. Gray matter atrophy associated with extrapyramidal signs in the Lewy body variant of Alzheimer's disease.

Author: Choi SH, Olabarrieta M, Lopez OL, Maruca V, Dekosky ST, Hamilton RL, Becker JT, Choi, Seong Hye, Olabarrieta, Mikel, Lopez, Oscar L, Maruca, Victoria, Dekosky, Steven T, Hamilton, Ronald L, and Becker, James T
Abstract: Up to 60% of the patients with Alzheimer's disease (AD) can have cortical or brainstem Lewy bodies (LB), and extrapyramidal signs (EPS) have been found to be associated with LB in AD patients. However, the relationship between EPS and brain volumes has not been studied in the LB variant of AD using structural magnetic resonance imaging (MRI). The purpose of this study was to determine the relationship between patterns of brain atrophy and clinical EPS in patients with pathologically confirmed AD. We compared gray matter structure using voxel-based morphometry in 29 Definite AD cases, 16 (55%) of whom also had LBs identified with α-synuclein immunohistochemistry. Multivariate models analyzed brain volume at a voxel level accounting for subject group, Mini-Mental State Examination (MMSE), EPS, total brain volume, and the time from MRI scan to death. There was no significant difference in gray matter volume in the Definite AD patients as a function of LB. There was a significant association between gray matter volumes and the MMSE in AD patients, both with and without LBs. There was a significant correlation between gray matter volume and EPS only in the group of AD patients with LBs, and not in those with pure AD. These findings suggest that that the etiology of EPS in patients with the LB variant of AD is associated with neuronal loss in the nigrostriatal tracts. By contrast, the source of the EPS in AD alone appears to be less well localized. [ABSTRACT FROM AUTHOR]
Published: 2012
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20. Induction of CD8+ T-cell responses against novel glioma-associated antigen peptides and clinical activity by vaccinations with {alpha}-type 1 polarized dendritic cells and polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose...

Author: Okada H, Kalinski P, Ueda R, Hoji A, Kohanbash G, Donegan TE, Mintz AH, Engh JA, Bartlett DL, Brown CK, Zeh H, Holtzman MP, Reinhart TA, Whiteside TL, Butterfield LH, Hamilton RL, Potter DM, Pollack IF, Salazar AM, and Lieberman FS
Published: 2011
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21. Isolation and characterization of three endosomal fractions from the liver of normal rats after lipoprotein loading

Author: Jäckle, S, primary, Runquist, E, additional, Brady, S, additional, Hamilton, RL, additional, and Havel, RJ, additional
Published: 1991
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22. Isolation and properties of nascent lipoproteins from highly purified rat hepatocytic Golgi fractions

Author: Hamilton, RL, primary, Moorehouse, A, additional, and Havel, RJ, additional
Published: 1991
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23. Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease.

Author: Ikonomovic MD, Klunk WE, Abrahamson EE, Mathis CA, Price JC, Tsopelas ND, Lopresti BJ, Ziolko S, Bi W, Paljug WR, Debnath ML, Hope CE, Isanski BA, Hamilton RL, DeKosky ST, Ikonomovic, Milos D, Klunk, William E, Abrahamson, Eric E, Mathis, Chester A, and Price, Julie C
Abstract: The positron emission tomography (PET) radiotracer Pittsburgh Compound-B (PiB) binds with high affinity to beta-pleated sheet aggregates of the amyloid-beta (Abeta) peptide in vitro. The in vivo retention of PiB in brains of people with Alzheimer's disease shows a regional distribution that is very similar to distribution of Abeta deposits observed post-mortem. However, the basis for regional variations in PiB binding in vivo, and the extent to which it binds to different types of Abeta-containing plaques and tau-containing neurofibrillary tangles (NFT), has not been thoroughly investigated. The present study examined 28 clinically diagnosed and autopsy-confirmed Alzheimer's disease subjects, including one Alzheimer's disease subject who had undergone PiB-PET imaging 10 months prior to death, to evaluate region- and substrate-specific binding of the highly fluorescent PiB derivative 6-CN-PiB. These data were then correlated with region-matched Abeta plaque load and peptide levels, [(3)H]PiB binding in vitro, and in vivo PET retention levels. We found that in Alzheimer's disease brain tissue sections, the preponderance of 6-CN-PiB binding is in plaques immunoreactive to either Abeta42 or Abeta40, and to vascular Abeta deposits. 6-CN-PiB labelling was most robust in compact/cored plaques in the prefrontal and temporal cortices. While diffuse plaques, including those in caudate nucleus and presubiculum, were less prominently labelled, amorphous Abeta plaques in the cerebellum were not detectable with 6-CN-PiB. Only a small subset of NFT were 6-CN-PiB positive; these resembled extracellular 'ghost' NFT. In Alzheimer's disease brain tissue homogenates, there was a direct correlation between [(3)H]PiB binding and insoluble Abeta peptide levels. In the Alzheimer's disease subject who underwent PiB-PET prior to death, in vivo PiB retention levels correlated directly with region-matched post-mortem measures of [(3)H]PiB binding, insoluble Abeta peptide levels, 6-CN-PiB- and Abeta plaque load, but not with measures of NFT. These results demonstrate, in a typical Alzheimer's disease brain, that PiB binding is highly selective for insoluble (fibrillar) Abeta deposits, and not for neurofibrillary pathology. The strong direct correlation of in vivo PiB retention with region-matched quantitative analyses of Abeta plaques in the same subject supports the validity of PiB-PET imaging as a method for in vivo evaluation of Abeta plaque burden. [ABSTRACT FROM AUTHOR]
Published: 2008
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24. Lewy bodies in the amygdala increase risk for major depression in subjects with Alzheimer disease.

Author: Lopez OL, Becker JT, Sweet RA, Martin-Sanchez FJ, and Hamilton RL
Published: 2006
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25. Apolipoprotein E localization in rat hepatocytes by immunogold labeling of cryothin sections

Author: Hamilton, RL, primary, Wong, JS, additional, Guo, LS, additional, Krisans, S, additional, and Havel, RJ, additional
Published: 1990
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26. Psychotic symptoms in Alzheimer's disease are not associated with more severe neuropathologic features.

Author: Sweet RA, Hamilton RL, Lopez OL, Klunk WE, Wisniewski SR, Kaufer DI, Healy MT, DeKosky ST, Sweet, R A, Hamilton, R L, Lopez, O L, Klunk, W E, Wisniewski, S R, Kaufer, D I, Healy, M T, and DeKosky, S T
Published: 2000

27. Meta-analysis of genetic association with diagnosed Alzheimer’s disease identifies novel risk loci and implicates Abeta, Tau, immunity and lipid processing

Author: Kunkle, BW, Grenier-Boley, B, Sims, R, Bis, JC, Naj, AC, Boland, A, Vronskaya, M, Van Der Lee, SJ, Amlie-Wolf, A, Bellenguez, C, Frizatti, A, Chouraki, V, Martin, ER, Sleegers, K, Badarinarayan, N, Jakobsdottir, J, Hamilton-Nelson, KL, Aloso, R, Raybould, R, Chen, Y, Kuzma, AB, Hiltunen, M, Morgan, T, Ahmad, S, Vardarajan, BN, Epelbaum, J, Hoffmann, P, Boada, M, Beecham, GW, Garnier, JG, Harold, D, Fitzpatrick, AL, Valladares, O, Moutet, ML, Gerrish, A, Smith, AV, Qu, L, Bacq, D, Denning, N, Jian, X, Zhao, Y, Zompo, MD, Fox, NC, Grove, ML, Choi, SH, Mateo, I, Hughes, JT, Adams, HH, Malamon, J, Garcia, FS, Patel, Y, Brody, JA, Dombroski, B, Naranjo, MCD, Daniilidou, M, Eiriksdottir, G, Mukherjee, S, Wallon, D, Uphill, J, Aspelund, T, Cantwell, LB, Garzia, F, Galimberti, D, Hofer, E, Butkiewics, M, Fin, B, Scarpini, E, Sarnowski, C, Bush, W, Meslage, S, Kornhuber, J, White, CC, Song, Y, Barber, RC, Engelborghs, S, Pichler, S, Voijnovic, D, Adams, PM, Vandenberghe, R, Mayhaus, M, Cupples, LA, Albert, MS, De Deyn, PP, Gu, W, Himali, JJ, Beekly, D, Squassina, A, Hartmann, AM, Orellana, A, Blacker, D, Rodriguez-Rodriguez, E, Lovestone, S, Garcia, ME, Doody, RS, Fernadez, CM, Sussams, R, Lin, H, Fairchild, TJ, Benito, YA, Holmes, C, Comic, H, Frosch, MP, Thonberg, H, Maier, W, Roschupkin, G, Ghetti, B, Giedraitis, V, Kawalia, A, Li, S, Huebinger, RM, Kilander, L, Moebus, S, Hernández, I, Kamboh, MI, Brundin, R, Turton, J, Yang, Q, Katz, MJ, Concari, L, Lord, J, Beiser, AS, Keene, CD, Helisalmi, S, Kloszewska, I, Kukull, WA, Koivisto, AM, Lynch, A, Tarraga, L, Larson, EB, Haapasalo, A, Lawlor, B, Mosley, TH, Lipton, RB, Solfrizzi, V, Gill, M, Longstreth, WT, Montine, TJ, Frisardi, V, Ortega-Cubero, S, Rivadeneira, F, Petersen, RC, Deramecourt, V, Ciaramella, A, Boerwinkle, E, Reiman, EM, Fievet, N, Caltagirone, C, Rotter, JI, Reisch, JS, Hanon, O, Cupidi, C, Uitterlinden, AG, Royall, DR, Dufouil, C, Maletta, RG, Moreno-Grau, S, Sano, M, Brice, A, Cecchetti, R, St George-Hyslop, P, Ritchie, K, Tsolaki, M, Tsuang, DW, Dubois, B, Craig, D, Wu, CK, Soininen, H, Avramidou, D, Albin, RL, Fratiglioni, L, Germanou, A, Apostolova, LG, Keller, L, Koutroumani, M, Arnold, SE, Panza, F, Gkatzima, O, Asthana, S, Hannequin, D, Whitehead, P, Atwood, CS, Caffarra, P, Hampel, H, Baldwin, CT, Lannfelt, L, Rubinsztein, DC, Barnes, LL, Pasquier, F, Frölich, L, Barral, S, McGuinness, B, Beach, TG, Johnston, JI, Becker, JT, Passmore, P, Bigio, EH, Schott, JM, Bird, TD, Warren, JD, Boeve, BF, Lupton, MK, Bowen, JD, Proitsi, P, Boxer, A, Powell, JF, Burke, Kauwe, JK, Burns, JM, Mancuso, M, Buxbaum, JD, Bonuccelli, U, Cairns, NJ, McQuillin, A, Cao, C, Livingston, G, Carlson, CS, Bass, NJ, Carlsson, CM, Hardy, J, Carney, RM, Bras, J, Carrasquillo, MM, Guerreiro, R, Allen, M, Chui, HC, Fisher, E, Cribbs, DH, Masullo, C, Crocco, EA, DeCarli, C, Bisceglio, G, Dick, M, Ma, L, Duara, R, Graff-Radford, NR, Evans, DA, Hodges, A, Faber, KM, Scherer, M, Fallon, KB, Riemenschneider, M, Fardo, DW, Heun, R, Farlow, MR, Ferris, S, Leber, M, Foroud, TM, Heuser, I, Galasko, DR, Giegling, I, Gearing, M, Hüll, M, Geschwind, DH, Gilbert, Morris, J, Green, RC, Mayo, K, Growdon, JH, Feulner, T, Hamilton, RL, Harrell, LE, Drichel, D, Honig, LS, Cushion, TD, Huentelman, MJ, Hollingworth, P, Hulette, CM, Hyman, BT, Marshall, R, Jarvik, GP, Meggy, A, Abner, E, Menzies, G, Jin, LW, Leonenko, G, Jun, G, Grozeva, D, Karydas, A, Russo, G, Kaye, JA, Kim, R, Jessen, F, Kowall, NW, Vellas, B, Kramer, JH, Vardy, E, LaFerla, FM, Jöckel, KH, Lah, JJ, Dichgans, M, Leverenz, JB, Mann, D, Levey, AI, Pickering-Brown, S, Lieberman, AP, Klopp, N, Lunetta, KL, Wichmann, HE, Lyketsos, CG, Morgan, K, Marson, DC, Brown, K, Martiniuk, F, Medway, C, Mash, DC, Nöthen, MM, Masliah, E, Hooper, NM, McCormick, WC, Daniele, A, McCurry, SM, Bayer, A, McDavid, AN, Gallacher, J, McKee, AC, Van Den Bussche, H, Mesulam, M, Brayne, C, Miller, BL, Riedel-Heller, S, Miller, CA, Miller, JW, Al-Chalabi, A, Morris, JC, Shaw, CE, Myers, AJ, Wiltfang, J, O’Bryant, S, Coto, E, Olichney, JM, Alvarez, V, Parisi, JE, Singleton, AB, Paulson, HL, Collinge, J, Perry, W, Mead, S, Peskind, E, Rosser, M, Pierce, A, Ryan, N, Poon, WW, Nacmias, B, Potter, H, Sorbi, S, Quinn, JF, Sacchinelli, E, Raj, A, Spalletta, G, Raskind, M, Bossù, P, Reisberg, B, Clarke, R, Reitz, C, and S, AD
Subjects: 2 Aetiology, Aging, Prevention, Human Genome, 4202 Epidemiology, 42 Health Sciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurodegenerative, 3101 Biochemistry and Cell Biology, Alzheimer's Disease, 3105 Genetics, 3. Good health, Brain Disorders, Clinical Research, FOS: Biological sciences, Neurological, Acquired Cognitive Impairment, Genetics, 2.1 Biological and endogenous factors, Dementia, 31 Biological Sciences
Abstract: Introduction Late-onset Alzheimer’s disease (LOAD, onset age > 60 years) is the most prevalent dementia in the elderly 1 , and risk is partially driven by genetics 2 . Many of the loci responsible for this genetic risk were identified by genome-wide association studies (GWAS) 3–8 . To identify additional LOAD risk loci, the we performed the largest GWAS to date (89,769 individuals), analyzing both common and rare variants. We confirm 20 previous LOAD risk loci and identify four new genome-wide loci ( IQCK , ACE , ADAM10 , and ADAMTS1 ). Pathway analysis of these data implicates the immune system and lipid metabolism, and for the first time tau binding proteins and APP metabolism. These findings show that genetic variants affecting APP and Aβ processing are not only associated with early-onset autosomal dominant AD but also with LOAD. Analysis of AD risk genes and pathways show enrichment for rare variants ( P = 1.32 × 10 −7 ) indicating that additional rare variants remain to be identified.

28. Lipoprotein-related gene expression in the mouse yolk sac during embryonic development

Author: Terasawa, Y., Cases, Sj, Wong, Js, Jamil, H., Maret Traber, Packer, L., Hamilton, Rl, Gordon, Da, and Farese, Rv

29. In vivo CHI3L1 (YKL-40) expression in astrocytes in acute and chronic neurological diseases.

Author: Bonneh-Barkay D, Wang G, Starkey A, Hamilton RL, Wiley CA, Bonneh-Barkay, Dafna, Wang, Guoji, Starkey, Adam, Hamilton, Ronald L, and Wiley, Clayton A
Abstract: Background: CHI3L1 (YKL-40) is up-regulated in a variety of inflammatory conditions and cancers. We have previously reported elevated CHI3L1 concentration in the cerebrospinal fluid (CSF) of human and non-human primates with lentiviral encephalitis and using immunohistochemistry showed that CHI3L1 was associated with astrocytes.Methods: In the current study CHI3L1 transcription and expression were evaluated in a variety of acute and chronic human neurological diseases.Results: ELISA revealed significant elevation of CHI3L1 in the CSF of multiple sclerosis (MS) patients as well as mild elevation with aging. In situ hybridization (ISH) showed CHI3L1 transcription mostly associated with reactive astrocytes, that was more pronounced in inflammatory conditions like lentiviral encephalitis and MS. Comparison of CHI3L1 expression in different stages of brain infarction showed that YKL40 was abundantly expressed in astrocytes during acute phases and diminished to low levels in chronic infarcts.Conclusions: Taken together, these findings demonstrate that CHI3L1 is induced in astrocytes in a variety of neurological diseases but that it is most abundantly associated with astrocytes in regions of inflammatory cells. [ABSTRACT FROM AUTHOR]
Published: 2010
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30. Dermoid inclusion cysts and early spinal cord tethering after fetal surgery for myelomeningocele.

Author: Mazzola CA, Albright AL, Sutton LN, Tuite GF, Hamilton RL, and Pollack IF
Published: 2002

31. Intertumoral Heterogeneity within Medulloblastoma Subgroups

Author: Luca Massimi, Caterina Giannini, Betty Luu, Cynthia Hawkins, Byung Kyu Cho, James T. Rutka, G. Yancey Gillespie, Timothy E. Van Meter, Almos Klekner, Young Shin Ra, Carolina Nor, Anna Goldenberg, Rajeev Vibhakar, Hideo Nakamura, Gaetano Finocchiaro, Massimo Zollo, John Peacock, Marta Perek-Polnik, Keren Isaev, Alvaro Lassaletta, Amulya A. Nageswara Rao, Florence M.G. Cavalli, Maura Massimino, Livia Garzia, Jüri Reimand, Charles G. Eberhart, Maryam Fouladi, Enrique López-Aguilar, Annie Huang, Cécile Faure-Conter, Gary D. Bader, Jaume Mora, Ho Keung Ng, James M. Olson, Jennifer A. Chan, Erwin G. Van Meir, Daniela Pretti da Cunha Tirapelli, Hamza Farooq, Fernando Chico Ponce de León, Linda M. Liau, Kay Ka Wai Li, Shenandoah Robinson, Anne Jouvet, Tomoko Shofuda, José Pimentel, Reid C. Thompson, Yuan Yao Thompson, Ian F. Pollack, Nada Jabado, Boleslaw Lach, Pim J. French, Joshua B. Rubin, Eric Bouffet, Alexandre Vasiljevic, Ali G. Saad, Michael K. Cooper, Satoru Osuka, Peter B. Dirks, Jaroslav Sterba, Johan M. Kros, Claudia C. Faria, Kyu-Chang Wang, Seung-Ki Kim, Shin Jung, Craig Daniels, A. Sorana Morrissy, Ladislav Rampášek, Andrew R. Hallahan, Sarah Leary, Wiesława Grajkowska, Uri Tabori, Marc Remke, Samer K. Elbabaa, Michael D. Taylor, Andrew S. Moore, Toshihiro Kumabe, Mario Perezpeña-Diazconti, Vijay Ramaswamy, Ronald L. Hamilton, Claudia M. Kuzan-Fischer, Marie Lise C. van Veelen, Helen Wheeler, Michal Zapotocky, Ji Yeoun Lee, David Shih, Jeffrey R. Leonard, Karel Zitterbart, Carlos Gilberto Carlotti, Steffen Albrecht, Jonathon Torchia, Peter Hauser, Ute Bartels, William A. Weiss, Sameer Agnihotri, Lola B. Chambless, Neurosurgery, Pathology, Neurology, Cavalli, Fmg, Remke, M, Rampasek, L, Peacock, J, Shih, Djh, Luu, B, Garzia, L, Torchia, J, Nor, C, Morrissy, A, Agnihotri, S, Thompson, Yy, Kuzan-Fischer, Cm, Farooq, H, Isaev, K, Daniels, C, Cho, Bk, Kim, Sk, Wang, Kc, Lee, Jy, Grajkowska, Wa, Perek-Polnik, M, Vasiljevic, A, Faure-Conter, C, Jouvet, A, Giannini, C, Nageswara Rao, Aa, Li, Kkw, Ng, Hk, Eberhart, Cg, Pollack, If, Hamilton, Rl, Gillespie, Gy, Olson, Jm, Leary, S, Weiss, Wa, Lach, B, Chambless, Lb, Thompson, Rc, Cooper, Mk, Vibhakar, R, Hauser, P, van Veelen, Mc, Kros, Jm, French, Pj, Ra, Y, Kumabe, T, López-Aguilar, E, Zitterbart, K, Sterba, J, Finocchiaro, G, Massimino, M, Van Meir, Eg, Osuka, S, Shofuda, T, Klekner, A, Zollo, M, Leonard, Jr, Rubin, Jb, Jabado, N, Albrecht, S, Mora, J, Van Meter, Te, Jung, S, Moore, A, Hallahan, Ar, Chan, Ja, Tirapelli, Dpc, Carlotti, Cg, Fouladi, M, Pimentel, J, Faria, Cc, Saad, Ag, Massimi, L, Liau, Lm, Wheeler, H, Nakamura, H, Elbabaa, Sk, Perezpeña-Diazconti, M, Chico Ponce de León, F, Robinson, S, Zapotocky, M, Lassaletta, A, Huang, Weiping, Hawkins, Ce, Tabori, U, Bouffet, E, Bartels, U, Dirks, Pb, Rutka, Jt, Bader, Gd, Reimand, J, Goldenberg, A, Ramaswamy, V, Taylor, Md, Cavalli F.M.G., Remke M., Rampasek L., Peacock J., Shih D.J.H., Luu B., Garzia L., Torchia J., Nor C., Morrissy A.S., Agnihotri S., Thompson Y.Y., Kuzan-Fischer C.M., Farooq H., Isaev K., Daniels C., Cho B.-K., Kim S.-K., Wang K.-C., Lee J.Y., Grajkowska W.A., Perek-Polnik M., Vasiljevic A., Faure-Conter C., Jouvet A., Giannini C., Nageswara Rao A.A., Li K.K.W., Ng H.-K., Eberhart C.G., Pollack I.F., Hamilton R.L., Gillespie G.Y., Olson J.M., Leary S., Weiss W.A., Lach B., Chambless L.B., Thompson R.C., Cooper M.K., Vibhakar R., Hauser P., van Veelen M.-L.C., Kros J.M., French P.J., Ra Y.S., Kumabe T., Lopez-Aguilar E., Zitterbart K., Sterba J., Finocchiaro G., Massimino M., Van Meir E.G., Osuka S., Shofuda T., Klekner A., Zollo M., Leonard J.R., Rubin J.B., Jabado N., Albrecht S., Mora J., Van Meter T.E., Jung S., Moore A.S., Hallahan A.R., Chan J.A., Tirapelli D.P.C., Carlotti C.G., Fouladi M., Pimentel J., Faria C.C., Saad A.G., Massimi L., Liau L.M., Wheeler H., Nakamura H., Elbabaa S.K., Perezpena-Diazconti M., Chico Ponce de Leon F., Robinson S., Zapotocky M., Lassaletta A., Huang A., Hawkins C.E., Tabori U., Bouffet E., Bartels U., Dirks P.B., Rutka J.T., Bader G.D., Reimand J., Goldenberg A., Ramaswamy V., and Taylor M.D.
Subjects: 0301 basic medicine, Cancer Research, medulloblastoma, CURRENT CONSENSUS, copy number, Bioinformatics, subgroups, Cohort Studies, Individual data, Cluster Analysis, R PACKAGE, Precision Medicine, GENECHIP DATA, Sonic hedgehog, ADULT MEDULLOBLASTOMA, DNA Copy Number Variation, Cancer, Pediatric, Genomics, methylation, CANCER, 3. Good health, Oncology, DNA methylation, Human, Pediatric Research Initiative, DNA Copy Number Variations, Pediatric Cancer, Oncology and Carcinogenesis, Computational biology, Biology, Article, CLASSIFICATION, Homogeneous clusters, 03 medical and health sciences, Rare Diseases, Genetics, medicine, Humans, Oncology & Carcinogenesis, Cerebellar Neoplasms, RECURRENCE, neoplasms, Medulloblastoma, Cluster Analysi, gene expression, MUTATIONS, subgroup, Gene Expression Profiling, Human Genome, Neurosciences, integrative clustering, DNA Methylation, medicine.disease, Precision medicine, MEDULOBLASTOMA, Brain Disorders, nervous system diseases, Brain Cancer, Gene expression profiling, stomatognathic diseases, 030104 developmental biology, Genomic, biology.protein, MOLECULAR SUBGROUPS, GENOMIC DATA, Cohort Studie
Abstract: While molecular subgrouping has revolutionized medulloblastoma classification, the extent of heterogeneity within subgroups is unknown. Similarity network fusion (SNF) applied to genome-wide DNA methylation and gene expression data across 763 primary samples identifies very homogeneous clusters of patients, supporting the presence of medulloblastoma subtypes. After integration of somatic copy-number alterations, and clinical features specific to each cluster, we identify 12 different subtypes of medulloblastoma. Integrative analysis using SNF further delineates group 3 from group 4 medulloblastoma, which is not as readily apparent through analyses of individual data types. Two clear subtypes of infants with Sonic Hedgehog medulloblastoma with disparate outcomes and biology are identified. Medulloblastoma subtypes identified through integrative clustering have important implications for stratification of future clinical trials.
Published: 2017

32. Therapeutic impact of cytoreductive surgery and irradiation of posterior fossa ependymoma in the molecular era: A retrospective multicohort analysis

Author: Uri Tabori, Marta M. Alonso, Frank S. Lieberman, James T. Rutka, Xing Fan, Kevin Petrecca, Michael A. Grotzer, Lyndsey Emery, Jennifer A. Chan, Luca Massimi, Elizabeth Vera-Bolanos, Antonio Omuro, Richard Everson, Stewart Goldman, Sarah Leary, Alvaro Lassaletta, Sofia Nunes, Ralph P. Ermoian, Betty Luu, Cynthia Hawkins, Amulya A. Nageswara Rao, Jeffrey R. Leonard, Maura Massimino, Teresa Tuñón, Massimo Zollo, James M. Olson, Almos Klekner, Andrey Korshunov, Ute Bartels, Tong Lin, Roger J. Packer, Matthias A. Karajannis, David W. Ellison, Christopher Dunham, David D. Eisenstat, Jaume Mora, Martin Mynarek, Erwin G. Van Meir, Roger E. McLendon, Karel Zitterbart, Corrine Gardner, Giuseppe Cinalli, Amar Gajjar, Kenneth Aldape, Karin M. Muraszko, Vijay Ramaswamy, Thomas Hielscher, Ronald L. Hamilton, Lola B. Chambless, Michael D. Prados, David T.W. Jones, Harshad Ladha, Horacio Soto, Wiesława Grajkowska, Jason E. Cain, Felice Giangaspero, Marcel Kool, Eric S. Lipp, William H. Yong, Andrew J. Grossbach, Tibor Hortobágyi, Tarek Shalaby, Helen Wheeler, Peter Hauser, Marie Lise C. van Veelen, Kristian W. Pajtler, Dorcas Fulton, Mariarita Santi, László Bognár, Jaroslav Sterba, Jing Wu, Ji Yeoun Lee, Carlos Gilberto Carlotti, Katja von Hoff, Stefan Rutkowski, Michael D. Taylor, Daniela Pretti da Cunha Tirapelli, Phillipe Metellus, Stephen C. Mack, Thomas E. Merchant, Samer K. Elbabaa, Marc Remke, Girish Dhall, Riccardo Soffietti, Eric Bouffet, Miguel A. Guzman, Khalida Wani, Charles G. Eberhart, Terri S. Armstrong, Tom Mikkelsen, Francesca R. Buttarelli, Nada Jabado, Paul G. Fisher, Juliette Hukin, Maryam Fouladi, Sama Ahsan, Sueli Mieko Oba-Shinjo, Linda M. Liau, Satoru Osuka, Sridharan Gururangan, Peter B. Dirks, Eugene Hwang, Howard Colman, H. Ian Robins, Caterina Giannini, Suely Kazue Nagahashi Marie, Frank van Landeghem, Mark R. Gilbert, Ulrich Schüller, Florence M.G. Cavalli, David Zagzag, Ian F. Pollack, Claudia C. Faria, Stefan M. Pfister, Shin Jung, Ramaswamy, V, Hielscher, T, Mack, Sc, Lassaletta, A, Lin, T, Pajtler, Kw, Jones, Dt, Luu, B, Cavalli, Fm, Aldape, K, Remke, M, Mynarek, M, Rutkowski, S, Gururangan, S, Mclendon, Re, Lipp, E, Dunham, C, Hukin, J, Eisenstat, Dd, Fulton, D, van Landeghem, Fk, Santi, M, van Veelen, Ml, Van Meir, Eg, Osuka, S, Fan, X, Muraszko, Km, Tirapelli, Dp, Oba Shinjo, Sm, Marie, Sk, Carlotti, Cg, Lee, Jy, Rao, Aa, Giannini, C, Faria, Cc, Nunes, S, Mora, J, Hamilton, Rl, Hauser, P, Jabado, N, Petrecca, K, Jung, S, Massimi, L, Zollo, Massimo, Cinalli, G, Bognár, L, Klekner, A, Hortobágyi, T, Leary, S, Ermoian, Rp, Olson, Jm, Leonard, Jr, Gardner, C, Grajkowska, Wa, Chambless, Lb, Cain, J, Eberhart, Cg, Ahsan, S, Massimino, M, Giangaspero, F, Buttarelli, Fr, Packer, Rj, Emery, L, Yong, Wh, Soto, H, Liau, Lm, Everson, R, Grossbach, A, Shalaby, T, Grotzer, M, Karajannis, Ma, Zagzag, D, Wheeler, H, von Hoff, K, Alonso, Mm, Tuñon, T, Schüller, U, Zitterbart, K, Sterba, J, Chan, Ja, Guzman, M, Elbabaa, Sk, Colman, H, Dhall, G, Fisher, Pg, Fouladi, M, Gajjar, A, Goldman, S, Hwang, E, Kool, M, Ladha, H, Vera Bolanos, E, Wani, K, Lieberman, F, Mikkelsen, T, Omuro, Am, Pollack, If, Prados, M, Robins, Hi, Soffietti, R, Wu, J, Metellus, P, Tabori, U, Bartels, U, Bouffet, E, Hawkins, Ce, Rutka, Jt, Dirks, P, Pfister, Sm, Merchant, Te, Gilbert, Mr, Armstrong, T, Korshunov, A, Ellison, Dw, Taylor, M. d., Ramaswamy V., Hielscher T., Mack S.C., Lassaletta A., Lin T., Pajtler K.W., Jones D.T.W., Luu B., Cavalli F.M.G., Aldape K., Remke M., Mynarek M., Rutkowski S., Gururangan S., McLendon R.E., Lipp E.S., Dunham C., Hukin J., Eisenstat D.D., Fulton D., Van Landeghem F.K.H., Santi M., Van Veelen M.-L.C., Van Meir E.G., Osuka S., Fan X., Muraszko K.M., Tirapelli D.P.C., Oba-Shinjo S.M., Marie S.K.N., Carlotti C.G., Lee J.Y., Rao A.A.N., Giannini C., Faria C.C., Nunes S., Mora J., Hamilton R.L., Hauser P., Jabado N., Petrecca K., Jung S., Massimi L., Zollo M., Cinalli G., Bognar L., Klekner A., Hortobagyi T., Leary S., Ermoian R.P., Olson J.M., Leonard J.R., Gardner C., Grajkowska W.A., Chambless L.B., Cain J., Eberhart C.G., Ahsan S., Massimino M., Giangaspero F., Buttarelli F.R., Packer R.J., Emery L., Yong W.H., Soto H., Liau L.M., Everson R., Grossbach A., Shalaby T., Grotzer M., Karajannis M.A., Zagzag D., Wheeler H., Von Hoff K., Alonso M.M., Tunon T., Schuller U., Zitterbart K., Sterba J., Chan J.A., Guzman M., Elbabaa S.K., Colman H., Dhall G., Fisher P.G., Fouladi M., Gajjar A., Goldman S., Hwang E., Kool M., Ladha H., Vera-Bolanos E., Wani K., Lieberman F., Mikkelsen T., Omuro A.M., Pollack I.F., Prados M., Robins H.I., Soffietti R., Wu J., Metellus P., Tabori U., Bartels U., Bouffet E., Hawkins C.E., Rutka J.T., Dirks P., Pfister S.M., Merchant T.E., Gilbert M.R., Armstrong T.S., Korshunov A., Ellison D.W., Taylor M.D., and Neurosurgery
Subjects: Male, Ependymoma, Cancer Research, medicine.medical_treatment, cancer research, oncology, posterior fossa ependymoma, cytoreductive surgery, radiation therapy, Infratentorial Neoplasms, Cohort Studies, 0302 clinical medicine, Retrospective Studie, Medicine, Pediatric ependymoma, Child, 10. No inequality, Infratentorial Neoplasm, biology, Cytoreduction Surgical Procedures, Combined Modality Therapy, 3. Good health, Oncology, Child, Preschool, 030220 oncology & carcinogenesis, Female, Radiology, Human, Adult, medicine.medical_specialty, Adolescent, Fossa, Ependymoma, biomarkers, 03 medical and health sciences, Original Reports, Humans, Retrospective Studies, Chemotherapy, business.industry, Proportional hazards model, Infant, Retrospective cohort study, biology.organism_classification, medicine.disease, Surgery, Radiation therapy, Cohort Studie, business, 030217 neurology & neurosurgery
Abstract: Purpose Posterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known. Methods Four independent nonoverlapping retrospective cohorts of posterior fossa ependymomas (n = 820) were profiled using genome-wide methylation arrays. Risk stratification models were designed based on known clinical and newly described molecular biomarkers identified by multivariable Cox proportional hazards analyses. Results Molecular subgroup is a powerful independent predictor of outcome even when accounting for age or treatment regimen. Incompletely resected EPN_PFA ependymomas have a dismal prognosis, with a 5-year progression-free survival ranging from 26.1% to 56.8% across all four cohorts. Although first-line (adjuvant) radiation is clearly beneficial for completely resected EPN_PFA, a substantial proportion of patients with EPN_PFB can be cured with surgery alone, and patients with relapsed EPN_PFB can often be treated successfully with delayed external-beam irradiation. Conclusion The most impactful biomarker for posterior fossa ependymoma is molecular subgroup affiliation, independent of other demographic or treatment variables. However, both EPN_PFA and EPN_PFB still benefit from increased extent of resection, with the survival rates being particularly poor for subtotally resected EPN_PFA, even with adjuvant radiation therapy. Patients with EPN_PFB who undergo gross total resection are at lower risk for relapse and should be considered for inclusion in a randomized clinical trial of observation alone with radiation reserved for those who experience recurrence.
Published: 2016

33. Rapid Increase in Soil Respiration and Reduction in Soil Nitrate Availability Following CO 2 Enrichment in a Mature Oak Forest.

Author: Kourmouli A, Hamilton RL, Pihlblad J, Bartlett R, MacKenzie AR, Hartley IP, Ullah S, and Shi Z
Abstract: In the future, with elevated atmospheric CO 2 (eCO 2 ), forests are expected to increase woody biomass to capture more carbon (C), though this is dependent on soil nutrient availability. While young forests may access unused nutrients by growing into an unexplored soil environment, it is unclear how or if mature forests can adapt belowground under eCO 2 . Soil respiration ( R s ) and nutrient bioavailability are integrative ecosystem measures of below-ground dynamics. At Birmingham's Institute of Forest Research Free Air CO 2 Enrichment (BIFoR FACE) facility, we investigated the effects of eCO 2 (+150 ppm above ambient) on a mature oak forest during the first year of exposure. We observed an annual R s increase of ∼21.5%; 996 ± 398 g C m -2 year -1 (ambient) to 1210 ± 483 g C m -2 year -1 (eCO 2 ). The eCO 2 impact was greater on belowground nutrient cycling, with monthly nitrate availability decreasing by up to 36%. These results show that high C uptake resulted in higher soil respiration with a concomitant decrease in the level of soil nitrate during the first year. These belowground responses and their long-term dynamics will have implications for the carbon budget of mature forest ecosystems in changing climate., Competing Interests: The authors declare no competing financial interest., (© 2025 The Authors. Published by American Chemical Society.)
Published: 2025
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34. ZIC1 is a context-dependent medulloblastoma driver in the rhombic lip.

Author: Lee JJY, Tao R, You Z, Haldipur P, Erickson AW, Farooq H, Hendriske LD, Abeysundara N, Richman CM, Wang EY, Das Gupta N, Hadley J, Batts M, Mount CW, Wu X, Rasnitsyn A, Bailey S, Cavalli FMG, Morrissy S, Garzia L, Michealraj KA, Visvanathan A, Fong V, Palotta J, Suarez R, Livingston BG, Liu M, Luu B, Daniels C, Loukides J, Bendel A, French PJ, Kros JM, Korshunov A, Kool M, Chico Ponce de León F, Perezpeña-Diazconti M, Lach B, Singh SK, Leary SES, Cho BK, Kim SK, Wang KC, Lee JY, Tominaga T, Weiss WA, Phillips JJ, Dai S, Zadeh G, Saad AG, Bognár L, Klekner A, Pollack IF, Hamilton RL, Ra YS, Grajkowska WA, Perek-Polnik M, Thompson RC, Kenney AM, Cooper MK, Mack SC, Jabado N, Lupien M, Gallo M, Ramaswamy V, Suva ML, Suzuki H, Millen KJ, Huang LF, Northcott PA, and Taylor MD
Subjects: Humans, Animals, Mice, Gene Expression Regulation, Neoplastic, Cell Proliferation genetics, Hedgehog Proteins genetics, Hedgehog Proteins metabolism, Mutation, Loss of Function Mutation, Embryonic Structures, Metencephalon embryology, Medulloblastoma genetics, Medulloblastoma pathology, Medulloblastoma metabolism, Transcription Factors genetics, Transcription Factors metabolism, Cerebellar Neoplasms genetics, Cerebellar Neoplasms pathology, Cerebellar Neoplasms metabolism
Abstract: Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% of G4 medulloblastoma). In contrast, highly similar SHH medulloblastoma exhibits distinct and diametrically opposed gain-of-function mutations and copy number gains (20% of SHH medulloblastoma). Overexpression of ZIC1 suppresses the growth of group 3 medulloblastoma models, whereas it promotes the proliferation of SHH medulloblastoma precursor cells. SHH medulloblastoma ZIC1 mutants show increased activity versus wild-type ZIC1, whereas G4 medulloblastoma ZIC1 mutants exhibit LOF phenotypes. Distinct ZIC1 mutations affect cells of the rhombic lip in diametrically opposed ways, suggesting that ZIC1 is a critical developmental transcriptional regulator in both the normal and transformed rhombic lip and identifying ZIC1 as an exquisitely context-dependent driver gene in medulloblastoma., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)
Published: 2025
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35. Multi-ancestry genome-wide meta-analysis of 56,241 individuals identifies LRRC4C, LHX5-AS1 and nominates ancestry-specific loci PTPRK , GRB14 , and KIAA0825 as novel risk loci for Alzheimer's disease: the Alzheimer's Disease Genetics Consortium.

Author: Rajabli F, Benchek P, Tosto G, Kushch N, Sha J, Bazemore K, Zhu C, Lee WP, Haut J, Hamilton-Nelson KL, Wheeler NR, Zhao Y, Farrell JJ, Grunin MA, Leung YY, Kuksa PP, Li D, Lucio da Fonseca E, Mez JB, Palmer EL, Pillai J, Sherva RM, Song YE, Zhang X, Iqbal T, Pathak O, Valladares O, Kuzma AB, Abner E, Adams PM, Aguirre A, Albert MS, Albin RL, Allen M, Alvarez L, Apostolova LG, Arnold SE, Asthana S, Atwood CS, Ayres G, Baldwin CT, Barber RC, Barnes LL, Barral S, Beach TG, Becker JT, Beecham GW, Beekly D, Benitez BA, Bennett D, Bertelson J, Bird TD, Blacker D, Boeve BF, Bowen JD, Boxer A, Brewer J, Burke JR, Burns JM, Buxbaum JD, Cairns NJ, Cantwell LB, Cao C, Carlson CS, Carlsson CM, Carney RM, Carrasquillo MM, Chasse S, Chesselet MF, Chin NA, Chui HC, Chung J, Craft S, Crane PK, Cribbs DH, Crocco EA, Cruchaga C, Cuccaro ML, Cullum M, Darby E, Davis B, De Jager PL, DeCarli C, DeToledo J, Dick M, Dickson DW, Dombroski BA, Doody RS, Duara R, Ertekin-Taner N, Evans DA, Faber KM, Fairchild TJ, Fallon KB, Fardo DW, Farlow MR, Fernandez-Hernandez V, Ferris S, Foroud TM, Frosch MP, Fulton-Howard B, Galasko DR, Gamboa A, Gearing M, Geschwind DH, Ghetti B, Gilbert JR, Goate AM, Grabowski TJ, Graff-Radford NR, Green RC, Growdon JH, Hakonarson H, Hall J, Hamilton RL, Harari O, Hardy J, Harrell LE, Head E, Henderson VW, Hernandez M, Hohman T, Honig LS, Huebinger RM, Huentelman MJ, Hulette CM, Hyman BT, Hynan LS, Ibanez L, Jarvik GP, Jayadev S, Jin LW, Johnson K, Johnson L, Kamboh MI, Karydas AM, Katz MJ, Kauwe JS, Kaye JA, Keene CD, Khaleeq A, Kim R, Knebl J, Kowall NW, Kramer JH, Kukull WA, LaFerla FM, Lah JJ, Larson EB, Lerner A, Leverenz JB, Levey AI, Lieberman AP, Lipton RB, Logue M, Lopez OL, Lunetta KL, Lyketsos CG, Mains D, Margaret FE, Marson DC, Martin ERR, Martiniuk F, Mash DC, Masliah E, Massman P, Masurkar A, McCormick WC, McCurry SM, McDavid AN, McDonough S, McKee AC, Mesulam M, Miller BL, Miller CA, Miller JW, Montine TJ, Monuki ES, Morris JC, Mukherjee S, Myers AJ, Nguyen T, O'Bryant S, Olichney JM, Ory M, Palmer R, Parisi JE, Paulson HL, Pavlik V, Paydarfar D, Perez V, Peskind E, Petersen RC, Pierce A, Polk M, Poon WW, Potter H, Qu L, Quiceno M, Quinn JF, Raj A, Raskind M, Reiman EM, Reisberg B, Reisch JS, Ringman JM, Roberson ED, Rodriguear M, Rogaeva E, Rosen HJ, Rosenberg RN, Royall DR, Sager MA, Sano M, Saykin AJ, Schneider JA, Schneider LS, Seeley WW, Slifer SH, Small S, Smith AG, Smith JP, Sonnen JA, Spina S, St George-Hyslop P, Stern RA, Stevens AB, Strittmatter SM, Sultzer D, Swerdlow RH, Tanzi RE, Tilson JL, Trojanowski JQ, Troncoso JC, Tsuang DW, Van Deerlin VM, van Eldik LJ, Vance JM, Vardarajan BN, Vassar R, Vinters HV, Vonsattel JP, Weintraub S, Welsh-Bohmer KA, Whitehead PL, Wijsman EM, Wilhelmsen KC, Williams B, Williamson J, Wilms H, Wingo TS, Wisniewski T, Woltjer RL, Woon M, Wright CB, Wu CK, Younkin SG, Yu CE, Yu L, Zhu X, Kunkle BW, Bush WS, Wang LS, Farrer LA, Haines JL, Mayeux R, Pericak-Vance MA, Schellenberg GD, Jun GR, Reitz C, and Naj AC
Abstract: Limited ancestral diversity has impaired our ability to detect risk variants more prevalent in non-European ancestry groups in genome-wide association studies (GWAS). We constructed and analyzed a multi-ancestry GWAS dataset in the Alzheimer's Disease (AD) Genetics Consortium (ADGC) to test for novel shared and ancestry-specific AD susceptibility loci and evaluate underlying genetic architecture in 37,382 non-Hispanic White (NHW), 6,728 African American, 8,899 Hispanic (HIS), and 3,232 East Asian individuals, performing within-ancestry fixed-effects meta-analysis followed by a cross-ancestry random-effects meta-analysis. We identified 13 loci with cross-ancestry associations including known loci at/near CR1 , BIN1 , TREM2 , CD2AP , PTK2B , CLU , SHARPIN , MS4A6A , PICALM , ABCA7 , APOE and two novel loci not previously reported at 11p12 ( LRRC4C ) and 12q24.13 ( LHX5-AS1 ). Reflecting the power of diverse ancestry in GWAS, we observed the SHARPIN locus using 7.1% the sample size of the original discovering single-ancestry GWAS (n=788,989). We additionally identified three GWS ancestry-specific loci at/near ( PTPRK ( P =2.4×10 -8 ) and GRB14 ( P =1.7×10 -8 ) in HIS), and KIAA0825 ( P =2.9×10 -8 in NHW). Pathway analysis implicated multiple amyloid regulation pathways (strongest with P adjusted =1.6×10 -4 ) and the classical complement pathway ( P adjusted =1.3×10 -3 ). Genes at/near our novel loci have known roles in neuronal development ( LRRC4C, LHX5-AS1 , and PTPRK ) and insulin receptor activity regulation ( GRB14 ). These findings provide compelling support for using traditionally-underrepresented populations for gene discovery, even with smaller sample sizes.
Published: 2023
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36. Restoration impacts on rates of denitrification and greenhouse gas fluxes from tropical coastal wetlands.

Author: Comer-Warner SA, Nguyen ATQ, Nguyen MN, Wang M, Turner A, Le H, Sgouridis F, Krause S, Kettridge N, Nguyen N, Hamilton RL, and Ullah S
Subjects: Carbon Dioxide analysis, Denitrification, Ecosystem, Environmental Monitoring, Methane analysis, Nitrous Oxide analysis, Soil, Wetlands, Greenhouse Gases analysis
Abstract: Forested coastal wetlands are globally important systems sequestering carbon and intercepting nitrogen pollution from nutrient-rich river systems. Coastal wetlands that have suffered extensive disturbance are the target of comprehensive restoration efforts. Accurate assessment of restoration success requires detailed mechanistic understanding of wetland soil biogeochemical functioning across restoration chrono-sequences, which remains poorly understood for these sparsely investigated systems. This study investigated denitrification and greenhouse gas fluxes in mangrove and Melaleuca forest soils of Vietnam, using the 15 N-Gas flux method. Denitrification-derived N 2 O was significantly higher from Melaleuca than mangrove forest soils, despite higher potential rates of total denitrification in the mangrove forest soils (8.1 ng N g -1 h -1 ) than the Melaleuca soils (6.8 ng N g -1 h -1 ). Potential N 2 O and CO 2 emissions were significantly higher from the Melaleuca soils than from the mangrove soils. Disturbance and subsequent recovery had no significant effect on N biogeochemistry except with respect to the denitrification product ratio in the mangrove sites, which was highest from the youngest mangrove site. Potential CO 2 and CH 4 fluxes were significantly affected by restoration in the mangrove soils. The lowest potential CO 2 emissions were observed in the mid-age plantation and potential CH 4 fluxes decreased in the older forests. The mangrove system, therefore, may remove excess N and improve water quality with low greenhouse gas emissions, whereas in Melaleucas, increased N 2 O and CO 2 emissions also occur. These emissions are likely balanced by higher carbon stocks observed in the Melaleuca soils. These mechanistic insights highlight the importance of ecosystem restoration for pollution attenuation and reduction of greenhouse gas emissions from coastal wetlands. Restoration efforts should continue to focus on increasing wetland area and function, which will benefit local communities with improved water quality and potential for income generation under future carbon trading., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)
Published: 2022
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37. Experiences with implementation of continuous positive airway pressure for neonates and infants in low-resource settings: A scoping review.

Author: Dada S, Ashworth H, Sobitschka A, Raguveer V, Sharma R, Hamilton RL, and Burke T
Subjects: Continuous Positive Airway Pressure adverse effects, Continuous Positive Airway Pressure economics, Continuous Positive Airway Pressure statistics & numerical data, Developing Countries, Humans, Infant, Infant, Newborn, Respiratory Distress Syndrome, Newborn epidemiology, Continuous Positive Airway Pressure methods, Respiratory Distress Syndrome, Newborn therapy
Abstract: Background: Continuous positive airway pressure (CPAP) is the gold standard of care in providing non-invasive positive pressure support to neonates in respiratory distress in high-resource settings. While safety has been demonstrated in low-resource settings, there is a lack of knowledge on the barriers and facilitators to proper implementation., Objective: To identify and describe the barriers, facilitators, and priorities for future implementation of CPAP for neonates and infants in low-resource settings., Methods: A systematic search (database inception to March 6, 2020) was performed on MEDLINE, Embase, Web of Science, CINAHL, Global Health, and the WHO Global Index Medicus using PRISMA-ScR guidelines. Original research articles pertaining to implementation of CPAP devices in low-resource settings, provider or parent perspectives and experiences with CPAP, cost-benefit analyses, and cost-effectiveness studies were included. Inductive content analysis was conducted., Findings: 1385 article were screened and 54 studies across 19 countries met inclusion criteria. Six major themes emerged: device attributes, patient experiences, parent experiences, provider experiences, barriers, and facilitators. Nasal trauma was the most commonly reported complication. Barriers included unreliable electricity and lack of bioengineering support. Facilitators included training, mentorship and empowerment of healthcare providers. Device design, supply chain infrastructure, and training models were imperative to the adoption and sustainability of CPAP., Conclusion: Sustainable implementation of CPAP in low resource settings requires easy-to-use devices, ready access to consumables, and holistic, user-driven training. Further research is necessary on standardizing metrics, interventions that support optimal provider performance, and conditions needed for successful long-term health system integration., Competing Interests: At the time of submission, SD, HA, AS, VR, and TB were affiliated with the Vayu Global Health Foundation, which implements novel bubble CPAP systems in low-resource settings. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
Published: 2021
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38. The transcriptional landscape of Shh medulloblastoma.

Author: Skowron P, Farooq H, Cavalli FMG, Morrissy AS, Ly M, Hendrikse LD, Wang EY, Djambazian H, Zhu H, Mungall KL, Trinh QM, Zheng T, Dai S, Stucklin ASG, Vladoiu MC, Fong V, Holgado BL, Nor C, Wu X, Abd-Rabbo D, Bérubé P, Wang YC, Luu B, Suarez RA, Rastan A, Gillmor AH, Lee JJY, Zhang XY, Daniels C, Dirks P, Malkin D, Bouffet E, Tabori U, Loukides J, Doz FP, Bourdeaut F, Delattre OO, Masliah-Planchon J, Ayrault O, Kim SK, Meyronet D, Grajkowska WA, Carlotti CG, de Torres C, Mora J, Eberhart CG, Van Meir EG, Kumabe T, French PJ, Kros JM, Jabado N, Lach B, Pollack IF, Hamilton RL, Rao AAN, Giannini C, Olson JM, Bognár L, Klekner A, Zitterbart K, Phillips JJ, Thompson RC, Cooper MK, Rubin JB, Liau LM, Garami M, Hauser P, Li KKW, Ng HK, Poon WS, Yancey Gillespie G, Chan JA, Jung S, McLendon RE, Thompson EM, Zagzag D, Vibhakar R, Ra YS, Garre ML, Schüller U, Shofuda T, Faria CC, López-Aguilar E, Zadeh G, Hui CC, Ramaswamy V, Bailey SD, Jones SJ, Mungall AJ, Moore RA, Calarco JA, Stein LD, Bader GD, Reimand J, Ragoussis J, Weiss WA, Marra MA, Suzuki H, and Taylor MD
Subjects: Adolescent, Adult, Child, Child, Preschool, Female, Gene Regulatory Networks, Genetic Variation, Humans, Infant, Male, Middle Aged, Signal Transduction genetics, Young Adult, Cerebellar Neoplasms genetics, Gene Expression Regulation, Neoplastic, Hedgehog Proteins genetics, Medulloblastoma genetics, Transcriptome
Abstract: Sonic hedgehog medulloblastoma encompasses a clinically and molecularly diverse group of cancers of the developing central nervous system. Here, we use unbiased sequencing of the transcriptome across a large cohort of 250 tumors to reveal differences among molecular subtypes of the disease, and demonstrate the previously unappreciated importance of non-coding RNA transcripts. We identify alterations within the cAMP dependent pathway (GNAS, PRKAR1A) which converge on GLI2 activity and show that 18% of tumors have a genetic event that directly targets the abundance and/or stability of MYCN. Furthermore, we discover an extensive network of fusions in focally amplified regions encompassing GLI2, and several loss-of-function fusions in tumor suppressor genes PTCH1, SUFU and NCOR1. Molecular convergence on a subset of genes by nucleotide variants, copy number aberrations, and gene fusions highlight the key roles of specific pathways in the pathogenesis of Sonic hedgehog medulloblastoma and open up opportunities for therapeutic intervention.
Published: 2021
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39. Pattern of Relapse and Treatment Response in WNT-Activated Medulloblastoma.

Author: Nobre L, Zapotocky M, Khan S, Fukuoka K, Fonseca A, McKeown T, Sumerauer D, Vicha A, Grajkowska WA, Trubicka J, Li KKW, Ng HK, Massimi L, Lee JY, Kim SK, Zelcer S, Vasiljevic A, Faure-Conter C, Hauser P, Lach B, van Veelen-Vincent ML, French PJ, Van Meir EG, Weiss WA, Gupta N, Pollack IF, Hamilton RL, Nageswara Rao AA, Giannini C, Rubin JB, Moore AS, Chambless LB, Vibhakar R, Ra YS, Massimino M, McLendon RE, Wheeler H, Zollo M, Ferruci V, Kumabe T, Faria CC, Sterba J, Jung S, López-Aguilar E, Mora J, Carlotti CG, Olson JM, Leary S, Cain J, Krskova L, Zamecnik J, Hawkins CE, Tabori U, Huang A, Bartels U, Northcott PA, Taylor MD, Yip S, Hansford JR, Bouffet E, and Ramaswamy V
Subjects: Adolescent, Biomarkers, Tumor metabolism, Child, Cyclophosphamide therapeutic use, Female, Humans, Ifosfamide therapeutic use, Male, Medulloblastoma metabolism, Middle Aged, Neoplasm Recurrence, Local metabolism, Progression-Free Survival, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cerebellar Neoplasms drug therapy, Medulloblastoma drug therapy, Neoplasm Recurrence, Local drug therapy
Abstract: Over the past decade, wingless-activated (WNT) medulloblastoma has been identified as a candidate for therapy de-escalation based on excellent survival; however, a paucity of relapses has precluded additional analyses of markers of relapse. To address this gap in knowledge, an international cohort of 93 molecularly confirmed WNT MB was assembled, where 5-year progression-free survival is 0.84 (95%, 0.763-0.925) with 15 relapsed individuals identified. Maintenance chemotherapy is identified as a strong predictor of relapse, with individuals receiving high doses of cyclophosphamide or ifosphamide having only one very late molecularly confirmed relapse (p = 0.032). The anatomical location of recurrence is metastatic in 12 of 15 relapses, with 8 of 12 metastatic relapses in the lateral ventricles. Maintenance chemotherapy, specifically cumulative cyclophosphamide doses, is a significant predictor of relapse across WNT MB. Future efforts to de-escalate therapy need to carefully consider not only the radiation dose but also the chemotherapy regimen and the propensity for metastatic relapses., Competing Interests: DECLARATION OF INTERESTS The authors declare no competing interests.
Published: 2020
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40. Concomitant parasagittal meningioma and adjacent intracranial abscess of occult etiology.

Author: Chandra V, Agarwal N, Zenonos GA, Zhang X, Hamilton RL, and Gardner PA
Subjects: Aged, Brain Abscess diagnosis, Brain Abscess microbiology, Gram-Negative Bacterial Infections diagnosis, Gram-Negative Bacterial Infections microbiology, Gram-Positive Bacterial Infections diagnosis, Gram-Positive Bacterial Infections microbiology, Humans, Male, Meningeal Neoplasms diagnosis, Meningioma diagnosis, Brain Abscess complications, Gram-Negative Bacterial Infections complications, Gram-Positive Bacterial Infections complications, Meningeal Neoplasms complications, Meningioma complications
Abstract: Introduction: Abscesses associated with tumors are a rare entity. Imaging to differentiate abscess from other entities is often non-diagnostic, and often the source of infection is unknown. We present an unusual case of peritumoral abscess infected with both gram-negative and gram-positive bacteria., Methods: A 70-year-old, previously healthy male presented with a 1-day history of right-sided facial weakness sparing the forehead, as well as concomitant right upper and lower extremity numbness. A homogenously enhancing mass with adjacent rim-enhancing lesion with diffusion restricting cavity seen on magnetic resonance imaging (MRI) raised the possibility of abscess., Results: Separate biopsy specimens of both the tumor and adjacent fluid collection during drainage of the collection confirmed World Health Organization (WHO) grade I meningioma and bacterial abscess containing Streptococcus constellatus, Fusobacterium species, Prevotella dentalis, and Parvimonas micra. The histologic diagnosis therefore confirmed the preoperative radiologic findings of two different but associated lesions. Investigations to determine a definitive source of infection were inconclusive, including urinalysis, blood cultures, respiratory cultures, endoscopy, and an orthopantomogram., Conclusions: Gram-negative and gram-positive bacteria can both be culprits in the formation of peritumoral abscess. Although the source of infection is unconfirmed, the presence of oropharyngeal flora in the abscess suggests a subclinical odontogenic infection with hematogenous spread to the tumor and adjacent brain., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019. Published by Elsevier Ltd.)
Published: 2020
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41. GABA bouton subpopulations in the human dentate gyrus are differentially altered in mesial temporal lobe epilepsy.

Author: Alhourani A, Fish KN, Wozny TA, Sudhakar V, Hamilton RL, and Richardson RM
Subjects: Adult, Drug Resistant Epilepsy pathology, Drug Resistant Epilepsy surgery, Epilepsy, Temporal Lobe surgery, Female, Humans, Male, Microscopy, Fluorescence, Middle Aged, Sclerosis pathology, Dentate Gyrus cytology, Epilepsy, Temporal Lobe pathology, GABAergic Neurons ultrastructure, Interneurons ultrastructure, Parvalbumins metabolism, Presynaptic Terminals ultrastructure
Abstract: Medically intractable temporal lobe epilepsy is a devastating disease, for which surgical removal of the seizure onset zone is the only known cure. Multiple studies have found evidence of abnormal dentate gyrus network circuitry in human mesial temporal lobe epilepsy (MTLE). Principal neurons within the dentate gyrus gate entorhinal input into the hippocampus, providing a critical step in information processing. Crucial to that role are GABA-expressing neurons, particularly parvalbumin (PV)-expressing basket cells (PVBCs) and chandelier cells (PVChCs), which provide strong, temporally coordinated inhibitory signals. Alterations in PVBC and PVChC boutons have been described in epilepsy, but the value of these studies has been limited due to methodological hurdles associated with studying human tissue. We developed a multilabel immunofluorescence confocal microscopy and a custom segmentation algorithm to quantitatively assess PVBC and PVChC bouton densities and to infer relative synaptic protein content in the human dentate gyrus. Using en bloc specimens from MTLE subjects with and without hippocampal sclerosis, paired with nonepileptic controls, we demonstrate the utility of this approach for detecting cell-type specific synaptic alterations. Specifically, we found increased density of PVBC boutons, while PVChC boutons decreased significantly in the dentate granule cell layer of subjects with hippocampal sclerosis compared with matched controls. In contrast, bouton densities for either PV-positive cell type did not differ between epileptic subjects without sclerosis and matched controls. These results may explain conflicting findings from previous studies that have reported both preserved and decreased PV bouton densities and establish a new standard for quantitative assessment of interneuron boutons in epilepsy. NEW & NOTEWORTHY A state-of-the-art, multilabel immunofluorescence confocal microscopy and custom segmentation algorithm technique, developed previously for studying synapses in the human prefrontal cortex, was modified to study the hippocampal dentate gyrus in specimens surgically removed from patients with temporal lobe epilepsy. The authors discovered that chandelier and basket cell boutons in the human dentate gyrus are differentially altered in mesial temporal lobe epilepsy.
Published: 2020
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42. Correlations between genomic subgroup and clinical features in a cohort of more than 3000 meningiomas.

Author: Youngblood MW, Duran D, Montejo JD, Li C, Omay SB, Özduman K, Sheth AH, Zhao AY, Tyrtova E, Miyagishima DF, Fomchenko EI, Hong CS, Clark VE, Riche M, Peyre M, Boetto J, Sohrabi S, Koljaka S, Baranoski JF, Knight J, Zhu H, Pamir MN, Avşar T, Kilic T, Schramm J, Timmer M, Goldbrunner R, Gong Y, Bayri Y, Amankulor N, Hamilton RL, Bilguvar K, Tikhonova I, Tomak PR, Huttner A, Simon M, Krischek B, Kalamarides M, Erson-Omay EZ, Moliterno J, and Günel M
Abstract: Objective: Recent large-cohort sequencing studies have investigated the genomic landscape of meningiomas, identifying somatic coding alterations in NF2, SMARCB1, SMARCE1, TRAF7, KLF4, POLR2A, BAP1, and members of the PI3K and Hedgehog signaling pathways. Initial associations between clinical features and genomic subgroups have been described, including location, grade, and histology. However, further investigation using an expanded collection of samples is needed to confirm previous findings, as well as elucidate relationships not evident in smaller discovery cohorts., Methods: Targeted sequencing of established meningioma driver genes was performed on a multiinstitution cohort of 3016 meningiomas for classification into mutually exclusive subgroups. Relevant clinical information was collected for all available cases and correlated with genomic subgroup. Nominal variables were analyzed using Fisher's exact tests, while ordinal and continuous variables were assessed using Kruskal-Wallis and 1-way ANOVA tests, respectively. Machine-learning approaches were used to predict genomic subgroup based on noninvasive clinical features., Results: Genomic subgroups were strongly associated with tumor locations, including correlation of HH tumors with midline location, and non-NF2 tumors in anterior skull base regions. NF2 meningiomas were significantly enriched in male patients, while KLF4 and POLR2A mutations were associated with female sex. Among histologies, the results confirmed previously identified relationships, and observed enrichment of microcystic features among "mutation unknown" samples. Additionally, KLF4-mutant meningiomas were associated with larger peritumoral brain edema, while SMARCB1 cases exhibited elevated Ki-67 index. Machine-learning methods revealed that observable, noninvasive patient features were largely predictive of each tumor's underlying driver mutation., Conclusions: Using a rigorous and comprehensive approach, this study expands previously described correlations between genomic drivers and clinical features, enhancing our understanding of meningioma pathogenesis, and laying further groundwork for the use of targeted therapies. Importantly, the authors found that noninvasive patient variables exhibited a moderate predictive value of underlying genomic subgroup, which could improve with additional training data. With continued development, this framework may enable selection of appropriate precision medications without the need for invasive sampling procedures.
Published: 2019
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43. Author Correction: Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing.

Author: Kunkle BW, Grenier-Boley B, Sims R, Bis JC, Damotte V, Naj AC, Boland A, Vronskaya M, van der Lee SJ, Amlie-Wolf A, Bellenguez C, Frizatti A, Chouraki V, Martin ER, Sleegers K, Badarinarayan N, Jakobsdottir J, Hamilton-Nelson KL, Moreno-Grau S, Olaso R, Raybould R, Chen Y, Kuzma AB, Hiltunen M, Morgan T, Ahmad S, Vardarajan BN, Epelbaum J, Hoffmann P, Boada M, Beecham GW, Garnier JG, Harold D, Fitzpatrick AL, Valladares O, Moutet ML, Gerrish A, Smith AV, Qu L, Bacq D, Denning N, Jian X, Zhao Y, Del Zompo M, Fox NC, Choi SH, Mateo I, Hughes JT, Adams HH, Malamon J, Sanchez-Garcia F, Patel Y, Brody JA, Dombroski BA, Naranjo MCD, Daniilidou M, Eiriksdottir G, Mukherjee S, Wallon D, Uphill J, Aspelund T, Cantwell LB, Garzia F, Galimberti D, Hofer E, Butkiewicz M, Fin B, Scarpini E, Sarnowski C, Bush WS, Meslage S, Kornhuber J, White CC, Song Y, Barber RC, Engelborghs S, Sordon S, Voijnovic D, Adams PM, Vandenberghe R, Mayhaus M, Cupples LA, Albert MS, De Deyn PP, Gu W, Himali JJ, Beekly D, Squassina A, Hartmann AM, Orellana A, Blacker D, Rodriguez-Rodriguez E, Lovestone S, Garcia ME, Doody RS, Munoz-Fernadez C, Sussams R, Lin H, Fairchild TJ, Benito YA, Holmes C, Karamujić-Čomić H, Frosch MP, Thonberg H, Maier W, Roshchupkin G, Ghetti B, Giedraitis V, Kawalia A, Li S, Huebinger RM, Kilander L, Moebus S, Hernández I, Kamboh MI, Brundin R, Turton J, Yang Q, Katz MJ, Concari L, Lord J, Beiser AS, Keene CD, Helisalmi S, Kloszewska I, Kukull WA, Koivisto AM, Lynch A, Tarraga L, Larson EB, Haapasalo A, Lawlor B, Mosley TH, Lipton RB, Solfrizzi V, Gill M, Longstreth WT Jr, Montine TJ, Frisardi V, Diez-Fairen M, Rivadeneira F, Petersen RC, Deramecourt V, Alvarez I, Salani F, Ciaramella A, Boerwinkle E, Reiman EM, Fievet N, Rotter JI, Reisch JS, Hanon O, Cupidi C, Uitterlinden AGA, Royall DR, Dufouil C, Maletta RG, de Rojas I, Sano M, Brice A, Cecchetti R, George-Hyslop PS, Ritchie K, Tsolaki M, Tsuang DW, Dubois B, Craig D, Wu CK, Soininen H, Avramidou D, Albin RL, Fratiglioni L, Germanou A, Apostolova LG, Keller L, Koutroumani M, Arnold SE, Panza F, Gkatzima O, Asthana S, Hannequin D, Whitehead P, Atwood CS, Caffarra P, Hampel H, Quintela I, Carracedo Á, Lannfelt L, Rubinsztein DC, Barnes LL, Pasquier F, Frölich L, Barral S, McGuinness B, Beach TG, Johnston JA, Becker JT, Passmore P, Bigio EH, Schott JM, Bird TD, Warren JD, Boeve BF, Lupton MK, Bowen JD, Proitsi P, Boxer A, Powell JF, Burke JR, Kauwe JSK, Burns JM, Mancuso M, Buxbaum JD, Bonuccelli U, Cairns NJ, McQuillin A, Cao C, Livingston G, Carlson CS, Bass NJ, Carlsson CM, Hardy J, Carney RM, Bras J, Carrasquillo MM, Guerreiro R, Allen M, Chui HC, Fisher E, Masullo C, Crocco EA, DeCarli C, Bisceglio G, Dick M, Ma L, Duara R, Graff-Radford NR, Evans DA, Hodges A, Faber KM, Scherer M, Fallon KB, Riemenschneider M, Fardo DW, Heun R, Farlow MR, Kölsch H, Ferris S, Leber M, Foroud TM, Heuser I, Galasko DR, Giegling I, Gearing M, Hüll M, Geschwind DH, Gilbert JR, Morris J, Green RC, Mayo K, Growdon JH, Feulner T, Hamilton RL, Harrell LE, Drichel D, Honig LS, Cushion TD, Huentelman MJ, Hollingworth P, Hulette CM, Hyman BT, Marshall R, Jarvik GP, Meggy A, Abner E, Menzies GE, Jin LW, Leonenko G, Real LM, Jun GR, Baldwin CT, Grozeva D, Karydas A, Russo G, Kaye JA, Kim R, Jessen F, Kowall NW, Vellas B, Kramer JH, Vardy E, LaFerla FM, Jöckel KH, Lah JJ, Dichgans M, Leverenz JB, Mann D, Levey AI, Pickering-Brown S, Lieberman AP, Klopp N, Lunetta KL, Wichmann HE, Lyketsos CG, Morgan K, Marson DC, Brown K, Martiniuk F, Medway C, Mash DC, Nöthen MM, Masliah E, Hooper NM, McCormick WC, Daniele A, McCurry SM, Bayer A, McDavid AN, Gallacher J, McKee AC, van den Bussche H, Mesulam M, Brayne C, Miller BL, Riedel-Heller S, Miller CA, Miller JW, Al-Chalabi A, Morris JC, Shaw CE, Myers AJ, Wiltfang J, O'Bryant S, Olichney JM, Alvarez V, Parisi JE, Singleton AB, Paulson HL, Collinge J, Perry WR, Mead S, Peskind E, Cribbs DH, Rossor M, Pierce A, Ryan NS, Poon WW, Nacmias B, Potter H, Sorbi S, Quinn JF, Sacchinelli E, Raj A, Spalletta G, Raskind M, Caltagirone C, Bossù P, Orfei MD, Reisberg B, Clarke R, Reitz C, Smith AD, Ringman JM, Warden D, Roberson ED, Wilcock G, Rogaeva E, Bruni AC, Rosen HJ, Gallo M, Rosenberg RN, Ben-Shlomo Y, Sager MA, Mecocci P, Saykin AJ, Pastor P, Cuccaro ML, Vance JM, Schneider JA, Schneider LS, Slifer S, Seeley WW, Smith AG, Sonnen JA, Spina S, Stern RA, Swerdlow RH, Tang M, Tanzi RE, Trojanowski JQ, Troncoso JC, Van Deerlin VM, Van Eldik LJ, Vinters HV, Vonsattel JP, Weintraub S, Welsh-Bohmer KA, Wilhelmsen KC, Williamson J, Wingo TS, Woltjer RL, Wright CB, Yu CE, Yu L, Saba Y, Pilotto A, Bullido MJ, Peters O, Crane PK, Bennett D, Bosco P, Coto E, Boccardi V, De Jager PL, Lleo A, Warner N, Lopez OL, Ingelsson M, Deloukas P, Cruchaga C, Graff C, Gwilliam R, Fornage M, Goate AM, Sanchez-Juan P, Kehoe PG, Amin N, Ertekin-Taner N, Berr C, Debette S, Love S, Launer LJ, Younkin SG, Dartigues JF, Corcoran C, Ikram MA, Dickson DW, Nicolas G, Campion D, Tschanz J, Schmidt H, Hakonarson H, Clarimon J, Munger R, Schmidt R, Farrer LA, Van Broeckhoven C, O'Donovan MC, DeStefano AL, Jones L, Haines JL, Deleuze JF, Owen MJ, Gudnason V, Mayeux R, Escott-Price V, Psaty BM, Ramirez A, Wang LS, Ruiz A, van Duijn CM, Holmans PA, Seshadri S, Williams J, Amouyel P, Schellenberg GD, Lambert JC, and Pericak-Vance MA
Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Published: 2019
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44. Identification of Novel RAS Signaling Therapeutic Vulnerabilities in Diffuse Intrinsic Pontine Gliomas.

Author: Koncar RF, Dey BR, Stanton AJ, Agrawal N, Wassell ML, McCarl LH, Locke AL, Sanders L, Morozova-Vaske O, Myers MI, Hamilton RL, Carcaboso AM, Kohanbash G, Hu B, Amankulor NM, Felker J, Kambhampati M, Nazarian J, Becher OJ, James CD, Hashizume R, Broniscer A, Pollack IF, and Agnihotri S
Subjects: Aniline Compounds pharmacology, Animals, Brain Stem Neoplasms drug therapy, Brain Stem Neoplasms genetics, Brain Stem Neoplasms pathology, Cell Line, Tumor, Cell Proliferation genetics, Diffuse Intrinsic Pontine Glioma drug therapy, Diffuse Intrinsic Pontine Glioma genetics, Diffuse Intrinsic Pontine Glioma pathology, Female, Gene Expression Regulation, Neoplastic, Genes, myc, Histones genetics, Histones metabolism, Humans, Indoles pharmacology, Lysine genetics, Lysine metabolism, Male, Mice, SCID, Mitogen-Activated Protein Kinase 7 antagonists & inhibitors, Mitogen-Activated Protein Kinase 7 genetics, Mitogen-Activated Protein Kinase 7 metabolism, Neural Stem Cells metabolism, Proto-Oncogene Mas, Receptor, Platelet-Derived Growth Factor alpha genetics, Receptor, Platelet-Derived Growth Factor alpha metabolism, ras Proteins genetics, Brain Stem Neoplasms metabolism, Diffuse Intrinsic Pontine Glioma metabolism, Mutation, ras Proteins metabolism
Abstract: Diffuse intrinsic pontine gliomas (DIPG) are incurable brain tumors with an aggressive onset. Apart from irradiation, there are currently no effective therapies available for patients with DIPG, who have a median survival time of less than one year. Most DIPG cells harbor mutations in genes encoding histone H3 (H3K27M) proteins, resulting in a global reduction of H3K27 trimethylation and activation of oncogenic signaling pathways. Here we show that the H3K27M mutations contribute to RAS pathway signaling, which is augmented by additional RAS activators including PDGFRA. H3K27M mutation led to increased expression of receptor tyrosine kinases (RTK). A RAS pathway functional screen identified ERK5, but not ERK1/2, as a RAS pathway effector important for DIPG growth. Suppression of ERK5 decreased DIPG cell proliferation and induced apoptosis in vitro and in vivo . In addition, depletion or inhibition of ERK5 significantly increased survival of mice intracranially engrafted with DIPG cells. Mechanistically, ERK5 directly stabilized the proto-oncogene MYC at the protein level. Collectively, our data demonstrate an underappreciated role of H3K27M in RAS activation and reveal novel therapeutic targets for treating DIPG tumors. SIGNIFICANCE: These findings identify the H3K27M mutation as an enhancer of RAS activation in DIPG and ERK5 as a novel, immediately actionable molecular target. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/79/16/4026/F1.large.jpg., (©2019 American Association for Cancer Research.)
Published: 2019
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45. Clinical Utility of GlioSeq Next-Generation Sequencing Test in Pediatric and Young Adult Patients With Brain Tumors.

Author: Roy S, Agnihotri S, El Hallani S, Ernst WL, Wald AI, Santana Dos Santos L, Hamilton RL, Horbinski CM, Wadhwani NR, Born DE, Pollack IF, Nikiforov YE, and Nikiforova MN
Abstract: Brain tumors are the leading cause of death in children. Establishing an accurate diagnosis and therapy is critical for patient management. This study evaluated the clinical utility of GlioSeq, a next-generation sequencing (NGS) assay, for the diagnosis and management of pediatric and young adult patients with brain tumors. Between May 2015 and March 2017, 142 consecutive brain tumors were tested using GlioSeq v1 and subset using GlioSeq v2. Out of 142 samples, 63% were resection specimens and 37% were small stereotactic biopsies. GlioSeq sequencing was successful in 100% and 98.6% of the cases for the detection of mutations and copy number changes, and gene fusions, respectively. Average turnaround time was 8.7 days. Clinically significant genetic alterations were detected in 95%, 66.6%, and 66.1% of high-grade gliomas, medulloblastomas, and low-grade gliomas, respectively. GlioSeq enabled molecular-based stratification in 92 (65%) cases by specific molecular subtype assignment (70, 76.1%), substantiating a neuropathologic diagnosis (18, 19.6%), and diagnostic recategorization (4, 4.3%). Fifty-seven percent of the cases harbored therapeutically actionable findings. GlioSeq NGS analysis offers rapid detection of a wide range of genetic alterations across a spectrum of pediatric brain tumors using formalin-fixed, paraffin-embedded specimens and facilitates integrated molecular-morphologic classification and personalized management of pediatric brain tumors., (© 2019 American Association of Neuropathologists, Inc. All rights reserved.)
Published: 2019
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46. Standardizing Brain Cancer Reporting.

Author: Glatzel M and Hamilton RL
Published: 2019
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47. Examination and prognostic implications of the unique microenvironment of breast cancer brain metastases.

Author: Sambade MJ, Prince G, Deal AM, Trembath D, McKee M, Garrett A, Keith K, Ramirez J, Midkiff B, Blackwell K, Sammons S, Leone JP, Brufsky A, Morikawa A, Brogi E, Seidman A, Ewend M, Carey LA, Moschos SJ, Hamilton RL, Vincent B, and Anders C
Subjects: Adult, Aged, Biological Specimen Banks, Biomarkers, Tumor immunology, Brain Neoplasms immunology, Female, Humans, Middle Aged, Prognosis, Survival Analysis, Triple Negative Breast Neoplasms immunology, Tumor Microenvironment, Brain Neoplasms secondary, Brain Neoplasms surgery, Craniotomy methods, Triple Negative Breast Neoplasms pathology
Abstract: Purpose: Brain metastases (BM) are a complication of advanced breast cancer (BC). Histology of melanoma BM offers prognostic value; however, understanding the microenvironment of breast cancer brain metastases (BCBM) is less characterized. This study reports on four histological biomarkers, gliosis, immune infiltrate, hemorrhage, necrosis, and their prognostic significance in BCBM., Methods: A biobank of 203 human tissues from patients who underwent craniotomy for BCBM was created across four academic institutions. Degree of gliosis, immune infiltrate, hemorrhage, and necrosis were identified and scored via representative H&E stain (0-3+). Overall survival (OS) was estimated using the Kaplan-Meier method. Cox proportional hazards regression evaluated prognostic value of the biomarkers in the context of standard clinical characteristics., Results: BCBM subtype (available for n = 158) was 36% Her2+, 26% hormone receptor (HR)+/Her2- 38% HR-/Her2- (triple negative, TN). Gliosis was observed in 82% (116/141) of BCBM, with immune infiltrate 44% (90/201), hemorrhage 82% (166/141), and necrosis 87% (176/201). Necrosis was significantly higher in TNBC (p < 0.01). Presence of gliosis, immune infiltrate, and hemorrhage correlated with improved OS (p = 0.03, p = 0.03, p = 0.1), while necrosis correlated with inferior OS (p = 0.01). Improved OS was associated with gliosis in TN (p = 0.02), and immune infiltrate (p = 0.001) and hemorrhage (p = 0.07) in HER2+. In a multivariable model for OS, incorporating these biomarkers with traditional clinical variables improved the model fit (p < 0.001)., Conclusion: Gliosis confers superior prognosis in TNBC BM; immune infiltrate and hemorrhage correlate with superior prognosis in HER2+ BCBM. Understanding the metastatic microenvironment of BCBM refines prognostic considerations and may unveil novel therapeutic strategies.
Published: 2019
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48. Transcriptome Characterization of Matched Primary Breast and Brain Metastatic Tumors to Detect Novel Actionable Targets.

Author: Varešlija D, Priedigkeit N, Fagan A, Purcell S, Cosgrove N, O'Halloran PJ, Ward E, Cocchiglia S, Hartmaier R, Castro CA, Zhu L, Tseng GC, Lucas PC, Puhalla SL, Brufsky AM, Hamilton RL, Mathew A, Leone JP, Basudan A, Hudson L, Dwyer R, Das S, O'Connor DP, Buckley PG, Farrell M, Hill ADK, Oesterreich S, Lee AV, and Young LS
Subjects: Adult, Animals, Brain Neoplasms secondary, Breast Neoplasms pathology, Case-Control Studies, Female, Follow-Up Studies, Gene Expression Profiling, Humans, Longitudinal Studies, Mice, Middle Aged, Neoplasm Recurrence, Local pathology, Prognosis, Survival Rate, Xenograft Model Antitumor Assays, Biomarkers, Tumor genetics, Brain Neoplasms genetics, Breast Neoplasms genetics, Gene Expression Regulation, Neoplastic, Neoplasm Recurrence, Local genetics, Transcriptome
Abstract: Background: Breast cancer brain metastases (BrMs) are defined by complex adaptations to both adjuvant treatment regimens and the brain microenvironment. Consequences of these alterations remain poorly understood, as does their potential for clinical targeting. We utilized genome-wide molecular profiling to identify therapeutic targets acquired in metastatic disease., Methods: Gene expression profiling of 21 patient-matched primary breast tumors and their associated brain metastases was performed by TrueSeq RNA-sequencing to determine clinically actionable BrM target genes. Identified targets were functionally validated using small molecule inhibitors in a cohort of resected BrM ex vivo explants (n = 4) and in a patient-derived xenograft (PDX) model of BrM. All statistical tests were two-sided., Results: Considerable shifts in breast cancer cell-specific gene expression profiles were observed (1314 genes upregulated in BrM; 1702 genes downregulated in BrM; DESeq; fold change > 1.5, Padj < .05). Subsequent bioinformatic analysis for readily druggable targets revealed recurrent gains in RET expression and human epidermal growth factor receptor 2 (HER2) signaling. Small molecule inhibition of RET and HER2 in ex vivo patient BrM models (n = 4) resulted in statistically significantly reduced proliferation (P < .001 in four of four models). Furthermore, RET and HER2 inhibition in a PDX model of BrM led to a statistically significant antitumor response vs control (n = 4, % tumor growth inhibition [mean difference; SD], anti-RET = 86.3% [1176; 258.3], P < .001; anti-HER2 = 91.2% [1114; 257.9], P < .01)., Conclusions: RNA-seq profiling of longitudinally collected specimens uncovered recurrent gene expression acquisitions in metastatic tumors, distinct from matched primary tumors. Critically, we identify aberrations in key oncogenic pathways and provide functional evidence for their suitability as therapeutic targets. Altogether, this study establishes recurrent, acquired vulnerabilities in BrM that warrant immediate clinical investigation and suggests paired specimen expression profiling as a compelling and underutilized strategy to identify targetable dependencies in advanced cancers., (© The Author(s) 2018. Published by Oxford University Press.)
Published: 2019
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49. Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing.

Author: Kunkle BW, Grenier-Boley B, Sims R, Bis JC, Damotte V, Naj AC, Boland A, Vronskaya M, van der Lee SJ, Amlie-Wolf A, Bellenguez C, Frizatti A, Chouraki V, Martin ER, Sleegers K, Badarinarayan N, Jakobsdottir J, Hamilton-Nelson KL, Moreno-Grau S, Olaso R, Raybould R, Chen Y, Kuzma AB, Hiltunen M, Morgan T, Ahmad S, Vardarajan BN, Epelbaum J, Hoffmann P, Boada M, Beecham GW, Garnier JG, Harold D, Fitzpatrick AL, Valladares O, Moutet ML, Gerrish A, Smith AV, Qu L, Bacq D, Denning N, Jian X, Zhao Y, Del Zompo M, Fox NC, Choi SH, Mateo I, Hughes JT, Adams HH, Malamon J, Sanchez-Garcia F, Patel Y, Brody JA, Dombroski BA, Naranjo MCD, Daniilidou M, Eiriksdottir G, Mukherjee S, Wallon D, Uphill J, Aspelund T, Cantwell LB, Garzia F, Galimberti D, Hofer E, Butkiewicz M, Fin B, Scarpini E, Sarnowski C, Bush WS, Meslage S, Kornhuber J, White CC, Song Y, Barber RC, Engelborghs S, Sordon S, Voijnovic D, Adams PM, Vandenberghe R, Mayhaus M, Cupples LA, Albert MS, De Deyn PP, Gu W, Himali JJ, Beekly D, Squassina A, Hartmann AM, Orellana A, Blacker D, Rodriguez-Rodriguez E, Lovestone S, Garcia ME, Doody RS, Munoz-Fernadez C, Sussams R, Lin H, Fairchild TJ, Benito YA, Holmes C, Karamujić-Čomić H, Frosch MP, Thonberg H, Maier W, Roshchupkin G, Ghetti B, Giedraitis V, Kawalia A, Li S, Huebinger RM, Kilander L, Moebus S, Hernández I, Kamboh MI, Brundin R, Turton J, Yang Q, Katz MJ, Concari L, Lord J, Beiser AS, Keene CD, Helisalmi S, Kloszewska I, Kukull WA, Koivisto AM, Lynch A, Tarraga L, Larson EB, Haapasalo A, Lawlor B, Mosley TH, Lipton RB, Solfrizzi V, Gill M, Longstreth WT Jr, Montine TJ, Frisardi V, Diez-Fairen M, Rivadeneira F, Petersen RC, Deramecourt V, Alvarez I, Salani F, Ciaramella A, Boerwinkle E, Reiman EM, Fievet N, Rotter JI, Reisch JS, Hanon O, Cupidi C, Andre Uitterlinden AG, Royall DR, Dufouil C, Maletta RG, de Rojas I, Sano M, Brice A, Cecchetti R, George-Hyslop PS, Ritchie K, Tsolaki M, Tsuang DW, Dubois B, Craig D, Wu CK, Soininen H, Avramidou D, Albin RL, Fratiglioni L, Germanou A, Apostolova LG, Keller L, Koutroumani M, Arnold SE, Panza F, Gkatzima O, Asthana S, Hannequin D, Whitehead P, Atwood CS, Caffarra P, Hampel H, Quintela I, Carracedo Á, Lannfelt L, Rubinsztein DC, Barnes LL, Pasquier F, Frölich L, Barral S, McGuinness B, Beach TG, Johnston JA, Becker JT, Passmore P, Bigio EH, Schott JM, Bird TD, Warren JD, Boeve BF, Lupton MK, Bowen JD, Proitsi P, Boxer A, Powell JF, Burke JR, Kauwe JSK, Burns JM, Mancuso M, Buxbaum JD, Bonuccelli U, Cairns NJ, McQuillin A, Cao C, Livingston G, Carlson CS, Bass NJ, Carlsson CM, Hardy J, Carney RM, Bras J, Carrasquillo MM, Guerreiro R, Allen M, Chui HC, Fisher E, Masullo C, Crocco EA, DeCarli C, Bisceglio G, Dick M, Ma L, Duara R, Graff-Radford NR, Evans DA, Hodges A, Faber KM, Scherer M, Fallon KB, Riemenschneider M, Fardo DW, Heun R, Farlow MR, Kölsch H, Ferris S, Leber M, Foroud TM, Heuser I, Galasko DR, Giegling I, Gearing M, Hüll M, Geschwind DH, Gilbert JR, Morris J, Green RC, Mayo K, Growdon JH, Feulner T, Hamilton RL, Harrell LE, Drichel D, Honig LS, Cushion TD, Huentelman MJ, Hollingworth P, Hulette CM, Hyman BT, Marshall R, Jarvik GP, Meggy A, Abner E, Menzies GE, Jin LW, Leonenko G, Real LM, Jun GR, Baldwin CT, Grozeva D, Karydas A, Russo G, Kaye JA, Kim R, Jessen F, Kowall NW, Vellas B, Kramer JH, Vardy E, LaFerla FM, Jöckel KH, Lah JJ, Dichgans M, Leverenz JB, Mann D, Levey AI, Pickering-Brown S, Lieberman AP, Klopp N, Lunetta KL, Wichmann HE, Lyketsos CG, Morgan K, Marson DC, Brown K, Martiniuk F, Medway C, Mash DC, Nöthen MM, Masliah E, Hooper NM, McCormick WC, Daniele A, McCurry SM, Bayer A, McDavid AN, Gallacher J, McKee AC, van den Bussche H, Mesulam M, Brayne C, Miller BL, Riedel-Heller S, Miller CA, Miller JW, Al-Chalabi A, Morris JC, Shaw CE, Myers AJ, Wiltfang J, O'Bryant S, Olichney JM, Alvarez V, Parisi JE, Singleton AB, Paulson HL, Collinge J, Perry WR, Mead S, Peskind E, Cribbs DH, Rossor M, Pierce A, Ryan NS, Poon WW, Nacmias B, Potter H, Sorbi S, Quinn JF, Sacchinelli E, Raj A, Spalletta G, Raskind M, Caltagirone C, Bossù P, Orfei MD, Reisberg B, Clarke R, Reitz C, Smith AD, Ringman JM, Warden D, Roberson ED, Wilcock G, Rogaeva E, Bruni AC, Rosen HJ, Gallo M, Rosenberg RN, Ben-Shlomo Y, Sager MA, Mecocci P, Saykin AJ, Pastor P, Cuccaro ML, Vance JM, Schneider JA, Schneider LS, Slifer S, Seeley WW, Smith AG, Sonnen JA, Spina S, Stern RA, Swerdlow RH, Tang M, Tanzi RE, Trojanowski JQ, Troncoso JC, Van Deerlin VM, Van Eldik LJ, Vinters HV, Vonsattel JP, Weintraub S, Welsh-Bohmer KA, Wilhelmsen KC, Williamson J, Wingo TS, Woltjer RL, Wright CB, Yu CE, Yu L, Saba Y, Pilotto A, Bullido MJ, Peters O, Crane PK, Bennett D, Bosco P, Coto E, Boccardi V, De Jager PL, Lleo A, Warner N, Lopez OL, Ingelsson M, Deloukas P, Cruchaga C, Graff C, Gwilliam R, Fornage M, Goate AM, Sanchez-Juan P, Kehoe PG, Amin N, Ertekin-Taner N, Berr C, Debette S, Love S, Launer LJ, Younkin SG, Dartigues JF, Corcoran C, Ikram MA, Dickson DW, Nicolas G, Campion D, Tschanz J, Schmidt H, Hakonarson H, Clarimon J, Munger R, Schmidt R, Farrer LA, Van Broeckhoven C, C O'Donovan M, DeStefano AL, Jones L, Haines JL, Deleuze JF, Owen MJ, Gudnason V, Mayeux R, Escott-Price V, Psaty BM, Ramirez A, Wang LS, Ruiz A, van Duijn CM, Holmans PA, Seshadri S, Williams J, Amouyel P, Schellenberg GD, Lambert JC, and Pericak-Vance MA
Subjects: Aged, Case-Control Studies, Female, Genetic Testing methods, Genome-Wide Association Study methods, Haplotypes genetics, Humans, Lipid Metabolism genetics, Male, Alzheimer Disease genetics, Amyloid beta-Peptides genetics, Genetic Loci genetics, Genetic Predisposition to Disease genetics, Immunity genetics, Lipids genetics, tau Proteins genetics
Abstract: Risk for late-onset Alzheimer's disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (IQCK, ACE, ADAM10, ADAMTS1, and WWOX), two of which (ADAM10, ACE) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimer's or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and Aβ processing are associated not only with early-onset autosomal dominant Alzheimer's disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (P = 1.32 × 10 -7 ), indicating that additional rare variants remain to be identified. We also identify important genetic correlations between LOAD and traits such as family history of dementia and education.
Published: 2019
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50. Clinical metric for differentiating intracranial hemangiopericytomas from meningiomas using diffusion weighted MRI.

Author: El-Ali AM, Agarwal V, Thomas A, Hamilton RL, and Filippi CG
Subjects: Adult, Aged, Aged, 80 and over, Brain Neoplasms diagnostic imaging, Brain Neoplasms pathology, Diagnosis, Differential, Female, Hemangiopericytoma diagnostic imaging, Hemangiopericytoma pathology, Humans, Magnetic Resonance Imaging methods, Male, Meningeal Neoplasms diagnostic imaging, Meningeal Neoplasms pathology, Meningioma diagnostic imaging, Meningioma pathology, Middle Aged, Sensitivity and Specificity, Young Adult, Brain Neoplasms diagnosis, Diffusion Magnetic Resonance Imaging methods, Hemangiopericytoma diagnosis, Meningeal Neoplasms diagnosis, Meningioma diagnosis
Abstract: Purpose: Intracranial Hemangiopericytomas (IHP) are dural based tumors that frequently recur/metastasize. Unfortunately, their imaging appearance overlaps significantly with more benign meningiomas. We evaluated the use of diffusion weighted imaging (DWI) to differentiate IHP from meningioma., Methods: We compared MRI of IHP tumors (WHO Grades II/III) (n = 20) to meningioma (n = 48, WHO Grade I/II)., Findings: ADC values differed between IHP (1.05 × 10-3 mm2/s) and meningiomas (0.89 × 10-3 mm2/s) (p = 0.05). Normalized ADC ratios (nADC), differed between IHP and meningiomas (1.30 vs 1.07, p = 0.03)., Conclusion: Importantly, a nADC cutoff of >1.3 was specific (96%) but not sensitive (35%) for identifying IHP., (Copyright © 2018 Elsevier Inc. All rights reserved.)
Published: 2019
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