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1. Coronal Heating as Determined by the Solar Flare Frequency Distribution Obtained by Aggregating Case Studies

Author

Mason, James Paul, Werth, Alexandra, West, Colin G., Youngblood, Allison A., Woodraska, Donald L., Peck, Courtney, Lacjak, Kevin, Frick, Florian G., Gabir, Moutamen, Alsinan, Reema A., Jacobsen, Thomas, Alrubaie, Mohammad, Chizmar, Kayla M., Lau, Benjamin P., Dominguez, Lizbeth Montoya, Price, David, Butler, Dylan R., Biron, Connor J., Feoktistov, Nikita, Dewey, Kai, Loomis, N. E., Bodzianowski, Michal, Kuybus, Connor, Dietrick, Henry, Wolfe, Aubrey M., Guerrero, Matt, Vinson, Jessica, Starbuck, Peter, Litton, Shelby D, Beck, M. G., Fisch, Jean-Paul, West, Ayana, Muniz, Alexis A., Chavez, Luis, Upthegrove, Zachary T., Runyon, Brenton M., Salazar, J., Kritzberg, Jake E., Murrel, Tyler, Ho, Ella, LaFemina, Quintin Y., Elbashir, Sara I., Chang, Ethan C., Hudson, Zachary A., Nussbaum, Rosemary O., Kennedy, Kellen, Kim, Kevin, Arango, Camila Villamil, Albakr, Mohammed A., Rotter, Michael, Garscadden, A. J., Salcido-Alcontar JR, Antonio, Pearl, Harrison M., Stepaniak, Tyler, Marquez, Josie A., Marsh, Lauren, Andringa, Jesse C, Osogwin, Austin, Shields, Amanda M., Brookins, Sarah, Hach, Grace K., Clausi, Alexis R., Millican, Emily B., Jaimes, Alan A, Graham, Alaina S., Burritt, John J., Perez, J. S., Ramirez, Nathaniel, Suri, Rohan, Myer, Michael S., Kresek, Zoe M., Goldsberry, C. A., Payne, Genevieve K., Jourabchi, Tara, Hu, J., Lucca, Jeffrey, Feng, Zitian, Gilpatrick, Connor B., Khan, Ibraheem A., Warble, Keenan, Sweeney, Joshua D., Dorricott, Philip, Meyer, Ethan, Kothamdi, Yash S., Sohail, Arman S., Grell, Kristyn, Floyd, Aidan, Bard, Titus, Mathieson, Randi M., Reed, Joseph, Cisneros, Alexis, Payne, Matthew P., Jarriel, J. R., Mora, Jacqueline Rodriguez, Sundell, M. E., Patel, Kajal, Alesmail, Mohammad, Alnasrallah, Yousef A, Abdullah, Jumana T., Molina-Saenz, Luis, Tayman, K. E., Brown, Gabriel T., Kerr-Layton, Liana, Berriman-Rozen, Zachary D., Hiatt, Quinn, Kalra, Etash, Ong, Jason, Vadayar, Shreenija, Shannahan, Callie D., Benke, Evan, zhang, Jinhua, Geisman, Jane, Martyr, Cara, Ameijenda, Federico, Akruwala, Ushmi H., Nehring, Molly, Kissner, Natalie, Rule, Ian C., Learned, Tyler, Smith, Alexandra N., Mazzotta, Liam, Rounsefell, Tyndall, Eyeson, Elizabeth A., Shelby, Arlee K., Moll, Tyler S, Menke, Riley, Shahba, Hannan, House Jr., Tony A., Clark, David B., Burns, Annemarie C., de La Beaujardiere, Tristan, Trautwein, Emily D., Plantz, Will, Reeves, Justin, Faber, Ian, Buxton, B. W., Highhouse, Nigel, Landrey, Kalin, Hansen, Connor M, Chen, Kevin, Hales, Ryder Buchanan, Borgerding, Luke R., Guo, Mutian, Crow, Christian J., Whittall, Lloyd C., Simmons, Conor, Folarin, Adeduni, Parkinson, Evan J., Rahn, Anna L., Blevins, Olivia, Morelock, Annalise M., Kelly, Nicholas, Parker, Nathan L., Smith, Kelly, Plzak, Audrey E., Saeb, David, Hares, Cameron T., Parker, Sasha R., McCoy, Andrew, Pham, Alexander V., Lauzon, Megan, Kennedy, Cayla J., Reyna, Andrea B., Acosta, Daniela M. Meza, Cool, Destiny J., Steinbarth, Sheen L., Mendoza-Anselmi, Patricia, Plutt, Kaitlyn E., Kipp, Isabel M, Rakhmonova, M., Brown, Cameron L., Van Anne, Gabreece, Moss, Alexander P., Golden, Olivia, Kirkpatrick, Hunter B., Colleran, Jake R., Sullivan, Brandon J, Tran, Kevin, Carpender, Michael Andrew, Mundy, Aria T., Koenig, Greta, Oudakker, Jessica, Engelhardt, Rasce, Ales, Nolan, Wexler, Ethan Benjamin, Beato, Quinn I, Chen, Lily, Cochran, Brooke, Hill, Paula, Hamilton, Sean R., Hashiro, Kyle, Khan, Usman, Martinez, Alexa M., Brockman, Jennifer L., Mallory, Macguire, Reed, Charlie, Terrile, Richard, Singh, Savi, Watson, James Adam, Creany, Joshua B., Price, Nicholas K., Miften, Aya M., Tran, Bryn, Kamenetskiy, Margaret, Martinez, Jose R., Opp, Elena N., Huang, Jianyang, Fails, Avery M., Belei, Brennan J., Slocum, Ryan, Astalos, Justin, East, Andrew, Nguyen, Lena P., Pherigo, Callie C, East, Andrew N., Li, David Y., Nelson, Maya LI, Taylor, Nicole, Odbayar, Anand, Rives, Anna Linnea, Mathur, Kabir P., Billingsley, Jacob, Polikoff, Hyden, Driscoll, Michael, Wilson, Orion K., Lahmers, Kyle, Toon, Nathaniel J., Lippincott, Sam, Musgrave, Andrew J., Gregory, Alannah H., Pitsuean-Meier, Sedique, Jesse, Trevor, Smith, Corey, Miles, Ethan J., Kainz, Sabrina J. H. T., Ji, Soo Yeun, Nguyen, Lena, Aryan, Maryam, Dinser, Alexis M., Shortman, Jadon, Bastias, Catalina S, Umbricht, Thomas D, Cage, Breonna, Randolph, Parker, Pollard, Matthew, Simone, Dylan M., Aramians, Andrew, Brecl, Ariana E., Robert, Amanda M., Zenner, Thomas, Saldi, Maxwell, Morales, Gavin, Mendez, Citlali, Syed, Konner, Vogel, Connor Maklain, Cone, Rebecca A., Berhanu, Naomi, Carpenter, Emily, Leoni, Cecilia, Bryan, Samuel, Ramachandra, Nidhi, Shaw, Timothy, Lee, E. C., Monyek, Eli, Wegner, Aidan B., Sharma, Shajesh, Lister, Barrett, White, Jamison R., Willard, John S., Sulaiman, S. A, Blandon, Guillermo, Narayan, Anoothi, Ruger, Ryan, Kelley, Morgan A., Moreno, Angel J., Balcer, Leo M, Ward-Chene, N. R. D., Shelby, Emma, Reagan, Brian D., Marsh, Toni, Sarkar, Sucheta, Kelley, Michael P., Fell, Kevin, Balaji, Sahana, Hildebrand, Annalise K., Shoha, Dominick, Nandu, Kshmya, Tucker, Julia, Cancio, Alejandro R., Wang, Jiawei, Rapaport, Sarah Grace, Maravi, Aimee S., Mayer, Victoria A., Miller, Andrew, Bence, Caden, Koke, Emily, Fauntleroy, John T, Doermer, Timothy, Al-Ghazwi, Adel, Morgan, Remy, Alahmed, Mohammed S., Mathavan, Adam Izz Khan Mohd Reduan, Silvester, H. K., Weiner, Amanda M., Liu, Nianzi, Iovan, Taro, Jensen, Alexander V., AlHarbi, Yazeed A., Jiang, Yufan, Zhang, Jiaqi, Jones, Olivia M., Huang, Chenqi, Reh, Eileen N., Alhamli, Dania, Pettine, Joshua, Zhou, Chongrui, Kriegman, Dylan, Yang, Jianing, Ash, Kevin, Savage, Carl, Kaiser, Emily, Augenstein, Dakota N., Padilla, Jacqueline, Stark, Ethan K., Hansen, Joshua A., Kokes, Thomas, Huynh, Leslie, Sanchez-Sanchez, Gustavo, Jeseritz, Luke A., Carillion, Emma L., Vepa, Aditya V., Khanal, Sapriya, Behr, Braden, Martin, Logan S., McMullan, Jesse J., Zhao, Tianwei, Williams, Abigail K., Alqabani, Emeen, Prinster, Gale H., Horne, Linda, Ruggles-Delgado, Kendall, Otto, Grant, Gomez, Angel R., Nguyen, Leonardo, Brumley, Preston J., Venegas, Nancy Ortiz, Varela, Ilian, Brownlow, Jordi, Cruz, Avril, Leiker, Linzhi, Batra, Jasleen, Hutabarat, Abigail P., Nunes-Valdes, Dario, Jameson, Connor, Naqi, Abdulaziz, Adams, Dante Q., Biediger, Blaine B., Borelli, William T, Cisne, Nicholas A., Collins, Nathaniel A., Curnow, Tyler L., Gopalakrishnan, Sean, Griffin, Nicholas F., Herrera, Emanuel, McGarvey, Meaghan V., Mellett, Sarah, Overchuk, Igor, Shaver, Nathan, Stratmeyer, Cooper N., Vess, Marcus T., Juels, Parker, Alyami, Saleh A., Gale, Skylar, Wallace, Steven P., Hunter, Samuel C, Lonergan, Mia C., Stewart, Trey, Maksimuk, Tiffany E., Lam, Antonia, Tressler, Judah, Napoletano, Elena R., Miller, Joshua B., Roy, Marc G., Chanders, Jasey, Fischer, Emmalee, Croteau, A. 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H., Vassilyev, Alexandr, Witkoff, Briahn, Wolle, Jackson R., Dice, Kenzie A., Behrer, Timothy A., Bowen, Troy, Campbell, Andrew J, Clarkson, Peter C, Duong, Tien Q., Hawat, Elijah, Lopez, Christian, Olson, Nathaniel P., Osborn, Matthew, Peou, Munisettha E., Vaver, Nicholas J., Husted, Troy, Kallemeyn, Nicolas Ian, Spangler, Ava A, Mccurry, Kyle, Schultze, Courtney, Troisi, Thomas, Thomas, Daniel, Ort, Althea E., Singh, Maya A., Soon, Caitlin, Patton, Catherine, Billman, Jayce A., Jarvis, Sam, Hitt, Travis, Masri, Mirna, Albalushi, Yusef J., Schofer, Matthew J, Linnane, Katherine B., Knott, Philip Whiting, Valencia, Whitney, Arias-Robles, Brian A., Ryder, Diana, Simone, Anna, Abrams, Jonathan M., Belknap, Annelene L., Rouse, Charlotte, Reynolds, Alexander, Petric, Romeo S. L., Gomez, Angel A., Meiselman-Ashen, Jonah B., Carey, Luke, Dias, John S., Fischer-White, Jules, Forbes, Aidan E., Galarraga, Gabriela, Kennedy, Forrest, Lawlor, Rian, Murphy, Maxwell J., Norris, Cooper, Quarderer, Josh, Waller, Caroline, Weber, Robert J., Gunderson, Nicole, Boyne, Tom, Gregory, Joshua A., Propper, Henry Austin, von Peccoz, Charles B. Beck, Branch, Donovan, Clarke, Evelyn, Cutler, Libby, Dabberdt, Frederick M., Das, Swagatam, Figueirinhas, John Alfred D., Fougere, Benjamin L., Roy, Zoe A., Zhao, Noah Y., Cox, Corben L., Barnhart, Logan D. W., Craig, Wilmsen B., Moll, Hayden, Pohle, Kyle, Mueller, Alexander, Smith, Elena K., Spicer, Benjamin C., Aycock, Matthew C., Bat-Ulzii, Batchimeg, Murphy, Madalyn C., Altokhais, Abdullah, Thornally, Noah R., Kleinhaus, Olivia R., Sarfaraz, Darian, Barnes, Grant M., Beard, Sara, Banda, David J, Davis, Emma A. B., Huebsch, Tyler J., Wagoner, Michaela, Griego, Justus, Hale, Jack J. 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V., Recchia, John C., Lengerich, Dylan, Taulman, Kyle, Romero, Andres C., Steward, Ellie N., Russell, Sloan, Hardwick, Dillon F., Wootten, Katelynn, Nguyen, Valerie A., Quispe, Devon, Ragsdale, Cameron, Young, Isabel, Atchley-Rivers, N. S., Stribling, Jordin L., Gentile, Julia G, Boeyink, Taylor A., Kwiatkowski, Daniel, Dupeyron, Tomi Oshima, Crews, Anastasia, Shuttleworth, Mitchell, Dresdner, Danielle C., Flackett, Lydia, Haratsaris, Nicholas, Linger, Morgan I, Misener, Jay H., Patti, Samuel, Pine, Tawanchai P., Marikar, Nasreen, Matessi, Giorgio, Routledge, Allie C., Alkaabi, Suhail, Bartman, Jessica L., Bisacca, Gabrielle E., Busch, Celeste, Edwards, Bree, Staudenmier, Caitlyn, Starling, Travis, McVey, Caden, Montano, Maximus, Contizano, Charles J., Taylor, Eleanor, McIntyre, James K., Victory, Andrew, McCammon, Glen S., Kimlicko, Aspen, Sheldrake, Tucker, Shelchuk, Grace, Von Reich, Ferin J., Hicks, Andrew J., O'neill, Ian, Rossman, Beth, Taylor, Liam C., MacDonald, William, Becker, Simone E., Han, Soonhee, O'Sullivan, Cian, Wilcove, Isaac, Brennan, David J., Hanley, Luke C., Hull, Owen, Wilson, Timothy R., Kalmus, Madison H., Berv, Owen A., Harris, Logan Swous, Doan, Chris H, Londres, Nathan, Parulekar, Anish, Adam, Megan M., Angwin, Abigail, Cabbage, Carter C., Colleran, Zachary, Pietras, Alex, Seux, Octave, Oros, Ryan, Wilkinson, Blake C., Nguyen, Khoa D, Trank-Greene, Maedee, Barone, Kevin M., Snyder, G. L., Biehle, Samuel J, Billig, Brennen, Almquist, Justin Thomas, Dixon, Alyssa M., Erickson, Benjamin, Evans, Nathan, Genne, SL, Kelly, Christopher M, Marcus, Serafima M., Ogle, Caleb, Patel, Akhil, Vendetti, Evan, Courtney, Olivia, Deel, Sean, Del Foco, Leonardo, Gjini, Michael, Haines, Jessica, Hoff, Isabelle J., Jones, M. R., Killian, Dominic, Kuehl, Kirsten, Kuester, Chrisanne, Lantz, Maxwell B., Lee, Christian J, Mauer, Graham, McKemey, Finbar K., Millican, Sarah J., Rosasco, Ryan, Stewart, T. C., VanEtten, Eleanor, Derwin, Zachary, Serio, Lauren, Sickler, Molly G., Blake, Cassidy A., Patel, Neil S., Fox, Margaret, Gray, Michael J, Ziegler, Lucas J., Kumar, Aman Priyadarshi, Polly, Madelyn, Mesgina, Sarah, McMorris, Zane, Griffin, Kyle J., Haile, L. N., Bassel, Claire, Dixon, Thomas J., Beattie, Ryan, Houck, Timothy J, Rodgers, Maeve, Trofino, Tyson R., Lukianow, Dax, Smart, Korben, Hall, Jacqueline L., Bone, Lauren, Baldwin, James O., Doane, Connor, Almohsen, Yousef A., Stamos, Emily, Acha, Iker, Kim, Jake, Samour II, Antonio E., Chavali, S., Kanokthippayakun, Jeerakit, Gotlib, Nicholas, Murphy, Ryan C., Archibald, Jack. W., Brimhall, Alexander J, Boyer, Aidan, Chapman, Logan T., Chadda, Shivank, Sibrell, Lisa, Vallery, Mia M., Conroy, Thomas C., Pan, Luke J., Balajonda, Brian, Fuhrman, Bethany E. S., Alkubaisi, Mohamed, Engelstad, Jacob, Dodrill, Joshua, Fuchs, Calvin R., Bullard-Connor, Gigi, Alhuseini, Isehaq, Zygmunt, James C., Sipowicz, Leo, Hayrynen, Griffin A., McGill, Riley M., Keating, Caden J., Hart, Omer, Cyr, Aidan St., Steinsberger, Christopher H., Thoman, Gerig, Wood, Travis M., Ingram, Julia A., Dominguez, J., Georgiades, Nathaniel James, Johnson, Matthew, Johnson, Sawyer, Pedersen, Alexander J., Ralapanawe, Anoush K, Thomas, Jeffrey J., Sato, Ginn A., Reynolds, Hope, Nasser, Liebe, Mizzi, Alexander Z., Damgaard, Olivia, Baflah, Abdulrahman A., Liu, Steven Y., Salindeho, Adam D., Norden, Kelso, Gearhart, Emily E., Krajnak, Zack, Szeremeta, Philip, Amos, Meggan, Shin, Kyungeun, Muckenthaler, Brandon A., Medialdea, Melissa, Beach, Simone, Wilson, Connor B., Adams, Elena R, Aldhamen, Ahmed, Harris, Coyle M., Hesse, Troy M., Golding, Nathan T., Larter, Zachary, Hernandez, Angel, Morales, Genaro, Traxler, Robert B., Alosaimi, Meshal, Fitton, Aidan F., Aaron, James Holland, Lee, Nathaniel F., Liao, Ryan Z., Chen, Judy, French, Katherine V., Loring, Justin, Colter, Aurora, McConvey, Rowan, Colozzi, Michael, Vann, John D., Scheck, Benjamin T., Weigand, Anthony A, Alhabeeb, Abdulelah, Idoine, Yolande, Woodard, Aiden L., Medellin, Mateo M., Ratajczyk, Nicholas O, Tobin, Darien P., Collins, Jack C., Horning, Thomas M., Pellatz, Nick, Pitten, John, Lordi, Noah, Patterson, Alyx, Hoang, Thi D, Zimmermann, Ingrid H, Wang, Hongda, Steckhahn, Daniel, Aradhya, Arvind J., Oliver, Kristin A., Cai, Yijian, Wang, Chaoran, Yegovtsev, Nikolay, Wu, Mengyu, Ganesan, Koushik, Osborne, Andrew, Wickenden, Evan, Meyer, Josephine C., Chaparro, David, Visal, Aseem, Liu, Haixin, Menon, Thanmay S., Jin, Yan, Wilson, John, Erikson, James W., Luo, Zheng, Shitara, Nanako, Nelson, Emma E, Geerdts, T. R., Ortiz, Jorge L Ramirez, and Lewandowski, H. J.

Subjects
Astrophysics - Solar and Stellar Astrophysics
Abstract

Flare frequency distributions represent a key approach to addressing one of the largest problems in solar and stellar physics: determining the mechanism that counter-intuitively heats coronae to temperatures that are orders of magnitude hotter than the corresponding photospheres. It is widely accepted that the magnetic field is responsible for the heating, but there are two competing mechanisms that could explain it: nanoflares or Alfv\'en waves. To date, neither can be directly observed. Nanoflares are, by definition, extremely small, but their aggregate energy release could represent a substantial heating mechanism, presuming they are sufficiently abundant. One way to test this presumption is via the flare frequency distribution, which describes how often flares of various energies occur. If the slope of the power law fitting the flare frequency distribution is above a critical threshold, $\alpha=2$ as established in prior literature, then there should be a sufficient abundance of nanoflares to explain coronal heating. We performed $>$600 case studies of solar flares, made possible by an unprecedented number of data analysts via three semesters of an undergraduate physics laboratory course. This allowed us to include two crucial, but nontrivial, analysis methods: pre-flare baseline subtraction and computation of the flare energy, which requires determining flare start and stop times. We aggregated the results of these analyses into a statistical study to determine that $\alpha = 1.63 \pm 0.03$. This is below the critical threshold, suggesting that Alfv\'en waves are an important driver of coronal heating., Comment: 1,002 authors, 14 pages, 4 figures, 3 tables, published by The Astrophysical Journal on 2023-05-09, volume 948, page 71

Published
2023
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3. Matched control analysis suggests that R-CHOP followed by (R)-ICE may improve outcome in non-GCB DLBCL compared with R-CHOP

Author

Bantilan, Kurt S., Smith, Alexandra N., Maurer, Matthew J., Teruya-Feldstein, Julie, Matasar, Matthew J., Moskowitz, Alison J., Straus, David J., Noy, Ariela, Palomba, M. Lia, Horwitz, Steven M., Hamlin, Paul A., Portlock, Carol S., Cerhan, James R., Habermann, Thomas M., Salles, Gilles A., Nowakowski, Grzegorz S., Moskowitz, Craig H., and Zelenetz, Andrew D.

Published
2024
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4. Sex-Specific Correlates of Metabolic Syndrome Risk in College-Aged Young Adults

Author

Higgins, Simon, Smith, Alexandra N., Williams, Ewan R., Das, Bhibha M., Fedewa, Michael V., and Evans, Ellen M.

Abstract

Objective: To identify the sex-specific prevalence of metabolic syndrome (MetS) risk factors and their physiological, psychosocial, and behavioral correlates in a college-aged population. Participants and methods: Cross-sectional assessment of MetS risk factors and potential correlates occurred in 379 first-year students (aged 18.34 ± 0.49 years, 67.3% female). Multivariable linear regression assessed the relationships between potential correlates and continuous MetS risk scores, derived from principal component analysis. Results: MetS risk factors were present in 58.4% of females and 68.5% of males, with 2.4% and 3.2% having defined MetS. In females, percent body fat ([beta] = 0.46, p < 0.001), stress ([beta] = 0.12, p = 0.031), % kcal from sugar ([beta] = 0.18, p = 0.001), and moderate-to-vigorous physical activity ([beta]=-0.12, p = 0.036) were associated with risk score. Whereas, correlates in males included percent body fat ([beta] = 0.54, p < 0.001), C-reactive protein ([beta] = 0.15, p = 0.045), and AUDIT alcohol consumption score ([beta] = 0.15, p = 0.033). Conclusion: The sex-specific prevalence of MetS risk factors and correlates suggest that primary prevention strategies on college campuses should also follow a sex-specific approach.

Published
2022
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8. Coronal Heating as Determined by the Solar Flare Frequency Distribution Obtained by Aggregating Case Studies

Author

Mason, James Paul, primary, Werth, Alexandra, additional, West, Colin G., additional, Youngblood, Allison, additional, Woodraska, Donald L., additional, Peck, Courtney L., additional, Aradhya, Arvind J., additional, Cai, Yijian, additional, Chaparro, David, additional, Erikson, James W., additional, Ganesan, Koushik, additional, Geerdts, T. R., additional, Hoang, Thi D, additional, Horning, Thomas M., additional, Jin, Yan, additional, Liu, Haixin, additional, Lordi, Noah, additional, Luo, Zheng, additional, Menon, Thanmay S., additional, Meyer, Josephine C., additional, Nelson, Emma E, additional, Oliver, Kristin A., additional, Ramirez Ortiz, Jorge L, additional, Osborne, Andrew, additional, Patterson, Alyx, additional, Pellatz, Nick, additional, Pitten, John, additional, Shitara, Nanako, additional, Steckhahn, Daniel, additional, Visal, Aseem, additional, Wang, Hongda, additional, Wang, Chaoran, additional, Wickenden, Evan, additional, Wilson, John, additional, Wu, Mengyu, additional, Yegovtsev, Nikolay, additional, Zimmermann, Ingrid H, additional, Aaron, James Holland, additional, Abdullah, Jumana T., additional, Abrams, Jonathan M., additional, Abrashoff, Riley, additional, Acevedo, Andres B., additional, Acha, Iker, additional, Meza Acosta, Daniela M., additional, Adam, Megan M., additional, Adams, Dante Q., additional, Adams, Kalvyn N, additional, Adams, Elena R, additional, Akbar, Zainab A., additional, Akruwala, Ushmi H., additional, Al-Ghazwi, Adel, additional, Alabbas, Batool H., additional, Alawadhi, Areej A., additional, Alharbi, Yazeed A., additional, Alahmed, Mohammed S., additional, Albakr, Mohammed A., additional, Albalushi, Yusef J., additional, Albaum, Jonathan, additional, Aldhamen, Ahmed, additional, Ales, Nolan, additional, Alesmail, Mohammad, additional, Alhabeeb, Abdulelah, additional, Alhamli, Dania, additional, Alhuseini, Isehaq, additional, Alkaabi, Suhail, additional, Alkhezzi, Tameem, additional, Alkubaisi, Mohamed, additional, Allanqawi, Nasser, additional, Allsbrook, Martin, additional, Almohsen, Yousef A., additional, Almquist, Justin Thomas, additional, Alnaji, Teeb, additional, Alnasrallah, Yousef A, additional, Alonzi, Nicholas, additional, Alosaimi, Meshal, additional, Alqabani, Emeen, additional, Alrubaie, Mohammad, additional, Alsinan, Reema A., additional, Altenbern, Ava L., additional, Altokhais, Abdullah, additional, Alyami, Saleh A., additional, Ameijenda, Federico, additional, Amer, Hamzi, additional, Amos, Meggan, additional, Anderson, Hunter J., additional, Andrew, Carter, additional, Andringa, Jesse C, additional, Angwin, Abigail, additional, Van Anne, Gabreece, additional, Aramians, Andrew, additional, Arango, Camila Villamil, additional, Archibald, Jack. W., additional, Arias-Robles, Brian A., additional, Aryan, Maryam, additional, Ash, Kevin, additional, Astalos, Justin, additional, Atchley-Rivers, N. S., additional, Augenstein, Dakota N., additional, Austin, Bryce W., additional, Avula, Abhinav, additional, Aycock, Matthew C., additional, Baflah, Abdulrahman A., additional, Balaji, Sahana, additional, Balajonda, Brian, additional, Balcer, Leo M, additional, Baldwin, James O., additional, Banda, David J, additional, Bard, Titus, additional, Barmore, Abby, additional, Barnes, Grant M., additional, Barnhart, Logan D. W., additional, Barone, Kevin M., additional, Bartman, Jessica L., additional, Bassel, Claire, additional, Bastias, Catalina S, additional, Bat-Ulzii, Batchimeg, additional, Batra, Jasleen, additional, Battist, Lexi, additional, Bay, Joshua, additional, Beach, Simone, additional, Beard, Sara, additional, Beato, Quinn I, additional, Beattie, Ryan, additional, Beatty, Thomas, additional, De La Beaujardiere, Tristan, additional, Beauprez, Jacob N., additional, Beck, M. G., additional, Beck, Lily, additional, Becker, Simone E., additional, Behr, Braden, additional, Behrer, Timothy A., additional, Beijer, Joshua, additional, Belei, Brennan J., additional, Belknap, Annelene L., additional, Bell, Aislyn, additional, Bence, Caden, additional, Benke, Evan, additional, Berhanu, Naomi, additional, Berriman-Rozen, Zachary D., additional, Bertuccio, Chrisanna, additional, Berv, Owen A., additional, Biediger, Blaine B., additional, Biehle, Samuel J, additional, Billig, Brennen, additional, Billingsley, Jacob, additional, Billman, Jayce A., additional, Biron, Connor J., additional, Bisacca, Gabrielle E., additional, Blake, Cassidy A., additional, Blandon, Guillermo, additional, Blevins, Olivia, additional, Blouin, Ethan, additional, Bodzianowski, Michal, additional, Boeyink, Taylor A., additional, Bondar, Matthew, additional, Bone, Lauren, additional, De Los Monteros Bonilla, Alberto Espinosa, additional, Borelli, William T, additional, Borgerding, Luke R., additional, Bowen, Troy, additional, Boyer, Christine, additional, Boyer, Aidan, additional, Boyle, Aidan P., additional, Boyne, Tom, additional, Branch, Donovan, additional, Brecl, Ariana E., additional, Brennan, David J., additional, Brimhall, Alexander J, additional, Brockman, Jennifer L., additional, Brookins, Sarah, additional, Brown, Gabriel T., additional, Brown, Cameron L., additional, Brown, Ryan, additional, Brownlow, Jordi, additional, Brumage-Heller, Grant, additional, Brumley, Preston J., additional, Bryan, Samuel, additional, Brzostowicz, A., additional, Buhamad, Maryam, additional, Bullard-Connor, Gigi, additional, Bunsow, J. R. Ramirez, additional, Burns, Annemarie C., additional, Burritt, John J., additional, Burton, Nicholas David, additional, Burton, Taylor, additional, Busch, Celeste, additional, Butler, Dylan R., additional, Buxton, B. W., additional, C. Toups, Malena, additional, Cabbage, Carter C., additional, Cage, Breonna, additional, Cahn, Jackson R., additional, Campbell, Andrew J, additional, Canales, Braden P., additional, Cancio, Alejandro R., additional, Carey, Luke, additional, Carillion, Emma L., additional, Carpender, Michael Andrew, additional, Carpenter, Emily, additional, Chadda, Shivank, additional, Chambers, Paige, additional, Chanders, Jasey, additional, Chandler, Olivia M., additional, Chang, Ethan C., additional, Chapman, Mitchell G., additional, Chapman, Logan T., additional, Chavali, S., additional, Chavez, Luis, additional, Chen, Kevin, additional, Chen, Lily, additional, Chen, Sam, additional, Chen, Judy, additional, Chhetri, Jenisha, additional, Chiles, Bradyn, additional, Chizmar, Kayla M., additional, Christiansen, Katherine E, additional, Cisne, Nicholas A., additional, Cisneros, Alexis, additional, Clark, David B., additional, Clarke, Evelyn, additional, Clarkson, Peter C, additional, Clausi, Alexis R., additional, Cochran, Brooke, additional, Coe, Ryan W., additional, Coleman-Plante, Aislinn, additional, Colleran, Jake R., additional, Colleran, Zachary, additional, Collier, Curran, additional, Collins, Nathaniel A., additional, Collins, Sarah, additional, Collins, Jack C., additional, Colozzi, Michael, additional, Colter, Aurora, additional, Cone, Rebecca A., additional, Conroy, Thomas C., additional, Conti, Reese, additional, Contizano, Charles J., additional, Cool, Destiny J., additional, Cooper, Nicholas M., additional, Corbitt, Jessica S, additional, Courtney, Jonas, additional, Courtney, Olivia, additional, Cox, Corben L., additional, Craig, Wilmsen B., additional, Creany, Joshua B., additional, Crews, Anastasia, additional, Crocker, K. A., additional, Croteau, A. J., additional, Crow, Christian J., additional, Cruse, Zoe, additional, Cruz, Avril, additional, Curnow, Tyler L., additional, Current, Hayden, additional, Curry, Riley T., additional, Cutler, Libby, additional, Cyr, Aidan St., additional, Dabberdt, Frederick M., additional, Daboub, Johnston, additional, Damgaard, Olivia, additional, Das, Swagatam, additional, Davis, Emma A. B., additional, Debarros, Elyse, additional, Deel, Sean, additional, Delasantos, Megan E., additional, Deng, Tianyue, additional, Derwin, Zachary, additional, Desai, Om, additional, Dewey, Kai, additional, Dias, John S., additional, Dice, Kenzie A., additional, Dick, R., additional, Dicken, Cyrus A., additional, Dietrick, Henry, additional, Dinser, Alexis M., additional, Dixon, Alyssa M., additional, Dixon, Thomas J., additional, Do, Helen C., additional, Doan, Chris H, additional, Doane, Connor, additional, Dodrill, Joshua, additional, Doermer, Timothy, additional, Dominguez, Lizbeth Montoya, additional, Dominguez, J., additional, Domke, Emerson N., additional, Doran, Caroline R., additional, Dorr, Jackson A., additional, Dorricott, Philip, additional, Dresdner, Danielle C., additional, Driscoll, Michael, additional, Driscoll, Kailer H., additional, Duncan, Sheridan J., additional, Dunlap, Christian, additional, Dunn, Gabrielle M., additional, Duong, Tien Q., additional, Dupeyron, Tomi Oshima, additional, Dvorak, Peter, additional, East, Andrew, additional, East, Andrew N., additional, Edwards, Bree, additional, Ehrlich, Lauren, additional, Elbashir, Sara I., additional, Engelhardt, Rasce, additional, Engelstad, Jacob, additional, England, Colin, additional, Enrich, Andrew, additional, Erickson, Abbey, additional, Erickson, Benjamin, additional, Evans, Nathan, additional, Ewing, Calvin A, additional, Eyeson, Elizabeth A., additional, Faber, Ian, additional, Fails, Avery M., additional, Fauntleroy, John T, additional, Fell, Kevin, additional, Feng, Zitian, additional, Fenwick, Logan D., additional, Feoktistov, Nikita, additional, Fife, Ryann, additional, D. Figueirinhas, John Alfred, additional, Fisch, Jean-Paul, additional, Fischer, Emmalee, additional, Fischer-White, Jules, additional, Fitton, Aidan F., additional, Fix, Alexander, additional, Flackett, Lydia, additional, Flores, Fernando, additional, Floyd, Aidan, additional, Del Foco, Leonardo, additional, Folarin, Adeduni, additional, Forbes, Aidan E., additional, Fortino, Elise, additional, Fougere, Benjamin L., additional, Fowler, Alexandra A., additional, Fox, Margaret, additional, French, James M., additional, French, Katherine V., additional, Frick, Florian G., additional, Fuchs, Calvin R., additional, Fuhrman, Bethany E. S., additional, Furney, Sebastian, additional, Gabir, Moutamen, additional, Galarraga, Gabriela, additional, Gale, Skylar, additional, Gapin, Keala C., additional, Garscadden, A. J., additional, Gasser, Rachel, additional, Gayou, Lily, additional, Gearhart, Emily E., additional, Geisman, Jane, additional, Geneser, Julianne R., additional, Genne, Sl, additional, Gentile, Julia G, additional, Gentry, Eleanor, additional, George, Jacob D., additional, Georgiades, Nathaniel James, additional, Gerhardstein, Phillip, additional, Gersabeck, Clint, additional, Ghaith, Bandar Abu, additional, Ghiassi, Dorsa, additional, Giebner, B. C., additional, Gilmartin, Dalton, additional, Gilpatrick, Connor B., additional, Gjini, Michael, additional, Golden, Olivia, additional, Golding, Nathan T., additional, Goldsberry, C. A., additional, Gomez, Angel R., additional, Gomez, Angel A., additional, Gopalakrishnan, Sean, additional, Gopalani, Mariam, additional, Gotlib, Nicholas, additional, Graham, Alaina S., additional, Gray, Michael J, additional, Gregory, Alannah H., additional, Gregory, Joshua A., additional, Grell, Kristyn, additional, Griego, Justus, additional, Griffin, Nicholas F., additional, Griffin, Kyle J., additional, Guerrero, Matt, additional, Gunderson, Nicole, additional, Guo, Mutian, additional, Gustavsson, E. R., additional, Hach, Grace K., additional, Haile, L. N., additional, Haines, Jessica, additional, Mc Hale, Jack J., additional, Hales, Ryder Buchanan, additional, Haley, Mark S., additional, Hall, Jacqueline L., additional, Hamilton, Sean R., additional, Han, Soonhee, additional, Hand, Tyler, additional, Hanley, Luke C., additional, Hansen, Connor M, additional, Hansen, Joshua A., additional, Hansson, Jonathan, additional, Hao, Tony Yunfei, additional, Haratsaris, Nicholas, additional, Hardie, Isabelle, additional, Hardwick, Dillon F., additional, Hares, Cameron T., additional, Harris, Logan Swous, additional, Harris, Coyle M., additional, Hart, Omer, additional, Hashiro, Kyle, additional, Hattendorf, Elsie, additional, Haubrich, Calder, additional, Hawat, Elijah, additional, Hayrynen, Griffin A., additional, Heintz, Danielle A., additional, Hellweg, Tim, additional, Hernandez, Angel, additional, Herrera, Emanuel, additional, Herrington, Robert N., additional, Herwig, Tim, additional, Hesse, Troy M., additional, Hiatt, Quinn, additional, Hibbard, Lea Pearl, additional, Hicks, Imari R., additional, Hicks, Andrew J., additional, Highhouse, Nigel, additional, Hildebrand, Annalise K., additional, Hill, Paula, additional, Hill, Hallie, additional, Hintsa, Evan, additional, Hirschmann, Anna E., additional, Hitt, Travis, additional, Ho, Ella, additional, Hoff, Isabelle J., additional, Hoffman, Alex, additional, Hogen, Blake A., additional, Horne, Linda, additional, Houck, Timothy J, additional, Howell, Noah H., additional, Hrudka, E. M., additional, Hu, J., additional, Huang, Jianyang, additional, Huang, Chenqi, additional, Huang, Shancheng, additional, Hudson, Zachary A., additional, Hudson, Nathan C., additional, Huebsch, Tyler J., additional, Hull, Owen, additional, Hunter, Samuel C, additional, Husted, Troy, additional, Hutabarat, Abigail P., additional, Huynh, Leslie, additional, Samour Ii, Antonio E., additional, Idoine, Yolande, additional, Ingram, Julia A., additional, Iovan, Taro, additional, Isert, Samuel A., additional, Salcido-Alcontar, Antonio, additional, Jacobsen, Thomas, additional, Jaimes, Alan A, additional, Jameson, Connor, additional, Jarriel, J. R., additional, Jarvis, Sam, additional, Jenkins, Josh, additional, Jensen, Alexander V., additional, Jeong, Jacob, additional, Jeseritz, Luke A., additional, Jesse, Trevor, additional, Ji, Soo Yeun, additional, Jiang, Yufan, additional, Johnson, Owen, additional, Johnson, Matthew, additional, Johnson, Sawyer, additional, Johnston, Julia, additional, Johnston, Braedon Y., additional, Jones, Olivia M., additional, Jones, M. R., additional, Jourabchi, Tara, additional, House, Tony A., additional, Juels, Parker, additional, T. Kainz, Sabrina J. H., additional, Kaiser, Emily, additional, Kallemeyn, Nicolas Ian, additional, Kalmus, Madison H., additional, Kalra, Etash, additional, Kamenetskiy, Margaret, additional, Kanokthippayakun, Jeerakit, additional, Kapla, Shaun D., additional, Karsh, Brennan J., additional, Keating, Caden J., additional, Kelley, Morgan A., additional, Kelley, Michael P., additional, Kelly, Nicholas, additional, Kelly, James, additional, Kelly, Teagan, additional, Kelly, Christopher M, additional, Kennedy, Kellen, additional, Kennedy, Cayla J., additional, Kennedy, Forrest, additional, Kennedy, Abigail, additional, Kerr-Layton, Liana, additional, Ketterer, Marilyn, additional, Khan, Ibraheem A., additional, Khan, Usman, additional, Khanal, Sapriya, additional, Kiechlin, Jack L., additional, Killian, Dominic, additional, Kim, Kevin, additional, Kim, Brian T., additional, Kim, Matthew M., additional, Kim, Jake, additional, Kimlicko, Aspen, additional, Kipp, Isabel M, additional, Kirkpatrick, Hunter B., additional, Kissner, Natalie, additional, Kite, Emily R., additional, Kleinhaus, Olivia R., additional, Knott, Philip Whiting, additional, Koch, Will, additional, Koenig, Greta, additional, Koke, Emily, additional, Kokes, Thomas, additional, Kothamdi, Yash S., additional, Krajnak, Zack, additional, Kresek, Zoe M., additional, Kriegman, Dylan, additional, Kritzberg, Jake E., additional, Krueger, Davis J., additional, Kubiak, Bartlomiej, additional, Kuehl, Kirsten, additional, Kuester, Chrisanne, additional, Kuiper, Nicolas A., additional, Kumar, Aman Priyadarshi, additional, Kuybus, Connor, additional, Kwiatkowski, Daniel, additional, Lafemina, Quintin Y., additional, Lacjak, Kevin, additional, Lahmers, Kyle, additional, Lam, Antonia, additional, Landrey, Kalin, additional, Lantz, Maxwell B., additional, Larter, Zachary, additional, Lau, Benjamin P., additional, Lauzon, Megan, additional, Lawlor, Rian, additional, Learned, Tyler, additional, Lee, E. C., additional, Lee, Junwon, additional, Lee, Adrianna J., additional, Lee, Justin, additional, Lee, Alexis Ying-Shan, additional, Lee, Christian J, additional, Lee, Nathaniel F., additional, Leiker, Linzhi, additional, Lengerich, Dylan, additional, Leoni, Cecilia, additional, Lezak, Adrienne R., additional, Li, David Y., additional, Li, Isaac, additional, Liao, Ryan Z., additional, Linders, Bridget, additional, Linger, Morgan I, additional, Linnane, Katherine B., additional, Lippincott, Sam, additional, Lister, Barrett, additional, Litton, Shelby D, additional, Liu, Nianzi, additional, Liu, Steven Y., additional, Logan, Timothy W., additional, Londres, Nathan, additional, Lonergan, Mia C., additional, Lookhoff, Emily, additional, Loomis, N. E., additional, Lopez, Christian, additional, Loring, Justin, additional, Lucca, Jeffrey, additional, Lukianow, Dax, additional, M. Cheang, Nathan, additional, Macdonald, William, additional, Madonna, Claire A., additional, Madsen, Kasey O., additional, Maksimuk, Tiffany E., additional, Mallory, Macguire, additional, Malone, Ryan A., additional, Maly, Blake, additional, Manzanares, Xander R., additional, Maravi, Aimee S., additional, Marcus, Serafima M., additional, Marikar, Nasreen, additional, Marquez, Josie A., additional, Marquez, Mathew J., additional, Marsh, Lauren, additional, Marsh, Toni, additional, Martin, Logan S., additional, Martinez, Alexa M., additional, Martinez, Jose R., additional, Martinez, Hazelia K., additional, Martyr, Cara, additional, Masri, Mirna, additional, Matessi, Giorgio, additional, Khan Mohd Reduan Mathavan, Adam Izz, additional, Mathieson, Randi M., additional, Mathur, Kabir P., additional, Mauer, Graham, additional, Mayer, Victoria A., additional, Mazzotta, Liam, additional, Mccammon, Glen S., additional, Mcconvey, Rowan, additional, Mccormick, Tyler, additional, Mccoy, Andrew, additional, Mcentee, Kelleen, additional, Mcgarvey, Meaghan V., additional, Mcgill, Riley M., additional, Mcintyre, James K., additional, Mckemey, Finbar K., additional, Mcmorris, Zane, additional, Mcmullan, Jesse J., additional, Mcquaid, Ella, additional, Mcvey, Caden, additional, Mccurry, Kyle, additional, Medellin, Mateo M., additional, Medialdea, Melissa, additional, Mehidic, Amar, additional, Meillon, Stella, additional, Meiselman-Ashen, Jonah B., additional, Mellett, Sarah, additional, Menassa, Dominic, additional, Mendez, Citlali, additional, Mendoza-Anselmi, Patricia, additional, Menke, Riley, additional, Mesgina, Sarah, additional, Mewhirter, William J., additional, Meyer, Ethan, additional, Miften, Aya M., additional, Miles, Ethan J., additional, Miller, Andrew, additional, Miller, Joshua B., additional, Millican, Emily B., additional, Millican, Sarah J., additional, Mills, Dylan P., additional, Minimo, Josh, additional, Misener, Jay H., additional, Mitchell, Alexander J., additional, Mizzi, Alexander Z., additional, Molina-Saenz, Luis, additional, Moll, Tyler S, additional, Moll, Hayden, additional, Montano, Maximus, additional, Montoya, Michael, additional, Monyek, Eli, additional, Mora, Jacqueline Rodriguez, additional, Morales, Gavin, additional, Morales, Genaro, additional, Morelock, Annalise M., additional, Morency, Cora, additional, Moreno, Angel J., additional, Morgan, Remy, additional, Moss, Alexander P., additional, Muckenthaler, Brandon A., additional, Mueller, Alexander, additional, Mulcahy, Owen T., additional, Mundy, Aria T., additional, Muniz, Alexis A., additional, Murphy, Maxwell J., additional, Murphy, Madalyn C., additional, Murphy, Ryan C., additional, Murrel, Tyler, additional, Musgrave, Andrew J., additional, Myer, Michael S., additional, Nandu, Kshmya, additional, Napoletano, Elena R., additional, Naqi, Abdulaziz, additional, Narayan, Anoothi, additional, Nasser, Liebe, additional, Neeland, Brenna K, additional, Nehring, Molly, additional, Nelson, Maya Li, additional, Nguyen, Lena P., additional, Nguyen, Lena, additional, Nguyen, Leonardo, additional, Nguyen, Valerie A., additional, Nguyen, Khoa D, additional, Norden, Kelso, additional, Norris, Cooper, additional, Nunes-Valdes, Dario, additional, Nussbaum, Rosemary O., additional, O’Sullivan, Cian, additional, O’Neill, Ian, additional, Oakes, S. H., additional, Odbayar, Anand, additional, Ogle, Caleb, additional, Oishi-Holder, Sean, additional, Olguin, Nicholas, additional, Olson, Nathaniel P., additional, Ong, Jason, additional, Opp, Elena N., additional, Orbidan, Dan, additional, Oros, Ryan, additional, Ort, Althea E., additional, Osborn, Matthew, additional, Osogwin, Austin, additional, Otto, Grant, additional, Oudakker, Jessica, additional, Overchuk, Igor, additional, Padgette, Hannah M., additional, Padilla, Jacqueline, additional, Palizzi, Mallory, additional, Palmgren, Madeleine L., additional, Palos, Adler, additional, Pan, Luke J., additional, Parker, Nathan L., additional, Parker, Sasha R., additional, Parkinson, Evan J., additional, Parulekar, Anish, additional, Pastor, Paige J., additional, Patel, Kajal, additional, Patel, Akhil, additional, Patel, Neil S., additional, Patti, Samuel, additional, Patton, Catherine, additional, Payne, Genevieve K., additional, Payne, Matthew P., additional, Pearl, Harrison M., additional, Beck Von Peccoz, Charles B., additional, Pedersen, Alexander J., additional, Pelster, Lily M., additional, Peou, Munisettha E., additional, Perez, J. S., additional, Perez, Freddy, additional, Pesce, Anneliese, additional, Petersen, Audrey J., additional, Peterson, B., additional, Petric, Romeo S. L., additional, Pettine, Joshua, additional, Phalen, Ethan J., additional, Pham, Alexander V., additional, Phan, Denise M., additional, Pherigo, Callie C, additional, Phillips, Lance, additional, Phillips, Justin, additional, Phommatha, Krista, additional, Pietras, Alex, additional, Pine, Tawanchai P., additional, Pitsuean-Meier, Sedique, additional, Pixley, Andrew M., additional, Plantz, Will, additional, Plummer, William C., additional, Plutt, Kaitlyn E., additional, Plzak, Audrey E., additional, Pohle, Kyle, additional, Polikoff, Hyden, additional, Pollard, Matthew, additional, Polly, Madelyn, additional, Porter, Trevor J., additional, Price, David, additional, Price, Nicholas K., additional, Prinster, Gale H., additional, Propper, Henry Austin, additional, Quarderer, Josh, additional, Quinn, Megan S., additional, Quinonez, Oliver, additional, Quispe, Devon, additional, Ragsdale, Cameron, additional, Rahn, Anna L., additional, Rakhmonova, M., additional, Ralapanawe, Anoush K, additional, Ramachandra, Nidhi, additional, Ramirez, Nathaniel, additional, Ramirez, Ariana C., additional, Ramirez, Sacha, additional, Randolph, Parker, additional, Ranjan, Anurag, additional, Rankin, Frederick C, additional, Rapaport, Sarah Grace, additional, Ratajczyk, Nicholas O, additional, Ray, Mia G. V., additional, Reagan, Brian D., additional, Recchia, John C., additional, Reddy, Brooklyn J., additional, Reed, Joseph, additional, Reed, Charlie, additional, Reeves, Justin, additional, Reh, Eileen N., additional, Von Reich, Ferin J., additional, Reyna, Andrea B., additional, Reynolds, Alexander, additional, Reynolds, Hope, additional, Rippel, Matthew, additional, Rivas, Guillermo A., additional, Rives, Anna Linnea, additional, Robert, Amanda M., additional, Robertson, Samuel M., additional, Rodgers, Maeve, additional, Rojec, Stewart, additional, Romero, Andres C., additional, Rosasco, Ryan, additional, Rossman, Beth, additional, Rotter, Michael, additional, Rounsefell, Tyndall, additional, Rouse, Charlotte, additional, Routledge, Allie C., additional, Roy, Marc G., additional, Roy, Zoe A., additional, Ruger, Ryan, additional, Ruggles-Delgado, Kendall, additional, Rule, Ian C., additional, Rumley, Madigan, additional, Runyon, Brenton M., additional, Ruprecht, Collin, additional, Russell, Bowman, additional, Russell, Sloan, additional, Ryder, Diana, additional, Saeb, David, additional, Salazar, J., additional, Salazar, Violeta, additional, Saldi, Maxwell, additional, Salgado, Jose A., additional, Salindeho, Adam D., additional, Sanchez, Ethan S., additional, Sanchez-Sanchez, Gustavo, additional, Sarfaraz, Darian, additional, Sarkar, Sucheta, additional, Sato, Ginn A., additional, Savage, Carl, additional, Schaller, Marcus T., additional, Scheck, Benjamin T., additional, Schlenker, Jared A. W., additional, Schofer, Matthew J, additional, Schubert, Stephanie H., additional, Schultze, Courtney, additional, Schumacher, Grace K, additional, Seglem, Kasper, additional, Serio, Lauren, additional, Seux, Octave, additional, Shahba, Hannan, additional, Shannahan, Callie D., additional, Sharma, Shajesh, additional, Shaver, Nathan, additional, Shaw, Timothy, additional, Shelby, Arlee K., additional, Shelby, Emma, additional, Shelchuk, Grace, additional, Sheldrake, Tucker, additional, Sherry, Daniel P., additional, Shi, Kyle Z., additional, Shields, Amanda M., additional, Shin, Kyungeun, additional, Shockley, Michael C., additional, Shoha, Dominick, additional, Shortman, Jadon, additional, Shuttleworth, Mitchell, additional, Sibrell, Lisa, additional, Sickler, Molly G., additional, Siles, Nathan, additional, Silvester, H. K., additional, Simmons, Conor, additional, Simone, Dylan M., additional, Simone, Anna, additional, Singh, Savi, additional, Singh, Maya A., additional, Sinkovic, Madeline, additional, Sipowicz, Leo, additional, Sjoroos, Chris, additional, Slocum, Ryan, additional, Slyne, Colin, additional, Smart, Korben, additional, Smith, Alexandra N., additional, Smith, Kelly, additional, Smith, Corey, additional, Smith, Elena K., additional, Smith, Samantha M., additional, Smith, Percy, additional, Smith, Trevor J, additional, Snyder, G. L., additional, Soby, Daniel A., additional, Sohail, Arman S., additional, Solorio, William J., additional, Solt, Lincoln, additional, Soon, Caitlin, additional, Spangler, Ava A, additional, Spicer, Benjamin C., additional, Srivastava, Ashish, additional, Stamos, Emily, additional, Starbuck, Peter, additional, Stark, Ethan K., additional, Starling, Travis, additional, Staudenmier, Caitlyn, additional, Steinbarth, Sheen L., additional, Steinsberger, Christopher H., additional, Stepaniak, Tyler, additional, Steward, Ellie N., additional, Stewart, Trey, additional, Stewart, T. C., additional, Stratmeyer, Cooper N., additional, Stratton, Grant L., additional, Stribling, Jordin L., additional, Sulaiman, S. A, additional, Sullivan, Brandon J, additional, Sundell, M. E., additional, Sur, Sohan N., additional, Suri, Rohan, additional, Swartz, Jason R., additional, Sweeney, Joshua D., additional, Syed, Konner, additional, Szabo, Emi, additional, Szeremeta, Philip, additional, Ta, Michael-Tan D., additional, Tanguma, Nolan C., additional, Taulman, Kyle, additional, Taylor, Nicole, additional, Taylor, Eleanor, additional, Taylor, Liam C., additional, Tayman, K. E., additional, Tellez, Yesica, additional, Terrile, Richard, additional, Tesdahl, Corey D, additional, Thielmann, Quinn N., additional, Thoman, Gerig, additional, Thomas, Daniel, additional, Thomas, Jeffrey J., additional, Thompson, William N., additional, Thornally, Noah R., additional, Tobin, Darien P., additional, Ton, Kelly, additional, Toon, Nathaniel J., additional, Tran, Kevin, additional, Tran, Bryn, additional, Trank-Greene, Maedee, additional, Trautwein, Emily D., additional, Traxler, Robert B., additional, Tressler, Judah, additional, Trofino, Tyson R., additional, Troisi, Thomas, additional, Trunko, Benjamin L., additional, Truong, Joshua K., additional, Tucker, Julia, additional, Umbricht, Thomas D, additional, Uphoff, C. H., additional, Upthegrove, Zachary T., additional, Vadayar, Shreenija, additional, Valencia, Whitney, additional, Vallery, Mia M., additional, Vanetten, Eleanor, additional, Vann, John D., additional, Varela, Ilian, additional, Vassilyev, Alexandr, additional, Vaver, Nicholas J., additional, Velamala, Anjali A., additional, Vendetti, Evan, additional, Venegas, Nancy Ortiz, additional, Vepa, Aditya V., additional, Vess, Marcus T., additional, Veta, Jenna S., additional, Victory, Andrew, additional, Vinson, Jessica, additional, Vogel, Connor Maklain, additional, Wagoner, Michaela, additional, Wallace, Steven P., additional, Wallace, Logan, additional, Waller, Caroline, additional, Wang, Jiawei, additional, Warble, Keenan, additional, Ward-Chene, N. R. D., additional, Watson, James Adam, additional, Weber, Robert J., additional, Wegner, Aidan B., additional, Weigand, Anthony A, additional, Weiner, Amanda M., additional, West, Ayana, additional, Wexler, Ethan Benjamin, additional, Wheeler, Nicola H., additional, White, Jamison R., additional, White, Zachary, additional, White, Oliver S., additional, Whittall, Lloyd C., additional, Wilcove, Isaac, additional, Wilkinson, Blake C., additional, Willard, John S., additional, Williams, Abigail K., additional, Williams, Sajan, additional, Wilson, Orion K., additional, Wilson, Evan M., additional, Wilson, Timothy R., additional, Wilson, Connor B., additional, Witkoff, Briahn, additional, Wolfe, Aubrey M., additional, Wolle, Jackson R., additional, Wood, Travis M., additional, Woodard, Aiden L., additional, Wootten, Katelynn, additional, Xiao, Catherine, additional, Yang, Jianing, additional, Yang, Zhanchao, additional, Young, Trenton J., additional, Young, Isabel, additional, Zenner, Thomas, additional, Zhang, Jiaqi, additional, Zhao, Tianwei, additional, Zhao, Tiannie, additional, Zhao, Noah Y., additional, Zhou, Chongrui, additional, Ziebold, Josh J, additional, Ziegler, Lucas J., additional, Zygmunt, James C., additional, Zhang, Jinhua, additional, and Lewandowski, H. J., additional

Published
2023
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9. Cell of origin is not associated with outcomes of relapsed or refractory diffuse large B cell lymphoma

Author

Desai, Sanjal H., primary, Mwangi, Raphael, additional, Smith, Alexandra N., additional, Maurer, Matthew J., additional, Farooq, Umar, additional, King, Rebecca L., additional, Cerhan, James R., additional, Feldman, Andrew L., additional, Habermann, Thomas M., additional, Thompson, Carrie A., additional, Wang, Yucai, additional, Ansell, Stephen M., additional, Witzig, Thomas E., additional, and Nowakowski, Grzegorz S., additional

Published
2022
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10. Behavior Change Trajectories and Metabolic Syndrome Risk Factor Clustering During the Transition to College: A Feasibility Pilot Study

Author

SMITH, ALEXANDRA N., HIGGINS, LAUREN Q., and HIGGINS, SIMON

Subjects
Original Research
Abstract

Metabolic syndrome (MetS) is typically diagnosed in adults; however, MetS risk factors are growing in prevalence during youth and young adulthood. Though the transition from high school to college is associated with adverse changes in lifestyle behaviors that may contribute to MetS risk factor development, the relationship between pre-college MetS risk status and transition-related behavior change is unknown. This prospective study aimed to describe the relationship between pre-college MetS risk status and transition-related behavior change trajectories in college-bound students. Moreover, it aimed to assess the feasibility of the study design, including acceptability to both participants and investigators, prior to implementation in a larger sample. Participants (n = 21, 18.3 ± 0.3 y/o) were assessed for MetS risk factors during their last semester of high school. Self-report behavioral data on dietary habits, physical activity, sleep, stress, and alcohol consumption were collected at baseline and during the fall and spring semesters of the first year of college. Linear mixed models revealed drastic increases in alcohol consumption (β(11) = 0.39, p < 0.001) and apparent decreases in moderate-vigorous physical activity (β(11) = −0.15, p = 0.185) during the college transition. Furthermore, 47.6% of students had ≥ 1 MetS risk factor at baseline and those with a greater number of risk factors experienced a more severe alcohol-related behavior change trajectory (β(11) = 0.29, p < 0.050). These findings highlight the importance of primordial prevention strategies against early MetS risk development, given the potential relationship with future behavioral trajectories. Future research should aim to further characterize this relationship using comprehensive, longitudinal measures that span the college transition in larger, more diverse samples.

Published
2022

11. Cell of origin is not associated with outcomes of relapsed or refractory diffuse large B cell lymphoma.

Author

Desai, Sanjal H., Mwangi, Raphael, Smith, Alexandra N., Maurer, Matthew J., Farooq, Umar, King, Rebecca L., Cerhan, James R., Feldman, Andrew L., Habermann, Thomas M., Thompson, Carrie A., Wang, Yucai, Ansell, Stephen M., Witzig, Thomas E., and Nowakowski, Grzegorz S.

Subjects
B cell lymphoma, DIFFUSE large B-cell lymphomas, GENE expression profiling, PROGNOSIS, DISEASE relapse, B cells
Abstract

Activated B cell (ABC) type diffuse large B cell lymphoma (DLBCL), double hit lymphoma (DHL) and double expressor lymphoma (DEL) have poor outcomes to frontline R‐CHOP but impact of these molecular features on outcomes of relapsed/refractory (R/R) disease is not well‐characterized. We evaluated the association of diagnostic cell of origin (COO), double hit and double expressor status with overall survival after first relapse in DLBCL patients who were enrolled into the Molecular Epidemiology Resource (MER) cohort. COO was available from immunohistochemistry (IHC) using Hans criteria or gene expression profiling (GEP) (Nanostring) on the diagnostic FFPE biopsy. Of 373 pts with R/R DLBCL, 278 had COO by IHC: 152 were GCB, 107 were non‐GCB. One hundred and fourty had COO by GEP: 44 were ABC, 65 were GCB and 13 were unclassifiable. Nineteen out of 163 (12%) were DHL; 30 out of 135 (22%) had DEL. COO, either by IHC (2 years OS GCB: 45% [CI95: 38–54] vs. non‐GCB: 44% [CI95:36–55], p > 0.05) or GEP (2 years OS ABC: 42% [CI95: 29–59] vs. GCB: 40% [CI95: 30–54], p > 0.05), was not associated with difference in OS. DHL (2 years OS 16 [CI95:6–45] vs. 45% [CI95: 34–59], p < 0.01) and DEL (2 years OS 33% [CI95: 20–56], vs. 50% [CI95: 41–60], p < 0.05) had lower OS than non‐DHL and non‐DEL/non‐DHL counterparts, respectively. COO by IHC or GEP was not associated with OS in R/R DLBCL while DHL and DEL were adverse prognostic markers in DLBCL at first relapse. [ABSTRACT FROM AUTHOR]

Published
2023
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12. Longitudinal GWAS Identifies Novel Genetic Variants and Complex Traits Associated with Resilience to Alzheimer's Disease.

Author

Phillips, Jared, Dumitrescu, Logan, Archer, Derek B, Smith, Alexandra N., Mukherjee, Shubhabrata, Lee, Michael L., Choi, Seo‐Eun, Scollard, Phoebe, Trittschuh, Emily H., Mez, Jesse B., Mahoney, Emily R., Bush, William S., Engelman, Corinne D, Lu, Qiongshi, Fardo, David W., Widaman, Keith F., Buckley, Rachel F., Mormino, Elizabeth C., Harrison, Theresa M., and Sanders, Elizabeth

Abstract

Background: We completed a large genetic analysis of resilience to cognitive decline in Alzheimer's Disease (AD) and discovered novel variants, genes, and complex traits associated with better‐than or worse‐than‐expected cognitive performance given an individual's age, sex, and APOE genotype. Method: Leveraging 15,933 non‐Hispanic white participants across four longitudinal cohort studies of aging and AD (Figure 1), our group determined the effects of genetic variants on resilience metrics using mixed‐effects regressions. Models adjusted for age, sex, APOE ε4 allele count, presence of the APOE ε2 allele and all covariate interactions with interval (years from baseline). The outcomes of interest were residual cognitive resilience, quantified from residuals in three cognitive domains (memory, executive function, and language), and combined resilience, summarized as the covariance of educational attainment with residual cognitive resilience. Post‐GWAS analyses included gene tests using MAGMA and estimates of genetic correlation with 65 complex traits using GNOVA. Result: We observed genome‐wide significant associations at multiple established AD loci, including BIN1 and CR1 (Figure 2). We observed a novel association with combined resilience on chromosome 13 (top SNP: rs11838654, MAF = 0.06, P = 4.7×10−8; Figure 3) and a novel signal on chromosome 1 approaching significance (top SNP: rs2817183, MAF = 0.41, P = 5.1×10−8). Interestingly, rs11838654 is an eQTL for four genes in hippocampus (WBP4, COG6, MRPS31, and NHLRC3I; Braineac database). We also observed an association with residual cognitive resilience on chromosome 5 that approached genome‐wide significance (top SNP: rs4482935, MAF = 0.25, P = 5.5×10−8; Figure 2). Gene‐level tests identified associations of CD2AP (P.fdr = 0.027) and ZNF146 (P.fdr = 0.049) with residual cognitive resilience and combined resilience, respectively. Additionally, we identified negative genetic correlations of combined resilience with ischemic stroke and coronary artery disease (all P.fdr<2.5×10−2; Figure 4). Conclusion: Compared to models of resilience that regress out the effects of AD neuropathology on cognition, the present models benefit from larger sample size at the cost of molecular precision. Although the genetic architecture of resilience from these less precise models more closely resembles that of clinical AD, we uncovered novel genetic drivers of resilience through this approach. Such findings will require future replication but suggest a trajectory‐based definition of resilience holds substantial promise for discovery. [ABSTRACT FROM AUTHOR]

Published
2022
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13. Sex‐specific genetic predictors of memory, executive function, and language performance.

Author

Eissman, Jaclyn M., Smith, Alexandra N., Mukherjee, Shubhabrata, Lee, Michael L., Choi, Seo‐Eun, Scollard, Phoebe, Trittschuh, Emily H., Mez, Jesse B., Bush, William S., Engelman, Corinne D., Lu, Qiongshi, Fardo, David W., Widaman, Keith F., Buckley, Rachel F., Mormino, Elizabeth C., Kunkle, Brian W., Naj, Adam C., Clark, Lindsay R., Gifford, Katherine A., and Cuccaro, Michael L.

Abstract

Background: Alzheimer's disease (AD) is more prevalent in women than men, and robust evidence shows sex differences in the biological response to the AD neuropathological cascade. However, there is a lack of large‐scale genetic studies on sex‐specific genetic predictors of AD‐related cognitive outcomes. Thus, we sought to elucidate the sex‐specific genetic etiology of memory, executive function, and language performance. Method: This study included six cohorts of cognitive aging (Nmales=7,267, Nfemales=9,518). We applied psychometric approaches to build harmonized memory, executive function, and language composite scores. Next, for all domains, we calculated slopes from the cognitive scores (two or more timepoints) with linear mixed effects models. Then we performed sex‐stratified and sex‐interaction GWAS on these phenotypes, covarying for baseline age and the first three genetic principal components. We meta‐analyzed across cohorts with a fixed‐effects model. Sensitivity analyses for all models restricted the sample to cognitively unimpaired individuals. Result: In addition to well‐established associations with cognition at the APOE locus, we identified three genetic loci that showed sex‐specific effects with cognition. A chromosome 16 locus (rs114106271), a splicing‐quantitative trait locus for RP11‐152O14.4 and LINC02180 in the testis (GTEx), associated with baseline memory performance in men (β=0.13, P=2.40×10‐8; PInteraction=8.96×10‐6; Figures 1‐2) but not in women (β=‐0.01, P=0.76). A chromosome 14 locus (rs34074573), an expression‐quantitative trait locus (GTEx) for HOMEZ (a homeobox gene), and for BCL2L2 (a previously reported AD risk gene), associated with longitudinal memory performance in men (β=‐0.01, P=4.15×10‐8; PInteraction=5.83×10‐7; Figures 3‐4) but not in women (β=0.001, P=0.09). Finally, a chromosome 6 locus (rs9382966) associated with longitudinal language performance in men with near genome‐wide significance (β=‐0.004, P=6.29×10‐8; PInteraction=2.01×10‐4) but not in women (β=‐0.0003, P=0.61). Conclusion: Our results highlight some key sex differences in the genetic architecture of cognitive outcomes. Findings further suggest that some sex‐specific genetic predictors have domain‐specific associations, providing an exciting opportunity to better understand the molecular basis of memory, executive function, and language through genomic analysis. Although our findings need to be replicated, our GWAS analyses highlight the contribution of sex‐specific genetic predictors beyond the APOE locus in conferring risk for late‐life cognitive decline. [ABSTRACT FROM AUTHOR]

Published
2022
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14. Sex differences in the genetic architecture of cognitive resilience to Alzheimer's disease.

Author

Eissman, Jaclyn M, Dumitrescu, Logan, Mahoney, Emily R, Smith, Alexandra N, Mukherjee, Shubhabrata, Lee, Michael L, Scollard, Phoebe, Choi, Seo Eun, Bush, William S, Engelman, Corinne D, Lu, Qiongshi, Fardo, David W, Trittschuh, Emily H, Mez, Jesse, Kaczorowski, Catherine C, Saucedo, Hector Hernandez, Widaman, Keith F, Buckley, Rachel F, Properzi, Michael J, and Mormino, Elizabeth C

Subjects
MULTIPLE sclerosis, HUMAN reproduction, RESEARCH, ALZHEIMER'S disease, SEQUENCE analysis, RESEARCH methodology, COGNITION, EVALUATION research, COMPARATIVE studies, DISEASE susceptibility, RESEARCH funding
Abstract

Approximately 30% of elderly adults are cognitively unimpaired at time of death despite the presence of Alzheimer's disease neuropathology at autopsy. Studying individuals who are resilient to the cognitive consequences of Alzheimer's disease neuropathology may uncover novel therapeutic targets to treat Alzheimer's disease. It is well established that there are sex differences in response to Alzheimer's disease pathology, and growing evidence suggests that genetic factors may contribute to these differences. Taken together, we sought to elucidate sex-specific genetic drivers of resilience. We extended our recent large scale genomic analysis of resilience in which we harmonized cognitive data across four cohorts of cognitive ageing, in vivo amyloid PET across two cohorts, and autopsy measures of amyloid neuritic plaque burden across two cohorts. These data were leveraged to build robust, continuous resilience phenotypes. With these phenotypes, we performed sex-stratified [n (males) = 2093, n (females) = 2931] and sex-interaction [n (both sexes) = 5024] genome-wide association studies (GWAS), gene and pathway-based tests, and genetic correlation analyses to clarify the variants, genes and molecular pathways that relate to resilience in a sex-specific manner. Estimated among cognitively normal individuals of both sexes, resilience was 20-25% heritable, and when estimated in either sex among cognitively normal individuals, resilience was 15-44% heritable. In our GWAS, we identified a female-specific locus on chromosome 10 [rs827389, β (females) = 0.08, P (females) = 5.76 × 10-09, β (males) = -0.01, P(males) = 0.70, β (interaction) = 0.09, P (interaction) = 1.01 × 10-04] in which the minor allele was associated with higher resilience scores among females. This locus is located within chromatin loops that interact with promoters of genes involved in RNA processing, including GATA3. Finally, our genetic correlation analyses revealed shared genetic architecture between resilience phenotypes and other complex traits, including a female-specific association with frontotemporal dementia and male-specific associations with heart rate variability traits. We also observed opposing associations between sexes for multiple sclerosis, such that more resilient females had a lower genetic susceptibility to multiple sclerosis, and more resilient males had a higher genetic susceptibility to multiple sclerosis. Overall, we identified sex differences in the genetic architecture of resilience, identified a female-specific resilience locus and highlighted numerous sex-specific molecular pathways that may underly resilience to Alzheimer's disease pathology. This study illustrates the need to conduct sex-aware genomic analyses to identify novel targets that are unidentified in sex-agnostic models. Our findings support the theory that the most successful treatment for an individual with Alzheimer's disease may be personalized based on their biological sex and genetic context. [ABSTRACT FROM AUTHOR]

Published
2022
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16. Cross-Species Analyses Identify Dlgap2 as a Regulator of Age-Related Cognitive Decline and Alzheimer’s Dementia

Author

Ouellette, Andrew R., primary, Neuner, Sarah M., additional, Dumitrescu, Logan, additional, Anderson, Laura C., additional, Gatti, Daniel M., additional, Mahoney, Emily R., additional, Bubier, Jason A., additional, Churchill, Gary, additional, Peters, Luanne, additional, Huentelman, Matthew J., additional, Herskowitz, Jeremy H., additional, Yang, Hyun-Sik, additional, Smith, Alexandra N., additional, Reitz, Christiane, additional, Kunkle, Brian W., additional, White, Charles C., additional, De Jager, Philip L., additional, Schneider, Julie A., additional, Bennett, David A., additional, Seyfried, Nicholas T., additional, Chesler, Elissa J., additional, Hadad, Niran, additional, Hohman, Timothy J., additional, and Kaczorowski, Catherine C., additional

Published
2020
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17. Sex‐specific genetic predictors of memory performance.

Author

Smith, Alexandra N., Dumitrescu, Logan, Mukherjee, Shubhabrata, Lee, Michael L., Choi, Seo‐Eun, Trittschuh, Emily H., Mez, Jesse, Mahoney, Emily R., Bush, William S., Engelman, Corinne D., Lu, Qiongshi, Fardo, David W., Widaman, Keith F., Buckley, Rachel F., Mormino, Elizabeth C., Harrison, Theresa M., Sanders, R. Elizabeth, Clark, Lindsay R., Gifford, Katherine A., and Vardarajan, Badri N.

Abstract

Background: There are notable sex differences in the clinical manifestation of Alzheimer's disease (AD), including differences in baseline and longitudinal changes in memory performance. However, sex‐stratified models have not been routinely incorporated into genetic studies of cognitive performance or decline. We sought to identify sex‐specific genetic predictors of memory performance in aging adults. Method: We obtained harmonized memory scores from 11,601 females and 8,885 males from 7 cohorts of cognitive aging. We calculated scores using latent variable modeling techniques anchored on overlapping neuropsychological test items across datasets to perform both sex‐stratified and sex‐interaction genome‐wide association studies in each cohort using mixed‐effects regression models to assess genetic associations with baseline memory score and rate of memory decline. Covariates included age at baseline and population principal components. We then combined results in a fixed‐effect meta‐analysis. Results: As expected, we observed robust associations at the APOE locus in males and females in both baseline and longitudinal models. Additionally, we identified a sex‐specific locus for longitudinal memory performance (interaction‐p=2.54e‐6) on chromosome 7 within LINC‐PINT that was genome‐wide significant in males (index SNP= rs66754621; p=1.62e‐8; MAF=0.20), but not females (p=0.65). This variant is in an enhancer region within several brain regions, as well as within a promoter‐anchored chromatin interaction loop and a methylation eQTL in the prefrontal cortex. No female‐specific loci were identified. Interestingly, we did observe nominal associations in baseline memory at some known AD loci, including male‐specific effects at MS4A6A, FERMT2, and KAT8 (interaction ps=0.0026, 0.027, and 0.0058, respectively) and opposing effects between males and females at INPP5D (interaction p=0.0021). Conclusion: These results highlight a novel male‐specific locus of memory performance on chromosome 7 near the LINC‐PINT gene. LINC‐PINT is upregulated in the substantia nigra in Parkinson's disease and is downregulated in multiple brain regions over the course of normal aging, making it a fascinating male‐specific candidate gene. Replicate and functional analyses of the region are ongoing to verify our finding and elucidate the biological mechanism. Our results add to the growing body of literature suggesting that there are sex‐specific genetic contributors to cognitive decline. [ABSTRACT FROM AUTHOR]

Published
2021
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18. Increased Expression of Kif11/Kinesin‐5 mRNA Offsets Cognitive Deficits In An Alzheimer's Mouse Model, Blocks Aβ‐Mediated Decreases in Long‐Term Potentiation and Spine Density, and is Associated With Better Cognitive...

Author

Lucero, Esteban M, Freund, Ron, Smith, Alexandra N., Johnson, Noah R, Dooling, Breanna, Sullivan, Emily, Prikhodko, Olga, Ahmed, Md. Mahiuddin, Bennett, David A, Hohman, Timothy J., DellAcqua, Mark, Chial, Heidi J, and Potter, Huntington

Abstract

Background: Interactions between the Aβ with intra‐ and extra‐cellular molecules disrupt neuronal structures and functions, leading to cognitive dysfunction in Alzheimer's disease (AD). We previously have shown that Aβ competitively inhibits the microtubule motor protein KIF11 (Kinesin‐5/Eg5), which regulates microtubule dynamics, cellular trafficking, neuronal migration, and neuronal structures important for learning and memory. In vitro cell culture and ex vivo electrophysiology experiments later revealed that the inhibition of KIF11 by Aβ underlies multiple phenotypes associated with AD, including decreases in LTP, breakdown of the microtubule network, and deficits in neurotransmitter receptor localization and function. Here we aimed to determine whether increased Kif11 expression overrides phenotypes associated with AD. Methods: Kif11 overexpressing mice were crossed with the 5xFAD mouse model of AD to generate 5xFAD mice that overexposes Kif11. Learning and memory of these mice was measured through the performance of 6‐8 month old mice in the radial‐arm water maze and LTP was measured by the fEPSP response to high‐frequency stimulation of the CA1 region in hippocampal slices of our transgenic mice. Primary rat neurons were transiently transfected to express human APP harboring the Swedish mutation (APPswe) with or without Kif11 overexpression to determine whether increased Kif11 expression affects Aβ‐mediated decreases in dendritic spine, We then evaluated cognitive function in amyloid positive individuals in the ROS/MAP study with their KIF11 mRNA expression in 4 brain regions, the DLPFC (N = 939), PCC (N = 527), and the CN (N = 715). Results: KIF11 overexpression overrides Aβ toxicity and rescues Aβ‐mediated decreases in LTP in hippocampal slices and dendritic spine density in cultured neurons. Furthermore, we found that spatial and working memory deficits were prevented in a 5xFAD Alzheimer's mouse model that overexpresses Kif11. Analyses of RNAseq data from human participants in the Religious Order Study and Memory and Aging (ROS/MAP) revealed that higher KIF11 expression in AD patients correlated with better cognitive performance. Conclusion: KIF11 is essential for maintaining synaptic structures and functions critical for learning and memory in AD, and preventing or overriding the inhibitory interaction of Aβ with Kif11 could be a promising therapeutic target for multiple AD phenotypes. [ABSTRACT FROM AUTHOR]

Published
2023
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21. Cross-Species Analyses Identify Dlgap2as a Regulator of Age-Related Cognitive Decline and Alzheimer’s Dementia

Author

Ouellette, Andrew R., Neuner, Sarah M., Dumitrescu, Logan, Anderson, Laura C., Gatti, Daniel M., Mahoney, Emily R., Bubier, Jason A., Churchill, Gary, Peters, Luanne, Huentelman, Matthew J., Herskowitz, Jeremy H., Yang, Hyun-Sik, Smith, Alexandra N., Reitz, Christiane, Kunkle, Brian W., White, Charles C., De Jager, Philip L., Schneider, Julie A., Bennett, David A., Seyfried, Nicholas T., Chesler, Elissa J., Hadad, Niran, Hohman, Timothy J., and Kaczorowski, Catherine C.

Abstract

Genetic mechanisms underlying age-related cognitive decline and dementia remain poorly understood. Here, we take advantage of the Diversity Outbred mouse population to utilize quantitative trait loci mapping and identify Dlgap2as a positional candidate responsible for modifying working memory decline. To evaluate the translational relevance of this finding, we utilize longitudinal cognitive measures from human patients, RNA expression from post-mortem brain tissue, data from a genome-wide association study (GWAS) of Alzheimer’s dementia (AD), and GWAS results in African Americans. We find an association between Dlgap2and AD phenotypes at the variant, gene and protein expression, and methylation levels. Lower cortical DLGAP2expression is observed in AD and is associated with more plaques and tangles at autopsy and faster cognitive decline. Results will inform future studies aimed at investigating the cross-species role of Dlgap2in regulating cognitive decline and highlight the benefit of using genetically diverse mice to prioritize novel candidates.

Published
2020
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22. Sex differences in the genetic architecture of cognitive resilience to Alzheimer's disease.

Author

Eissman JM, Dumitrescu L, Mahoney ER, Smith AN, Mukherjee S, Lee ML, Scollard P, Choi SE, Bush WS, Engelman CD, Lu Q, Fardo DW, Trittschuh EH, Mez J, Kaczorowski CC, Hernandez Saucedo H, Widaman KF, Buckley RF, Properzi MJ, Mormino EC, Yang HS, Harrison TM, Hedden T, Nho K, Andrews SJ, Tommet D, Hadad N, Sanders RE, Ruderfer DM, Gifford KA, Zhong X, Raghavan NS, Vardarajan BN, Pericak-Vance MA, Farrer LA, Wang LS, Cruchaga C, Schellenberg GD, Cox NJ, Haines JL, Keene CD, Saykin AJ, Larson EB, Sperling RA, Mayeux R, Cuccaro ML, Bennett DA, Schneider JA, Crane PK, Jefferson AL, and Hohman TJ

Subjects
Cognition, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Sex Characteristics, Alzheimer Disease genetics, Alzheimer Disease pathology, Cognitive Dysfunction genetics, Multiple Sclerosis
Abstract

Approximately 30% of elderly adults are cognitively unimpaired at time of death despite the presence of Alzheimer's disease neuropathology at autopsy. Studying individuals who are resilient to the cognitive consequences of Alzheimer's disease neuropathology may uncover novel therapeutic targets to treat Alzheimer's disease. It is well established that there are sex differences in response to Alzheimer's disease pathology, and growing evidence suggests that genetic factors may contribute to these differences. Taken together, we sought to elucidate sex-specific genetic drivers of resilience. We extended our recent large scale genomic analysis of resilience in which we harmonized cognitive data across four cohorts of cognitive ageing, in vivo amyloid PET across two cohorts, and autopsy measures of amyloid neuritic plaque burden across two cohorts. These data were leveraged to build robust, continuous resilience phenotypes. With these phenotypes, we performed sex-stratified [n (males) = 2093, n (females) = 2931] and sex-interaction [n (both sexes) = 5024] genome-wide association studies (GWAS), gene and pathway-based tests, and genetic correlation analyses to clarify the variants, genes and molecular pathways that relate to resilience in a sex-specific manner. Estimated among cognitively normal individuals of both sexes, resilience was 20-25% heritable, and when estimated in either sex among cognitively normal individuals, resilience was 15-44% heritable. In our GWAS, we identified a female-specific locus on chromosome 10 [rs827389, β (females) = 0.08, P (females) = 5.76 × 10-09, β (males) = -0.01, P(males) = 0.70, β (interaction) = 0.09, P (interaction) = 1.01 × 10-04] in which the minor allele was associated with higher resilience scores among females. This locus is located within chromatin loops that interact with promoters of genes involved in RNA processing, including GATA3. Finally, our genetic correlation analyses revealed shared genetic architecture between resilience phenotypes and other complex traits, including a female-specific association with frontotemporal dementia and male-specific associations with heart rate variability traits. We also observed opposing associations between sexes for multiple sclerosis, such that more resilient females had a lower genetic susceptibility to multiple sclerosis, and more resilient males had a higher genetic susceptibility to multiple sclerosis. Overall, we identified sex differences in the genetic architecture of resilience, identified a female-specific resilience locus and highlighted numerous sex-specific molecular pathways that may underly resilience to Alzheimer's disease pathology. This study illustrates the need to conduct sex-aware genomic analyses to identify novel targets that are unidentified in sex-agnostic models. Our findings support the theory that the most successful treatment for an individual with Alzheimer's disease may be personalized based on their biological sex and genetic context., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Published
2022
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23. Behavior Change Trajectories and Metabolic Syndrome Risk Factor Clustering During the Transition to College: A Feasibility Pilot Study.

Author

Smith AN, Higgins LQ, and Higgins S

Abstract

Metabolic syndrome (MetS) is typically diagnosed in adults; however, MetS risk factors are growing in prevalence during youth and young adulthood. Though the transition from high school to college is associated with adverse changes in lifestyle behaviors that may contribute to MetS risk factor development, the relationship between pre-college MetS risk status and transition-related behavior change is unknown. This prospective study aimed to describe the relationship between pre-college MetS risk status and transition-related behavior change trajectories in college-bound students. Moreover, it aimed to assess the feasibility of the study design, including acceptability to both participants and investigators, prior to implementation in a larger sample. Participants ( n = 21, 18.3 ± 0.3 y/o) were assessed for MetS risk factors during their last semester of high school. Self-report behavioral data on dietary habits, physical activity, sleep, stress, and alcohol consumption were collected at baseline and during the fall and spring semesters of the first year of college. Linear mixed models revealed drastic increases in alcohol consumption (β 11 = 0.39, p < 0.001) and apparent decreases in moderate-vigorous physical activity (β 11 = -0.15, p = 0.185) during the college transition. Furthermore, 47.6% of students had ≥ 1 MetS risk factor at baseline and those with a greater number of risk factors experienced a more severe alcohol-related behavior change trajectory (β 11 = 0.29, p < 0.050). These findings highlight the importance of primordial prevention strategies against early MetS risk development, given the potential relationship with future behavioral trajectories. Future research should aim to further characterize this relationship using comprehensive, longitudinal measures that span the college transition in larger, more diverse samples.

Published
2022

24. Serotonergic activation during courtship and aggression in the brown anole, Anolis sagrei .

Author

Hartline JT, Smith AN, and Kabelik D

Abstract

The role of serotonin (5-hydroxytryptamine, 5-HT) in social behavior regulation is not fully understood. While 5-HT release in nuclei of the social behavior network has generally been associated with inhibition of aggressive behavior across multiple classes of vertebrates, less is known about its effects on sexual, especially non-copulatory courtship display behaviors. Furthermore, most research has examined effects at 5-HT release sites, while studies examining the behavioral relevance of source cell populations have generated contradictory findings. This study utilized immunohistochemistry to examine the colocalization of 5-HT with Fos, an immediate early gene product and marker of neural activity, in the raphe and superior reticular nuclei of male brown anoles ( Anolis sagrei ) exposed to either aggression, courtship, or control social interactions. Supporting previous research, copulation was associated with a decrease in 5-HT activity, while a novel link between 5-HT activity and latency to non-copulatory courtship was also found. Within the aggression group, intensity and frequency of behavior were both associated with decreased 5-HT activity. An effect of social context was also seen, with anoles exposed to either courtship or aggression encounters showing decreased 5-HT activity in certain raphe and superior reticular nuclei populations compared to controls. Interestingly, context effects and behavioral effects were seen at separate brain nuclei, suggesting the presence of separate systems with distinct functional roles., Competing Interests: The authors declare there are no competing interests.

Published
2017
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