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7. Reduction of sporadic and neurofibromatosis type 2–associated vestibular schwannoma growth in vitro and in vivo after treatment with the c-Jun N-terminal kinase inhibitor AS602801

Author

Dougherty, Mark C., Shibata, Seiji B., Clark, J. Jason, Canady, Franklin J., Yates, Charles W., and Hansen, Marlan R.

Subjects
Laboratory Investigation, General Medicine
Abstract

OBJECTIVE Vestibular schwannomas (VSs) are benign nerve sheath tumors that result from mutation in the tumor suppressor gene NF2, with functional loss of the protein merlin. The authors have previously shown that c-Jun N-terminal kinase (JNK) is constitutively active in human VS cells and plays a central role in their survival by suppressing accumulation of mitochondrial superoxides, implicating JNK inhibitors as a potential systemic treatment for VS. Thus, the authors hypothesized that the adenosine 5ʹ-triphosphate–competitive JNK inhibitor AS602801 would demonstrate antitumor activity in multiple VS models. METHODS Treatment with AS602801 was tested in primary human VS cultures, human VS xenografts, and a genetic mouse model of schwannoma (Postn-Cre;Nf2flox/flox). Primary human VS cell cultures were established from freshly obtained surgical tumor specimens; treatment group media was enriched with AS602801. VS xenograft tumors were established in male athymic nude mice from freshly collected human tumor. Four weeks postimplantation, a pretreatment MRI scan was obtained, followed by 65 days of AS602801 (n = 18) or vehicle control (n = 19) treatment. Posttreatment MRI scans were used to measure final tumor volume. Tumors were then harvested. Finally, Postn-Cre;Nf2flox/flox mice were treated with AS602801 (n = 10) or a vehicle (n = 13) for 65 days. Posttreatment auditory brainstem responses were obtained. Dorsal root ganglia from Postn-Cre;Nf2flox/flox mice were then harvested. In all models, schwannoma identity was confirmed with anti-S100 staining, cell proliferation was measured with the EdU assay, and cell death was measured with terminal deoxynucleotidyl transferase–mediated dUTP nick-end labeling staining. All protocols were approved by the local institutional review board and Institutional Animal Care and Use Committees. RESULTS Treatment with AS602801 decreased cell proliferation and increased apoptosis in primary human VS cultures. The systemic administration of AS602801 in mice with human VS xenografts reduced tumor volume and cell proliferation. Last, the AS602801-treated Postn-Cre;Nf2flox/flox mice demonstrated decreased cell proliferation in glial cells in the dorsal root ganglia. However, AS602801 did not significantly delay hearing loss in Postn-Cre;Nf2flox/flox mice up to 3 months posttreatment. CONCLUSIONS The data suggest that JNK inhibition with AS602801 suppresses growth of sporadic and neurofibromatosis type 2–associated VSs. As such, AS602801 is a potential systemic therapy for VS and warrants further investigation.

Published
2022
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15. Future Approaches for Inner Ear Protection and Repair

Author

Shibata, Seiji B. and Raphael, Yehoash

Abstract

Health care professionals tending to patients with inner ear disease face inquiries about therapy options, including treatments that are being developed for future use but not yet available. The devastating outcome of sensorineural hearing loss, combined with the permanent nature of the symptoms, make these inquiries demanding and frequent. The vast information accessible online and the publicity for breakthroughs in research add to patient requests for access to advanced and innovative therapies, even before these are available for clinical use. This can sometimes be taxing on the health care provider who is in contact with the patients. Here we aim to equip the provider with information about some of the progress made for protective and reparative approaches for treating inner ears. Learning outcomes: (1) Readers will be able to explain why hearing loss is irreversible and common, (2) readers will be able to explain the importance of protective measures and the progress made in discovery and design of novel biological protective molecules, (3) readers will be able to describe reparative approaches currently under investigation (such as tissue engineering), the main difficulties in the design of such therapies and the major hurdles that remain for making novel technologies clinically viable, and (4) readers will be able to explain to their patients some of the progress in developing new treatments without making the promise of imminent clinical use. With this information, readers will be able to guide patients to make better choices for their treatment and to guide students toward research in this exciting field. (Contains 1 figure.)

Published
2010
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27. Contributors

Author

Agrawal, Sumit K., Anderson, Shane R., Arriaga, Moisés A., Aylward, Alana, Banakis Hartl, Renee M., Berenholz, Leonard P., Brackmann, Derald E., Brown, C. Scott, Carey, John P., Carrau, Ricardo L., Casazza, Geoffrey C., Cass, Nathan D., Cass, Stephen P., Cassis, Adam M., Chang, Ray C., Chen, Douglas A., Christopher, Laura H., Connell, Sarah S., Corrales, C. Eduardo, Crane, Benjamin T., Crowson, Matthew G., Cullen, Robert D., Cumpston, Evan C., DeTorres, Alvin, Dewyer, Nicholas A., Dornhoffer, John, Eppsteiner, Robert W., Erbele, Isaac D., Eshraghi, Adrien A., Fayad, Jose N., Friedman, Rick A., Gantz, Bruce J., Gardner, Gale, Gary, Celeste C., Goddard, John C., Gubbels, Samuel P., Gurgel, Richard K., Handzel, Ophir, Hetzler, Laura T., Hillman, Todd A., House, John W., Isaacson, Brandon, Jackler, Robert K., Jenkins, Herman A., Jones, Joel W., Kassam, Amin B., Kaylie, David M., Kesser, Bradley W., Kutz, J. Walter, Jr., Lee, John Y.K., Lippy, William H., Littlefield, Philip D., Liu, Yuan F., London, Nyall R., Jr., Lupo, J. Eric, Mahboubi, Hossein, Manzoor, Nauman, Maxwell, Anne K., McElveen, John T., Jr., McKenna, Michael J., McRackan, Theodore R., Mehta, Rahul, Minor, Lloyd B., Monsell, Edwin M., Muelleman, Thomas J., Nadol, Joseph B., Jr., Nassiri, Ashley M., Netterville, James L., Otto, Steven R., Parnes, Lorne S., Patel, Neil S., Peng, Kevin A., Perry, Brian P., Poe, Dennis S., Prevedello, Daniel M., Redleaf, Miriam I., Rivas, Alejandro, Roberson, Joseph B., Jr., Roberts, Daniel S., Roche, Joseph P., Roland, Peter S., Rybak, Leonard P., Santa Maria, Peter L., Schwam, Zachary G., Schwartz, Marc S., Shea, Martin Coyle, Jr., Sheehy, James L., Shelton, Clough, Shibata, Seiji B., Sinha, Saurabh, Slattery, William H., III, Sowder, Justin C., Sullivan, C. Blake, Sullivan, Christopher A., Syms, Charles A., III, Syms, Mark, Tawfik, Kareem O., Telian, Steven A., Telischi, Fred F., Tjellström, Anders, Wackym, P. Ashley, Wanna, George B., Ward, P. Daniel, Weiner, Joseph P., Weinreich, Heather M., Wiet, R. Mark, Wiet, Richard J., and Wilkinson, Eric P.

Published
2023
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31. Transmastoid and Transtemporal Drainage of Petrous Apicitis with Otitis Media.

Author

Isaac, Heba, Liu, Andrew, Shibata, Seiji B., and Hansen, Marlan R.

Subjects
ANTIBIOTICS, MASTOID process surgery, TEMPORAL bone surgery, COMPUTED tomography, INTRAVENOUS therapy, MAGNETIC resonance imaging, OTITIS media, TEMPORAL bone diseases, TREATMENT effectiveness, MEDICAL drainage, DISEASE complications
Abstract

Background: Petrous apicitis (PA) is a serious infection involving the apical portion of the petrous temporal bone. The classic triad of purulent otorrhea, ipsilateral abducens nerve palsy and retroorbital pain is rarely seen due to early detection and widespread use of antibiotics. Medical management is the primary treatment modality with surgery reserved for cases of recalcitrant petrous apex abscess. Methods and Results: We presented a case of PA with previously untreated otitis media. After multidisciplinary evaluation, the patient was initially treated with intravenous antibiotics followed by drainage of the abscess using a combined transmastoid and middle cranial fossa (MCF) approach. The patient recovered well with no recurrence of the infection based on imaging and symptoms. Discussion: While a variety of different surgical approaches can be used in treatment of PA, we recommend the MCF approach in cases where access to the anterior petrous apex may be challenging via transcanal or transmastoid approach. [ABSTRACT FROM AUTHOR]

Published
2021
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32. Effects of Neurod1 Expression on Mouse and Human Schwannoma Cells.

Author

Kersigo, Jennifer, Gu, Lintao, Xu, Linjing, Pan, Ning, Vijayakuma, Sarath, Jones, Timothy, Shibata, Seiji B., Fritzsch, Bernd, and Hansen, Marlan R.

Abstract

Objectives: The objective was to explore the effect of the proneuronal transcription factor neurogenic differentiation 1 (Neurod1, ND1) on Schwann cells (SC) and schwannoma cell proliferation.Methods: Using a variety of transgenic mouse lines, we investigated how expression of Neurod1 effects medulloblastoma (MB) growth, schwannoma tumor progression, vestibular function, and SC cell proliferation. Primary human vestibular schwannoma (VS) cell cultures were transduced with adenoviral vectors expressing Neurod1. Cell proliferation was assessed by 5-ethynyl-2'-deoxyuridine (EdU) uptake.Study Design: Basic science investigation.Results: Expression of Neurod1 reduced the growth of slow-growing but not fast-growing MB models. Gene transfer of Neurod1 in human schwannoma cultures significantly reduced cell proliferation in dose-dependent way. Deletion of the neurofibromatosis type 2 (Nf2) tumor-suppressor gene via Cre expression in SCs led to increased intraganglionic SC proliferation and mildly reduced vestibular sensory-evoked potentials (VsEP) responses compared to age-matched wild-type littermates. The effect of Neurod1-induced expression on intraganglionic SC proliferation in animals lacking Nf2 was mild and highly variable. Sciatic nerve axotomy significantly increased SC proliferation in wild-type and Nf2-null animals, and expression of Neurod1 reduced the proliferative capacity of both wild-type and Nf2-null SCs following nerve injury.Conclusion: Expression of Neurod1 reduces slow-growing MB progression and reduces human SC proliferation in primary VS cultures. In a genetic mouse model of schwannomas, we find some effects of Neurod1 expression; however, the high variability indicates that more tightly regulated Neurod1 expression levels that mimic our in vitro data are needed to fully validate Neurod1 effects on schwannoma progression.Level Of Evidence: NA Laryngoscope, 131:E259-E270, 2021. [ABSTRACT FROM AUTHOR]

Published
2021
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33. Contributors

Author

Abdul-Aziz, Dunia, Abuzeid, Waleed M., Adams, Meredith E., Adamson, Peter A., Agamah, Edem S., Agrawal, Yuri, Ahmad, Faisal I., Ahmed, Mostafa M., Akst, Seth A., Albergotti, W. Greer, Albers, Sheri L., Allen, Clint T., Alsaied, Abdulmalik S., Alwani, Mohamedkazim, Alyono, Jennifer Christy, Anderson, Carryn, Armstrong, William B., Arnold, Michelle G., Arriaga, Moises A., Arts, H. Alexander, Arvedson, Joan C., Ashram, Yasmine A., Aygun, Nafi, Backous, Douglas D., Baker, Shan R., Balkany, Thomas J., Balsalobre, Leonardo, Baroody, Fuad M., Bastian, Robert W., Basura, Gregory J., Batra, Pete S., Beadle, Beth M., Beckmann, Nicholas A., Bekeny, James R., Bell, Diana M., Bell, Elizabeth Bradford, Benninger, Michael S., Bernknopf, Heidi J., Beswick, Daniel M., Bhattarai, Mukul, Bleier, Benjamin S., Blevins, Nikolas H., Blitzer, Andrew, Boahene, Kofi, Bohm, Lauren A., Bottros, Michael M., Brackmann, Derald E., Bradford, Carol R., Branham, Gregory H., Branstetter, Barton F., IV, Brant, Jason A., Brietzke, Scott E., Brinkmeier, Jennifer, Brodie, Hilary A., Brown, Bena, Budenz, Cameron L., Burns, Clare, Byrd, J. Kenneth, Byrne, Patrick, Cai, Yi, Calloway, Hollin, Campisi, Paolo, Carey, John P., Carniol, Eric T., Carr, Simon D., Casazza, Geoffrey C., Casper, Keith, Castelnuovo, Paolo, Cejas, Ivette, Chang, Kay W., Chegar, Burke E., Cheng, Alan G., Cheng, Alan T.L., Chepeha, Douglas B., Chien, Wade W., Chin, Oliver Y., Choi, Sukgi S., Chole, Richard A., Choudhury, Baishakhi, Christian, James M., Chun, Robert H., Citardi, Martin J., Compton, Andrew Michael, Cosetti, Maura K., Council, M. Laurin, Courey, Mark S., Cover, Renee, Cox, Daniel R., Crane, Benjamin T., Creighton, Francis X., Jr, Crowson, Matthew G., Culicchia, Frank, Cummings, Charles W., Cunningham, Calhoun D., III, Cushing, Sharon L., Dahlin, Brian C., Daniel, Sam J., Dassi, Camila Soares, Day, Terry A., Dedhia, Kavita, Dedmon, Matthew M., Deep, Nicholas L., Della Santina, Charles C., Demke, Joshua C., Derkay, Craig S., Dewyer, Nicholas A., Diaz, Rodney C., Dilger, Amanda E., Driver, Lynn E., Durham, Alison B., Eisbruch, Avraham, Eisele, David W., Eisenberg, Laurie, El-Deiry, Mark, El Rassi, Edward, El-Kashlan, Hussam K., Elliott, Anila B., Elluru, Ravindhra G., Emmett, Susan D., Eu, Donovan, Fakhri, Samer, Fakhry, Carole, Farrior, Edward H., Feller-Kopman, David, Felts, Charles B., Fink, Daniel S., Fletcher, Kenneth C., Jr, Flint, Paul W., Floyd, Elizabeth M., Fokkens, Wytske J., Francis, Howard W., Friedland, David R., Friedman, Oren, Friedman, Rick A., Frodel, John L., Jr, Ganly, Ian, Gantous, Andres, Gantz, Bruce J., Garrett, C. Gaelyn, Gillespie, M. Boyd, Girod, Douglas A., Glick, Hannah, Goddard, John C., Goding, George S., Jr, Goldberg, Andrew N., Goldenberg, David, Goldstein, Nira A., Gonik, Nathan J., Gonzalez, Debra, Gourin, Christine G., Graham, M. Elise, Green, Glenn E., Green, Stephen T., Grégoire, Vincent, Grimmer, J. Fredrik, Gruffi, Catherine A., Gubbels, Samuel P., Gupta, Piyush, Gurgel, Richard K., Gurrola, Jose G., II, Ha, Jennifer F., Ha, Patrick K., Hajnas, Natalia M., Hamilton, Bronwyn E., Hamilton, Grant S., III, Hamoir, Marc, Hanna, Ehab Y., Harmon, Jeffrey J., Jr, Harréus, Ulrich, Banakis Hartl, Renee, Harvey, Richard, Haughey, Bruce H., Hawkins, Peter, Hellings, Peter, Hellstein, John W., Herzer, Kurt, Hilgers, Frans J.M., Hill, Justin D., Hillel, Alexander T., Hinni, Michael L., Hirce, Kellie J., Hoffman, Henry T., Holman, Ashlee E., Hom, David B., Hopkins, Claire, Houlton, Jeffrey J., House, John W., Hullar, Timothy E., Hummel, Thomas, Humtsoe, Joseph O., Hwang, Peter H., Ishman, Stacey L., Jabbour, Jad, Jackler, Robert K., Jackson, Neal M., James, Adrian L., Jameson, Brian, Jan, Taha A., Jenkins, Herman A., Jiam, Nicole T., Jin, Hong-Ryul, Johnson, Christopher M., Johnson, Timothy M., Kamani, Dipti, Karle, William E., Kavitt, Robert T., Kaylie, David M., Kellman, Robert M., Kennedy, David W., Kern, Robert C., Kerolus, Julia L., Kesser, Bradley W., Khan, Majid, Kileny, Paul R., Kim, Jennifer, Kimple, Adam J., King, Ericka F., Kirke, Diana N., Knecht, Elizabeth, Konior, Raymond J., Kraft, Shannon M., Kridel, Russell W.H., Kuan, Edward C., Kumar, Parvesh, Kunduk, Melda, Laccourreye, Ollivier, Lai, Stephen Y., Lal, Devyani, Lalwani, Anil K., Lam, Derek J., Lambert, Paul R., Larsen, Christopher G., Latchaw, Richard E., Lawlor, Claire M., Le Prell, Colleen G., Leahy, Kevin P., Lee, Daniel J., Lee, Edward R., Lee, Nancy, Lesperance, Marci M., Lester, Laeben, Levi, Jessica, Lewis, James S., Jr, Li, Daqing, Lian, Timothy S., Liddy, Whitney, Limb, Charles J., Lin, Frank R., Linkov, Gary, Loh, Thomas, Lorenz, Kai Johannes, Lott, David G., Lund, Valerie J., Lustig, Lawrence R., Lysakowski, Anna, Maisel, Robert H., Makki, Fawaz, Mangat, Devinder S., Marchioni, Daniele, Mark, Lynette J., Markt, Jeffery C., Marsh, Michael, Mattavelli, Davide, Mattox, Douglas E., McCrary, Hilary C., McGee, JoAnn, McGinn, Johnathan D., Mehta, Kinneri, Meier, Jeremy D., Merati, Albert L., Messing, Barbara P., Messner, Anna H., Meyer, Anna, Mierzwa, Michelle, Milczuk, Henry A., Millar, Jennifer L., Miller-Thomas, Michelle, Minor, Lloyd B., Misono, Stephanie, Mitchell, Jenna L., Mobley, Steven Ross, Moore, Eric J., Mostovych, Nadia K., Mowry, Sarah, Muntz, Harlan R., Mydlarz, Wojciech K., Nadimi, Sahar, Nadol, Joseph B., Jr, Naples, James G., Nassif, Paul S., Naunheim, Matthew R., Neel, Gregory S., Nelson, Marc E., Nelson, Rick F., Nicolai, Piero, Nieman, Carrie L., Noel, Richard J., Nouraei, S.A. Reza, Nugent, Ajani, Nuss, Daniel W., Nussenbaum, Brian, Odland, Rick M., Ohye, Richard G., O'Malley, Bert W., Jr, O'Reilly, Robert C., Orlandi, Richard R., Orlowski, Hilary L.P., Ottaviano, Giancarlo, Pagedar, Nitin A., Palmer, James N., Papsin, Blake C., Park, Albert H., Park, Stephen S., Parsons, Matthew S., Patterson, G. Alexander, Pellitteri, Phillip K., Perkins, Jonathan A., Perkins, Stephen W., Pierce, Bailey, Pignatari, Shirley S.N., Pletcher, Steven D., Poe, Dennis S., Popovtzer, Aron, Postma, Gregory N., Prueter, James C., Puglia, Michael P., II, Qian, Z. Jason, Quesnel, Alicia M., Rahbar, Reza, Ramachandran, Virginia, Ramakrishnan, Vijay R., Randolph, Gregory W., Rao, Krishna, Rao, Lesley, Rassekh, Christopher H., Reid, Lisa M., Reinisch, Lou, Rettig, Eleni, Rigby, Matthew H., Rivas, Alejandro, Robbins, K. Thomas, Roberts, Daniel S., Roby, Brianne, Roland, J. Thomas, Jr, Ronen, Ohad, Rosbe, Kristina W., Rosenfeld, Richard M., Rotter, Bruce E., Roxbury, Christopher R., Ruckenstein, Michael J., Runge, Christina L., Rybak, Leonard P., Saadi, Robert, Salinas, Thomas J., Samant, Sandeep, Samlan, Robin A., Sandhu, Guri S., Sarber, Kathleen M., Sauder, Cara L., Scher, Richard L., Schilder, Anne G.M., Schindler, Joshua S., Schmalbach, Cecelia E., Schoem, Scott R., Schubert, Michael C., Schulte, Joseph, Schwarz, Yehuda, Sciubba, James J., Sclafani, Anthony P., Seikaly, Hadi R., Selesnick, Samuel H., Senior, Brent A., Sharma, Anu, Sharon, Jeffrey D., Shearer, A. Eliot, Shelton, Clough, Shibata, Seiji B., Shnayder, Yelizaveta, Shuman, Elizabeth A., Sidell, Douglas R., Sinha, Parul, Sirjani, Davud B., Skirko, Jonathan R., Slager, Heidi K., Slattery, William H., III, Smith, Kristine A., Smith, Richard J.H., Smith, Ryan M., Smith, Timothy L., Soler, Zachary M., Spector, Matthew E., Sperry, Steven M., Stach, Brad A., Stachecki, Robert P., Stamm, Aldo Cassol, Stankiewicz, James A., Steitz, Jeffrey T., Stevens, Shawn M., Steward, David L., Stoddard, David G., Jr, Stokken, Janalee K., Sturm, Angela, Subramanian, Melanie, Sunwoo, John B., Swarm, Robert A., Sykes, Jonathan M., Syme, Noah P., Tardy, M. Eugene, Jr., Tatum, Sherard A., III, Taylor, S. Mark, Teasley, Rod A., Telian, Steven A., Terris, David J., Thatcher, Aaron L., Thomas, J. Regan, Timmons, Sherry R., Tjoa, Tjoson, Toriumi, Dean M., Trimarchi, Matteo, Tsue, Terance T., Tu, Nathan C., Turner, Michael D., Uppaluri, Ravindra, Vaezi, Michael F., Van Abel, Kathryn M., van den Brekel, Michiel W.M., Van Gerven, Laura, Venekamp, Roderick P., Verma, Sunil P., Villwock, Jennifer A., Vivas, Esther X., Vokes, David, Wackym, P. Ashley, Walsh, Edward J., Walvekar, Rohan R., Wang, Jennifer R., Wang, Tom D., Ward, Bryan K., Weber, Randal S., Wein, Richard O., Weinstein, Gregory S., Weitzel, Erik K., Welling, D. Bradley, Whitcroft, Katherine Lisa, Wiggins, Richard H., III, Wilkerson, Brent J., Wilkinson, Eric P., Wingo, Melissa L., Wise, Sarah K., Wishart, Laurelie R., Woodson, Erika, Woodson, Gayle Ellen, Wormald, Peter J., Worrall, Douglas M., Wrobel, Bozena B., Xu, Mary Jue, Yackel, Thomas R., Yan, Carol H., Yingling, Charles D., Yu, Diana H., Yu, Yao, Yueh, Bevan, Zafereo, Mark E., Zaldivar, Renzo, Zanation, Adam M., Zdanski, Carlton J., Zee, David S., Zeitler, Daniel M., Zimbler, Marc S., Zinreich, S. James, Zopf, David, and Zwolan, Teresa A.

Published
2021
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37. HOMER2, a Stereociliary Scaffolding Protein, Is Essential for Normal Hearing in Humans and Mice

Author

Azaiez, Hela, primary, Decker, Amanda R., additional, Booth, Kevin T., additional, Simpson, Allen C., additional, Shearer, A. Eliot, additional, Huygen, Patrick L. M., additional, Bu, Fengxiao, additional, Hildebrand, Michael S., additional, Ranum, Paul T., additional, Shibata, Seiji B., additional, Turner, Ann, additional, Zhang, Yuzhou, additional, Kimberling, William J., additional, Cornell, Robert A., additional, and Smith, Richard J. H., additional

Published
2015
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40. Colaboradores

Author

Abuzeid, Waleed M., Adams, Meredith E., Adamson, Peter A., Adenis, Antoine, Akst, Seth A., Albers, Sheri L., Allen, Clint T., Anderson, Carryn, Armstrong, William B., Arnold, Michelle G., Arriaga, Moisés A., Arts, H. Alexander, Ashram, Yasmine A., Aygun, Nafi, Backous, Douglas D., Baker, Shan R., Balkany, Thomas J., Balsalobre, Leonardo, Baroody, Fuad M., Bartlett, Nancy L., Bastian, Robert W., Basura, Gregory J., Bauer, Carol A., Bearelly, Shethal, Been, Mark J., Bell, Diana M., Benninger, Michael S., Bewley, Arnaud F., Bhama, Prabhat K., Bhatti, Nasir Islam, Bhrany, Amit D., Bleier, Benjamin S., Blitzer, Andrew, Bottros, Michael M., Brackmann, Derald E., Bradford, Carol R., Branham, Gregory H., Branstetter, Barton F., IV, Brant, Jason A., Brenner, Michael J., Brietzke, Scott, Briggs, Robert J.S., Brinkmeier, Jennifer Veraldi, Brodie, Hilary A., Brown, Carolyn J., Brown, David J., Brown, Kevin D., Brown, Lisa M., Budenz, Cameron L., Carey, John P., Casselbrandt, Margaretha L., Castelnuovo, Paolo, Chan, Kenny H., Chegar, Burke E., Chen, Eunice Y., Cheng, Alan G., Chepeha, Douglas B., Chiang, Tendy, Chien, Wade W., Choi, Sukgi S., Chole, Richard A., Christian, James M., Chu, Eugene A., Chun, Robert, Citardi, Martin J., Compton, Andrew Michael, Cotton, Robin T., Couch, Marion Everett, Council, Martha Laurin, Courey, Mark S., Crane, Benjamin T., Cruz, Oswaldo Laércio M., Culicchia, Frank, Cummings, Charles W., Cunningham, Calhoun D., III, Dahlin, Brian C., Daniel, Sam J., Darr, E. Ashlie, Day, Terry A., Santina, Charles C. Della, Demke, Joshua C., Denoyelle, Françoise, Derkay, Craig S., Diaz, Rodney C., Dobie, Robert A., Durham, Alison B., Eggers, Scott D.Z., Eisbruch, Avraham, Eisele, David W., Eisler, Lindsay S., El-Deiry, Mark, El-Kashlan, Hussam K., Elluru, Ravindhra G., Emmett, Susan D., Fakhri, Samer, Fakhry, Carole, Cardenas, Marcela Fandiño, Farrior, Edward H., Farrior, Richard T., Faust, Russell A., Ferguson, Berrylin J., Fink, Daniel S., Flint, Paul W., Fokkens, Wytske J., Francis, Howard W., Friedland, David R., Friedman, Oren, Friedman, Rick A., Frodel, John L., Jr, Gailey, Michael P., Galli, Suzanne K. Doud, Ganly, Ian, Gantz, Bruce J., Garrett, C. Gaelyn, Gillespie, M. Boyd, Girod, Douglas A., Goddard, Adam C., Goddard, John C., Goding, George S., Jr, Goldberg, Andrew N., Goldenberg, David, Goldstein, Nira A., Gonzalez, Debra, Gourin, Christine G., Green, Glenn, Grégoire, Vincent, Gries, Heike, Griffin, Garrett, Guardiani, Elizabeth, Gubbels, Samuel P., Ha, Patrick K., Hamilton, Bronwyn E., Hamilton, Grant S., III, Hamoir, Marc, Handelsman, Jaynee A., Hanna, Ehab Y., Harmych, Brian M., Harréus, Uli, Harrison, Robert V., Haughey, Bruce H., Heider, Amer, Hellstein, John, Herzer, Kurt R., Hilgers, Frans J.M., Hill, Justin D., Hillel, Alexander T., Hinni, Michael L., Ho, Allen S., Ho, Maria K., Hoffman, Henry T., Holbrook, Eric H., Hom, David B., Houlton, Jeffrey J., House, John W., Hullar, Timothy E., Ing, Steven, Ishman, Stacey L., Jackler, Robert K., Jackson, Neal M., Jackson, Ryan S., Jameson, Brian, Jenkins, Herman A., Jin, Hong-Ryul, Joe, John K., Joe, Stephanie A., Johnson, Christopher M., Johnson, Tiffany A., Johnson, Timothy M., Jones, Nicholas S., Jorissen, Mark, Julieron, Morbize, Kanaan, Alyssa A., Kavitt, Robert T., Kellman, Robert M., Kennedy, David W., Kepchar, Jessica, Kern, Robert C., Kies, Merrill S., Kileny, Paul R., Kim, Alyn J., Kim, Jason H., Kim, Theresa, Kimberling, William J., King, Ericka F., Koh, Jeffrey, Konior, Raymond J., Kozak, Frederick K., Kraft, Shannon M., Kridel, Russell, Kumar, Parvesh, Kunduk, Melda, Laccourreye, Ollivier, Lai, Stephen Y., Lal, Devyani, Lalwani, Anil K., Lam, Derek J., Lambert, Paul R., Larsen, Christopher G., Lassig, Amy Anne, Latchaw, Richard E., Leahy, Kevin P., Lee, Daniel J., Lee, Nancy, Lee, Stella, Lefton-Greif, Maureen A., Leopold, Donald A., Lesperance, Marci M., Levi, Jessica, Lewis, James S., Jr, Li, Daqing, Lian, Timothy S., Liddy, Whitney, Limb, Charles J., Liu, Judy Z., Logemann, Jeri A., Loh, Thomas, Lominska, Christopher, Lonsbury-Martin, Brenda L., Lott, David G., Lustig, Lawrence R., Lysakowski, Anna, Maisel, Robert H., Mandel, Ellen M., Mandel, Susan J., Mangat, Devinder S., Mark, Lynette J., Markt, Jeffrey C., Marsh, Michael, Martin, Glen K., Mattox, Douglas E., McCaffrey, Thomas V., McGee, JoAnn, McGinn, Johnathan D., McGuire, John F., McJunkin, Jonathan, McMurray, J. Scott, Meier, Jeremy D., Merati, Albert L., Merchant, Saumil N., Messner, Anna H., Meyer, Anna, Michelson, James D., Milczuk, Henry A., Millar, Jennifer L., Miller-Thomas, Michelle, Minor, Lloyd B., Mitchell, Jenna L., Mobley, Steven Ross, Moore, Eric J., Muntz, Harlan, Murakami, Craig S., Myers, Jeffrey N., Naclerio, Robert M., Nadol, Joseph B., Jr, Nassif, Paul, Nelson, Marc, Nelson, Rick F., Nicolai, Piero, Nielsen, David R., Niparko, John K., Noel, Richard J., Nouraei, S.A. Reza, Nugent, Ajani, Nuss, Daniel W., Nussenbaum, Brian, Oakley, Gretchen M., Odland, Rick M., Ohye, Richard G., O’Malley, Bert W., Jr, O’Reilly, Robert C., Ospina, Juan Camilo, Ossoff, Robert H., Packer, Mark D., Pagedar, Nitin A., Pallanch, John, Park, Stephen S., Parsons, Matthew S., Patel, Hetal H., Patterson, G. Alexander, Pellitteri, Phillip K., Perkins, Jonathan A., Perkins, Stephen W., Pignatari, Shirley S.N., Pletcher, Steven D., Popovtzer, Aron, Postma, Gregory N., Poti, Shannon M., Potsic, William P., Pross, Seth E., Puscas, Liana, Qian, Zhen Jason, Ramachandran, Virginia, Randolph, Gregory W., Rao, Lesley, Rassekh, Christopher H., Reinisch, Lou, Rhoton, Albert L., Jr, Riaz, Nadeem, Richmon, Jeremy D., Ridgway, James M., Rigby, Matthew H., Rizzi, Mark D., Robbins, K. Thomas, Roberts, Daniel, Roediger, Frederick C., Ronen, Ohad, Rosbe, Kristina W., Rosenfeld, Richard M., Rotter, Bruce E., Rubinstein, Jay T., Ruckenstein, Michael J., Runge, Christina L., Rybak, Leonard P., Saade, Rami E., Sadoughi, Babak, Salinas, Thomas J., Samant, Sandeep, Samlan, Robin A., Samy, Ravi N., Sandhu, Guri S., Sauder, Cara, Scher, Richard L., Schindler, Joshua S., Schmalbach, Cecelia E., Schoem, Scott R., Schubert, Michael C., Schwedt, Todd J., Sciubba, James J., Sclafani, Anthony P., Seshamani, Meena, Shearer, A. Eliot, Shelton, Clough, Shepard, Neil T., Shibata, Seiji B., Shnayder, Yelizaveta, Sie, Kathleen C.Y., Simmen, Daniel B., Singer, Michael C., Sinha, Parul, Slattery, William H., III, Smeds, Henrik, Smith, Marshall E., Smith, Richard J.H., Smith, Timothy L., Sobel, Ryan H., Sofferman, Robert A., Soler, Zachary M., Spear, Samuel A., Sperry, Steven M., Sritharan, Niranjan, Stach, Brad A., Stachecki, Robert P., Staecker, Hinrich, Stamm, Aldo Cassol, Stankiewicz, James A., Stevens, Shawn M., Steward, David L., Stoddard, David G., Jr, Stokken, Janalee K., Sturm-O’Brien, Angela, Sunwoo, John B., Swanson, Veronica C., Swarm, Robert A., Sykes, Jonathan M., Tan, Luke, Tan, Marietta, Taneja, Pravin A., Tardy, M. Eugene, Jr, Tatum, Sherard A., III, Taylor, S. Mark, Teasley, Rod A., Tedeschi, Helder, Telian, Steven A., Terris, David J., Thomas, J. Regan, Tomeh, Chafeek, Toriumi, Dean M., Tran, Aline, Travers, Joseph B., Travers, Susan P., Truong, Mai Thy, Tsue, Terance T., Turner, Michael D., Uppaluri, Ravindra, Vaezi, Michael F., Van Abel, Kathryn M., van den Brekel, Michiel W.M., Van Riper, Lori A., Verma, Sunil P., Vila, Peter M., Vokes, David E., Wackym, P. Ashley, Wakefield, Tamekia L., Walden, Michael J., Walker, Thomas J., Walsh, Edward J., Walvekar, Rohan R., Wang, Tom D., Wang, Tzu-Fei, Warren, Frank M., III, Waters, Heather H., Weber, Randal S., Wein, Richard O., Weinstein, Gregory S., Weitzel, Erik K., Welling, D. Bradley, Wemer, Richard D., Wetmore, Ralph F., Wiggins, Richard H., III, Wilkerson, Brent J., Wippold, Franz J., II, Woodson, Gayle Ellen, Wormald, Peter J., Wright, Harry V., Yellon, Robert F., Yingling, Charles D., Yueh, Bevan, Yung, Rex C., Zaldívar, Renzo A., Zalzal, George H., Zanation, Adam M., Zee, David S., Zimbler, Marc S., Zinreich, S. James, and Zwolan, Teresa A.

Published
2017

42. Contributors

Author

Abuzeid, Waleed M., Adams, Meredith E., Adamson, Peter A., Adenis, Antoine, Akst, Seth A., Albers, Sheri L., Allen, Clint T., Anderson, Carryn, Armstrong, William B., Arnold, Michelle G., Arriaga, Moisés A., Arts, H. Alexander, Ashram, Yasmine A., Aygun, Nafi, Backous, Douglas D., Baker, Shan R., Balkany, Thomas J., Balsalobre, Leonardo, Baroody, Fuad M., Bartlett, Nancy L., Bastian, Robert W., Basura, Gregory J., Bauer, Carol A., Bearelly, Shethal, Been, Mark J., Bell, Diana M., Benninger, Michael S., Bewley, Arnaud F., Bhama, Prabhat K., Bhatti, Nasir Islam, Bhrany, Amit D., Bleier, Benjamin S., Blitzer, Andrew, Bottros, Michael M., Brackmann, Derald E., Bradford, Carol R., Branham, Gregory H., Branstetter, Barton F., IV, Brant, Jason A., Brenner, Michael J., Brietzke, Scott, Briggs, Robert J.S., Brinkmeier, Jennifer Veraldi, Brodie, Hilary A., Brown, Carolyn J., Brown, David J., Brown, Kevin D., Brown, Lisa M., Budenz, Cameron L., Carey, John P., Casselbrandt, Margaretha L., Castelnuovo, Paolo, Chan, Kenny H., Chegar, Burke E., Chen, Eunice Y., Cheng, Alan G., Chepeha, Douglas B., Chiang, Tendy, Chien, Wade W., Choi, Sukgi S., Chole, Richard A., Christian, James M., Chu, Eugene A., Chun, Robert, Citardi, Martin J., Compton, Andrew Michael, Cotton, Robin T., Couch, Marion Everett, Council, Martha Laurin, Courey, Mark S., Crane, Benjamin T., Cruz, Oswaldo Laércio M., Culicchia, Frank, Cummings, Charles W., Cunningham, Calhoun D., III, Dahlin, Brian C., Daniel, Sam J., Darr, E. Ashlie, Day, Terry A., Della Santina, Charles C., Demke, Joshua C., Denoyelle, Françoise, Derkay, Craig S., Diaz, Rodney C., Dobie, Robert A., Durham, Alison B., Eggers, Scott D.Z., Eisbruch, Avraham, Eisele, David W., Eisler, Lindsay S., El-Deiry, Mark, El-Kashlan, Hussam K., Elluru, Ravindhra G., Emmett, Susan D., Fakhri, Samer, Fakhry, Carole, Cardenas, Marcela Fandiño, Farrior, Edward H., Farrior, Richard T., Faust, Russell A., Ferguson, Berrylin J., Fink, Daniel S., Flint, Paul W., Fokkens, Wytske J., Francis, Howard W., Friedland, David R., Friedman, Oren, Friedman, Rick A., Frodel, John L., Jr, Gailey, Michael P., Doud Galli, Suzanne K., Ganly, Ian, Gantz, Bruce J., Garrett, C. Gaelyn, Gillespie, M. Boyd, Girod, Douglas A., Goddard, Adam C., Goddard, John C., Goding, George S., Jr, Goldberg, Andrew N., Goldenberg, David, Goldstein, Nira A., Gonzalez, Debra, Gourin, Christine G., Green, Glenn, Grégoire, Vincent, Gries, Heike, Griffin, Garrett, Guardiani, Elizabeth, Gubbels, Samuel P., Ha, Patrick K., Hamilton, Bronwyn E., Hamilton, Grant S., III, Hamoir, Marc, Handelsman, Jaynee A., Hanna, Ehab Y., Harmych, Brian M., Harréus, Uli, Harrison, Robert V., Haughey, Bruce H., Heider, Amer, Hellstein, John, Herzer, Kurt R., Hilgers, Frans J.M., Hill, Justin D., Hillel, Alexander T., Hinni, Michael L., Ho, Allen S., Ho, Maria K., Hoffman, Henry T., Holbrook, Eric H., Hom, David B., Houlton, Jeffrey J., House, John W., Hullar, Timothy E., Ing, Steven, Ishman, Stacey L., Jackler, Robert K., Jackson, Neal M., Jackson, Ryan S., Jameson, Brian, Jenkins, Herman A., Jin, Hong-Ryul, Joe, John K., Joe, Stephanie A., Johnson, Christopher M., Johnson, Tiffany A., Johnson, Timothy M., Jones, Nicholas S., Jorissen, Mark, Julieron, Morbize, Kanaan, Alyssa A., Kavitt, Robert T., Kellman, Robert M., Kennedy, David W., Kepchar, Jessica, Kern, Robert C., Kies, Merrill S., Kileny, Paul R., Kim, Alyn J., Kim, Jason H., Kim, Theresa, Kimberling, William J., King, Ericka F., Koh, Jeffrey, Konior, Raymond J., Kozak, Frederick K., Kraft, Shannon M., Kridel, Russell, Kumar, Parvesh, Kunduk, Melda, Laccourreye, Ollivier, Lai, Stephen Y., Lal, Devyani, Lalwani, Anil K., Lam, Derek J., Lambert, Paul R., Larsen, Christopher G., Lassig, Amy Anne, Latchaw, Richard E., Leahy, Kevin P., Lee, Daniel J., Lee, Nancy, Lee, Stella, Lefton-Greif, Maureen A., Leopold, Donald A., Lesperance, Marci M., Levi, Jessica, Lewis, James S., Jr, Li, Daqing, Lian, Timothy S., Liddy, Whitney, Limb, Charles J., Liu, Judy Z., Logemann, Jeri A., Loh, Thomas, Lominska, Christopher, Lonsbury-Martin, Brenda L., Lott, David G., Lustig, Lawrence R., Lysakowski, Anna, Maisel, Robert H., Mandel, Ellen M., Mandel, Susan J., Mangat, Devinder S., Mark, Lynette J., Markt, Jeffrey C., Marsh, Michael, Martin, Glen K., Mattox, Douglas E., McCaffrey, Thomas V., McGee, JoAnn, McGinn, Johnathan D., McGuire, John F., McJunkin, Jonathan, McMurray, J. Scott, Meier, Jeremy D., Merati, Albert L., Merchant, Saumil N., Messner, Anna H., Meyer, Anna, Michelson, James D., Milczuk, Henry A., Millar, Jennifer L., Miller-Thomas, Michelle, Minor, Lloyd B., Mitchell, Jenna L., Mobley, Steven Ross, Moore, Eric J., Muntz, Harlan, Murakami, Craig S., Myers, Jeffrey N., Naclerio, Robert M., Nadol, Joseph B., Jr, Nassif, Paul, Nelson, Marc, Nelson, Rick F., Nicolai, Piero, Nielsen, David R., Niparko, John K., Noel, Richard J., Nouraei, S.A. Reza, Nugent, Ajani, Nuss, Daniel W., Nussenbaum, Brian, Oakley, Gretchen M., Odland, Rick M., Ohye, Richard G., O'Malley, Bert W., Jr, O'Reilly, Robert C., Ospina, Juan Camilo, Ossoff, Robert H., Packer, Mark D., Pagedar, Nitin A., Pallanch, John, Park, Stephen S., Parsons, Matthew S., Patel, Hetal H., Patterson, G. Alexander, Pellitteri, Phillip K., Perkins, Jonathan A., Perkins, Stephen W., Pignatari, Shirley S.N., Pletcher, Steven D., Popovtzer, Aron, Postma, Gregory N., Poti, Shannon M., Potsic, William P., Pross, Seth E., Puscas, Liana, Qian, Zhen Jason, Ramachandran, Virginia, Randolph, Gregory W., Rao, Lesley, Rassekh, Christopher H., Reinisch, Lou, Rhoton, Albert L., Jr, Riaz, Nadeem, Richmon, Jeremy D., Ridgway, James M., Rigby, Matthew H., Rizzi, Mark D., Robbins, K. Thomas, Roberts, Daniel, Roediger, Frederick C., Ronen, Ohad, Rosbe, Kristina W., Rosenfeld, Richard M., Rotter, Bruce E., Rubinstein, Jay T., Ruckenstein, Michael J., Runge, Christina L., Rybak, Leonard P., Saade, Rami E., Sadoughi, Babak, Salinas, Thomas J., Samant, Sandeep, Samlan, Robin A., Samy, Ravi N., Sandhu, Guri S., Sauder, Cara, Scher, Richard L., Schindler, Joshua S., Schmalbach, Cecelia E., Schoem, Scott R., Schubert, Michael C., Schwedt, Todd J., Sciubba, James J., Sclafani, Anthony P., Seshamani, Meena, Shearer, A. Eliot, Shelton, Clough, Shepard, Neil T., Shibata, Seiji B., Shnayder, Yelizaveta, Sie, Kathleen C.Y., Simmen, Daniel B., Singer, Michael C., Sinha, Parul, Slattery, William H., III, Smeds, Henrik, Smith, Marshall E., Smith, Richard J.H., Smith, Timothy L., Sobel, Ryan H., Sofferman, Robert A., Soler, Zachary M., Spear, Samuel A., Sperry, Steven M., Sritharan, Niranjan, Stach, Brad A., Stachecki, Robert P., Staecker, Hinrich, Stamm, Aldo Cassol, Stankiewicz, James A., Stevens, Shawn M., Steward, David L., Stoddard, David G., Jr, Stokken, Janalee K., Sturm-O'Brien, Angela, Sunwoo, John B., Swanson, Veronica C., Swarm, Robert A., Sykes, Jonathan M., Tan, Luke, Tan, Marietta, Taneja, Pravin A., Tardy, M. Eugene, Jr, Tatum, Sherard A., III, Taylor, S. Mark, Teasley, Rod A., Tedeschi, Helder, Telian, Steven A., Terris, David J., Thomas, J. Regan, Tomeh, Chafeek, Toriumi, Dean M., Tran, Aline, Travers, Joseph B., Travers, Susan P., Truong, Mai Thy, Tsue, Terance T., Turner, Michael D., Uppaluri, Ravindra, Vaezi, Michael F., Van Abel, Kathryn M., van den Brekel, Michiel W.M., Van Riper, Lori A., Verma, Sunil P., Vila, Peter M., Vokes, David E., Wackym, P. Ashley, Wakefield, Tamekia L., Walden, Michael J., Walker, Thomas J., Walsh, Edward J., Walvekar, Rohan R., Wang, Tom D., Wang, Tzu-Fei, Warren, Frank M., III, Waters, Heather H., Weber, Randal S., Wein, Richard O., Weinstein, Gregory S., Weitzel, Erik K., Welling, D. Bradley, Wemer, Richard D., Wetmore, Ralph F., Wiggins, Richard H., III, Wilkerson, Brent J., Wippold, Franz J., II, Woodson, Gayle Ellen, Wormald, Peter J., Wright, Harry V., Yellon, Robert F., Yingling, Charles D., Yueh, Bevan, Yung, Rex C., Zaldívar, Renzo A., Zalzal, George H., Zanation, Adam M., Zee, David S., Zimbler, Marc S., Zinreich, S. James, and Zwolan, Teresa A.

Published
2015
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43. TBC1 D24 Mutation Causes Autosomal-Dominant Nonsyndromic Hearing Loss.

Author

Azaiez, Hela, Booth, Kevin T., Bu, Fengxiao, Huygen, Patrick, Shibata, Seiji B., Shearer, A. Eliot, Kolbe, Diana, Meyer, Nicole, Black‐Ziegelbein, E. Ann, and Smith, Richard J.H.

Abstract

ABSTRACT Hereditary hearing loss is extremely heterogeneous. Over 70 genes have been identified to date, and with the advent of massively parallel sequencing, the pace of novel gene discovery has accelerated. In a family segregating progressive autosomal-dominant nonsyndromic hearing loss ( NSHL), we used Oto SCOPE® to exclude mutations in known deafness genes and then performed segregation mapping and whole-exome sequencing to identify a unique variant, p.Ser178Leu, in TBC1 D24 that segregates with the hearing loss phenotype. TBC1 D24 encodes a GTPase-activating protein expressed in the cochlea. Ser178 is highly conserved across vertebrates and its change is predicted to be damaging. Other variants in TBC1 D24 have been associated with a panoply of clinical symptoms including autosomal recessive NSHL, syndromic hearing impairment associated with onychodystrophy, osteodystrophy, mental retardation, and seizures ( DOORS syndrome), and a wide range of epileptic disorders. [ABSTRACT FROM AUTHOR]

Published
2014
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44. Mutation-agnostic RNA interference with engineered replacement rescues Tmc1 -related hearing loss.

Author

Iwasa Y, Klimara MJ, Yoshimura H, Walls WD, Omichi R, West CA, Shibata SB, Ranum PT, and Smith RJ

Subjects
Membrane Proteins genetics, Mutation genetics, RNA Interference, Hearing Loss, Sensorineural, Mice, Animals, Hearing Loss genetics, Hearing Loss therapy, Mechanotransduction, Cellular
Abstract

Hearing loss is the most common sensory deficit, of which genetic etiologies are a frequent cause. Dominant and recessive mutations in TMC1 , a gene encoding the pore-forming subunit of the hair cell mechanotransduction channel, cause DFNA36 and DFNB7/11, respectively, accounting for ∼2% of genetic hearing loss. Previous work has established the efficacy of mutation-targeted RNAi in treatment of murine models of autosomal dominant non-syndromic deafness. However, application of such approaches is limited by the infeasibility of development and validation of novel constructs for each variant. We developed an allele-non-specific approach consisting of mutation-agnostic RNAi suppression of both mutant and WT alleles, co-delivered with a knockdown-resistant engineered WT allele with or without the use of woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) to augment transgene expression. This therapeutic construct was delivered into the mature murine model of DFNA36 with an AAV vector and achieved robust hair cell and auditory brainstem response preservation. However, WPRE-enhanced Tmc1 expression resulted in inferior outcomes, suggesting a role for gene dosage optimization in future TMC1 gene therapy development., (© 2022 Iwasa et al.)

Published
2022
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45. An Osseous Destructive Mass of the Infratemporal Fossa.

Author

Vesole AS, Shibata SB, and Hansen MR

Subjects
Aged, Humans, Infratemporal Fossa diagnostic imaging, Infratemporal Fossa surgery, Magnetic Resonance Imaging, Male, Neoplasm Invasiveness, Rhabdomyosarcoma classification, Rhabdomyosarcoma diagnostic imaging, Rhabdomyosarcoma surgery, Risk Factors, Skull Base Neoplasms classification, Skull Base Neoplasms diagnostic imaging, Skull Base Neoplasms surgery, Tomography, X-Ray Computed, Infratemporal Fossa pathology, Rhabdomyosarcoma pathology, Skull Base Neoplasms pathology
Published
2020
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