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2. Quantifying interictal intracranial EEG to predict focal epilepsy

Author

Gallagher, Ryan S, Sinha, Nishant, Pattnaik, Akash R, Ojemann, William K. S., Lucas, Alfredo, LaRocque, Joshua J., Bernabei, John M, Greenblatt, Adam S, Sweeney, Elizabeth M, Chen, H Isaac, Davis, Kathryn A, Conrad, Erin C, and Litt, Brian

Subjects
Quantitative Biology - Neurons and Cognition
Abstract

Intracranial EEG (IEEG) is used for 2 main purposes, to determine: (1) if epileptic networks are amenable to focal treatment and (2) where to intervene. Currently these questions are answered qualitatively and sometimes differently across centers. There is a need for objective, standardized methods to guide surgical decision making and to enable large scale data analysis across centers and prospective clinical trials. We analyzed interictal data from 101 patients with drug resistant epilepsy who underwent presurgical evaluation with IEEG. We chose interictal data because of its potential to reduce the morbidity and cost associated with ictal recording. 65 patients had unifocal seizure onset on IEEG, and 36 were non-focal or multi-focal. We quantified the spatial dispersion of implanted electrodes and interictal IEEG abnormalities for each patient. We compared these measures against the 5 Sense Score (5SS), a pre-implant estimate of the likelihood of focal seizure onset, and assessed their ability to predict the clinicians choice of therapeutic intervention and the patient outcome. The spatial dispersion of IEEG electrodes predicted network focality with precision similar to the 5SS (AUC = 0.67), indicating that electrode placement accurately reflected pre-implant information. A cross-validated model combining the 5SS and the spatial dispersion of interictal IEEG abnormalities significantly improved this prediction (AUC = 0.79; p<0.05). The combined model predicted ultimate treatment strategy (surgery vs. device) with an AUC of 0.81 and post-surgical outcome at 2 years with an AUC of 0.70. The 5SS, interictal IEEG, and electrode placement were not correlated and provided complementary information. Quantitative, interictal IEEG significantly improved upon pre-implant estimates of network focality and predicted treatment with precision approaching that of clinical experts., Comment: 25 pages, 4 Figures, 1 table

Published
2023

3. Support Experiences of Beginning Teachers in an Alternate Route Graduate Program in Mississippi

Author

Sweeney, Elizabeth Young

Abstract

Beginning teachers are the group of teachers most at risk of leaving the profession, while research has shown that novice teachers who receive support, such as mentorship or cohort programs, are more likely to continue to teach than those who do not. This study explored supports that beginning teachers in an alternate route graduate program in Mississippi experience and perceive as beneficial. A qualitative research design utilizing a phenomenological approach was used to explore the lived experiences of participants and supports they experience as beginning teachers. Thirteen beginning teachers, each teaching for less than three years, were interviewed using a semi-structured interview protocol. A social support framework provided a lens for examining supports and "un-supports" that these beginning teachers experienced. In vivo and pattern coding were used to generate codes based on participants' words and organize them into categories. Provisional coding applied codes from the theoretical framework. Major findings were that beginning teachers benefit from a network of people supports and from a structured program that provides intentional and multiple forms of support. In addition, teachers want to help and support each other. Findings suggest that beginning teachers should be provided an intentional orientation at one's school and connected to a wide range of people supports in one's district. Structured programs should be established through which to scaffold supports for beginning teachers, and teachers should be provided time and space to talk to each other and collaborate. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]

Published
2023

4. Mapping the Relationship of White Matter Lesions to Depression in Multiple Sclerosis

Author

Baller, Erica B., Sweeney, Elizabeth M., Cieslak, Matthew, Robert-Fitzgerald, Timothy, Covitz, Sydney C., Martin, Melissa L., Schindler, Matthew K., Bar-Or, Amit, Elahi, Ameena, Larsen, Bart S., Manning, Abigail R., Markowitz, Clyde E., Perrone, Christopher M., Rautman, Victoria, Seitz, Madeleine M., Detre, John A., Fox, Michael D., Shinohara, Russell T., and Satterthwaite, Theodore D.

Published
2024
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5. Regulatory elements in SEM1-DLX5-DLX6 (7q21.3) locus contribute to genetic control of coronal nonsyndromic craniosynostosis and bone density-related traits

Author

Nicoletti, Paola, Zafer, Samreen, Matok, Lital, Irron, Inbar, Patrick, Meidva, Haklai, Rotem, Evangelista, John Erol, Marino, Giacomo B., Ma’ayan, Avi, Sewda, Anshuman, Holmes, Greg, Britton, Sierra R., Lee, Won Jun, Wu, Meng, Ru, Ying, Arnaud, Eric, Botto, Lorenzo, Brody, Lawrence C., Byren, Jo C., Caggana, Michele, Carmichael, Suzan L., Cilliers, Deirdre, Conway, Kristin, Crawford, Karen, Cuellar, Araceli, Di Rocco, Federico, Engel, Michael, Fearon, Jeffrey, Feldkamp, Marcia L., Finnell, Richard, Fisher, Sarah, Freudlsperger, Christian, Garcia-Fructuoso, Gemma, Hagge, Rhinda, Heuzé, Yann, Harshbarger, Raymond J., Hobbs, Charlotte, Howley, Meredith, Jenkins, Mary M., Johnson, David, Justice, Cristina M., Kane, Alex, Kay, Denise, Gosain, Arun Kumar, Langlois, Peter, Legal-Mallet, Laurence, Lin, Angela E., Mills, James L., Morton, Jenny E.V., Noons, Peter, Olshan, Andrew, Persing, John, Phipps, Julie M., Redett, Richard, Reefhuis, Jennita, Rizk, Elias, Samson, Thomas D., Shaw, Gary M., Sicko, Robert, Smith, Nataliya, Staffenberg, David, Stoler, Joan, Sweeney, Elizabeth, Taub, Peter J., Timberlake, Andrew T., Topczewska, Jolanta, Wall, Steven A., Wilson, Alexander F., Wilson, Louise C., Boyadjiev, Simeon A., Wilkie, Andrew O.M., Richtsmeier, Joan T., Jabs, Ethylin Wang, Romitti, Paul A., Karasik, David, Birnbaum, Ramon Y., and Peter, Inga

Published
2024
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6. A genome-wide association study implicates the BMP7 locus as a risk factor for nonsyndromic metopic craniosynostosis

Author

Justice, Cristina M, Cuellar, Araceli, Bala, Krithi, Sabourin, Jeremy A, Cunningham, Michael L, Crawford, Karen, Phipps, Julie M, Zhou, Yan, Cilliers, Deirdre, Byren, Jo C, Johnson, David, Wall, Steven A, Morton, Jenny EV, Noons, Peter, Sweeney, Elizabeth, Weber, Astrid, Rees, Katie EM, Wilson, Louise C, Simeonov, Emil, Kaneva, Radka, Yaneva, Nadezhda, Georgiev, Kiril, Bussarsky, Assen, Senders, Craig, Zwienenberg, Marike, Boggan, James, Roscioli, Tony, Tamburrini, Gianpiero, Barba, Marta, Conway, Kristin, Sheffield, Val C, Brody, Lawrence, Mills, James L, Kay, Denise, Sicko, Robert J, Langlois, Peter H, Tittle, Rachel K, Botto, Lorenzo D, Jenkins, Mary M, LaSalle, Janine M, Lattanzi, Wanda, Wilkie, Andrew OM, Wilson, Alexander F, Romitti, Paul A, and Boyadjiev, Simeon A

Subjects
Genetics, Complementary and Alternative Medicine, Paediatrics and Reproductive Medicine, Genetics & Heredity, Reproductive medicine
Abstract

Our previous genome-wide association study (GWAS) for sagittal nonsyndromic craniosynostosis (sNCS) provided important insights into the genetics of midline CS. In this study, we performed a GWAS for a second midline NCS, metopic NCS (mNCS), using 215 non-Hispanic white case-parent triads. We identified six variants with genome-wide significance (P ≤ 5 × 10–8): rs781716 (P = 4.71 × 10–9; odds ratio [OR] = 2.44) intronic to SPRY3; rs6127972 (P = 4.41 × 10–8; OR = 2.17) intronic to BMP7; rs62590971 (P = 6.22 × 10–9; OR = 0.34), located ~ 155 kb upstream from TGIF2LX; and rs2522623, rs2573826, and rs2754857, all intronic to PCDH11X (P = 1.76 × 10–8, OR = 0.45; P = 3.31 × 10–8, OR = 0.45; P = 1.09 × 10–8, OR = 0.44, respectively). We performed a replication study of these variants using an independent non-Hispanic white sample of 194 unrelated mNCS cases and 333 unaffected controls; only the association for rs6127972 (P = 0.004, OR = 1.45; meta-analysis P = 1.27 × 10–8, OR = 1.74) was replicated. Our meta-analysis examining single nucleotide polymorphisms common to both our mNCS and sNCS studies showed the strongest association for rs6127972 (P = 1.16 × 10–6). Our imputation analysis identified a linkage disequilibrium block encompassing rs6127972, which contained an enhancer overlapping a CTCF transcription factor binding site (chr20:55,798,821–55,798,917) that was significantly hypomethylated in mesenchymal stem cells derived from fused metopic compared to open sutures from the same probands. This study provides additional insights into genetic factors in midline CS.

Published
2020

8. A multi-institutional machine learning algorithm for prognosticating facial nerve injury following microsurgical resection of vestibular schwannoma

Author

Heman-Ackah, Sabrina M., primary, Blue, Rachel, additional, Quimby, Alexandra E., additional, Abdallah, Hussein, additional, Sweeney, Elizabeth M., additional, Chauhan, Daksh, additional, Hwa, Tiffany, additional, Brant, Jason, additional, Ruckenstein, Michael J., additional, Bigelow, Douglas C., additional, Jackson, Christina, additional, Zenonos, Georgios, additional, Gardner, Paul, additional, Briggs, Selena E., additional, Cohen, Yale, additional, and Lee, John Y. K., additional

Published
2024
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19. Relating multi-sequence longitudinal intensity profiles and clinical covariates in new multiple sclerosis lesions

Author

Sweeney, Elizabeth M., Shinohara, Russell T., Dewey, Blake E., Schindler, Matthew K., Muschelli, John, Reich, Daniel S., Crainiceanu, Ciprian M., and Eloyan, Ani

Subjects
Statistics - Applications
Abstract

Structural magnetic resonance imaging (MRI) can be used to detect lesions in the brains of multiple sclerosis (MS) patients. The formation of these lesions is a complex process involving inflammation, tissue damage, and tissue repair, all of which are visible on MRI. Here we characterize the lesion formation process on longitudinal, multi-sequence structural MRI from 34 MS patients and relate the longitudinal changes we observe within lesions to therapeutic interventions. In this article, we first outline a pipeline to extract voxel level, multi-sequence longitudinal profiles from four MRI sequences within lesion tissue. We then propose two models to relate clinical covariates to the longitudinal profiles. The first model is a principal component analysis (PCA) regression model, which collapses the information from all four profiles into a scalar value. We find that the score on the first PC identifies areas of slow, long-term intensity changes within the lesion at a voxel level, as validated by two experienced clinicians, a neuroradiologist and a neurologist. On a quality scale of 1 to 4 (4 being the highest) the neuroradiologist gave the score on the first PC a median rating of 4 (95% CI: [4,4]), and the neurologist gave it a median rating of 3 (95% CI: [3,3]). In the PCA regression model, we find that treatment with disease modifying therapies (p-value < 0.01), steroids (p-value < 0.01), and being closer to the boundary of abnormal signal intensity (p-value < 0.01) are associated with a return of a voxel to intensity values closer to that of normal-appearing tissue. The second model is a function-on-scalar regression, which allows for assessment of the individual time points at which the covariates are associated with the profiles. In the function-on-scalar regression both age and distance to the boundary were found to have a statistically significant association with the profiles.

Published
2015

20. Photothermal Prussian blue nanoparticles generate potent multi‐targeted tumor‐specific T cells as an adoptive cell therapy.

Author

Sweeney, Elizabeth E., Sekhri, Palak, Muniraj, Nethaji, Chen, Jie, Feng, Sally, Terao, Joshua, Chin, Samantha J., Schmidt, Danielle E., Bollard, Catherine M., Cruz, Conrad Russell Y., and Fernandes, Rohan

Subjects
*T cells, *PRUSSIAN blue, *CELLULAR therapy, *T cell receptors, *CELL populations, *NANOPARTICLES, *IMMUNOLOGIC memory
Abstract

Prussian blue nanoparticle‐based photothermal therapy (PBNP‐PTT) is an effective tumor treatment capable of eliciting an antitumor immune response. Motivated by the ability of PBNP‐PTT to potentiate endogenous immune responses, we recently demonstrated that PBNP‐PTT could be used ex vivo to generate tumor‐specific T cells against glioblastoma (GBM) cell lines as an adoptive T cell therapy (ATCT). In this study, we further developed this promising T cell development platform. First, we assessed the phenotype and function of T cells generated using PBNP‐PTT. We observed that PBNP‐PTT facilitated CD8+ T cell expansion from healthy donor PBMCs that secreted IFNγ and TNFα and upregulated CD107a in response to engagement with target U87 cells, suggesting specific antitumor T cell activation and degranulation. Further, CD8+ effector and effector memory T cell populations significantly expanded after co‐culture with U87 cells, consistent with tumor‐specific effector responses. In orthotopically implanted U87 GBM tumors in vivo, PBNP‐PTT‐derived T cells effectively reduced U87 tumor growth and generated long‐term survival in >80% of tumor‐bearing mice by Day 100, compared to 0% of mice treated with PBS, non‐specific T cells, or T cells expanded from lysed U87 cells, demonstrating an enhanced antitumor efficacy of this ATCT platform. Finally, we tested the generalizability of our approach by generating T cells targeting medulloblastoma (D556), breast cancer (MDA‐MB‐231), neuroblastoma (SH‐SY5Y), and acute monocytic leukemia (THP‐1) cell lines. The resulting T cells secreted IFNγ and exerted increased tumor‐specific cytolytic function relative to controls, demonstrating the versatility of PBNP‐PTT in generating tumor‐specific T cells for ATCT. [ABSTRACT FROM AUTHOR]

Published
2024
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21. Photothermal Prussian blue nanoparticles generate potent multi‐targeted tumor‐specific T cells as an adoptive cell therapy

Author

Sweeney, Elizabeth E., primary, Sekhri, Palak, additional, Muniraj, Nethaji, additional, Chen, Jie, additional, Feng, Sally, additional, Terao, Joshua, additional, Chin, Samantha J., additional, Schmidt, Danielle E., additional, Bollard, Catherine M., additional, Cruz, Conrad Russell Y., additional, and Fernandes, Rohan, additional

Published
2023
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22. Mapping the Relationship of White Matter Lesions to Depression in Multiple Sclerosis

Author

Baller, Erica B., primary, Sweeney, Elizabeth M., additional, Cieslak, Matthew, additional, Robert-Fitzgerald, Timothy, additional, Covitz, Sydney C., additional, Martin, Melissa L., additional, Schindler, Matthew K., additional, Bar-Or, Amit, additional, Elahi, Ameena, additional, Larsen, Bart S., additional, Manning, Abigail R., additional, Markowitz, Clyde E., additional, Perrone, Christopher M., additional, Rautman, Victoria, additional, Seitz, Madeleine M., additional, Detre, John A., additional, Fox, Michael D., additional, Shinohara, Russell T., additional, and Satterthwaite, Theodore D., additional

Published
2023
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27. De novo CCND2 mutations leading to stabilization of cyclin D2 cause megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome

Author

Mirzaa, Ghayda M, Parry, David A, Fry, Andrew E, Giamanco, Kristin A, Schwartzentruber, Jeremy, Vanstone, Megan, Logan, Clare V, Roberts, Nicola, Johnson, Colin A, Singh, Shawn, Kholmanskikh, Stanislav S, Adams, Carissa, Hodge, Rebecca D, Hevner, Robert F, Bonthron, David T, Braun, Kees PJ, Faivre, Laurence, Rivière, Jean-Baptiste, St-Onge, Judith, Gripp, Karen W, Mancini, Grazia MS, Pang, Ki, Sweeney, Elizabeth, van Esch, Hilde, Verbeek, Nienke, Wieczorek, Dagmar, Steinraths, Michelle, Majewski, Jacek, Boycott, Kym M, Pilz, Daniela T, Ross, M Elizabeth, Dobyns, William B, and Sheridan, Eamonn G

Subjects
Pediatric, 2.1 Biological and endogenous factors, Aetiology, Abnormalities, Multiple, Animals, Base Sequence, Blotting, Western, Bromodeoxyuridine, Cyclin D2, Electroporation, Exome, Female, HEK293 Cells, Humans, Hydrocephalus, Immunohistochemistry, Malformations of Cortical Development, Megalencephaly, Mice, Microscopy, Fluorescence, Molecular Sequence Data, Mutagenesis, Site-Directed, Polydactyly, Sequence Analysis, DNA, Syndrome, FORGE Canada Consortium, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Activating mutations in genes encoding phosphatidylinositol 3-kinase (PI3K)-AKT pathway components cause megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (MPPH, OMIM 603387). Here we report that individuals with MPPH lacking upstream PI3K-AKT pathway mutations carry de novo mutations in CCND2 (encoding cyclin D2) that are clustered around a residue that can be phosphorylated by glycogen synthase kinase 3β (GSK-3β). Mutant CCND2 was resistant to proteasomal degradation in vitro compared to wild-type CCND2. The PI3K-AKT pathway modulates GSK-3β activity, and cells from individuals with PIK3CA, PIK3R2 or AKT3 mutations showed similar CCND2 accumulation. CCND2 was expressed at higher levels in brains of mouse embryos expressing activated AKT3. In utero electroporation of mutant CCND2 into embryonic mouse brains produced more proliferating transfected progenitors and a smaller fraction of progenitors exiting the cell cycle compared to cells electroporated with wild-type CCND2. These observations suggest that cyclin D2 stabilization, caused by CCND2 mutation or PI3K-AKT activation, is a unifying mechanism in PI3K-AKT-related megalencephaly syndromes.

Published
2014

29. NOTES FOR NOTES

Author

Sweeney, Elizabeth, Smith-Borne, Holling, Smith, Jeremy A., Testa, Matthew, Vick, Liza, Brower, Mary, McKnight, Mark, and Campana, Deborah

Published
2018

31. ER

Author

Sweeney, Elizabeth E., Jordan, V. Craig, and Marshall, John L., editor

Published
2017
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35. 57. Depression as a Disease of White Matter Network Disruption: Characterizing the Relationship Between White Matter Lesions and Depression in Patients With Multiple Sclerosis

Author

Baller, Erica, primary, Sweeney, Elizabeth, additional, Bar-Or, Amit, additional, Cieslak, Matthew, additional, Covitz, Sydney, additional, Detre, John, additional, Elahi, Ameena, additional, Manning, Abigail, additional, Markowitz, Clyde, additional, Martin, Melissa, additional, Perrone, Christopher, additional, Rautman, Victoria, additional, Robert-Fitzgerald, Timothy, additional, Schindler, Matthew, additional, Siddiqi, Shan, additional, Thomas, Sunil, additional, Fox, Michael, additional, Shinohara, Russell, additional, and Satterthwaite, Theodore, additional

Published
2023
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38. Introduction to the Special Issue on Heirs’ Property.

Author

Zabawa, Robert, Green, John J., and Sweeney, Elizabeth Young

Subjects
AFRICAN Americans, HEIRS, TRANSFER (Law), REAL property
Abstract

This essay presents a brief introduction to the special issue of the Journal of Rural Social Sciences focused on heirs’ property. Real property transferred over generations without a proper will or other transfer device, heirs’ property and heirs’ property owners are vulnerable to a range of challenges, from limited productive land use to the actual loss of land. A situation that is national in scope, heirs’ property rates are particularly high in the southern region of the United States and among African Americans. Articles in this special issue address operationalizing and measuring heirs’ property at the county-level, describing the characteristics of people seeking assistance with heirs’ property, and the situation and implications faced in a state with limited protections of families with heirs’ property. [ABSTRACT FROM AUTHOR]

Published
2024

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