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2. Integrated multimodal cell atlas of Alzheimer’s disease

Author

Gabitto, Mariano, primary, Travaglini, Kyle, additional, Ariza, Jeannelle, additional, Kaplan, Eitan, additional, Long, Brian, additional, Rachleff, Victoria, additional, Ding, Yi, additional, Mahoney, Joseph, additional, Dee, Nick, additional, Goldy, Jeff, additional, Melief, Erica, additional, Brouner, Krissy, additional, Compos, Jazmin, additional, Campos, John, additional, Carr, Ambrose, additional, Casper, Tamara, additional, Chakrabarty, Rushil, additional, Clark, Michael, additional, Cool, Jonah, additional, Dalley, Rachel, additional, Darvas, Martin, additional, Dolbeare, Tim, additional, Ding, Song-Lin, additional, Egdorf, Tom, additional, Esposito, Luke, additional, Ferrer, Rebecca, additional, Gala, Rohan, additional, Gary, Amanda, additional, Gloe, Jessica, additional, Guilford, Nathan, additional, Guzman, Junitta, additional, Ho, Windy, additional, Jarsky, Tim, additional, Johansen, Nelson, additional, Kalmbach, Brian, additional, Keene, Lisa, additional, Khawand, Sarah, additional, Kilgore, Mitchell, additional, Kirkland, Amanda, additional, Kunst, Michael, additional, Lee, Brian, additional, Donald, Christine Mac, additional, Malone, Jocelin, additional, Maltzer, Zoe, additional, Martin, Naomi, additional, McCue, Rachel, additional, McMillen, Delissa, additional, Meyerdierks, Emma, additional, Meyers, Kelly, additional, Mollenkopf, Tyler, additional, Montine, Mark, additional, Nolan, Amber, additional, Nyhus, Julie, additional, Olsen, Paul, additional, Pacleb, Maiya, additional, Pham, Trangthanh, additional, Pom, Christina, additional, Postupna, Nadia, additional, Ruiz, Augustin, additional, Schantz, Aimee, additional, Sorensen, Staci, additional, Staats, Brian, additional, Sullivan, Matt, additional, Sunkin, Susan, additional, Thompson, Carol, additional, Tieu, Michael, additional, Ting, Jonathan, additional, Torkelson, Amy, additional, Tran, Tracy, additional, Cuevas, Nasmil Valera, additional, Wang, Ming-Qiang, additional, Waters, Jack, additional, Wilson, Angela, additional, Haynor, David, additional, Gatto, Nicole, additional, Jayadev, Suman, additional, Mufti, Shoaib, additional, Ng, Lydia, additional, Mukherjee, Shubhabrata, additional, Crane, Paul, additional, Latimer, Caitlin, additional, Levi, Boaz, additional, Smith, Kimberly, additional, Close, Jennie, additional, Miller, Jeremy, additional, Hodge, Rebecca, additional, Larson, Eric, additional, Grabowski, Thomas, additional, Hawrylycz, Michael, additional, Keene, C., additional, and Lein, Ed, additional

Published
2023
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3. Integrated multimodal cell atlas of Alzheimer’s disease

Author

Gabitto, Mariano I., primary, Travaglini, Kyle J., additional, Rachleff, Victoria M., additional, Kaplan, Eitan S., additional, Long, Brian, additional, Ariza, Jeanelle, additional, Ding, Yi, additional, Mahoney, Joseph T., additional, Dee, Nick, additional, Goldy, Jeff, additional, Melief, Erica J., additional, Brouner, Krissy, additional, Campos, Jazmin, additional, Campos, John, additional, Carr, Ambrose J., additional, Casper, Tamara, additional, Chakrabarty, Rushil, additional, Clark, Michael, additional, Cool, Jonah, additional, Valera Cuevas, Nasmil J., additional, Dalley, Rachel, additional, Darvas, Martin, additional, Ding, Song-Lin, additional, Dolbeare, Tim, additional, Mac Donald, Christine L., additional, Egdorf, Tom, additional, Esposito, Luke, additional, Ferrer, Rebecca, additional, Gala, Rohan, additional, Gary, Amanda, additional, Gloe, Jessica, additional, Guilford, Nathan, additional, Guzman, Junitta, additional, Hirschstein, Daniel, additional, Ho, Windy, additional, Jarksy, Tim, additional, Johansen, Nelson, additional, Kalmbach, Brian E., additional, Keene, Lisa M., additional, Khawand, Sarah, additional, Kilgore, Mitch, additional, Kirkland, Amanda, additional, Kunst, Michael, additional, Lee, Brian R., additional, Malone, Jocelin, additional, Maltzer, Zoe, additional, Martin, Naomi, additional, McCue, Rachel, additional, McMillen, Delissa, additional, Meyerdierks, Emma, additional, Meyers, Kelly P., additional, Mollenkopf, Tyler, additional, Montine, Mark, additional, Nolan, Amber L., additional, Nyhus, Julie, additional, Olsen, Paul A., additional, Pacleb, Maiya, additional, Peña, Nicholas, additional, Pham, Thanh, additional, Pom, Christina Alice, additional, Postupna, Nadia, additional, Ruiz, Augustin, additional, Schantz, Aimee M., additional, Shapovalova, Nadiya V., additional, Sorensen, Staci A., additional, Staats, Brian, additional, Sullivan, Matt, additional, Sunkin, Susan M., additional, Thompson, Carol, additional, Tieu, Michael, additional, Ting, Jonathan, additional, Torkelson, Amy, additional, Tran, Tracy, additional, Wang, Ming-Qiang, additional, Waters, Jack, additional, Wilson, Angela M., additional, Haynor, David, additional, Gatto, Nicole, additional, Jayadev, Suman, additional, Mufti, Shoaib, additional, Ng, Lydia, additional, Mukherjee, Shubhabrata, additional, Crane, Paul K., additional, Latimer, Caitlin S., additional, Levi, Boaz P., additional, Smith, Kimberly, additional, Close, Jennie L., additional, Miller, Jeremy A., additional, Hodge, Rebecca D., additional, Larson, Eric B., additional, Grabowski, Thomas J., additional, Hawrylycz, Michael, additional, Dirk Keene, C., additional, and Lein, Ed S., additional

Published
2023
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5. Integrated multimodal cell atlas of Alzheimer’s disease

Author

Gabitto, Mariano I., Travaglini, Kyle J., Rachleff, Victoria M., Kaplan, Eitan S., Long, Brian, Ariza, Jeanelle, Ding, Yi, Mahoney, Joseph T., Dee, Nick, Goldy, Jeff, Melief, Erica J., Agrawal, Anamika, Kana, Omar, Zhen, Xingjian, Barlow, Samuel T., Brouner, Krissy, Campos, Jazmin, Campos, John, Carr, Ambrose J., Casper, Tamara, Chakrabarty, Rushil, Clark, Michael, Cool, Jonah, Dalley, Rachel, Darvas, Martin, Ding, Song-Lin, Dolbeare, Tim, Egdorf, Tom, Esposito, Luke, Ferrer, Rebecca, Fleckenstein, Lynn E., Gala, Rohan, Gary, Amanda, Gelfand, Emily, Gloe, Jessica, Guilford, Nathan, Guzman, Junitta, Hirschstein, Daniel, Ho, Windy, Hupp, Madison, Jarsky, Tim, Johansen, Nelson, Kalmbach, Brian E., Keene, Lisa M., Khawand, Sarah, Kilgore, Mitchell D., Kirkland, Amanda, Kunst, Michael, Lee, Brian R., Leytze, Mckaila, Mac Donald, Christine L., Malone, Jocelin, Maltzer, Zoe, Martin, Naomi, McCue, Rachel, McMillen, Delissa, Mena, Gonzalo, Meyerdierks, Emma, Meyers, Kelly P., Mollenkopf, Tyler, Montine, Mark, Nolan, Amber L., Nyhus, Julie K., Olsen, Paul A., Pacleb, Maiya, Pagan, Chelsea M., Peña, Nicholas, Pham, Trangthanh, Pom, Christina Alice, Postupna, Nadia, Rimorin, Christine, Ruiz, Augustin, Saldi, Giuseppe A., Schantz, Aimee M., Shapovalova, Nadiya V., Sorensen, Staci A., Staats, Brian, Sullivan, Matt, Sunkin, Susan M., Thompson, Carol, Tieu, Michael, Ting, Jonathan T., Torkelson, Amy, Tran, Tracy, Valera Cuevas, Nasmil J., Walling-Bell, Sarah, Wang, Ming-Qiang, Waters, Jack, Wilson, Angela M., Xiao, Ming, Haynor, David, Gatto, Nicole M., Jayadev, Suman, Mufti, Shoaib, Ng, Lydia, Mukherjee, Shubhabrata, Crane, Paul K., Latimer, Caitlin S., Levi, Boaz P., Smith, Kimberly A., Close, Jennie L., Miller, Jeremy A., Hodge, Rebecca D., Larson, Eric B., Grabowski, Thomas J., Hawrylycz, Michael, Keene, C. Dirk, and Lein, Ed S.

Abstract

Alzheimer’s disease (AD) is the leading cause of dementia in older adults. Although AD progression is characterized by stereotyped accumulation of proteinopathies, the affected cellular populations remain understudied. Here we use multiomics, spatial genomics and reference atlases from the BRAIN Initiative to study middle temporal gyrus cell types in 84 donors with varying AD pathologies. This cohort includes 33 male donors and 51 female donors, with an average age at time of death of 88 years. We used quantitative neuropathology to place donors along a disease pseudoprogression score. Pseudoprogression analysis revealed two disease phases: an early phase with a slow increase in pathology, presence of inflammatory microglia, reactive astrocytes, loss of somatostatin+inhibitory neurons, and a remyelination response by oligodendrocyte precursor cells; and a later phase with exponential increase in pathology, loss of excitatory neurons and Pvalb+and Vip+inhibitory neuron subtypes. These findings were replicated in other major AD studies.

Published
2024
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8. Differences in Pain Experience by Race, Ethnicity, and Socioeconomic Status Among People with Burn Injury.

Author

Pacleb, Maiya, Stewart, Barclay, Carrougher, Gretchen, Kowalske, Karen, Mandell, Samuel, Schneider, Jeffrey, Silver, Julie, McMullen, Kara, Orton, Caitlin, Sibbett, Stephen, and Ashford, Nathaniel

Abstract

Introduction: Disparities in pain experience and treatment amongst people of different races and ethnicities have been described for several conditions. However, the relationship between race, ethnicity, socioeconomic status (SES) and pain reported by people with burn injury is not well understood. This study compares pain intensity and interference with daily activities among burn-injured adults of various sociodemographic backgrounds. We hypothesized that minority and low-income populations will report greater pain intensity and interference, necessitating additional strategies to address pain disparity. Methods: Adult multicenter national database participants with complete PROMIS® pain intensity and pain interference measures at 6 and 12 months after injury were analyzed. Linear regression models examined associations between sex, race, ethnicity, education, income, burn size and pain interference and intensity scores. Regression model diagnostics were tested, and final models used robust standard errors to account for heteroskedasticity. Results: Data from 656 participants were analyzed, with a mean age of 47.1 ± 16.2. Racial representation was 84.0% White, 8.8% African American/Black, 2.5% Asian/Native Hawaiian/Pacific Islander, 1.9% American India laskan Native, and 2.8% other/more than one race; 80.4% were non- Hispanic and 19.6% Hispanic. Weighted regression models revealed that pain intensity at 6 mo (®=1.25, p=0.029) and interference at 12 mo (β=6.71, p=0.013) among Black participants were markedly higher than White participants. Hispanic participants reported lower pain intensity (β=-0.86, p=0.036) and interference (β=-4.06, p=0.007) compared to non-Hispanic participants at 6 mo. Average pain intensity at 6 mo varied significantly by income (p=0.01), with the highest pain intensity (mean 3.8, SD 3.0) reported by those making < $25,000/year. Females reported greater pain intensity at 6 mo than males (β=0.63, p=0.029). Conclusions: Greater pain intensity and interference were reported by Black participants compared to White participants, while Hispanic participants reported lower pain outcomes. Lower income was also associated with worse pain outcomes. Targeted study of pre-injury pain experiences, pain management, psychosocial health, and financial toxicity are required to identify opportunities for intervention on the many dimensions and causal factors of unsatisfactory pain experiences. Applicability of Research to Practice: Systematic screening for pain intensity and interference after burn injury may find sociodemographic groups with high pain levels and a need for interdisciplinary pain and psychosocial health management. Comprehensive pain treatment following burn injury should account for social determinants of health and impact of bias to further improve quality care for all people. [ABSTRACT FROM AUTHOR]

Published
2023
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9. The Impact of Body Image on Physical Function and Return to Work After Burn: A Burn Model System Study.

Author

Ali M, McMullen K, Solis-Beach K, Roaten K, Ryan CM, Pacleb MI, Carrougher GJ, Yenikomshian HA, and Kowalske K

Abstract

Burn injury can have a lasting impact on quality of life beyond the initial injury. The aim of this study was to examine the recovery process through analyzing the relationship between body image, physical function, and return to work. This study uses data from the Burn Model System (BMS) National Longitudinal Database and includes 1,001 participants injured between 2015 and 2023 who were measured using Patient-Reported Outcomes Measurement Information System (PROMIS-29) Physical Function, Employment Status, and the Body Image subscale. Associations were explored using multivariate linear and logistic regression analyses. Physical function was positively associated with body image and negatively associated with burn size, age, and amputation. Employment was positively correlated with body image and employment at injury, while negatively correlated with age. Other variables including burn etiology, burn center site, race, and ethnicity were significant at different time points. By understanding how these factors change and are associated with outcomes across recovery, the healthcare team can make more tailored efforts to improve the psychosocial and physical well-being of burn survivors., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Published
2024
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10. Integrated multimodal cell atlas of Alzheimer's disease.

Author

Gabitto MI, Travaglini KJ, Rachleff VM, Kaplan ES, Long B, Ariza J, Ding Y, Mahoney JT, Dee N, Goldy J, Melief EJ, Brouner K, Campos J, Carr AJ, Casper T, Chakrabarty R, Clark M, Compos J, Cool J, Valera Cuevas NJ, Dalley R, Darvas M, Ding SL, Dolbeare T, Mac Donald CL, Egdorf T, Esposito L, Ferrer R, Gala R, Gary A, Gloe J, Guilford N, Guzman J, Ho W, Jarksy T, Johansen N, Kalmbach BE, Keene LM, Khawand S, Kilgore M, Kirkland A, Kunst M, Lee BR, Malone J, Maltzer Z, Martin N, McCue R, McMillen D, Meyerdierks E, Meyers KP, Mollenkopf T, Montine M, Nolan AL, Nyhus J, Olsen PA, Pacleb M, Pham T, Pom CA, Postupna N, Ruiz A, Schantz AM, Sorensen SA, Staats B, Sullivan M, Sunkin SM, Thompson C, Tieu M, Ting J, Torkelson A, Tran T, Wang MQ, Waters J, Wilson AM, Haynor D, Gatto N, Jayadev S, Mufti S, Ng L, Mukherjee S, Crane PK, Latimer CS, Levi BP, Smith K, Close JL, Miller JA, Hodge RD, Larson EB, Grabowski TJ, Hawrylycz M, Keene CD, and Lein ES

Abstract

Alzheimer's disease (AD) is the most common cause of dementia in older adults. Neuropathological and imaging studies have demonstrated a progressive and stereotyped accumulation of protein aggregates, but the underlying molecular and cellular mechanisms driving AD progression and vulnerable cell populations affected by disease remain coarsely understood. The current study harnesses single cell and spatial genomics tools and knowledge from the BRAIN Initiative Cell Census Network to understand the impact of disease progression on middle temporal gyrus cell types. We used image-based quantitative neuropathology to place 84 donors spanning the spectrum of AD pathology along a continuous disease pseudoprogression score and multiomic technologies to profile single nuclei from each donor, mapping their transcriptomes, epigenomes, and spatial coordinates to a common cell type reference with unprecedented resolution. Temporal analysis of cell-type proportions indicated an early reduction of Somatostatin-expressing neuronal subtypes and a late decrease of supragranular intratelencephalic-projecting excitatory and Parvalbumin-expressing neurons, with increases in disease-associated microglial and astrocytic states. We found complex gene expression differences, ranging from global to cell type-specific effects. These effects showed different temporal patterns indicating diverse cellular perturbations as a function of disease progression. A subset of donors showed a particularly severe cellular and molecular phenotype, which correlated with steeper cognitive decline. We have created a freely available public resource to explore these data and to accelerate progress in AD research at SEA-AD.org., Competing Interests: Additional Declarations: There is NO Competing Interest.

Published
2023
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