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Article ; Online: Using Global Health Lessons to Sustain Medical Student Activism Beyond COVID-19.

Hassan, Amir / Suwondo, Peter E / Roberts, Jackson A

Academic medicine : journal of the Association of American Medical Colleges

2022 Volume 97, Issue 7, Page(s) 947–949

MeSH term(s)	COVID-19/epidemiology ; Global Health ; Humans ; Social Behavior ; Students, Medical
Language	English
Publishing date	2022-06-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	96192-9
ISSN	1938-808X ; 1040-2446
ISSN (online)	1938-808X
ISSN	1040-2446
DOI	10.1097/ACM.0000000000004433
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Article ; Online: Herpes simplex virus 2 serology is associated with thinner whole-brain cortex in community-dwelling older adults.

Roberts, Jackson A / Elkind, Mitchell S V / Liu, Minghua / Wright, Clinton B / Rundek, Tatjana / Gutierrez, Jose

Journal of the neurological sciences

2023 Volume 454, Page(s) 120856

Abstract: Prior work in the Northern Manhattan Study (NOMAS) identified impaired cognition in cross-sectional analyses and more rapid memory decline in individuals with evidence of prior common infectious disease exposures. In this study, we sought to determine ... ...

Abstract	Prior work in the Northern Manhattan Study (NOMAS) identified impaired cognition in cross-sectional analyses and more rapid memory decline in individuals with evidence of prior common infectious disease exposures. In this study, we sought to determine the cross-sectional relationship between prior exposure to cytomegalovirus, herpes simplex viruses 1 and 2, Chlamydia pneumoniae, and Helicobacter pylori and three magnetic resonance imaging (MRI) signatures (whole-brain cortical thickness, a previously validated AD signature, and hippocampal volume) in 455 NOMAS participants. We performed confounder-adjusted linear regression analyses between neuroimaging scores and both continuous serologies and categorical seropositivity of each pathogen, as well as a combined infectious burden index (IBI). We identified that increased serologic titers of herpes simplex virus 2 were associated with reduced whole-brain cortical thickness, and a combined score of HSV-2 and C. pneumoniae displayed an additive effect on reduced cortical thickness. Our findings suggest herpes simplex virus 2 seropositivity may contribute to accelerated brain aging, possibly resulting in an increased vulnerability to cognitive impairment and neurodegenerative disease in aging populations.
MeSH term(s)	Humans ; Aged ; Herpesvirus 2, Human ; Neurodegenerative Diseases/complications ; Independent Living ; Noma/complications ; Brain ; Herpes Simplex/complications ; Herpes Simplex/diagnostic imaging ; Alzheimer Disease/complications
Language	English
Publishing date	2023-10-29
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80160-4
ISSN	1878-5883 ; 0022-510X ; 0374-8642
ISSN (online)	1878-5883
ISSN	0022-510X ; 0374-8642
DOI	10.1016/j.jns.2023.120856
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Article ; Online: Unbiased proteomics and multivariable regularized regression techniques identify SMOC1, NOG, APCS, and NTN1 in an Alzheimer's disease brain proteomic signature.

Roberts, Jackson A / Varma, Vijay R / Candia, Julián / Tanaka, Toshiko / Ferrucci, Luigi / Bennett, David A / Thambisetty, Madhav

npj aging

2023 Volume 9, Issue 1, Page(s) 18

Abstract: Advancements in omics methodologies have generated a wealth of high-dimensional Alzheimer's disease (AD) datasets, creating significant opportunities and challenges for data interpretation. In this study, we utilized multivariable regularized regression ... ...

Abstract	Advancements in omics methodologies have generated a wealth of high-dimensional Alzheimer's disease (AD) datasets, creating significant opportunities and challenges for data interpretation. In this study, we utilized multivariable regularized regression techniques to identify a reduced set of proteins that could discriminate between AD and cognitively normal (CN) brain samples. Utilizing eNetXplorer, an R package that tests the accuracy and significance of a family of elastic net generalized linear models, we identified 4 proteins (SMOC1, NOG, APCS, NTN1) that accurately discriminated between AD (n = 31) and CN (n = 22) middle frontal gyrus (MFG) tissue samples from Religious Orders Study participants with 83 percent accuracy. We then validated this signature in MFG samples from Baltimore Longitudinal Study of Aging participants using leave-one-out logistic regression cross-validation, finding that the signature again accurately discriminated AD (n = 31) and CN (n = 19) participants with a receiver operating characteristic curve area under the curve of 0.863. These proteins were strongly correlated with the burden of neurofibrillary tangle and amyloid pathology in both study cohorts. We additionally tested whether these proteins differed between AD and CN inferior temporal gyrus (ITG) samples and blood serum samples at the time of AD diagnosis in ROS and BLSA, finding that the proteins differed between AD and CN ITG samples but not in blood serum samples. The identified proteins may provide mechanistic insights into the pathophysiology of AD, and the methods utilized in this study may serve as the basis for further work with additional high-dimensional datasets in AD.
Language	English
Publishing date	2023-07-06
Publishing country	England
Document type	Journal Article
ISSN	2731-6068
ISSN (online)	2731-6068
DOI	10.1038/s41514-023-00112-6
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Article ; Online: Serum Proteomic Signatures of Common Health Outcomes among Older Adults.

Roberts, Jackson A / Basu-Roy, Sayantani / Shin, Jong / Varma, Vijay R / Williamson, Andrew / Blackshear, Chad / Griswold, Michael E / Candia, Julián / Elango, Palchamy / Karikkineth, Ajoy C / Tanaka, Toshiko / Ferrucci, Luigi / Thambisetty, Madhav

Gerontology

2024 Volume 70, Issue 3, Page(s) 269–278

Abstract: Introduction: In aging populations, the coexistence of multiple health comorbidities represents a significant challenge for clinicians and researchers. Leveraging advances in omics techniques to characterize these health conditions may provide insight ... ...

Abstract	Introduction: In aging populations, the coexistence of multiple health comorbidities represents a significant challenge for clinicians and researchers. Leveraging advances in omics techniques to characterize these health conditions may provide insight into disease pathogenesis as well as reveal biomarkers for monitoring, prognostication, and diagnosis. Researchers have previously established the utility of big data approaches with respect to comprehensive health outcome measurements in younger populations, identifying protein markers that may provide significant health information with a single blood sample. Methods: Here, we employed a similar approach in two cohorts of older adults, the Baltimore Longitudinal Study of Aging (mean age = 76.12 years) and InCHIANTI Study (mean age = 66.05 years), examining the relationship between levels of serum proteins and 5 key health outcomes: kidney function, fasting glucose, physical activity, lean body mass, and percent body fat. Results: Correlations between proteins and health outcomes were primarily shared across both older adult cohorts. We further identified that most proteins associated with health outcomes in the older adult cohorts were not associated with the same outcomes in a prior study of a younger population. A subset of proteins, adiponectin, MIC-1, and NCAM-120, were associated with at least three health outcomes in both older adult cohorts but not in the previously published younger cohort, suggesting that they may represent plausible markers of general health in older adult populations. Conclusion: Taken together, these findings suggest that comprehensive protein health markers have utility in aging populations and are distinct from those identified in younger adults, indicating unique mechanisms of disease with aging.
MeSH term(s)	Humans ; Aged ; Longitudinal Studies ; Proteomics ; Aging ; Body Composition ; Outcome Assessment, Health Care
Language	English
Publishing date	2024-01-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	193798-4
ISSN	1423-0003 ; 0304-324X
ISSN (online)	1423-0003
ISSN	0304-324X
DOI	10.1159/000534753
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Article ; Online: FSH/AMH Ratio and Adipocyte Size are Linked to Ovarian Dysfunction.

Roberts, Jackson A / Carpenter, Ryann M / Blythe, Sarah N / Toporikova, Natalia

Endocrine research

2020 Volume 45, Issue 3, Page(s) 174–189

Abstract: Background and aim: While the relationship between obesity and reproductive dysfunction is well known, the physiological mechanism behind obesity-related infertility remains unclear. Previous work suggests that follicle development prior to ovulation is ...

Abstract	Background and aim: While the relationship between obesity and reproductive dysfunction is well known, the physiological mechanism behind obesity-related infertility remains unclear. Previous work suggests that follicle development prior to ovulation is disrupted in obese individuals. Follicle-stimulating hormone (FSH) and anti-Mullerian hormone (AMH) are two key regulators of follicle development, and the poorest reproductive outcomes have been recorded when these hormones are imbalanced. In order to understand how obesity impacts the reproductive axis, the present study induces reproductive dysfunction in female rats using a high-fat, high-sugar diet (HFHS).
MeSH term(s)	Adipocytes/metabolism ; Animals ; Anti-Mullerian Hormone/blood ; Corpus Luteum/metabolism ; Diet, Carbohydrate Loading/adverse effects ; Diet, High-Fat/adverse effects ; Disease Models, Animal ; Estrous Cycle/metabolism ; Female ; Follicle Stimulating Hormone/blood ; Obesity/complications ; Obesity/metabolism ; Ovarian Cysts/etiology ; Ovarian Cysts/metabolism ; Ovarian Diseases/etiology ; Ovarian Diseases/metabolism ; Ovarian Follicle/growth & development ; Rats
Chemical Substances	Anti-Mullerian Hormone (80497-65-0) ; Follicle Stimulating Hormone (9002-68-0)
Language	English
Publishing date	2020-01-27
Publishing country	England
Document type	Journal Article
ZDB-ID	605823-1
ISSN	1532-4206 ; 0743-5800
ISSN (online)	1532-4206
ISSN	0743-5800
DOI	10.1080/07435800.2020.1721015
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Article ; Online: Comparison of quantitative ultrasonography and dual X-ray absorptiometry for bone status assessment in South African children living with HIV.

Roberts, Jackson A / Shen, Yanhan / Strehlau, Renate / Patel, Faeezah / Kuhn, Louise / Coovadia, Ashraf / Kaufman, Jonathan J / Shiau, Stephanie / Arpadi, Stephen M / Yin, Michael T

PloS one

2022 Volume 17, Issue 10, Page(s) e0276290

Abstract: Children living with HIV (CLHIV) have decreased bone mineral content (BMC) and density (BMD), increasing risk for fracture and future osteoporosis. While DXA is the gold-standard for bone assessments, it lacks availability in resource-constrained ... ...

Abstract	Children living with HIV (CLHIV) have decreased bone mineral content (BMC) and density (BMD), increasing risk for fracture and future osteoporosis. While DXA is the gold-standard for bone assessments, it lacks availability in resource-constrained settings (RCS). Quantitative ultrasound (QUS) offers an alternative owing to its portability, low cost, ease of handling, and lack of ionizing radiation. While QUS has detected reduced bone quality in CLHIV, the relationship between QUS and DXA in this population remains unexplored. At baseline and 12 months, BMC and BMD of the whole body, lumbar spine, and radius were measured by DXA in a longitudinal cohort of CLHIV in Johannesburg, South Africa. Calcaneal speed of sound (SOS) and broadband ultrasound attenuation (BUA) and radius SOS were obtained by QUS, and calcaneal stiffness index (SI) was calculated. Spearman correlations, with and without HIV stratification, were performed between QUS and DXA measurements at each visit and for absolute difference in measurements between visits. At baseline and 12-months, calcaneal BUA and SI displayed strong positive correlations with DXA, with only modest correlations between radial QUS and DXA at baseline. Longitudinal measures of QUS did not correlate with DXA. At both baseline and 12-months, individuals with DXA whole-body BMD z-score < -1 displayed significantly lower calcaneal BUA and SI. Cross-sectionally, calcaneal QUS correlates strongly with whole body DXA and may represent a viable diagnostic alternative in RCS. Longitudinally, the two methods do not correlate well, possibly reflecting that each method assesses distinct aspects of bone architecture.
MeSH term(s)	Absorptiometry, Photon/methods ; Bone Density ; Calcaneus/diagnostic imaging ; Child ; HIV Infections/diagnostic imaging ; Humans ; South Africa ; Ultrasonography
Language	English
Publishing date	2022-10-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0276290
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Article ; Online: Acid ceramidase promotes senescent cell survival.

Munk, Rachel / Anerillas, Carlos / Rossi, Martina / Tsitsipatis, Dimitrios / Martindale, Jennifer L / Herman, Allison B / Yang, Jen-Hao / Roberts, Jackson A / Varma, Vijay R / Pandey, Poonam R / Thambisetty, Madhav / Gorospe, Myriam / Abdelmohsen, Kotb

Aging

2021 Volume 13, Issue 12, Page(s) 15750–15769

Abstract: Cellular senescence is linked to chronic age-related diseases including atherosclerosis, diabetes, and neurodegeneration. Compared to proliferating cells, senescent cells express distinct subsets of proteins. In this study, we used cultured human diploid ...

Abstract	Cellular senescence is linked to chronic age-related diseases including atherosclerosis, diabetes, and neurodegeneration. Compared to proliferating cells, senescent cells express distinct subsets of proteins. In this study, we used cultured human diploid fibroblasts rendered senescent through replicative exhaustion or ionizing radiation to identify proteins differentially expressed during senescence. We identified acid ceramidase (ASAH1), a lysosomal enzyme that cleaves ceramide into sphingosine and fatty acid, as being highly elevated in senescent cells. This increase in ASAH1 levels in senescent cells was associated with a rise in the levels of
MeSH term(s)	Acid Ceramidase/genetics ; Acid Ceramidase/metabolism ; Cell Line ; Cell Proliferation/genetics ; Cell Survival ; Cellular Senescence ; Ceramides/metabolism ; Fibroblasts/cytology ; Fibroblasts/enzymology ; Gene Silencing ; Humans ; Metabolome ; Protein Biosynthesis/genetics ; RNA Stability/genetics
Chemical Substances	Ceramides ; ASAH1 protein, human (EC 3.5.1.23) ; Acid Ceramidase (EC 3.5.1.23)
Language	English
Publishing date	2021-06-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural
ISSN	1945-4589
ISSN (online)	1945-4589
DOI	10.18632/aging.203170
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Article ; Online: Blood Metabolite Signature of Metabolic Syndrome Implicates Alterations in Amino Acid Metabolism: Findings from the Baltimore Longitudinal Study of Aging (BLSA) and the Tsuruoka Metabolomics Cohort Study (TMCS).

Roberts, Jackson A / Varma, Vijay R / Huang, Chiung-Wei / An, Yang / Oommen, Anup / Tanaka, Toshiko / Ferrucci, Luigi / Elango, Palchamy / Takebayashi, Toru / Harada, Sei / Iida, Miho / Thambisetty, Madhav

International journal of molecular sciences

2020 Volume 21, Issue 4

Abstract: Rapid lifestyle and dietary changes have contributed to a rise in the global prevalence of metabolic syndrome (MetS), which presents a potential healthcare crisis, owing to its association with an increased burden of multiple cardiovascular and ... ...

Abstract	Rapid lifestyle and dietary changes have contributed to a rise in the global prevalence of metabolic syndrome (MetS), which presents a potential healthcare crisis, owing to its association with an increased burden of multiple cardiovascular and neurological diseases. Prior work has identified the role that genetic, lifestyle, and environmental factors can play in the prevalence of MetS. Metabolomics is an important tool to study alterations in biochemical pathways intrinsic to the pathophysiology of MetS. We undertook a metabolomic study of MetS in serum samples from two ethnically distinct, well-characterized cohorts-the Baltimore Longitudinal Study of Aging (BLSA) from the U.S. and the Tsuruoka Metabolomics Cohort Study (TMCS) from Japan. We used multivariate logistic regression to identify metabolites that were associated with MetS in both cohorts. Among the top 25 most significant (lowest
MeSH term(s)	Aged ; Aged, 80 and over ; Aging/genetics ; Aging/metabolism ; Aging/pathology ; Amino Acids/metabolism ; Female ; Humans ; Longitudinal Studies ; Male ; Metabolic Syndrome/blood ; Metabolic Syndrome/pathology ; Metabolome/genetics ; Metabolomics
Chemical Substances	Amino Acids
Language	English
Publishing date	2020-02-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21041249
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Article: Abnormal brain cholesterol homeostasis in Alzheimer's disease-a targeted metabolomic and transcriptomic study.

Varma, Vijay R / Büşra Lüleci, H / Oommen, Anup M / Varma, Sudhir / Blackshear, Chad T / Griswold, Michael E / An, Yang / Roberts, Jackson A / O'Brien, Richard / Pletnikova, Olga / Troncoso, Juan C / Bennett, David A / Çakır, Tunahan / Legido-Quigley, Cristina / Thambisetty, Madhav

NPJ aging and mechanisms of disease

2021 Volume 7, Issue 1, Page(s) 11

Abstract: The role of brain cholesterol metabolism in Alzheimer's disease (AD) remains unclear. Peripheral and brain cholesterol levels are largely independent due to the impermeability of the blood brain barrier (BBB), highlighting the importance of studying the ... ...

Abstract	The role of brain cholesterol metabolism in Alzheimer's disease (AD) remains unclear. Peripheral and brain cholesterol levels are largely independent due to the impermeability of the blood brain barrier (BBB), highlighting the importance of studying the role of brain cholesterol homeostasis in AD. We first tested whether metabolite markers of brain cholesterol biosynthesis and catabolism were altered in AD and associated with AD pathology using linear mixed-effects models in two brain autopsy samples from the Baltimore Longitudinal Study of Aging (BLSA) and the Religious Orders Study (ROS). We next tested whether genetic regulators of brain cholesterol biosynthesis and catabolism were altered in AD using the ANOVA test in publicly available brain tissue transcriptomic datasets. Finally, using regional brain transcriptomic data, we performed genome-scale metabolic network modeling to assess alterations in cholesterol biosynthesis and catabolism reactions in AD. We show that AD is associated with pervasive abnormalities in cholesterol biosynthesis and catabolism. Using transcriptomic data from Parkinson's disease (PD) brain tissue samples, we found that gene expression alterations identified in AD were not observed in PD, suggesting that these changes may be specific to AD. Our results suggest that reduced de novo cholesterol biosynthesis may occur in response to impaired enzymatic cholesterol catabolism and efflux to maintain brain cholesterol levels in AD. This is accompanied by the accumulation of nonenzymatically generated cytotoxic oxysterols. Our results set the stage for experimental studies to address whether abnormalities in cholesterol metabolism are plausible therapeutic targets in AD.
Language	English
Publishing date	2021-06-01
Publishing country	England
Document type	Journal Article
ZDB-ID	2836493-4
ISSN	2056-3973
ISSN	2056-3973
DOI	10.1038/s41514-021-00064-9
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Article ; Online: High-Fat, High-Sugar Diet Disrupts the Preovulatory Hormone Surge and Induces Cystic Ovaries in Cycling Female Rats.

Volk, Katrina M / Pogrebna, Veronika V / Roberts, Jackson A / Zachry, Jennifer E / Blythe, Sarah N / Toporikova, Natalia

Journal of the Endocrine Society

2017 Volume 1, Issue 12, Page(s) 1488–1505

Abstract: Diet-induced obesity has been associated with various metabolic and reproductive disorders, including polycystic ovary syndrome. However, the mechanisms by which obesity influences the reproductive system are still not fully known. Studies have suggested ...

Abstract	Diet-induced obesity has been associated with various metabolic and reproductive disorders, including polycystic ovary syndrome. However, the mechanisms by which obesity influences the reproductive system are still not fully known. Studies have suggested that impairments in hormone signaling are associated with the development of symptoms such as acyclicity and ovarian cysts. However, these studies have often failed to address how these hormonal changes arise and how they might contribute to the progression of reproductive diseases. In the present study, we used a high-fat, high-sugar (HFHS) diet to induce obesity in a female rodent model to determine the changes in critical reproductive hormones that might contribute to the development of irregular estrous cycling and reproductive cycle termination. The HFHS animals exhibited impaired estradiol, progesterone (P4), and luteinizing hormone (LH) surges before ovulation. The HFHS diet also resulted in altered basal levels of testosterone (T) and LH. Furthermore, alterations in the basal P4/T ratio correlated strongly with ovarian cyst formation in HFHS rats. Thus, this model provides a method to assess the underlying etiology of obesity-related reproductive dysfunction and to examine an acyclic reproductive phenotype as it develops.
Language	English
Publishing date	2017-11-02
Publishing country	United States
Document type	Journal Article
ISSN	2472-1972
ISSN (online)	2472-1972
DOI	10.1210/js.2017-00305
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