Neurology Commons^™

Surgeons’ Knowledge Regarding Perioperative Pain Management In Patients With Opioid Use Disorder: A Survey Among 260 Members Of The American College Of Surgeons, Caroline E Crocker, Romana Sharmeen, Thu T Tran, Amir M Khan, Wen Li, Joseph L Alcorn

Faculty, Staff and Student Publications

Surfactant protein A (SP-A) has important roles in innate immunity and modulation of pulmonary and extrapulmonary inflammation. Given SP-A has been detected in rat and human brain, we sought to determine if SP-A has a role in modulating inflammation in the neonatal mouse brain. Neonatal wildtype (WT) and SP-A-deficient (SP-A

Glutamatergic Cerebellar Neurons Differentially Contribute To The Acquisition Of Motor And Social Behaviors, Meike E Van Der Heijden, Alejandro G Rey Hipolito, Linda H Kim, Dominic J Kizek, Ross M Perez, Tao Lin, Roy V Sillitoe

Duncan NRI Faculty and Staff Publications

Insults to the developing cerebellum can cause motor, language, and social deficits. Here, we investigate whether developmental insults to different cerebellar neurons constrain the ability to acquire cerebellar-dependent behaviors. We perturb cerebellar cortical or nuclei neuron function by eliminating glutamatergic neurotransmission during development, and then we measure motor and social behaviors in early postnatal and adult mice. Altering cortical and nuclei neurons impacts postnatal motor control and social vocalizations. Normalizing neurotransmission in cortical neurons but not nuclei neurons restores social behaviors while the motor deficits remain impaired in adults. In contrast, manipulating only a subset of nuclei neurons leaves social …

Ragd Auto-Activating Mutations Impair Mit/Tfe Activity In Kidney Tubulopathy And Cardiomyopathy Syndrome, Irene Sambri, Marco Ferniani, Giulia Campostrini, Marialuisa Testa, Viviana Meraviglia, Mariana E G De Araujo, Ladislav Dokládal, Claudia Vilardo, Jlenia Monfregola, Nicolina Zampelli, Francesca Del Vecchio Blanco, Annalaura Torella, Carolina Ruosi, Simona Fecarotta, Giancarlo Parenti, Leopoldo Staiano, Milena Bellin, Lukas A Huber, Claudio De Virgilio, Francesco Trepiccione, Vincenzo Nigro, Andrea Ballabio

Duncan NRI Faculty and Staff Publications

Heterozygous mutations in the gene encoding RagD GTPase were shown to cause a novel autosomal dominant condition characterized by kidney tubulopathy and cardiomyopathy. We previously demonstrated that RagD, and its paralogue RagC, mediate a non-canonical mTORC1 signaling pathway that inhibits the activity of TFEB and TFE3, transcription factors of the MiT/TFE family and master regulators of lysosomal biogenesis and autophagy. Here we show that RagD mutations causing kidney tubulopathy and cardiomyopathy are "auto- activating", even in the absence of Folliculin, the GAP responsible for RagC/D activation, and cause constitutive phosphorylation of TFEB and TFE3 by mTORC1, without affecting the phosphorylation …

Dextromethorphan/Quinidine For The Pseudobulbar Affect In Neurological Disorders And Injuries: Systematic Review And Meta-Analysis, Magnolia Livingston

Honors Theses

AVP-923, commonly known as Nuedexta or Zenvia, is a drug that has recently been suggested as a potential treatment for Pseudobulbar Affect in patients affected by different neurological disorders and injuries. Studies have been done to examine the effectiveness of AVP-923 on PBA, but the results of these studies don’t seem to be comparable. The goal of this meta-analysis is to assess the efficacy and safety of AVP-923. 781 individuals from six trials were included in the analysis. The analysis's findings revealed that AVP-923 considerably lowered the Center for Neurological Study Lability Scale (CNS-LS) scores and the frequency and severity …

Lipoxin A4 (Lxa4) Reduces Alkali-Induced Corneal Inflammation And Neovascularization And Upregulates A Repair Transcriptome, Jiucheng He, Thang L. Pham, Azucena H. Kakazu, Abhilash Ponnath, Khanh V. Do, Haydee E.P. Bazan

School of Graduate Studies Faculty Publications

Purpose: To investigate the anti-inflammatory and anti-angiogenic effects of the bioactive lipid mediator LXA4 on a rat model of severe corneal alkali injury. Methods: To induce a corneal alkali injury in the right eyes of anesthetized Sprague Dawley rats. They were injured with a Φ 4 mm filter paper disc soaked in 1 N NaOH placed on the center of the cornea. After injury, the rats were treated topically with LXA4 (65 ng/20 μL) or vehicle three times a day for 14 days. Corneal opacity, neovascularization (NV), and hyphema were recorded and evaluated in a blind manner. Pro-inflammatory cytokine expression …

Automated Subfield Volumetric Analysis Of Amygdala, Hippocampus, And Thalamic Nuclei In Mesial Temporal Lobe Epilepsy, Arichena Manmatharayan, Michael Kogan, Caio Matias, Mashaal Syed, India Shelley, Amar Chinni, Kichang Kang, Kiran Talekar, Scott H. Faro, Feroze B. Mohamed, Ashwini Sharan, Chengyuan Wu, Mahdi Alizadeh

Department of Neurosurgery Faculty Papers

Purpose: Identifying relationships between clinical features and quantitative characteristics of the amygdala-hippocampal and thalamic subregions in mesial temporal lobe epilepsy (mTLE) may offer insights into pathophysiology and the basis for imaging prognostic markers of treatment outcome. Our aim was to ascertain different patterns of atrophy or hypertrophy in mesial temporal sclerosis (MTS) patients and their associations with postsurgical seizure outcomes. To assess this aim, this study is designed in 2 folds: (1) hemispheric changes within MTS group and (2) association with postsurgical seizure outcomes.

Methods and materials: 27 mTLE subjects with mesial temporal sclerosis (MTS) were scanned for conventional 3D …

Dynamic Role Of Exosome Micrornas In Cancer Cell Signaling And Their Emerging Role As Noninvasive Biomarkers, Jaya Aseervatham

Department of Neurology Faculty Papers

Exosomes are extracellular vesicles that originate from endosomes and are released by all cells irrespective of their origin or type. They play an important role in cell communication and can act in an autocrine, endocrine, or paracrine fashion. They are 40–150 nm in diameter and have a similar composition to the cell of origin. An exosome released by a particular cell is unique since it carries information about the state of the cell in pathological conditions such as cancer. miRNAs carried by cancer-derived exosomes play a multifaceted role by taking part in cell proliferation, invasion, metastasis, epithelial–mesenchymal transition, angiogenesis, apoptosis, …

Efficient Cancer Modeling Through Crispr-Cas9/Hdr-Based Somatic Precision Gene Editing In Mice, Wen Bu, Chad J Creighton, Kelsey S Heavener, Carolina Gutierrez, Yongchao Dou, Amy T Ku, Yiqun Zhang, Weiyu Jiang, Jazmin Urrutia, Wen Jiang, Fei Yue, Luyu Jia, Ahmed Atef Ibrahim, Bing Zhang, Shixia Huang, Yi Li

Faculty, Staff and Student Publications

CRISPR-Cas9 has been used successfully to introduce indels in somatic cells of rodents; however, precise editing of single nucleotides has been hampered by limitations of flexibility and efficiency. Here, we report technological modifications to the CRISPR-Cas9 vector system that now allows homology-directed repair-mediated precise editing of any proto-oncogene in murine somatic tissues to generate tumor models with high flexibility and efficiency. Somatic editing of either

A Nine-Year Longitudinal Case Study Of A 27-Year-Old Male With Neurocysticercosis Presenting With New Onset Seizures, Ciara Doyle, Veronica Thompson, Amanda Ho, Joy Zarandy

Research Day

Background:

Taenia solium is a cestode endemic to regions of Latin America, Asia, sub-Saharan Africa and Oceania, and serves as the most common cause of acquired epilepsy in the world. T. solium eggs are transmitted fecal-orally when a human or pig host ingests contaminated food or water. Larvae hatch from the intestines and invade into muscle, tissue, or organs, forming cysts called cysticerci. Cysticerci involving the central nervous system is termed neurocysticercosis (NCC). Patients with NCC typically remain asymptomatic for 3-5 years in the viable stage until the host’s immune response is activated in the degenerating stage. Immune-mediated degradation of …

Participation Of Children And Youth With And Without Cerebral Palsy Across Settings: An Exploratory Study, Teresa Long Pierce, Alyssa Laforme Fiss

Research Day

Introduction: Cerebral Palsy is one of the most common pediatric health conditions resulting in childhood disability. Children with CP experience varying levels of functional impairments due to muscle weakness, alterations in muscle tone, balance deficits, and loss of selective motor control. These impairments and activity limitations are thought to contribute to lower levels of participation. Studies examining participation of children with CP have found that participation is positively correlated with increased physical activity and have concluded that environment is a significant predictor of participation. However, research examining participation across specific environments is lacking. Additionally, research investigating the influence of various …

A Headfirst Approach – Concussion Management And Novel Diagnostic Testing, Madison Cohen, Kevin Wang, Julienne Ryland, Donald Penney

Research Day

INTRODUCTION: The incidence of concussions has become increasingly prevalent across a multitude of sports. Despite this, the current guidelines for concussion management are not well defined, which creates a significant barrier to proper evaluation and care.

OBJECTIVES: This manuscript was designed to help physicians, athletic trainers, coaches, and parents understand the clinical signs of concussion and management from the moment of injury to the athlete’s return to play. Additionally, we reviewed post-concussion sequelae and their incidence following concussion management.

METHODS: In order to better define the current approach to the management of sports-related concussions we completed a comprehensive literature review …

The Effect Of Microglial Cell Dysfunction On Multi-Modal Pre-Pulse Inhibition, Michelle Besser

Dissertations, 2020-current

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by persistent deficits in social communication, restricted behaviors, and executive functioning deficits. Mutations in fractalkine signaling, particularly in CX3CR1, in the brain have been linked to ASD and other neurodevelopmental disorders. This investigation examined wild-type mice and mice with one or two copies of mutated CX3CR1 and their uni-modal (auditory and somatosensory) and multi-modal (combined) pre-pulse inhibitions (PPI). PPI is an unconditioned response – a decrement in the acoustic startle reflex when the mouse detects a non-startling stimulus presented a few hundred ms before the startling sound. In this study, the …

Logical Definition-Based Identification Of Potential Missing Concepts In Snomed Ct, Xubing Hao, Rashmie Abeysinghe, Kirk Roberts, Licong Cui

Faculty, Staff and Student Publications

Background

Biomedical ontologies are representations of biomedical knowledge that provide terms with precisely defined meanings. They play a vital role in facilitating biomedical research in a cross-disciplinary manner. Quality issues of biomedical ontologies will hinder their effective usage. One such quality issue is missing concepts. In this study, we introduce a logical definition-based approach to identify potential missing concepts in SNOMED CT. A unique contribution of our approach is that it is capable of obtaining both logical definitions and fully specified names for potential missing concepts.

Method

The logical definitions of unrelated pairs of fully defined concepts in non-lattice subgraphs …

Tfeb And Tfe3 Drive Kidney Cystogenesis And Tumorigenesis, Chiara Di Malta, Angela Zampelli, Letizia Granieri, Claudia Vilardo, Rossella De Cegli, Laura Cinque, Edoardo Nusco, Salvatore Pece, Daniela Tosoni, Francesca Sanguedolce, Nicolina Cristina Sorrentino, Maria J Merino, Deborah Nielsen, Ramaprasad Srinivasan, Mark W Ball, Christopher J Ricketts, Cathy D Vocke, Martin Lang, Baktiar Karim, Luisa Lanfrancone, Laura S Schmidt, W Marston Linehan, Andrea Ballabio

Duncan NRI Faculty and Staff Publications

Birt-Hogg-Dubé (BHD) syndrome is an inherited familial cancer syndrome characterized by the development of cutaneous lesions, pulmonary cysts, renal tumors and cysts and caused by loss-of-function pathogenic variants in the gene encoding the tumor-suppressor protein folliculin (FLCN). FLCN acts as a negative regulator of TFEB and TFE3 transcription factors, master controllers of lysosomal biogenesis and autophagy, by enabling their phosphorylation by the mechanistic Target Of Rapamycin Complex 1 (mTORC1). We have previously shown that deletion of Tfeb rescued the renal cystic phenotype of kidney-specific Flcn KO mice. Using Flcn/Tfeb/Tfe3 double and triple KO mice, we now show that both Tfeb …

Tmem106b Regulates Microglial Proliferation And Survival In Response To Demyelination, Tingting Zhang, Weilun Pang, Tuancheng Feng, Jennifer Guo, Kenton Wu, Mariela Nunez Santos, Akshayakeerthi Arthanarisami, Alissa L Nana, Quynh Nguyen, Peter J Kim, Joanna L Jankowsky, William W Seeley, Fenghua Hu

Faculty, Staff and Students Publications

TMEM106B, a lysosomal transmembrane protein, has been closely associated with brain health. Recently, an intriguing link between TMEM106B and brain inflammation has been discovered, but how TMEM106B regulates inflammation is unknown. Here, we report that TMEM106B deficiency in mice leads to reduced microglia proliferation and activation and increased microglial apoptosis in response to demyelination. We also found an increase in lysosomal pH and a decrease in lysosomal enzyme activities in TMEM106B-deficient microglia. Furthermore, TMEM106B loss results in a significant decrease in the protein levels of TREM2, an innate immune receptor essential for microglia survival and activation. Specific ablation of TMEM106B …

Differential Degeneration Of Neurons In A Mouse Model Of Canavan Disease, Vibha Chauhan, Quy Nguyen, Jeremy Francis, Paola Leone

Rowan-Virtua Research Day

Canavan disease (CD) is an inherited leukodystrophy caused by inactivating mutations to the glial enzyme aspartoacylase (ASPA). ASPA catabolizes neuronal N-acetylaspartate (NAA) into free acetate and aspartate and loss of this function results in the chronic elevation of non-catabolized NAA and the failure of developmental myelination. Elevated NAA is thought to cause damage to myelin and myelin-producing cells (oligodendrocytes, but the viability of neurons in CD is relatively unexplored. We compare here the progressive degeneration of neurons in two regions of the CD mouse brain, the thalamus and the cortex, distinguished by differing degrees of vacuolation, and show that the …

The Impact Of Covid-19 On Post-Recovery Memory, Chelsea Mcnamara, Alison Mancuso

Rowan-Virtua Research Day

The SARS-CoV-2 virus, responsible for the covid-19 pandemic, has had profound effects on countries worldwide. As the pandemic progressed, clinical and patient data continued to mount. A subset of symptoms named “Long Covid Syndrome” persisted in patients after recovering from infection. One commonly reported but understudied symptom was a deficit in memory function. Although commonly reported, prevalence of ‘brain fog’ has yet to be characterized using patient data. Using Rowan Medicine electronic patient data, we were able to collect information on patients before and after the emergence of the coronavirus. Data was collected on reported memory-related symptoms as well as …

Obstructive Hydrocephalus Caused By A Colloid Cyst Presenting As A Transient Ischemic Attack (Tia), Muhammad Nadeem

Rowan-Virtua Research Day

Colloid cysts are benign growths commonly found in the third ventricle or at the Foramen of Monroe. They are composed of epithelial lining filled with gelatinous material that contain cholesterol, mucin, old blood and ions. Most colloid cysts are asymptomatic but can present with a variety of symptoms that range from headaches, diplopia, memory problems, and vertigo. They can also present as an obstructive hydrocephalus with the classic “Wet, wacky and wobbly” triad. Rarely colloid cysts have been reported to cause sudden death. They can present to the ED with any spectrum of these symptoms.

Dancing Through Parkinson’S: Investigating The Impact Of Argentine Tango On Motor, Cognitive And Psychosocial Function, Suraj Pothineni, Fazal Choudhary

Rowan-Virtua Research Day

Background: People with Parkinson’s Disease (PD) undergo progressive motor, cognitive, and psychosocial symptoms, which decrease their quality of life (QOL). Adapted tango (AT) has recently emerged as a promising approach to ameliorating functional mobility, balance, and gait seen in people with PD.

Methods: A comprehensive literature review is conducted using databases such as PubMed, SCOPUS, and Embase. A wide variety of search terms are used, including but not limited to Parkinson’s disease, exercise, dance, tango, motor, cognitive, psychosocial effects, freezing of gait, and balance.

Results: People with PD who have undergone AT have improved in certain motor, cognitive and psychosocial …

Mesenchymal Stem Cell Therapy For Amyotrophic Lateral Sclerosis, Vrushank Shah, Usmaan Al-Shehab, Keyur Patel, Alexander King

Rowan-Virtua Research Day

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig disease, is a fatal neurodegenerative disease affecting motor neurons in the brain and spinal cord. Progressive muscle weakness, atrophy, and spasticity characterize the condition, which eventually leads to paralysis and respiratory failure. There is currently no cure for ALS, and the standard of care is supportive, with riluzole being the only approved medication that has been shown to slightly slow disease progression (1).

However, the use of mesenchymal stem cells (MSCs) in the treatment of ALS is a new area of research in regenerative medicine. MSCs are multipotent stem cells that …

Case Study: Posterior Reversible Encephalopathy Syndrome (Pres) In A Stroke Patient With Seizures, Akhmad Ernazarov, Shikhar Manchanda, Yvette Wang

Rowan-Virtua Research Day

Posterior Reversible Encephalopathy Syndrome (PRES) is a condition in which patients present with visual disturbances, headaches, seizures, and impaired consciousness. It can affect a wide variety of patients ranging from infants to elderly, but young and middle aged adults are most commonly affected; females are more likely to be affected by PRES than males. Risk factors such as hypertension, pre-eclampsia/eclampsia, renal failure, cytotoxic conditions and autoimmune conditions predispose patients to PRES. In this unique case, a 63 female patient was admitted to Jefferson Washington Hospital exhibiting classic stroke like symptoms. Patient also began seizing in the ED which was unusual …

Chronic Headache Leading To The Diagnosis Of Empty Sella, Melissa Itidiare Locke, Rachel Burke

Rowan-Virtua Research Day

Headaches are one of the most common chief complaints presenting to the Emergency Department. The differential is broad. The workup is tailored to the patient’s history. Here we present the case of a young female who developed headaches over the past year. After numerous imaging studies of her brain, the most recent revealed an Empty Sella diagnosis.

The Correlation Between Traumatic Brain Injury And Incarceration Among Adult Males In The United States, Shadi Shams

Rowan-Virtua Research Day

The United States has one of the largest growing prison populations in the world. A large amount of social and economic resources go towards the cost and maintenance of correctional facilities each year. Additionally, the current correctional programs are insufficient in assisting inmates with getting back to society; especially those with traumatic brain injury (TBI) who often remain undiagnosed and are usually treated unfairly in the prison system instead of receiving the appropriate help. Prior scholarly work has shown that patients in the post-TBI stage are more likely to enter the judicial system. In the recent population-based cohort study, the …

Case Study Of Horner Syndrome Due To Internal Carotid Artery Dissection, Kajel Patel

Rowan-Virtua Research Day

Carotid artery dissection can occur either spontaneously or because of trauma. It is usually the most common cause of stroke in middle-aged patients. The symptoms can be transient or persistent and typically occur a few days after the inciting traumatic event.

A 5-Year Clinical Course Of Phenocopy Syndrome Of Behavioral Variant Frontotemporal Dementia: Case Report And Literature Review, Joseph Melillo, Keyur Patel, Christian White

Rowan-Virtua Research Day

Frontotemporal dementia is a neurocognitive disease which affects language, behavior, or executive functioning. This disease includes a spectrum of presentations which includes multiple variants. The phenocopy syndrome of behavioral variant frontotemporal dementia is one which mimics the behavioral variant of frontotemporal dementia. Patients with this condition show a decline in personality, social conduct and cognitive ability but often display no signs of neurological imaging and exhibit slow progression. This case focuses on a now 70-year-old male who has shown signs of behavioral changes with a slowly progressive clinical course and minimal findings on PET scan, but moderate changes seen on …

Case Report: Abrupt Psychosis Or Nmda Receptor Encephalitis?, Alexis Dunn, Neelesh Parikh, James Espinosa, Alan Lucerna

Rowan-Virtua Research Day

We report a case of a 46-year-old female who was initially committed to a psychiatric facility for new onset schizophrenia symptoms. She later had an extensive workup in the hospital due to leukocytosis and was believed to have NMDA Receptor Encephalitis as the cause for her new behavioral symptoms. This case report aims to educate EM (emergency medicine) physicians to keep a broad differential diagnosis on patients who present with new onset, unprovoked psychosis later in life.

Hypokalemic Periodic Paralysis Secondary To Thyrotoxicosis, Anugraha Kutty, Alexandra Hart, Danielle Palaferro, Pavel Itersky

Research Day

Background:

Hypokalemic Periodic Paralysis (HPP) is a rare neuromuscular disorder characterized by acute, transient muscle weakness and paralysis secondary to hypokalemia and can be complicated by cardiac arrhythmias. Thyrotoxic Periodic Paralysis (TPP) is an acquired type of HPP seen in the setting of thyrotoxicosis. Most TPP patients present with subtle signs and symptoms of thyrotoxicosis prior to an acute muscle paralysis event. Therefore, recognizing TPP in the emergency setting is critical in preventing life-threatening cardiac, respiratory, renal, or other systemic complications induced by a hypokalemic state.

Case Report:

An 18-year-old Hispanic male presented to the emergency department, with no past …

Vision Loss: A Rare Complication Of Intravenous T-Pa In The Treatment Of Acute Ischemic Stroke, Shreya Dundumalla, Brian Smith

Research Day

An 86-year-old African American female presented to a community hospital with intractable left shoulder pain and was admitted for the correction of electrolyte abnormalities. Three days into her hospital course, she developed altered mental status, dysarthria, and facial droop. A CT scan showed no evidence of acute intracranial hemorrhage. After neurologic evaluation and informed consent was given by the patient’s daughter, the decision was made to administer intravenous t-PA for the treatment of acute ischemic stroke. Two hours after tPA administration, a CT scan showed no evidence of hemorrhagic conversion. Four hours later, the patient began to complain of redness, …

Examining The Utility Of The Canadian Occupational Performance Measure (Copm) Vs. Cognitive Mapping And Motivational Interviewing (Cm/Mi) To Provide Person-Centered Care (Pcc) For People With Parkinson’S Disease (Pwpd), Mary Lagasca, Karen Aranha

Spring 2023 Virtual OTD Capstone Symposium

Background: Parkinson’s disease (PD) limits occupational engagement and quality of life. Clinicians need tools to help understand the lived experiences of people with PD to provide more person-centered care (PCC). The Canadian Occupational Performance Model (COPM) is one tool used with this population, but its predetermined categories may be limiting. In contrast, Cognitive Mapping and Motivational Interviewing (CM/MI) is a non-standardized method that may provide more insight. Objective: To identify the benefits of the COPM to CM/MI in delivering more person-centered care (PCC). Methodology: A qualitative phenomenological self-study was used. Data collection compared the assessments and reflected on determining if …

Association Of Mitochondrial Dna Copy Number With Brain Mri Markers And Cognitive Function: A Meta-Analysis Of Community-Based Cohorts, Yuankai Zhang, Xue Liu, Kerri L Wiggins, Nuzulul Kurniansyah, Xiuqing Guo, Amanda L Rodrigue, Wei Zhao, Lisa R Yanek, Scott M Ratliff, Achilleas Pitsillides, Juan Sebastian Aguirre Patiño, Tamar Sofer, Dan E Arking, Thomas R Austin, Alexa S Beiser, John Blangero, Eric Boerwinkle, Jan Bressler, Joanne E Curran, Lifang Hou, Timothy M Hughes, Sharon L R Kardia, Lenore J Launer, Daniel Levy, Thomas H Mosley, Ilya M Nasrallah, Stephen S Rich, Jerome I Rotter, Sudha Seshadri, Wassim Tarraf, Kevin A González, Vasan Ramachandran, Kristine Yaffe, Paul A Nyquist, Bruce M Psaty, Charles S Decarli, Jennifer A Smith, David C Glahn, Hector M González, Joshua C Bis, Myriam Fornage, Susan R Heckbert, Annette L Fitzpatrick, Chunyu Liu, Claudia L Satizabal

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVES: Previous studies suggest that lower mitochondrial DNA (mtDNA) copy number (CN) is associated with neurodegenerative diseases. However, whether mtDNA CN in whole blood is related to endophenotypes of Alzheimer disease (AD) and AD-related dementia (AD/ADRD) needs further investigation. We assessed the association of mtDNA CN with cognitive function and MRI measures in community-based samples of middle-aged to older adults.

METHODS: We included dementia-free participants from 9 diverse community-based cohorts with whole-genome sequencing in the Trans-Omics for Precision Medicine (TOPMed) program. Circulating mtDNA CN was estimated as twice the ratio of the average coverage of mtDNA to nuclear …