Digital Commons Network^™

Airway Management In Emergency Department Thoracotomy: A Narrative Review, Aaron J Lacy, Adam Liebendorfer, Sarah M Guess, Rami S Al-Aref, Anthony P Kronfli, Rachel E Armstrong, Amelia W Maiga, Alexander Bracey, Ryan N Barnicle

2020-Current year OA Pubs

INTRODUCTION: Emergency department thoracotomy (EDT) is a high-risk, life-saving intervention for patients in traumatic cardiac arrest. A critical component of EDT is airway management, typically performed by emergency physicians, yet formal guidance regarding optimal strategies remains limited. Airway management in this setting is uniquely complex due to concurrent anatomic injury, physiologic instability, and the procedural demands of thoracotomy.

DISCUSSION: Endotracheal intubation (ETI) during EDT presents multiple challenges. Anatomic difficulties may arise from facial or cervical trauma, restricted positioning, and the presence of cervical collars. Cognitive load is heightened by the chaotic, multidisciplinary environment, requiring strategies such as pre-briefing, checklists, and …

Identification Of Distinct Subtypes In Immune Tolerance After Hematopoietic Cell Transplantation Using The Prospective Able1.0 Pediatric Study Cohort, Bernard Ng, Shalini Shenoy, Et Al.

2020-Current year OA Pubs

The lack of immune tolerance after hematopoietic cell transplantation (HCT) can result in chronic graft-versus-host disease (cGvHD), which is the primary nonrelapse limitation of successful HCT. To date, immune tolerance has been considered a single biological entity, but we hypothesized that post-HCT immune tolerance could develop through multiple pathways. Using the ABLE network database, which comprises measurements of 75 cell populations, 10 cytokines and chemokines, lymphocyte population telomere length, KRECs and TRECs, and 132 metabolites from the largest pediatric cGvHD cohort (n = 241), we applied clustering analysis to patients with primary immune tolerance (PIT; no acute GvHD [aGvHD] or …

Excellent Outcomes In Feasibility Study Of Radiation-Free Conditioning And Transplant In Pediatric Severe Aplastic Anemia, Mithra Lakshmi Narasimhan, Irem Eldem, Jeffrey J Bednarski, Ginny L Schulz, Robert J Hayashi, Shalini Shenoy

2020-Current year OA Pubs

Severe aplastic anemia (SAA) is treated with a hematopoietic cell transplant (HCT) in the presence of an HLA-matched sibling donor (MSD) with disease-free survival (DFS) of >90%. In the absence of an MSD, immunosuppressive therapy (IST) can induce remission but concerns for relapsed/refractory disease and clonal hematopoiesis persist. IST failure is an indication for HCT. Modern HCT approaches target barriers such as graft rejection (GR), graft-versus-host disease (GVHD), and transplant-related toxicities. Traditionally, total body irradiation (TBI) inclusive HCT conditioning helps decrease GR, but the use of TBI in children increases concerns for late effects such as malignancies. To describe outcomes …

Comparison Of Breast And Gastric Her2 Immunohistochemistry (Ihc) Scoring Criteria In The Assessment Of Endometrial Carcinoma, Rachel L Furuya, Whitney Grither, Matthew A Powell, Premal H Thaker, Et Al.

2020-Current year OA Pubs

BACKGROUND: Immunohistochemistry (IHC) testing is the primary method to determine HER2 status at many institutions, often with reflex to in situ hybridization (ISH). DNA- and RNA- based platforms are emerging for HER-2 assessment. While approved IHC algorithms exist for HER2 scoring in breast and gastric carcinomas, neither has been validated in endometrial cancer. This study seeks to compare them and evaluate patterns of DNA and RNA expression.

METHODS: 263 endometrioid endometrial adenocarcinoma (EEA), 275 serous endometrial carcinoma (SEC), and 214 uterine carcinosarcoma (UCS) specimens were randomly selected. Previously stained HER2 IHC slides underwent blinded review by two board-certified pathologists and …

Atomic Models Of The Toxoplasma Cell Invasion Machinery, Jianwei Zeng, Yong Fu, Pengge Qian, Wei Huang, Qingwei Niu, Wandy L Beatty, Alan Brown, L David Sibley, Rui Zhang

2020-Current year OA Pubs

Apicomplexan parasites, responsible for toxoplasmosis, cryptosporidiosis and malaria, invade host cells through a unique gliding motility mechanism powered by actomyosin motors and a dynamic organelle called the conoid. Here, using cryo-electron microscopy, we determined structures of four essential complexes of the Toxoplasma gondii conoid: the preconoidal P2 ring, tubulin-based conoid fibers, and the subpellicular and intraconoidal microtubules. Our analysis identified 40 distinct conoid proteins, several of which are essential for parasite lytic growth, as revealed through genetic disruption studies. Comparative analysis of the tubulin-containing complexes sheds light on their functional specialization by microtubule-associated proteins, while the structure of the preconoidal …

Mapping The Genetic Landscape Across 14 Psychiatric Disorders, Andrew D. Grotzinger, Alexander S. Hatoum, Emma C. Johnson, Et Al.

2020-Current year OA Pubs

No abstract provided.

Evaluation Of Mycoplasma Genitalium Positivity And Co-Infection With Chlamydia Trachomatis And/Or Neisseria Gonorrhoeae At Various Care Sites Across The United States, Rebecca Lillis, Stacey House, Et Al.

2020-Current year OA Pubs

OBJECTIVES: We evaluated Mycoplasma genitalium (MG) positivity and co-infection with Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG), based on results from a trial assessing clinical performance of the Cobas® Liat CT/NG/MG point-of-care test.

METHODS: A prospective, US, multicenter, noninterventional study assessed MG positivity in prospective urine samples (male) and clinician-collected vaginal swabs (female) from symptomatic/asymptomatic patients aged ≥14 years attending various clinical settings. Participants were designated positive or negative for MG, CT, and NG based on combined results from three US Food and Drug Administration-approved assays and one laboratory-developed test. MG co-infection with CT and/or NG was assessed.

RESULTS: Among …

An Integrated Analysis Of Three Medulloblastoma Clinical Trials Refines Risk-Stratification Approaches For Reducing Toxicity And Improving Survival, Kyle S Smith, Jeff M Michalski, Et Al.

2020-Current year OA Pubs

BACKGROUND: The identification of clinical and molecular heterogeneity in medulloblastoma has produced risk-stratified therapy, but establishing the most effective yet least toxic regimens has remained elusive owing to numerous treatment options. To improve risk-stratification, we performed an integrated analysis from three clinical trials.

METHODS: Medulloblastoma patients from ACNS0331/NCT00085735, ACNS0332/NCT00392327, and SJMB03/NCT00085202 were included if they had methylation profiling. Molecular groups [WNT, SHH, Group 3 (G3), and Group 4 (G4)], subgroups, and copy number variations were procured from methylation profiles and mutations from next-generation sequencing. Data was assembled into an interactive portal to capture patient characteristics. Cross-trial comparisons, univariable, and multivariable …

Identifying Disparities In Same-Day Surgery Cancellations: Impact Of Race And Socioeconomic Factors In A Pediatric Health System, Nicole M Santucci, Daniel Alligood, Amanda Maytin-Hevia, Danyi Wang, Kelly Chilson, Jesse Vrecenak, Andrew Yeh, Colin A Martin

2020-Current year OA Pubs

PURPOSE: Same-day surgery (SDS) cancellations have significant implications on patients and hospitals. This study aimed to identify demographic and socioeconomic factors that impact SDS cancellations across a single pediatric health system.

METHODS: A case-control retrospective review captured patients (age < 18) who underwent SDS procedures from July 2022 to August 2024. Patients were included if they underwent any procedure at three operative sites: a tertiary pediatric academic hospital (PAH) and two outpatient surgery centers (OSC). Patients whose SDS was cancelled (n = 2,034) were compared to those whose surgeries proceeded as scheduled (n = 25,573). Patient zip codes were matched to Child Opportunity Index (COI) 2.0 data.

RESULTS: The overall SDS cancellation rate was 7.37 %, with a significantly higher rate observed at the PAH compared to OSC (11.4 % vs 53 %, p < 0.001). Patients with cancelled cases were more likely to identify as Black and have the lowest quintile COI (p < 0.001). Cancelled in preop and no shows were two reasons with the most racial disparities. In a sub-analysis comparing cancelled cases between operating sites, PAH cancelled patients tended to be Black (23.8 % vs 11.7 %, p < 0.001) and have very low COI (20.1 % vs. 10.6 %, p < 0.001).

CONCLUSION: SDS cancellation rates are significantly higher amongst patients who identify as Black and reside in low opportunity neighborhoods. Disparities in cancellation rate are more significant in patients scheduled at the urban PAH compared …

Beyond Restless Sleep: A Cross-Sectional Study Of Obstructive Sleep Apnea Risk, Aging Biomarkers, And Chronic Low Back Pain, Khalid W Freij, Fiona Bat Agbor, Philemon Domoyeri, Kiari R Kinnie, Asia M Wiggins, Demario S Overstreet, Tammie L Quinn, Shivraj S Grewal, S Justin Thomas, Walid W Freij, Shameka L Cody, Michael A Owens, Robert E Sorge, Burel R Goodin, Edwin N Aroke

2020-Current year OA Pubs

This secondary data analysis aimed to determine the nature of the relationship between obstructive sleep apnea (OSA) risk, biological age acceleration, and nonspecific chronic low back pain (CLBP). In total, 199 adults aged 18-82 years who filled both STOPBANG and pain questionnaires subsetted for secondary analysis. Based on the STOPBANG questionnaire, 104 had a low OSA risk and 95 had an intermediate or high OSA risk. Dunedin Pace of Aging Computed from the Epigenome (DunedinPACE), Horvath's, Hannum's, PhenoAge, and GrimAge clocks were used to determine biological age and pace of biological aging. Individuals with low OSA risk reported increased DunedinPACE …

An Integrated View Of The Structure And Function Of The Human 4d Nucleome, Job Dekker, Ting Wang, Daofeng Li, Et Al.

2020-Current year OA Pubs

The dynamic three-dimensional (3D) organization of the human genome (the 4D nucleome) is linked to genome function. Here we describe efforts by the 4D Nucleome Project

Lost Before Forgetting: Objective Driving Metrics Track Navigation Deficits Tied To Preclinical Alzheimer's Disease, Yiqi Zhu, Ramkrishna K Singh, Semere Bekena, David C Brown, Chen Chen, Matthew Blake, Jean-François Trani, Ganesh M Babulal

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES: Navigation is a complex, multisensory process in which subtle changes may emerge before the onset of symptomatic Alzheimer's disease (AD). This study investigated whether navigation abilities were associated with amyloid and tau pathology in cognitively normal older adults.

RESEARCH DESIGN AND METHODS: Among 285 cognitively unimpaired older adults, navigation and objective driving behaviors were assessed using the self-reported Santa Barbara Sense of Direction Scale (SBSOD) and a datalogger, respectively. Amyloid and tau burden were quantified using PET-MRI 2 years post-initial driving data collection. Linear mixed-effects models were used to evaluate the associations between biomarker status and longitudinal …

Advancing Inter-Brain Synchrony Measurement: A Comparative Hyperscanning Study Of Diffuse Optical Tomography And Functional Near-Infrared Spectroscopy, Shuo Guan, Yuhang Li, Yingbo Geng, Dongyun Li, Qiong Xu, Peisong Niu, Dalin Yang, Adam Eggebrecht, Yingchun Zhang, Rihui Li

2020-Current year OA Pubs

Inter-brain synchrony (IBS), measured by hyperscanning, refers to the synchronization of multiple individuals' brain activities during social interactions. Traditional fNIRS-based hyperscanning suffers shortcomings like low spatial resolution and high susceptibility to superficial interference, causing imprecise estimation of IBS in complex social tasks. This study aims to fill the knowledge gap by comprehensively assessing diffuse optical tomography (DOT), an enhanced alternative to fNIRS, can benefit hyperscanning studies of complex social interactions. Sixteen dyads were engaged in both collaborative and individual tangram puzzle tasks, and their brain activities were recorded simultaneously using DOT and fNIRS. We found that DOT demonstrated significantly stronger …

Abnormalities In Sensorimotor Brain Function Are Related To Chronicity Of Low Back Pain, Jo Armour Smith, Rongwen Tain, Kelli G Sharp, Laura M Glynn, Linda R Van Dillen, Jesse V Jacobs, Steven C Cramer

2020-Current year OA Pubs

Maladaptive plasticity in the brain may contribute to chronic low back pain (LBP) and underlie the altered postural control of the lumbopelvic musculature that is evident in some individuals with LBP. We recently described an MRI-compatible leg-raise paradigm to measure brain activity associated with lumbopelvic postural control. The objective of this study was to compare brain function in young adults with and without a history of LBP and to determine relationships between brain function, pain, and postural control characteristics. We recruited 55 participants with a history of LBP, who were asymptomatic when studied, and 30 healthy controls. Postural control during …

Clinical Outcomes Following Mechanical Thrombectomy In Pulmonary Embolism Response Team-Consulted Patients: A Retrospective Analysis, Ryan Nolan, Maanasi Samant, Suresh Vedantham, Westley Ohman, Nathan Droz, Kristen Sanfilippo, Pavan Kavali

2020-Current year OA Pubs

PURPOSE: To determine if use of mechanical thrombectomy (MT) impacts survival and additional outcomes in patients with acute intermediate-high-risk and high-risk pulmonary embolism (PE) who were evaluated by a Pulmonary Embolism Response Team (PERT).

METHODS: This retrospective, single-center study included patients with intermediate-high-risk and high-risk PE who received PERT evaluation over 3.5 years and were treated with anticoagulation (AC) alone or MT + AC. The primary outcome was 30-day all-cause mortality, measured with inverse probability of treatment weighting. Exploratory outcomes included survival during the study period, PE-associated/caused mortality, hospital length of stay (LOS), supplemental oxygen at discharge, and MT-related metrics. …

Modeling Clinical Relevance And Risk In Yttrium-90 Radioembolization Of The Liver: Lung Shunt Fraction Variability According To Imaging Modality, Cancer Type, And Tumor Size, M Allan Thomas, Tharun Alamuri, Ryan C Lee, Dan Giardina, John Karageorgiou, Naganathan Mani, Daniel A Braga, Christopher D Malone

2020-Current year OA Pubs

PURPOSE: To test the hypothesis that lung shunt fraction (LSF) in yttrium-90 (

MATERIALS AND METHODS: This was a retrospective analysis of 354 consecutive cases from a 34-month period at a single institution. Cancer type (hepatocellular carcinoma [HCC] vs non-HCC) and maximum tumor size were tracked. LSF was computed from planar imaging (LSF

RESULTS: Median LSF was significantly different (all P < .001) among LSF

CONCLUSIONS: Despite significant variations with imaging modality and correction methods, consistent trends in LSF magnitude with cancer type and tumor size were still uncovered. The relative risk of observing clinically relevant LSF can be modeled for different liver tumor …

Knowledge, Interest, And Willingness Of Hematologists And Oncologists To Care For Adults With Vascular Anomalies, Bryan A Sisk, Anna M Kerr, Sally Cohen-Cutler, Margaret T Lee, Katie Harmoney, Alexandra Borst, Shelley E Crary, Shelbie Fishman, Stephanie Chen, Danielle Cicka, Stephanie Milam, Christine Bereitschaft, Kristen M Sanfilippo

2020-Current year OA Pubs

BACKGROUND: Vascular anomalies (VAs) are rare diseases that cause significant morbidity. Adults with VAs struggle to access expert care. Hematologists and oncologists in adult medicine are positioned to provide expert care, but no prior studies have characterized their openness to this role.

OBJECTIVES: This study characterized the experience, confidence, willingness, and motivating factors for hematologists/oncologists to care for adults with VAs.

METHODS: We surveyed United States hematologists and oncologists in adult medicine between October 2024 and March 2025. The questionnaire assessed knowledge, experience, confidence, and willingness to care for adults with VAs, as well as open-ended questions assessing factors influencing …

Cgrp Expression And Signaling Sensitization In A Mouse Model Of Chronic Oxaliplatin-Induced Peripheral Neuropathy, Junwei Du, Leland C Sudlow, Margaret H Johnson, Kanishk Satish, Abraham Villagomez, Hongzhen Hu, Mikhail Y Berezin

2020-Current year OA Pubs

Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent and dose-limiting side effect of oxaliplatin treatment, yet its molecular mechanisms remain incompletely understood. Calcitonin gene-related peptide alpha (CGRPα, encoded by

The Impact Of Fixation Method And Surgical Approach On Outcomes Following Hip Hemiarthroplasty For Femoral Neck Fracture, Brian D Rust, Mitchel R Obey, Jenna-Leigh Wilson, Christopher M Mcandrew, Marschall B Berkes

2020-Current year OA Pubs

INTRODUCTION: Hip hemiarthroplasty is commonly performed for displaced femoral neck fractures in older adults, with implants placed either cemented or uncemented. While cemented fixation offers immediate stability, uncemented fixation reduces operative time and pulmonary complications. Large single-center analyses comparing these techniques remain limited, and this study aims to assess this.

METHODS: We conducted a retrospective case-control study of 634 adult patients undergoing hip hemiarthroplasty at a single Level 1 trauma center from 2019 to 2025. Patients were classified by cemented (n=403) or uncemented (n=231) fixation and further stratified by surgical approach (anterolateral vs posterior). Outcomes included length of stay, postoperative …

Sonobiopsy For Enrichment Of Circulating Micrornas In Glioma Patients, Jinyun Yuan, Yuanxiang Li, Chih-Yen Chien, Lu Xu, Andrew H Stark, Siaka Fadera, Zhaoning Gu, Yu Xuan Chin, Kevin Xu, Arash Nazeri, Umeshkumar Athiraman, Xiaowei Wang, Hong Chen, Eric C Leuthardt

2020-Current year OA Pubs

BACKGROUND: Sonobiopsy is a promising new technique that employs focused ultrasound (FUS) to noninvasively enrich brain tumor-derived biomarkers from spatially targeted brain location into the bloodstream. Building upon our recent first-in-human sonobiopsy trial demonstrating enrichment of circulating tumor DNA (ctDNA), here we investigated whether sonobiopsy can enhance the release and detection of tumor-derived microRNAs (miRNAs).

METHODS: Eleven patients with glioma underwent FUS sonication immediately prior to surgical resection. Peripheral blood samples were collected 5 min before and 5, 10, and 30 min after sonication. Plasma and brain tissue miRNA levels were quantified through small RNA sequencing and compared among different …

Psychological And Clinical Risk Factors For Substance Use In People With And Without Hiv, Joanna M Hobson, Shameka L Cody, Shannon R Gilstrap, Michael A Owens, Myles D Moody, Dyan M White-Gilliam, Stephen Justin Thomas, Emily J Bartley, Burel R Goodin

2020-Current year OA Pubs

BackgroundDespite growing concerns, limited research has demonstrated how psychological factors influence substance use in people with HIV (PWH). Therefore, we examined the association between heightened vigilance and substance use outcomes in people with (PWH) and without HIV (PWoH), while accounting for key risk factors.MethodsParticipants (n = 138) were recruited from an HIV clinic and the surrounding community, completing a urine drug screener (UDS) and questionnaires.ResultsPWH reported greater insomnia (

Characteristics Of Cerebral Palsy In The Midwestern Us, Susie Kim, Kelsey Steffen, Lauren Gottschalk-Henneberry, Jennifer Miros, Amy Robichaux-Viehoever, Karen Taca, Bhooma R Aravamuthan

2020-Current year OA Pubs

OBJECTIVE: Cerebral palsy (CP) is the most common lifelong motor disability worldwide. Yet, data is limited on how CP manifests in the US. Our objective was to characterize and determine factors affecting functional outcomes in a large population of young people with CP in the Midwestern US.

METHODS: We integrated caregiver and clinician-facing standardized data entry into routine clinical care at a tertiary care CP center (https://bit.ly/CP-Intake-Methodology). We extracted this data for people with an ICD10 diagnosis of CP seen between March 22, 2023 and December 28, 2023 and used it to describe CP characteristics and determine factors affecting the …

Nanoparticle Albumin-Bound Paclitaxel And Nivolumab For Pd-1 Inhibitor-Refractory Recurrent Or Metastatic Head And Neck Squamous-Cell Carcinoma, Douglas Adkins, Jessica C Ley, Christine Auberle, Brendan Knapp, Jesse Zaretsky, Jingxia Liu, Peter Oppelt

2020-Current year OA Pubs

INTRODUCTION: Standard therapy for PD-1 inhibitor-refractory recurrent or metastatic head and neck squamous-cell carcinoma (RM-HNSCC) has limited activity. Drugs bound to albumin selectively target cancer cells with upregulated macropinocytosis, a process driven by constitutively hyper-activated EGFR/RAS/PIK3CA signaling, which is common in HNSCC. Nanoparticle albumin-bound (nab)-paclitaxel is active in PD-1 inhibitor-naïve RM-HNSCC and alters immune cells to potentially prime tumor response and reverse resistance to PD-1 inhibitors.

METHODS: In a single-arm phase 2 trial, patients with PD-1 inhibitor-refractory RM-HNSCC received nab-paclitaxel and nivolumab given in 28-day cycles. The primary endpoint was objective response rate (ORR), using RECIST1.1. Key secondary endpoints were …

Application Of Machine Learning To Blood-Based Biomarkers Of Alzheimer's Disease In Down Syndrome, Patrick H Luckett, Melissa Petersen, Sid O'Bryant, Mark Mapstone, Brad T Christian, Benjamin Handen, Elizabeth Head, Beau M Ances, Alzheimer's Biomarker Consortium‐Down Syndrome

2020-Current year OA Pubs

INTRODUCTION: Blood-based biomarkers can improve Alzheimer's disease (AD) characterization in Down syndrome (DS). This study applied hierarchical clustering and machine learning-based feature selection to identify biomarkers associated with disease progression.

METHODS: Cross-sectional blood-based biomarkers were analyzed from 211 DS participants (

RESULTS: The strongest predictors overall were neurofilament light chain (NfL), tau/amyloid beta (Aβ)40, Aβ42/Aβ40, alpha-2-macroglobulin (A2M), and interleukin (IL)-10. Within the CS group, NfL, tau/Aβ40, A2M, and IL-10 were strong predictors. In MCI, Aβ42/Aβ40, NfL, A2M, and IL-10 were strong predictors. In DS-AD, Aβ42/Aβ40, NfL, and tau/Aβ40 were the top predictors. Cluster membership varied based on disease stage.

DISCUSSION: …

Perception Of Dementia Risk Among Black Adults: An Ecological Analysis Of Causal Loop Diagrams With A Structural And Social Determinant Of Health Composite Index, Jean-Francois Trani, Ramkrishna K Singh, Alexis Ib Walker, Semere Bekena, Yiqi Zhu, Ganesh M Babulal, Robbie Hart

2020-Current year OA Pubs

INTRODUCTION: To investigate drivers of dementia risk disparities among older Black Americans using a community-based system dynamics (CBSD) approach.

METHODS: Over 18 months, 234 participants created 36 causal loop diagrams (CLDs) on dementia risk. An ecological analysis compared structural differences across groups based on scores on a structural and social determinants of health composite index (S/SDOH-CI).

RESULTS: Groups in the highest SDOH-CI quantile were more likely to identify key protective pathways linking mental health, substance use, exercise, medication, and community support to reduce dementia risk. In contrast, fewer than 25% of low-SDOH-CI groups identified these connections, and under 15% recognized …

Development Of Colonic Polyposis In A Woman With Chronic Myeloid Leukemia Treated With Dasatinib, Guido Pelaez, Behram Suha Yildiz, Mert Candan, Mohammad Ismail, Francesca Vacca, Marianna B Ruzinova, Samuel Ballentine, Kathleen Byrnes, Armin Ghobadi

2020-Current year OA Pubs

INTRODUCTION: Chronic myeloid leukemia (CML) is a hematopoietic malignancy driven by constitutive tyrosine kinase activity. Dasatinib, a second-generation (2G) tyrosine kinase inhibitor (TKI), is a preferred treatment due to its superior, durable, and rapid response rates. While dasatinib has known gastrointestinal (GI) side effects, colonic polyposis is a rare complication, not well described in the literature.

CASE PRESENTATION: Upon routine colonoscopy, a 66-year-old woman with chronic-phase CML was incidentally discovered to have asymptomatic colonic polyposis after 11 months of dasatinib therapy. Histopathology revealed reactive inflammatory changes without evidence of dysplasia or neoplasia. The polyposis resolved completely after cessation of dasatinib. …

Towards Precision Functional Brain Network Mapping In Parkinson's Disease, Jacob Chernicky, Ally Dworetsky, Sarah Grossen, Emma Carr, Abdulmunaim Eid, Meghan C Campbell, Caterina Gratton

2020-Current year OA Pubs

BACKGROUND: Parkinson's disease (PD) is a complex neurodegenerative condition that leads to widespread disruption of large-scale brain networks and is further complicated by substantial individual variability in symptomology, progression rates, and treatment response. Consequently, the investigation of individual differences in networks measured via resting state functional connectivity (RSFC) may provide insight. However, most RSFC studies are unable to identify interindividual differences due to poor reliability and group average network definitions. "Precision" RSFC addresses these shortcomings through extended data collection, strict denoising, and individual network definition, but remains untested in PD.

OBJECTIVES: To evaluate the feasibility and reliability of precision RSFC …

Novel Insights Into Early Alzheimer's Disease: Quantitative Gradient Recalled Echo Mri Reveals Preatrophic Neuronal And Myelin Injury Concurrent With Emerging Amyloid Pathology, Satya V V N Kothapalli, Tammie L S Benzinger, Randall J Bateman, Melody Li, Cihat Eldeniz, John C Morris, Dmitriy A Yablonskiy

2020-Current year OA Pubs

BACKGROUND: Brain amyloid accumulation is considered an early sign of Alzheimer's disease (AD) pathology, appearing decades before manifestation of clinical symptoms. However, very little is known about neurodegeneration during this early AD stage. Herein we use quantitative gradient recalled echo (qGRE) magnetic resonance imaging (MRI) to reveal preatrophic microstructural neuronal and myelin damage concurrent with amyloid pathology.

METHODS: qGRE MRI and positron emission tomography (PET) amyloid [

RESULTS: qGRE detected significantly lower gray matter neuronal density and white matter myelination in the group of participants with amyloid level below the conventional amyloid-positive threshold (mean cortical standardized uptake value ratio of …

Treating Alzheimer's Disease In A Person Living With Hiv, David B Clifford, Tammie L S Benzinger, Jee-Young Han, Savannah Powles, Madeline Paczynski, Beau M Ances, J William Campbell

2020-Current year OA Pubs

INTRODUCTION: Human immunodeficiency virus (HIV) therapies now support survival into advanced ages by suppressing HIV replication and preserving immune function. Alzheimer's disease (AD), the most common neurologic degenerative condition, may now be treated with anti-amyloid therapies (AAT). HIV was an exclusionary criterion in clinical trials for AAT, leaving the safety and efficacy of these medications unknown in this setting.

METHODS: We report the development of AD supported by careful evaluations and biomarkers over a 10-year period in a person living with well-controlled HIV infection.

RESULTS: AD was diagnosed with consistent clinical and biomarker evidence. AAT was successfully administered without complications. …

Biological Aging Acceleration In Major Depressive Disorder: A Multi-Omics Analysis, Breno Satler Diniz, Shangshu Zhao, Gabin Drouard, Eero Vuoksimaa, Miina Ollikainen, Eric J Lenze, Ming Xu, Richard H Fortinsky, George A Kuchel, Jaakko Kaprio, Chia-Ling Kuo

2020-Current year OA Pubs

Major depressive disorder (MDD) is linked to a higher risk of premature aging, but the mechanisms underlying this association remain unclear. Using data from two population cohorts (UK Biobank and Finnish Twin Cohort), we evaluate the relationship between systemic and organ-specific proteomic and epigenetic aging acceleration and MDD. A lifetime history of MDD was associated with accelerated proteomic aging at both systemic and organ-specific levels-including the brain-in both cohorts, with stronger associations than those observed with systemic epigenetic aging. Systemic and brain-specific proteomic aging acceleration were linked to higher risks of incident MDD and a greater risk of Alzheimer's disease, …