Digital Commons Network^™

Criterion And Convergent Validity Of Plasma Biomarkers In Early-Onset Alzheimer's Disease: Initial Findings From Leads, Dustin B Hammers, Kyle Womack, Erik Musiek, Et Al.

2020-Current year OA Pubs

No abstract provided.

Epithelial-Mesenchymal Transition And Stress Adaptations Underlie Yttrium-90 Resistance In Liver Cancer Cell Lines, Alexander Zheleznyak, Dhanusha Duraiyan, Prasanth Thunuguntla, Jessica Camacho, Shuang Wu, Jingxia Liu, Jason D Weber, Daniel L J Thorek, Benjamin S Strnad, Ryan C Fields, Matthew A Ciorba, Christine Yoon, Valerie Blanc, Nicholas Davidson, Jessica Silva-Fisher, Christopher D Malone

2020-Current year OA Pubs

UNLABELLED: Molecular signatures predict prognosis in hepatocellular carcinoma, but their relevance to transarterial radioembolization (TARE) with yttrium-90 (90Y) is unknown. We aimed to identify baseline and treatment-induced pathways associated with response and nominate biomarkers. Ten transcriptomically diverse human liver cancer cell lines were exposed to escalating activities of glass 90Y microspheres for 10 days. Normalized AUC values quantified sensitivity. Whole-transcriptome RNA sequencing at baseline and after treatment was analyzed with elastic net regression and gene set enrichment. Findings were corroborated by qRT-qPCR and exploratory analysis of pretreatment tumor samples from patients undergoing TARE. Liver cancer cell line responses to 90Y …

Focused Ultrasound-Enhanced Nose-To-Brain Delivery Of A Therapeutic Antibody In A Large-Animal Model, Siaka Fadera, Cristian Antonio Wieczorek Villas Boas, Yimei Yue, Zhaoning Gu, Jinyun Yuan, Debolina De, Buck E Rogers, Arash Nazeri, Hong Chen

2020-Current year OA Pubs

No abstract provided.

Coordinated Regulation Of Capping Protein By Carmil And V-1/Myotrophin, John A Hammer, John A Cooper

2020-Current year OA Pubs

Capping Protein (CP) plays a central role in controlling actin filament dynamics in almost all eukaryotic cell types by virtue of its ability to block monomer addition and loss at the barbed end of the actin filament. Like other proteins that control actin assembly, CP is subject to regulation. Here we focus on two direct regulators of CP-CARMIL and V-1/Myotrophin. Specifically, we review recent biochemical, structural, imaging, and cell biological data that argue these two proteins cooperate to create a regulatory cycle for CP that controls its availability, activity, and site of action in the cell. Finally, we discuss unresolved …

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 …

Influence Of Obesity And Insulin Resistance With Hepatic Steatosis On The Human Plasma Lipidome, Max C Petersen, Gordon I Smith, Aaron M Armando, Xiong Su, Oswald Quehenberger, Edward A Dennis, Samuel Klein

2020-Current year OA Pubs

Insulin resistance accompanied by hepatic steatosis is a common complication of obesity. In an effort to identify plasma lipids that could be biomarkers or causes of insulin resistance with steatosis in people with obesity, we evaluated the plasma lipidome in three distinct groups separated by adiposity, hepatic steatosis, and insulin sensitivity, assessed by using the hyperinsulinemic-euglycemic clamp procedure: i) insulin-sensitive lean (ISL, n = 13); ii) insulin-sensitive obese (ISO, n = 14); and iii) insulin-resistant obese with hepatic steatosis (IROS, n = 13). We evaluated 759 complex lipid species in 16 subclasses (including phospholipids, glycerolipids, sphingolipids, acylcarnitines, and cholesteryl esters) …

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 …

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: …

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, …

Mapping Functional Connectivity In The Pigeon Brain With Wide-Field Optical Imaging, Kathryn C Chenard, Annie R Bice, Seana H Bice, Joseph P Culver, Paula Gerliz, Xavier Helluy, Onur Güntürkün, Jason W Trobaugh, Mehdi Behroozi, Carlos A Botero

2020-Current year OA Pubs

SIGNIFICANCE: Adapting optical imaging technology to avian models can overcome many limitations imposed by functional magnetic resonance imaging (fMRI), which currently restricts the number of species used to study functional connectivity. Developing advanced technology to expand the diversity of species that can be effectively imaged is crucial for addressing significant questions that are currently unreachable, such as understanding the evolution of cognition from a comparative perspective.

AIM: We assessed the potential of optical imaging technology to measure functional connectivity in birds, utilizing pigeons as an avian model. We evaluated whether we could partition the dorsal surface of the pigeon brain …

Lack Of Disparities In Postoperative Care After Ileocecal Resection In Patients With Crohn's Disease At Tertiary Inflammatory Bowel Diseases Centers, Shannon Coombs, Molly Powell, Kemmian Johnson, Jessica Hu, Mollie Webb, Philip Mcdaniel, Parakkal Deepak, Edward L Barnes

2020-Current year OA Pubs

BACKGROUND: Prior studies suggest that longer drive time (DT) to specialists and higher area deprivation index (ADI) are linked to worse outcomes in inflammatory bowel disease (IBD), but their impact on postileocolic resection (ICR) care in patients with Crohn's disease (CD) is not well defined.

OBJECTIVES: We aimed to evaluate disparities in post-ICR care based on DT and ADI.

METHODS: Spatial analysis was performed with ArcGIS Pro to geocode patient and medical facility addresses with StreetMap Premium locators. High DT was defined as >60 min from the center. Data were analyzed using basic statistics and multivariate logistic regression.

DESIGN: A …

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 …

Mutations In Hsp40 Co-Chaperone Change The Canonical Interdomain Interactions Stimulating Lgmdd1 Myopathy, Ankan K Bhadra, Geetika Aggarwal, Anshuman Jaysingh, Daniel Chen, Jil Daw, Conrad C Weihl, Heather L True

2020-Current year OA Pubs

Limb-girdle muscular dystrophy D1 (LGMDD1) is a rare, dominantly inherited neuromuscular protein-misfolding chaperonopathy caused by mutations in the Hsp40 co-chaperone DNAJB6, primarily in the glycine-phenylalanine (GF) or J-domains. Currently, no treatments are available, and a challenge in understanding the disease is identifying a specific client protein for DNAJB6 in skeletal muscle. DNAJB6 has homology to the yeast DNAJ family member, Sis1. Our previous research indicated that LGMDD1 GF domain mutants in Sis1 exhibit substrate-specific effects, influenced by Hsp70 activity. Herein, we employed functional assays along with advanced molecular simulation studies to understand the regulatory interdomain interactions in disease-causing mutants of …

Oculomics And Ai: The Eye As A Biomarker For Health Span, Joy Le Yi Wong, Rajendra S Apte, Et Al.

2020-Current year OA Pubs

As the world's population ages, the focus of healthcare is shifting from extending life span to promoting health span. There is an unmet need to identify sensitive and reliable markers of health span through more cost-effective and non-invasive methods, to enable early and effective intervention on modifiable aging factors. The eye offers a unique window into systemic health, providing direct visualization of the body's vascular and neural health. This review presents an overview of how various ocular structures can serve as biomarkers of health span-drawing on insights from ocular imaging, metabolomics, and proteomics, with evidence from basic science, animal models, …

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 …

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 …

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 …

Mouse Alport Podocytes Are Susceptible To Aav9 Transduction In Vivo, Meei-Hua Lin, Kohei Omachi, Joshua F Begin, Jennifer L Richardson, Jeffrey H Miner

2020-Current year OA Pubs

INTRODUCTION: Alport syndrome features a defective glomerular basement membrane (GBM) due to variants in COL4A3, COL4A4, and COL4A5. The most severe forms, which lack the GBM's collagen α3α4α5(IV) network, progress from hematuria in early childhood to proteinuria, chronic kidney disease, and kidney failure by the age of ∼30. As a monogenic disease without specific treatments, and with podocytes being the only glomerular cells that synthesize collagen α3α4α5(IV), the ability to efficiently deliver genes to Alport podocytes could open up new possibilities for treatment.

METHODS: As a proof-of-concept study, we investigated whether podocytes in X-linked Alport mice were susceptible to transduction …

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

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 (

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 …

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 …

The Association Between Major Depressive Disorder, Plasma Biomarkers Of Alzheimer's Disease, And Mild Behavioral Impairment Among Older Adults, Yiqi Zhu, Jean-Francois Trani, Ramkrishna K Singh, Semere Bekena, Jonathan Williams, Eric J Lenze, Ganesh M Babulal

2020-Current year OA Pubs

INTRODUCTION: Plasma biomarkers and mild behavioral impairment (MBI) are associated with dementia risk, but their relationships with major depressive disorder (MDD) are understudied. This study aimed to examine associations between plasma biomarkers of Alzheimer's disease (AD) and MBI among older adults with and without MDD.

METHODS: Older adults aged ≥65 were recruited from longitudinal studies of depression and AD (

RESULTS: Older adults with MDD were more likely to endorse MBI. After adjustment, Aβ42/Aβ40 and p-tau217/np-tau217 positivity were associated with MBI among those with MDD but not among those without.

DISCUSSION: Neuropsychatric symptoms (NPS) and biomarkers are AD risk factors. …

The Impact Of Congenital Heart Disease On The Timing Of Alzheimer's Disease In Down Syndrome, Julianne G Clina, Beau Ances, Et Al.

2020-Current year OA Pubs

INTRODUCTION: The incidence of Alzheimer's disease (AD) in Down syndrome (DS) exceeds 90%. Approximately 50% of people with DS have congenital heart disease (CHD). Having CHD increases risk for early-onset AD in populations without DS, but it is unclear if CHD influences AD in DS.

METHODS: Data from the Alzheimer Biomarker Consortium-Down Syndrome (ABC-DS) were used. Participants with CHD (

RESULTS: People with CHD scored lower for visuospatial ability (

DISCUSSION: Presence of CHD may influence AD progression in DS.

HIGHLIGHTS: In adults with Down syndrome (DS), those with congenital heart disease (CHD) had higher amyloid beta and reached the …

Alzheimer's Disease Stage 1 And 2: Biology, Diagnostics, And Treatment, Suzanne E. Schindler, Sarah M. Hartz, Et Al.

2020-Current year OA Pubs

No abstract provided.

Eligibility For Anti-Amyloid Treatment In A Multiethnic Community-Based Study, Lydia Trudel, Joseph Therriault, Arthur C Macedo, Karin L Meeker, Meredith N Braskie, Arthur W Toga, Serge Gauthier, Paolo Vitali, Suzanne E Schindler, Sid E O'Bryant, Pedro Rosa-Neto

2020-Current year OA Pubs

INTRODUCTION: The approval of anti-amyloid monoclonal antibodies (mAbs), including lecanemab and donanemab, represents a significant advance in disease-modifying therapies (DMTs) for early Alzheimer's disease (AD). While appropriate use recommendations (AURs) have been established to guide clinical decision-making, the proportion of individuals with cognitive impairment in real-world, multiethnic populations meeting eligibility criteria remains unknown, as do potential differences in treatment-related risks across ethnic groups.

METHODS: We included 513 cognitively impaired individuals from the Health and Aging Brain Study-Health Disparities study, a multiethnic community-based cohort. Eligibility for lecanemab and donanemab was determined using published AUR criteria. Counts of amyloid-related imaging abnormalities were …

Rationale And Trial Design Of Ribolaris: A Phase Ii Trial Of Neoadjuvant And Adjuvant Ribociclib Plus Endocrine Therapy For Clinically High-Risk Hr+/Her2-Negative Breast Cancer, Paul Cottu, Cynthia X Ma, Et Al.

2020-Current year OA Pubs

BACKGROUND: Despite advances in endocrine therapy, patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) early breast cancer (eBC) remain at risk of recurrence (ROR). Chemotherapy is often used in high-risk cases, but not all patients benefit.

OBJECTIVES: To evaluate whether chemotherapy can be safely omitted in patients with stage II, grade 2/3 HR+/HER2- eBC who convert to low genomic risk (ROR-low) following neoadjuvant ribociclib plus letrozole.

METHODS: RIBOLARIS (NCT05296746) is an open-label, multicenter phase II trial in patients with stage II, grade 2 or 3, HR+/HER2- eBC defined as high risk based on a Ki-67 index ⩾20% …

Establishing Demographic-Based Normative Values For Neurofilament Light Chain And Glial Fibrillary Acidic Protein In Serum And Plasma Samples, Tyler L Borko, Salim Chahin, Et Al.

2020-Current year OA Pubs

BACKGROUND: Interpretation of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) levels in blood requires reference ranges from healthy cohorts, accounting for demographic features.

OBJECTIVE: To compare serum and plasma NfL and GFAP in healthy individuals, accounting for age, sex, and body mass index (BMI).

METHODS: Adolescents through older adults were recruited at Colorado community events and a senior clinic. A neurologist reviewed self-reported medical histories. Paired serum and EDTA plasma samples were assayed using the Quanterix SR-X Simoa Neuro 4-Plex. Log-linear models estimated percent change per year of age, per BMI unit, and sex ratios. GFAP used …

Concordance Of Fluorescence In Situ Hybridization, Whole-Exome Sequencing, And Chromosomal Microarray For Evaluating High-Risk Molecular Features In Meningiomas, Brenndan Crumley, Emilie Russler-Germain, Sonika Dahiya

2020-Current year OA Pubs

BACKGROUND: Meningiomas are the most common primary intracranial tumors, classified into three WHO grades based on histologic and/or molecular criteria. cIMPACT-NOW Update 8 underscores the increasing importance of molecular testing in grading and risk stratification, noting that morphologically WHO grade 1 tumors with concurrent 1p and 22q losses demonstrate clinical behavior comparable to WHO grade 2 meningiomas. This study aimed to assess the concordance of fluorescence in situ hybridization (FISH), chromosomal microarray analysis (CMA), and whole-exome sequencing (WES) in defining the molecular risk profile of meningiomas.

METHODS: A total of 113 meningiomas were analyzed by WHO grade to assess the …

Membrane Il-18 Identifies A Human Macrophage Subset With Distinct Proteomic And Functional Traits, Chiara Vitale, Marco Colonna, Et Al.

2020-Current year OA Pubs

This study contributes to the characterization of human macrophages in normal and pathological conditions such as cancer. We characterized a macrophage population expressing membrane-associated IL-18 (mIL-18) that shows peculiar proteomic, phenotypic, ultrastructural, and functional properties. mIL-18+ macrophages exhibit increased levels of key proteins involved in pathogen recognition, activation, migration, and endocytosis. They also display specialized functions in vesicle and actin filament transport and lipid metabolism, and have typical mitochondrial traits. Importantly, mIL-18+ cells dominate the peritoneal fluid of adult cancer patients and are present in the bone marrow of children with neuroblastoma. They express high levels of TREM2 but display …