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Head-To-Head Preclinical Treatment Design Prioritizes Promising Therapies For Neurofibromatosis Type 1 Optic Glioma Clinical Translation, Talia Eligator, Jit Chatterjee, Shintaro Yamada, Anthony Kirchner, Hareesh B Nair, Jason R Fangusaro, David H Gutmann

2020-Current year OA Pubs

BACKGROUND: Authenticated preclinical brain tumor models provide unprecedented opportunities to evaluate next-generation treatments. However, some therapies with robust anti-tumor activity in mice fail in human trials, highlighting the need to better prioritize candidates for clinical translation. Herein, we implemented a head-to-head preclinical strategy using a well-characterized murine model of NF1-optic pathway glioma (

METHODS:

RESULTS: While all agents restored normal tissue architecture, reduced ON proliferation, and decreased TME soluble mediator and tumor cell marker RNA expression, only lamotrigine and mirdametinib also reduced ON volume. Everolimus, lamotrigine, and HBS-101 restored RNFL thickness to wild-type levels, whereas carboplatin showed a trend towards …

Abdominal Myosteatosis Measured With Computed Tomography Predicts Poor Outcomes In Patients With Glioblastoma, Farzaneh Rahmani, David H Ballard, Tammie L S Benzinger, Sonika Dahiya, John Evans, Sara Hosseinzadeh Kassani, Cyrus A Raji, Marilyn J Siegel, Joseph E Ippolito, Et Al.

2020-Current year OA Pubs

BACKGROUND: Alterations in cellular metabolism affect cancer survival and can manifest in metrics of body composition. We investigated the effects of various body composition metrics on survival in patients with glioblastoma (GBM).

METHODS: We retrospectively analyzed patients who had an abdominal and pelvic computed tomography (CT) scan performed within 1 month of diagnosis of GBM (178 participants, 102 males, 76 females, median age: 62.1 years). Volumetric body composition metrics were derived using automated CT segmentation of adipose tissue, skeletal muscle, and aortic calcification from L1 to L5. Univariable and multivariable Cox proportional hazards models were performed separately in males and …

Patient Stratification By Genetic Risk In Alzheimer's Disease Is Only Effective In The Presence Of Phenotypic Heterogeneity, Jack Euesden, Muhammad Ali, Chloe Robins, Praveen Surendran, Padhraig Gormley, Alzheimer’S Disease Neuroimaging Initiative, David Pulford, Carlos Cruchaga

2020-Current year OA Pubs

Case-only designs in longitudinal cohorts are a valuable resource for identifying disease-relevant genes, pathways, and novel targets influencing disease progression. This is particularly relevant in Alzheimer's disease (AD), where longitudinal cohorts measure disease "progression," defined by rate of cognitive decline. Few of the identified drug targets for AD have been clinically tractable, and phenotypic heterogeneity is an obstacle to both clinical research and basic science. In four cohorts (n = 7241), we performed genome-wide association studies (GWAS) and Mendelian randomization (MR) to discover novel targets associated with progression and assess causal relationships. We tested opportunities for patient stratification by deriving …

Prevention And Management Of Posterior Wound Complications Following Oncologic Spine Surgery: Narrative Review Of Available Evidence And Proposed Clinical Decision-Making Algorithm, Owen P Leary, Matthew L Goodwin, Et Al.

2020-Current year OA Pubs

STUDY DESIGN: Narrative Review.

OBJECTIVE: Contextualized by a narrative review of recent literature, we propose a wound complication prevention and management algorithm for spinal oncology patients. We highlight available strategies and motivate future research to identify optimal and individualized wound management for this population.

METHODS: We conducted a search of recent studies (2010-2022) using relevant keywords to identify primary literature in support of current strategies for wound complication prevention and management following spine tumor surgery. When primary literature specific to spine tumor cases was not available, data were extrapolated from studies of other spine surgery populations. Results were compiled into …

Improving Outcomes Of Single-Sided Deaf Cochlear Implant Users By Reducing Interaural Frequency And Loudness Mismatches Through Device Programming, Laura K Holden, Rosalie M Uchanski, Noël Y Dwyer, Ruth M Reeder, Timothy A Holden, Jill B Firszt

2020-Current year OA Pubs

The study aimed to improve outcomes in Nucleus cochlear implant (CI) recipients with single-sided deafness (SSD) by reducing interaural frequency and loudness mismatches through device programming. In Experiment 1a, a modified frequency allocation table (FAT) was created to better match the tonotopicity of the contralateral ear and reduce interaural frequency mismatch. Twenty experienced SSD-CI users completed localization and speech recognition tests with their everyday FAT. Tests were repeated after 6 weeks' use of the modified FAT. Participants compared both FATs for 2 weeks before being tested again with each. For 10 newly implanted SSD-CI recipients (Experiment 1b), Group A was …

Articles That May Change Your Practice: Reviewing Intraosseous Or Intravenous? Reviewing Intraosseous Versus Intravenous First Approach To Access In Out-Of-Hospital Cardiac Arrest Data From Randomized Controlled Trials, Blaise Loughman, Fatou Ndaw, Aaron J Lacy, James L Li

2020-Current year OA Pubs

No abstract provided.

Usability Of The Mayo Test Drive Remote Self-Administered Web-Based Cognitive Screening Battery In Adults Aged 35-100 With And Without Cognitive Impairment, Jay S Patel, Jason Hassenstab, Et Al.

2020-Current year OA Pubs

BACKGROUND: Mayo Test Drive (MTD): Mayo Test Development through Rapid Iteration, Validation and Expansion, is a web-based remote cognitive assessment platform for self-administered neuropsychological measures with previously demonstrated validity and reliability. We examined the usability of MTD and hypothesized that completion rates would be greater than 90%. We explored whether completion and participation rates differed by cognitive status and demographic factors.

METHODS: A total of 1,950 Mayo Clinic Study of Aging and Mayo Alzheimer's Disease Research Center participants (97% White, 99% Non-Hispanic) were invited to participate in this ancillary, uncompensated remote study. Most invitees were cognitively unimpaired (CU;

RESULTS: Baseline …

Effects Of Obesity On Plasma Biomarker And Amyloid Pet Trajectories In Alzheimer's Disease, Soheil Mohammadi, Farzaneh Rahmani, Mahsa Dolatshahi, Suzanne E Schindler, Cyrus A Raji, Adni Collaborators

2020-Current year OA Pubs

INTRODUCTION: Obesity is a risk factor for Alzheimer's disease (AD), but its impact on AD blood biomarker (BBM) and amyloid positron emission tomography (PET) trajectories is unknown.

METHODS: One thousand two hundred twenty-eight plasma samples from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were assessed using six leading commercial tests (C2N, Fujirebio, Janssen, ALZpath, Roche, and Quanterix). Amyloid PET scans were used to assess amyloid burden in Centiloids (CLs). Spearman partial correlations assessed cross-sectional associations, while linear mixed-effects models examined the longitudinal impact of obesity status on BBMs and CLs.

RESULTS: Higher body mass index at baseline was correlated with lower …

System Readiness And The Patient Care Pathway For Alzheimer's Disease Diagnosis And Treatment, B Joy Snider, Et Al.

2020-Current year OA Pubs

Promising therapeutic interventions that target the underlying pathophysiology are changing the landscape of Alzheimer's disease (AD) research. The AD care pathway must be transformed to meet the challenge of bringing these new therapies to the increasing number of people living with AD within the existing healthcare framework. Challenges include identifying patients who may benefit from treatment interventions early in the course of the disease, ensuring that diagnostic tools are accessible and accurate, and developing capabilities to monitor the effectiveness of interventions over time. These challenges must be addressed at all levels, from primary care settings to tertiary treatment centers; this …

Qualitative And Quantitative Analysis Of A Novel Dental Health Education Program To Improve Dental Care Utilization By Bhutanese-, Burmese-, And Swahili-Speaking Refugees In A Midwestern United States City, Chandra Swanson, Katherine Gordon, Kelly Kreisler, Elizabeth Montgomery Collins

2020-Current year OA Pubs

No abstract provided.

Estimating Preclinical Amyloid Positivity: A Case Study Transporting Adni To Aric, Emma K Stapp, Elizabeth Rose Mayeda, Elizabeth A Stuart, Rebecca F Gottesman, Scott C Zimmerman, Dean F Wong, Thomas H Mosley, Michael E Griswold, M Maria Glymour, Melinda C Power, Alzheimer's Disease Neuroimaging Initiative

2020-Current year OA Pubs

INTRODUCTION: Alzheimer's disease and related dementias researchers have benefited from deeply phenotyped clinical samples; however, there is a critical need for estimates that generalize to diverse, representative populations. Use of a statistical approach from causal inference, "transport," may allow generalization of findings from clinical samples to other target populations. Here we explore the feasibility and validity of extending results from a clinical sample, the Alzheimer's Disease Neuroimaging Initiative (ADNI), to a community-based target sample, the Atherosclerosis Risk in Communities Study Positron Emission Tomography Amyloid Imaging Study (ARIC-PET) using transport estimation and a standard approach, direct standardization, which itself can be …

Data-Driven Approach To Dynamic Resting State Functional Connectivity In Post-Traumatic Stress Disorder: An Enigma-Pgc Ptsd Study, Carissa W. Tomas, Evan M. Gordon, Et Al

2020-Current year OA Pubs

No abstract provided.

Iliac Crest Bone Block Autograft Transfer For Ballistic Posterior Glenoid Fracture: A Case Report, Jordan Cook Serotte, Hayden Baker, Cody Lee, Jason A Strelzow

2020-Current year OA Pubs

No abstract provided.

Multi-Echo Acquisition And Thermal Denoising Advances Precision Functional Imaging, Julia Moser, Alyssa K Labonte, Michael J Myers, Babatunde Adeyemo, Abraham Z Snyder, Evan M Gordon, Nico U F Dosenbach, Timothy O Laumann, Chad M Sylvester, Et Al.

2020-Current year OA Pubs

The characterization of individual functional brain organization with Precision Functional Mapping has provided important insights in recent years in adults. However, little is known about the ontogeny of inter-individual differences in brain functional organization during human development. Precise characterization of systems organization during periods of high plasticity is likely to be essential for discoveries promoting lifelong health. Obtaining precision functional magnetic resonance imaging (fMRI) data during development has unique challenges that highlight the importance of establishing new methods to improve data acquisition, processing, and analysis. Here, we investigate two methods that can facilitate attaining this goal: multi-echo (ME) data acquisition …

Proceedings Of The 12th Annual Deep Brain Stimulation Think Tank: Cutting Edge Technology Meets Novel Applications, Alfonso Enrique Martinez-Nunez, Nico U F Dosenbach, Evan M Gordon, Et Al.

2020-Current year OA Pubs

The Deep Brain Stimulation (DBS) Think Tank XII was held on August 21st to 23rd. This year we showcased groundbreaking advancements in neuromodulation technology, focusing heavily on the novel uses of existing technology as well as next-generation technology. Our keynote speaker shared the vision of using neuro artificial intelligence to predict depression using brain electrophysiology. Innovative applications are currently being explored in stroke, disorders of consciousness, and sleep, while established treatments for movement disorders like Parkinson's disease are being refined with adaptive stimulation. Neuromodulation is solidifying its role in treating psychiatric disorders such as depression and obsessive-compulsive disorder, particularly for …

Cervical Cancer In Women With Hiv: A Call To Action For Equitable Prevention In Low- And Middle-Income Countries, Jonathan Klutse, Yeena Abla Tay, Dzidzor Aku Attoh, Emmanuel Frimpong Gyekye, Charlotte Borteley Bortey, Esenam Dzifa Buatsi, Charlayne Cherylyn Oppong, Helena Lamptey, Collins Stephen Ahorlu, George Boateng Kyei, Evelyn Yayra Bonney

2020-Current year OA Pubs

Cervical cancer is preventable; however, it remains the leading cause of death in low- and middle-income countries (LMICs). Women with HIV (WWHs) have a sixfold higher risk of developing and dying from cervical cancer than women without HIV. Cervical cancer can be prevented by vaccination against high-risk human papillomaviruses (hrHPVs) and by screening for and treating precancer cervical lesions. While these preventive measures are routinely available to WWHs in developed countries, they are lacking in most LMICs, where the burden of HIV and cervical cancer is the highest. To prevent cervical cancer deaths among WWHs in LMICs, it is imperative …

Discovering Subtypes With Imaging Signatures In The Motoric Cognitive Risk Syndrome Consortium Using Weakly Supervised Clustering, Bhargav Teja Nallapu, Kellen K Petersen, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Understanding the heterogeneity of brain structure in individuals with the Motoric Cognitive Risk Syndrome (MCR) may improve the current risk assessments of dementia.

METHODS: We used data from six cohorts from the

RESULTS: Three subgroups (Groups A, B, and C) were identified through MRI-based clustering with significant differences in regional brain volumes, gait speeds, and performance on Trail Making (Part-B) and Free and Cued Selective Reminding Tests.

DISCUSSION: Based on structural MRI, our results reflect heterogeneity in the population with moderate and slow gait, including those with MCR. Such a data-driven approach could help pave new pathways toward dementia …

Physical Activity As A Resistance Or Resilience Mechanism In Down Syndrome Alzheimer's Disease, Victoria L Fleming, Beau M Ances, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Adults with Down syndrome (DS) are at risk for Alzheimer's disease (AD). Lifestyle factors such as engagement in moderate-to-vigorous physical activity (MVPA) reduce risk or delay the onset of AD. This study aimed to determine whether MVPA confers a

METHODS: Analyses included 69 adults with DS (aged 26-58) who participated in a longitudinal study across 3.29 years. An actigraphy accelerometer assessed MVPA across 7 days. Directly administered and informant-reported measures assessed cognitive functioning, specifically memory and dementia symptoms. Neuroimaging biomarkers quantified amyloid beta (Aβ) burden, as assessed via positron emission tomography imaging.

RESULTS: In regression models, baseline MVPA was …

Case Report: Molecular Characterization Of Adult Atypical Teratoid Rhabdoid Tumor And Review Of The Literature, Miguel A Hernandez-Rovira, Michelle Connor, Robert C Osorio, Emilie Russler-Germain, Robert Schmidt, Gabrielle W Johnson, Julie Silverstein, Sonika Dahiya, Nyssa Fox Farrell, Mia C Weiss, Gregory J Zipfel, Jiayi Huang, Dimitrios Mathios

2020-Current year OA Pubs

BACKGROUND AND IMPORTANCE: Atypical teratoid rhabdoid tumors (ATRTs) are typically aggressive pediatric tumors with a median survival of 11 months. Due to the paucity of cases in adults, the clinical behavior of these pathologies is not well understood. Here we present the case of a 41-year-old female patient with postoperative hyperprogression of a sellar ATRT and provide a detailed description of the molecular composition of this tumor, the protocol used to treat this patient, and the ultimate outcome of this patient.

CLINICAL PRESENTATION: The patient is a 41-year-old woman who presented with headaches and double vision. MRI revealed a sellar/suprasellar …

The Evolution And Application Of Multi-Omic Analysis For Pituitary Neuroendocrine Tumors, Sangami Pugazenthi, Shree S Pari, Ziyan Zhang, Julie Silverstein, Albert H Kim, Bhuvic Patel

2020-Current year OA Pubs

Pituitary neuroendocrine tumors (PitNETs) are a heterogeneous group of intracranial neoplasms that vary in hormonal activity, histological features, and clinical behavior. The rise of high-throughput sequencing and molecular profiling technologies has enabled multiomic approaches-including genomics, transcriptomics, epigenomics, proteomics, and metabolomics-to deepen our understanding of PitNET pathogenesis. These studies have identified key mutations, transcriptional lineages, epigenetic modifications, and proteomic features that contribute to tumor subtype classification, invasiveness, and treatment response. Integrative multi-omic analyses have further revealed distinct molecular subtypes, complex regulatory networks, and molecular profiles that can predict recurrence and therapeutic efficacy. These approaches hold strong potential for advancing personalized medicine …

Sensorimotor Faculties Bias Choice Behavior, Jan Kubanek, Lawrence H Snyder, Richard A Abrams

2020-Current year OA Pubs

Decision-making is a deliberate process that seemingly evolves under our own volition. Yet, research on embodied cognition has demonstrated that higher-order cognitive processes may be influenced, in unexpected ways, by properties of motor and sensory systems. Here we tested whether and how decisions are influenced by handedness and by asymmetries in the auditory system. Right- and left- handed participants performed an auditory decision task. In the task, subjects decided whether they heard more click sounds in the right ear or in the left ear, and pressed a key with either their right or left index finger, according to an instructed …

Identification Of Candidate Cardiomyopathy Modifier Genes Through Genome Sequencing And Rna Profiling, Malene E Lindholm, Gerald W Dorn, Et Al.

2020-Current year OA Pubs

BACKGROUND: Phenotypic heterogeneity is apparent among individuals with putative monogenic disease, such as familial hypertrophic cardiomyopathy. Genome sequencing (GS) allows interrogation of the full spectrum of inborn genetic variation in an individual and RNA profiling provides a snapshot of the cardiac-specific pathogenic effects on gene expression.

OBJECTIVES: Identify candidate genetic modifiers of hypertrophic cardiomyopathy phenotype.

METHODS: We performed GS of 48 individuals with variants in

RESULTS: GS identified the

CONCLUSION: Evaluation of the whole genome, even in the case of alleged monogenic disease, leads to important new insights. The identified variants, regions, and genes are candidates to modify disease presentation …

Mapping Of Rorγt+ Dendritic Cells In Human Tissues Establishes Their Preferential Niche In Adult Lymph Nodes, Silvia Lonardi, Shitong Wu, Alina Ulezko Antonova, Yizhou A Liu, Marina Cella, Marco Colonna, William Vermi, Et Al.

2020-Current year OA Pubs

BACKGROUND: The retinoic-acid-receptor-related orphan receptor gamma t (RORγt) isoform is required for the development of lymphoid organs, T-helper 17 cells (Th17), and innate lymphoid cells (ILC3s). Recent data in mouse and human have revealed non-T, non-ILC3 cell populations with antigen presenting features that express RORγt. This study maps the presence of RORγt cells with dendritic cell (DC) features in human adult and fetal lymphoid tissues.

METHODS: By combining multicolor flow cytometry, RNAseq of peripheral blood cells, analysis of lymph node scRNAseq datasets, and microscopic analysis on human tissue sections and single-cell suspensions, this study maps the presence of RORγt cells …

"I Feel Like People Would Look At Me Like I'M Dirty Or Like I'M A Thief:" A Qualitative Exploration Of Interpersonal And Intrapersonal Experiences That Influence Recovery Among Adults At Risk Of Opioid-Related Overdose, Hannah S Szlyk, Sara Jones, Jordan Michener, Zhuoran Zhang, Nina Kaiser, Heidi Holtz, Melody Rachel Konadu Frempong, Husain Lateef, William Hutson, Patricia Cavazos-Rehg

2020-Current year OA Pubs

OBJECTIVE: Due to the nature of early termination of treatment and the transient lifestyles of many people who use substances, many providers are unaware of the factors that may have contributed to their client's engagement in treatment. Treatment providers and researchers need a better understanding of intrapersonal and interpersonal factors that impact recovery from the clients' perspective. This study uses qualitative methods to explore these factors.

METHODS: Eligible participants were adults who had used opioids and/or stimulants and were receiving treatment at a consenting facility. Participants completed one-month follow-up interviews after using a mobile health intervention. Transcripts were analyzed using …

Barriers And Facilitators To Implementing A Task-Sharing Mental Health Intervention For Sickle Cell Disease Populations In Low- And Middle-Income Countries: A Qualitative Analysis Using The Consolidated Framework For Implementation Research (Cfir), John Patena, Leah Elster, Tania Hameed, Sumedha Kulkarni, Alden Yuanhong Lai, Annika C Sweetland, Joyce Gyamfi, Temitope Ojo, Angela Odoms-Young, Charmaine Royal, Emmanuel Peprah

2020-Current year OA Pubs

BACKGROUND: People living with Sickle Cell Disease (SCD) experience higher rates of common mental disorders (CMD). There is an alarming treatment gap in the provision of adequate mental health services for CMDs in low- and middle-income countries (LMIC). One solution is the implementation of task-sharing interventions such as the Friendship Bench which utilizes concepts of problem-solving therapy (PST). This investigation uses a qualitative study design to evaluate the acceptability and feasibility of implementing a PST-based task-sharing mental health intervention for SCD populations in LMICs using the Consolidated Framework for Implementation Research (CFIR).

METHODS: Purposive, convenience, and snowball sampling strategies were …