Medicine and Health Sciences Commons^™

Trajectories And Predictors Of Activity Participation Among People With Parkinson Disease: A 3-Year Longitudinal Study, Moon Young Kim, Yejin Lee, Carolyn M Baum, Lisa T Connor, Chih-Hung Chang, Linda Tickle-Degnen, Erin R Foster

2020-Current year OA Pubs

OBJECTIVE: To investigate how participation changes over time among individuals with Parkinsondisease (PD) and identify factors influencing these changes, focusing on impairment level and social factors.

DESIGN: Secondary analysis of a 3-year prospective cohort study of social self-management of PD. Data were collected during 4 in-person assessments conducted at baseline and then annually thereafter. Multilevel modeling was used to analyze data from the 4 time points.

SETTING: Department of Occupational Therapy Research Laboratory and Department of Neurology Movement Disorder Clinic.

PARTICIPANTS: A total of 86 individuals (N = 86) with idiopathic PD (Hoehn & Yahr stages I-IV; mean age ± …

Bach2 Regulates T Cell Lineage State To Enhance Car T Cell Function, Tien-Ching Chang, Amanda Heard, John Lattin, John M Warrington, Amanda Barrett, Jack H Landmann, Yangdon Tenzin, Vishaal Ganesh, Bryant Thompson, Sadia Afrin, Deepesh Kumar Gupta, Ju-Fang Chang, Julie Ritchey, Mehmet Emrah Selli, Yu-Sung Hsu, A J Federico, Avery Horn, Michael P Meers, John F Dipersio, Nathan Singh, Et Al.

2020-Current year OA Pubs

Nearly all chimeric antigen receptors (CARs) signal in the absence of antigen, referred to as 'tonic signaling'. Tonic signaling of CARs containing 41BB domains enhances T cell fitness and function, in contrast to the exhaustion driven by CD28-containing CARs. Here we show that 41BB induces BACH2, a transcriptional regulator that directs stem and memory programs. Overexpression of BACH2 successfully prevented exhaustion but locked CAR T cells in a quiescent state. We linked BACH2 to a degradation domain to tune BACH2, enabling us to prevent exhaustion while enabling potent effector function that broadly enhanced the long-term efficacy of CAR T cells …

Intraocular Amyloidosis Presenting With Secondary Glaucoma: A Clinical-Pathologic Report And Literature Review, Joseph B Lin, James C Liu, Rajendra S Apte, George J Harocopos

2020-Current year OA Pubs

PURPOSE: We describe a case of intraocular amyloidosis presenting as secondary glaucoma, highlighting the clinical presentation and pathologic correlates. We also review the medical literature on all prior reported cases and discuss the diagnostic challenges pertinent to this particular case.

OBSERVATIONS: We report the case of a 72-year-old man presenting with medically intractable elevations of intraocular pressure. On clinical examination, the anterior segment was unremarkable, but there were significant vitreous opacities. The patient underwent tube shunt surgery, and a simultaneous aqueous humor biopsy was acellular and nondiagnostic. A subsequent pars plana vitrectomy demonstrated amyloid aggregates on histology. Mass spectrometric analysis …

Recent Trends In The Utilization Of Molecular Breast Imaging In The United States, Ria Dave, Lin Gu, Heather V Garrett, Debbie Bennett, Dustin Stwalley, Sydney Singer, Sherwin Chiu, Michelle V Lee

2020-Current year OA Pubs

OBJECTIVE: The objective of this study was to assess trends in Molecular Breast Imaging (MBI) utilization among privately insured women in the United States (U.S.) from 2017 to 2022.

METHODS: The utilization of MBI among women aged 25-64 years from January 1, 2017, to December 31, 2022, was obtained using the Merative MarketScan Commercial Database. MBI utilization was captured from the outpatient services file using Current Procedural Terminology (CPT) or Healthcare Common Procedure Coding System (HCPCS) codes for MBI.

RESULTS: During the 6-year retrospective claims analysis, 3024 study-eligible women underwent 3648 MBI exams. The overall trend in MBI utilization was …

Emerging Options And Future Strategies In Immunotherapy For Advanced Lung Squamous-Cell Carcinoma, Y Wang, R Rosell, F R Hirsch, S Lu, R Govindan, K Park, S Peters, J J Zhang

2020-Current year OA Pubs

Advanced-stage lung squamous-cell carcinoma (LUSC) remains a therapeutic challenge. Although immune checkpoint inhibitors (ICIs) have revolutionized LUSC treatment, only a small subset of LUSC patients can achieve durable clinical benefits, underscoring the need for novel strategies. Emerging immunotherapy strategies have demonstrated early evidence of promise for LUSC patients, particularly multi-specific antibodies and fusion proteins, antibody-drug conjugates, adoptive cell therapies, and cancer vaccines. Additionally, advances in multi-omics and artificial intelligence offer potential for precise immunotherapy by deciphering the complex tumor-immune microenvironment and predicting therapeutic responses. The future of LUSC treatment lies in rational multi-target and biological therapies to boost immune cytotoxicity, …

Finding Significant Hits In Networks: A Network-Based Tool For Analyzing Gene-Level P-Values To Identify Significant Genes Missed By Standard Methods, Sandeep Acharya, Vaha Akbary Moghaddam, Wooseok J Jung, Yu S Kang, Shu Liao, Michael A Province, Michael R Brent

2020-Current year OA Pubs

Finding Significant Hits in Networks (FISHNET) uses prior biological knowledge, represented as gene interaction networks and gene function annotations, to identify genes that do not meet the genome-wide significance threshold but replicate, nonetheless. Its input is gene-level P-values from any source, including omicsWAS, aggregation of genome-wide association studies P-values, CRISPR screens, or differential expression analysis. It is based on the idea that genes whose P-values are low purely by chance are distributed randomly across networks and functions, so genes with suggestive P-values that cluster in densely connected subnetworks and share common functions are less likely to reflect chance and more …

Comparison Of Variant Callers Using 60 532 Multi-Ancestry Whole Genome Sequences, Hufeng Zhou, Nathan O Stitziel, Et Al.

2020-Current year OA Pubs

Whole genome sequencing (WGS) studies play a pivotal role in studying the genetic underpinnings of human diseases and traits. High quality and reproducible variant calling is the cornerstone for the success of downstream analyses, including WGS association studies and polygenic risk prediction. This paper compares the data quality, performance, and concordance of two widely used WGS variant callers, the Genome Analysis Toolkit (GATK) and Variant Tool set that discovers short variants (VT), using 60 532 multi-ancestry whole genomes sequenced by the Centers for Common Disease Genomics (CCDGs) of the NHGRI Genome Sequencing Program. Our findings show that both QCed GATK …

Astrocyte-Specific Deletion Of Lrrc8a Causes Neurological Dysfunction But Not Chronic White Matter Edema, Sven Kerst, Leoni Hoogterp, Marjolein Breur, Gemma M Van Rooijen-Van Leeuwen, Marianna Bugiani, Rajan Sah, Huibert D Mansvelder, Marjo S Van Der Knaap, Rogier Min

2020-Current year OA Pubs

Volume-regulated anion channels (VRACs) are central to cell volume homeostasis. They mediate swelling-induced efflux of chloride and organic osmolytes to drive regulatory volume decrease. In the brain, VRACs have been proposed to play a key role in astrocytic volume regulation. Genetic defects in astrocytic VRAC modulating proteins (MLC1, GlialCAM, Aquaporin-4, GPRC5B) cause the leukodystrophy Megalencephalic leukoencephalopathy with subcortical cysts (MLC), characterized by chronic white matter edema and myelin vacuolization. Disrupted VRAC activity in MLC-patient-derived lymphoblasts and primary astrocytes from MLC mice further supports a pathogenic link between defective VRAC activity and MLC. Here, we studied the physiological and pathological consequences …

From Damage Signals To Immune Modulators: Oxidized Lipids In Immunometabolic Inflammation, Neetu Srivastava, Xiaoxiao Wan

2020-Current year OA Pubs

Oxidized lipids, once viewed as byproducts of oxidative stress, are now recognized as critical mediators linking metabolism, redox imbalance, and immunity. Generated through enzymatic and nonenzymatic oxidation of polyunsaturated fatty acids, oxidized phospholipids, lipid aldehydes, and oxidized lipoproteins act as context-dependent signals regulating immune activation, resolution, and metabolic adaptation. In metabolic inflammation, these lipids engage scavenger and Toll-like receptors to influence macrophage polarization, dendritic-cell function, and T-cell differentiation. Their context and concentration determine whether oxidized lipids amplify inflammation or promote immune tolerance. Accumulation of these species connects oxidative stress to immune dysfunction, contributing to diseases, such as atherosclerosis, obesity, diabetes, …

Patient And Chondral Defect-Specific Characteristics And Associated Matrix-Induced Autologous Chondrocyte Implantation Conversion Rates Following Biopsy, Derrick M Knapik, Daniel C Touhey, S Ryan Pierson, Christopher K Bozorgmehr, Matthew V Smith, Matthew J Matava, Robert H Brophy

2020-Current year OA Pubs

BACKGROUND: Focal chondral defects in the knee lead to swelling, discomfort, and mechanical symptoms, resulting in disability and loss of function. Matrix-induced autologous chondrocyte implantation (MACI) has emerged as a viable treatment option, with satisfactory clinical outcomes reported compared with microfracture. Patient and lesion-specific variables associated with MACI after biopsy remain largely underreported.

PURPOSE: To examine patient- and defect-specific characteristics associated with conversion to MACI after biopsy from a single institution.

STUDY DESIGN: Cohort study; Level of evidence, 3.

METHODS: A retrospective chart review of prospectively collected data from June 2018 to March 2025 was performed. Inclusion criteria included patients …

What Constitutes Risk In Implementation Research? Perspectives From A Qualitative Key-Informant Study, Emmanuel K Tetteh, Gifty Aboagye-Mensah, Nwaliweaku Anidi, Elvin H Geng, Byron J Powell, Enola K Proctor, Mark D Huffman, Alison L Antes

2020-Current year OA Pubs

BACKGROUND: As implementation research increasingly occurs within routine care settings, determining what constitutes minimal risk is critical to ensuring that ethical oversight is appropriate and proportional. Current regulatory definitions often do not reflect the unique features of implementation studies, including implementation strategy-related risks and system-level effects. Yet, little empirical evidence exists on how researchers themselves interpret minimal risk in this context.

METHODS: We conducted semi-structured qualitative interviews with 11 key informants, including investigators with experience in domestic and global implementation research. Participants were recruited through purposive sampling. Interviews explored how participants interpret the concept of minimal risk, identify risk-related concerns, …

Comparing Ckd Populations With T1d And T2d: A Perspective Based On The Fine-One And Fidelity Populations, Hiddo J L Heerspink, Janet B Mcgill, Et Al.

2020-Current year OA Pubs

Chronic kidney disease (CKD) is a common comorbidity of both type 1 diabetes (T1D) and type 2 diabetes (T2D) and is associated with increased mortality, end-stage kidney disease and cardiovascular disease risk. Despite standard-of-care treatment with renin-angiotensin system inhibitors added to blood pressure and glycaemic control, people with CKD and T1D have a residual risk of CKD progression. Advances in therapeutic management have been limited over the past 3 decades, especially compared with CKD in T2D, for which new treatment options have emerged in the last 5 years. In this review article we discuss the similarities and differences between T1D …

Recognizing Structural And Social Determinants Of Health In The Diagnosis And Care Of Dementia, Shana D Stites, Sharnita Midgett, Nisha Patel, Kimberly Halberstadter, Rosalie Schumann, Marissa L Streitz, Yidan Shi, John C Morris, Jason Flatt, Crystal M Glover, Dawn Mechanic-Hamilton

2020-Current year OA Pubs

Structural and social determinants of health are environmental conditions that affect individuals' health and functioning across the life course. These determinants are salient factors at the apex of individual psychology, community variables, and larger sociological factors, exerting prominent effects on individuals' wellbeing. The National Institute on Aging seeks to understand their influence on aging and Alzheimer's disease. We propose that the benefits of doing so may reach beyond knowledge of disease mechanisms - it may also improve clinical outcomes. We describe efforts introducing structural and social determinants of health data into the national network of Alzheimer's disease research centers. We …

Laser Interstitial Thermal Therapy And Adjuvant Pembrolizumab In Recurrent High-Grade Astrocytoma: A Phase 1/Randomized Phase 2b Trial, Jian L Campian, Omar H Butt, Yifei Xu, Jingxia Liu, William A Leidig, Tanner Johanns, George Ansstas, Alice Y Zhou, Sangami Pugazenthi, Jiayi Huang, Milan G Chheda, Albert H Kim, Eric C Leuthardt, Et Al.

2020-Current year OA Pubs

Immune checkpoint inhibitors (ICIs) show minimal efficacy in recurrent high-grade astrocytoma (rHGA). Laser interstitial thermal therapy (LITT), a minimally invasive cytoreductive approach, may prime rHGA for ICI response. A phase 1/randomized phase 2b trial (ClinicalTrials.gov: NCT02311582 ) was designed to test pembrolizumab in combination with LITT in patients with rHGA. Nine patients were enrolled in the phase I dose-escalation lead-in study. No dose-limiting toxicities were observed and 200 mg of pembrolizumab every three weeks was determined as the recommended phase 2 dose. The phase 2b study was initially designed to randomize (up to 45) patients 1:1 to either LITT followed …

Applying Frame-Is To Characterize Provider-Led Adaptations To A Cervical Cancer Prevention Intervention In Kenya, Harriet Fridah Adhiambo, Katherine Thomas, Megan M Coe, Lynda Oluoch, Valary Ihaji, Mary Bernadette Kerubo, Alex Kinyua, Sarah Njoroge, Kenneth Ngure, Michelle Shin, Thomas A Odeny, Bryan Weiner, Nelly Mugo, Sarah Gimbel

2020-Current year OA Pubs

BACKGROUND: Implementation strategies that are contextually refined are essential for optimizing the delivery of evidence-based interventions (EBI) to prevent cervical cancer in low-resource settings. This paper reports the application of the Framework for Reporting Adaptations and Modifications to Evidence-based Implementation Strategies (FRAME-IS) to capture and disseminate strategy adaptations made to a single-visit, screen-and-treat approach with thermal ablation (SV-SAT + TA) strategy aimed at establishing sustainable cervical cancer prevention services in Kenya.

METHODS: A FRAME-IS-based tracking spreadsheet was developed to document bundled site-specific implementation strategy adaptations and across 10 facilities. Data was collected during technical assistants' (TAs) site visits, phone calls, …

Feasibility, Acceptability And Implementation Of A Whole-Family Mental Health Intervention For Displaced Adolescent Girls In Colombia: A Mixed-Methods Pilot Randomized Controlled Trial, Ilana Seff, Arturo Harker Roa, Byron Powell, Natalia Cordoba, Carolina Rodriguez, Julianne Deitch, Elvia Tamaity Ariza Pena, Feven Gebrekidan, Lindsay Stark

2020-Current year OA Pubs

Adolescent girls affected by displacement face substantial mental-health risks. The Sibling Support for Adolescent Girls in Emergencies (SSAGE) is a 12-week, gender-transformative, family-based program designed to improve adolescent girls' mental health in humanitarian settings. This mixed-methods pilot randomized controlled trial (RCT) assessed SSAGE's feasibility, acceptability and potential effects among 186 Venezuelan migrant and Colombian returnee families in Colombia. Adolescent girls aged 13-19 years, their male siblings and caregivers participated in parallel sessions on gender dynamics, communication and relationships. Implementation outcomes drew on the Mental Health Implementation Science Tools (acceptability and feasibility subscales), attendance records and qualitative interviews. Analyses followed an …

Ketogenic Diet Dampens Excitatory Neurotransmission By Shrinking Synaptic Vesicle Pools, Marion I Stunault, Pan-Yue Deng, Anjali Yadav, Erica M Periandri, Francisca N De Luna Vitorino, Michael B Thomsen, Jasmin Sponagel, Amelia J Barfield, Renzelle J Ponce, Layla Foroughi, Benjamin A Garcia, Gabor Egervari, Vitaly A Klyachko, Ghazaleh Ashrafi

2020-Current year OA Pubs

Ketogenic diet (KD) is used for the treatment of drug-resistant childhood epilepsy and has been proposed to improve outcomes in neurodegenerative diseases. However, the mechanisms by which KD alters brain circuitry remain unclear. Here, we investigated the impact of KD on hippocampal function through integrative analysis of gene expression and neurotransmission. We found that KD induces extensive transcriptional reprogramming, including altered expression of numerous synaptic genes. Proteomic and genomic profiling revealed significant changes in histone modifications, particularly at promoters of KD-regulated genes. Electrophysiological recordings showed that KD reduces excitatory synaptic gain and short-term plasticity at CA3-CA1 synapses, dampening the summation …

Estimating The Baseline Age When Longitudinal Changes In Biomarkers Accelerate: Application To An Imaging Study Of Preclinical Alzheimer Disease, Chengjie Xiong, Folasade Agboola, Jingqin Luo

2020-Current year OA Pubs

BACKGROUND: Biomarkers are routinely measured from human biospecimens and imaging scans in Alzheimer disease (AD) research. Age is a well-known risk factor for AD. Detecting the baseline age at which the longitudinal change in biomarkers starts to accelerate is important to design preventive interventions. METHODS: We analyzed longitudinal biomarker data by a random intercept and random slope model where the slope (longitudinal rate of change) was modeled as a piecewise linear and continuous function of baseline age. We proposed to estimate the baseline age at the intersection of the two linear functions by multiple methods: maximum (profile) likelihood, minimum squared …

Regional Brain Age Is Decreased In Children With Sickle Cell Anemia, Amy E Mirro, Landon C Power, Jinli Wang, Paula Germino-Watnick, Heather Roberts, Yonca Cam, Kristin P Guilliams, Slim Fellah, Yasheng Chen, Hongyu An, Jin-Moo Lee, Andria L Ford, Melanie E Fields

2020-Current year OA Pubs

DeepBrainNet, a machine learning tool, uses magnetic resonance imaging (MRI) to predict an individual's brain age, allowing calculation of the brain age gap (predicted chronological age) for use as a biomarker of brain health. We tested the DeepBrainNet tool in sickle cell anemia (SCA) on 210 brain MRIs from 130 children (90 with SCA; 40 healthy controls) to investigate the hypothesis that children with SCA would have a younger predicted brain age than healthy controls as an index of aberrant brain development. DeepBrainNet estimates brain age from 80 axial slices of each brain, with the median used as global brain …

Benefit Of Rituximab Maintenance After First-Line Bendamustine-Rituximab In Patients With Mantle Cell Lymphoma, Yucai Wang, Imran A Nizamuddin, Brad S Kahl, Et Al.

2020-Current year OA Pubs

The benefit of rituximab maintenance after first-line (1L) bendamustine-rituximab (BR) in patients with mantle cell lymphoma (MCL) remains uncertain, with inconsistent results from the phase 2 MAINTAIN trial and several retrospective studies. We conducted a large retrospective study at 27 US and Canadian academic centers to examine the benefit of rituximab maintenance after BR. A total of 911 patients received 1L BR between 2010 and 2020, and 703 had an objective response and no evidence of disease progression at the 3-month post-BR landmark. Among those, 394 (56%) received rituximab maintenance and 309 (44%) did not, with largely similar baseline patient …

Stereotactic Adaptive Radiation Therapy For Borderline Resectable Or Locally Advanced Pancreatic Cancer To Minimize Gastrointestinal Toxicity (Artia-Pancreas): Protocol For A Single-Arm Prospective Trial, Lauren E Henke, Hyun Kim, Eric Laugeman, Steven Kohlmyer, Claire Mccann, Kate Pietrovito, Kenneth Russell, Jennifer Woo, Alex T Price

2020-Current year OA Pubs

BACKGROUND: Computed tomography (CT)-guided online stereotactic adaptive radiotherapy (CT-STAR) allows for ablative radiation doses to be delivered to selected patients with borderline resectable (BR) or locally advanced pancreatic cancer (LAPC) or unresectable pancreatic cancer. However, the use of CT-STAR to deliver an ablative dose to the pancreas while minimizing gastrointestinal (GI) side effects to reduce acute and late toxicity rates compared to historic controls has yet to be prospectively evaluated.

OBJECTIVE: The primary objective of this prospective, single-arm, multicenter phase 2 clinical trial (Adaptive Radiation Therapy Individualized Approach [ARTIA]-Pancreas) is to evaluate the rate of acute grade 3+ GI toxicity …

Economic Evaluation Of Perioperative Pembrolizumab Plus Standard Of Care As Treatment For Resectable Locally Advanced Head And Neck Squamous Cell Carcinoma In The United States, Feng Qian, Arielle G Bensimon, Anjela Tzontcheva, Kimberly Benjamin, Ravindra Uppaluri, Douglas Adkins, Geoffrey Johnson, Catherine Fernan, Dandan Zheng, Yuexin Tang, Biruk Chafamo, Dominic Muston

2020-Current year OA Pubs

AIMS: In the phase 3 KEYNOTE-689 trial (NCT03765918) among patients with resectable locally advanced head and neck squamous cell carcinoma (LA HNSCC), perioperative pembrolizumab (pembrolizumab before surgery, then continued with standard-of-care [SOC] radiotherapy +/- cisplatin after surgery followed by pembrolizumab alone) significantly prolonged event-free survival vs. SOC alone, both in the intention-to-treat population and PD-L1 combined positive score (CPS) ≥1 subgroup. Perioperative pembrolizumab + SOC received Food and Drug Administration approval in June 2025 for resectable LA HNSCC expressing PD-L1 (CPS ≥ 1). The present study evaluated the cost-effectiveness of perioperative pembrolizumab + SOC versus SOC in this indication, from …

Strain-Level Heterogeneity In Gardnerella Urinary Tract Persistence And Pathogenesis In An In Vivo Model Is Consistent With Comparative Phylogenomic Analyses, Lokesh Kumar, Sonia N Whang, Deborah K Verges, Robert F Potter, Nicole M Gilbert

2020-Current year OA Pubs

BACKGROUND: Gardnerella is a bacterial genera commonly present in the female urogenital tract, especially in bacterial vaginosis. Gardnerella are frequently detected in urine collected directly from the bladder and have been implicated in urinary incontinence and recurrent urinary tract infections. Understanding the contribution of Gardnerella to pathogenesis is complicated by its genetic heterogeneity and a shortage of data from in vivo models. One clinical isolate of Gardnerella triggered urothelial exfoliation and promoted urinary tract infection by uropathogenic E. coli in a mouse model. This study was designed to compare diverse Gardnerella strains in vivo to identify genomic variation associated with …

Genetic Modifiers Of Apoe-Ε4-Associated Cognitive Decline, Alex G Contreras, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer's disease. However, APOE-ε4 is not deterministic, highlighting the need to identify additional genetic and environmental factors. APOE-ε4 has been linked to accelerated cognitive decline, so we sought to investigate genetic factors that modify APOE-ε4-associated cognitive decline. We conduct cross-ancestry APOE-ε4-stratified and interaction GWAS using harmonized cognitive data from 32,778 participants, including 29,354 non-Hispanic White and 3,424 non-Hispanic Black individuals. Our primary outcome is late-life cognition, measured using harmonized composite scores for memory, executive function, and language, modeled as continuous traits reflecting both normative cognitive aging and disease-related decline. …

Cell-Cell Communication As Underlying Principle Governing Color Pattern Formation In Teleost Fishes, Marleen Klann, Lila Solnica-Krezel, Et Al.

2020-Current year OA Pubs

The diverse pigmentation patterns of animals are crucial for predation avoidance and behavioral display. This diversity arises from interactions among distinct pigment cell types, yet mechanisms generating pattern variation across teleost fishes remain incompletely understood. In zebrafish, Turing models have been proposed to explain stripe patterns, but it is unclear if they apply to other fishes. Here, we investigate the Snowflake mutant of the anemonefish Amphiprion ocellaris, which displays enlarged white bars with irregular boundaries. Using genome-wide association mapping and targeted sequencing, we identify a missense mutation (E42K) in gja5b, encoding the gap junction protein Connexin 41.8. CRISPR/Cas9-mediated genome editing …

The Effect Of Increased Weight Loading On Body Weight Is Partly Dependent On Piezo1 In Osteoblast-Lineage Cells And Trka Signaling, Daniel Hägg, Lei Li, Alec T Beeve, Erica L Scheller, Jakob Bellman, Fredrik Anesten, Jovana Zlatkovic, Adrià Dalmau Gasull, Ferran Font-Gironès, Sofia Movérare-Skrtic, John-Olov Jansson, Claes Ohlsson

2020-Current year OA Pubs

UNLABELLED: Obesity is a complex disease driven by multiple factors, and a deeper understanding of its underlying mechanisms could enable the development of novel treatments. Based on our previous experimental studies, we have proposed a homeostatic mechanism regulating adiposity involving mechano-sensing of body weight by osteoblast-lineage cells in the lower extremities. However, the molecular mechanism underlying this proposed weight-sensing pathway remains to be elucidated. Recent studies have demonstrated that Piezo1-mediated mechano-sensing in osteoblast-lineage cells, as well as TrkA-dependent signaling, are essential for the normal bone anabolic response to high-intensity mechanical loading. We hypothesized that these pathways within bone may also …

Associations Between The Microbiome And Immune Responses To An Adenovirus-Based Hiv-1 Candidate Vaccine Are Distinct Between African And Us Cohorts, Yuhao Li, Daniel J Stieh, Lindsay Droit, Andrew Hyoungjin Kim, Rachel Rodgers, Kathie A Mihindukulasuriya, Leran Wang, Maria G Pau, Olive Yuan, Herbert W Virgin, Dan H Barouch, Megan T Baldridge, Scott A Handley

2020-Current year OA Pubs

Optimization of prophylactic vaccine regimens to elicit strong, long-lasting immunity is an urgent need highlighted by the COVID-19 pandemic. Stronger vaccine immunogenicity is frequently reported in individuals living in high-income countries compared to individuals living in low- and middle-income countries. While numerous host genetic and immune factors may influence vaccine responses, geographic restrictions to vaccine effectiveness may also be influenced by the intestinal microbiota, which modulates host immune systems. However, the potential role of the gut microbiota on responses to HIV-1 vaccines has not yet been explored. We analyzed the bacteriome by targeted 16S sequencing and the virome by virus-like …

Community Engagement And Implementation Science: A Hermeneutic Review For Implementation Scientists, Minh X Nguyen, Zhuoheng Yin, Ye Liu, Cory D Bradley, Elvin Geng, Mayuko Itofukunaga, Nyanyiwe M Mbeye, Rayner K J Tan, Sherika Hanley, Radhika Sundararajan, Joseph D Tucker

2020-Current year OA Pubs

BACKGROUND: Community engagement is increasingly part of implementation research. However, some implementation scientists are less familiar with how to use community engagement approaches in implementation research. This hermeneutic review explores the gaps in community engagement within implementation research and examines community engagement approaches for implementation researchers.

METHODS: We conducted a hermeneutic review to synthesize information in the literature on community engagement in implementation research. We searched PubMed related to community engagement and implementation research. Articles were eligible for inclusion if they were published in English, had full-text available and were likely to add meaning and valuable insights to address our …

General Anesthesia Versus Conscious Sedation For Mechanical Thrombectomy In Patients With Acute Ischemic Stroke In The Most Trial, Umeshkumar Athiraman, Akash Roy, Andrew Barreto, Joseph Broderick, Colin Derdeyn, Jordan Elm, James C Grotta, James Ingles, Achala Vagal, Max Wintermark, Opeolu Adeoye

2020-Current year OA Pubs

BACKGROUND: Several observational studies have supported the use of conscious sedation (CS) for endovascular thrombectomy in patients with acute ischemic stroke and associated general anesthesia (GA) with poor functional outcomes. Recently, few randomized controlled trials have shown no difference in the functional outcomes between GA and CS. The aim of this paper is to compare the outcomes of GA versus CS in patients with acute ischemic stroke undergoing mechanical thrombectomy in the MOST (Multi-arm Optimization of Stroke Thrombolysis) trial.

METHODS: Patients who underwent mechanical thrombectomy for acute ischemic stroke under GA or CS in the MOST trial were included. The …

Community-Associated Quinolone-Resistant And Extended-Spectrum Beta-Lactamase-Producing Escherichia Coli Isolates Are Similar To Clinical Infection Isolates By Sequence Type And Resistome, Emily E Benedict, Wesley Agee, Tiffany Hink, Katelyn L Parrish, Kimberly A Reske, Kate Peacock, Rachel E Bosserman, Alyssa Valencia, Akshay Saluja, Elianora Ovchiyan, Olivia Arter, Kevin Jolani, Erik R Dubberke, Gautam Dantas, Jennie H Kwon

2020-Current year OA Pubs

No abstract provided.