Medicine and Health Sciences Commons^™

For Girls And Women (4gw) Hpv Rct Protocol: A Crowdsourced, Pragmatic Stepped-Wedge Cluster Randomized Trial To Improve Uptake Of Hpv Vaccination And Screening Among Mother-Daughter Dyads In Nigeria, Juliet Iwelunmor, Ekenechukwu Kokelu, Temitope Ojo, Olufunto Olusanya, Titilola Gbaja-Biamila, Peter Kalulu, Angel Obiorah, Maria Afadapa, Nkiruka Obodoechina, Onyeka Anikamadu, Et Al.

2020-Current year OA Pubs

BACKGROUND: Expanding human papillomavirus (HPV) vaccination for girls and HPV self-collection for women can reduce the global burden of cervical cancer. However, HPV vaccination and self-collection services are rarely implemented simultaneously in mother-daughter dyads, leaving a critical gap in cervical cancer prevention. From 2023 to 2024, a community-engaged model for combined HPV vaccination and screening was co-designed using crowdsourcing open calls and designathons with mother-daughter teams and pilot-tested by trained research facilitators. This study explores the impact of this crowdsourced, community-engaged mother-daughter campaign and implementation strategy bundle on HPV vaccination among girls and HPV screening among their mothers in Nigeria …

Treatment Patterns And Survival Among Veterans With De Novo Metastatic Hormone-Sensitive Prostate Cancer, Martin W Schoen, Saira Khan, Eric M Knoche, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Combination therapy for metastatic hormone-sensitive prostate cancer (mHSPC) has been widely adopted, yet clinical use and outcomes are unknown. Furthermore, optimal therapy is uncertain due to lack of direct comparison of androgen receptor pathway inhibitors (ARPIs) and docetaxel in high-volume disease.

OBJECTIVE: To evaluate the use of combination therapy and its association with overall survival among patients with mHSPC and to compare ARPIs vs docetaxel doublet therapy by volume of disease.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cross-sectional study was conducted in the US Veterans Health Administration among 6216 US veterans with de novo mHSPC from January 1, 2013, …

Research Participant Interest In Learning Results Of Biomarker Tests For Alzheimer Disease, Spondita Goswami, Sarah M Hartz, Amy Oliver, Sacha Jackson, Tomi Ogungbenle, Alissa Evans, Erin Linnenbringer, Krista L Moulder, John C Morris, Jessica Mozersky

2020-Current year OA Pubs

IMPORTANCE: While available evidence suggests there are not major psychosocial harms of return of research results, there are limited data on uptake of Alzheimer disease (AD) research results or reasons for declining to learn results among participants in AD research studies.

OBJECTIVES: To quantitatively and qualitatively evaluate who declines to learn individual AD biomarker research results and what factors are associated with the decision.

DESIGN, SETTING, AND PARTICIPANTS: This observational cohort study was conducted between November 1, 2020, and April 15, 2024, among participants aged 65 years or older with unimpaired cognition and available biomarker data (apolipoprotein E genotype and …

Clinical Validation Of A Vaginal Cervical Cancer Screening Self-Collection Method For At-Home Use: A Nonrandomized Clinical Trial, Megan B Fitzpatrick, Colleen Mcnicholas, Lindsay Kuroki, Et Al.

2020-Current year OA Pubs

IMPORTANCE: One-quarter of US women who are at risk for cervical cancer delay screening. Self-collected (SC) cervical screening was recently US Food and Drug Administration (FDA)-approved in the US for use in a health care setting only; an at-home SC option is crucial to address clinic-related barriers to screening.

OBJECTIVE: To clinically validate the use of an SC device that was designed for optimal at-home performance, safety, ease-of-use, and dry storage and transport.

DESIGN, SETTING, AND PARTICIPANTS: This nonrandomized clinical trial used a prospective method comparison study design. Participants aged 25 to 65 years were recruited from 16 clinical sites …

Combining Exercise Training And Testosterone Therapy In Older Women After Hip Fracture: The Step-Hi Randomized Clinical Trial, Ellen F Binder, Peter M Doré, Camelia Guild, Kelly M Monroe, Dominic Reeds, Kenneth B Schechtman, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Despite receiving postacute rehabilitation services, many older women with a recent hip fracture repair are unable to return to their prefracture level of function. Whether testosterone therapy can enhance recovery after hip fracture in older women with persistent mobility impairments has not been fully examined.

OBJECTIVE: To evaluate the effects of a supervised exercise program combined with topical testosterone therapy on functional outcomes in older women with a recent hip fracture.

DESIGN, SETTING, AND PARTICIPANTS: This phase 3 double-blind, placebo-controlled randomized clinical trial, Starting a Testosterone and Exercise Program After Hip Injury (STEP-HI), was conducted at 8 US sites …

High-Dimensional Mediation Analysis For Longitudinal Mediators And Survival Outcomes, Lili Liu, Haixiang Zhang, Yinan Zheng, Tao Gao, Cheng Zheng, Kai Zhang, Lifang Hou, Lei Liu

2020-Current year OA Pubs

Mediation analysis with high-dimensional mediators is crucial for identifying epigenetic pathways linking environmental exposures to health outcomes. However, high-dimensional mediation analysis methods for longitudinal mediators and a survival outcome remain underdeveloped. This study fills that gap by introducing a method that captures mediation effects over time using multivariate, longitudinally measured time-varying mediators. Our approach uses a longitudinal mixed effects model to examine the relationship between the exposure and the mediating process. We connect the mediating process to the survival outcome using a Cox proportional hazards model with time-varying mediators. To handle high-dimensional data, we first employ a mediation-based sure independence …

Early-Life Factors And Body Mass Index Trajectories Among Children In The Echo Cohort, Chang Liu, Katherine Rivera-Spoljaric, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Identifying atypical body mass index (BMI) trajectories in children and understanding associated, modifiable early-life factors may help prevent childhood obesity.

OBJECTIVE: To characterize multiphase BMI trajectories in children and identify associated modifiable early-life factors.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included longitudinal data obtained from January 1997 to June 2024, from the Environmental influences on Child Health Outcomes (ECHO) cohort, which included children aged 1 to 9 years with 4 or more weight and height assessments. Analyses were conducted from January to June 2024.

EXPOSURES: Prenatal exposure to substances and stress (smoking, alcohol, depression, anxiety), maternal characteristics (prepregnancy …

Simulation-Guided Pan-Cancer Analysis Identifies A Novel Regulator Of Cpg Island Hypermethylation Heterogeneity, Xianglin Zhang, Wei Zhang, Jinyi Zhang, Xiuhong Lyu, Haoran Pan, Tianwei Jia, Ting Wang, Xiaowo Wang, Haiyang Guo

2020-Current year OA Pubs

CpG island hypermethylation, a hallmark of cancer, exhibits substantial heterogeneity across tumors, presenting both opportunities and challenges for cancer diagnostics and therapeutics. While this heterogeneity offers potential for patient stratification to predict clinical outcomes and personalize treatments, it complicates the development of robust biomarkers for early detection. Understanding the mechanisms driving this heterogeneity is essential for advancing biomarker design. Here, simulation-based analyses demonstrate that tumor purity and the high prevalence of low epi-mutation samples significantly obscure the identification of negative, rather than positive, regulators of CpG island hypermethylation, limiting a comprehensive understanding of heterogeneity sources. By addressing these confounders, we …

Three-Year Analysis Of Adult Patients With Relapsed Or Refractory B-Cell Acute Lymphoblastic Leukemia Treated With Brexucabtagene Autoleucel In Zuma-3, Bijal D Shah, Armin Ghobadi, Et Al.

2020-Current year OA Pubs

Brexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 CAR T-cell therapy approved in the US to treat adults aged ≥18 years (≥26 years in the EU) with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). Brexu-cel showed an overall complete remission (CR)/CR with incomplete hematologic recovery (CRi) rate of 73% (CR rate 60%) and median overall survival (OS) of 25.4 months in 78 patients with R/R B-ALL after 2 years in ZUMA-3. Here, we report updated outcomes after >3 years median follow-up. As of July 23, 2022, median follow-up in all patients (N = 78) was 41.6 months. Median OS (95% CI) …

Multiregional Implementation Initiative's Impact On Guideline-Based Performance Measures For Patients Hospitalized With Heart Failure: Implement-Hf, Andrew J. Sauer, Nancy Sweitzer, Et Al.

2020-Current year OA Pubs

BACKGROUND: Despite randomized data for survival benefit (with class 1 recommendations) for treating heart failure (HF) with reduced ejection fraction using quadruple medical therapy (QMT)-defined as evidence-based β-blockers, sodium-glucose cotransporter 2 inhibitor, preferably angiotensin receptor/neprilysin inhibitor, and mineralocorticoid receptor antagonist-it is underutilized. IMPLEMENT-HF is a multiregional HF quality improvement initiative to improve care and outcomes for patients with HF by enhancing the use of QMT in routine practice.

METHODS: This analysis of HF with reduced ejection fraction treatment in patients from hospitals participating in the American Heart Association's Get With The Guidelines-HF who volunteered to participate in IMPLEMENT-HF in 7 …

Automated Extraction Of Functional Biomarkers Of Verbal And Ambulatory Ability From Multi-Institutional Clinical Notes Using Large Language Models, Levi Kaster, Ethan Hillis, Inez Y Oh, Bhooma R Aravamuthan, Virginia C Lanzotti, Casey R Vickstrom, Brain Gene Registry Consortium, Christina A Gurnett, Philip R O Payne, Aditi Gupta

2020-Current year OA Pubs

BACKGROUND: Functional biomarkers in neurodevelopmental disorders, such as verbal and ambulatory abilities, are essential for clinical care and research activities. Treatment planning, intervention monitoring, and identifying comorbid conditions in individuals with intellectual and developmental disabilities (IDDs) rely on standardized assessments of these abilities. However, traditional assessments impose a burden on patients and providers, often leading to longitudinal inconsistencies and inequities due to evolving guidelines and associated time-cost. Therefore, this study aimed to develop an automated approach to classify verbal and ambulatory abilities from EHR data of IDD and cerebral palsy (CP) patients. Application of large language models (LLMs) to clinical …

Histidine-Rich Enantiomeric Peptide Coacervates Enhance Antigen Sequestration And Presentation To T Cells, Ushasi Pramanik, Anirban Das, Elise M Brown, Heather L Struckman, Huihao Wang, Samuel Stealey, Macy L Sprunger, Abdul Wasim, Jonathan Fascetti, Jagannath Mondal, Jonathan R Silva, Silviya P Zustiak, Meredith E Jackrel, Jai S Rudra

2020-Current year OA Pubs

Peptides and peptidomimetics that self-assemble through LLPS have recently emerged as vital building blocks for creating functional biomaterials, thanks to their unique physicochemical properties and dynamic nature. One of life's most distinctive features is its selectivity for chiral molecules. To date, coacervates comprised of d-amino acids have not been reported. Here, we demonstrate that histidine-rich repeats of (GHGXY)

Synergies, Partnership Outcomes, And Lessons Learned: A Qualitative Evaluation Of Cancer Center-Coalition Engagement, Aubrey Villalobos, Sarah Chavez, Bettina Drake, Et Al.

2020-Current year OA Pubs

BACKGROUND: Nine National Cancer Institute-Designated Cancer Centers received supplemental funding to expand community outreach and engagement activities through a partnership with Centers for Disease Control and Prevention-funded comprehensive cancer control coalitions. This article reports on an evaluation of these awards focused on organizational relationships and partnership outcomes.

METHODS: The National Cancer Institute, community outreach and engagement, and coalition representatives co-designed the evaluation, which involved document review and 18 semistructured interviews with 16 community outreach and engagement and 19 coalition representatives. Artificial intelligence-generated interview transcripts were dual-coded in NVivo, version 20/R1, software.

RESULTS: The funding generated a diverse collection of projects …

A Secretome Atlas Of Cardiac Fibroblasts From Healthy And Infarcted Mouse Hearts, Jasmin Bahr, Junedh M Amrute, Kory J Lavine, Et Al.

2020-Current year OA Pubs

Cardiac fibroblasts (CF) are key players after myocardial infarction (MI), but their signaling is only incompletely understood. Here we report a first secretome atlas of CF in control (cCF) and post-MI mouse hearts (miCF), combining a rapid cell isolation technique with SILAC and click chemistry. In CF, numerous paracrine factors involved in immune homeostasis are identified. Comparing secretome, transcriptome (SLAMseq), and cellular proteome disclose protein turnover. In miCF at day 5 post-MI, significantly upregulated proteins include SLIT2, FN1, and CRLF1 in mouse and human samples. Comparing the miCF secretome at days 3 and 5 post-MI reveals the dynamic nature of …

Distinct Oxytocin Signaling Pathways Synergistically Mediate Rescue-Like Behavior In Mice, Feng-Rui Zhang, Juan Liu, Jieqi Wen, Zi-Yan Zhang, Yijia Li, Eric Song, Li Hu, Zhou-Feng Chen

2020-Current year OA Pubs

Spontaneous rescue behavior enhances the well-being and survival of social animals, yet the neural mechanisms underlying the recognition and response to conspecifics in need remain unclear. Here, we report that observer mice experience distress when encountering anesthetized conspecifics, prompting spontaneous rescue-like behavior toward the unconscious mice. This behavior facilitates the earlier awakening of anesthetized mice while simultaneously alleviating stress in the helper mice. Our findings reveal that endogenous oxytocin (OXT) release from the hypothalamic paraventricular nucleus (PVN) to the oxytocin receptor (OXTR) in the central nucleus of the amygdala (CeA) regulates the emotional component of rescue-like behavior. In contrast, OXT …

Patient-Generated Health Data: Impact On Promoting Patient-Centered Point Of Care Tobacco Treatment In Patients With Cancer, Jessica Liu, Jingling Chen, Nina Smock, Nicholas B Griffith, Ramaswamy Govindan, Paula Goldberg, Jodi Thole, Kristin Daly, James Reddy, Alex T Ramsey, Laura J Bierut, Aimee James, Robert A Schnoll, Ross C Brownson, Li-Shiun Chen, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Guideline-based tobacco treatment is infrequently offered. Electronic health record-enabled patient-generated health data (PGHD) has the potential to increase patient treatment engagement and satisfaction.

METHODS: We evaluated outcomes of a strategy to enable PGHD in a medical oncology clinic from July 1, 2021 to December 31, 2022. Among 12,777 patients, 82.1% received a tobacco screener about use and interest in treatment as part of eCheck-in via the patient portal.

RESULTS: We attained a broad reach (82.1%) and moderate response rate (30.9%) for this low-burden PGHD strategy. Patients reporting current smoking (

DISCUSSION: PGHD via patient portal appears to be a …

Place-Based Harms And Hidden Strengths: A Qualitative Study Exploring Facets Of Neighborhood Disinvestment Driving Opioid Overdose Among Black Individuals, Kaytryn D Campbell, Rachel P Winograd, Maria E Paschke, Alex Duello, Devin E Banks

2020-Current year OA Pubs

BACKGROUND: Despite significant efforts to address the opioid overdose crisis, Black people who use drugs (PWUD) face unabating, disproportionate increases in opioid overdose death (OOD) rates. These inequities persist in treatment admissions, utilization of medication for opioid use disorder, and treatment retention. Research has linked neighborhood disinvestment - a process of urban decline driven by policy-related changes in neighborhood demand and desirability leading to decreased population, physical and economic erosion, and poorer quality of life for residents - to increased rates of OOD. However, given recent increases in OOD inequities, more research is needed to determine the specific aspects of …

Functional Connectivity Between The Visual And Salience Networks And Autistic Social Features At School-Age, Jessica B Girault, Tomoyuki Nishino, Muhamed Talović, Margaret Reynolds, Abraham Z Snyder, Kelly N Botteron, Natasha Marrus, Robert C Mckinstry, Alexandre A Todorov, John R Pruett Jr, Et Al.

2020-Current year OA Pubs

BACKGROUND: Autism spectrum disorder (ASD) is highly heritable and phenotypically variable. Neuroimaging markers reflecting variation in behavior will provide insights into circuitry subserving core features. We examined functional correlates of ASD symptomology at school-age, while accounting for associated behavioral and cognitive domains, in a longitudinal sample followed from infancy and enriched for those with a genetic liability for ASD.

METHODS: Resting state functional connectivity MRIs (fcMRI) and behavioral data were analyzed from 97 school-age children (8.1-12.0 years, 55 males, 15 ASD) with (n = 63) or without (n = 34) a family history of ASD. fcMRI enrichment analysis (EA) was …

Perspectives On The Current Diagnostic And Treatment Paradigms In Secondary Hemophagocytic Lymphohistiocytosis (Hlh), Leonard Naymagon, Jeffrey Bednarski, Et Al.

2020-Current year OA Pubs

Improved awareness of hemophagocytic lymphohistiocytosis (HLH) among clinicians has led to an increase in its diagnosis. Often diagnosis is made based on the HLH- 2004 criteria. While these criteria have considerable strengths, they lack specificity and may be fulfilled in the setting of many pro-inflammatory disorders. Genetic defects affecting cellular cytotoxicity cause familial (primary) HLH. On the other hand, secondary HLH is more a pathophysiologic process common to many conditions, rather than a singular disease entity. Improved genetic, immunologic, and functional testing have changed not only the way we diagnose HLH, but also how we treat it. In 2004, there …

Functional Screening Identifies Kinesin Spindle Protein Inhibitor Filanesib As A Potential Treatment Option For Hepatoblastoma, Ruth Nousiainen, Katja Eloranta, Jani Saarela, Antti Hassinen, Tamara J Luck, Stefano Cairo, Emilie Indersie, Swapnil Potdar, Michaela J Feodoroff, Jouko Lohi, Lassi Paavolainen, David B Wilson, Vilja Pietiäinen, Markku Heikinheimo, Marjut Pihlajoki

2020-Current year OA Pubs

Hepatoblastoma is a rare pediatric liver malignancy usually treated with surgery and chemotherapy. To explore new treatment options for hepatoblastoma, drug screening was performed using six cell models established from aggressive hepatoblastoma tumors and healthy pediatric primary hepatocytes. Of the 527 screened compounds, 98 demonstrated cancer-selective activity in at least one hepatoblastoma model. The kinesin spindle protein (KSP) inhibitor filanesib was effective in all models and was further evaluated. Filanesib induced G2/M arrest and apoptosis in hepatoblastoma cells at concentrations tolerable to primary hepatocytes. Prominent nuclear fragmentation was observed in filanesib-treated hepatoblastoma cells. Genes participating in cell cycle regulation were …

Deciphering Distinct Genetic Risk Factors For Ftld-Tdp Pathological Subtypes Via Whole-Genome Sequencing, Cyril Pottier, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

Frontotemporal lobar degeneration with neuronal inclusions of the TAR DNA-binding protein 43 (FTLD-TDP) is a fatal neurodegenerative disorder with only a limited number of risk loci identified. We report our comprehensive genome-wide association study as part of the International FTLD-TDP Whole-Genome Sequencing Consortium, including 985 patients and 3,153 controls compiled from 26 institutions/brain banks in North America, Europe and Australia, and meta-analysis with the Dementia-seq cohort. We confirm UNC13A as the strongest overall FTLD-TDP risk factor and identify TNIP1 as a novel FTLD-TDP risk factor. In subgroup analyzes, we further identify genome-wide significant loci specific to each of the three …

Adipose-Derived Leptin And Complement Factor D Mediate Osteoarthritis Severity And Pain, Kelsey H Collins, Kristin L Lenz, Hope D Welhaven, Erica Ely, Luke E Springer, Sophie Paradi, Ruhang Tang, Lauryn Braxton, Antonina Akk, Huimin Yan, Bo Zhang, Xiaobo Wu, John P Atkinson, Arin K Oestreich, Ron K June, Christine T N Pham, Farshid Guilak

2020-Current year OA Pubs

Obesity is a risk factor for osteoarthritis (OA), and leptin is among the adipokines implicated in obesity-induced OA. However, the specific role of leptin in OA severity and pain is not known. Using lipodystrophic (LD) mice, we show that fat-secreted factors are required for knee OA development, implicating a fat-cartilage cross-talk. Fat pad implantation or systemic leptin restoration in LD mice reintroduced structural OA and pain, whereas implantation of leptin-deficient fat pad did not change OA susceptibility. Isochronic parabiosis and spatial transcriptomics confirmed that a fat-joint cross-talk likely occurred via soluble mediators. Global unsupervised multiomics of conditioned media from fat …

Development And Evaluation Of A Non-Invasive Brain-Spine Interface Using Transcutaneous Spinal Cord Stimulation, Carolyn Atkinson, Lorenzo Lombardi, Meredith Lang, Rodolfo Keesey, Rachel Hawthorn, Zachary Seitz, Eric C Leuthardt, Peter Brunner, Ismael Seáñez

2020-Current year OA Pubs

Motor rehabilitation is a therapeutic process to facilitate functional recovery in people with spinal cord injury (SCI). However, its efficacy is limited to areas with remaining sensorimotor function. Spinal cord stimulation (SCS) creates a temporary prosthetic effect that may allow further rehabilitation-induced recovery in individuals without remaining sensorimotor function, thereby extending the therapeutic reach of motor rehabilitation to individuals with more severe injuries. In this work, we report our first steps in developing a non-invasive brain-spine interface (BSI) based on electroencephalography (EEG) and transcutaneous spinal cord stimulation (tSCS). The objective of this study was to identify EEG-based neural correlates of …

Comparative Efficacy And Acceptability Of Interventions For Universal, Selective And Indicated Prevention Of Eating Disorders: Study Protocol For A Systematic Review And Network Meta-Analysis, Sandra Schlegl, Felicitas Hirler, Andreas Gerich, Mikkel Højlund, Eric Stice, Tracey Wade, Denise Wilfley, James Downs, Ulrich Voderholzer, Jasmine Perry, Verena Haas, Marco Solmi, Christoph Correll

2020-Current year OA Pubs

BACKGROUND: Eating disorders (EDs) are severe psychiatric conditions, with prevalence rates ranging from 5.5 to 17.9% in women and 0.6 to 2.4% in men. EDs carry a high risk of chronicity and mortality, highlighting the need for effective prevention strategies. Primary prevention can target the entire population (universal), high-risk groups (selective), or individuals with early signs (indicated). Despite substantial research, prior reviews often show limitations, such as single-author data extraction, lack of quality assessment, reliance on endpoint data, exclusion of obesity prevention programs, or outdated findings. No review has yet evaluated the comparative effectiveness of multiple interventions across risk groups. …

Implementation Of The Extension For Community Healthcare Outcomes Model For Hypertension Education Of Frontline Health Care Workers In The Federal Capital Territory, Nigeria: Explanatory Sequential Mixed Methods Evaluation, Abigail S Baldridge, Mark D Huffman, Et Al.

2020-Current year OA Pubs

BACKGROUND: The Extension for Community Healthcare Outcomes (ECHO) model was adapted for hypertension education of community health extension workers in the Federal Capital Territory, Nigeria, and delivered as a 7-part series.

OBJECTIVE: This study aims to evaluate implementation outcomes of the hypertension ECHO series mapped to the first 3 levels of the Kirkpatrick model. Outcomes included reach, appropriateness (level 1), effectiveness (level 2), and penetration (level 3).

METHODS: From August 2022 to April 2023, 7 hypertension ECHO sessions were delivered via Zoom (Zoom Video Communications, Inc) to a health care worker audience including targeted community health extension workers at 12 …

Induction Of Cardiac Fibulin-4 Protects Against Pressure Overload-Induced Cardiac Hypertrophy And Heart Failure, E D Van Deel, C M Halabi, Et Al.

2020-Current year OA Pubs

The prevailing view of fibulin-4 deficient mice is that the cardiac phenotype is the result of aortic and/or valvular disease. In the present study, we have tested whether the cardiac phenotype is, at least in part, the consequence of primary cardiac effects of fibulin-4. We have found fibulin-4 expression to be activated throughout the myocardium in wildtype (fibulin-4

Samd9 Senses Cytosolic Double-Stranded Nucleic Acids In Epithelial And Mesenchymal Cells To Induce Antiviral Immunity, Gaopeng Hou, Wandy Beatty, Juhee Son, Yinxing Zhu, Qingyu Sheng, Wanyi Huang, Dian Li, Constin Liu, Chen Shen, L David Sibley, Siyuan Ding, Et Al.

2020-Current year OA Pubs

Sensing of cytosolic, double-stranded (ds) DNA or dsRNA molecules derived from microbial or endogenous sources triggers cell-intrinsic innate immunity, but sensors recognizing both cytosolic dsDNA and dsRNA are sparsely reported. Here we find that full-length human SAMD9 protein directly binds to synthetic or viral dsDNA or dsRNA. Overexpression of SAMD9 from various vertebrate species leads to robust production of interferons and pro-inflammatory cytokines. By contrast, loss of endogenous SAMD9 impairs the interferon responses to cytosolic dsDNA and dsRNA stimulation in multiple cell types and enhances the infectivity of pathogenic dsDNA and dsRNA viruses. Mice lacking Samd9l, the human SAMD9 homolog, …

Disuse-Driven Plasticity In The Human Thalamus And Putamen, Roselyne J Chauvin, Dillan J Newbold, Ashley N Nielsen, Ryland L Miller, Samuel R Krimmel, Athanasia Metoki, Anxu Wang, Andrew N Van, David F Montez, Scott Marek, Vahdeta Suljic, Noah J Baden, Nadeshka Ramirez-Perez, Kristen M Scheidter, Julia S Monk, Forrest I Whiting, Babatunde Adeyemo, Jarod L Roland, Abraham Z Snyder, Benjamin P Kay, Marcus E Raichle, Timothy O Laumann, Evan M Gordon, Nico U F Dosenbach

2020-Current year OA Pubs

Subcortical plasticity has mainly been studied using invasive electrophysiology in animals. Here, we leverage precision functional mapping (PFM) to study motor plasticity in the human subcortex during 2 weeks of upper-extremity immobilization with daily resting-state and motor task fMRI. We found previously that, in the cortex, limb disuse drastically impacts disused primary motor cortex functional connectivity (FC) and is associated with spontaneous fMRI pulses. It remains unknown whether disuse-driven plasticity pulses and FC changes are cortex specific or whether they could also affect movement-critical nodes in the thalamus and striatum. Tailored analysis methods now show spontaneous disuse pulses and FC …

Sars-Cov-2 N Protein And Anti-Spike Serologies: Insights Into Covid-19 Disease Severity And Mortality-A Secondary Analysis Of The Activ-1 Trial, Alfredo J Mena Lora, Kimi Enders, Huimin Wu, Luis Parra-Rodriguez, Christopher Palma, Katy Saliba, Sylvain Laverdurre, P Brian Smith, Kevin J Anstrom, Samuel A Bozzette, William G Powderly

2020-Current year OA Pubs

BACKGROUND: Understanding factors that predict progression to severe COVID-19 is critical. Antibodies targeting SARS-CoV-2 spike protein confer protection, while the N protein of SARS-CoV-2 plays roles in viral replication and immune dysfunction. This study explores the significance of N protein and anti-spike antibodies on disease severity, progression, and mortality.

OBJECTIVES: To evaluate the relationship between SARS-CoV-2 N protein and anti-spike antibody levels with disease severity, clinical outcomes, and mortality in hospitalized patients with COVID-19.

DESIGN: A secondary analysis of serologic data from participants in the ACTIV-1 randomized clinical trial, which evaluated immunomodulators for the treatment of hospitalized patients with COVID-19. …

Center-Ing Black Voices: Incorporating Lived Experience Across The Research Process To Advance Equity In Drug Treatment And Outcomes, Devin E Banks, Maria E Paschke, Kaytryn D Campbell, Daje D Bradshaw-Glenn, Rashmi Ghonasgi, Burton Barr, Arial Collins, Gerald Dennis, Keith Lofton, Alfred Long, Harriet Montgomery, Andreas Prince, Rachel P Winograd

2020-Current year OA Pubs

BACKGROUND: Black people in the United States face persistent and increasing inequities in addiction treatment access and drug overdose death. Incorporating people with lived experience through community based participatory research (CBPR) approaches can improve understanding of drivers of and solutions to such inequities. However, practical and systemic challenges limit incorporating Black people with lived experience with substance use across each step of the research process. This paper describes the methods, recommendations, and lessons learned from a research team and Black-led community advisory board (CAB) working together across the research process to promote equity in harm reduction and addiction treatment.

METHODS: …