Digital Commons Network^™

A Cluster-Randomized Controlled Trial Assessing The Effectiveness Of A Multifaceted Versus A Discrete Implementation Strategy On Fidelity To An Occupational Guideline For The Prevention Of Mental Health Problems At The Workplace: A Dual Perspective From Swedish Schools, Andreas Rödlund, Anna Toropova, Rebecca Lengnick-Hall, Byron J Powell, Liselotte Schäfer Elinder, Christina Björklund, Lydia Kwak

2020-Current year OA Pubs

BACKGROUND: Although the management of psychosocial risks in the work environment represents an evidence-based approach to the prevention of mental health problems, its implementation is limited, including in schools, and knowledge on how to support better implementation is scarce. This study compares the effectiveness of a multifaceted vs. a discrete implementation strategy on fidelity to an occupational guideline for the prevention of mental health problems. Dual perspectives were used to assess fidelity, an important aspect of the measurement agenda.

METHODS:  A cluster-randomized controlled trial was conducted among 55 schools in Sweden. A multifaceted strategy (educational meeting, implementation teams, ongoing training, …

Mu-Glioma Post: A Comprehensive Dataset Of Automated Mr Multi-Sequence Segmentation And Clinical Features, Esmat Mahmoud, Jaime Gass, Yaseen Dhemesh, Josh Greaser, Karolina Pogorzelski, Edvin Isufi, Filip Garrett, Jonathan Thacker, Nourel Hoda Tahon, Jason Sinclair, Lester Layfield, Talissa Altes, Ayman Nada

2020-Current year OA Pubs

Gliomas represent a heterogenous group of primary brain tumors with overlapping imaging phenotypes. Treatment typically includes surgery and/or chemoradiation, however this varies based on the overall lesion and clinical presentation. This heterogeneity in both lesion characteristics and management strategies contributes to a lack of reliable findings when evaluating treatment outcomes with conventional MRI. The overlapping imaging features of radiation necrosis and tumor progression post-treatment can be particularly challenging for radiologists. We present a dataset of 203 glioma patients with 594 post-treatment timepoints of relevant clinical history and routine T1, T1 postcontrast, T2, and FLAIR weighted MR sequences. Preprocessing of the …

Assessing The Usability Of A Novel Toolkit For Creating Visual Key Information Pages For Informed Consent For Research: Mixed Methods Usability Study, Eliana Charlotte Goldstein, Zoe Troubh, Krista E Cooksey, Molly Volkmar, Victor Catalan Gallegos, Kimberly A Kaphingst, Clara N Lee, Ashley J Housten, Jessica Mozersky, Mary C Politi

2020-Current year OA Pubs

BACKGROUND: Key information pages for informed consent require a concise summary of information to improve participant understanding but have not widely incorporated health literacy best practices.

OBJECTIVE: We previously developed a visual key information template to improve informed consent. In this study, we conducted usability testing of this customizable one-page key information template.

METHODS: We used the Designing for Accelerated Translation framework to plan for actionable, efficient usability testing. Participants (N=15) were asked to spend about 20 minutes using the visual key information template and engaging in a think-aloud protocol. They then responded to qualitative debrief questions about the template …

Modulation Of Dorsal Hippocampal Sk2 Channels Regulates Morphine-Enhanced Neuronal Oscillations And Morphine-Induced Contextual Memory Encoding And Retrieval, Khairunisa Mohamad Ibrahim, Dominika J Burek, Azra Zec, Olayinka Idowu, Will W Post, Alice Zheng, Basma Daham, Justin D Meyer, Sidney Williams, Nicolas Massaly, Jose A Morón

2020-Current year OA Pubs

Persistent maladaptive drug-context associations are a key component of relapse vulnerability and pose a major obstacle in treating opioid use disorder. Although the dorsal hippocampus (dHPC) is critical for contextual memory formation, the synaptic mechanisms by which opioids alter hippocampal circuits to sustain these associations remain unclear. We previously found that repeated context-paired morphine exposure impairs dHPC long-term potentiation (LTP) through enhanced activity of small-conductance calcium-activated potassium (SK2) channels. Here, we investigated the role of SK2 channels in morphine-context associative learning and memory by combining in vivo electrophysiology, molecular analyses, and behavioral pharmacology with the morphine-conditioned place preference (MorCPP) paradigm …

Design And Implementation Of A Drug Revolving Fund For Hypertension Treatment In Primary Care Setting Of The Federal Capital Territory, Nigeria, Grace Julcit Shedul, Erica L Jamro, Mark D Huffman, Et Al.

2020-Current year OA Pubs

BACKGROUND: Expanding treatment for hypertension requires ensuring access to affordable, high-quality blood pressure (BP) lowering medications. We describe the design, implementation and evaluation of a BP-lowering medication drug revolving fund (DRF) embedded in the Hypertension Treatment in Nigeria (HTN) Programme in 60 primary healthcare centres (PHCs) in the Federal Capital Territory, Nigeria.

METHODS: We used the exploration, preparation, implementation and sustainment framework to describe the DRF design and implementation and the reach, effectiveness, adoption, implementation and maintenance framework to report implementation outcomes. From June 2022 to December 2023, the DRF programme was implemented, and the data were collected from PHCs' …

Two Unrelated Pseudomonas Aeruginosa Phages Require The Exopolysaccharide Psl For Infection, Kristen Amyx-Sherer, Leila C Awasthi, Amanda Zheng, Anna Johannesman, Michele Leroux, Courtney Reichhardt

2020-Current year OA Pubs

Bacteria commonly protect themselves from a variety of threats by forming biofilms, which are communities of bacteria that are tightly packed together within an extracellular matrix. Biofilm formation has generally been thought to protect bacteria from phage infection. The opportunistic pathogen Pseudomonas aeruginosa produces biofilm matrices that can contain three distinct exopolysaccharides that contribute to the difficulty in treating infected patients. Here, we demonstrate that two diverse P. aeruginosa phages have evolved to exploit this biofilm matrix to access the bacterial cells by both binding to and degrading a major biofilm exopolysaccharide, Psl. We examined the effect of these phages …

Depth-Variant Deconvolution Applied To Widefield Microscopy For Rapid Large-Volume Tissue Imaging, Daniel D Lee, Kevin A Telfer, Mark A J Koenis, Yim K Lee, Kevin W Namink, Brian T Saunders, Heyun Lee, Hailey Kelley, Heather S Ruiz, Joseph P Gaut, Gwendalyn J Randolph, Bernd H Zinselmeyer

2020-Current year OA Pubs

Innovations in 3D tissue imaging have revolutionized research, but limitations stemming from lengthy protocols and equipment accessibility persist. Widefield microscopy is fast and accessible but often excluded from 3D imaging workflows due to its lack of optical sectioning. Here we combine tissue clearing with a commercial depth-variant deconvolution approach that we optimized for large-volume widefield imaging. By implementing prefiltering with z-brick splitting, we achieve subnuclear axial resolution in tissues to a depth of 500 µm in multi-tile scan images. We illustrate the utility of this method in a model of ileitis and to gain a 3D perspective in thick brain …

Bladder Health And The Urogenital Microbiome In Community-Dwelling Adult Females, L Brubaker, D Mcdonald, S Putnam, C Brennan, C S Fok, C E Lewis, J L Lowder, M G Mueller, L M Rickey, E R Mueller, S J Song, K Rudser, R Knight, E S Lukacz, Plus Consortium

2020-Current year OA Pubs

UNLABELLED: Despite the established association with lower urinary tract symptoms, the relationship between a healthy bladder and the urogenital microbiome is unknown. This observational cohort study of 435 community-dwelling women examined bladder health and function using a validated instrument. Voided urine samples were self-collected, shipped to a repository, and underwent 16S rRNA amplicon sequencing. Two hundred seventy-four (56%) samples were retained following a limit-of-detection analysis for low biomass samples. A differential abundance analysis showed that

IMPORTANCE: There is increasing awareness that human microbiomes impact health and modulate certain health conditions. Recently, investigators developed a validated assessment of bladder health in …

High-Sensitivity Plasma Proteomics Reveals Disease-Specific Signatures And Predictive Biomarkers Of Alzheimer's Disease Phenotypes In A Large Mixed-Dementia Cohort, Katherine Gong, Jigyasha Timsina, Muhammad Ali, Yike Chen, Menghan Liu, Ciyang Wang, Cyril Pottier, Geoffrey K Feld, Gyujin Heo, Tammie L S Benzinger, Cyrus A Raji, Beau Ances, Brian A Gordon, Julie K Wisch, Suzanne E Schindler, John C Morris, David M Holtzman, Laura Ibanez, Carlos Cruchaga

2020-Current year OA Pubs

Novel plasma assays enabled accurate blood-based biomarkers for neurodegenerative diseases with minimally invasive options for clinical use. Large-scale studies encompassing multiple neurodegenerative diseases using novel multiplex platforms are essential to uncover disease-specific biomarkers and pathways. We generated and analyzed plasma biomarker data using the NULISAseq™ CNS Panel from 3,232 participants with Alzheimer disease (AD), Dementia with Lewy bodies (DLB), Frontotemporal dementia (FTD), Parkinson disease (PD) and cognitively unimpaired individuals, from the Charles F. and Joanne Knight Alzheimer Disease Research Center. We identified proteins associated with disease status and AD-related phenotypes (Clinical Dementia Rating®, CSF Aβ42/Aβ40, Amyloid-PET, and Tau-PET). These proteins …

Dietary Sources Of Sodium Intake In Nigerian Adults: A Population-Based Cross-Sectional Study, Clementina E Okoro, Erica L Jamro, Guhan Iyer, Mark D Huffman, Et Al.

2020-Current year OA Pubs

Nigeria seeks to address the growing burden of hypertension and related diseases by reducing excessive dietary sodium through national dietary policymaking. This study aims to describe the levels and sources of dietary sodium intake among Nigerian adults to inform these policies. From June 2023 to July 2023, adults aged 18 to 69 years old were recruited from the Federal Capital Territory, Kano, and Ogun states to participate in a population-based, cross-sectional demographic health survey. Data were also collected to assess levels and dietary sources of sodium through four 24-h dietary recalls by trained study personnel. The primary analyses included the …

Ptbp1 Variants Displaying Altered Nucleocytoplasmic Distribution Are Responsible For A Neurodevelopmental Disorder With Skeletal Dysplasia, Aymeric Masson, Catherine Gooch, Et Al.

2020-Current year OA Pubs

Polypyrimidine tract-binding protein 1 (PTBP1) is a heterogeneous nuclear ribonucleoprotein primarily known for its alternative splicing activity. It shuttles between the nucleus and cytoplasm via partially overlapping N-terminal nuclear localization (NLS) and export (NES) signals. Despite its fundamental role in cell growth and differentiation, its involvement in human disease remains poorly understood. We identified 27 individuals from 25 families harboring de novo or inherited pathogenic variants - predominantly start-loss (89%) and, to a lesser extent, missense (11%) - affecting NES/NLS motifs. Affected individuals presented with a syndromic neurodevelopmental disorder and variable skeletal dysplasia with disproportionate short stature with short limbs. …

Strategies To Improve Healthcare Team Communication Structure And Quality In Resource-Variable Childhood Cancer Hospitals (Teamtalk): A Study Protocol, Asya Agulnik, Dylan E Graetz, Bobbi J Carothers, Jocelyn Rivera, Erin Abu-Rish Blakeney, Samantha Hayes, Veronica L Chaitan, Leopoldo Cabassa, Charles W Goss, Douglas A Luke, Sara Malone

2020-Current year OA Pubs

BACKGROUND: Healthcare team communication is essential to high-quality childhood cancer care, especially during high-acuity events such as clinical deterioration and in resource-variable settings, where supportive interventions to resolve deterioration are less available. Communication quality has traditionally been understudied in these settings, and there is a notable lack of communication interventions that are appropriate and feasible in settings across resource levels. We propose addressing this challenge in this study protocol, which will co-develop and pilot a multi-level intervention to improve communication and outcomes for children receiving cancer treatment.

METHODS/DESIGN: This study leverages systems and implementation science methodologies to evaluate and improve …

Developing A Genetic Return Of Results Service Core, Jennifer A Mckenzie, Erin Mcroy, Kevin M Bowling, Jorge Luis Granadillo De Luque, Jessica Mozersky, Erin Linnenbringer, Dustin Baldridge, Jonathan W Heusel, Julie A Neidich, Amanda F Cashen, Laura J Bierut, Sarah M Hartz, Christina A Gurnett

2020-Current year OA Pubs

Research participants should be informed of genetic test results that could impact their health, particularly when they have expressed interest in receiving such information. Furthermore, the return of genetic test results is essential to improve trust, transparency, and health equity. However, investigators often encounter barriers in returning genetic test results to research participants. We examined genomic research at a large, research-intensive medical school and found less than 6% of protocols included plans to return results to participants. This study describes our development of protocols for returning primary and secondary genetic test results and implementation of a Genomic Return of Results …

The Effects Of Marital Status, Partner Drinking, And Sex Differences On The Likelihood Of Remission From Alcohol Use Disorder, Christina Garasky, Alexis Duncan, Fanghong Dong, Jared Balbona, Andrey Anokhin, Emma Johnson, Arpana Agrawal, Kathleen Bucholz, Vivia Mccutcheon, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Marriage is associated with improved health and alcohol outcomes, yet prior research has often combined diverse non-marital relationships, obscuring whether benefits are unique to marriage or a result of strong interpersonal relationships. This study examines whether marriage, compared to cohabitation, exclusive dating, or being single, is associated with alcohol use disorder (AUD) remission and whether this varies by sex and partner drinking.

METHOD: Participants were adults from the Collaborative Study on the Genetics of Alcoholism Lifespan Study (n = 1494; 54.4% female) who met criteria for lifetime DSM-5 AUD. Multivariate logistic regression models examined the association between marital status …

Intersectional Stigma And Resilience In The Uptake Of Cervical Cancer Prevention Services In Nigeria: A Qualitative Study, Agatha Eileen Wapmuk, Titilola Abike Gbaja-Biamila, Ekenechukwu Kokelu, Juliet Iwelunmor, Et Al.

2020-Current year OA Pubs

BACKGROUND: Cervical cancer is one of the leading causes of death among women in Africa, but stigma often delays cervical cancer prevention. We explore the perceptions, enablers and nurturers through the lens of intersectional stigma in the uptake of cervical cancer prevention services in Nigeria.

METHOD: Indepth interviews and focus group discussions were conducted among women aged 30-65 years and girls aged 9-26 years in Lagos, Nigeria. Data were analysed thematically. Using the relationships and expectation domain of the PEN-3 cultural model, we identified perceptions, enablers and nurturers related to the uptake of primary and secondary cervical cancer prevention services …

Generation And Characterization Of A Knockout Mouse Of An Enhancer Of Ebf3, Emily Cordova Hurtado, Janine M Wotton, Alexander Gulka, Crystal Burke, Jeffrey K Ng, Ibrahim Bah, Juana Manuel, Hillary Heins, Stephen A Murray, David U Gorkin, Jacqueline K White, Kevin A Peterson, Tychele N Turner

2020-Current year OA Pubs

Genomic studies of neurodevelopmental disorders (NDDs) have identified several relevant genomic variants. EBF3 is a gene with an excess of protein-coding de novo variants and underlies Hypotonia, Ataxia, and Delayed Development Syndrome. We previously identified noncoding de novo variants in an enhancer of EBF3 and further found enrichment of deletions of this enhancer in NDDs. In this study, we generated a novel mouse line that deletes the highly conserved, orthologous mouse region within the Rr169617 regulatory region, and characterized the molecular and phenotypic aspects of this mouse model. We found a deviation from Mendelian expectation (P=0.02) with significant depletion of …

Validation Of A Two-Item Short Form Of The Perceived Health Competence Scale, Devika Nair, Jacquelyn S Pennings, Hayden B Bosworth, Kenneth E Freedland, Sunil Kripalani, Elisa J Gordon, Gurjeet S Birdee, Justin M Bachmann

2020-Current year OA Pubs

BACKGROUND: Perceived health competence is a construct encompassing individuals’ confidence in managing their health and health-related behaviors. The 8-item Perceived Health Competence Scale (PHCS-8), developed to measure this construct, has established psychometric properties including test-retest reliability and predictive validity for health behaviors and clinical outcomes. We aimed to validate the 2-item Perceived Health Competence Scale (PHCS-2), an abbreviated version of the PHCS-8, for use in clinical and research settings where respondent burden is a primary concern. METHODOLOGY: We conducted a psychometric validation study using pooled data from 482 participants across two cohort studies conducted in an integrative medicine clinic. Participants …

Mta-Cooperative Prmt5 Inhibitors Are Efficacious In Mtap-Deleted Malignant Peripheral Nerve Sheath Tumor Models, Xiaochun Zhang, Dana C Borcherding, Yang Lyu, Guangfeng Wang, Kevin He, Gorkem Oztosun, Ishita Sachdeva, Liuzhan Yang, Kuangying Yang, Angela C Hirbe, Et Al.

2020-Current year OA Pubs

PURPOSE: Malignant peripheral nerve sheath tumors (MPNST) are highly aggressive sarcomas with poor prognosis. The enzyme methylthioadenosine phosphorylase (MTAP) is lost in ∼25% to 50% of MPNSTs, which is associated with loss of the tumor suppressor gene CDKN2A. Inhibition of PRMT5 was found to be synthetically lethal in cells with MTAP loss due to accumulation of the substrate methylthioadenosine (MTA), an endogenous PRMT5 inhibitor. TNG908 and TNG462 are clinical-stage MTA-cooperative PRMT5 inhibitors that demonstrate selectivity for MTAP-deleted (null) cells over MTAP-proficient [wild-type (WT)] cells. Both compounds drive durable tumor regressions in various cancer xenograft models with MTAP loss.

EXPERIMENTAL DESIGN: …

Lair1 Prevents Excess Inflammatory Tissue Damage In Staphylococcus Aureus Skin Infection And Cutaneous T-Cell Lymphoma, Hannah K. Dorando, Evan C. Mutic, Kelly L. Tomaszewski, Yulia Korshunova, Ling Tian, Mellisa K. Stefanov, Chaz C. Quinn, Deborah J. Veis, Juliane Bubeck Wardenburg, Amy C. Musiek, Neha Mehta-Shah, Jacqueline E. Payton

2020-Current year OA Pubs

Patients with cutaneous T cell lymphoma (CTCL) experience high morbidity and mortality due to S. aureus skin infections and sepsis, but the underlying mechanisms remain unclear. We have previously identified high levels of LAIR2, a decoy protein for the inhibitory receptor LAIR1, in advanced CTCL. Mice lack a LAIR2 homolog, so we used Lair1 knock-out (KO) mice to model LAIR2 overexpression. In a model of S. aureus skin infection, Lair1 KO mice had significantly larger abscesses and areas of dermonecrosis compared to WT despite similar bacterial burdens. Lair1 KO exhibited a pattern of increased inflammatory responses in infection and sterile …

Targeting Tomm40 And Tomm22 To Rescue Statin-Impaired Mitochondrial Function, Dynamics, And Mitophagy In Skeletal Myotubes, Neil V Yang, Sean Rogers, Rachel Guerra, Justin Y Chao, David J Pagliarini, Elizabeth Theusch, Ronald M Krauss

2020-Current year OA Pubs

Statins are the drugs most commonly used for lowering plasma low-density lipoprotein (LDL) cholesterol levels and reducing cardiovascular disease risk. Although generally well-tolerated, statins can induce myopathy, a major cause of non-adherence to treatment. Impaired mitochondrial function has been implicated in the development of statin-induced myopathy, but the underlying mechanism remains unclear. We have shown that simvastatin downregulates the transcription of

The Mediating Role Of Social Connectedness Between Inflexibility, The Suppression Of Emotional Expression, And Symptoms Of Eating Disorders And Depression In Adolescents With Restrictive Eating Disorders Referred For Radically Open Dialectical Behaviour Therapy (Ro Dbt), Julian Baudinet, Lucinda J Gledhill, Molly Fennig Steinhoff, Kirsten Gilbert, Mima Simic

2020-Current year OA Pubs

BACKGROUND: Overcontrol is a transdiagnostic phenotype which has been associated with restrictive eating disorders and depression. It is characterised by traits such as cognitive and behavioural inflexibility, risk aversion, suppression of emotional expression, reduced reward sensitivity and higher temperamental anxiety. Two aspects of the overcontrol phenotype (inflexibility and the suppression of emotional expression) have been particularly linked with poorer mental health. Additionally, social connectedness has been shown to protect against mental health symptom severity. The current study aimed to test whether the relationship between these factors and mental health symptom severity, namely, eating disorder and depression, is mediated by social …

Host Cysteine Proteases Promote The Severity Of Catheter-Associated Urinary Tract Infection And Kidney Fibrosis, Wei Xu, Jian Chen, Lisa K Mclellan, Ana L Flores-Mireles, David A Hunstad, Michael G Caparon

2020-Current year OA Pubs

UNLABELLED: The bacterium

IMPORTANCE: Catheter-associated urinary tract infections (CAUTIs) are the most prevalent healthcare-associated infection globally, with

Metabolic Dysfunction-Associated Steatotic Liver Disease And Colorectal Neoplasms Risk: A Global Propensity Score-Matched Retrospective Cohort Study, Mohammad Aldiabat, Ali Osman, Malek Ayoub, Mahmoud Y Madi, Kamran Qureshi, Wing-Kin Syn

2020-Current year OA Pubs

OBJECTIVES: To evaluate the association between metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic-associated steatohepatitis (MASH), and the risk of colorectal cancer (CRC) and benign colorectal neoplasms (BCN), and to explore whether liver fibrosis/cirrhosis modifies these associations.

DESIGN: Retrospective cohort study with 1:1 propensity score matching.

SETTING: Global, multicentre real-world analysis using deidentified electronic health records from over 130 healthcare organisations in the TriNetX Global Collaborative Network.

PARTICIPANTS: Hospitalised adults aged 45-75 years between October 2019 and October 2024. Patients with prior diagnoses of colorectal neoplasia or other chronic liver diseases were excluded. Final matched cohorts included 138 902 MASLD and …

Integrated Analysis Of The Safety Of Fecal Microbiota, Live-Jslm In Adults With Recurrent Clostridioides Difficile Infection From Five Prospective Clinical Trials: An Update, Christine Lee, Paul Feuerstadt, Thomas Louie, Lindy Bancke, Beth Guthmueller, Adam Harvey, Frederikke Hoeyer, Robert Orenstein, Erik R Dubberke, Sahil Khanna

2020-Current year OA Pubs

BACKGROUND: Fecal microbiota, live-jslm (RBL) is approved in the United States and Canada for prevention of recurrent

OBJECTIVES: Provide an updated integrated safety analysis, incorporating final safety data from Punch CD3-OLS.

DESIGN: Safety data were combined from five RBL trials: three phase II and two phase III trials.

METHODS: Adult participants had documented rCDI and completed SOC therapy before receiving one or two doses of RBL or placebo, rectally administered as one treatment course. Treatment-emergent adverse events (TEAEs) were recorded for ⩽6 months.

RESULTS: TEAEs were reported in 70.9% (845/1192) of RBL recipients; most TEAEs were mild to moderate and …

The Gut Microbiome As A Modulator Of Traumatic Brain Injury Pathology And Symptoms, Cole Vonder Haar, Marta Celorrio, Kris M Martens, Stuart H Friess, Sonia Villapol, Randal J Urban, Richard Pyles, Richelle Mychasiuk, Dennis Simon, Amanda Dave

2020-Current year OA Pubs

Traumatic brain injuries (TBIs) affect millions annually, leading to devastating neurobehavioral consequences and increasing risk for neurodegenerative and psychiatric diseases. However, therapies are lacking. Starting in 2018, dysbiosis of the gut microbiome was identified as an acute, and potentially chronic, pathology originating from TBI. Recent studies established that the microbiome contributes to the evolution of TBI pathology and functional impairments. The gut microbiome is the collection of microorganisms that inhabit the stomach through colon and is indicated as a contributor to myriad neurological and psychiatric conditions. This makes it an intriguing target to understand in the context of TBI. Thus, …

Anticipation Of A Therapeutic Odyssey Following Predictive Testing For Autism, Katherine E Macduffie, Aurora M Washington, Catherine A Burrows, Stephen R Dager, Jed T Elison, Annette M Estes, Rebecca Grzadzinski, Chimei M Lee, Joseph Piven, Mark D Shen, Benjamin S Wilfond, Jason Wolff, Lonnie Zwaigenbaum, John R Pruett Jr

2020-Current year OA Pubs

Brain-based tools are being developed to identify infants at ultra-high likelihood for developing autism and enable presymptomatic intervention, though such interventions are not yet clinically available. Given persistent challenges in accessing autism services, we sought to understand how families might use early predictive results to seek support. We analyzed 55 interviews with parents of infants aged 6-13 months; one group had experience parenting an older autistic child (n = 30), the other had no prior autism parenting experience (n = 25). All parents were asked what steps they would take if told their infant was likely to develop autism. Both …

Impact Of Radiotherapy Site, Modality, And Dose On Subsequent Clonal Hematopoiesis, Alexander G Goglia, Griffen R Mustion, Leslie A Modlin, Ross L Levine, Kelly L Bolton, Lior Z Braunstein

2020-Current year OA Pubs

No abstract provided.

Concordance Of Cancer-Associated Cytokines And Mitochondrial Dna Deletions In Individuals With Hepatocellular Carcinoma And People Living With Hiv In Ghana, James Odame Aboagye, Ruth Ayanful-Torgby, Lei Zhou, Prince Peter Wormenor, Vincent Ganu, Kenneth Tachi, Bernard Nii Akrashie Attoh, Miriam Mensah, Timothy Kuuguu, Sedzro Kojo Mensah, George Boateng Kyei, Elijah Paintsil

2020-Current year OA Pubs

BACKGROUND: Hepatocellular carcinoma (HCC) is becoming increasingly prevalent as a non-AIDS-defining cancer closely tied to chronic HIV infection. It is associated with increased secretion of inflammatory cytokines, immune system dysfunction, and alterations in mitochondrial function. The objective of this study was to investigate the levels of cytokine secretion and mitochondrial DNA (mtDNA) deletion in people living with HIV (PLWH) compared with individuals diagnosed with HCC without HIV.

METHODS: A cross-sectional study was conducted with PLWH and HCC patients recruited from the Korle-Bu Teaching Hospital, Accra, Ghana. Participants donated whole blood for the isolation of plasma and peripheral blood mononuclear cells …

Protocol For A Multicenter, Cluster-Randomized, Stepped-Wedge, Implementation Trial Of A Prehospital Sepsis Protocol, Shamie Das, Stacey House, Melissa Kroll, Et Al.

2020-Current year OA Pubs

BACKGROUND: Sepsis is a common, life-threatening medical emergency in which early recognition and treatment are cornerstones of management. Best practice guidelines recommend standardized sepsis screening in hospitals to facilitate early recognition. In contrast, very little is known about the efficacy and safety of standardized sepsis screening in the prehospital Emergency Medical Services (EMS) environment. To help address this knowledge gap, this study protocol will evaluate the impact of implementing an evidence-based sepsis protocol in ambulances.

METHODS: We plan to conduct a multicenter, stepped-wedge, cluster-randomized trial at 3 sites and enroll 984 participants over 24 months. EMS personnel will be trained …

Cgas-Agonistic Spherical Nucleic Acids Reprogram The Glioblastoma Immune Microenvironment And Promote Antitumor Immunity, Akanksha S Mahajan, Corey Dussold, Seunghyun Kim, Rachel Jarvis, Lisa A Hurley, Serena Tommasini-Ghelfi, Jungsoo Park, Connor M Forsyth, Bin Zhang, Jason Miska, Amy B Heimberger, Chad A Mirkin, Alexander H Stegh

2020-Current year OA Pubs

The cyclic GMP-AMP synthase-Stimulator of Interferon Genes (cGAS-STING) pathway is an important DNA-sensing mechanism that increases T cell trafficking and activation in tumors and reverses the immunosuppressive phenotype of myeloid cells. Therefore, direct STING targeting using synthetic cyclic dinucleotides (CDNs) is an attractive strategy for treating lymphocyte-depleted and myeloid cell-enriched tumors, such as glioblastoma (GBM). However, inadequate bioavailability and poor cellular accumulation limit the clinical development of CDNs, particularly for noninvasive administration strategies. Spherical nucleic acids (SNAs) have emerged as promising modular constructs for creating therapeutic lead compounds for many diseases, including different forms of cancer. Here, we report the …