Digital Commons Network^™

Chemical Inhibition Of Papd5/7 Rescues Telomerase Function And Hematopoiesis In Dyskeratosis Congenita, Siddharth Shukla, Ho-Chang Jeong, Christopher M. Sturgeon, Roy Parker, Luis Francisco Zirnberger Batista

Open Access Publications

No abstract provided.

Alterations In Plasma Triglycerides And Ceramides: Links With Cardiac Function In Humans With Type 2 Diabetes, Linda R. Peterson, Xuntian Jiang, Ling Chen, Anne C. Goldberg, Marsha S. Farmer, Daniel S. Ory, Jean E. Schaffer

Open Access Publications

No abstract provided.

The Tethering Function Of Mitofusin2 Controls Osteoclast Differentiation By Modulating The Ca2+–Nfatc1 Axis, Anna Ballard, Rong Zeng, Allahdad Zarei, Christine Shao, Linda Cox, Hui Yan, Antonietta Franco, Gerald W. Dorn Ii, Roberta Faccio, Deborah J. Veis

Open Access Publications

No abstract provided.

Impact Of Gender And Caregiving Responsibilities On Academic Success In Hematology, Allison A. King, Sara K. Vesely, Emily Vettese, Sadie Cook, Adam Cuker, Wendy Stock, Morgan Homer, Josel Fritz, Lilian Sung

Open Access Publications

No abstract provided.

Effects Of Remote Limb Ischemic Conditioning On Muscle Strength In Healthy Young Adults: A Randomized Controlled Trial, Swati M. Surkar, Marghuretta D. Bland, Anna E. Mattlage, Ling Chen, Jeffrey M. Gidday, Jin-Moo Lee, Tamara Hershey, Catherine E. Lang

Open Access Publications

Remote limb ischemic conditioning (RLIC) is a clinically feasible method in which brief, sub-lethal bouts of ischemia protects remote organs or tissues from subsequent ischemic injury. A single session of RLIC can improve exercise performance and increase muscle activation. The purpose of this study, therefore, was to assess the effects of a brief, two-week protocol of repeated RLIC combined with strength training on strength gain and neural adaptation in healthy young adults. Participants age 18-40 years were randomized to receive either RLIC plus strength training (n = 15) or sham conditioning plus strength training (n = 15). Participants received RLIC …

Refined National Institutes Of Health Response Algorithm For Chronic Graft-Versus-Host Disease In Joints And Fascia, Yoshihiro Inamoto, Stephanie J. Lee, Lynn E. Onstad, Mary E.D. Flowers, Betty K. Hamilton, Madan H. Jagasia, Paul J. Martin, Steven Z. Pavletic, Joseph A. Pidala, Iskra Pusic, Georgia B. Vogelsang, Daniel Wolff, Paul A. Carpenter

Open Access Publications

No abstract provided.

Photoreceptor Responses To Light In The Pathogenesis Of Diabetic Retinopathy, Shahriyar P Majidi, Rithwick Rajagopal

Open Access Publications

Vision loss, among the most feared complications of diabetes, is primarily caused by diabetic retinopathy, a disease that manifests in well-recognized, characteristic microvascular lesions. The reasons for retinal susceptibility to damage in diabetes are unclear, especially considering that microvascular networks are found in all tissues. However, the unique metabolic demands of retinal neurons could account for their vulnerability in diabetes. Photoreceptors are the first neurons in the visual circuit and are also the most energy-demanding cells of the retina. Here, we review experimental and clinical evidence linking photoreceptors to the development of diabetic retinopathy. We then describe the influence of …

The Immunologic Effect Of Early Intravenous Two And Four Gram Bolus Dosing Of Tranexamic Acid Compared To Placebo In Patients With Severe Traumatic Bleeding (Tampiti): A Randomized, Double-Blind, Placebo-Controlled, Single-Center Trial, Philip C Spinella, Kimberly A Thomas, Isaiah R Turnbull, Anja Fuchs, Kelly Bochicchio, Douglas Schuerer, Stacey Reese, Adrian A Coleoglou Centeno, Christopher B Horn, Jack Baty, Susan M Shea, M Adam Meledeo, Anthony E Pusateri, Jerrold H Levy, Andrew P Cap, Grant V Bochicchio, Tampiti Investigators

Open Access Publications

Background: The hemostatic properties of tranexamic acid (TXA) are well described, but the immunological effects of TXA administration after traumatic injury have not been thoroughly examined. We hypothesized TXA would reduce monocyte activation in bleeding trauma patients with severe injury.

Methods: This was a single center, double-blinded, randomized controlled trial (RCT) comparing placebo to a 2 g or 4 g intravenous TXA bolus dose in trauma patients with severe injury. Fifty patients were randomized into each study group. The primary outcome was a reduction in monocyte activation as measured by human leukocyte antigen-DR isotype (HLA-DR) expression on monocytes 72 h …

Bet Bromodomain Inhibition Attenuates Cardiac Phenotype In Myocyte-Specific Lamin A/C-Deficient Mice, Gaelle Auguste, Leila Rouhi, Scot J Matkovich, Cristian Coarfa, Matthew J Robertson, Grazyna Czernuszewicz, Priyatansh Gurha, Ali J Marian

Open Access Publications

Mutation in the LMNA gene, encoding lamin A/C, causes a diverse group of diseases called laminopathies. Cardiac involvement is the major cause of death and manifests as dilated cardiomyopathy, heart failure, arrhythmias, and sudden death. There is no specific therapy for LMNA-associated cardiomyopathy. We report that deletion of Lmna in cardiomyocytes in mice leads to severe cardiac dysfunction, conduction defect, ventricular arrhythmias, fibrosis, apoptosis, and premature death within 4 weeks. The phenotype is similar to LMNA-associated cardiomyopathy in humans. RNA sequencing, performed before the onset of cardiac dysfunction, led to identification of 2338 differentially expressed genes (DEGs) in Lmna-deleted cardiomyocytes. …

Neutrophil Swarming Delays The Growth Of Clusters Of Pathogenic Fungi, Alex Hopke, Allison Scherer, Samantha Kreuzburg, Michael S. Abers, Christa S. Zerbe, Mary C. Dinauer, Michael K. Mansour, Daniel Irimia

Open Access Publications

No abstract provided.

Single Cell Transcriptomics Reveals Opioid Usage Evokes Widespread Suppression Of Antiviral Gene Program, Tanya T. Karagiannis, John P. Cleary Jr., Busra Gok, Andrew J. Henderson, Nicholas G. Martin, Masanao Yajima, Elliot C. Nelson, Christine S. Cheng

Open Access Publications

No abstract provided.

The De-Implementation And Persistence Of Low-Value Hiv Prevention Interventions In The United States: A Cross-Sectional Study, Virginia R Mckay, Todd B Combs, M Margaret Dolcini, Ross C Brownson

Open Access Publications

BACKGROUND: As more effective or efficient interventions emerge out of scientific advancement to address a particular public health issue, it may be appropriate to de-implement low-value interventions, or interventions that are less effective or efficient. Furthermore, factors that contribute to appropriate de-implementation are not well identified. We examined the extent to which low-value interventions were de-implemented among public health organizations providing HIV prevention services, as well as explored socio-economic, organizational, and intervention characteristics associated with de-implementation.

METHODS: We conducted an online cross-sectional survey from the fall of 2017 to the spring of 2019 with organizations (

RESULTS: Organizations reported 359 …

Early Diagnosis And Intervention In Cystic Fibrosis: Imagining The Unimaginable, Andrea M Coverstone, Thomas W Ferkol

Open Access Publications

Cystic fibrosis is the most common life-shortening genetic disease affecting Caucasians, clinically manifested by fat malabsorption, poor growth and nutrition, and recurrent sinopulmonary infections. Newborn screening programs for cystic fibrosis are now implemented throughout the United States and in many nations worldwide. Early diagnosis and interventions have led to improved clinical outcomes for people with cystic fibrosis. Newer cystic fibrosis transmembrane conductance regulator potentiators and correctors with mutation-specific effects have increasingly been used in children, and these agents are revolutionizing care. Indeed, it is possible that highly effective modulator therapy used early in life could profoundly affect the trajectory of …

Direct Neuronal Reprogramming Of Common Marmoset Fibroblasts By Ascl1, Microrna-9/9*, And Microrna-124 Overexpression, Akisa Nemoto, Reona Kobayashi, Sho Yoshimatsu, Yuta Sato, Takahiro Kondo, Andrew S Yoo, Seiji Shiozawa, Hideyuki Okano

Open Access Publications

The common marmoset (

Characterization Of Missense Mutations In The Signal Peptide And Propeptide Of Fix In Hemophilia B By A Cell-Based Assay, Wenwen Gao, Yaqi Xu, Hongli Liu, Meng Gao, Qing Cao, Yiyi Wang, Longteng Cui, Rong Huang, Yan Shen, Sanqiang Li, Haiping Yang, Yixiang Chen, Chaokun Li, Haichuan Yu, Weikai Li, Guomin Shen

Open Access Publications

No abstract provided.

Relationships Between Big-Five Personality Factors And Alzheimer's Disease Pathology In Autosomal Dominant Alzheimer's Disease, Andrew J Aschenbrenner, Jennifer Petros, Eric Mcdade, Guoqiao Wang, David A Balota, Tammie Ls Benzinger, Carlos Cruchaga, Chengjie Xiong, Richard Perrin, Anne M Fagan, John C Morris, Randall Bateman, Jason Hassenstab, Et Al

Open Access Publications

Introduction: Changes in personality characteristics are associated with the onset of symptoms in Alzheimer's disease (AD) and may even precede clinical diagnosis. However, personality changes caused by disease progression can be difficult to separate from changes that occur with normal aging. The Dominantly Inherited Alzheimer Network (DIAN) provides a unique cohort in which to relate measures of personality traits to in vivo markers of disease in a much younger sample than in typical late onset AD.

Methods: Personality traits measured with the International Personality Item Pool at baseline from DIAN participants were analyzed as a function of estimated years to …

Identifying Barriers, Facilitators, And Implementation Strategies For A Faith-Based Physical Activity Program, Jessica Haughton, Michelle L Takemoto, Jennifer Schneider, Steven P Hooker, Borsika Rabin, Ross C Brownson, Elva M Arredondo

Open Access Publications

BACKGROUND: Community engagement is critical to the acceleration of evidence-based interventions into community settings. Harnessing the knowledge and opinions of community leaders increases the likelihood of successful implementation, scale-up, and sustainment of evidence-based interventions.

METHODS: We conducted in-depth interviews using a semi-structured interview guide based on the Consolidated Framework for Implementation Research (CFIR) at various Catholic and Protestant churches with large Latino membership in San Diego County, California to explore barriers and facilitators to implementation of

RESULTS: Pastors and church staff described barriers and facilitators to implementation within three domains of CFIR: characteristics of individuals (lack of self-efficacy for and …

Therapeutic Enhancement Of Blood-Brain And Blood-Tumor Barriers Permeability By Laser Interstitial Thermal Therapy, Afshin Salehi, Mounica R Paturu, Bhuvic Patel, Matthew D Cain, Tatenda Mahlokozera, Alicia B Yang, Tsen-Hsuan Lin, Eric C Leuthardt, Hiroko Yano, Sheng-Kwei Song, Robyn S Klein, Robert Schmidt, Albert H Kim

Open Access Publications

BACKGROUND: The blood-brain and blood-tumor barriers (BBB and BTB), which restrict the entry of most drugs into the brain and tumor, respectively, are a significant challenge in the treatment of glioblastoma. Laser interstitial thermal therapy (LITT) is a minimally invasive surgical technique increasingly used clinically for tumor cell ablation. Recent evidence suggests that LITT might locally disrupt BBB integrity, creating a potential therapeutic window of opportunity to deliver otherwise brain-impermeant agents.

METHODS: We established a LITT mouse model to test if laser therapy can increase BBB/BTB permeability in vivo. Mice underwent orthotopic glioblastoma tumor implantation followed by LITT in combination …

Practitioner Perspectives On Building Capacity For Evidence-Based Public Health In State Health Departments In The United States: A Qualitative Case Study, Stephanie Mazzucca, Cheryl A Valko, Amy A Eyler, Marti Macchi, Andrew Lau, Jeanne Alongi, John Robitscher, Ross C Brownson

Open Access Publications

BACKGROUND: Public health agencies are responsible for implementing effective, evidence-based public health programs and policies to reduce the burden of chronic diseases. Evidence-based public health can be facilitated by modifiable administrative evidence-based practices (A-EBPs) (e.g., workforce development, organizational climate), yet little is known about how practitioners view A-EBPs. Thus, the purpose of this qualitative study was to understand state health department practitioners' perceptions about how A-EBPs are implemented and what facilitators and barriers exist to using A-EBPs.

METHODS: Chronic disease prevention and health promotion program staff who were members of the National Association of Chronic Disease Directors were recruited to …

Antipsychotic Effects On Cortical Morphology In Schizophrenia And Bipolar Disorders, Ruiqi Feng, Fay Y Womer, Et Al

Open Access Publications

No abstract provided.

Integration Of Mobile Health Into Sickle Cell Disease Care To Increase Hydroxyurea Utilization: Protocol For An Efficacy And Implementation Study, Jane S Hankins, Cecelia Calhoun, Ana Baumann, Lisa Klesges, Et Al

Open Access Publications

BACKGROUND: Hydroxyurea prevents disease complications among patients with sickle cell disease (SCD). Although its efficacy has been endorsed by the National Health Lung and Blood Institute evidence-based guidelines, its adoption is low, both by patients with SCD and providers. Mobile health (mHealth) apps provide benefits in improving medication adherence and self-efficacy among patients with chronic diseases and have facilitated prescription among medical providers. However, mHealth has not been systematically tested as a tool to increase hydroxyurea adherence nor has the combination of mHealth been assessed at both patient and provider levels to increase hydroxyurea utilization.

OBJECTIVE: This study aims to …

Induction Of Wnt16 Via Peptide-Mrna Nanoparticle-Based Delivery Maintains Cartilage Homeostasis, Huimin Yan, Ying Hu, Antonina Akk, Muhammad Farooq Rai, Hua Pan, Samuel A Wickline, Christine T N Pham

Open Access Publications

Osteoarthritis (OA) is a progressive joint disease that causes significant disability and pain and for which there are limited treatment options. We posit that delivery of anabolic factors that protect and maintain cartilage homeostasis will halt or retard OA progression. We employ a peptide-based nanoplatform to deliver Wingless and the name Int-1 (WNT) 16 messenger RNA (mRNA) to human cartilage explants. The peptide forms a self-assembled nanocomplex of approximately 65 nm in size when incubated with WNT16 mRNA. The complex is further stabilized with hyaluronic acid (HA) for enhanced cellular uptake. Delivery of peptide-WNT16 mRNA nanocomplex to human cartilage explants …

5-Fluorocytosine Resistance Is Associated With Hypermutation And Alterations In Capsule Biosynthesis In Cryptococcus, R. Blake Billmyre, Shelly Applen Clancey, Lucy X. Li, Tamara L. Doering, Joseph Heitman

Open Access Publications

No abstract provided.

Structural Basis For Adhesion G Protein-Coupled Receptor Gpr126 Function, Katherine Leon, Rebecca L. Cunningham, Joshua A. Riback, Ezra Feldman, Jingxian Li, Tobin R. Sosnick, Minglei Zhao, Kelly R. Monk, Demet Araç

Open Access Publications

No abstract provided.

Structure Of A Rabies Virus Polymerase Complex From Electron Cryo-Microscopy, Joshua A. Horwitz, Simon Jenni, Stephen C. Harrison, Sean P. J. Whelan

Open Access Publications

No abstract provided.

Tumor Infiltrating Neutrophils Are Enriched In Basal-Type Urothelial Bladder Cancer, Giulio Eugenio Mandelli, Francesco Missale, Debora Bresciani, Luisa Benerini Gatta, Patrizia Scapini, Elena Caveggion, Elisa Roca, Mattia Bugatti, Matilde Monti, Luca Cristinelli, Sandra Belotti, Claudio Simeone, Stefano Calza, Laura Melocchi, William Vermi

Open Access Publications

BACKGROUND: Urothelial bladder cancers (UBCs) are distinct in two main molecular subtypes, namely basal and luminal type. Subtypes are also diverse in term of immune contexture, providing a rationale for patient selection to immunotherapy.

METHODS: By digital microscopy analysis of a muscle-invasive BC (MIBC) cohort, we explored the density and clinical significance of CD66b

RESULTS: Basal type BC contained a significantly higher density of CD66b

CONCLUSIONS: TAN are recruited in basal type MIBC by pro-inflammatory CKs. This finding establishes a groundwork for a better understanding of the UBC immunity and its relevance.

A Meta-Analysis Of Genome-Wide Association Studies Of Multiple Myeloma Among Men And Women Of African Ancestry, Zhaohui Du, Graham A. Colditz, Mark A. Fiala, Ravi Vij, Et Al.

Open Access Publications

No abstract provided.

Loss-Of-Function Mutations In Udp-Glucose 6-Dehydrogenase Cause Recessive Developmental Epileptic Encephalopathy, Holger Hengel, Marisa V. Andrews, Marcia C. Willing, Et Al.

Open Access Publications

No abstract provided.

Confidential Genetic Testing And Electronic Health Records: A Survey Of Current Practices Among Huntington Disease Testing Centers, Celeste C Eno, Stacey K Barton, Naghmeh Dorrani, Stephen D Cederbaum, Joshua L Deignan, Wayne W Grody

Open Access Publications

BACKGROUND: Clinical care teams providing presymptomatic genetic testing often employ advanced confidentiality practices for documentation and result storage. However, patient requests for increased confidentiality may be in conflict with the legal obligations of medical providers to document patient care activities in the electronic health record (EHR). Huntington disease presents a representative case study for investigating the ways centers currently balance the requirements of EHRs with the privacy demands of patients seeking presymptomatic genetic testing.

METHODS: We surveyed 23 HD centers (53% response rate) regarding their use of the EHR for presymptomatic HD testing.

RESULTS: Our survey revealed that clinical care …

Medulloblastoma Has A Global Impact On Health Related Quality Of Life: Findings From An International Cohort, Cynthia B De Medeiros, Josh Rubin, Et Al

Open Access Publications

BACKGROUND: Understanding the global impact of medulloblastoma on health related quality of life (HRQL) is critical to characterizing the broad impact of this disease and realizing the benefits of modern treatments. We evaluated HRQL in an international cohort of pediatric medulloblastoma patients.

METHODS: Seventy-six patients were selected from 10 sites across North America, Europe, and Asia, who participated in the Medulloblastoma Advanced Genomics International Consortium (MAGIC). The Health Utilities Index (HUI) was administered to patients and/or parents at each site. Responses were used to determine overall HRQL and attributes (ie specific subdomains). The impact of various demographic and medical variables …