Digital Commons Network^™

Toll-Like Receptor And Cytokine Expression Throughout The Bone Marrow Differs Between Patients With Low- And High-Risk Myelodysplastic Syndromes, Luana Chiquetto Paracatu, Darlene A Monlish, Zev J Greenberg, Daniel A C Fisher, Matthew J Walter, Stephen T Oh, Laura G Schuettpelz

2020-Current year OA Pubs

Myelodysplastic syndromes (MDS) are hematopoietic stem cell disorders, the pathogenesis of which involves enhanced immune signaling that promotes or selects for mutant hematopoietic stem and progenitor cells (HSPCs). In particular, toll-like receptor (TLR) expression and signaling are enhanced in MDS, and their inhibition is an attractive therapeutic strategy. Although prior studies have reported increased expression of TLR2 and its binding partners TLR1 and TLR6 in the CD34

Escape-Noncapture Bigeminy, Lisa M. Roelle, George F. Van Hare

2020-Current year OA Pubs

No abstract provided.

Protein Proximity Networks And Functional Evaluation Of The Casein Kinase 1 Gamma Family Reveal Unique Roles For Ck1Γ3 In Wnt Signaling, Megan J. Agajanian, Frances M. Potjewyd, Brittany M. Bowman, Smaranda Solomon, Kyle M. Lapak, Dhaval P. Bhatt, Jeffery L. Smith, Dennis Goldfarb, Alison D. Axtman, Michael B. Major

2020-Current year OA Pubs

Aberrant activation or suppression of WNT/β-catenin signaling contributes to cancer initiation and progression, neurodegeneration, and bone disease. However, despite great need and more than 40 years of research, targeted therapies for the WNT pathway have yet to be fully realized. Kinases are considered exceptionally druggable and occupy key nodes within the WNT signaling network, but several pathway-relevant kinases remain understudied and "dark." Here, we studied the function of the casein kinase 1γ (CSNK1γ) subfamily of human kinases and their roles in WNT signaling. miniTurbo-based proximity biotinylation and mass spectrometry analysis of CSNK1γ1, CSNK1γ2, and CSNK1γ3 revealed numerous components of the …

An Examination Of The Sex-Specific Nature Of Nutrition Assessment Within The Nutrition Care Process: Considerations For Nutrition And Dietetics Practitioners Working With Transgender And Gender Diverse Clients, Whitney Linsenmeyer, Sarah Garwood, Jennifer Waters

2020-Current year OA Pubs

No abstract provided.

Joint Eanm, Snmmi And Iaea Enabling Guide: How To Set Up A Theranostics Centre, Ken Herrmann, Richard L Wahl, Et Al.

2020-Current year OA Pubs

The theranostics concept using the same target for both imaging and therapy dates back to the middle of the last century, when radioactive iodine was first used to treat thyroid diseases. Since then, radioiodine has become broadly established clinically for diagnostic imaging and therapy of benign and malignant thyroid disease, worldwide. However, only since the approval of SSTR2-targeting theranostics following the NETTER-1 trial in neuroendocrine tumours and the positive outcome of the VISION trial has theranostics gained substantial attention beyond nuclear medicine. The roll-out of radioligand therapy for treating a high-incidence tumour such as prostate cancer requires the expansion of …

Assessing Researchers' Capabilities, Opportunities, And Motivation To Conduct Equity-Oriented Dissemination And Implementation Research, An Exploratory Cross-Sectional Study, Ana A Baumann, Eva N Woodward, Rajinder Sonia Singh, Prajakta Adsul, Rachel C Shelton

2020-Current year OA Pubs

BACKGROUND: A recent paradigm shift has led to an explicit focus on enhancing health equity through equity-oriented dissemination and implementation (D&I) research. However, the integration and bidirectional learning across these two fields is still in its infancy and siloed. This exploratory study aimed to examine participants' perceived capabilities, opportunities, and motivations to conduct equity-oriented D&I research.

METHODS: We conducted an exploratory cross-sectional survey distributed online from December 2020 to April 2021. Participants were recruited at either D&I or health disparities-oriented conferences, meetings, through social media, or personal outreach via emails. Informed by the Capability, Opportunity, and Motivation Model (COM-B), the …

Determination Of The Electronic Portal Imaging Device Pixel-Sensitivity-Map For Quality Assurance Applications. Part 2: Photon Beam Dependence, Michael Paul Barnes, Baozhou Sun, Brad Michael Oborn, Bishnu Lamichhane, Stuart Szwec, Matthew Schmidt, Bin Cai, Frederick Menk, Peter Greer

2020-Current year OA Pubs

PURPOSE: The EPID PSM is a useful EPID calibration method for QA applications. The dependence of the EPID PSM on the photon beam used to acquire it has been investigated in this study for the four available PSM methods. The aim is to inform upon the viability of applying a single PSM for all available photon beams to simplify PSM implementation and maintenance.

METHODS: Four methods of PSM determination were each measured once in a single session on a single TrueBeam ® STx linac using 6 MV, 10 MV, 6 MV Flattening-Filter-Free (FFF), and 10 MV FFF photon beams. The …

Association Of Molecular Senescence Markers In Late-Life Depression With Clinical Characteristics And Treatment Outcome, Breno S Diniz, Benoit H Mulsant, Charles F Reynolds, Daniel M Blumberger, Jordan F Karp, Meryl A Butters, Ana Paula Mendes-Silva, Erica L Vieira, George Tseng, Eric J Lenze

2020-Current year OA Pubs

Importance: Many older adults with depression do not experience remission with antidepressant treatment, and markers of cellular senescence in late-life depression (LLD) are associated with greater severity of depression, greater executive dysfunction, and higher medical illness burden. Since these clinical characteristics are associated with remission in LLD, molecular and cellular senescence abnormalities could be a possible biological mechanism underlying poor treatment response in this population.

Objective: To examine whether the senescence-associated secretory phenotype (SASP) index was associated with the likelihood of remission from a depressive episode in older adults.

Design, Setting, and Participants: A nonrandomized, open-label clinical trial was conducted …

Intracorporeal And Extracorporeal Anastomosis For Robotic-Assisted And Laparoscopic Right Colectomy: Short-Term Outcomes Of A Multi-Center Prospective Trial, Robert K Cleary, Matthew Silviera, Et Al.

2020-Current year OA Pubs

BACKGROUND: Studies to date show contrasting conclusions when comparing intracorporeal and extracorporeal anastomoses for minimally invasive right colectomy. Large multi-center prospective studies comparing perioperative outcomes between these two techniques are needed. The purpose of this study was to compare intracorporeal and extracorporeal anastomoses outcomes for robotic assisted and laparoscopic right colectomy.

METHODS: Multi-center, prospective, observational study of patients with malignant or benign disease scheduled for laparoscopic or robotic-assisted right colectomy. Outcomes included conversion rate, gastrointestinal recovery, and complication rates.

RESULTS: There were 280 patients: 156 in the robotic assisted and laparoscopic intracorporeal anastomosis (IA) group and 124 in the robotic …

A Single-Center Experience Comparing First- Versus Second-Generation Insertable Cardiac Monitors In Pediatric Patients, Nathan Miller, Lisa Roelle, Dean Lorimer Jr, Aarti S Dalal, William B Orr, George F Van Hare, Jennifer N Avari Silva

2020-Current year OA Pubs

Insertable cardiac monitors (ICMs) have undergone advancements in size and functionality over the past decade, resulting in the introduction of small, easily insertable devices capable of long-term remote monitoring. We define first-generation ICMs as implantable cardiac monitoring devices that require an incision and surgical creation of a subcutaneous pocket and second-generation ICMs as devices implanted using a custom-made tool for subcutaneous insertion, respectively. The aim of this study was to understand the differences between first- and second-generation pediatric ICM implants, implant indications, and time to diagnosis. We performed a retrospective, single-center chart review of patients who underwent ICM implantation from …

Translating Data Analytics Into Improved Spine Surgery Outcomes: A Roadmap For Biomedical Informatics Research In 2021, Jacob K. Greenberg, Ayodamola Otun, Zoher Ghogawala, Po-Yin Yen, Camilo A. Molina, David D. Limbrick, Randi E. Foraker, Michael P. Kelly, Wilson Z. Ray

2020-Current year OA Pubs

STUDY DESIGN: Narrative review.

OBJECTIVES: There is growing interest in the use of biomedical informatics and data analytics tools in spine surgery. Yet despite the rapid growth in research on these topics, few analytic tools have been implemented in routine spine practice. The purpose of this review is to provide a health information technology (HIT) roadmap to help translate data assets and analytics tools into measurable advances in spine surgical care.

METHODS: We conducted a narrative review of PubMed and Google Scholar to identify publications discussing data assets, analytical approaches, and implementation strategies relevant to spine surgery practice.

RESULTS: A …

Raising Anesthesiology Diversity And Antiracism: Launching A National Initiative, Matthew C. Wixson, Allison D. Mitchell, Scott D. Markowitz, Kate M. Malicke, Michael S. Avidan, George A. Mashour

2020-Current year OA Pubs

No abstract provided.

Serum Cholesterol Efflux Capacity In Age-Related Macular Degeneration And Polypoidal Choroidal Vasculopathy, Yasuo Yanagi, Richard M C Yu, Waseem Ahamed, Marco Yu, Kelvin Yi Chong Teo, Anna C S Tan, Ching-Yu Cheng, Tien Yin Wong, Rajendra S Apte, Chui Ming Gemmy Cheung

2020-Current year OA Pubs

PURPOSE: To investigate serum cholesterol efflux capacity (the ability of the serum to accept cholesterol) and factors that regulate it using nuclear magnetic resonance-quantified measures of lipoprotein particle composition and size and apolipoproteins metrics in patients with age-related macular degeneration (AMD).

DESIGN: Case-control study.

PARTICIPANTS: Four hundred two serum samples from 80 patients with early AMD (eAMD), and 212 patients with neovascular AMD (nAMD), including 80 with typical nAMD (tAMD) and 132 with polypoidal choroidal vasculopathy (PCV), and 110 age- and gender matched control participants.

METHODS: Serum from participants showed cholesterol efflux capacity measured using in vitro cell assays and …

Ultrapotent And Broad Neutralization Of Sars-Cov-2 Variants By Modular, Tetravalent, Bi-Paratopic Antibodies, Shane Miersch, Nitin Sharma, Reza Saberianfar, Chao Chen, Francesca Caccuri, Alberto Zani, Arnaldo Caruso, James Brett Case, Michael S Diamond, Gaya K Amarasinghe, Giuseppe Novelli, Sachdev S Sidhu

2020-Current year OA Pubs

Neutralizing antibodies (nAbs) that target the SARS-CoV-2 spike protein have received emergency use approval for treatment of COVID-19. However, with the emergence of variants of concern, there is a need for new treatment options. We report a format that enables modular assembly of bi-paratopic tetravalent nAbs with antigen-binding sites from two distinct nAbs. The tetravalent nAb purifies in high yield and exhibits biophysical characteristics that are comparable to those of clinically used therapeutic antibodies. The tetravalent nAb binds to the spike protein trimer at least 100-fold more tightly than bivalent IgGs (apparent K

Wireless Implantable Optical Probe For Continuous Monitoring Of Oxygen Saturation In Flaps And Organ Grafts, Hexia Guo, Yameng Xu, Lauren Jacobson, Amanda M Westman, Matthew R Macewan, Mitchell A Pet, Et Al.

2020-Current year OA Pubs

Continuous, real-time monitoring of perfusion after microsurgical free tissue transfer or solid organ allotransplantation procedures can facilitate early diagnosis of and intervention for anastomotic thrombosis. Current technologies including Doppler systems, cutaneous O

The H3k27m Mutation Alters Stem Cell Growth, Epigenetic Regulation, And Differentiation Potential, N Kfoury-Beaumont, R Prakasam, S Pondugula, J S Lagas, S Matkovich, P Gontarz, L Yang, H Yano, A H Kim, J B Rubin, K L Kroll

2020-Current year OA Pubs

BACKGROUND: Neurodevelopmental disorders increase brain tumor risk, suggesting that normal brain development may have protective properties. Mutations in epigenetic regulators are common in pediatric brain tumors, highlighting a potentially central role for disrupted epigenetic regulation of normal brain development in tumorigenesis. For example, lysine 27 to methionine mutation (H3K27M) in the H3F3A gene occurs frequently in Diffuse Intrinsic Pontine Gliomas (DIPGs), the most aggressive pediatric glioma. As H3K27M mutation is necessary but insufficient to cause DIPGs, it is accompanied by additional mutations in tumors. However, how H3K27M alone increases vulnerability to DIPG tumorigenesis remains unclear.

RESULTS: Here, we used human …

Beyond Inhibition: A Novel Strategy Of Targeting Hiv-1 Protease To Eliminate Viral Reservoirs, Josh G Kim, Liang Shan

2020-Current year OA Pubs

HIV-1 protease (PR) is a viral enzyme that cleaves the Gag and Gag-Pol polyprotein precursors to convert them into their functional forms, a process which is essential to generate infectious viral particles. Due to its broad substrate specificity, HIV-1 PR can also cleave certain host cell proteins. Several studies have identified host cell substrates of HIV-1 PR and described the potential impact of their cleavage on HIV-1-infected cells. Of particular interest is the interaction between PR and the caspase recruitment domain-containing protein 8 (CARD8) inflammasome. A recent study demonstrated that CARD8 can sense HIV-1 PR activity and induce cell death. …

The Differences In The Susceptibility Patterns To Triclabendazole Sulfoxide In Field Isolates Of Fasciola Hepatica Are Associated With Geographic, Seasonal, And Morphometric Variations, Martha V Fernandez-Baca, Cristian Hoban, Rodrigo A Ore, Pedro Ortiz, Young-Jun Choi, César Murga-Moreno, Makedonka Mitreva, Miguel M Cabada

2020-Current year OA Pubs

Triclabendazole (TCBZ) resistance is an emerging problem in fascioliasis that is not well understood. Studies including small numbers of parasites fail to capture the complexity of susceptibility variations between and within

Multisystem Proteinopathy Due To Vcp Mutations: A Review Of Clinical Heterogeneity And Genetic Diagnosis, Gerald Pfeffer, Grace Lee, Carly S Pontifex, Roberto D Fanganiello, Allison Peck, Conrad C Weihl, Virginia Kimonis

2020-Current year OA Pubs

In this work, we review clinical features and genetic diagnosis of diseases caused by mutations in the gene encoding valosin-containing protein (VCP/p97), the functionally diverse AAA-ATPase. VCP is crucial to a multitude of cellular functions including protein quality control, stress granule formation and clearance, and genomic integrity functions, among others. Pathogenic mutations in

Shiny Gatom: Omics-Based Identification Of Regulated Metabolic Modules In Atom Transition Networks, Mariia Emelianova, Anastasiia Gainullina, Nikolay Poperechnyi, Alexander Loboda, Maxim Artyomov, Alexey Sergushichev

2020-Current year OA Pubs

Multiple high-throughput omics techniques provide different angles on systematically quantifying and studying metabolic regulation of cellular processes. However, an unbiased analysis of such data and, in particular, integration of multiple types of data remains a challenge. Previously, for this purpose we developed GAM web-service for integrative metabolic network analysis. Here we describe an updated pipeline GATOM and the corresponding web-service Shiny GATOM, which takes as input transcriptional and/or metabolomic data and finds a metabolic subnetwork most regulated between the two conditions of interest. GATOM features a new metabolic network topology based on atom transition, which significantly improves interpretability of the …

Cardiovascular Tropism And Sequelae Of Sars-Cov-2 Infection, Oleksandr Dmytrenko, Kory J Lavine

2020-Current year OA Pubs

The extrapulmonary manifestation of coronavirus disease-19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), became apparent early in the ongoing pandemic. It is now recognized that cells of the cardiovascular system are targets of SARS-CoV-2 infection and associated disease pathogenesis. While some details are emerging, much remains to be understood pertaining to the mechanistic basis by which SARS-CoV-2 contributes to acute and chronic manifestations of COVID-19. This knowledge has the potential to improve clinical management for the growing populations of patients impacted by COVID-19. Here, we review the epidemiology and pathophysiology of cardiovascular sequelae of COVID-19 and outline …

A Genetically Distinct Pediatric Subtype Of Primary Cns Large B-Cell Lymphoma Is Associated With Favorable Clinical Outcome, Ekin Güney, Sonika Dahiya, Et Al.

2020-Current year OA Pubs

No abstract provided.

Surprise And Recency In Novelty Detection In The Primate Brain, Kaining Zhang, Ethan S Bromberg-Martin, Fatih Sogukpinar, Kim Kocher, Ilya E Monosov

2020-Current year OA Pubs

Primates and other animals must detect novel objects. However, the neuronal mechanisms of novelty detection remain unclear. Prominent theories propose that visual object novelty is either derived from the computation of recency (how long ago a stimulus was experienced) or is a form of sensory surprise (stimulus unpredictability). Here, we use high-channel electrophysiology in primates to show that in many primate prefrontal, temporal, and subcortical brain areas, object novelty detection is intertwined with the computations of recency and sensory surprise. Also, distinct circuits could be engaged by expected versus unexpected sensory surprise. Finally, we studied neuronal novelty-to-familiarity transformations during learning …

Adherence And Engagement With A Cognitive Behavioral Therapy-Based Conversational Agent (Wysa For Chronic Pain) Among Adults With Chronic Pain: Survival Analysis, Chaitali Sinha, Abby L Cheng, Madhura Kadaba

2020-Current year OA Pubs

BACKGROUND: Digital applications are commonly used to support mental health and well-being. However, successfully retaining and engaging users to complete digital interventions is challenging, and comorbidities such as chronic pain further reduce user engagement. Digital conversational agents (CAs) may improve user engagement by applying engagement principles that have been implemented within in-person care settings.

OBJECTIVE: To evaluate user retention and engagement with an artificial intelligence-led digital mental health app (Wysa for Chronic Pain) that is customized for individuals managing mental health symptoms and coexisting chronic pain.

METHODS: In this ancillary survival analysis of a clinical trial, participants included 51 adults …

Development And Testing Of An Instrument To Measure Contextual Factors Influencing Self-Care Decisions Among Adults With Chronic Illness, Shayleigh Dickson Page, Christopher Lee, Subhash Aryal, Kenneth Freedland, Anna Stromberg, Ercole Vellone, Heleen Westland, Douglas J Wiebe, Tiny Jaarsma, Barbara Riegel

2020-Current year OA Pubs

BACKGROUND: Decisions about how to manage bothersome symptoms of chronic illness are complex and influenced by factors related to the patient, their illness, and their environment. Naturalistic decision-making describes decision-making when conditions are dynamically evolving, and the decision maker may be uncertain because the situation is ambiguous and missing information. Contextual factors, including time stress, the perception of high stakes, and input from others may facilitate or complicate decisions about the self-care of symptoms. There is no valid instrument to measure these contextual factors. The purpose of this study was to develop and test a self-report instrument measuring the contextual …

Integrative Genomic Analysis Reveals Low T-Cell Infiltration As The Primary Feature Of Tobacco Use In Hpv-Positive Oropharyngeal Cancer, Benjamin M Wahle, Paul Zolkind, Ricardo J Ramirez, Zachary L Skidmore, Sydney R Anderson, Angela Mazul, D Neil Hayes, Vlad C Sandulache, Wade L Thorstad, Douglas Adkins, Obi L Griffith, Malachi Griffith, Jose P Zevallos

2020-Current year OA Pubs

Although tobacco use is an independent adverse prognostic feature in HPV(+) oropharyngeal squamous cell carcinoma (OPSCC), the biologic features associated with tobacco use have not been systematically investigated. We characterized genomic and immunologic features associated with tobacco use through whole exome sequencing, mRNA hybridization, and immunohistochemical staining in 47 HPV(+) OPSCC tumors. Low expression of transcripts in a T cell-inflamed gene expression profile (TGEP) was associated with tobacco use at diagnosis and lower overall and disease-free survival. Tobacco use was associated with an increased proportion of T > C substitutions and a lower proportion of expected mutational signatures, but not with …

Measurement Error Affecting Web- And Paper-Based Dietary Assessment Instruments: Insights From The Multi-Cohort Eating And Activity Study For Understanding Reporting Error, Sharon I Kirkpatrick, Yikyung Park, Et Al.

2020-Current year OA Pubs

Few biomarker-based validation studies have examined error in online self-report dietary assessment instruments, and food records (FRs) have been considered less than food frequency questionnaires (FFQs) and 24-hour recalls (24HRs). We investigated measurement error in online and paper-based FFQs, online 24HRs, and paper-based FRs in 3 samples drawn primarily from 3 cohorts, comprising 1,393 women and 1,455 men aged 45-86 years. Data collection occurred from January 2011 to October 2013. Attenuation factors and correlation coefficients between reported and true usual intake for energy, protein, sodium, potassium, and respective densities were estimated using recovery biomarkers. Across studies, average attenuation factors for …

Poly(Gr) And Poly(Ga) In Cerebrospinal Fluid As Potential Biomarkers For C9orf72-Als/Ftd, Gopinath Krishnan, Timothy M Miller, Et Al

2020-Current year OA Pubs

GGGGCC repeat expansion in C9ORF72, which can be translated in both sense and antisense directions into five dipeptide repeat (DPR) proteins, including poly(GP), poly(GR), and poly(GA), is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we developed sensitive assays that can detect poly(GA) and poly(GR) in the cerebrospinal fluid (CSF) of patients with C9ORF72 mutations. CSF poly(GA) and poly(GR) levels did not correlate with age at disease onset, disease duration, or rate of decline of ALS Functional Rating Scale, and the average levels of these DPR proteins were similar in symptomatic and pre-symptomatic …

Belimumab For Systemic Lupus Erythematosus - Focus On Lupus Nephritis, Marlene Plüß, Silvia Piantoni, Björn Tampe, Alfred H J Kim, Peter Korsten

2020-Current year OA Pubs

In recent years, advances in the treatment and management of patients with systemic lupus erythematosus (SLE) have improved their life expectancy and quality of life. However, lupus nephritis (LN) still represents a major life-threatening complication of the disease. Belimumab (BEL), a fully human monoclonal IgG1λ antibody neutralizing soluble B cell activating factor, was approved more than ten years ago as add-on therapy in adults and pediatric patients with a highly active, autoantibody-positive disease despite standard of care (SoC). Recently, the superiority of the addition of BEL to SoC was also demonstrated in LN. In this review, we provide a comprehensive …

The Plasmodium Falciparum Abc Transporter Abci3 Confers Parasite Strain-Dependent Pleiotropic Antimalarial Drug Resistance, James M Murithi, Eva S Istvan, Daniel E Goldberg, Et Al.

2020-Current year OA Pubs

Widespread Plasmodium falciparum resistance to first-line antimalarials underscores the vital need to develop compounds with novel modes of action and identify new druggable targets. Here, we profile five compounds that potently inhibit P. falciparum asexual blood stages. Resistance selection studies with three carboxamide-containing compounds, confirmed by gene editing and conditional knockdowns, identify point mutations in the parasite transporter ABCI3 as the primary mediator of resistance. Selection studies with imidazopyridine or quinoline-carboxamide compounds also yield changes in ABCI3, this time through gene amplification. Imidazopyridine mode of action is attributed to inhibition of heme detoxification, as evidenced by cellular accumulation and heme …