Digital Commons Network^™

Engineering Chimeric Antigen Receptor Cd4 T Cells For Alzheimer's Disease, Pavle Boskovic, Rotem Shalita, Wenqing Gao, Hailey Vernon, Yu Lin Deng, Marco Colonna, Robbie G Majzner, Ido Amit, Jonathan Kipnis

2020-Current year OA Pubs

Alzheimer's disease (AD) is the prevailing cause of age-associated dementia worldwide. Current standard of care relies on antibody-based immunotherapy. However, antibody-based approaches carry risks for patients, and their effects on cognition are marginal. Increasing evidence suggests that T cells contribute to AD onset and progression. Unlike the cytotoxic effects of CD8

Larval Zebrafish Minimize Energy Consumption During Hunting Via Adaptive Movement Selection, Thomas Darveniza, Robert Wong, Shuyu I Zhu, Zac Pujic, Biao Sun, Matthew Levendosky, Ramesh Agarwal, Michael H Mccullough, Geoffrey J Goodhill

2020-Current year OA Pubs

Animals must balance behavioral goals with the energetic costs of movement. How such trade-offs are implemented algorithmically during natural behavior, and how they adapt to changing energetic constraints, remains poorly understood. Here we show that larval zebrafish adjust their motor strategies during prey hunting to minimize energy expenditure. Using high-speed video tracking and 3D computational fluid dynamics simulations, we quantified the energy costs (in Joules) of different movement types across three developmental stages. While the structure of discrete movement types ("bouts") remained stable with age, their selection probabilities changed depending on their energetic cost, such that more expensive bouts were …

Accurate Interpretation Of Within-Host Dissemination Using Barcoded Bacteria, Rachel T Giorgio, My T Le, Ting Zhang, Caitlyn L Holmes, Karthik Hullahalli

2020-Current year OA Pubs

Bacterial dissemination across tissues is a critically important process influencing infection outcomes. Monitoring within-host dissemination is challenging because conventional measures of bulk bacterial burden cannot distinguish between lineages that are shared between tissues and those that replicate locally. This limitation can be overcome using barcoded bacteria, where deep sequencing of the barcode locus and comparisons of barcodes between tissues define which lineages spread within the host. Numerous studies have used barcoded bacteria to generate high-resolution maps of dissemination. However, since multiple cells in the infectious inoculum can contain identical barcodes, inferences about dissemination can be confounded when distinct lineages from …

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

2020-Current year OA Pubs

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

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

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

2020-Current year OA Pubs

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

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

Long-Acting Interleukin-7 Improves The Efficacy Of Oncolytic Viral Therapy In Glioblastoma, Yuping Derek Li, David A Giles, Yi Huang, Ashwani Kesarwani, Tong Hu, Logan Page, Amanda De Andrade Costa, Jingqin Luo, Mai T Dang, Albert H Kim, John F Dipersio, David T Curiel, Michael S Diamond, Milan G Chheda, Et Al.

2020-Current year OA Pubs

Despite advances in immunotherapy, the prognosis for patients with glioblastoma (GBM) remains poor. The efficacy of GBM-targeted immunotherapies is limited by the paucity of functional T cells in the tumor microenvironment, a consequence of the local and systemic immunosuppression prevalent in patients with GBM. To overcome these challenges, here we develop a treatment strategy we term "expand and pull," which uses systemic administration of rhIL-7-hyFc, a long-acting recombinant human interleukin-7, to increase peripheral T cell abundance ("expand"), followed by intratumoral oncolytic virus treatment to recruit these cells to the tumor microenvironment ("pull"). We show that rhIL-7-hyFc improves the efficacy of …

Non-Canonical Role Of Dna Mismatch Repair On Sensory Processing In Mice, Sadia N Rahman, Demetrios Neophytou, Siboney Oviedo-Gray, Bao Q Vuong, Hysell V Oviedo

2020-Current year OA Pubs

DNA repair mechanisms are essential for cellular development and function. In post-mitotic neurons, deficiencies in DNA damage response proteins can lead to severe neurodegenerative and neurodevelopmental disorders. One highly conserved factor involved in DNA repair is MutS Homolog 2 (Msh2), which is responsible for correcting base-base mismatches and insertion/deletion loops during cell proliferation. However, its role in mature neurons remains poorly understood. This study investigates the impact of Msh2 loss on sensory processing in mice. Using electrophysiological and molecular assays, we identifiedsignificant deficits in cortical and thalamic sound processing in Msh2

A Damaging Mutation In Col6a3 Alters The Mechanobiologic Response Of Chondrocytes Derived From Human Induced Pluripotent Stem Cells, Zainab Harissa, Niek Bloks, Nancy Steward, Sara F Tufa, Douglas R Keene, Yolande F M Ramos, Ingrid Meulenbelt, Farshid Guilak

2020-Current year OA Pubs

Osteoarthritis (OA) is a complex disease associated with genetic, biological, and mechanical risk factors that act, in part, to alter chondrocyte homeostasis. Our recent exome sequencing studies identified a damaging genetic variant in COL6A3, a monomeric unit of collagen type VI and a distinguishing component of the pericellular matrix (PCM) of articular cartilage, a transducer of mechanical and biochemical signals for the chondrocyte. To study the effect of this genetic variant, human induced pluripotent stem cell (hiPSC)-derived chondrocytes, genetically edited to harbor the COL6A3 mutation, were used as an in vitro model to investigate chondrocyte mechanobiology and pathobiology. The COL6A3 …

Association Of Germline Variants With Kras-Mutation Status In Colorectal Cancer, Nijole Pollock Tjader, Yin Cao, Et Al.

2020-Current year OA Pubs

Somatic mutations in KRAS are a common driver of colorectal cancer (CRC) and present at different frequencies by race, sex, tumor site, ethnicity, and genetic similarity. Inherited germline variants may influence tumor somatic mutation frequency by altering mutation or DNA repair processes or altering cellular, immunological and/or microenvironmental responses after a mutation. We hypothesized that the germline genetic background modifies somatic KRAS mutation frequency in CRC. To test this, we performed a genome-wide association study (GWAS) in 7071 individuals with CRC, using KRAS mutation status as the phenotype. Single-nucleotide variants were chosen for validation analyses based on P values from …

Oxaliplatin-Induced Cardiotoxicity In Mice Is Connected To The Changes In Energy Metabolism In The Heart Tissue, Junwei Du, Leland C Sudlow, Kiana Shahverdi, Haiying Zhou, Megan S Michie, Thomas H Schindler, Joshua D Mitchell, Shamim Mollah, Mikhail Y Berezin

2020-Current year OA Pubs

Oxaliplatin is a platinum-based alkylating chemotherapeutic agent used for cancer treatment. At high cumulative dosage, the negative effect of oxaliplatin on the heart becomes evident and is linked to a growing number of clinical reports. The aim of this study was to determine how chronic oxaliplatin treatment causes the changes in energy-related metabolic activity in the heart that leads to cardiotoxicity and heart damage in mice. C57BL/6 male mice were treated with a human equivalent dosage of intraperitoneal oxaliplatin (0 and 10 mg/kg) once a week for eight weeks. During the treatment, mice were followed with ECG, histology and RNA …

Sting Activation Induces Cytotoxic And Immune Responses In Meningiomas Via Inflammatory Cell Death Pathways, Mark W Youngblood, Alexander H Stegh, Et Al.

2020-Current year OA Pubs

Meningiomas are common tumors of the central nervous system that are typically treated with surgery or radiation, but lack established systemic therapies. Activation of the stimulator of interferon genes pathway with an agonist such as 8803 can trigger anti-tumor immune responses. Using integrated molecular approaches, here we show that this pathway is targetable in both neoplastic and immune populations within the meningioma microenvironment. Meningioma tumor cells exhibit promoter hypomethylation and increased chromatin accessibility of the STING genomic locus, associated with robust expression of this gene. Treatment of diverse patient meningiomas ex vivo with 8803 induces direct tumor cytotoxicity through inflammatory …

Geometry Of Neural Dynamics Along The Cortical Attractor Landscape Reflects Changes In Attention, Hayoung Song, Ruiqi Chen, Thomas L Botch, Todd S Braver, Monica D Rosenberg, Jeffrey M Zacks, Shinung Ching

2020-Current year OA Pubs

Large-scale brain activity reflects changes in attention. To understand how, we tested a hypothesis that the geometry of neural dynamics on the cortical attractor landscape, or movement along its "hills and valleys", reflects attentional states. A dynamical systems model separating intrinsic dynamics from stimulus-driven influences was fit to fMRI data collected during rest, tasks, and movie-watching. Model simulations revealed a set of attractors aligned with canonical functional brain networks. The speed and direction of neural trajectories toward these attractors varied systematically with attentional states over time and across contexts. When participants were paying attention to effortful tasks, neural dynamics converged …

Trends In The Psychedelic Renaissance: Applying Artificial Intelligence To Measure Media Portrayal Of Psychedelic Drugs In The 21st Century, David A Bender, Harrison M Dunn, Arushi D Mohite, Akila Anandarajah, Jacob Steinle, Suraj Shankar, Brandon Kiley, Sara Martin, Rishi Gonuguntla, Mia Stonov, Nithya Pippala, Rana Abdalla, Madison K Stille, Gibson Werner, Melinda Daniels-Tineo, Hannah Wang, Sonali Sharma, Jatin Sridhar, Adebusola Adeyemi, Kayla Smart, Baris C Ercal, Et Al.

2020-Current year OA Pubs

BACKGROUND: The relationship between media portrayal of psychedelic drugs, scientific research and drug policy is an area of debate.

AIMS: To apply artificial intelligence technology to measure trends in media sentiment towards the therapeutic potential of psychedelic drugs.

METHOD: Up to 300 of the most relevant articles from Google News searches for the term 'psychedelics' were sampled for each year from 2000 to 2025. A large language model, ChatGPT, evaluated subject matter and sentiment.

RESULTS: In total, 88.3% of screened URLs (3308 of 3747) were included in the analysis. The proportion of articles focusing on the therapeutic potential of psychedelics …

Bioactive Lipid-Mediated Structural And Functional Regulation Of The Essential Human Potassium Channel Kir7.1, Qingwei Niu, Simon Vu, Yuanjian Xu, Mingxing Qian, Anastasiia Rudenko, Jin Ye, Jianwei Zeng, Wei Huang, Douglas F Covey, Rui Zhang, Ziao Fu, Polina V Lishko

2020-Current year OA Pubs

The inwardly rectifying potassium channel Kir7.1 is essential for the physiological function of diverse tissues, including the retinal pigment epithelium and the gestational myometrium. Loss-of-function mutations in KCNJ13, which encodes Kir7.1, or conditional ablation of Kir7.1 in the retinal pigment epithelium, lead to early-onset vision loss. Despite strong genetic evidence supporting Kir7.1 as a therapeutic target, its regulation by endogenous ligands-beyond phosphoinositides-remains poorly understood. Here, we report cryo-electron microscopy structures of human Kir7.1 in multiple functional states at resolutions ranging from 2.8 Å to 4.0 Å. These structures uncover the molecular basis of Kir7.1 modulation by PI

Targeting The Lung Innate Pathways During Tuberculosis Can Improve Vaccine-Induced Protection Via Th17 Responses In Diversity Outbred Mice, Mushtaq Ahmed, Shibali Das, Bruce A Rosa, Javier Rangel Moreno, Deepak Kaushal, Makedonka Mitreva, Shabaana A Khader

2020-Current year OA Pubs

UNLABELLED: Tuberculosis (TB), caused by the bacterium

IMPORTANCE: Bacille Calmette Guerin (BCG) vaccination in genetically diverse outbred (DO) mice provides significant protection against

Heme And Hemozoin Induce Platelet Cell Death Through Upr-Induced Apoptosis And Ferroptosis In Vivax Malaria, Milena Tavares Gomes, Robert A Campbell, Et Al.

2020-Current year OA Pubs

Malaria is a highly prevalent infectious disease caused by Plasmodium parasites. Plasmodium intraerythrocytic replication leads to hemolysis-driven intermittent febrile crises in patients. In addition, the lysis of unparasitized red blood cells contributes to anemia and endotoxemia. Because thrombocytopenia is an important feature of vivax and severe falciparum malaria, we hypothesized that increased hemolysis in malaria contributes to severe thrombocytopenia by releasing endogenous and parasite toxins (ie, heme and hemozoin) capable of inducing programmed cell death in platelets. Using complementary biochemical, ultrastructural, pharmacological, and molecular approaches, we examined response to stress and cell death pathways that were elevated in the transcriptome …

Outcomes Following Matched Sibling Donor Transplantation For Severe Combined Immunodeficiency: A Report From The Pidtc, Ahmad Rayes, Jeffrey J Bednarski, Et Al.

2020-Current year OA Pubs

The Primary Immune Deficiency Treatment Consortium performed a retrospective analysis of 133 patients with severe combined immunodeficiency (SCID) receiving matched sibling donor (MSD) hematopoietic cell transplantation (HCT) between 1980 and 2023 at 30 North American institutions. In this largest cohort of MSD outcomes in patients with SCID to date, we examined the impact of conditioning regimen and graft-versus-host disease (GVHD) prophylaxis on survival and immune recovery. Outcomes after MSD HCT for SCID were excellent. Patients without an active infection or failure to thrive (FTT) at the time of HCT had 5-year overall survival superior to those with infection or FTT. …

Derivation And External Validation Of A Venous Thromboembolism Risk Prediction Model In Asparaginase-Treated All, Daniela R Anderson, Kristen Sanfilippo, Et Al.

2020-Current year OA Pubs

The incidence of venous thromboembolism (VTE) in patients with acute lymphoblastic leukemia (ALL) receiving asparaginase-based induction is high despite primary thromboprophylaxis. Our aim was to derive and externally validate a VTE risk prediction model in patients with ALL receiving asparaginase-based induction. We conducted a multicenter retrospective cohort study of patients (aged ≥18 years) with newly diagnosed ALL receiving asparaginase-based induction. The derivation and external validation cohorts included 306 and 94 patients, respectively. Primary outcome was VTE at any site. A cause-specific Cox proportional hazards model stratified by thromboprophylaxis and center was performed to identify VTE risk factors in the derivation …

Smoldering Multiple Myeloma In The United States: A Population-Based Analysis, Shi-Yi Wang, Rong Wang, Martin Schoen, John H Huber, Eric J Feuer, Jennifer Ruhl, Natalia Neparidze, Xiaomei Ma, Amy J Davidoff, Su-Hsin Chang

2020-Current year OA Pubs

No abstract provided.

Decitabine-Cedazuridine In Patients With Mds And Tp53 Mutations, Samuel Urrutia, Koji Sasaki, Alex Bataller, Hagop Kantarjian, Guillermo Montalban-Bravo, James Mccloskey, Elizabeth A Griffiths, Karen Yee, Amer Zeidan, Michael Savona, Aram Oganesian, Yuri Sano, Harold N Keer, Guillermo Garcia-Manero

2020-Current year OA Pubs

No abstract provided.

Ex Vivo Microfluidic Model Identifies A Role For Shear Stress During Ovarian Tumor Cell Attachment To Peritoneal Mesothelial Cells, Vasilios A Morikis, Breanna Baker, Jillian A Martin, Angela Schab, Alessandra Dimauro, Gregory D Longmore, Whitney R Grither

2020-Current year OA Pubs

Ascites, or a pathologic accumulation of intra-abdominal fluid, is a key feature of intraperitoneally disseminating cancers, such as ovarian cancer. This pathological fluid buildup can influence the adhesive abilities of ovarian cancer cells, as they spread throughout the abdominal cavity to form metastatic implants on organs lined with a specialized monolayer of mesothelial cells. Robust methods for assessing the impact of fluid shear stress on this cell-cell interaction are lacking. Here, we develop and characterize a novel microfluidic device that allows for the determination of the attachment of ovarian tumor cells to mesothelial cells under the influence of fluid flow. …

Ex Vivo Microfluidic Model Identifies A Role For Shear Stress During Ovarian Tumor Cell Attachment To Peritoneal Mesothelial Cells, Vasilios A Morikis, Breanna Baker, Jillian A Martin, Angela Schab, Alessandra Dimauro, Gregory D Longmore, Whitney R Grither

2020-Current year OA Pubs

Ascites, or a pathologic accumulation of intra-abdominal fluid, is a key feature of intraperitoneally disseminating cancers, such as ovarian cancer. This pathological fluid buildup can influence the adhesive abilities of ovarian cancer cells, as they spread throughout the abdominal cavity to form metastatic implants on organs lined with a specialized monolayer of mesothelial cells. Robust methods for assessing the impact of fluid shear stress on this cell-cell interaction are lacking. Here, we develop and characterize a novel microfluidic device that allows for the determination of the attachment of ovarian tumor cells to mesothelial cells under the influence of fluid flow. …

Phytic Acid (Insp6) Activates Hdac3 Epigenetic Axis To Maintain Intestinal Barrier Function, Sujan Chatterjee, Katherine Huang, Kayci Huff-Hardy, Richard Rood, Anas Gremida, Martin Gregory, Chien-Huan Chen, Parakkal Deepak, Et Al.

2020-Current year OA Pubs

HDAC inhibition shows promise in cancer treatment but pan-HDAC inhibitors cause gastrointestinal issues in 48% of patients. Understanding HDAC activation mechanisms is crucial to treating diverse diseases beyond cancer. Our study reveals that inositol polyphosphate multikinase (IPMK) and inositol hexakisphosphate (InsP

Schwannomatosis Tumor Modeling: Progress And Prospects For Translational Research, Mackenzie S Madison, Huazhen Xu, Yarelis Gonzalez-Vargas, Marybeth G Yonk, Charee M Thompson, Hurley Haney, Danielle Babbitt, Yuhong Du, Angela C Hirbe, Nicholas M Boulis, Ren-Yuan Bai, Kecheng Lei

2020-Current year OA Pubs

BACKGROUND: Schwannomatosis (SWN) is a rare genetic condition characterized by the development of benign schwannomas along peripheral and spinal nerves, and this tumor development often results in chronic peripheral pain and significant neurological deficits. Despite surgical resection being the current standard of care for SWN-related pain, scientists are searching for accurate preclinical models that can be used for drug efficacy testing, but existing models often fail to fully recapitulate the complex genotypic diversity and tumor-nerve interface pathology seen in patients. MAIN TEXT: This review first summarizes the genotypic and phenotypic characteristics of SWN subtypes resulting from key mutations in NF2, …

Therapeutic Reprogramming Of Tumour-Associated Macrophages In Pancreatic Cancer Using A Cytotoxic Ccr2-Targeted Nanotheranostic, Vikas Kumar Somani, Xiaohui Zhang, Timothy Hung-Po Chen, Ashenafi Bulle, Sapana Bansod, Lin Li, Yutong Geng, Liang-I Kang, Gyu Seong Heo, Hannah Luehmann, Yuena Zhang, Muhammad A Saeed, Kory J Lavine, David G Denardo, Russell K Pachynski, Yongjian Liu, Kian-Huat Lim

2020-Current year OA Pubs

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) exhibits a profoundly immunosuppressive tumour microenvironment (TME) dominated by inflammatory monocytes (IMs) and tumour-associated macrophages (TAMs), which restrict adaptive immunity and drive resistance to immune checkpoint blockade (ICB). Recruitment of CCR2⁺ IMs by tumour-derived CCL2 is a central mechanism underlying TAM accumulation. Conventional gemcitabine (GEM) and small-molecule CCR2 inhibitors provide limited benefit due to poor intratumoural delivery, transient target engagement, and compensatory myeloid recruitment. METHODS: We engineered a CCR2-targeted nanotheranostic by conjugating a CCR2-binding peptide (ECL1i) and GEM onto ultrasmall copper nanoclusters (CuNCs-ECL1i-GEM; C-E-G). Therapeutic efficacy and immune remodelling were evaluated using orthotopic subcutaneous and …

Leveraging The Translational Science Benefits Model To Plan And Measure Early Impact In The Heart Failure Polypill Implementation Trial In Sri Lanka, Adam Hively, Anna La Manna, Ella Clark, Douglas Luke, Asita De Silva, Mansi Agarwal, Mark D Huffman, Abdul Salam, Anubha Agarwal, Emmanuel K Tetteh

2020-Current year OA Pubs

No abstract provided.

Toward Integrating Clinical And Non-Clinical Associates Of Suicidality To Inform Potential Intervention Points Among Youth In Nairobi Metropolitan, Kenya, David Ndetei, Danuta Wasserman, Victoria Mutiso, Kamaldeep Bhui, Jenelle Shanley, Christine Musyimi, Samantha Winter, Pascalyne Nyamai, Samuel Walusaka, Veronica Onyango, Eric Jeremiah, Tom Lee Osborn, Monica Swahn, Andre Sourander, Daniel Mamah

2020-Current year OA Pubs

Suicide is a significant global public health concern, particularly among adolescents, with substantial implications for economies, societies and individuals' mental well-being. Understanding its patterns and intention and psychosocial determinants in a given context can suggest potential intervention points. This population-based cross-sectional study aimed to document suicidal ideas, behaviors and intensity among youths aged 14 to 25 in the Nairobi metropolitan area and associated socio-economic position, demographic indicators and potential intervention points. A diverse sample of 1,972 participants was recruited from urban and peri-urban settings within the Nairobi metropolitan area. Data analysis included descriptive statistics, chi-square tests and logistic regression. Our …

Targeting Tau In Alzheimer's Disease: Rationale, Approach And Challenges, Aram Aslanyan, Martha S Foiani, Tatiana A Giovannucci, Eric Mcdade, Karen E Duff, Catherine J Mummery, Michael Schöll, Kristin R Wildsmith, Ross W Paterson

2020-Current year OA Pubs

Alzheimer’s Disease (AD) is the most common neurodegenerative disorder and the leading cause of dementia characterised by the accumulation of beta amyloid (Aβ) plaques and neurofibrillary tangles (NFT). Several monoclonal antibodies against amyloid in early AD have shown the utility of reducing brain amyloid in large phase 3 studies, resulting in modest clinical benefit. To further slow, or even halt disease progression, targeting additional pathobiological pathways is likely to be necessary. In this review, we aim to appraise the scientific rationale for targeting tau in AD. The burden of tau pathology is correlated with disease severity and its role in …

Sclerostin Deficiency Sensitizes White Adipocytes To Thermogenic Signals That Induce Beiging In Mice, Gillian M Choquette, Soohyun P Kim, Kevin J Wilkinson, Belen C Avelar, Sushrut Pathy, Zhu Li, Jasmine Wu, Susan Aja, Daniel L J Thorek, Michael J Wolfgang, Ryan C Riddle

2020-Current year OA Pubs

Maintenance of bone mass is coordinated with adipose tissue function through the secretion of hormones and endocrine factors that act on the opposing tissue. Sclerostin, a small glycoprotein produced by osteocytes embedded within the bone matrix, potently suppresses bone formation by antagonizing Wnt/β-catenin signaling while stimulating adipose tissue accumulation via the same mechanism of action. Since sclerostin-deficient mice develop pockets of multilocular adipocytes in subcutaneous adipose, we investigate the influence of sclerostin on thermogenic and β3-adrenergic stimuli-induced white adipose tissue beiging. Here, we report that Sost gene expression in bone and serum sclerostin levels are induced by β3-adrenergic agonists via …

Heterogeneity In The Association Of Genetic Risk For Ra And Resultant Ra Phenotypes, Thomas R Riley, Iris Lee, Et Al.

2020-Current year OA Pubs

OBJECTIVES: The impact of the genetic risk for RA on resultant disease phenotype in RA is incompletely understood. Using individual genetic variants associated with RA and a polygenic score (PGS), we hypothesized that those with higher genetic risk for RA would demonstrate a more severe disease course.

METHODS: We genotyped participants from the Veterans Affairs RA registry (VARA), a prospective cohort of RA. We evaluated associations between PTPN22 R620W genotype, HLA-DRB1 shared epitope (SE; 0, 1, or 2 copies of a high-risk HLA allele), and a non-HLA PGS with RA disease activity scores and disease characteristics using linear and logistic …