tbuckley/cabot-search huggingface dataset:
Abstract 468: Identification of a New Component of the Na <sub>v</sub> 1.5 Complex: αB-crystallin Interacts with Na <sub>v</sub> 1.5 and Regulates Ubiquitination and Internalization of Cell Surface Na <sub>v</sub> 1.5
Authors: Yuan Huang, Zhijie Wang, Yinan Liu, Qiuyun Chen, Qing k. Wang
Journal: Circulation Research (2016)

Mutations in cardiac Na + channel Na v 1.5 cause cardiac arrhythmias and sudden death. The cardiac Na + channel functions as a protein complex, however, its complete components remain to be fully elucidated. A yeast two-hybrid screen identified a new candidate Na v 1.5-interacting protein, αB-crystallin. GST-pull-down, co-immunoprecipitation and immunostaining analyses validated the interaction between Na v 1.5 and αB-crystallin. Overexpression of αB-crystallin significantly increased peak sodium current ( I Na ) density, and the underlying molecular mechanism is the increased cell surface expression level of Na v 1.5 via reduced internalization of cell surface Na v 1.5 and ubiquitination of Na v 1.5. Knockout of αB-crystallin expression significantly decreased the cell-surface expression level of Na v 1.5. αB-crystallin interacted with Nedd4-2, however, a catalytically inactive Nedd4-2-C801S mutant reduced the interaction between αB-crystallin and Nedd4-2 and also blocked the increase of peak I Na density by αB-crystallin. Na v 1.5 mutation V1980A at the interaction site for Nedd4-2 eliminated the effect of αB-crystallin on reduction of Na v 1.5 ubiquitination and increases of I Na density. The data suggest that the interactions between αB-crystallin and functionally active Nedd4-2 and between αB-crystallin and Na v 1.5 are critical to increased I Na density by αB-crystallin. Multiple mutations in αB-crystallin have been associated with human diseases. Two mutations, R109H and R151X, eliminated the effect of αB-crystallin on I Na . This study identifies αB-crystallin as a new binding partner for Na v 1.5. αB-crystallin interacts with Na v 1.5 and increases I Na by modulating the expression level and internalization of cell surface Na v 1.5 and ubiquitination of Na v 1.5, which requires the protein-protein interactions between αB-crystallin and Na v 1.5 and between αB-crystallin and functionally active Nedd4-2.
Abstract 383: Immunotherapy With <i>Trypanosoma cruzi</i> Genes Prevents the Severity of Heart Damage in Experimental Chagasic Dogs Evaluated by Electrocardiography and Macroscopic Findings at Necropsy
Authors: Olivia Rodríguez-Morales, Silvia C Carrillo-Sánchez, Martha Rios-Castro, Minerva Arce-Fonseca
Journal: Circulation Research (2016)

Chagas disease is a chronic and potentially lethal disorder caused by the parasite Trypanosoma cruzi. The main importance of this parasitosis is its high prevalence, its wide geographical distribution and the great economic losses because it affects young adults in productive life causing deterioration of cardiovascular health and sudden death in apparently healthy people. Currently, there is no effective treatment, since only two drugs with trypanocidal activity can cause cure in 80% of patients only if they are treated promptly during the acute phase of the disease. The aim of this study was to test whether immunotherapy with parasite DNA is able to avoid, reduce or delay the chagasic cardiomyopathy in experimentally infected dogs. Thirty Beagle adult dogs were used; five groups were infected with 3,500 metacyclic trypomastigotes of T. cruzi H8 strain/kg, two weeks later 500 ug of plasmid DNA containing TcSP , TcSSP4 and the mixture of both genes were injected thrice at 2-week intervals. Empty vector and saline solution were used as controls. Prior to infection/immunotherapy electrocardiographic features were recorded in all dogs as well as at 3, 6 and 12 months later. Hearts, spleens and lymph nodes were collected after euthanasia to determine cardiomegaly, splenomegaly and lymphadenomegaly, respectively, in infected/treated dogs. The results were that the DNA vaccines used as immunotherapy had moderate efficacy in preventing cardiac complications or delay its onset associated with chronic chagasic cardiomyopathy evaluated by electrocardiography such as left ventricle enlargement, left and right bundle branch block and ischaemia. T. cruzi genes administered separately prevented cardiomegaly. In conclusion, the use of DNA with TcSSP4 and TcSP genes is an alternative use of new therapeutic tool against CD, which in recent years has taken off by gathering efforts of researchers and physicians from several countries, not only in Latin America.
Biomimetic Liposome with Surface‐Bound Elastase for Enhanced Tumor Penetration and Chemo‐Immumotherapy
Authors: Yong‐Jiang Li, Jun‐Yong Wu, Xiong‐Bin Hu, Tianjinhao Ding, Tiantian Tang, Da‐Xiong Xiang
Journal: Advanced Healthcare Materials (2021)

Abstract Dense extracellular matrix (ECM) in the tumor stroma has been a challenge for drug penetration and cytotoxic T lymphocyte (CTL) infiltration. Neutrophil elastase (NE), in surface‐bound form, can destruct ECM rapidly, may be used for remodeling tumor ECM, and overcoming tumor stromal barrier. Focusing on elastosis in triple‐negative breast tumor, biomimetic liposomes with chimeric cell membrane proteins (LMP) are developed and for the first time, it is demonstrated that LMP with surface‐bound elastase (NE‐LMP) can target and degrade ECM effectively in tumor stroma, with minimal toxicity to normal tissues. The pretreatment of NE‐LMP increases the accumulation of chemotherapeutics at the tumor site and enhances antitumor effects. Also, NE‐LMP facilitates CTL infiltration in tumors and exhibits enhanced chemo‐immunotherapy in combination of PD‐1 immune checkpoint blockade treatment in orthotopic 4T1 tumor‐bearing mice, with significantly prolonged survival. Moreover, the remodeling of the tumor ECM by NE‐LMP shows inhibiting effects on metastasis in the lung. Findings from this study suggest that NE‐LMP holds promise for enhancing deep penetration of drug and infiltration of CTL in desmoplastic tumor by effective degrading ECM in the tumor stroma.
Erratum: "Xanthine oxidase inhibition reduces reactive nitrogen species production in COPD airways" (European Respiratory Journal (2003) vol. 22 (457-461))
Authors: M. Ichinose, H. Sugiura, S. Yamagata, A. Koarai, M. Tomaki, H. Ogawa, Y. Komaki, P. J. Barnes, K. Shirato, Toshio Hattori
Journal: European Respiratory Journal (2004)
Safety Concerns or Adverse Effects as the Main Reason for Human Papillomavirus Vaccine Refusal
Authors: Onyema Greg Chido-Amajuoyi, Rajesh Talluri, Sahil S. Shete, Sanjay Shete
Journal: JAMA Pediatrics (2021)

Vaccination against the human papillomavirus (HPV) is effective at preventing several squamous cell carcinomas, yet the population-level uptake of the vaccine remains low in the US. Several factors contribute to HPV vaccine hesitancy and refusal; of note, safety concerns rank consistently high as a reason for nonvaccination.1,2 The COVID-19 pandemic has brought to the forefront the fragility of public confidence in the safety of vaccines.3 Therefore, this study examines safety concerns or adverse effects of the HPV vaccine as the main reason for nonvaccination over an 11-year period.
Genomic Epidemiology of SARS-CoV-2 in Pakistan
Authors: Shuhui Song, Cuiping Li, Lu Kang, Dongmei Tian, Nazish Badar, Wentai Ma, Shilei Zhao, Xuan Jiang, Chun Wang, Yongqiao Sun, Wenjie Li, Meng Lei, Shuangli Li, Qiuhui Qi, Aamer Ikram, Muhammad Salman, Massab Umair, Huma Shireen, Fatima Batool, Bing Zhang, Hua Chen, Yun-Gui Yang, Amir Ali Abbasi, Mingkun Li, Yongbiao Xue, Yiming Bao
Journal: Genomics Proteomics & Bioinformatics (2021)

Abstract COVID-19 has swept globally and Pakistan is no exception. To investigate the initial introductions and transmissions of the SARS-CoV-2 in Pakistan, we performed the largest genomic epidemiology study of COVID-19 in Pakistan and generated 150 complete SARS-CoV-2 genome sequences from samples collected from March 16 to June 1, 2020. We identified a total of 347 mutated positions, 31 of which were over-represented in Pakistan. Meanwhile, we found over 1000 intra-host single-nucleotide variants (iSNVs). Several of them occurred concurrently, indicating possible interactions among them or coevolution. Some of the high-frequency iSNVs in Pakistan were not observed in the global population, suggesting strong purifying selections. The genomic epidemiology revealed five distinctive spreading clusters. The largest cluster consisted of 74 viruses which were derived from different geographic locations of Pakistan and formed a deep hierarchical structure, indicating an extensive and persistent nation-wide transmission of the virus that was probably attributed to a signature mutation (G8371T in ORF1ab) of this cluster. Furthermore, 28 putative international introductions were identified, several of which are consistent with the epidemiological investigations. In all, this study has inferred the possible pathways of introductions and transmissions of SARS-CoV-2 in Pakistan, which could aid ongoing and future viral surveillance and COVID-19 control.
Effect of Targeted Messaging on Return to In-Person Visits During the COVID-19 Pandemic
Authors: Anne R. Cappola, Emily R. Schriver, Danielle L. Mowery, Colin Wollack, Camelot T. Ives, Ryan Gonzales, Joseph N. Cappella
Journal: JAMA Network Open (2021)

a P < .05for pairwise comparison with the no letter group, adjusted via the Holm method.
Risk of Hyponatremia and Associated Clinical Characteristics in Patients with Acute Lymphoblastic Leukemia after CD19 Targeted Chimeric Antigen Receptor (CAR) T-Cells
Authors: Brianne N. Dixon, Ryan J. Daley, Troy Z. Horvat, Larry W Buie, Meier Hsu, Sheron Latcha, Renier J. Brentjens, Jae H. Park
Journal: Blood (2017)
Abstract 16066: Accuracy of Transthoracic Echocardiography in the Anatomic Description of Double Outlet Right Ventricle in Patients Undergoing Biventricular Repair
Authors: Jessica Tang, Jamie K Harrington, Heather Griffis, Antara Mondal, Christopher Mascio, Paul M Weinberg, Andrew J Powell, Meryl S Cohen
Journal: Circulation (2019)

Introduction: Double outlet right ventricle (DORV) represents a rare subset of congenital heart defects for which the type of ventricular septal defect (VSD) often dictates the surgical strategy. T...
Online Exercise Plus Text Messages Improve Knee Osteoarthritis
Authors: Anita Slomski
Journal: JAMA (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Impaired Skeletal Muscle Energy Metabolism Limits Aerobic Exercise Capacity in Patients with Metabolic Syndrome
Authors: Tsutsui H, Okita K, Morita N, Ono T, Sobirin Ma, Hamaguchi S, Matsushima S, Ohta Y, Yokota T, Kinugawa S, Hirabayashi K, Suga T, Inoue N
Journal: Circulation (2008)
Targeted cell therapy for partial-thickness cartilage defects using membrane modified mesenchymal stem cells by transglutaminase 2
Authors: Hui Li, Yuhong Jin, Yu Zhao, Wenjing Li, Zihao He, Qingxi Zhang, Hesuyuan Huang, Jianjing Lin, Yuyang Chen, Dan Xing, Yanan Du, Jianhao Lin
Journal: Biomaterials (2021)
AP-2α–Mediated Activation of E2F and EZH2 Drives Melanoma Metastasis
Authors: Jeffrey R. White, Dakota T. Thompson, Kelsey E. Koch, Boris S. Kiriazov, Anna C. Beck, Dana M. van der Heide, Benjamin G. Grimm, Mikhail V. Kulak, Ronald J. Weigel
Journal: Cancer Research (2021)

Abstract In melanoma metastasis, the role of the AP-2α transcription factor, which is encoded by TFAP2A, is controversial as some findings have suggested tumor suppressor activity while other studies have shown high TFAP2A expression in node-positive melanoma associated with poor prognosis. Here we demonstrate that AP-2α facilitates melanoma metastasis through transcriptional activation of genes within the E2F pathway including EZH2. A BioID screen found that AP-2α interacts with members of the nucleosome remodeling and deacetylase (NuRD) complex. Loss of AP-2α removed activating chromatin marks in the promoters of EZH2 and other E2F target genes through activation of the NuRD repression complex. In melanoma cells, treatment with tazemetostat, an FDA-approved and highly specific EZH2 inhibitor, substantially reduced anchorage-independent colony formation and demonstrated heritable antimetastatic effects, which were dependent on AP-2α. Single-cell RNA sequencing analysis of a metastatic melanoma mouse model revealed hyperexpansion of Tfap2aHigh/E2F-activated cell populations in transformed melanoma relative to progenitor melanocyte stem cells. These findings demonstrate that melanoma metastasis is driven by the AP-2α/EZH2 pathway and suggest that AP-2α expression can be used as a biomarker to predict responsiveness to EZH2 inhibitors for the treatment of advanced melanomas. Significance: AP-2α drives melanoma metastasis by upregulating E2F pathway genes including EZH2 through inhibition of the NuRD repression complex, serving as a biomarker to predict responsiveness to EZH2 inhibitors.
Home Health Management of Parkinson Disease Deep Brain Stimulation
Authors: Gordon Duffley, Barbara J. Lutz, Aniko Szabo, Adrienne Wright, Christopher W. Hess, Adolfo Ramirez-Zamora, Pamela Zeilman, Shannon Chiu, Kelly D. Foote, Michael S. Okun, Christopher R. Butson
Journal: JAMA Neurology (2021)

The travel required to receive deep brain stimulation (DBS) programming causes substantial burden on patients and limits who can access DBS therapy.To evaluate the efficacy of home health DBS postoperative management in an effort to reduce travel burden and improve access.This open-label randomized clinical trial was conducted at University of Florida Health from November 2017 to April 2020. Eligible participants had a diagnosis of Parkinson disease (PD) and were scheduled to receive DBS independently of the study. Consenting participants were randomized 1:1 to receive either standard of care or home health postoperative DBS management for 6 months after surgery. Primary caregivers, usually spouses, were also enrolled to assess caregiver strain.The home health postoperative management was conducted by a home health nurse who chose DBS settings with the aid of the iPad-based Mobile Application for PD DBS system. Prior to the study, the home health nurse had no experience providing DBS care.The primary outcome was the number of times each patient traveled to the movement disorders clinic during the study period. Secondary outcomes included changes from baseline on the Unified Parkinson's Disease Rating Scale part III.Approximately 75 patients per year were scheduled for DBS. Of the patients who met inclusion criteria over the entire study duration, 45 either declined or were excluded for various reasons. Of the 44 patients enrolled, 19 of 21 randomized patients receiving the standard of care (mean [SD] age, 64.1 [10.0] years; 11 men) and 23 of 23 randomized patients receiving home health who underwent a minimum of 1 postoperative management visit (mean [SD] age, 65.0 [10.9] years; 13 men) were included in analysis. The primary outcome revealed that patients randomized to home health had significantly fewer clinic visits than the patients in the standard of care arm (mean [SD], 0.4 [0.8] visits vs 4.8 [0.4] visits; P < .001). We found no significant differences between the groups in the secondary outcomes measuring the efficacy of DBS. No adverse events occurred in association with the study procedure or devices.This study provides evidence supporting the safety and feasibility of postoperative home health DBS management.ClinicalTrials.gov Identifier: NCT02474459.
Abstract 55: Use of a Novel Electrogram Filter to Visualise the Conduction Tissue Signals in the Ventricle in Sinus Rhythm and Arrhythmia: Canine Studies
Authors: Deepak Padmanabhan, Chance Witt, Alan Sugrue, Ammar Killu, Niyada Naksuk, Christopher Desimone, Dorothy Ladewig, Joanne Powers, Scott Suddendorf, Samuel Asirvatham
Journal: Circulation Research (2017)

Background: Conduction tissue in the ventricles is closely intertwined with myocardium. Owing to high velocity of conduction, there is near simultaneous activation , making it difficult to discern. Restricted sampling rates and limited dynamic range make real time signal processing challenging for these signals in routine recording systems. Objectives: We aimed to use novel signal processing techniques in a new system to isolate the conduction tissue signals from the rest of the myocardial activation. Methods: We used the PURE-EP™ (BioSig Technologies, MN) signal processing system to record endocardial and epicardial signals from 6 anesthetized canines in an acute study setting. A novel filter based on proprietary algorithms to isolate the high frequency signal was applied at sites where the electrogram signals were thought to have a conduction tissue component to them. . In addition, ventricular fibrillation (VF) was induced at the end of the experiment and signals were then recorded from the endocardium and the conduction system. Results: This filter was successfully able to isolate conduction tissue signals in the myocardium from those of the ventricular muscle. It did over sense atrial signals at the basal left ventricular septum owing to the high frequency components of the atrial signal at this location. When applied to epicardial signals, it did not pick up any conduction tissue signals. In VF, we could discern signals originating from the conduction system endocardially. (Figure 1) Conclusions: This filter can isolate conduction tissue signals from those of the myocardium and may prove to be a useful adjunct in mapping arrhythmias originating near the conduction system.
A multidisciplinary approach to the management of inflammatory bowel diseases: surgical complications — how not to miss by therapist
Authors: T.B. Nechypurenko
Journal: GASTROENTEROLOGY (2021)

The article deals with a condition that is complex for diagnostic search — inflammatory bowel diseases (IBD). Frequent complication of IBD by acute surgical manifestations, the possibility of the onset of diseases from surgical lesions determines the practical need for physicians to be aware of the management of IBD with complicated pathology. The article presents a clinical case — the complication of ulcerative colitis by multiple colonic perforations, which were not detected in time. The diagnostic search allowed us to find out intraoperatively the causes of acute surgical manifestations, to diagnose complications, and the prescribed adequate postoperative treatment stabilized the patient’s state.
Overcoming T Cell Exhaustion via Immune Checkpoint Modulation with a Dendrimer‐Based Hybrid Nanocomplex
Authors: Yue Gao, Zhijun Ouyang, Chao Yang, Cong Song, Chunjuan Jiang, Shaoli Song, Mingwu Shen, Xiangyang Shi
Journal: Advanced Healthcare Materials (2021)

Abstract T cell exhaustion, in which dysfunctional T cells are limited in cytokine release and constrained in immune response, leads to immune escape of cancer cells and decreased efficiency of cancer immunotherapy. Direct regulation or blocking of programmed death 1 (PD‐1) represents a promising strategy to overcome T cell exhaustion for reinvigorating anticancer immunity. Here, the construction of a 1,3‐propanesultone (1,3‐PS)‐grafted zwitterionic dendrimer‐entrapped gold nanoparticle platform chelated with Gd(III) (Gd‐Au DENP‐PS) for immune checkpoint modulation is reported. The developed Gd‐Au DENP‐PS possesses good stability, antifouling property, biocompatibility, and dual‐mode computed tomography (CT)/magnetic resonance (MR) imaging functions, and allows for efficient packaging and serum‐enhanced delivery of PD‐1 siRNA to mediate PD‐1 gene silencing in T cells in vitro, and also in vivo in a melanoma‐bearing mouse model and in healthy aging mice. The dendrimer nanocomplexes or T cell‐laden nanocomplexes enable suppression of tumor growth through the generation of significant effector CD8+ and CD4+ T cells, and the tumor immunotherapeutic potency can be further improved by combination with an indoleamine 2,3‐dioxygenase inhibitor. This study identifies a new possibility with a functional dendrimer‐based nanohybrid platform for dual‐mode CT/MR imaging‐guided cancer immunotherapy via the regulation of T cell exhaustion.
Abstract 17000: Pre-Conditioning with an Apo-lipoprotein Mimetic Peptide Recruits Adiponectin Dependent p-AMPK and Prevents Ischemic Cardiac Injury
Authors: Stephen J Peterson, Jian Cao, Luigi F Rodella, Rita Rezzani, Francesco Piccolomini, Luca Vanella, Antonio L'Abbate
Journal: Circulation (2011)

Objectives: Heme-heme oxygenase (HO) system is one of the first line defenses against alterations in cellular redox, and, has been show to protect against vascular endothelial dysfunction in chronic diseased states, such as obesity and diabetes. We tested the hypothesis that pre-conditioning with L4F attenuates ischemia induced cardiac dysfunction in diabetic mice. Methods: db/db mice were treated with either L-4F (an apo-lipoprotein mimetic inducer of HO) or vehicle for 8 weeks. Glucose, insulin, adiponectin, and pro-inflammatory cytokines (IL-1beta, TNF-alpha, MCP-1) were measured in plasma so as to confirm a diabetic, inflammatory state. Trans-thoracic echocardiography was performed at the completion of the experiment after which, isolated hearts were subjected to ischemia/reperfusion (IR) while mounted on a Langendorff's preparation. Isolated hearts were then analyzed for HO-1, pAMPK, peNOS, iNOS, adiponectin and superoxide levels. Results: As shown before, db/db mice developed hyperglycemia with hyperinsulinemia and exhibited significantly increased (p&lt;0.05) circulating levels of inflammatory cytokines including, TNFalpha, MCP-1 and IL1beta. Cardiac function was significantly compromised (p&lt;0.05) in db/db mice with enhancement of coronary resistance (CR) and reduced LVDevp and reduced cardiac muscle shortening (dP/dT). L-4F treatment increased insulin sensitivity and adiponectin levels (p&lt;0.05), while lowering inflammatory cytokines (p&lt;0.05) in these mice. Also, L-4F normalized LV function by increasing (p&lt;0.05) fractional shortening and decreasing (p&lt;0.05) LV dimensions. In I/R experiments, L-4F prevented coronary microvascular resistance from increasing and LV function from deteriorating in the db/db mice (p&lt;0.05). These changes were associated with increased cardiac expression of HO-1, pAMPK, peNOS and adiponectin and decreased levels of superoxide and iNOS (p&lt;0.01). Conclusion: Attenuation of L-4F-induced myocardial and coronary functional abnormalities in db/db mice, involves HO induction and recruitment of adiponectin-dependent anti-inflammatory, anti-oxidative, and vasodilatory pathways; including activation of pAMPK and peNOS.
Reply: Comment on: Notch‐1 and Notch‐3 mediates hypoxia‐induced synovial fibroblasts activation in rheumatoid arthritis
Authors: Jianhai Chen, Antonia Sun, Jian Li, Wenxiang Cheng, Peng Zhang
Journal: Arthritis & Rheumatology (2021)

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