tbuckley/cabot-search huggingface dataset:
Ezrin, a Membrane Cytoskeleton Cross-Linker Protein, as a Marker of Epithelial Damage in Asthma
Authors: Man Jia, Xiaoyi Yan, Xinyu Jiang, Yunhui Wu, Jiayan Xu, Yaqi Meng, Yi Yang, Xia Shan, Xiuwedi Zhang, Shan Mao, Wei Gu, Stelios Pavlidis, Peter J. Barnes, Ian M. Adcock, Mao Huang, Xin Yao
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Bronchial epithelial cell damage occurs in patients with bronchial asthma. Ezrin, a membrane-cytoskeleton protein, maintains cellular morphology and intercellular adhesion and protects the barrier function of epithelial cells.To study the role of ezrin in bronchial epithelial cells injury and correlate its expression with asthma severity.Levels of ezrin were measured in exhaled breath condensate (EBC) and serum in patients with asthma and BAL fluid (BALF) from a mouse model of asthma by ELISA. The regulation of IL-13 on ezrin protein levels was studied in primary bronchial epithelial cells. Ezrin knockdown using shRNA was studied in human bronchial epithelial 16HBE cells.Ezrin levels were decreased in asthmatic EBC (92.7 ± 34.99 vs. 150.5 ± 10.22 pg/ml, P < 0.0001) and serum (700.7 ± 55.59 vs. 279.2 ± 25.83 pg/ml, P < 0.0001) compared with normal subjects. Levels were much lower in uncontrolled (P < 0.001) and partly controlled patients (P < 0.01) compared with well-controlled subjects. EBC and serum ezrin levels correlated with lung function in patients with asthma and serum ezrin levels were negatively correlated with serum IL-13 and periostin. IL-13-induced downregulation of ezrin expression in primary bronchial epithelial cells was significantly attenuated by the Janus tyrosine kinase 2 inhibitor, TG101348. Ezrin knockdown changed 16HBE cell morphology, enlarged intercellular spaces, and increased their permeability. Ezrin expression was decreased in the lung tissue and BALF of "asthmatic" mice and negatively correlated with BALF IL-13 level.Ezrin downregulation is associated with IL-13-induced epithelial damage and might be a potential biomarker of asthma control.
Provider Specialty, Anticoagulation, and Stroke Risk in Patients With Atrial Fibrillation and Cancer
Authors: Wesley T. O’Neal, J’Neka S. Claxton, Pratik B. Sandesara, Richard F. MacLehose, Lin Y. Chen, Lindsay G.S. Bengtson, Alanna M. Chamberlain, Faye L. Norby, Pamela L. Lutsey, Alvaro Alonso
Journal: Journal of the American College of Cardiology (2018)
Abstract 16001: Relationship Between Serum n-3 to n-6 Poly-unsaturated Fatty Acid Ratios and Coronary Plaque Components Identified by iMap-Intravascular Ultrasound in Patients With Stable Angina Pectoris
Authors: Keisuke Kojima, Shigeki Kimura, Toru Misawa, Kazuto Hayasaka, Masafumi Mizusawa, Yosuke Yamakami, Yuichiro Sagawa, Hirofumi Otani, Keiichi Hishikari, Hiroyuki Hikita, Atsushi Takahashi
Journal: Circulation (2015)

Background: Residual risk of cardiovascular disease exists even in patients achieving low-density lipoprotein cholesterol (LDL-C) goals. A low value of serum eicosapentaenoic acid to arachidonic acid (EPA/AA) ratio is well known to be associated with cardiovascular events. However, the association between serum EPA/AA ratio and coronary plaque components has not been fully investigated. Purpose: We evaluated the relationships between serum EPA/AA ratio and coronary plaque morphology on iMap-intravascular ultrasound (IVUS) which is a 40 MHz IVUS tissue characteristic system. Methods: We investigated 80 consecutive coronary culprit lesions with stable angina pectoris (SAP) patients, who underwent pre-intervention iMap-IVUS. All patients were divided into two groups; groups with higher values of the median EPA/AA ratio and lower values of the median EPA/AA ratio. We assessed the relationship between the two groups. Results: Median values of EPA, AA and EPA/AA ratio were 67.5 (44.3-100.3) μg/ml, 174.2 (145.5-202.9) μg/ml, and 0.38 (0.23-0.60). Patients in lower EPA/AA ratio group (&lt;0.38) showed younger age (65±11 vs 70±6, p=0.02), more OMI patients (40 vs 18%, p=0.03), higher value of LDL-C (94.5±29.3 vs 80.9±26.5 mg/dl, p=0.03), lower ejection fraction (61.4±8.8 vs 65.4±7.2%, p=0.04), greater lesion plaque area (11.5±4.4 vs 9.6±4.4 mm2, p&lt;0.05), compared with higher EPA/AA ratio group. In multivariate analysis, LDL-C value was an independent predictor of lower EPA/AA ratio (odds ratio 1.02, 95% confidence interval 1.00-1.04, p= 0.04). In lower LDL-C group (&lt;70 mg/dl), EPA/AA inversely correlated with %-necrotic area and volume (r=-0.56, p=0.004, and r=-0.54, p=0.01), and positively correlated with %-fibrotic area and volume (r=0.57, p=0.003, and r=0.54, p=0.01), although EPA/AA ratio did not correlate with plaque components in higher LDL-C groups. In lower LDL-C group, for prediction of the highest %-necrotic volume tertile (&gt;42.1%), cut-off value of EPA/AA ratio was 0.20 (sensitivity 50%, specificity 94%, area under the curve 0.77, p=0.02). Conclusion: serum EPA/AA ratio may be related to plaque components at the culprit site in SAP patients with low LDL-C values.
Supercritical Fluid‐Assisted Porous Microspheres for Efficient Delivery of Insulin and Inhalation Therapy of Diabetes
Authors: Xiao‐Fen Lin, Ranjith Kumar Kankala, Na Tang, Pei‐Yao Xu, Liu‐Zhi Hao, Da‐Yun Yang, Shi‐Bin Wang, Yu Shrike Zhang, Ai‐Zheng Chen
Journal: Advanced Healthcare Materials (2018)

Abstract Pulmonary delivery of drugs has attracted increasing attention in healthcare, as the lungs are an easily accessible site for noninvasive systemic delivery of drugs. Although pulmonary inhalation of porous microparticles has been shown to sustain drug delivery, there are limited reports on efficient delivery of insulin and inhalation therapy of diabetes based on supercritical carbon dioxide (SC‐CO 2 ) technology. Herein, this study reports the fabrication of insulin‐loaded poly‐ l ‐lactide porous microspheres (INS‐PLLA PMs) by using the SC‐CO 2 technology, and their use as an inhalation delivery system potentially for diabetes therapy. Biocompatibility and delivery efficiency of the PLLA PMs in the lungs are investigated. The PLLA PMs show negligible toxicity to lung‐derived cells, resulting in no significant reduction in cell viability, as well as levels of various inflammatory mediators such as interleukin (IL)‐6, IL‐8, and tumor necrosis factor‐α, compared with the negative control group. INS‐PLLA PMs are further efficiently deposited in the trachea and the bronchi of superior lobes of the lungs, which exhibit pronounced hypoglycemic activity in induced diabetic rats. Together, the results demonstrate that the INS‐PLLA PMs have a strong potential as an effective strategy for inhalation treatment of diabetes.
Chelation, formulation, encapsulation, retention, and in vivo biodistribution of hydrophobic nanoparticles labelled with 57Co-porphyrin: Oleylamine ensures stable chelation of cobalt in nanoparticles that accumulate in tumors
Authors: Pablo Hervella, Johan Hygum Dam, Helge Thisgaard, Christina Baun, Birgitte Brinkmann Olsen, Poul Flemming Høilund-Carlsen, David Needham
Journal: Journal of Controlled Release (2018)
RCGP chair refutes tech companies claims that GPs are “technophobic dinosaurs”
Authors: Abi Rimmer
Journal: BMJ (2018)

The chair of the Royal College of General Practitioners has accused technology companies of cherry picking patients and denied claims that GPs are “technophobic dinosaurs.”

Speaking at the college’s annual conference in Glasgow on 4 October, Helen Stokes-Lampard said, “I get exasperated when I hear accusations that GPs are technophobic dinosaurs. What utter nonsense.”

She added, “GPs are not ‘afraid’ of technology or innovation. But robots don’t come cheap, tech costs money, and for GP practices that are already on the brink, implementing new, good technology is unfeasible.”

Stokes-Lampard accused technology companies that offer digital consultations of creating a divide between young and fit patients and those who are more in need.

“Those with the latest smartphone, those …
B Cells Are the Dominant Antigen-Presenting Cells that Activate Naive CD4+ T Cells upon Immunization with a Virus-Derived Nanoparticle Antigen
Authors: Sheng Hong, Zhimin Zhang, Hongtao Liu, Meijie Tian, Xiping Zhu, Zhuqiang Zhang, Weihong Wang, Xuyu Zhou, Fuping Zhang, Qing Ge, Bing Zhu, Hong Tang, Zhaolin Hua, Baidong Hou
Journal: Immunity (2018)
Abstract 15335: Albuminuria as a Predictor of Cardiovascular Outcomes in Patients With Acute Myocardial Infarction
Authors: Yejin Mok, Shoshana Ballew, Morgan Grams, Josef Coresh, Juan-Jesus Carrero, Marie Evans, Peter Barany, Kunihiro Matsushita
Journal: Circulation (2017)

Background: Current guidelines recommend characterizing chronic kidney disease (CKD) with both glomerular filtration rate (GFR) and albuminuria. Reduced GFR is common and predicts poor prognosis in...
Variable RNA sequencing depth impacts gene signatures and target compound robustness – case study examining brain tumour (glioma) disease progression
Authors: Dr Alexey Stupnikov, Dr Caitríona McInerney, Dr Paul O’reilly, Aideen Roddy, Dr Philip Dunne, Mr Alan Gilmore, Dr Hayley Ellis, Mr Tom Flannery, Dr Estelle Healy, Dr Stuart Mcintosh, Dr Kienan Savage, Prof Manuel Salto-Tellez, Dr Frank Emmert-streib, Dr Kathreena Kurian, Prof Kevin Prise, Dr Darragh McArt
Journal: Neuro-Oncology (2018)

Available treatments for glioma have limited effectiveness rendering this a disease of poor clinical outcome. Gene expression profiling can uncover the biological mechanisms underlying disease, information that is crucial for drug development or repurposing. RNA sequencing (RNA-seq) is routinely used to assess gene expression but costs remain high. Whilst sample multiplexing reduces RNA-seq costs, the lowered cDNA sequencing depth of multiplexed samples may hinder accurate differential gene expression detection. The impact of sequencing depth alteration on RNA-seq-based downstream analyses such as gene expression connectivity mapping is not known. Connectivity mapping is a method used to identify potential therapeutic compounds for drug repurposing. In this study, published RNA-seq from brain tumour (glioma) patients were analysed and assembled into two gene signature contrasts for astrocytoma disease progression (WHO Grade II-III; III-IV). Gene signatures were subsampled to simulate sequencing depth alterations and analysed in connectivity mapping to investigate target compound robustness. Data loss to gene signatures led to the loss, gain and consistent identification of significant connections to target compounds. The most accurate gene signature contrast with consistent patient gene expression profiles was more resilient to data loss and identified robust target compounds. Target compounds lost included candidate compounds of potential clinical utility in glioma (e.g. Suramin, Dasatinib). Lost connections may have been linked to low abundance genes in the gene signature that closely characterised the disease phenotype. Consistently identified connections may have related to highly expressed abundant genes that were ever-present in gene signatures, despite data reductions. Potential noise surrounding findings included false positive connections that were gained as a result of gene signature modification with data loss. Findings highlight the necessity for gene signature accuracy for connectivity mapping, which should improve the clinical utility of future target compounds identified for drug repurposing.
A Premature Termination Codon Mutation in MYBPC3 Causes Hypertrophic Cardiomyopathy via Chronic Activation of Nonsense-Mediated Decay
Authors: Timon Seeger, Rajani Shrestha, Chi Keung Lam, Caressa Chen, Wesley L. McKeithan, Edward Lau, Alexa Wnorowski, George McMullen, Matthew Greenhaw, Jaecheol Lee, Angelos Oikonomopoulos, Soah Lee, Huaxiao Yang, Mark Mercola, Matthew Wheeler, Euan A. Ashley, Fan Yang, Ioannis Karakikes, Joseph C. Wu
Journal: Circulation (2019)

Hypertrophic cardiomyopathy (HCM) is frequently caused by mutations in myosin-binding protein C3 ( MYBPC3) resulting in a premature termination codon (PTC). The underlying mechanisms of how PTC mutations in MYBPC3 lead to the onset and progression of HCM are poorly understood. This study's aim was to investigate the molecular mechanisms underlying the pathogenesis of HCM associated with MYBPC3 PTC mutations by utilizing human isogenic induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs).Isogenic iPSC lines were generated from HCM patients harboring MYBPC3 PTC mutations (p.R943x; p.R1073P_Fsx4) using genome editing. Comprehensive phenotypic and transcriptome analyses were performed in the iPSC-CMs.We observed aberrant calcium handling properties with prolonged decay kinetics and elevated diastolic calcium levels in the absence of structural abnormalities or contracile dysfunction in HCM iPSC-CMs as compared to isogenic controls. The mRNA expression levels of MYBPC3 were significantly reduced in mutant iPSC-CMs, but the protein levels were comparable among isogenic iPSC-CMs, suggesting that haploinsufficiency of MYBPC3 does not contribute to the pathogenesis of HCM in vitro. Furthermore, truncated MYBPC3 peptides were not detected. At the molecular level, the nonsense-mediated decay pathway was activated, and a set of genes involved in major cardiac signaling pathways was dysregulated in HCM iPSC-CMs, indicating an HCM gene signature in vitro. Specific inhibition of the nonsense-mediated decay pathway in mutant iPSC-CMs resulted in reversal of the molecular phenotype and normalization of calcium-handling abnormalities.iPSC-CMs carrying MYBPC3 PTC mutations displayed aberrant calcium signaling and molecular dysregulations in the absence of significant haploinsufficiency of MYBPC3 protein. Here we provided the first evidence of the direct connection between the chronically activated nonsense-mediated decay pathway and HCM disease development.
Abstract P165: Lifestyle Counseling Practices and Referrals for CVD Prevention by Primary Care Providers
Authors: John D Omura, Kathleen B Watson, Fleetwood Loustalot, Gayathri Kumar, Susan A Carlson
Journal: Circulation (2017)

Background: The US Preventive Services Task Force recommends that adults who are overweight or obese and have additional cardiovascular disease (CVD) risk factors be offered or referred to intensive behavioral counseling interventions to promote a healthful diet and physical activity for CVD prevention. However, it is unknown what resources primary care providers (PCPs) refer patients to for this service. This study determined the proportion of PCPs who referred patients to different health sector and community resources to receive intensive behavioral counseling and whether this differed by physical activity counseling frequency. Methods: DocStyles 2016, a Web-based panel survey of 1256 PCPs (response rate=64.5%), assessed physical activity counseling practices for those patients at risk for CVD(overweight or obese and with hypertension, dyslipidemia, impaired fasting glucose, or metabolic syndrome). Results: Overall, 78.0% (SE=1.2) of PCPs referred any of their at risk patients to intensive behavioral counseling. The providers and services to which these PCPs referred patients to ranged from 25.4% to a healthcare worker within their practice or group to 41.3% to an organized program in a medical facility (TABLE). PCPs who discussed physical activity with many or most of their at risk patients were more likely to refer to an organized program within the community setting and less likely to refer to a healthcare worker outside their practice or group than their respective counterparts. Conclusion: Differences in the providers and services PCPs referred to for intensive behavioral counseling were observed by physical activity counseling frequency. Future work could explore the influence that the availability of different resources, especially community programs, has on improving PCPs’ physical activity counseling practices.
MEPOLIZUMAB FOR THE TREATMENT OF PATIENTS WITH EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS: A PHASE III RANDOMISED, PLACEBO-CONTROLLED TRIAL
Authors: ME Wechsler, P Akuthota, David Jayne, P Khoury, A Klion, C Langford, PA Merkel, F Moosig, U Specks, MC Cid, R Luqmani, J Brown, S Mallett, R Philipson, SW Yancey, J Steinfeld, PF Weller, G Gleich
Journal: American Journal of Respiratory and Critical Care Medicine (2017)
Bilateral Lower Extremity Skin Eruptions in an HIV-Positive Man Receiving Pembrolizumab Monotherapy for Non–Small Cell Lung Cancer
Authors: Emily Boozalis, Shawn G. Kwatra, Kristen A. Marrone
Journal: JAMA Oncology (2018)

An HIV-positive man in his 30s being treated with pembrolizumab for metastatic programmed cell death ligand 1–positive squamous non–small cell lung cancer presents with pruritic, mildly painful, hyperpigmented papules and plaques on both feet. What is your diagnosis?
Disclosures Can Always Be Improved—Reply
Authors: Ioana-Alina Cristea, John P. A. Ioannidis
Journal: JAMA Psychiatry (2018)

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 Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Psychiatry journal
Patterns of regional lung physiology in cystic fibrosis using ventilation magnetic resonance imaging and multiple-breath washout
Authors: Laurie J. Smith, Guilhem J. Collier, Helen Marshall, Paul J.C. Hughes, Alberto M. Biancardi, Martin Wildman, Ina Aldag, Noreen West, Alex Horsley, Jim M. Wild
Journal: European Respiratory Journal (2018)

Hyperpolarised helium-3 ( 3 He) ventilation magnetic resonance imaging (MRI) and multiple-breath washout (MBW) are sensitive methods for detecting lung disease in cystic fibrosis (CF). We aimed to explore their relationship across a broad range of CF disease severity and patient age, as well as assess the effect of inhaled lung volume on ventilation distribution. 32 children and adults with CF underwent MBW and 3 He-MRI at a lung volume of end-inspiratory tidal volume (EI V T ). In addition, 28 patients performed 3 He-MRI at total lung capacity. 3 He-MRI scans were quantitatively analysed for ventilation defect percentage (VDP), ventilation heterogeneity index (VHI) and the number and size of individual contiguous ventilation defects. From MBW, the lung clearance index, convection-dependent ventilation heterogeneity (Scond) and convection–diffusion-dependent ventilation heterogeneity (Sacin) were calculated. VDP and VHI at EI V T strongly correlated with lung clearance index (r=0.89 and r=0.88, respectively), Sacin (r=0.84 and r=0.82, respectively) and forced expiratory volume in 1 s (FEV 1 ) (r=−0.79 and r=−0.78, respectively). Two distinct 3 He-MRI patterns were highlighted: patients with abnormal FEV 1 had significantly (p&lt;0.001) larger, but fewer, contiguous defects than those with normal FEV 1 , who tended to have numerous small volume defects. These two MRI patterns were delineated by a VDP of ∼10%. At total lung capacity, when compared to EI V T , VDP and VHI reduced in all subjects (p&lt;0.001), demonstrating improved ventilation distribution and regions of volume-reversible and nonreversible ventilation abnormalities.
Abstract 13554: Left Atrial Function in Children by Volume and Strain Analysis: Impact of Congenital Aortic Stenosis
Authors: Divya Shakti, Kevin G Freidman, David M Harrild, Kimberly Gauvreau, Tal Geva, Steven D Colan, David W Brown
Journal: Circulation (2015)

Background: Left atrial (LA) function by volume and strain analysis in children has been little studied. LA dysfunction related to aortic stenosis has been reported in adults. Hypotheses: 1. LA volume and strain analysis is feasible and reproducible in normal children. 2. Children with isolated congenital aortic stenosis (AS) as compared to matched controls have higher maximal LA volume (LAV) and lower total longitudinal LA strain. Methods: Retrospective chart review and offline analysis of 2D echocardiogram images for phasic LAVs, volume indices, and longitudinal LA strain (Fig 1) by speckle tracking (TomTec software) in: 1. Healthy children with a normal echocardiogram; and, 2. Children ≥1 years of age with significant (≥ moderate) isolated AS. AS cases were compared with age, gender and BSA-matched normal controls. Results: There were 67 normal subjects [age: 10.5 (1.3-22.1) yrs; 50 males, 17 females; BSA 1.22 (0.44-2.39) m2] studied. No significant inter-observer and intra-observer differences were noted in normal subjects (Fig 2). Between June 2004 and October 2012, there were 41 eligible AS cases [Age: 11.7 (1.6-26.8) yrs; 32 males, 9 females] with median maximal Doppler aortic stenosis gradient of 63 (43-94) mm Hg. Significantly higher phasic indexed LAVs and indexed active LA stroke volume (pump function) and lower strain values for LA reservoir and conduit function were noted in AS cases (Fig 2). Conclusions: LA volume and strain analysis is reproducible and feasible in children. Children with significant AS have abnormal LA function with higher phasic LA volumes, higher LA pump function, and lower strain-derived reservoir and conduit LA function.
Blood-Based Prediction of Tumor Relapse: The cfDNA Forecast
Authors: Giulia Siravegna, Ryan B. Corcoran
Journal: Cancer Discovery (2018)

Abstract Summary: Khan and colleagues demonstrate how serial blood-based liquid biopsies integrated with imaging and mathematical modeling can accurately “forecast” the time to treatment failure in patients with metastatic colorectal cancer treated with EGFR blockade, by early detection of molecular alterations associated with drug resistance in cell-free DNA. Cancer Discov; 8(10); 1213–5. ©2018 AACR. See related article by Khan et al., p. 1270.