tbuckley/cabot-search huggingface dataset:
Inhibitory effect of glucocorticoids on TGF-β1-mediated epithelial-to-mesenchymal transition of airway epithelium via MAPK and Snail/Slug signaling pathways
Authors: Heung Man Lee, Hyun-Woo Yang, Seoung Ae Lee, Joo-Hoo Park, Min-jeong Heo, Jae-Min Shin
Journal: Journal of Allergy and Clinical Immunology (2018)
Comparison of Physician Visual Assessment With Quantitative Coronary Angiography in Assessment of Stenosis Severity in China
Authors: Haibo Zhang, Lin Mu, Shuang Hu, Brahmajee K. Nallamothu, Alexandra J. Lansky, Bo Xu, Georgios Bouras, David J. Cohen, John A. Spertus, Frederick A. Masoudi, Jeptha P. Curtis, Runlin Gao, Junbo Ge, Yuejin Yang, Jing Li, Xi Li, Xin Zheng, Yetong Li, Harlan M. Krumholz, Lixin Jiang
Journal: JAMA Internal Medicine (2018)

<h3>Importance</h3> Although physician visual assessment (PVA) of stenosis severity is a standard clinical practice to support decisions for coronary revascularization, there are concerns about its accuracy. <h3>Objective</h3> To compare PVA with quantitative coronary angiography (QCA) as a means of assessing stenosis severity among patients undergoing percutaneous coronary intervention (PCI) in China. <h3>Design, Setting, and Participants</h3> A cross-sectional study (2012-2013) of a random subset of 1295 patients from the China Patient-centered Evaluative Assessment of Cardiac Events (PEACE) Prospective PCI Study was carried out. The PEACE Prospective PCI study recruited a consecutive sample of patients undergoing PCI at 35 hospitals in 18 provinces of China. The coronary angiograms of this subset of participants were reviewed using QCA by 2 independent core laboratories blinded to PVA readings. <h3>Main Outcomes and Measures</h3> Differences between PVA and QCA assessments of stenosis severity for lesions for which PCI was performed and variation of these differences among hospitals and physicians, stratified by the diagnosis of acute myocardial infarction (AMI). <h3>Results</h3> In patients without AMI, the mean (SD) age was 62 (10) years, and 217 (31.5%) were women; in patients with AMI, the mean (SD) age was 60 (11) years, and 153 (25.2%) were women. The mean (SD) percent diameter stenosis by PVA was 16.0% (11.5%) greater than that by QCA in patients without AMI and 10.2% (12.3%) in those with AMI (<i>P</i> &lt; .001 for both comparisons). In patients without AMI, of 837 lesions with 70% or more stenosis by PVA, 427 (50.6%) were less than 70% by QCA; in patients with AMI, similar patterns were observed to a lesser extent. Among patients without AMI, only 4 (0.47%) lesions were additionally assessed with fractional flow reserve. Among 30 hospitals, the difference between PVA and QCA readings of stenosis severity varied from 7.6% (95% CI, 0.4%-14.7%) to 21.3% (95% CI, 17.1%-24.9%) among non-AMI patients. Across 57 physicians, this difference varied from 6.9% (95% CI, −1.4%-15.3%) to 26.4% (95% CI, 21.5%-31.4%). <h3>Conclusions and Relevance</h3> For coronary lesions treated with PCI in China, PVA reported substantially higher readings of stenosis severity than QCA, with large variation across hospitals and physicians. These findings highlight the need to improve the accuracy of information used to guide treatment decisions in catheterization laboratories.
Nondestructive Analysis of Tumor-Associated Membrane Protein Integrating Imaging and Amplified Detection in situ Based on Dual-Labeled DNAzyme
Authors: Xiaoxia Chen, Jing Zhao, Tianshu Chen, Tao Gao, Xiaoli Zhu, Genxi Li
Journal: Theranostics (2018)

Comprehensive analysis of the expression level and location of tumor-associated membrane proteins (TMPs) is of vital importance for the profiling of tumor cells.Currently, two kinds of independent techniques, i.e. ex situ detection and in situ imaging, are usually required for the quantification and localization of TMPs respectively, resulting in some inevitable problems.Methods: Herein, based on a well-designed and fluorophore-labeled DNAzyme, we develop an integrated and facile method, in which imaging and quantification of TMPs in situ are achieved simultaneously in a single system.The labeled DNAzyme not only produces localized fluorescence for the visualization of TMPs but also catalyzes the cleavage of a substrate to produce quantitative fluorescent signals that can be collected from solution for the sensitive detection of TMPs.Results: Results from the DNAzyme-based in situ imaging and quantification of TMPs match well with traditional immunofluorescence and western blotting.In addition to the advantage of two-in-one, the DNAzyme-based method is highly sensitivity, allowing the detection of TMPs in only 100 cells.Moreover, the method is nondestructive.Cells after analysis could retain their physiological activity and could be cultured for other applications. Conclusion:The integrated system provides solid results for both imaging and quantification of TMPs, making it a competitive method over some traditional techniques for the analysis of TMPs, which offers potential application as a toolbox in the future.
Executive summary of the methods report for ‘The EAACI/GA<sup>2</sup>LEN/EDF/WAO Guideline for the Definition, Classification, Diagnosis and Management of Urticaria. The 2017 Revision and Update’
Authors: C. Dressler, S. Rosumeck, R. N. Werner, M. Magerl, M. Metz, M. Maurer, A. Nast, T. Zuberbier
Journal: Allergy (2018)

None Declared. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
O Programa de Formação em Epidemiologia de Campo (FETP) na Alemanha
Authors: L R Petersen, T Breuer, O Hamouda, A Ammon
Journal: Eurosurveillance (2001)

O Programa Alemao de Formacao em Epidemiologia de Campo (FETP), iniciado em Janeiro de 1996, faz parte de um esforco nacional para a melhoria da capacidade de investigacao epidemiologica das doencas infecciosas na Alemanha (1). O objectivo do programa, com a duracao de dois anos, consiste no desenvolvimento de um nucleo de epidemiologistas capazes de efectuarem investigacoes de surtos, investigacao epidemiologica e vigilância a nivel dos padroes internacionais, conforme os artigos publicados nos jornais internacionais da especialidade. Sera igualmente solicitado a estes epidemiologistas que facultem formacao aos epidemiologistas futuros e ao pessoal que trabalha na area da saude publica. O programa e semelhante ao do Epidemic Intelligence Service (EIS) nos Centers for Disease Control and Prevention (CDC)) dos Estados Unidos e ao Programa Europeu de Formacao em Epidemiologia de Intervencao (EPIET) (2,3). O Ministerio Federal Alemao da Educacao e Investigacao financiou as despesas para que um epidemiologista senior, com a ajuda do CDC, iniciasse este programa.
Airway IL-1α promotes development of allergen-specific follicular helper T (Tfh) cells and production of IgE antibody
Authors: Takayasu Nomura, Takao Kobayashi, Koji Iijima, Hirohito Kita
Journal: Journal of Allergy and Clinical Immunology (2018)

Recent literature suggests that Tfh cells that produce IL-4 play a pivotal role in allergic immune responses. However, the molecular and immunological mechanisms involved in the development of Tfh cells are not fully understood. The goal of this study was to test the hypothesis that IL-1α released from alveolar macrophage plays a pivotal role in respiratory allergy. Naïve wild-type BALB/c mice and IL-4 reporter 4get mice were exposed intranasally (i.n.) to a model antigen ovalbumin (OVA) with or without serial dilutions of IL-1α. Development of allergic immune responses was analyzed by collecting mediastinal lymph nodes (mLNs) and sera, and by challenging the animals i.n. with OVA antigen. Alveolar macrophages were isolated of naïve BALB/c mice and stimulated in vitro with pollens of short ragweed or Japanese cedar. The mice exposed i.n. to OVA with IL-1α produced OVA-specific IgE antibody; the IgE response was dependent on the doses of IL-1α. These mice showed airway eosinophilia and increased lung levels of type 2 cytokines when challenged i.n. with OVA. Marked increase in the IL-4eGFP+CD4+CXCR5+ST2- Tfh cell population was observed in mLNs of mice exposed OVA plus IL-1α as compared to those mice exposed to OVA alone. Furthermore, alveolar macrophages produced and released IL-1α extracellular when they were exposed to allergen pollens in vitro. IL-1α produced by alveolar macrophages by airway allergen exposure may paly a pivotal role to promote generation of antigen-specific Tfh cells and hence development of respiratory allergy.
Optimal Use of Preoperative Imaging in Primary Hyperparathyroidism
Authors: Emma Collins, Sriram Vaidyanathan, Andrew Scarsbrook
Journal: JAMA Surgery (2018)

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Screening for Adolescent Idiopathic Scoliosis
Authors: David C. Grossman, Susan J. Curry, Douglas K. Owens, Michael J. Barry, Karina W. Davidson, Chyke A. Doubeni, John W. Epling, Alex R. Kemper, Alex H. Krist, Ann E. Kurth, C. Seth Landefeld, Carol M. Mangione, Maureen G. Phipps, Michael Silverstein, Melissa A. Simon, Chien-Wen Tseng
Journal: JAMA (2018)

<h3>Importance</h3> Adolescent idiopathic scoliosis, a lateral curvature of the spine of unknown cause with a Cobb angle of at least 10°, occurs in children and adolescents aged 10 to 18 years. Idiopathic scoliosis is the most common form and usually worsens during adolescence before skeletal maturity. Severe spinal curvature may be associated with adverse long-term health outcomes (eg, pulmonary disorders, disability, back pain, psychological effects, cosmetic issues, and reduced quality of life). Early identification and effective treatment of mild scoliosis could slow or stop curvature progression before skeletal maturity, thereby improving long-term outcomes in adulthood. <h3>Objective</h3> To update the 2004 US Preventive Services Task Force (USPSTF) recommendation on screening for idiopathic scoliosis in asymptomatic adolescents. <h3>Evidence Review</h3> The USPSTF reviewed the evidence on the benefits and harms of screening for and treatment of adolescent idiopathic scoliosis. <h3>Findings</h3> The USPSTF found no direct evidence on screening for adolescent idiopathic scoliosis and health outcomes and no evidence on the harms of screening. The USPSTF found inadequate evidence on treatment with exercise and surgery. It found adequate evidence that treatment with bracing may slow curvature progression in adolescents with mild or moderate curvature severity (Cobb angle &lt;40° to 50°); however, evidence on the association between reduction in spinal curvature in adolescence and long-term health outcomes in adulthood is inadequate. The USPSTF found inadequate evidence on the harms of treatment. Therefore, the USPSTF concludes that the current evidence is insufficient and that the balance of benefits and harms of screening for adolescent idiopathic scoliosis cannot be determined. <h3>Conclusions and Recommendation</h3> The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for adolescent idiopathic scoliosis in children and adolescents aged 10 to 18 years. (I statement)
Mitigating risk of injury in alpine skiing in the Pyeongchang 2018 Paralympic Winter Games: the time is now!
Authors: Wayne Derman, Cheri Blauwet, Nick Webborn, Martin Schwellnus, Peter Van de Vliet, Dimitrije Lazarovski
Journal: British Journal of Sports Medicine (2018)

The sport of Para alpine skiing at the Sochi 2014 Paralympic Winter Games has been under the spotlight as having the highest injury incidence rate (IR) compared with other sports on the programme,1 and also compared with alpine skiing at any previous Paralympic Winter Games.2 3 A secondary analysis of the Paralympic Injury and Illness Survey for the Sochi Games has allowed for a more detailed reporting of injury mechanism.

In Sochi, a total of 175 athletes (131 male, 44 female) participated in the Para alpine skiing competitions. This comprised 65 seated athletes and 110 standing athletes. The overall injury IR in alpine skiing was 48.3 (95% CI 40.1 to 56.4) injuries per 1000 athlete-days, while the overall injury proportion was 30.9 (95% CI 24.0 to 37.7) injuries per 100 athletes. The comparative injury IR in the different athlete categories is shown in figure 1.



Figure 1 
Injury incidence rate (IR) in Para alpine skiing at the Sochi 2014 Paralympic Winter Games.



Upon further analysis of the data, …
Impact of denosumab (DMB) compared with zoledronic acid (ZA) on renal function in the treatment of myeloma bone disease.
Authors: Noopur S. Raje, G. David Roodman, Wolfgang Willenbacher, Kazuyuki Shimizu, Ramon Garcia-Sanz, Brian G. Durie, Li Zhu, Paul C. Cheng, Sumita Bhatta, Evangelos Terpos
Journal: Journal of Clinical Oncology (2017)

8005 Background: Osteolytic bone disease and renal dysfunction are complications of multiple myeloma. ZA, used for the prevention and treatment of bone complications, can be nephrotoxic. DMB inhibits RANKL and thereby osteoclast function, and is not renally cleared. This international, phase III, randomized, double blind study evaluates the efficacy and safety of DMB compared with ZA in newly diagnosed myeloma patients (pts). Methods: Eligible pts were randomized 1:1 to DMB 120mg SC Q4W or ZA 4mg (renally adjusted) IV Q4W along with anti-myeloma therapy. Pts with baseline CrCl&lt;30mL/min were excluded due to ZA dosing restrictions. The primary endpoint was non-inferiority of DMB to ZA with respect to time to first on-study SRE. Overall survival (OS) was a secondary endpoint; progression-free survival (PFS) was an exploratory endpoint. Renal toxicity and safety were assessed. Results: 1718 pts were randomized, 859 to each arm. Baseline renal insufficiency (CrCl ≤ 60mL/min) was reported in 26.7% of pts. DMB was non-inferior to ZA ( P = 0.01) in delaying time to first on-study SRE. Fewer AEs potentially related to renal toxicity were reported with DMB compared to ZA overall (10.0% vs 17.1%, P &lt; 0.001) in those with baseline CrCl &gt; 60mL/min (8.8% vs 14.2%) and particularly in those with baseline CrCl ≤ 60mL/min (12.9% vs 26.4%). 12.5% of pts on DMB experienced an increase in creatinine, compared to 20.8% of those on ZA. Median cumulative exposure (Q1, Q3) to DMB was 15.75 months (8.18, 25.79) compared to 14.78 months (7.46, 24.87) for ZA. PFS yielded a HR (95%CI) of 0.82 (0.68, 0.99); descriptive P = 0.036. OS HR (95%CI) between DMB and ZA was 0.9 ([0.70, 1.16]; P = 0.41), with fewer deaths in DMB (121 [14.1%]) than in ZA (129 [15.0%]). Conclusions: DMB achieved the primary endpoint of non-inferiority to ZA in delaying time to first on study SRE in pts with newly diagnosed MM. Pts on DMB had a significantly lower rate of renal AEs compared to ZA; more importantly this rate was 2-fold lower in pts with renal insufficiency (CrCl≤60mL/min). The bone specific benefits in combination with the renal function results and possible prolongation of PFS with DMB therapy is promising. Clinical trial information: NCT01345019.
Cellular Defects Amongst Common Variable Immunodeficiency (CVID) Patients with Chronic Lung Disease in the USIDNET (United States Immunodeficiency Network) Cohort
Authors: Erinn S. Kellner, Ramsay L. Fuleihan, Charlotte Cunningham-Rundles, Joshua B. Wechsler
Journal: Journal of Allergy and Clinical Immunology (2018)
MiR-205-5p and miR-342-3p cooperate in the repression of the E2F1 transcription factor in the context of anticancer chemotherapy resistance
Authors: Xin Lai, Shailendra K Gupta, Ulf Schmitz, Stephan Marquardt, Susanne Knoll, Alf Spitschak, Olaf Wolkenhauer, Brigitte M Pützer, Julio Vera
Journal: Theranostics (2018)

High rates of lethal outcome in tumour metastasis are associated with the acquisition of invasiveness and chemoresistance.Several clinical studies indicate that E2F1 overexpression across high-grade tumours culminates in unfavourable prognosis and chemoresistance in patients.Thus, fine-tuning the expression of E2F1 could be a promising approach for treating patients showing chemoresistance.Methods: We integrated bioinformatics, structural and kinetic modelling, and experiments to study cooperative regulation of E2F1 by microRNA (miRNA) pairs in the context of anticancer chemotherapy resistance.Results: We showed that an enhanced E2F1 repression efficiency can be achieved in chemoresistant tumour cells through two cooperating miRNAs.Sequence and structural information were used to identify potential miRNA pairs that can form tertiary structures with E2F1 mRNA.We then employed molecular dynamics simulations to show that among the identified triplexes, miR-205-5p and miR-342-3p can form the most stable triplex with E2F1 mRNA.A mathematical model simulating the E2F1 regulation by the cooperative miRNAs predicted enhanced E2F1 repression, a feature that was verified by in vitro experiments.Finally, we integrated this cooperative miRNA regulation into a more comprehensive network to account for E2F1-related chemoresistance in tumour cells.The network model simulations and experimental data indicate the ability of enhanced expression of both miR-205-5p and miR-342-3p to decrease tumour chemoresistance by cooperatively repressing E2F1.Conclusions: Our results suggest that pairs of cooperating miRNAs could be used as potential RNA therapeutics to reduce E2F1-related chemoresistance.
The Emergence of Clinical Research Ethics Consultation: Insights From a National Collaborative
Authors: Kathryn M. Porter, Marion Danis, Holly A. Taylor, Mildred K. Cho, Benjamin S. Wilfond
Journal: The American Journal of Bioethics (2018)

The increasing complexity of human subjects research and its oversight has prompted researchers, as well as institutional review boards (IRBs), to have a forum in which to discuss challenging or novel ethical issues not fully addressed by regulations. Research ethics consultation (REC) services provide such a forum. In this article, we rely on the experiences of a national Research Ethics Consultation Collaborative that collected more than 350 research ethics consultations in a repository and published 18 challenging cases with accompanying ethical commentaries to highlight four contexts in which REC can be a valuable resource. REC assists: 1) investigators before and after the regulatory review; 2) investigators, IRBs, and other research administrators facing challenging and novel ethical issues; 3) IRBs and investigators with the increasing challenges of informed consent and risk/benefit analysis; and 4) in providing flexible and collaborative assistance to overcome study hurdles, mediate conflicts within a team, or directly engage with research participants. Institutions that have established, or plan to establish, REC services should work to raise the visibility of their service and engage in open communication with existing clinical ethics consult services as well as the IRB. While the IRB system remains the foundation for the ethical review of research, REC can be a valuable service for investigators, regulators, and research participants aligned with the goal of supporting ethical research.
Epithelial-mesenchymal transition leads to NK cell–mediated metastasis-specific immunosurveillance in lung cancer
Authors: Peter J. Chockley, Jun Chen, Guoan Chen, David G. Beer, Theodore J. Standiford, Venkateshwar G. Keshamouni
Journal: Journal of Clinical Investigation (2018)

During epithelial-mesenchymal transition (EMT) epithelial cancer cells transdifferentiate into highly motile, invasive, mesenchymal-like cells, giving rise to disseminating tumor cells. Few of these disseminated cells successfully metastasize. Immune cells and inflammation in the tumor microenvironment were shown to drive EMT, but few studies investigated the consequences of EMT for tumor immunosurveillance. In addition to initiating metastasis, we demonstrate that EMT confers increased susceptibility to natural killer (NK) cells and contributes, in part, to the inefficiency of the metastatic process. Depletion of NK cells allowed spontaneous metastasis without affecting primary tumor growth. EMT-induced modulation of E-cadherin and cell adhesion molecule 1 (CADM1) mediated increased susceptibility to NK cytotoxicity. Higher CADM1 expression correlates with improved patient survival in 2 lung and 1 breast adenocarcinoma patient cohorts and decreased metastasis. Our observations reveal a novel NK-mediated, metastasis-specific immunosurveillance in lung cancer and present a window of opportunity for preventing metastasis by boosting NK cell activity.
Abstract 17989: Early Tricuspid Regurgitation in Hypoplastic Left Heart Syndrome is Not Related to Right Ventricular Function or Mechanical Dyssynchrony
Authors: Silvia Alvarez, Nee Khoo, Kandice Mah, Nassiba Alami Laroussi, Edythe Tham, Shelby Kutty, Jeffrey Smallhorn, Timothy Colen
Journal: Circulation (2016)

Background:  Tricuspid regurgitation (TR) is associated with morbidity and mortality in hypoplastic left heart syndrome (HLHS). We have previously demonstrated that TR prior to stage 2 (S2) surgical palliation is related to tricuspid valve (TV) abnormalities, including dilated annulus and increased leaflet prolapse. Right ventricular (RV) dysfunction and mechanical dyssynchrony have been reported as causes for TR. Thus, we hypothesized that TR and abnormal TV parameters are associated with RV dysfunction. This study explored the relationship between TV and RV function using quantitative three dimensional echocardiography (3DE) measure of TV parameters and speckle tracking echocardiography (STE) of RV deformation, in HLHS with and without TR.   Methods and Results:  Forty-four HLHS patients with median age of 4.7 months (IQR 3.9-5.3) were prospectively recruited prior to S2 palliation. TV parameters assessed using 3DE, included vena contracta area (VCA), leaflet area, prolapse volume, tethering volume, annular bending angle and papillary muscle angle. RV systolic function was assessed by fractional area change and STE derived longitudinal and circumferential strain, strain rate and mechanical dyssynchrony index (MDI). The group was divided into those with (group A) and those without (group B) significant TR by qualitative assessment. RV functional parameters were compared between the two groups using Mann-Whitney signed rank test and Spearman correlation of TV leaflet and annulus area, prolapse and tethering volume, bending angle and VCA, to longitudinal and circumferential strain, strain rate and MDI were performed. Fourteen patients (32%) had moderate or greater TR (group A). RV function parameters were not different between group A and group B. There was no correlation between all 3DE TV parameters and STE RV deformation parameters.   Conclusion:  Contrary to our hypothesis, HLHS RV systolic dysfunction and mechanical dyssynchrony do not play a significant role in early TR. This finding suggests the mechanisms of early TR in HLHS are likely to be secondary to valve and leaflet differences.