tbuckley/cabot-search huggingface dataset:
Abstract 12203: Fxr1 Regulates Inflammatory mRA Stability and Vascular Disease
Authors: Allison Herman, Sheri Kelemen, Dale Haines, Michael Autieri
Journal: Circulation (2016)

Introduction: Vascular smooth muscle cells (VSMC) play a critical role in the etiology and progression of many vascular diseases, and reduction of inflammatory gene expression in VSMC is a rational approach to limit the severity of these diseases. HuR is an mRNA stability protein that recognizes AU-rich elements (ARE) present almost exclusively in the 3’UTR of pro-inflammatory gene mRNA. Proteins and pathways which limit HuR activity in vascular cells may reduce inflammatory mRNA stability, but are currently uncharacterized. Using un-biased LC-MS/MS to identify HuR-interacting proteins under different inflammatory conditions, we identified one protein termed Fragile X-related protein (FXR1), which interacts with HuR in inflammatory, but not basal conditions. Results and Conclusions: Using immunohistochemical and molecular biological approaches, preliminary data shows that FXR1 expression is increased in VSMC in plaque from atherosclerotic mouse and human arteries. FXR1 translocates from the nucleus into the cytoplasm and co-localizes with HuR in cytoplasm. FXR1 expression is also increased by TNFα and oxLDL stimulation of cultured human VSMC. Importantly, siRNA knock down of FXR1 in VSMC increases inflammatory mRNA stability, increases abundance of ARE-containing inflammatory proteins, and increases cholesterol uptake. Surprisingly, FXR1 expression is also increased by anti-inflammatory interleukins. Since FXR1 is induced by both pro-inflammatory stimuli as well as IL-19, and yet deletion of FXR1 leads to enhanced expression of pro-inflammatory proteins, our overall hypothesis is that FXR1 expression is a negative, compensatory, counter-regulatory mechanism used by VSMC to respond to and dampen inflammation. Our specific hypothesis is that FXR1 antagonizes HuR function by numerous mechanisms leading to a reduction in stability of pro-inflammatory, ARE-containing mRNA. Currently, very little is understood concerning negative regulation of inflammatory mRNA stability, particularly so in vascular disease. Nothing at all is known about FXR1 expression and function in VSMC and vascular disease. This work may identify FXR1 as part of an anti-inflammatory gene expression program and uncover a novel role for FXR1 in vascular disease.
Youth Opinions About Guns and Gun Control in the United States
Authors: Murphy Van Sparrentak, Tammy Chang, Alison L. Miller, Lauren P. Nichols, Kendrin R. Sonneville
Journal: JAMA Pediatrics (2018)

Young activists and mass-shooting survivors in the United States have recently been organizing protests and demanding increased gun control measures.Although national polls have tracked adult opinions about gun control policies for decades, little is known about how youth feel about guns and/or gun control.Because the youth perspective is a powerful factor in the public debate, the goal of this study was to characterize youth opinions on guns and gun control.Methods | Participants came from the National MyVoice Text Message Cohort 1 and were recruited through targeted Facebook and Instagram advertisements to match national benchmarks based on weighted samples from the 2016 American Community Survey, including age, gender, race/ ethnicity, educational level, family income, and region of the country.MyVoice is a large-scale longitudinal mixed methods study of youth.Although MyVoice is not a nationally representative sample, participants are recruited on the basis of the American Community Survey benchmarks to ensure a meaningful and diverse sample.
Prophylactic Haloperidol for Critically Ill Adults—Reply
Authors: Mark van den Boogaard, Arjen J. C. Slooter, Peter Pickkers
Journal: JAMA (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 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
Detection of EGFR mutations in plasma circulating tumour DNA as a selection criterion for first-line gefitinib treatment in patients with advanced lung adenocarcinoma (BENEFIT): a phase 2, single-arm, multicentre clinical trial
Authors: Zhijie Wang, Ying Cheng, Tongtong An, Hongjun Gao, Kai Wang, Qing Zhou, Yanping Hu, Yong Song, Cuimin Ding, Feng Peng, Li Liang, Yi Hu, Cheng Huang, Caicun Zhou, Yuankai Shi, Li Zhang, Xin Ye, Meizhuo Zhang, Shaokun Chuai, Guanshan Zhu, Jin Hu, Yi-long Wu, Jie Wang
Journal: The Lancet Respiratory Medicine (2018)
Pregnane X Receptor Regulates Liver Size and Liver Cell Fate by Yes‐Associated Protein Activation in Mice
Authors: Yiming Jiang, Dechun Feng, Xiaochao Ma, Shicheng Fan, Yue Gao, Kaili Fu, Ying Wang, Jiahong Sun, Xinpeng Yao, Conghui Liu, Huizhen Zhang, Leqian Xu, Aiming Liu, Frank J. Gonzalez, Yingzi Yang, Bin Gao, Min Huang, Huichang Bi
Journal: Hepatology (2018)

Activation of pregnane X receptor (PXR), a nuclear receptor that controls xenobiotic and endobiotic metabolism, is known to induce liver enlargement, but the molecular signals and cell types responding to PXR-induced hepatomegaly remain unknown. In this study, the effect of PXR activation on liver enlargement and cell change was evaluated in several strains of genetically modified mice and animal models. Lineage labeling using AAV-Tbg-Cre-treated Rosa26EYFP mice or Sox9-CreERT, Rosa26EYFP mice was performed and Pxr-null mice or AAV Yap short hairpin RNA (shRNA)-treated mice were used to confirm the role of PXR or yes-associated protein (YAP). Treatment with selective PXR activators induced liver enlargement and accelerated regeneration in wild-type (WT) and PXR-humanized mice, but not in Pxr-null mice, by increase of cell size, induction of a regenerative hybrid hepatocyte (HybHP) reprogramming, and promotion of hepatocyte and HybHP proliferation. Mechanistically, PXR interacted with YAP and PXR activation induced nuclear translocation of YAP. Blockade of YAP abolished PXR-induced liver enlargement in mice. Conclusion: These findings revealed a function of PXR in enlarging liver size and changing liver cell fate by activation of the YAP signaling pathway. These results have implications for understanding the physiological functions of PXR and suggest the potential for manipulation of liver size and liver cell fate.
Former GP partner who recorded images of female patients is found guilty of voyeurism
Authors: Clare Dyer
Journal: BMJ (2018)

A former partner in a general practice has been found guilty of voyeurism after secretly using mobile phones to record images of women during examinations and consultations.

A jury at Newcastle Crown Court took only an hour to convict Thair Altaii, 55, on three counts of voyeurism involving two patients between 2008 and 2014 and 300 pictures. He will be sentenced in August …
Sensitivity of Rapid Antigen Detection Tests for Chlamydia trachomatis Screening-Reply
Authors: Thomas C. Quinn
Journal: JAMA (1995)

<h3>In Reply.</h3> —We are pleased that Dr Ferris and colleagues agree that<i>C trachomatis</i>antigen detection tests, which provide results rapidly while patients are still present in clinics, provide an appealing approach to augment efforts to control<i>Chlamydia</i>infections. As suggested by our study, even with less than optimal sensitivity, such a strategy would be useful for dealing with patients who may not return for treatment. Despite our agreement in concept, however, we remain unconvinced that the performance of any currently (or previously) available rapid chlamydial antigen detection test is sufficiently sensitive to recommend widespread use. Like Ferris and colleagues, we have conducted head-to-head comparisons of the TestPack and Surecell rapid chlamydial antigen detection tests. In a subsequent multicenter study in which one of us (E.W.H.) participated,<sup>1</sup>the Surecell test performed only marginally (but not significantly) better than the TestPack. The combined sensitivities of the TestPack and Surecell tests
Decreased Expression of the Cardiac LIM Domain Protein MLP in Chronic Human Heart Failure
Authors: OliverZolk, PicoCaroni, MichaelBöhm
Journal: Circulation (2000)

Background—The cardiac LIM domain protein MLP, a member of the cysteine-rich protein family, is an essential regulator of cardiac muscle development. Mice with a disruption of the MLP gene resemble the morphological and clinical picture of dilated cardiomyopathy and heart failure in humans. We investigated whether altered MLP expression is significant for the pathogenesis of human heart failure. Methods and Results—Immunohistochemistry and in situ hybridization confirmed the expression of MLP protein and mRNA in human cardiomyocytes. Western blot analysis revealed that the MLP peptide was present in the contractile protein fraction but not in the cytosolic or membrane fraction and that the binding of MLP to myofibrils required functional zinc finger domains. MLP immunoreactivity was decreased ≈50% (P<0.05) in the left ventricular myocardium of patients with chronic heart failure due to dilated or ischemic cardiomyopathy compared with non-failing donor hearts. MLP mRNA expression, as assessed by Northern b...
Measuring health and economic wellbeing in the Sustainable Development Goals era: development of a poverty-free life expectancy metric and estimates for 90 countries
Authors: Carlos Riumallo-Herl, David Canning, Joshua A Salomon
Journal: The Lancet Global Health (2018)

BackgroundThe Sustainable Development Goals (SDGs), adopted in September, 2015, emphasise the link between health and economic development policies. Despite this link, and the multitude of targets and indicators in the SDGs and other initiatives, few monitoring tools explicitly incorporate measures of both health and economic status. Here we propose poverty-free life expectancy (PFLE) as a new metric that uses widely available data to provide a composite measure of population health and economic wellbeing.MethodsWe developed a population-level measure of PFLE and computed this summary measure for 90 countries with available data. Specifically, we used Sullivan's method, as in many health expectancy measures, to incorporate the prevalence of poverty by age and sex from household economic surveys into demographic life tables based on mortality rates from the 2015 Global Burden of Disease Study (GBD). For comparison, we also recalculated all PFLE measures using life tables from WHO and the UN. PFLE estimates for each country, stratified by sex, are the average number of poverty-free years a person could expect to live if exposed to current mortality rates and poverty prevalence in that country.FindingsThe average PFLE in the 90 countries included in this study was 66·0 years (95% uncertainty interval [UI] 64·5–67·3) for females and 61·6 years (60·1–62·9) for males, whereas life expectancy estimates were 76·3 years (95% UI 74·0–78·2) for females and 71·0 years (68·7–73·0) for males. PFLE varied widely between countries, ranging from 9·9 years (95% UI 9·1–10·5) for both sexes combined in Malawi, to 83·2 years (83·0–83·5) in Iceland, the latter differing only marginally from life expectancy in that country. In 67 of 90 countries, the difference between life expectancy and PFLE was greater for females than for males, indicating that women generally live more years of life in poverty than men do. Results were consistent when using GBD, WHO, or UN life tables.InterpretationDifferences in PFLE between countries are substantially greater than differences in life expectancy. Despite general improvements in survival in most regions of the world in the past decades, the focus in the SDG era on ending poverty brings into sharp relief the importance of ensuring that years of added life are lived with at least a minimum standard of economic wellbeing. Although summary measures of population health provide overall measures of survivorship and functional health, our new measure of PFLE provides complementary information that can inform and benchmark policies seeking to improve both health and economic wellbeing.FundingNone.
Femoral artery ultrasound for improving the detection of atherosclerosis in psoriasis
Authors: Alvaro González-Cantero, Jorge Gonzalez-Cantero, Ana Isabel Sanchez-Moya, Cristina Perez-Hortet, Salvador Arias-Santiago, Jose Luis Martin-Rodriguez, Cristina Schoendorff-Ortega, Jorge Luis Gonzalez-Calvin
Journal: Journal of the American Academy of Dermatology (2018)
Abstract 13902: Endocardial Homogeneization of the Scar Improves the Long-term Outcomes of Catheter Ablation of Ventricular Arrhythmias in Patients With Ischemic Cardiomyopathy and Cardiac Bypass Surgery
Authors: Luigi Di Biase, Pasquale Santangeli, J. David D Burkhardt, Prasant Mohanty, Corrado Carbucicchio, Javier Sanchez, Rong Bai, Sanghamitra Mohanty, Chintan Trivedi, Francesco Santoro, Antonio Dello Russo, Michela Casella, Richard Hongo, Steven Hao, Salwa Beheiry, Rodney Horton, Dhanunjay Lakkireddy, Madhu Reddy, Robert A. Schweikert, Claude S. Elayi, Claudio Tondo, Andrea Natale
Journal: Circulation (2013)

Background: Catheter ablation of ventricular arrhythmias (VA) has shown moderate success rate at long term follow-up in patients with ischemic cardiomyopathy and previous cardiac bypass surgery (CABG). Objective: We compared two different substrate approaches for the treatment of these arrhythmias. Methods: 104 consecutive patients with ischemic cardiomyopathy and with previous CABG underwent catheter ablation for VA. Patients were treated either with limited substrate ablation confined to the endocardial isthmus responsible for the VT (Group 1, n= 52, 82% male, 62±8 years, LVEF 27±5%), or underwent endocardial ablation of all abnormal potentials within the scar in sinus rhythm (homogenization of the scar, Group 2, n=52, 80% male, 61±10 years, LVEF 26±8%). Results: Baseline characteristics were not different between groups. During a mean follow-up of 22±8 months, the VAs recurrence from any VTs was 56% (29/52 pts) in Group 1 and 25% (13/52 pts) in Group 2 (log-rank p<0.001) (figure). In addition, a higher...
Human polyspecific immunoglobulin attenuates group A streptococcal virulence factor activity and reduces disease severity in a murine necrotizing fasciitis model
Authors: A. Tarnutzer, F. Andreoni, N. Keller, C. Zürcher, A. Norrby-Teglund, R.A. Schüpbach, A.S. Zinkernagel
Journal: Clinical Microbiology and Infection (2018)
Xpert MTB/RIF Ultra assay for the diagnosis of pulmonary tuberculosis in children: a multicentre comparative accuracy study
Authors: Issa Sabi, Andrea Rachow, Daniel Mapamba, Petra Clowes, Nyanda E. Ntinginya, Mohamed Sasamalo, Lujeko Kamwela, Frederick Haraka, Michael Hoelscher, Daniel H. Paris, Elmar Saathoff, Klaus Reither
Journal: Journal of Infection (2018)
Health and wellbeing is the most common reason for doctors to take a break from training
Authors: Tom Moberly
Journal: BMJ (2018)

Health and wellbeing is the most common reason for doctors to take a break from training Tom Moberly UK editorThe BMJ Health and emotional wellbeing is the most common reason for doctors to take a from training, data from the GMC show.In total, 43% of doctors who took a break from training said they had done so for reasons related to their health and emotional wellbeing, while 32% cited career or specialty choice, and 26% cited their training or work environment.The results were drawn from the reasons provided to the GMC by 585 doctors who had taken a break from training and completed a survey on flexibility or taken part in interviews.
The Splicing Factor PTBP1 Promotes Expression of Oncogenic Splice Variants and Predicts Poor Prognosis in Patients with Non–muscle-Invasive Bladder Cancer
Authors: Pamela Bielli, Valentina Panzeri, Rossano Lattanzio, Simona Mutascio, Marco Pieraccioli, Elisabetta Volpe, Vincenzo Pagliarulo, Mauro Piantelli, Antonella Giannantoni, Savino M. Di Stasi, Claudio Sette
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Non–muscle-invasive bladder cancer (NMIBC) is a malignant disease characterized by high heterogeneity, which corresponds to dysregulated gene expression and alternative splicing (AS) profiles. Bioinformatics analyses of splicing factors potentially linked to bladder cancer progression identified the heterogeneous nuclear ribonucleoprotein I (i.e., PTBP1) as candidate. This study aimed at investigating whether PTBP1 expression associates with clinical outcome in patients with NMIBC. Experimental Design: A cohort of 152 patients presenting with primary NMIBC (pTa-pT1) was enrolled. Primary NMIBCs were assessed for PTBP1 expression by IHC, and the results were correlated with clinical data using Kaplan–Meier curves and Cox regression analyses. Cell proliferation and survival assays were performed to assess the function of PTBP1. Furthermore, the impact of PTBP1 on the AS pattern of specific bladder cancer–related genes was investigated in cancer cell lines and in patients' specimens. Results: Public datasets querying highlighted a positive correlation between PTBP1 expression and NMIBC progression, which was then confirmed by IHC analysis. High PTBP1 expression was associated with worse clinical outcome in terms of incidence of tumor relapse and survival in patients with NMIBC. Interestingly, downregulation of PTBP1 in bladder cancer cell lines affected prosurvival features. Accordingly, PTBP1 modulated AS of bladder cancer–related genes in cell lines and patient's specimens. Conclusions: PTBP1 expression correlates with disease progression, poor prognosis, and worse survival in patients with NMIBC. Downregulation of PTBP1 expression affects prosurvival features of bladder cancer cells and modulates AS of genes with relevance for bladder cancer, suggesting its role as an outcome-predictor in this disease. Clin Cancer Res; 24(21); 5422–32. ©2018 AACR.
Endothelial cell CD36 optimizes tissue fatty acid uptake
Authors: Ni-Huiping Son, Debapriya Basu, Dmitri Samovski, Terri A. Pietka, Vivek S. Peche, Florian Willecke, Xiang Fang, Shui-Qing Yu, Diego Scerbo, Hye Rim Chang, Fei Sun, Svetlana Bagdasarov, Konstantinos Drosatos, Steve T. Yeh, Adam E. Mullick, Kooresh I. Shoghi, Namrata Gumaste, KyeongJin Kim, Lesley-Ann Huggins, Tenzin Lhakhang, Nada A. Abumrad, Ira J. Goldberg
Journal: Journal of Clinical Investigation (2018)

Movement of circulating fatty acids (FAs) to parenchymal cells requires their transfer across the endothelial cell (EC) barrier. The multiligand receptor cluster of differentiation 36 (CD36) facilitates tissue FA uptake and is expressed in ECs and parenchymal cells such as myocytes and adipocytes. Whether tissue uptake of FAs is dependent on EC or parenchymal cell CD36, or both, is unknown. Using a cell-specific deletion approach, we show that EC, but not parenchymal cell, CD36 deletion increased fasting plasma FAs and postprandial triglycerides. EC-Cd36–KO mice had reduced uptake of radiolabeled long-chain FAs into heart, skeletal muscle, and brown adipose tissue; these uptake studies were replicated using [11C]palmitate PET scans. High-fat diet–fed EC-CD36–deficient mice had improved glucose tolerance and insulin sensitivity. Both EC and cardiomyocyte (CM) deletion of CD36 reduced heart lipid droplet accumulation after fasting, but CM deletion did not affect heart glucose or FA uptake. Expression in the heart of several genes modulating glucose metabolism and insulin action increased with EC-CD36 deletion but decreased with CM deletion. In conclusion, EC CD36 acts as a gatekeeper for parenchymal cell FA uptake, with important downstream effects on glucose utilization and insulin action.
Disease‐Modifying Osteoarthritis Treatment With Interleukin‐1 Receptor Antagonist Gene Therapy in Small and Large Animal Models
Authors: Alan J. Nixon, Matthew W. Grol, Hayley M. Lang, Merry Z. C. Ruan, Adrianne Stone, Laila Begum, Yuqing Chen, Brian Dawson, Francis Gannon, Stanislav Plutizki, Brendan H. L. Lee, Kilian Guse
Journal: Arthritis & Rheumatology (2018)

Gene therapy holds great promise for the treatment of osteoarthritis (OA) because a single intraarticular injection can lead to long-term expression of therapeutic proteins within the joint. This study was undertaken to investigate the use of a helper-dependent adenovirus (HDAd)-mediated intraarticular gene therapy approach for long-term expression of interleukin-1 receptor antagonist (IL-1Ra) as sustained symptomatic and disease-modifying therapy for OA.In mouse models of OA, efficacy of HDAd-IL-1Ra was evaluated by histologic analysis, micro-computed tomography (micro-CT), and hot plate analysis. In a horse OA model, safety and efficacy of HDAd-IL-1Ra were evaluated by blood chemistry, analyses of synovial fluid, synovial membrane, and cartilage, and gross pathology and lameness assessments.In skeletally immature mice, HDAd-IL-1Ra prevented development of cartilage damage, osteophytes, and synovitis. In skeletally immature and mature mice, treatment with HDAd-interleukin-1 receptor antagonist post-OA induction resulted in improved-albeit not significantly-cartilage status assessed histologically and significantly increased cartilage volume, cartilage surface, and bone surface covered by cartilage as assessed by micro-CT. Fewer osteophytes were observed in HDAd-IL-1Ra-treated skeletally immature mice. Synovitis was not affected in skeletally immature or mature mice. HDAd-IL-1Ra protected against disease-induced thermal hyperalgesia in skeletally mature mice. In the horse OA model, HDAd-IL-1Ra therapy significantly improved lameness parameters, indicating efficient symptomatic treatment. Moreover, macroscopically and histologically assessed cartilage and synovial membrane parameters were significantly improved, suggesting disease-modifying efficacy.These data from OA models in small and large animals demonstrated safe symptomatic and disease-modifying treatment with an HDAd-expressing IL-1Ra. Furthermore, this study establishes HDAd as a vector for joint gene therapy.
Dexamethasone prodrugs as potent suppressors of the immunostimulatory effects of lipid nanoparticle formulations of nucleic acids
Authors: Sam Chen, Josh Zaifman, Jayesh A. Kulkarni, Igor V. Zhigaltsev, Ying K. Tam, Marco A. Ciufolini, Yuen Yi C. Tam, Pieter R. Cullis
Journal: Journal of Controlled Release (2018)
Blocking Monocytic Myeloid-Derived Suppressor Cell Function via Anti-DC-HIL/GPNMB Antibody Restores the <i>In Vitro</i> Integrity of T Cells from Cancer Patients
Authors: Masato Kobayashi, Jin-Sung Chung, Muhammad Beg, Yull Arriaga, Udit Verma, Kevin Courtney, John Mansour, Barbara Haley, Saad Khan, Yutaka Horiuchi, Vijay Ramani, David Harker, Purva Gopal, Farshid Araghizadeh, Ponciano D. Cruz, Kiyoshi Ariizumi
Journal: Clinical Cancer Research (2018)

Blocking the function of myeloid-derived suppressor cells (MDSC) is an attractive approach for cancer immunotherapy. Having shown DC-HIL/GPNMB to be the T-cell-inhibitory receptor mediating the suppressor function of MDSCs, we evaluated the potential of anti-DC-HIL mAb as an MDSC-targeting cancer treatment.