tbuckley/cabot-search huggingface dataset:
Abstract 14430: The Novel Phosphodiesterase 3 Inhibitor K-134 Improves Walking Performance in Japanese Patients with Intermittent Claudication
Authors: Hiroshi Shigematsu
Journal: Circulation (2011)

Background: Patients with intermittent claudication (IC) associated with Peripheral Arterial Disease (PAD) are restricted in their walking performance by misbalance between oxygen supply and metabo...
Expression of T helper cytokines associated with MUC5AC secretion in eosinophil‐based endotypes of nasal polyps
Authors: Yu Zhang, Xiangdong Wang, Jian Jiao, Ying Li, Xicheng Song, Luo Zhang
Journal: Allergy (2020)

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.
18632 Incorporation of dermoscopy improves inter-observer agreement among dermatopathologists in histologic assessment of melanocytic neoplasms
Authors: Elsy V. Compres, Katherine Shi, Kara E. Walton, Lauren S. Mohan, Bin Zhang, Ayesha U. Khan, Daniel Kim, Elnaz Panah, Pedram Yazdan, June Robinson, Pedram Gerami
Journal: Journal of the American Academy of Dermatology (2020)
18223 Long-term proactive management of psoriasis vulgaris with fixed-dose combination of 0.005% calcipotriene and 0.064% betamethasone dipropionate foam: Results of a phase III randomized controlled trial
Authors: Mark Lebwohl, Jean-Philippe Lacour, Monika Liljedahl, Charles Lynde, Marie Holst Mørch, Anja Marieke Snel-Prentø, Diamant Thaçi, Richard B. Warren
Journal: Journal of the American Academy of Dermatology (2020)
Abstract 16393: Left Atrial Calcification on Cardiac Computed Tomography and Rhythm Outcome in Patient Underwent Mitral Valve Surgery
Authors: Chi Young Shim, Shinjeong Song, Jah Yeon Choi, Young-Ju Seo, Young Jin Kim, Ji Won Seo, Geu-Ru Hong, Jong-Won Ha
Journal: Circulation (2019)

Introduction: Left atrial (LA) calcification (LAC) is often observed in patients who underwent mitral valve (MV) surgery, little is known about its association with sinus node dysfunction (SND) and...
COPD-derived fibroblasts secrete higher levels of senescence-associated secretory phenotype proteins
Authors: Roy R Woldhuis, Irene H Heijink, Maarten van den Berge, Wim Timens, Brian G G Oliver, Maaike de Vries, Corry-Anke Brandsma
Journal: Thorax (2020)

COPD-derived fibroblasts have increased cellular senescence. Senescent cell accumulation can induce tissue dysfunction by their senescence-associated secretory phenotype (SASP). We aimed to determine the SASP of senescent fibroblasts and COPD-derived lung fibroblasts, including severe, early-onset (SEO)-COPD. SASP protein secretion was measured after paraquat-induced senescence in lung fibroblasts using Olink Proteomics and compared between (SEO-)COPD-derived and control-derived fibroblasts. We identified 124 SASP proteins of senescent lung fibroblasts, of which 42 were secreted at higher levels by COPD-derived fibroblasts and 35 by SEO-COPD-derived fibroblasts compared with controls. Interestingly, the (SEO-)COPD-associated SASP included proteins involved in chronic inflammation, which may contribute to (SEO-)COPD pathogenesis.
Long‐Term Safety and Efficacy of Anifrolumab in Adults With Systemic Lupus Erythematosus: Results of a Phase II Open‐Label Extension Study
Authors: W. Winn Chatham, Richard Furie, Amit Saxena, Philip Brohawn, Erik Schwetje, Gabriel Abreu, Raj Tummala
Journal: Arthritis & Rheumatology (2020)

To investigate long-term safety and tolerability of anifrolumab, a human monoclonal antibody to the type I interferon (IFN) receptor subunit 1, in patients with moderate-to-severe systemic lupus erythematosus (SLE).This 3-year, multinational, open-label extension study included adult patients who completed treatment (48 weeks of anifrolumab or placebo; 12-week follow-up) in the MUSE phase IIb randomized controlled trial (RCT). Patients initially received 1,000 mg of anifrolumab intravenously every 4 weeks, which was reduced to 300 mg every 4 weeks based on the benefit/risk profile established in the MUSE trial. Adverse events (AEs) were assessed monthly. Exploratory end points included the SLE Disease Activity Index 2000 (SLEDAI-2K), Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), pharmacodynamics, and health-related quality of life (HRQoL).Of the 246 patients who completed the RCT, 218 (88.6%) enrolled in the open-label extension study, of which 139 (63.8%) completed 3 years of treatment. Approximately 69.7% of patients reported ≥1 AE during the first year of open-label extension treatment. Frequency and patterns of serious AEs and AEs of special interest over 3 years were consistent with those reported for 1 year of treatment in the RCT. Few patients (6.9%) discontinued treatment due to AEs. No new safety signals were identified. Improvement in the SLEDAI-2K was sustained over 3 years. SDI and Short Form 36 health survey scores remained stable. Neutralization of type I IFN gene signatures was maintained in the IFN-high population, and C3, C4, and anti-double-stranded DNA showed trends toward sustained improvement.Long-term anifrolumab treatment demonstrates an acceptable safety profile with sustained improvement in SLE disease activity, HRQoL, and serologic measures.
Coronary Artery Calcium to Improve the Efficiency of Randomized Controlled Trials in Primary Cardiovascular Prevention
Authors: Miguel Cainzos-Achirica, Marcio Sommer Bittencourt, Albert D. Osei, Waqas Haque, Deepak L. Bhatt, Roger S. Blumenthal, Ron Blankstein, Kausik K. Ray, Michael J. Blaha, Khurram Nasir
Journal: JACC. Cardiovascular imaging (2020)
Abstract PO-04: Noncoding mutations in mantle cell lymphoma disrupt regulation of HNRNPH1 by alternative splicing
Authors: Krysta M. Coyle, Quratulain Qureshi, Prasath Pararajalingam, Nicole Thomas, Timothy E. Audas, Ryan D. Morin
Journal: Blood Cancer Discovery (2020)

Abstract Non-Hodgkin lymphomas (NHL) are a collection of cancers with each malignancy having distinct clinical management and prognosis. Mantle cell lymphoma (MCL) is particularly genetically heterogeneous and is considered incurable. Through a combination of exome, genome, and targeted sequencing of MCL tumors, we identified recurrent mutations in HNRNPH1 (heterogeneous nuclear ribonucleoprotein H1). These mutations are largely intronic or silent and are associated with a putative cis regulatory region involving a single exon. In RNA-seq data from matched cases, we identified variable representation of two distinct HNRNPH1 isoforms. Based on the reading frame of the affected exons, canonical splicing is predicted to produce a functional protein, while alternative splicing introduces a premature termination codon leading to nonsense-mediated decay. We observed a significantly higher proportion of canonical transcripts in MCL tumors bearing HNRNPH1 mutations, leading us to conclude that mutations in HNRNPH1 significantly alter its splicing. Furthermore, increased canonical splicing results in higher HNRNPH1 protein abundance as determined by immunohistochemical analysis of an MCL tissue microarray. HNRNPH1 mutation status and splicing ratio are associated with shorter survival of MCL patients. We developed an in vitro reporter minigene and introduced three specific mutations corresponding to the patient-identified mutations in HNRNPH1. These mutations lead to an increase in canonical splicing and translation of the HNRNPH1 minigene-derived peptide. Additionally, when HNRNPH1 is overexpressed, we observe a decrease of this peptide, implicating HNRNPH1 in the regulation of its own splicing. This is supported by preliminary data indicating that HNRNPH1 binds its own RNA. Beyond its own splicing, HNRNPH1 is likely also involved in the splicing of additional splicing factors. Overexpression of HNRNPH1 affects the splicing of SRSF3 and HNRNPDL, and many other targets are likely to be identified. This work elucidates a functional role for recurrent noncoding HNRNPH1 mutations and implicates HNRNPH1 expression and splicing of its downstream targets in lymphomagenesis. We continue to explore trans regulatory targets of HNRNPH1 using in vitro and cell-based models. While splicing is a growing field of interest in lymphoma biology, the unique pattern and consequences of these largely silent mutations specifically implicate alternative splicing as an oncogenic mechanism in MCL. Citation Format: Krysta M. Coyle, Quratulain Qureshi, Prasath Pararajalingam, Nicole Thomas, Timothy E. Audas, Ryan D. Morin. Noncoding mutations in mantle cell lymphoma disrupt regulation of HNRNPH1 by alternative splicing [abstract]. In: Proceedings of the AACR Virtual Meeting: Advances in Malignant Lymphoma; 2020 Aug 17-19. Philadelphia (PA): AACR; Blood Cancer Discov 2020;1(3_Suppl):Abstract nr PO-04.
Inhibition of Long Noncoding RNA Linc‐Pint by Hepatitis C Virus in Infected Hepatocytes Enhances Lipogenesis
Authors: Mousumi Khatun, Subhayan Sur, Robert Steele, Ranjit Ray, Ratna B. Ray
Journal: Hepatology (2020)

Background and Aims HCV often causes chronic infection in liver, cirrhosis, and, in some instances, HCC. HCV encodes several factors' those impair host genes for establishment of chronic infection. The long noncoding RNAs (lncRNAs) display diverse effects on biological regulations. However, their role in virus replication and underlying diseases is poorly understood. In this study, we have shown that HCV exploits lncRNA long intergenic nonprotein‐coding RNA, p53 induced transcript (Linc‐Pint) in hepatocytes for enhancement of lipogenesis. Approach and Results We identified a lncRNA, Linc‐Pint, which is significantly down‐regulated in HCV‐replicating hepatocytes and liver specimens from HCV infected patients. Using RNA pull‐down proteomics, we identified serine/arginine protein specific kinase 2 (SRPK2) as an interacting partner of Linc‐Pint. A subsequent study demonstrated that overexpression of Linc‐Pint inhibits the expression of lipogenesis‐related genes, such as fatty acid synthase and ATP‐citrate lyase. We also observed that Linc‐Pint significantly inhibits HCV replication. Furthermore, HCV‐mediated enhanced lipogenesis can be controlled by exogenous Linc‐Pint expression. Together, our results suggested that HCV‐mediated down‐regulation of Linc‐Pint enhances lipogenesis favoring virus replication and liver disease progression. Conclusions We have shown that SRPK2 is a direct target of Linc‐Pint and that depletion of SRPK2 inhibits lipogenesis. Our study contributes to the mechanistic understanding of the role of Linc‐Pint in HCV‐associated liver pathogenesis.
Efficacy in myopia control
Authors: Noel A. Brennan, Youssef M. Toubouti, Xu Cheng, Mark A. Bullimore
Journal: Progress in Retinal and Eye Research (2020)

There is rapidly expanding interest in interventions to slow myopia progression in children and teenagers, with the intent of reducing risk of myopia-associated complications later in life. Despite many publications dedicated to the topic, little attention has been devoted to understanding 'efficacy' in myopia control and its application. Treatment effect has been expressed in multiple ways, making comparison between therapies and prognosis for an individual patient difficult. Available efficacy data are generally limited to two to three years making long-term treatment effect uncertain. From an evidence-based perspective, efficacy projection should be conservative and not extend beyond that which has been empirically established. Using this principle, review of the literature, data from our own clinical studies, assessment of demonstrated myopia control treatments and allowance for the limitations and context of available data, we arrive at the following important interpretations: (i) axial elongation is the preferred endpoint for assessing myopic progression; (ii) there is insufficient evidence to suggest that faster progressors, or younger myopes, derive greater benefit from treatment; (iii) the initial rate of reduction of axial elongation by myopia control treatments is not sustained; (iv) consequently, using percentage reduction in progression as an index to describe treatment effect can be very misleading and (v) cumulative absolute reduction in axial elongation (CARE) emerges as a preferred efficacy metric; (vi) maximum CARE that has been measured for existing myopia control treatments is 0.44 mm (which equates to about 1 D); (vii) there is no apparent superior method of treatment, although commonly prescribed therapies such as 0.01% atropine and progressive addition spectacles lenses have not consistently provided clinically important effects; (viii) while different treatments have shown divergent efficacy in the first year, they have shown only small differences after this; (ix) rebound should be assumed until proven otherwise; (x) an illusion of inflated efficacy is created by measurement error in refraction, sample bias in only treating 'measured' fast progressors and regression to the mean; (xi) decision to treat should be based on age of onset (or refraction at a given age), not past progression; (xii) the decreased risk of complications later in life provided by even modest reductions in progression suggest treatment is advised for all young myopes and, because of limitations of available interventions, should be aggressive.
Cracking the Mysteries of Diastolic Function in Atrial Fibrillation: New Technology for an Old Problem⁎⁎Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.
Authors: Zoran B. Popović, Allan L. Klein
Journal: JACC. Cardiovascular imaging (2009)
403P Clinical profile, practice pattern and outcomes in ALK-positive lung cancer: Real-world data from India
Authors: A. Kapoor, V. Noronha, V.M. Patil, A.S. Joshi, N. Menon, R. Kumar, A. Mahajan, K. Prabhash, A. Janu, A. Chougule, O. Shetty
Journal: Annals of Oncology (2020)
The circular RNA circ-ERBIN promotes growth and metastasis of colorectal cancer by miR-125a-5p and miR-138-5p/4EBP-1 mediated cap-independent HIF-1α translation
Authors: Liang-Yan Chen, Lian Wang, Yue-Xiang Ren, Zheng Pang, Yao Liu, Xiao-Dong Sun, Jian Tu, Zheng Zhi, Yan Qin, Li-Na Sun, Jian-Ming Li
Journal: Molecular Cancer (2020)

Abstract Background Circular RNA (circRNAs) and hypoxia have been found to play the key roles in the pathogenesis and progression of cancer including colorectal cancer (CRC). However, the expressions and functions of the specific circRNAs in regulating hypoxia-involved CRC metastasis, and the circRNAs that are relevant to regulate HIF-1α levels in CRC remain elusive. Methods qRT-PCR was used to detect the expression of circRNAs and mRNA in CRC cells and tissues. Fluorescence in situ hybridization (FISH) was used to analyze the location of circ-ERBIN. Function-based experiments were performed using circ-ERBIN overexpression and knockdown cell lines in vitro and in vivo, including CCK8, colony formation, EdU assay, transwell, tumor growth and metastasis models. Mechanistically, luciferase reporter assay, western blots and immunohistochemical stainings were performed. Results Circ-Erbin was highly expressed in the CRC cells and Circ-Erbin overexpression facilitated the proliferation, migration and metastasis of CRC in vitro and in vivo. Notably, circ-Erbin overexpression significantly promoted angiogenesis by increasing the expression of hypoxia induced factor (HIF-1α) in CRC. Mechanistically, circ-Erbin accelerated a cap-independent protein translation of HIF-1α in CRC cells as the sponges of miR-125a-5p and miR-138-5p, which synergistically targeted eukaryotic translation initiation factor 4E binding protein 1(4EBP-1). Conclusions Our findings uncover a key mechanism for circ-Erbin mediated HIF-1α activation by miR-125a-5p-5p/miR-138-5p/4EBP-1 axis and circ-ERBIN is a potential target for CRC treatment.
18228 A novel acetyl dipeptide demonstrates pleiotropic gene expression, optimized bioavailability, and perceived anti-aging benefits
Authors: David Byren, Daphne Meza, Ramine Parsa, Allison Rush, Brenda Edison, Jing Yang, Derrick Chua, Gabriella John, arisa Dufort, Neena Tierney, Barbara Green
Journal: Journal of the American Academy of Dermatology (2020)
FRI0055 Experience with commercial remicade (infliximab) at a large community-based rheumatology practice
Authors: W Shergy, RM Phillips, RE Hunt, J Hernandez
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Infliximab, a monoclonal antibody that binds with high affinity and specificity to TNF-alpha and neutralises its biologic activity, is approved for the reduction of the signs and symptoms of rheumatoid arthritis (RA). The Rheumatology Associates of North Alabama (RANA) is a large, community-based rheumatology practice that treats approximately 6,000 patients with RA. <h3>Objectives</h3> To document the experience with commercial infliximab in patients with RA treated in a community rheumatology practice. <h3>Methods</h3> In an ongoing chart review of all patients receiving infliximab at RANA, the following information was documented: age, concomitant medication use, tender and swollen joint counts, and adverse side effects. <h3>Results</h3> Baseline information was collected for 137 patients with RA. These patients ranged in age from 33 to 84 yrs (mean of 62.7 yrs). Among the 114 patients receiving concomitant methotrexate (MTX), doses ranged from 2.5 to 30 mg/day (mean of 17.2 mg/day). At baseline (prior to the first infliximab dose), the mean dose of prednisone was 6.2 mg/day, and the mean tender and swollen joint counts were 22.4 and 13.7, respectively. Patients were treated with the currently recommended dosing regimen of 3 mg/kg at Weeks 0, 2, and 6 followed by q 8 wk dosing. Forty (29%) patients received concomitant disease-modifying antirheumatic drugs (DMARDs); 15 of these patients received concomitant leflunomide (12 with and 3 without MTX). Nine patients received infliximab without a concomitant DMARD. Data were available for 74 of these patients at Week 14 (fourth infliximab infusion). At this time point, the mean prednisone dose was 5.1 mg/day, and mean tender and swollen joint counts had improved by 65% and 69% (to 7.8 and 4.3), respectively. Improvements in steroid use and tender and swollen joint counts also were observed at Week 30 (n = 42; mean prednisone dose of 2.9 mg/day and tender/swollen joint counts of 4.4/1.7) and Week 54 (n = 14; mean prednisone dose of 2.1 mg/day and tender/swollen joint counts of 1.6/0.8) among the patients who had received treatment this long. Ten patients discontinued the use of infliximab due to lack of response (3 patients), rash (3 patients), cost (2 patients), abdominal pain (1 patient), and an unrelated side effect (neck pain in 1 patient). Five patients experienced infections (shingles, soft tissue abscess, pneumonia, and bronchitis in 2 patients); all patients responded to antibiotic therapy and continued treatment with infliximab. <h3>Conclusion</h3> In a community rheumatology practice, infliximab 3 mg/kg, both with and without MTX, produced compelling improvement in the signs and symptoms of RA. Infliximab was safe and well tolerated when administered in the outpatient infusion setting.
380MO A phase II trial of atezolizumab, bevacizumab, pemetrexed and carboplatin combination for metastatic EGFR-mutated NSCLC after TKI failure
Authors: T.C. Lam, K. Tsang, H. Choi, V.H.F. Lee, K.O. Lam, C.L. Chiang, T.H. So, W.W. Chan, S.F. Nyaw, F. Lim, J.O. Lau, J. Chik, S.F. Kong, A.W.M. Lee
Journal: Annals of Oncology (2020)
Influence of methylation of the Wnt-antagonist SFRP1 and Dkk1 on outcome in colorectal cancer is reversed by K-Ras mutation
Authors: Satoru Iida, Ken Hinoue, Toshiaki Ishikawa, Masamichi Yasuno, Tetsuro Higuchi, Masayuki Enomoto, Hiroyuki Uetake, Kenichi Sugihara
Journal: Cancer Research (2008)

990  Epigenetic alteration such as promoter hypermethylation of gene, as well as genetic abnormality such as gene mutation, occurs frequently during the pathogenesis of human cancers. Recent studies exhibit the increasing observations that both epigenetic and genetic changes combine to determine the phenotype of cancer. Aberrant Wnt signaling is an early progression event in 90% of colorectal cancers (CRC) and occurs through mutations mainly of APC and less often of β-catenin. Recently, it has been reported that promoter methylation of Wnt-antagonist genes, such as SFRPs, Dkks and Wif-1, contributes to the initiation and progression of CRC. In this study, we aimed to clarify whether DNA promoter methylation of SFRP1 and Dkk1 may be used as parameters for predicting prognosis in CRC, and whether K-Ras mutation, which is commonly observed in CRC, has any association with these methylations. In addition, we analyzed the influence of the combination of SFRP1 and Dkk1 methylation and K-Ras mutation on prognosis in CRC. Tissue samples from 118 CRC patients who underwent surgical resection were examined. The methylation status of SFRP1 and Dkk1 and the sequences of exon 1 of K-Ras were determined by methylation specific PCR and direct sequencing, respectively, using genomic DNA extracted from paraffin-embedded blocks. Correlation between these factors and clinicopathologic findings/patients survival were examined. As a result, DNA methylations of SFRP1 and Dkk1 were detected in 75 of 118 (63.6%) tumors and in 26 (22.0%), respectively. K-Ras mutations were identified in 40 of 118 (33.9%). There was a significant correlation between K-Ras mutation and SFRP1 (77.5%; 31 of 40; p=0.03) but not Dkk1 (30.0%; 12 of 40; p=0.13). SFRP1 and Dkk1 methylation showed no associations with overall survival and other clinicopathological findings in CRC patients. In CRC without K-Ras mutation, however, patients with at least one or two methylated genes had poorer overall survival compared with no methylated genes (p=0.035). To contrary, in the cases of K-Ras mutation, patients with the methylation of either or both genes tended to have better survival than patients with no methylation (p=0.052). Classifying CRC based on SFRP1 and Dkk1 methylation status and K-Ras mutation may be a clinically powerful predictor of patient outcome.
Progression of Myocardial Fibrosis in Hypertrophic Cardiomyopathy
Authors: Manhal Habib, Arnon Adler, Kimia Fardfini, Sara Hoss, Kate Hanneman, Ethan J. Rowin, Martin S. Maron, Barry J. Maron, Harry Rakowski, Raymond H. Chan
Journal: JACC. Cardiovascular imaging (2020)
Imaging Atherosclerosis With F18-Fluorodeoxyglucose Positron Emission Tomography: What Are We Actually Seeing?⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Joseph C. Wu, Patricia K. Nguyen
Journal: Journal of the American College of Cardiology (2011)
NHS’s plan to abolish CCGs must not dilute primary care’s influence, say leaders
Authors: Gareth Iacobucci
Journal: BMJ (2020)

NHS England has proposed abolishing clinical commissioning groups (CCGs) by April 2022 and moving their functions to statutory integrated care systems.

A document outlining NHS England’s legislative recommendations proposes that integrated care systems become “a statutory corporate NHS body . . . that additionally brings CCG statutory functions into the ICS.”1

Until now, NHS England has avoided recommending a wholesale NHS reorganisation to achieve its vision for integration. But it said that the covid-19 pandemic had “increased the appetite for statutory clarity for [integrated care systems] and the organisations within them.”

Abolishing CCGs is one of two options proposed—the other is a less radical move to create “a statutory committee model . . . that binds together current statutory organisations.” But NHS England indicated that its preference was to make …