tbuckley/cabot-search huggingface dataset:
<i>CARMN</i> Is an Evolutionarily Conserved Smooth Muscle Cell–Specific LncRNA That Maintains Contractile Phenotype by Binding Myocardin
Authors: Kunzhe Dong, Jian Shen, Xiangqin He, Guoqing Hu, Liang Wang, Islam Osman, Kristopher M. Bunting, Rachael Dixon-Melvin, Zeqi Zheng, Hongbo Xin, Meixiang Xiang, Almira Vazdarjanova, David J.R. Fulton, Jiliang Zhou
Journal: Circulation (2021)

Background: Vascular homeostasis is maintained by the differentiated phenotype of vascular smooth muscle cells (VSMCs). The landscape of protein coding genes comprising the transcriptome of differentiated VSMCs has been intensively investigated but many gaps remain including the emerging roles of noncoding genes. Methods: We reanalyzed large-scale, publicly available bulk and single-cell RNA sequencing datasets from multiple tissues and cell types to identify VSMC-enriched long noncoding RNAs. The in vivo expression pattern of a novel smooth muscle cell (SMC)–expressed long noncoding RNA, Carmn (cardiac mesoderm enhancer-associated noncoding RNA), was investigated using a novel Carmn green fluorescent protein knock-in reporter mouse model. Bioinformatics and quantitative real-time polymerase chain reaction analysis were used to assess CARMN expression changes during VSMC phenotypic modulation in human and murine vascular disease models. In vitro, functional assays were performed by knocking down CARMN with antisense oligonucleotides and overexpressing Carmn by adenovirus in human coronary artery SMCs. Carotid artery injury was performed in SMC-specific Carmn knockout mice to assess neointima formation and the therapeutic potential of reversing CARMN loss was tested in a rat carotid artery balloon injury model. The molecular mechanisms underlying CARMN function were investigated using RNA pull-down, RNA immunoprecipitation, and luciferase reporter assays. Results: We identified CARMN , which was initially annotated as the host gene of the MIR143/145 cluster and recently reported to play a role in cardiac differentiation, as a highly abundant and conserved, SMC-specific long noncoding RNA. Analysis of the Carmn GFP knock-in mouse model confirmed that Carmn is transiently expressed in embryonic cardiomyocytes and thereafter becomes restricted to SMCs. We also found that Carmn is transcribed independently of Mir143/145 . CARMN expression is dramatically decreased by vascular disease in humans and murine models and regulates the contractile phenotype of VSMCs in vitro. In vivo, SMC-specific deletion of Carmn significantly exacerbated, whereas overexpression of Carmn markedly attenuated, injury-induced neointima formation in mouse and rat, respectively. Mechanistically, we found that Carmn physically binds to the key transcriptional cofactor myocardin, facilitating its activity and thereby maintaining the contractile phenotype of VSMCs. Conclusions: CARMN is an evolutionarily conserved SMC-specific long noncoding RNA with a previously unappreciated role in maintaining the contractile phenotype of VSMCs and is the first noncoding RNA discovered to interact with myocardin.
In HFpEF, adding empagliflozin to usual care reduced a composite of CV death or HF hospitalization at a median 26 mo
Authors: Eric R. Bates
Journal: Annals of Internal Medicine (2022)

ACP Journal ClubJanuary 2022In HFpEF, adding empagliflozin to usual care reduced a composite of CV death or HF hospitalization at a median 26 moEric R. Bates, MDEric R. Bates, MDUniversity of Michigan, Ann Arbor, Michigan, USA (E.R.B.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/J21-0006 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationAnker SD, Butler J, Filippatos G, et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med. 2021;385:1451-61. https://pubmed.ncbi.nlm.nih.gov/34449189Clinical Impact RatingsGIM/FP/GP: Cardiology: References1. Redfield MM. Heart failure with preserved ejection fraction. N Engl J Med. 2016;375:1868-77. [PMID: 27959663] Google Scholar2. Zelniker TA, Wiviott SD, Raz I, et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet. 2019;393:31-9. [PMID: 30424892] Google Scholar3. McMurray JJ, Solomon SD, Inzucchi SE, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381:1995-2008. [PMID: 31535829] Google Scholar4. Packer M, Anker SD, Butler J, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med. 2020;383:1413-24. [PMID: 32865377] Google Scholar5. Kosiborod M. Effects of dapagliflozin on symptoms, function, and quality of life in patients with heart failure and preserved ejection fraction: main results from the PRESERVED-HF trial. Presented on 12 Sep 2021 at Heart Failure Society of America annual scientific meeting, 10–13 Sep 2021. Google Scholar Author, Article, and Disclosure InformationAffiliations: University of Michigan, Ann Arbor, Michigan, USA (E.R.B.)Disclosures: The commentator has reported no disclosures of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=J21-0006.This article was published at Annals.org on 4 January 2022. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics January 2022Volume 175, Issue 1Page: JC4KeywordsDrugsEjection fractionEstimated glomerular filtration rateHazard ratioHeart failureHospitalizationsLeft ventricular ejection fractionType 2 diabetesWalking ePublished: 4 January 2022 Issue Published: January 2022 Copyright & PermissionsCopyright © 2022 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
132P 20 years of real life nationwide epidemiological data on lung cancer in non-academic French public hospitals: KBP-2020-CPHG compared to 2000 and 2010 studies
Authors: D. Debieuvre, J.B. Auliac, O. Bylicki, L. Moreau, R. Corre, J. Pinsolle, A. Bizieux Thaminy, S. Schneider, B. Godbert, P.A. Renault, P. Brun, M. Bernardi, E. Briens, M. Lepoulain Doubliez, B. Delclaux, L. Petit, J.L. Bizec, G. Milliet de Faverges, F. Al Freijat, J. Quieffin
Journal: Annals of Oncology (2022)
Tofacitinib in juvenile idiopathic arthritis: a double-blind, placebo-controlled, withdrawal phase 3 randomised trial
Authors: Nicolino Ruperto, Hermine I Brunner, Olga Synoverska, Tracy V Ting, Carlos Abud Mendoza, Alberto Spindler, Yulia Vyzhga, Katherine Marzan, Lyudmila Grebenkina, Irit Tirosh, Lisa Imundo, Rita Jerath, Daniel J Kingsbury, Betul Sozeri, Sheetal S Vora, Sampath Prahalad, Elena Zholobova, Yonatan Butbul Aviel, Vyacheslav Chasnyk, Melissa Lerman, Kabita Nanda, Heinrike Schmeling, Heather Tory, Yosef Uziel, Diego O Viola, Holly B Posner, Keith S Kanik, Ann Wouters, Cheng Chang, Richard Zhang, Irina Lazariciu, Ming-Ann Hsu, Ricardo M Suehiro, Alberto Martini, Daniel J Lovell, R Cuttica, J Akikusa, J Chaitow, C Wouters, S Oliveira, CLS Neiva, M Santiago, CA Silva, MT Terreri, C Magalhaes, V De Souza, M Bandeira, G Chédeville, K Houghton, M Vazquez-Del Mercado, J Rizo Rodriguez, K Kobusinska, E Alexeeva, I Calvo Penades, AL Boteanu, O Kasapcopur, MH Poyrazoglu, M Erguven, S Ozen, E Al-Abadi, J Bohnsack, R Carrasco, J Dare, B Gottlieb, D Wahezi, L Jung, M Klein-Gitelman, Y Zhang, L Wagner-Weiner, S Tarvin, RK Vehe, P Chiraseveenuprapund, R Rivas-Chacon, W De La Pena, ACP Sagcal-Gironella, JE Weiss
Journal: The Lancet (2021)
Abstract 11509: Social Media is Not Just for Posting Selfies Anymore: Social Media as a Medical Educational Tool Among Medical Trainees
Authors: Pranati Sreepathy, Sophie Gough, Aishwarya Pastapur, Adhir R Shroff
Journal: Circulation (2021)

Introduction: Social media (SoMe) platforms such as Twitter, Instagram, and Facebook are increasingly popular tools for dissemination of information. Currently, there is little research into SoMe and its utility in medical education (MedEd) at various training levels. Hypothesis: We hypothesize that residents will be more likely than medical students to use SoMe for MedEd and professional networking; that Twitter will be the dominant platform used by trainees for MedEd; that time constraints will be the primary barrier preventing trainees from using SoMe for MedEd; and that trainees who do use SoMe academically do so to network and collaborate. Methods: A survey based study was conducted at the University of Illinois College of Medicine. Surveys were sent to medical students and Internal Medicine residents and their responses recorded. Responses were anonymous. A Pearson Chi-Square analysis was used to analyze the categorical data. Results: Total of 294 responses were collected, 61 residents and 215 students. 51% (148) of responses were women. 50% (11/22) of medical students using Twitter use it for MedEd, vs 100% (9/9) of residents using Twitter use it for MedEd (p-value = 0.008). Only 22% (18/82, 7/31) of both residents and medical students using Instagram use it for MedEd. For residents and students alike, SoMe for MedEd was primarily used for up-to-date clinical guidelines rather than professional networking on both Twitter and Instagram (88% (14/16) and 67% (16/24) respectively). Among Instagram users, 71% (15/21) of trainees chose time constraint as the primary barrier to MedEd use. For Twitter, 100% (5/5) of trainees chose not knowing where to start as the primary barrier. Conclusion: Our study demonstrates that SoMe is a valid, but underutilized, education tool. Trainees most often utilized SoMe to keep up to date with clinical guidelines with Twitter being the most prominent platform for MedEd overall and engaging more residents than students. Targeted educational initiatives on these platforms may be a powerful platform to recruit trainees into the field of cardiology.
Putative Biomarkers of Clinical Benefit With Pembrolizumab in Advanced Urothelial Cancer: Results from the KEYNOTE-045 and KEYNOTE-052 Landmark Trials
Authors: Joaquim Bellmunt, Ronald de Wit, Yves Fradet, Miguel A. Climent, Daniel P. Petrylak, Jae-Lyun Lee, Lawrence Fong, Andrea Necchi, Cora N. Sternberg, Peter H. O'Donnell, Thomas Powles, Elizabeth R. Plimack, Dean F. Bajorin, Arjun V. Balar, Daniel Castellano, Toni K. Choueiri, Stephane Culine, Winald Gerritsen, Howard Gurney, David I. Quinn, Jacqueline Vuky, Nicholas J. Vogelzang, Razvan Cristescu, Jared Lunceford, Assieh Saadatpour, Andrey Loboda, Junshui Ma, Mohini Rajasagi, James Luke Godwin, Blanca Homet Moreno, Petros Grivas
Journal: Clinical Cancer Research (2022)

In an exploratory analysis, we investigated the association between programmed death ligand 1 (PD-L1), tumor mutational burden (TMB), T-cell-inflamed gene expression profile (TcellinfGEP), and stromal signature with outcomes of pembrolizumab in urothelial carcinoma (UC).Patients with advanced UC received first-line pembrolizumab 200 mg every 3 weeks in the single-arm phase II KEYNOTE-052 trial (NCT02335424) and salvage pembrolizumab 200 mg every 3 weeks or chemotherapy (paclitaxel/docetaxel/vinflunine) in the randomized phase III KEYNOTE-045 trial (NCT02256436). The association of each biomarker (continuous variable) with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) was evaluated using logistic regression (ORR) and Cox PH (PFS, OS), adjusted for ECOG PS; nominal P values were calculated without multiplicity adjustment (one-sided, pembrolizumab; two-sided, chemotherapy). Significance was prespecified at α = 0.05.In KEYNOTE-052, PD-L1, TMB, and TcellinfGEP were significantly associated with improved outcomes; stromal signature was significantly associated with worse outcomes. In KEYNOTE-045, although findings for TMB and TcellinfGEP with pembrolizumab were consistent with those of KEYNOTE-052, PD-L1 was not significantly associated with improved outcomes, nor was stromal signature associated with worse outcomes with pembrolizumab; chemotherapy was not associated with outcomes in a consistent manner for any of the biomarkers. Hazard ratio (HR) estimates at prespecified cutoffs showed an advantage for pembrolizumab versus chemotherapy regardless of PD-L1 or TMB, with a trend toward lower HRs in the combined positive score ≥10 and the TMB ≥175 mutation/exome subgroup. For TcellinfGEP, PFS and OS HRs were lower in the TcellinfGEP-nonlow subgroup regardless of treatment.Multiple biomarkers characterizing the tumor microenvironment may help predict response to pembrolizumab monotherapy in UC, and potential clinical utility of these biomarkers may be context-dependent.
Clarification of Conflict of Interest Disclosures
Authors: Beth D. Darnall
Journal: JAMA Internal Medicine (2022)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals 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 Internal Medicine journal
IDH1 Inhibition Reawakens the Immune Response against Cholangiocarcinoma
Authors: Yan Zhu, Lawrence N. Kwong
Journal: Cancer Discovery (2022)

Isocitrate dehydrogenase 1 mutations (mIDH1) are common in cholangiocarcinoma, but their exact mechanisms in cholangiocarcinoma initiation and maintenance are unclear. In this issue of Cancer Discovery, Wu and colleagues identify immune suppression via TET2 inactivation as the primary means by which mIDH1 maintains cholangiocarcinoma survival, leading to an efficacious new combination of mIDH1 inhibitors and immune checkpoint blockade targeting regulatory T cells. See related article by Wu et al., p. 812 (9).
Can virtual events achieve co-benefits for climate, participation, and satisfaction? Comparative evidence from five international Agriculture, Nutrition and Health Academy Week conferences
Authors: Joe Yates, Suneetha Kadiyala, Yuemeng Li, Sylvia Levy, Abel Endashaw, Hallie Perlick, Parke Wilde
Journal: The Lancet Planetary Health (2022)

The advancement of science and evidence-based solutions for planetary health increasingly require interdisciplinary and international learning and sharing. Yet aviation travel to academic conferences is carbon-intensive and expensive, thus perpetuating planetary health and equity challenges. Using data from five annual international Agriculture, Nutrition and Health Academy Week conferences from 2016 to 2020, we explore whether moving to virtual conferencing produced co-benefits for climate, participation, attendee interaction, and satisfaction. We report on: absolute number of attendees, proportion of attendees from countries of different income levels, number of participants at social events, aviation CO
Efficacy and safety of baricitinib plus standard of care for the treatment of critically ill hospitalised adults with COVID-19 on invasive mechanical ventilation or extracorporeal membrane oxygenation: an exploratory, randomised, placebo-controlled trial
Authors: E Wesley Ely, Athimalaipet V Ramanan, Cynthia E Kartman, Stephanie de Bono, Ran Liao, Maria Lucia B Piruzeli, Jason D Goldman, José Francisco Kerr Saraiva, Sujatro Chakladar, Vincent C Marconi
Journal: The Lancet Respiratory Medicine (2022)
Analysis of the Estrogen Receptor-Associated LncRNA Landscape Identifies a Role for ERLC1 in Breast Cancer Progression
Authors: Hui Yuan, Linlin Yan, Mingming Wu, Yinzhong Shang, Qianying Guo, Xin Ma, Xiao Zhang, Yong Zhu, Zhengsheng Wu, Peter E. Lobie, Tao Zhu
Journal: Cancer Research (2021)

Abstract Estrogen receptor alpha (ERα) plays a vital role in the development of normal breast tissue and in breast cancer. By cross-analyzing The Cancer Genome Atlas (TCGA) database, ERα-regulated long noncoding RNA 1 (ERLC1) was identified as a long noncoding RNA exhibiting a strong association with ERα signaling and high specificity of expression in breast tissue. ERLC1 was transcriptionally activated by ERα, and ERLC1 stabilized the ESR1 transcript by sequestering miR-129 and tethering FXR1 to maintain a positive feedback loop that potentiated ERα signaling. ERLC1 was elevated in tamoxifen-resistant breast cancer cells, where ERLC1 depletion restored sensitivity to tamoxifen and increased the efficacy of palbociclib or fulvestrant therapy. Collectively, these data warrant further investigation of ERLC1 as a modulator of therapeutic response and potential therapeutic target in ER+ breast cancer. Significance: This study identifies an estrogen-regulated lncRNA and the mechanism by which it positively regulates ERα activity, demonstrating a feedback loop that can promote resistance to antiestrogen therapies in ER+ breast cancer.
Hemoglobin and Clinical Outcomes in the Vericiguat Global Study in Patients With Heart Failure and Reduced Ejection Fraction (VICTORIA)
Authors: Justin A. Ezekowitz, Yinggan Zheng, Alain Cohen-Solal, Vojtěch Melenovský, Jorge Escobedo, Javed Butler, Adrian F. Hernandez, Carolyn S.P. Lam, Christopher M. O’Connor, Burkert Pieske, Piotr Ponikowski, Adriaan A. Voors, Christopher deFilippi, Cynthia M. Westerhout, Ciaran McMullan, Lothar Roessig, Paul W. Armstrong
Journal: Circulation (2021)

In the VICTORIA trial (Vericiguat Global Study in Patients with Heart Failure with Reduced Ejection Fraction), anemia occurred more often in patients treated with vericiguat (7.6%) than with placebo (5.7%). We explored the association between vericiguat, randomization hemoglobin, development of anemia, and whether the benefit of vericiguat related to baseline hemoglobin.Anemia was defined as hemoglobin <13.0 g/dL in men and <12.0 g/dL in women (World Health Organization Anemia). Adverse events reported as anemia were also evaluated. We assessed the risk-adjusted relationship between hemoglobin and hematocrit with the primary outcome (composite of cardiovascular death or heart failure hospitalization) and the time-updated hemoglobin relationship to outcomes.At baseline, 1719 (35.7%) patients had World Health Organization anemia; median hemoglobin was 13.4 g/L (25th, 75th percentile: 12.1, 14.7 g/dL). At 16 weeks from randomization, 1643 patients had World Health Organization anemia (284 new for vericiguat and 219 for placebo), which occurred more often with vericiguat than placebo (P<0.001). After 16 weeks, no further decline in hemoglobin occurred over 96 weeks of follow-up and the ratio of hemoglobin/hematocrit remained constant. Overall, adverse event anemia occurred in 342 patients (7.1%). A lower hemoglobin was unrelated to the treatment benefit of vericiguat (versus placebo) on the primary outcome. In addition, analysis of time-updated hemoglobin revealed no association with the treatment effect of vericiguat (versus placebo) on the primary outcome.Anemia was common at randomization and lower hemoglobin was associated with a greater frequency of clinical events. Although vericiguat modestly lowered hemoglobin by 16 weeks, this effect did not further progress nor was it related to the treatment benefit of vericiguat. Registration: URL: https://www.clinicaltrials.gov: Unique identifier: NCT02861534.
40P Immune-related adverse events (irAEs) in advanced non-small cell lung cancer (aNSCLC) patients (pts): A real-world analysis
Authors: G. Pretelli, A. Pavan, A. Dal Maso, M.V. Resi, C. Mulargiu, A. Ferro, B. Benetti, M. Lorenzi, G.M. Marinato, S. Frega, G. Pasello, P.F. Conte, V. Guarneri, L. Bonanno
Journal: Annals of Oncology (2022)
The antitumoral activity of TLR7 ligands is corrupted by the microenvironment of pancreatic tumors
Authors: Marie Rouanet, Naima Hanoun, None Hubert Lulka, Cindy Ferreira, Pierre Garcin, Martin Sramek, Godefroy Jacquemin, Agnès Coste, Delphine Pagan, Carine Valle, Emeline Sarot, Vera Pancaldi, Frédéric Lopez, Louis Buscail, Pierre Cordelier
Journal: Molecular Therapy (2022)

Toll-like receptors (TLRs) are key players in the innate immune system. Recent studies have suggested that they may affect the growth of pancreatic cancer, a disease with no cure. Among them, TLR7 shows promise for therapy but may also promotes tumor growth. Thus, we aimed to clarify the therapeutic potential of TLR7 ligands in experimental pancreatic cancer models, to open the door for clinical applications. In vitro, we found that TLR7 ligands strongly inhibit the proliferation of both human and murine pancreatic cancer cells, compared with TLR2 agonists. Hence, TLR7 treatment alters cancer cells' cell cycle and induces cell death by apoptosis. In vivo, TLR7 agonist therapy significantly delays the growth of murine pancreatic tumors engrafted in immunodeficient mice. Remarkably, TLR7 ligands administration instead increases tumor growth and accelerates animal death when tumors are engrafted in immunocompetent models. Further investigations revealed that TLR7 agonists modulate the intratumoral content and phenotype of macrophages and that depleting such tumor-associated macrophages strongly hampers TLR7 agonist-induced tumor growth. Collectively, our findings shine a light on the duality of action of TLR7 agonists in experimental cancer models and call into question their use for pancreatic cancer therapy. Toll-like receptors (TLRs) are key players in the innate immune system. Recent studies have suggested that they may affect the growth of pancreatic cancer, a disease with no cure. Among them, TLR7 shows promise for therapy but may also promotes tumor growth. Thus, we aimed to clarify the therapeutic potential of TLR7 ligands in experimental pancreatic cancer models, to open the door for clinical applications. In vitro, we found that TLR7 ligands strongly inhibit the proliferation of both human and murine pancreatic cancer cells, compared with TLR2 agonists. Hence, TLR7 treatment alters cancer cells' cell cycle and induces cell death by apoptosis. In vivo, TLR7 agonist therapy significantly delays the growth of murine pancreatic tumors engrafted in immunodeficient mice. Remarkably, TLR7 ligands administration instead increases tumor growth and accelerates animal death when tumors are engrafted in immunocompetent models. Further investigations revealed that TLR7 agonists modulate the intratumoral content and phenotype of macrophages and that depleting such tumor-associated macrophages strongly hampers TLR7 agonist-induced tumor growth. Collectively, our findings shine a light on the duality of action of TLR7 agonists in experimental cancer models and call into question their use for pancreatic cancer therapy.