tbuckley/cabot-search huggingface dataset:
Thyroid Hormone Therapy for Subclinical Hypothyroidism—Reply
Authors: Martin Feller, Nicolas Rodondi, Olaf M. Dekkers
Journal: JAMA (2019)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Update in Cardiology: Evidence Published in 2016
Authors: Rita F. Redberg
Journal: Annals of Internal Medicine (2017)

Updates4 April 2017Update in Cardiology: Evidence Published in 2016Rita F. Redberg, MDRita F. Redberg, MDFrom UCSF School of Medicine, University of California, San Francisco.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M17-0137 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail 2016 was another great year for cardiology education. There were many randomized trials that informed important clinical questions about treatment of coronary artery disease (CAD), heart failure, and primary prevention, and surprising findings on the history of the role of sugar in CAD. Several trials compared devices and procedures with medical therapy. For this Update, I chose articles that address relatively common clinical issues and have important messages for practicing clinicians.Prevention StudiesAspirin Has a Net Benefit for Primary Prevention of CVD in Middle-Aged Persons With Higher CVD Risk ... Author, Article, and Disclosure InformationAffiliations: From UCSF School of Medicine, University of California, San Francisco.Disclosures: The author has disclosed no conflicts. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M17-0137.Corresponding Author: Rita F. Redberg, MD, Division of Cardiology, UCSF School of Medicine, 505 Parnassus Avenue, Suite M-1180, San Francisco, CA 94143-0124; e-mail, rita.[email protected]edu.Author Contributions: Drafting of the article: R. Redberg.Final approval of the article: R. Redberg.This article was published at Annals.org on 30 March 2017. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 4 April 2017Volume 166, Issue 7Page: W16-W19KeywordsBlood pressureCardiovascular diseasesCohort studiesDietGeneticsHeart failureImplantable cardioverter defibrillatorsLow density lipoprotein cholesterolMortalityProteins ePublished: 30 March 2017 Issue Published: 4 April 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
CD84: A Potential Novel Therapeutic Target in Multiple Myeloma
Authors: Emine Gulsen Gunes, Hadas Lewinsky, Domenico Viola, Enrico Caserta, Michael Rosenzweig, Myo Htut, James F Sanchez, Ralf Buettner, Guido Marcucci, Jonathan J Keats, Amrita Krishnan, Steven T Rosen, Idit Shachar, Flavia Pichiorri
Journal: Blood (2018)
Transcriptional Signaling Centers Govern Human Erythropoiesis and Harbor Genetic Variations of Red Blood Cell Traits
Authors: Avik Choudhuri, Eirini Trompouki, Brian J. Abraham, Leandro Colli, William Mallard, Min-Lee Yang, Divya Vinjamur, Alireza Ghamari, Satish Nandakumar, Kanen Hoi, Barbara Hummel, Sonja Boatman, Victoria Chan, Teresa V. Bowman, Song Yang, Yi Zhou, Sinichiro Takahashi, Alan B. Cantor, Vijay G. Sankaran, Santhi Ganesh, Daniel E. Bauer, John Rinn, Stephen J Chanock, Richard A. Young, Leonard I. Zon
Journal: Blood (2018)
Correction: Molecular Chaperone HSP90 Is Necessary to Prevent Cellular Senescence via Lysosomal Degradation of p14ARF
Authors: Su Yeon Han, Aram Ko, Haruhisa Kitano, Chel Hun Choi, Min-Sik Lee, Jinho Seo, Junya Fukuoka, Soo-Youl Kim, Stephen M. Hewitt, Joon-Yong Chung, Jaewhan Song
Journal: Cancer Research (2018)
P056 A novel PGC-1Β/NFATc-1 pathway in monocytes facilitates osteoclastogenesis in rheumatoid arthritis
Authors: J-D Ma, J Jing, Y-Q Mo, Li Q-H, J-Z Lin, L-F Chen, L Dai
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Resident. <h3>Introduction</h3> The underlying mechanism of excessive osteoclastogenesis causing bone erosion in rheumatoid arthritis (RA) remains elusive. PGC-1β is implicated in transcriptional regulation of osteoclastogenesis but its role in RA pathogenesis is unknown. <h3>Objectives</h3> To investigate whether PGC-1β regulated osteoclastogenesis in RA. <h3>Methods</h3> PGC-1β expression in peripheral CD14+ monocytes from RA patients were detected by immunofluorescence, flow cytometry and western blot. Peripheral CD14+ monocytes from RA patients or healthy controls were transfected with lentivirus for PGC-1β gene silencing or over-expression and cultured with M-CSF and RANKL. Mature osteoclasts and their bone resorption activity were determined by TRAP, F-actin and toluidine blue staining. DC-STAMP and bone degrading enzymes as well as signaling molecules were detected by western blot. <h3>Results</h3> Increased nuclear accumulation of PGC-1β was observed in peripheral CD14+ monocytes from RA patients and their relative PGC-1β protein expression was higher than that in healthy controls. Cultured with RANKL and M-CSF, the cell counts of mature osteoclasts on day 14 and 21 and the pit area of bone resorption lacunae on day 21 were significantly higher in RA patients than those in healthy controls. PGC-1β knockdown in monocytes suppressed the expression of cathepsin K, TRAP and MMP-9 as well as osteoclast differentiation and bone resorption activity, while PGC-1β over-expression markedly promoted these indicators and osteoclastogenesis. Furtherly, over-expressed PGC-1β increased the nuclear expression of NFATc-1. VIVIT, inhibitor of NFATc-1 activation, limited the effect of over-expressed PGC-1β on promoting the expression of cathepsin K, TRAP and MMP-9 in peripheral CD14+ monocytes from healthy controls. ChIP-QPCR analysis confirmed the immunoprecipitation of PGC-1β and the NFATc-1 promoter which indicated that PGC-1β binds to the NFATc-1 promoter region. Dual-luciferase reporter gene assay showed that over-expressed PGC-1β on the peripheral CD14+ monocytes from healthy controls increased the transcriptional activity of NFATc-1 in a dose-dependent manner. <h3>Conclusions</h3> Our data revealed a novel PGC-1β/NFATc-1 pathway contributing to excessive osteoclastogenesis in RA, which implied a potential therapeutic target of PGC-1β for osteoclast inhibition in RA. <h3>Acknowledgements</h3> This work was supported by National Natural Science Foundation of China (81471597, 81671612 and 81601427) and Guangdong Natural Science Foundation (2017A030313576 and 2017A030310236). <h3>Disclosure of Interest</h3> None declared.
Exposure to Residential Greenness as a Predictor of Cause-Specific Mortality and Stroke Incidence in the Rome Longitudinal Study
Authors: Riccardo Orioli, Chiara Antonucci, Matteo Scortichini, Francesco Cerza, Federica Marando, Carla Ancona, Fausto Manes, Marina Davoli, Paola Michelozzi, Francesco Forastiere, Giulia Cesaroni
Journal: Environmental Health Perspectives (2019)

Living in areas with higher levels of surrounding greenness and access to urban green areas have been associated with beneficial health outcomes. Some studies suggested a beneficial influence on mortality, but the evidence is still controversial.We used longitudinal data from a large cohort to estimate associations of two measures of residential greenness exposure with cause-specific mortality and stroke incidence.We studied a population-based cohort of 1,263,721 residents in Rome aged [Formula: see text], followed from 2001 to 2013. As greenness exposure, we utilized the leaf area index (LAI), which expresses the tree canopy as the leaf area per unit ground surface area, and the normalized difference vegetation index (NDVI) within 300- and [Formula: see text] buffers around home addresses. We estimated the association between the two measures of residential greenness and the outcomes using Cox models, after controlling for relevant individual covariates and contextual characteristics, and explored potential mediation by air pollution [fine particulate matter with aerodynamic diameter [Formula: see text] [Formula: see text] and [Formula: see text]] and road traffic noise.We observed 198,704 deaths from nonaccidental causes, 81,269 from cardiovascular diseases [CVDs; 29,654 from ischemic heart disease (IHD)], 18,090 from cerebrovascular diseases, and 29,033 incident cases of stroke. Residential greenness, expressed as interquartile range (IQR) increase in LAI within [Formula: see text], was inversely associated with stroke incidence {hazard ratio (HR) 0.977 [95% confidence interval (CI): 0.961, 0.994]} and mortality for nonaccidental [HR 0.988 (95% CI: 0.981, 0.994)], cardiovascular [HR 0.984 (95% CI: 0.974, 0.994)] and cerebrovascular diseases [HR 0.964 (95% CI: 0.943, 0.985)]. Similar results were obtained using NDVI with 300- or [Formula: see text] buffers.Living in greener areas was associated with better health outcomes in our study, which could be partly due to reduced exposure to environmental hazards. Further research is required to understand the underlying mechanisms. https://doi.org/10.1289/EHP2854.
Influence of respiration on left ventricular diastolic velocities in longitudinal Axis as assessed by duppler tissue imaging in normal subjects
Authors: Antônio Pazin-Filho, Minna M. Dias, André Schmidt, Oswaldo C. Almeida Filho, José Antônio Marin-Neto, Lourenço Gallo Júnior, Benedito Carlos Maciel
Journal: Journal of the American College of Cardiology (2000)
Brain Tumor Microenvironment and Host State: Implications for Immunotherapy
Authors: William Tomaszewski, Luis Sanchez-Perez, Thomas F. Gajewski, John H. Sampson
Journal: Clinical Cancer Research (2019)

Abstract Glioblastoma (GBM) is a highly lethal brain tumor with poor responses to immunotherapies that have been successful in more immunogenic cancers with less immunosuppressive tumor microenvironments (TME). The GBM TME is uniquely challenging to treat due to tumor cell–extrinsic components that are native to the brain, as well as tumor-intrinsic mechanisms that aid in immune evasion. Lowering the barrier of immunosuppression by targeting the genetically stable tumor stroma presents opportunities to treat the tumor in a way that circumvents the complications of targeting a constantly mutating tumor with tumor antigen–directed therapies. Tumor-associated monocytes, macrophages, and microglia are a stromal element of particular interest. Macrophages and monocytes compose the bulk of infiltrating immune cells and are considered to have protumor and immunosuppressive effects. Targeting these cells or other stromal elements is expected to convert what is considered the “cold” TME of GBM to a more “hot” TME phenotype. This conversion could increase the effectiveness of what have become conventional frontline immunotherapies in GBM—creating opportunities for better treatment through combination therapy.
P108/O28 Fatty acid oxidation can drive human monocyte derived CCL20 in the RA synovial environment
Authors: LC Rodgers, J Cole, K Rattigan, MP Barrett, N Kurian, IB McInnes, CS Goodyear
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Post-doctoral fellow. <h3>Introduction</h3> Metabolic pathways are considered to have a governing role in inflammatory cascades in myeloid cells. This is particularly evident in murine macrophages where glycolysis and fatty acid oxidation (FAO) have been implicated in inflammatory cascades and immune regulation respectively.<sup>1</sup> However, investigation of intracellular metabolism of human monocytes in the context of the hypoxic and inflammatory RA synovium is lacking. <h3>Objectives</h3> To mimic the hypoxic RA environment <i>in vitro</i> and metabolically profile human monocytes. Determine if altered metabolic pathways have a functional impact on monocytes under disease-relevant conditions. <h3>Methods</h3> Human monocytes were isolated from buffy coats and were exposed to hypoxia <i>in vitro</i>. Metabolic profiling of monocytes was carried out by LC-MS metabolomics. Inflammatory mediator release after LPS or RA-synovial fluid (RA-SF) stimulation was analysed by ELISA. FAO was inhibited by etomoxir or enhanced with exogenous carnitine supplements. Transcriptomics of RA blood monocytes and RA-SF macrophages was carried out by microarray. <h3>Results</h3> We report that hypoxia exacerbates CCL20 and IL-1β release in response to LPS and increases glycolytic intermediates at the expense of carnitines. Modulation of carnitine identified a novel role for FAO in the production of CCL20 in response to LPS. Transcriptomics of RA blood monocytes and RA-SF macrophages revealed that fatty acid metabolism was altered and CCL20 was increased when monocytes enter the RA milieu. <i>In vitro</i> analysis of monocytes showed that RA-SF increases carnitine abundance and CCL20 production in hypoxia, which was exacerbated by exogenous carnitine. <h3>Conclusions</h3> This work has revealed a novel inflammatory mechanism in RA which links FAO to CCL20 production in human monocytes. This may contribute to RA disease pathogenesis by promoting the recruitment of Th17 cells and osteoclastogenesis.<sup>2 3</sup> <h3>References</h3> O'Neill LA, <i>et al. Nat Rev Immunol</i> 2016;16:553–565. Hirota K, <i>et al. J Exp Med</i> 2007;204:2803–2812. Lisignoli G, <i>et al. J Cell Physiol</i> 2009;221:154–160. <h3>Disclosure of Interest</h3> None declared.
The clinical significance of NF-κΒ2, RelB, NIK, and BCL3 expression in NSCLC.
Authors: Fotinos-Ioannis D Dimitrakopoulos, Anna G Antonacopoulou, Anastasia E Kottorou, Fotini Kalofonou, Chrisoula D Scopa, Dimitrios Dougenis, Helen Papadaki, Haralabos Kalofonos
Journal: Journal of Clinical Oncology (2015)

e18511 Background: The aim of this study was to evaluate the expression of NF-κΒ2, RelB, NIK and BCL3 in NSCLC and to investigate their associations with clinicopathological parameters and overall survival outcomes. Methods: Immunohistochemical analysis for NF-κΒ2, RelB, NIK and BCL3 proteins was performed on 150 FFPE tissue specimens (140 tumor and 10 tumor-adjacent normal tissues) from NSCLC patients. In addition, we evaluated mRNA expression of NF-κΒ2, RELB, NIK and BCL3 in 60 NSCLC patients using real-time qPCR. Results: NF-kB2 and RelB protein levels were higher in tumor cells than in non-neoplastic adjacent tissues, whereas NIK and BCL3 were detected only in tumor tissues (p < 0.001). Cytoplasmic signal of NF-kB2 and RelB was correlated with stage (P = 0.03). Besides, regional lymph nodes infiltration was found to be correlated with nuclear expression of NF-kB2 (P = 0.04). NF-kB2 protein levels were found to be higher in lower grade tumors (P = 0.046), whereas expression of RelB was detected to have a type-specific pattern (p = 0.008). Furthermore, a significant association of RelB cytoplasmic expression with patients' two-year survival outcome was observed (P = 0.041). BCL3 protein expression was associated with maximum diameter (0.009), tumor grade (P = 0.013), relapse rate (P = 0.05), histological subtype (P = 0.031), disease stage (P = 0.045), the location of primary lesion (P = 0.045) and five-year survival (P = 0.039). Also, NIK expression was correlated with the disease stage (P = 0.005), the primary site (P = 0.032), the histological subtype (p = 0.008), the infiltration of the lymph nodes (P = 0.039) and the relapse rate (P = 0.008). With the exception of RELB (P = 0.009), mRNA levels of NF-κΒ2, NIK and BCL3 did not differ significantly between tumors and normal tissues. NF-κΒ2, RELB, and BCL3 mRNA levels were significantly related to the histological subtype and the maximum diameter of the tumor. Moreover, mRNA levels of RELB were correlated with relapse rate (P = 0.005) and of NF-κΒ2 with tumor grade (P = 0.016). Conclusions: The deregulation of the alternative NF-kB pathway in NSCLC seems to play a crucial role in the development and progression of the disease. This research has been co-financed by the EU and Greek national funds (Heracleitus II Program).
What Is Needed Now to Improve Cardiovascular Clinical Registries in the Future
Authors: Adrian F. Hernandez, Robert A. Harrington
Journal: JAMA Cardiology (2019)

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 Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
AKT as a Therapeutic Target for Cancer
Authors: Mengqiu Song, Ann M. Bode, Zigang Dong, Mee-Hyun Lee
Journal: Cancer Research (2019)

Many cellular processes in cancer are attributed to kinase signaling networks. V-akt murine thymoma viral oncogene homolog (AKT) plays a major role in the PI3K/AKT signaling pathways. AKT is activated by PI3K or phosphoinositide-dependent kinases (PDK) as well as growth factors, inflammation, and DNA damage. Signal transduction occurs through downstream effectors such as mTOR, glycogen synthase kinase 3 beta (GSK3β), or forkhead box protein O1 (FOXO1). The abnormal overexpression or activation of AKT has been observed in many cancers, including ovarian, lung, and pancreatic cancers, and is associated with increased cancer cell proliferation and survival. Therefore, targeting AKT could provide an important approach for cancer prevention and therapy. In this review, we discuss the rationale for targeting AKT and also provide details regarding synthetic and natural AKT-targeting compounds and their associated studies.
Phase 1 Open-Label, Multicenter Study of First-in-Class RORγ Agonist LYC-55716 (Cintirorgon): Safety, Tolerability, and Preliminary Evidence of Antitumor Activity
Authors: Devalingam Mahalingam, Judy S. Wang, Erika P. Hamilton, John Sarantopoulos, John Nemunaitis, Garry Weems, Laura Carter, Xiao Hu, Marshall Schreeder, H. Jeffrey Wilkins
Journal: Clinical Cancer Research (2019)

Transcription factor retinoic acid receptor-related orphan receptor γ (RORγ) regulates type 17 effector T-cell differentiation and function and is key to immune cell regulation. Synthetic RORγ agonists modulate immune cell gene expression to increase effector T-cell activity and decrease immune suppression. A phase 1 study evaluated the safety and tolerability of LYC-55716 (cintirorgon), a first-in-class, oral, small-molecule RORγ agonist in adults with relapsed/refractory metastatic cancer.Patients received 28-day treatment cycles of oral LYC-55716; dose and dosing regimen were determined according to pharmacokinetic profile and safety. Primary endpoints were safety and tolerability. Secondary endpoints included pharmacokinetics and objective tumor response rate.No dose-limiting toxicities occurred among the 32 enrolled patients who received LYC-55716 150 mg BID to 450 mg BID. Treatment-related adverse events (AE) were primarily grade 1-2 and included diarrhea (n = 11), fatigue (n = 7), anemia (n = 4), decreased appetite (n = 4), and nausea (n = 4). Grade 3 AEs were anemia (n = 2), elevated gamma-glutamyl transferase (n = 1), and hypophosphatemia (n = 1). Pharmacokinetic concentrations achieved levels expected for target gene regulation. Pharmacodynamic results indicated RORγ pathway engagement. Two patients (NSCLC and sarcomatoid breast cancer) had confirmed partial responses; 11 had disease stabilization for 2 to 12 months (6 received >4 months of treatment).These data support the safety and tolerability of LYC-55716 and selection of 450 mg BID dose for a phase 2a study assessing LYC-55716 clinical activity, safety, and biomarkers in patients with NSCLC, head and neck, gastroesophageal, renal cell, urothelial, and ovarian cancers.
Targeting CD37 in B-Cell Malignancies Using the Novel Therapeutic Duohexabody-CD37 Results in Efficient Killing of Tumor B-Cells Ex Vivo Via Complement-Dependent Cytotoxicity, Even in Relapsed and/or Refractory Patient Samples
Authors: Hilma J. Van Der Horst, Simone C. Oostindie, Saskia AGM Cillessen, Anne T Gelderloos, Marije B Overdijk, Martine E.D. Chamuleau, Esther C. W. Breij, Tuna Mutis
Journal: Blood (2018)
Safety and Efficacy of Alectinib in a Patient With Advanced NSCLC Undergoing Hemodialysis
Authors: Shinichiro Suzuki, Koji Haratani, Takayuki Takahama, Satomi Watanabe, Naoki Takegawa, Hidetoshi Hayashi, Masayuki Takeda, Kimio Yonesaka, Kazuhiko Nakagawa
Journal: Journal of Thoracic Oncology (2019)