tbuckley/cabot-search huggingface dataset:
Moral Dilemmas for Physicians Treating Terminal Patients
Authors: Robert. M. Taylor, Johnson Wu
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
Streptococcus mutans activates the AIM2, NLRP3 and NLRC4 inflammasomes in human THP-1 macrophages
Authors: Yuri Song, Hee Sam Na, Eunjoo Park, Mi Hee Park, Hyun Ah Lee, Jin Chung
Journal: International Journal of Oral Science (2018)

Streptococcus mutans (S. mutans), a major aetiologic agent of dental caries, is involved in systemic diseases, such as bacterial endocarditis, if it enters the bloodstream through temporary bacteraemia. Interleukin (IL)-1β, a proinflammatory cytokine, is related to the host defences against pathogens, and its synthesis, maturation, and secretion are tightly regulated by the activation of the inflammasome, an inflammatory signalling complex. This study examined the signalling mechanism of IL-1β secretion and the inflammasome pathway induced by S. mutans to explain the molecular mechanism through which systemic infection by oral streptococci can occur. After infection of THP-1 cells with S. mutans, the expression of inflammasome components was detected using various methods. S. mutans induced IL-1β secretion via caspase-1 activation, and S. mutans-induced IL-1β secretion required absent in melanoma (AIM2), NLR family pyrin domain-containing 3 (NLRP3) and NLR family CARD domain-containing 4 (NLRC4) inflammasome activation. In particular, the S. mutans-induced NLRP3 inflammasome was mediated by adenosine triphosphate (ATP) release, potassium depletion and lysosomal damage. Our study provides novel insight into the innate immune response against S. mutans infection.
Abstract 367: Plasma Based cBIN1 Correlates with Myocardial Health in Heart Failure with Reduced Ejection Fraction
Authors: Rachel Baum, Bing Xu, Yu Xie, Ronit Zadikany, Tara Hitzeman, Sosse Agvanian, Dael Geft, David Chang, Jaime Moriguchi, Antoine Hage, Babak Azarbal, Lawrence Czer, Michelle Kittleson, Jignesh Patel, Jon Kobashigawa, Michele Hamilton, TingTing Hong, Robin M Shaw
Journal: Circulation Research (2017)

Background: Acquired heart failure (HF) originates with failing heart muscle, yet it is currently not possible to assay the biochemical health of cardiomyocytes. A key pathophysiology of HF is weakened calcium transient under the regulation of a membrane deformation protein bridging integrator 1 (BIN1). BIN1 decreases with HF and is blood available. We hypothesized that a recently cloned cardiac BIN1 isoform (cBIN1, BIN1+13+17) can be selectively measured to diagnose heart muscle health. Methods: Expression of cBIN1 in human heart and plasma was determined by immunoprecipitation, western blotting, and mass spectrometry analysis. A cBIN1 specific ELISA was developed using the combination of anti-BIN1 exon 17 (clone 99D from Sigma) and 13 (gift from Sarcotein Diagnostics) antibodies. Plasma cBIN1 concentration was then measured in a large clinical cohort of HFrEF (N=180) patients and compared to a sex and age matched cohort of healthy volunteers. Plasma cBIN1 concentration was also compared to NT-proBNP for its ability to detect patients with HFrEF. Results: Biochemistry and mass spectrometry confirms that cBIN1 is expressed in human myocardium. An ELISA assay selects for the cBIN1 isoform which significantly reduced in HFrEF (3.0±0.3, n=286, mean±SEM, ng/ml, p&lt;0.001) versus matched healthy volunteers (3.0±0.3, n=340). Low plasma cBIN1 diagnoses HFrEF with a ROC area under the curve of 0.92. cBIN1 ROC characteristics are additive to those of NT-proBNP. In addition, low plasma cBIN1 predicts future cardiovascular hospitalization and death over a 12 month follow-up period. Conclusions: A cBIN1 specific ELISA can quantify cBIN1 in human plasma. Low plasma cBIN1 diagnoses diseased heart muscle in HFrEF patients and predicts future hospitalization and death.
What is required from HCV point-of-care tests to reduce the burden of hepatitis C infection? ‘<i>Development and clinical validation of the genedrive point-of-care test for qualitative detection of hepatitis C virus</i>’
Authors: Maud Lemoine, Hans L Tillmann
Journal: Gut (2018)

The major advances in hepatitis C virus (HCV) diagnosis and treatment now make hepatitis C infection a curable disease over a short period of time and thus, theoretically, an eliminable disease. In its viral hepatitis elimination plan, the WHO aims, by 2030, to scale-up HCV treatment coverage to 80% and reduce HCV incidence and related mortality by 90% and 65%, respectively.1 This plan is ambitious and requires new strategies for the identification of hepatitis C cases especially in resource-limited countries which bear the highest burden of disease. The WHO estimates that only 20% of the 71 million individuals infected with HCV globally have been diagnosed and <10% have been treated.2 These figures are even lower in resource-limited countries. This poor intervention coverage is not only related to limited access to direct antiviral agents at low cost but also to the high cost and complexity of the conventional HCV RNA tests required for the identification of patients with viraemia. As a result, inexpensive and simple alternatives to conventional HCV nucleic acid tests (NAT) are urgently needed not only for low-income and middle-income countries but also high-income countries where healthcare resources are not infinite and HCV mainly affects difficult to reach populations.

In Gut , Llibre et al report high diagnostic accuracy of a new point-of-care (POC) test for qualitative detection of HCV (Genedrive, Epistem, Manchester, UK). From a large case–control study including samples from HCV-infected -treatment naive- and uninfected patients identified in 2 European (France and UK) and 10 African countries, the authors assessed the performance of the new test for the detection of HCV RNA using the Abbott real-time PCR assay as a reference. …
Abstract 2869: Nintedanib abrogates the activation and tumor-promoting effects of fibroblasts from lung adenocarcinoma patients
Authors: Jordi Alcaraz, Marta Gabasa, Rafael Ikemori, Frank Hilberg, Noemí Reguart
Journal: Cancer Research (2018)

Abstract Nintedanib is a clinically-approved multikinase receptor inhibitor that, in combination with docetaxel, provides clinical benefits to advanced lung adenocarcinoma (ADC) patients but not to lung squamous cell carcinoma (SCC) patients. However, the mechanisms underlying the selective therapeutic effects of Nintedanib in ADC remain poorly understood. Of note, Nintedanib is also approved to treat patients with idiopathic pulmonary fibrosis (IPF), a rare disease characterised by an abundant desmoplastic stroma rich in pathologically activated fibroblasts. Since the tumor stroma in lung cancer is also desmoplastic, and we recently showed that tumor-associated fibroblasts (TAFs) derived from ADC and SCC patients exhibit different phenotypes in vitro, we hypothesized that TAFs may underlie the selective effects of Nintedanib in ADC. To test this hypothesis we activated TAFs in culture with the pro-fibrotic cytokine TGF-β1 in the presence of increasing concentrations of Nintedanib, and collected the corresponding conditioned medium. Remarkably SCC-TAFs showed very modest inhibition of a panel of fibrotic markers including α-SMA, P4HA2 and fibrillar collagens (COL1A1, COL3A) in response to Nintedanib, in striking contrast to ADC-TAFs and paired lung parenchyma fibroblasts, which were markedly affected. This was matched by a significant reduction in the abilities of the conditioned medium of ADC-TAFs but not SCC-TAFs to promote cancer cell growth and invasion in a panel of lung cancer cell lines after Nintedanib treatment. These results reveal that Nintedanib is an effective inhibitor of stromal fibrosis and its associated tumor-promoting effects in ADC, and that the poor antifibrotic response of SCC-TAFs to Nintedanib may contribute to the differential clinical benefit observed in both subtypes. Our findings also support that TGF-β signalling and aberrant TAF-carcinoma cross-talk are regulated by different mechanisms in ADC and SCC. In addition they support that preclinical models based on carcinoma-TAF interactions may help defining the mechanisms of the poor antifibrotic response of SCC-TAFs to Nintedanib and testing new combined therapies to further expand the therapeutic effects of this drug in solid tumors. Citation Format: Jordi Alcaraz, Marta Gabasa, Rafael Ikemori, Frank Hilberg, Noemí Reguart. Nintedanib abrogates the activation and tumor-promoting effects of fibroblasts from lung adenocarcinoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2869.
Abstract P273: Dietary Saturated Fatty Acids and Coronary Heart Disease Risk in a Dutch Elderly Population: Food Source and Carbon Chain Length Matter
Authors: Jaike Praagman, Ester A de Jonge, Jessica C Kiefte de Jong, Joline W Beulens, Ivonne Sluijs, Josje Schoufour, Albert Hofman, Yvonne T van der Schouw, Oscar H Franco
Journal: Circulation (2016)

Introduction: The association between dietary saturated fatty acids (SFA) and the risk of coronary heart disease (CHD) is heavily debated and appears to be more complex than initially thought. The food source and carbon chain length of SFA, as well as the macronutrient replacing SFA in the diet may affect the association between dietary SFA and CHD. Hypothesis: We assessed the hypothesis that the association between dietary SFA and incident CHD is dependent on the food source of SFA, the carbon chain length of SFA, and the substituting macronutrient. Methods: From the Rotterdam Study, we included 4,722 healthy men and women, aged 55 years or older. Baseline (1998-1993) SFA intake was assessed using a validated food frequency questionnaire. Incident CHD comprised fatal and non-fatal myocardial infarctions and coronary mortality up to January 2011, and was assessed through digital linkage with municipality records and general practitioners. We used multivariable Cox’ proportional hazard models to calculate CHD risks for higher intakes of total SFA, SFA from specific food sources, SFA differing in carbon chain length, and for higher intakes of other macronutrients at the expense of total SFA. Results: During a median follow up of 16.3 years 569 CHD events occurred. Median total SFA intake was 15.7 en% per day, and the top three food sources were cheese (20.0%), meat (17.8%), and milk and milk products (13.1%). Total SFA intake was not significantly associated with CHD risk (Hazard Ratio (HR) per 5 en%: 1.13, 95%CI: 0.94, 1.22). Neither was SFA from specific food sources, although the data suggested an increased CHD risk for a higher intake of SFA from meat (HR per 1 en%: 1.06, 95%CI: 0.99, 1.14). Regarding SFA differing in carbon chain lengths, a higher CHD risk was observed for C16:0 intake (HR 1en% : 1.18, 95%CI: 1.03, 1.35), but not for the remaining SFA. No significant associations with CHD risk were observed for each 5% lower intake of energy from SFA and a concomitant higher intake of 5% of energy from carbohydrates (HR 5en% : 0.90: 0.80, 1.02), polyunsaturated fatty acids (HR 5en% : 0.90, 95%CI: 0.71, 1.15), cis -monounsaturated fatty acids (HR 5en% :1.09, 95%CI: 0.98, 1.22), or vegetable protein (HR 5en% : 0.88, 95%CI: 0.50, 1.53).The exception was substitution of SFA with animal protein, which was associated with higher CHD risk (HR 5en% : 1.24, 95%CI: 1.01, 1.51). Conclusions: In this Dutch elderly population, with a high median intake of total SFA, the association between SFA intake and CHD risk depends on the SFA food source and carbon chain length. Future intervention studies are needed to determine the importance of the SFA food sources, and to confirm that C16:0 is more strongly related with CHD risk than other SFA.
Sclerosing Cholangitis–Like Changes on Magnetic Resonance Cholangiography in Patients With Drug Induced Liver Injury
Authors: Jawad Ahmad, Simona Rossi, Shuchi K. Rodgers, Marwan Ghabril, Robert J. Fontana, Andrew Stolz, Paul H. Hayashi, Huiman Barnhart, David E Kleiner, Einar S. Bjornsson
Journal: Clinical Gastroenterology and Hepatology (2018)
Prognostic and predictive biomarkers for patients with idiopathic pulmonary fibrosis treated with pirfenidone: post-hoc assessment of the CAPACITY and ASCEND trials
Authors: Margaret Neighbors, Christopher R Cabanski, Thirumalai R Ramalingam, X Rebecca Sheng, Gaik W Tew, Chunyan Gu, Guiquan Jia, Kun Peng, Jill M Ray, Brett Ley, Paul J Wolters, Harold R Collard, Joseph R Arron
Journal: The Lancet Respiratory Medicine (2018)
Conflicts of Interest in Nutrition Research
Authors: Lisa Bero, Quinn Grundy
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 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
A Schlemm Canal Microstent for Intraocular Pressure Reduction in Primary Open-Angle Glaucoma and Cataract
Authors: Thomas W. Samuelson, David F. Chang, Robert Marquis, Brian Flowers, K. Sheng Lim, Iqbal Ike K. Ahmed, Henry D. Jampel, Tin Aung, Alan S. Crandall, Kuldev Singh, Tom Walters, Robert Marquis, Brian Flowers, Jason Jones, Steven D. Vold, Stephen E. Smith, Gary Foster, Brennan P. Greene, Dan B. Tran, Husam Ansari, Kenneth Olander, Neil Atodaria, Cathleen McCabe, Richard Lewis, Mujtaba Qazi, Quang Nguyen, Edward Meier, David Godfrey, Mohammed El Mallah, Jason Levine, C. Stark Johnson, E. Randy Craven, Richard D. Hawkins, William Clifford, Inder Paul Singh, Y. Ralph Chu, Alan C. Crandall, Douglas Rhee, K. Sheng Lim, Jose Manuel Larrosa Poves, Marek Rekas, Robert Edward T. Ang, Sebastian Gagne, Leon Au, Michael Dorey, Marina Ramirez, Stefano Gandolfi, Julian Garcia-Feijoo, David Broadway, Norbert Pfeiffer
Journal: Ophthalmology (2018)
Abstract 3494: Downregulation of SREBPs inhibited colon cancer cell growth and tumor initiation by alteration of metabolism
Authors: Yang-an Wen, Xiaopeng Xiong, Yekaterina Zaytseva1, Tianyan Gao
Journal: Cancer Research (2018)

Abstract Sterol regulatory element binding proteins (SREBPs) belong to a family of transcription factors that regulate the expression of genes required for the synthesis of fatty acids and cholesterol. There are three SREBP isoforms, SREBP1a, SREBP1c and SREBP2, have been identified in mammalian cells. SREBP1a and SREBP1c are derived from a single gene through the use of alternative transcription start sites. Increasing evidence suggests that increased lipogenesis is needed for cancer cells to accommodate high rates of proliferation. Activation of SREBP1 and enhanced expression of its target genes have been observed in different types of human cancers. However, the functional importance of SREBPs in colon cancer remains to be fully elucidated. In this study, we investigated the role of SREBP-mediated lipid biosynthesis in promoting tumor growth and initiation by regulating cellular metabolism in colon cancer. Knockdown of SREBP-1 or SREBP-2 decreased the expression of target genes required for lipid biosynthesis and levels of fatty acids and triacylglycerides in colon cancer cells. Bioenergetic analysis using Seahorse XF96 Extracelluar Flux Analyzer revealed that silencing SREBP-1 or SREBP-2 expression reduced the mitochondrial respiration, glycolysis, as well as fatty acid oxidation suggesting an inhibition of cellular metabolism. As a result, the rate of cell proliferation and the ability of cancer cells to form tumor spheroids in suspension were decreased. Similar results were obtained in colon cancer cells in which SCAP, an upstream protease responsible for activating SREBP-1 and SREBP-2, was silenced. Mechanistically, downregulation of SREBPs inhibited the activation of AMPK and Akt signaling. Furthermore, knockdown of SREBP-1 or SREBP-2 inhibited xenograft tumor growth in vivo and significantly decreased the expression of genes associated cancer stem cells. Taken together, our findings establish the molecular basis of SREBPs-dependent metabolic regulation and provide a rationale for targeting fatty acid synthesis as a promising approach in colon cancer treatment. Citation Format: Yang-an Wen, Xiaopeng Xiong, Yekaterina Zaytseva1, Tianyan Gao. Downregulation of SREBPs inhibited colon cancer cell growth and tumor initiation by alteration of metabolism [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3494.
Standardization of Continuous Renal Replacement Therapy
Authors: Eric Y. Chang, Ifedolapo Odebunmi, Anam Umar
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
Etomoxir Actions on Regulatory and Memory T Cells Are Independent of Cpt1a-Mediated Fatty Acid Oxidation
Authors: Brenda Raud, Dominic G. Roy, Ajit S. Divakaruni, Tatyana N. Tarasenko, Raimo Franke, Eric H. Ma, Bozena Samborska, Wei Yuan Hsieh, Alison H. Wong, Philipp Stüve, Catharina Arnold-Schrauf, Melanie Guderian, Matthias Lochner, Shakuntala Rampertaap, Kimberly Romito, Joseph Monsale, Mark Brönstrup, Steven J. Bensinger, Anne N. Murphy, Peter J. McGuire, Russell G. Jones, Tim Sparwasser, Luciana Berod
Journal: Cell Metabolism (2018)
Abstract 668: Electron paramagnetic resonance (EPR) pO2 image-guided tumor biopsies to analyze hypoxia-induced proteins
Authors: Richard Miller, Boris Epel, Martyna Elas, Martyna Krzykawska-Serda, Matthew Maggio, Eugene Barth, Mihai Giurcanu, Howard Halpern
Journal: Cancer Research (2018)

Abstract Stereotactic MCa4 and FSa tumor tissue biopsies registered with electron paramagnetic resonance (EPR) O2 imaging were used to identify sampling sites suitable to measure protein levels of three hypoxic cell biomarkers, hypoxia-induced factor 1-alpha (HIF-1α), carbonic anhydrase IX (CA9), and vascular endothelial growth factor (VEGF). EPR imaging provided quantitative localization of pO2 levels in tumors grown in the legs of C3H mice. Since hypoxic cells (pO2 &amp;lt;10 torr) are up to three times more resistant than normoxic cells to radiation lethality, identification of hypoxic populations to predict radiotherapeutic outcome is important. The oxygen broadening of narrow EPR spectral lines, or, equivalently, the increase in relaxation rates of electron magnetization, displays pO2 with 1-2 torr resolution in image voxels less than 1 mm3. The pO2 reporter molecule OX063 was used to image hypoxic areas in tumors. The molecule is selectively retained in tumors with a half-life of ~30 minutes. We used inversion recovery electron spin echo (IRESE) to measure the T1 rate of the trityl inside the tumor-bearing leg of mice. Voxel maps with O2 levels less than 10 torr (HF10) were used to guide biopsy cannulas to obtain tumor cell samples. Each of these biopsy cores were further subdivided into samples from which protein amounts could be determined via ELISA. Results from MCa4 and FSa tumor cells indicate a strong correlation between EPR pO2-identified hypoxic areas (&amp;lt;10 torr) and HIF-1α, CA9, and VEGF protein. The activation of various genes, including stem-cell activation, angiogenesis, vasodilation, glucose metabolism, reduced apoptotic activity, and cell cycle changes, contributes to poor radiotherapeutic outcome. EPR pO2 imaging may be used to precisely identify hypoxic areas harboring cells that protect tumor tissue from the toxicity of conventional radiation leading to radiotherapeutic failure. Grant Support: This work was supported by grants from the NIH, including R01 CA98575 and P41 EB002034. Citation Format: Richard Miller, Boris Epel, Martyna Elas, Martyna Krzykawska-Serda, Matthew Maggio, Eugene Barth, Mihai Giurcanu, Howard Halpern. Electron paramagnetic resonance (EPR) pO2 image-guided tumor biopsies to analyze hypoxia-induced proteins [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 668.
CD8+ T-Cell Density Imaging with 64Cu-Labeled Cys-Diabody Informs Immunotherapy Protocols
Authors: Jai Woong Seo, Richard Tavaré, Lisa M. Mahakian, Matthew T. Silvestrini, Sarah Tam, Elizabeth S. Ingham, Felix B. Salazar, Alexander D. Borowsky, Anna M. Wu, Katherine W. Ferrara
Journal: Clinical Cancer Research (2018)

Noninvasive and quantitative tracking of CD8