tbuckley/cabot-search huggingface dataset:
Acid-degradable Dextran as an Image Guided siRNA Carrier for COX-2 Downregulation
Authors: Zhihang Chen, Balaji Krishnamachary, Marie-France Penet, Zaver M. Bhujwalla
Journal: Theranostics (2017)

Purpose: Effective in vivo delivery of siRNA to silence genes is a highly sought-after goal in the treatment of multiple diseases. Cyclooxygenase-2 (COX-2) is a major mediator of inflammation and its effective and specific downregulation has been of major interest to treat conditions ranging from auto-immune diseases to gastric inflammation and cancer. Here we developed a novel and efficient method to produce a multiple imaging reporter labeled cationic dextran nanopolymer with cleavable positive charge groups for COX-2 siRNA delivery. Methods: Small molecules containing amine groups were conjugated to the dextran scaffold through acetal bonds that were cleaved in weak acid conditions. With multiple imaging reporters located on different regions of the nanopolymer, cleavage of acetal bonds was visualized and quantified by imaging, for the first time, in cancer cells and tumors. Results: The biocompatibility of dextran and the rapid cleavage and release of amine groups minimized proinflammatory side effects and COX-2 induction observed with other siRNA carriers, to successfully achieve COX-2 downregulation in cancer cells and tumors. Imaging results confirmed that this nanoplex, consisting of the dextran nanopolymer with COX-2 siRNA, accumulated in tumors, and the amine functional groups were rapidly cleaved in cancer cells and tumors. Along with effective downregulation of COX-2, we also demonstrated, for the first time, effective downregulation of its major product prostaglandin E2 (PGE2). Conclusions: We successfully developed an efficient method to produce an acid-degradable dextran nanopolymer containing cleavable amine groups as the siRNA carrier. Because of its biocompatibility, this degradable dextran delivered COX-2 siRNA within tumors and efficiently downregulated COX-2 expression.
TCT-190 Dabigatran versus Warfarin for stroke prevention in Patients with Atrial Fibrillation: A Post-Hoc Analysis of RE-LY Correlating Body Mass Index with Outcome According to BMI Quintiles
Authors: Mark Jacobs, Javier Arce, Thomas McAndrew, Lars Wallentin, Michael Ezekowitz
Journal: Journal of the American College of Cardiology (2017)
TCT-135 The index of microvascular resistance as a surrogate for myocardial infarct extension and microvascular obstruction in patients with ST elevation myocardial infarction treated by primary angioplasty
Authors: Sergio Baptista, Mariana Faustino, Luis Brizida, Jose Loureiro, Antonio Freitas, João Augusto, João Abecasis, Célia Monteiro, Paulo Leal, Maura Nedio, Cláudia Antunes, Pedro Farto e Abreu, Victor Gil, Carlos Morais
Journal: Journal of the American College of Cardiology (2017)
The Unrecognized Challenges of the Patient-Physician Relationship
Authors: Tamara L. McCarron, Manal S. Sheikh, Fiona Clement
Journal: JAMA Internal Medicine (2017)

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
PTEN Is Fundamental for Elimination of Leukemia Stem Cells Mediated by GSK126 Targeting EZH2 in Chronic Myelogenous Leukemia
Authors: Jingfeng Zhou, Danian Nie, Juan Li, Xin Du, Yuhong Lu, Yangqiu Li, Chang Liu, Wei Dai, Yun Wang, Yanli Jin, Jingxuan Pan
Journal: Clinical Cancer Research (2017)

Purpose: Leukemia stem cells (LSCs) are an important source of tyrosine kinase inhibitor resistance and disease relapse in patients with chronic myelogenous leukemia (CML). Targeting LSCs may be an attractive strategy to override this thorny problem. Given that EZH2 was overexpressed in primary CML CD34+ cells, our purpose in this study was to evaluate the effects of targeting EZH2 on CML LSCs and clarify its underlying mechanism.Experimental Design: Human primary CML CD34+ cells and retrovirally BCR-ABL-driven CML mouse models were employed to evaluate the effects of suppression of EZH2 by GSK126- or EZH2-specific shRNA in vitro and in vivo Recruitment of EZH2 and H3K27me3 on the promoter of tumor-suppressor gene PTEN in CML cells was measured by chromatin immunoprecipitation assay.Results: Our results showed that pharmacologic inhibition of EZH2 by GSK126 not only elicited apoptosis and restricted cell growth in CML bulk leukemia cells, but also decreased LSCs in CML CD34+ cells while sparing those from normal bone marrow CD34+ cells. Suppression of EZH2 by GSK126 or specific shRNA prolonged survival of CML mice and reduced the number of LSCs in mice. EZH2 knockdown resulted in elevation of PTEN and led to impaired recruitment of EZH2 and H3K27me3 on the promoter of PTEN gene. The effect of EZH2 knockdown in the CML mice was at least partially reversed by PTEN knockdown.Conclusions: These findings improve the understanding of the epigenetic regulation of stemness in CML LSCs and warrant clinical trial of GSK126 in refractory patients with CML. Clin Cancer Res; 24(1); 145-57. ©2017 AACR.
The World Trade Organization's health agenda
Authors: D. J Lipson
Journal: BMJ (2001)

At the World Trade Organization's ministerial conference held last week in Doha, Qatar, world trade leaders from the organisation's 142 member governments focused attention on a critical health issue. Trade ministers debated the flexibility in the organisation's agreement on trade related aspects of intellectual property rights (TRIPS) for countries to protect public health in emergencies. Such clarification is critical for developing countries to improve access and affordability of essential medicines for millions of poor people suffering from HIV/AIDS and other life threatening diseases. But access to essential drugs is not the only health issue affected by global trade rules. Agreements made by the organisation also shape national policies and regulations on issues ranging from food safety and imports of hazardous goods to duties on tobacco.

And there is more to come. The World Trade Organization's negotiations launched in 2000 to further liberalise trade in services under the General Agreement on Trade in Services (GATS) could increase the organisation's influence on financing and delivery of health care. In contrast with other agreements, GATS gives countries considerable flexibility to decide which service sectors to open to …
Epigenetic suppression of hippocampal calbindin-D28k by ΔFosB drives seizure-related cognitive deficits
Authors: Jason C You, Kavitha Muralidharan, Jin W Park, Iraklis Petrof, Mark S Pyfer, Brian F Corbett, John J LaFrancois, Yi Zheng, Xiaohong Zhang, Carrie A Mohila, Daniel Yoshor, Robert A Rissman, Eric J Nestler, Helen E Scharfman, Jeannie Chin
Journal: Nature Medicine (2017)
All Thiopurines Are Equal But Some Thiopurines Are More Equal Than Others—Reply
Authors: Raoul Tibes, Nathalie Ertz-Archambault, Heidi Kosiorek
Journal: JAMA Oncology (2017)

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 Oncology 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 Oncology journal
Monitoring global health
Authors: Ilyas Mirza
Journal: BMJ (2005)

Monitoring global health Problems are primarily nationalEditor-Murray et al urge for improved global reporting of health data. 1 They also highlight the difficulty of showing national decision makers that good health data can strongly support decision making.Why is this?A reason may be that data are always subject to interpretation.The article by Murray et al is a case in point.They want to establish "an independent monitoring organisation," arguing that the World Health Organization is not fit to undertake the job because of tension between advocacy, monitoring, and evaluation.But evidence that it is this tension that leads to poor monitoring by WHO is weak, at best.In reality, the problems of global health reporting are primarily national (and subnational).The fact that the sum of deaths claimed by different programmes is greater than the actual number of deaths reflects epidemiological methods and the current limitations in global health reporting, more than any WHO failure.The global burden of disease project was limited by these issues, but it was undertaken as effectively in WHO as in any other organisation.Not only are there problems in capacity, understanding the value of surveillance, and coverage of health services.The reporting of health events can be politically sensitive or even economically damaging.It is therefore likely that political interference will continue (whoever collects the data) until governments can be shown that honesty pays.It is perhaps this failure that needs to be dealt with rather than setting up yet another organisation without a proper analysis of the reasons (and locus) for failures in global health reporting.
TCT-170 Bioresorbable scaffolds implantation for chronic total occlusion with bifurcation lesion
Authors: Magdalena Lanocha, Maciej Lesiak, Aleksander Araszkiewicz, Andrzej Siniawski, Przemyslaw Mitkowski, Wlodzimierz Skorupski, Marek Grygier, Malgorzata Pyda, Marta Kaluzna-Oleksy, Stanislaw Jankiewicz, Michal Lesiak, Sylwia Iwanczyk, Magdalena Dudek, Stefan Grajek
Journal: Journal of the American College of Cardiology (2017)
Margaret McCartney: Hydration, common sense, and evidence
Authors: Margaret McCartney
Journal: BMJ (2017)

“Remember—healthy pee is 1 to 3, 4 to 8 you must hydrate!” So goes a rhyming couplet from the Think Kidneys website, the online presence of the Transforming Participation in Chronic Kidney Disease programme. It comes with a colour chart, not unlike those available in shops selling paint, ranging from the off-white shade 1 (good) to shade 8, which I’d describe as orange with a hint of rust (severely dehydrated).1

I suspect that the normal colour of most doctors’ pee when at work—if they get to the loo at all—will range from “dehydrated” to “severely dehydrated” (that is, from mellow yellow to that classic dark orange). But is …
Comparative effectiveness of gemcitabine vs gemcitabine+nab-paclitaxel vs FOLFIRINOX for unresectable pancreatic cancer
Authors: Shun Yamamoto, Hideki Ueno, Midori Tanaka, Yuji Inagaki, Akihiro Ohba, Yasunari Sakamoto, Shunsuke Kondo, Chigusa Morizane, Takuji Okusaka
Journal: Annals of Oncology (2017)
CDK20 inhibition and immune checkpoint blockade: bringing cancer biology and tumour immunology together to develop novel treatment options for HCC
Authors: Tim F Greten, Firouzeh Korangy
Journal: Gut (2017)

On 22 September 2017 the Food and Drug Administration granted accelerated approval to nivolumab for the treatment of hepatocellular carcinoma (HCC) in patients who have been previously treated with sorafenib. Approval was based on a 154-patient subgroup of a multicentre, open-label trial conducted in patients with HCC and Child-Pugh A cirrhosis who progressed on or were intolerant to sorafenib.1 With an overall response rate of close to 15%, which lasted in more than 90% of the patients 6 months or longer, immune checkpoint blockade has become a treatment option for patients with HCC after many years of failures in drug development. However, these data also call for future combination studies, which will increase the number of patients responding to immunotherapy. But what is the best combination partner for an immune checkpoint inhibitor in HCC?

While immune checkpoint inhibitors successfully lead to activation of T cells in patients with HCC,2 they have no effect on the microenvironment and possible immunosuppressive mechanisms such as regulatory T cells and myeloid-derived suppressor cells (MDSCs). MDSCs represent a population of immature myeloid cells, composite of two major subsets, monocytic CD14+ …
TCT-42 Long-term Consequences Of Optical Coherence Tomography Findings During Percutaneous Coronary Intervention: The Centro Per La Lotta Contro l'Infarto - Optimization Of Percutaneous Coronary Intervention (CLI-OPCI) LATE Study
Authors: Enrico Romagnoli, Alessio La Manna, Francesco Burzotta, Laura Gatto, Valeria Marco, Chiara Russo, Alessandro Di Giorgio, Alberto Boi, Ugo Limbruno, Massimo Fineschi, Franco Fabbiocchi, Nevio Taglieri, Francesco Versaci, Carlo Trani, Corrado Tamburino, Fernando Alfonso, Gary Mintz, Francesco Prati
Journal: Journal of the American College of Cardiology (2017)
Precisely Enumerating Circulating Tumor Cells Utilizing a Multi-Functional Microfluidic Chip and Unique Image Interpretation Algorithm
Authors: Mingxing Zhou, Hui Zheng, Zhaoba Wang, Ren Li, Xiaoran Liu, Weikai Zhang, Zihua Wang, Huiping Li, Zewen Wei, Zhiyuan Hu
Journal: Theranostics (2017)

Enumerating circulating tumor cells (CTCs) has been demonstrably useful in cancer treatment. Although there are several approaches that have proved effective in isolating CTC-like cells, the crucial identification of CTCs continues to rely on the manual interpretation of immunofluorescence images of all cells that have been isolated. This procedure is time consuming and more importantly, CTC identification relies on subjective criteria that may differ between examiners. In this study, we describe the design, testing, and verification of a microfluidic platform that provides accurate and automated CTC enumeration using a common objective criterion.
Association between immune-related adverse events and efficacy of nivolumab in advanced non-small cell lung cancer
Authors: Yuko Usui, Hibiki Udagawa, Keisuke Kirita, Shigeki Umemura, Shingo Matsumoto, Kiyotaka Yoh, Seiji Niho, Koichi Goto
Journal: Annals of Oncology (2017)
Epigenetic reprogramming in liver fibrosis and cancer
Authors: Caroline L. Wilson, Derek A. Mann, Lee A. Borthwick
Journal: Advanced Drug Delivery Reviews (2017)

Novel insights into the epigenetic control of chronic liver diseases are now emerging. Recent advances in our understanding of the critical roles of DNA methylation, histone modifications and ncRNA may now be exploited to improve management of fibrosis/cirrhosis and cancer. Furthermore, improved technologies for the detection of epigenetic markers from patients' blood and tissues will vastly improve diagnosis, treatment options and prognostic tracking. The aim of this review is to present recent findings from the field of liver epigenetics and to explore their potential for translation into therapeutics to prevent disease promoting epigenome reprogramming and reverse epigenetic changes.
Intramyocardial inflammation predicts adverse outcome in patients with cardiac AL amyloidosis
Authors: Christine S. Siegismund, Felicitas Escher, Dirk Lassner, Uwe Kühl, Ulrich Gross, Friedrich Fruhwald, Philip Wenzel, Thomas Münzel, Norbert Frey, Reinhold P. Linke, Heinz‐Peter Schultheiss
Journal: European Journal of Heart Failure (2017)
Abstract 14763: Acute Effects of Exercise on Arterial Stiffness in Patients with Heart Failure with Preserved Ejection Fraction; The Role of Inflammatory Status
Authors: Mitsuru Masaki, Toshiaki Mano, Shinichi Hirotani, Akiyo Eguchi, Shohei Fujiwara, Masataka Sugahara, Masahiro Koshiba, Tohru Masuyama
Journal: Circulation (2014)

Aortic stiffening and endothelial dysfunction have been shown to be associated with heart failure with preserved EF (HFPEF). These were assessed at rest and after exercise in patients with HFPEF. T...
TCT-459 Simple vs complex strategy for the treatment of bifurcation lesions in the context of a coronary chronic total occlusion. A multicenter registry
Authors: Soledad Ojeda, Lorenzo Azzalini, Jorge Chavarria Viquez, Antonio Serra, Francisco Hidalgo, Susanna Benincasa, Livia L. Gheorghe, Roberto Diletti, Miguel Romero, Barbara Bellini, Alejandro Gutierrez-Barrios, Javier Suarez De Lezo, José Segura, Mauro Carlino, Antonio Colombo, Manuel Pan
Journal: Journal of the American College of Cardiology (2017)
TCT-38 Self-Expanding TAVR for Treatment of Aortic Insufficiency: An Analysis of the STS/ACC TVT Registry
Authors: Saif Anwaruddin, Nimesh Desai, Michael J. Reardon, James B. Hermiller, Paul Sorajja, Susheel Kodali, Jeffrey J. Popma, Jay Giri, Howard Herrmann, Gilbert Tang, Fenton McCarthy, Wilson Y. Szeto
Journal: Journal of the American College of Cardiology (2017)
Abstract 18961: Racial Differences in Plasma Ntprobnp Levels: The Regards Study
Authors: Navkaranbir S Bajaj, Suzanne E Judd, Garima Arora, Aleena Bennett, Orlando M Gutiérrez, Sumanth D Prabhu, George Howard, Virginia J Howard, Mary Cushman, Pankaj Arora
Journal: Circulation (2016)

Background: Natriuretic Peptides (NPs) are natriuretic and vasodilatory hormones synthesized from the heart. Whether NP system is endogenously suppressed in blacks free of prevalent cardiovascular ...
P2.05-039 Assessment of Lung Tumor Motion Comparing 4DCT, 4DCBCT and Motion of Implanted Beacons during Imaging and Irradiation
Authors: Elisabeth Steiner, Chun-Chien Shieh, Vincent Caillet, Nicholas Hardcastle, Carol Haddad, Paul Keall, Thomas Eade, Jeremy Booth
Journal: Journal of Thoracic Oncology (2017)
TCT-526 Mid-term clinical outcomes after bailout stenting with drug-eluting stent for suboptimal results of drug-coated balloon; Milan registry
Authors: Satoru Mitomo, Antonio Mangieri, Damiano Regazzoli, Marco Ancona, Francesco Giannini, Alaide Chieffo, Matteo Montorfano, Azeem Latib, Antonio Colombo
Journal: Journal of the American College of Cardiology (2017)
Adaptation of iCLIP to plants determines the binding landscape of the clock-regulated RNA-binding protein AtGRP7
Authors: Katja Meyer, Tino Köster, Christine Nolte, Claus Weinholdt, Martin Lewinski, Ivo Grosse, Dorothee Staiger
Journal: Genome biology (2017)

Functions for RNA-binding proteins in orchestrating plant development and environmental responses are well established. However, the lack of a genome-wide view of their in vivo binding targets and binding landscapes represents a gap in understanding the mode of action of plant RNA-binding proteins. Here, we adapt individual nucleotide resolution crosslinking and immunoprecipitation (iCLIP) genome-wide to determine the binding repertoire of the circadian clock-regulated Arabidopsis thaliana glycine-rich RNA-binding protein AtGRP7.iCLIP identifies 858 transcripts with significantly enriched crosslink sites in plants expressing AtGRP7-GFP that are absent in plants expressing an RNA-binding-dead AtGRP7 variant or GFP alone. To independently validate the targets, we performed RNA immunoprecipitation (RIP)-sequencing of AtGRP7-GFP plants subjected to formaldehyde fixation. Of the iCLIP targets, 452 were also identified by RIP-seq and represent a set of high-confidence binders. AtGRP7 can bind to all transcript regions, with a preference for 3' untranslated regions. In the vicinity of crosslink sites, U/C-rich motifs are overrepresented. Cross-referencing the targets against transcriptome changes in AtGRP7 loss-of-function mutants or AtGRP7-overexpressing plants reveals a predominantly negative effect of AtGRP7 on its targets. In particular, elevated AtGRP7 levels lead to damping of circadian oscillations of transcripts, including DORMANCY/AUXIN ASSOCIATED FAMILY PROTEIN2 and CCR-LIKE. Furthermore, several targets show changes in alternative splicing or polyadenylation in response to altered AtGRP7 levels.We have established iCLIP for plants to identify target transcripts of the RNA-binding protein AtGRP7. This paves the way to investigate the dynamics of posttranscriptional networks in response to exogenous and endogenous cues.
Surveillance de la résistance antimicrobienne chez l'homme, dans les denrées alimentaires et le bétail au Danemark
Authors: H C Wegener, F Bager, F M Aarestrup
Journal: Eurosurveillance (1997)

La resistance croissante des bacteries pathogenes aux agents antibacteriens souleve, a travers le monde, le probleme de l'utilisation de plus en plus repandue de ces agents dans la production animale, pouvant generer le developpement de bacteries resistantes ou de genes de resistance qui peuvent etre transferes a des bacteries qui causent des maladies a l'homme. Dans l'interet des consommateurs et plus largement de la sante humaine et animale, le ministre danois charge de l'Agriculture et de la Peche et le ministre charge de la Sante ont demande en 1995 au Laboratoire Veterinaire Danois, a l'Agence Danoise pour l'Alimentation et au Statens Serum Institut de collaborer pour la surveillance et la recherche dans le domaine de la resistance antimicrobienne.
Pharma gifts associated with higher number and cost of prescriptions written
Authors: Bob Roehr
Journal: BMJ (2017)

Drug prescribers in Washington, DC, who received gifts from pharmaceutical companies wrote more prescriptions, more costly prescriptions, and more branded prescriptions per patient than colleagues who did not receive such gifts, shows a new analysis that drew on local and federal database information.1

Some 2873 licensed professionals in the district—physicians, nurse practitioners, physician assistants, and others—wrote prescriptions under Medicare Part D, the part of the federal health insurance program covering seniors citizens that subsidizes the costs of prescription drugs. In 2013 a total of 1122 (39.1%) of these prescribers received gifts totaling $3.9m …