tbuckley/cabot-search huggingface dataset:
Abstract 19022: Clinical Predictors of Post-operative Permanent Pacemaker Implantation in Patients Undergoing Cardiac Surgery for Infective Endocarditis
Authors: Terence E Hill, Erich Kiehl, Nabin Shrestha, Steven Gordon, Chaitra Mohan, Venu Menon, Gosta Pettersson, Syed Hussain, Khaldoun G Tarakji
Journal: Circulation (2017)

Introduction: The incidence of infective endocarditis (IE) in the United States has been increasing over the last decade and many patients require surgical intervention. Cardiac conduction disease frequently complicates endocarditis. We sought to evaluate pre-operative risk factors for needing a permanent pacemaker (PPM) after surgery for infective endocarditis. Methods: Patients admitted to Cleveland Clinic for endocarditis from 1/1/2007 through 2/3/2013 who underwent cardiac surgery for endocarditis and did not have a pre-existing cardiac implantable electronic device were included. Cases of IE were ascertained through an IRB approved IE registry. Data were analyzed using multi-variable logistic regression to create a model for PPM requirement for atrioventricular block (AV) block after surgery. Patients who died post-operatively were excluded from the analysis. Results: Among 468 operated patients who met inclusion criteria, 24 patients who died during the index admission were excluded. The aortic valv...
Deoxyribozymes targeted to EBV-LMP1 mRNA induce apoptosis and enhance radiosensitivity in LMP1-positive cells
Authors: Zhong-Xin Lu, Ya Cao, Lun-Quan Sun
Journal: Cancer Research (2005)

573  Epstein-Barr Virus (EBV) is involved in the carcinogenesis of several human cancers such as nasopharyngeal carcinoma and Burkitt’s lymphoma. The latent membrane protein (LMP1) encoded by EBV is expressed in the majority of EBV-associated human malignancies and has been suggested to be one of the major oncogenic factors in EBV-mediated carcinogenesis. Therefore, genetic manipulation of LMP1 expression may provide a novel strategy for the treatment of the EBV-associated human cancers. Deoxyribozymes (DNAzymes) are catalytic nucleic acids that bind and cleave a target RNA in a highly sequence-specific manner. We have designed several LMP1-specific DNAzymes and tested their effect on cell proliferation and apoptosis in LMP1-positive cells. Here, we show that active DNAzymes down-regulated the EBV oncoprotein LMP1, associated with a decrease in the level of antiapoptotic Bcl-2 and a release of Cytochrome c from mitochondria in B95-8 cells. This effect was associated with inhibition of cell proliferation and stimulation of apoptosis. This was further confirmed by the result that the active DNAzymes significantly reduced the LMP1 and Bcl-2 protein expression, induced a release of Cytochrome c from mitochondria, inhibited cell proliferation and induced apoptosis in the nasopharyngeal carcinoma cell line CNE1-LMP1, which constitutively expresses the LMP1. In addition, when combined with radiation treatment, the DNAzymes significantly induced apoptosis in CNE1-LMP1 cells, leading to increased radiosensitivity. The present results indicate that LMP1 may represent a target for DNAzymes for EBV associated carcinoma via cell proliferation and apoptosis pathways. These results also provide the basis for a novel anticancer strategy to improve the therapeutic index in radiotherapy of EBV-related cancers.
Real-world treatment patterns and clinical outcomes in patients receiving second-line (2L) treatment for advanced or metastatic gastric cancer (GC).
Authors: Mayur Amonkar, David Gomez-Ulloa, Smita Kothari, Winson Y. Cheung, Ian Chau, John Raymond Zalcberg, Nuria Lara, Alfredo Falcone
Journal: Journal of Clinical Oncology (2019)

102 Background: Despite increased survival demonstrated for patients with advanced / metastatic GC due to 2L chemotherapy, different standard of care options exist. This study aims to describe RW treatment patterns and clinical outcomes in patients with advanced / metastatic GC receiving 2L treatment. Methods: Retrospective chart review study conducted in Australia, Canada, Italy and UK. Patients diagnosed with metastatic / unresectable GC receiving 2L treatment between January 2013 and July 2015 were enrolled. Patient characteristics, treatment patterns and clinical outcomes were captured for 12 months from the start of 2L treatment or until death. Results: 280 patients were included (mean age 60.9 years, 68.9% male). Half of the patients (51.8%) received monotherapy in 2L. Among these, taxanes were most prescribed (69.0%) followed by irinotecan (22.1%). Doublet chemotherapy was the most common combination therapy in 2L (75.6%) with fluoropyrimidine + irinotecan (33.3%) being the most used, followed by fluoropyrimidine + platinum (17.8%). Less than a third of patients (29.3%) received subsequent third-line (3L) treatment; 62.7% received monotherapy [mainly taxanes (69.2%) or irinotecan (19.2%)]. Most 3L patients who had combination therapy received a doublet (86.7%), most frequently fluoropyrimidine combined with irinotecan (53.3%) or platinum (20.0%). The majority of 2L patients (93.6%) had received combination therapy as first-line treatment, of whom 67.9% had received triplet chemotherapy, most commonly anthracycline + fluoropyrimidine + platinum (51.1%). Estimated median real-world progression free survival (PFS) and overall survival (OS) after 2L treatment initiation was 3.09 (95% CI: 2.76-3.68) and 6.54 (5.29-7.76) months, respectively, and estimated probability of PFS and OS at 12 months was 8% and 26%, respectively. Conclusions: The clinical management of advanced / metastatic GC patients in 2L treatment commonly involves taxanes or irinotecan as monotherapy, or irinotecan or platinum-based combinations with fluoropyrimidines. RW clinical outcomes for 2L treatment are similar to randomised controlled trials but remain poor.
Youth Vaping and Associated Risk Behaviors — A Snapshot of Colorado
Authors: Tista S Ghosh, Rickey Tolliver, Alison Reidmohr, Michelle Lynch
Journal: New England Journal of Medicine (2019)

In the report Public Health Consequences of E-Cigarettes, an expert committee of the National Academies of Sciences, Engineering, and Medicine presents 47 conclusions related to outcomes of e-cigarettes, including their key constituents, human health effects, initiation and cessation of combustible tobacco cigarette use, and harm reduction.The conclusions below are organized by level of evidence (with each level of evidence defined on page 2).
TCT-784 Transcatheter Aortic Valve Implantation In Patients With Severe Aortic Valve Stenosis and Large Aortic Annulus, Using the Self-Expanding 31-mm Medtronic CoreValve Prosthesis: First Clinical Experience
Authors: Freek Nijhoff, Pierfrancesco Agostoni, Hafid Amrane, Azeem Latib, Luca Testa, Jacopo A. Oreglia, Mariam Samim, Federico De Marco, Francesco Bedogni, Francesco Maisano, Giuseppe Bruschi, Antonio Colombo, A.J. van Boven, Pieter R. Stella
Journal: Journal of the American College of Cardiology (2013)
Integrative analysis of the intestinal metabolome of childhood asthma
Authors: Kathleen A. Lee-Sarwar, Rachel S. Kelly, Jessica Lasky-Su, Robert S. Zeiger, George T. O'Connor, Megan T. Sandel, Leonard B. Bacharier, Avraham Beigelman, Nancy Laranjo, Diane R. Gold, Scott T. Weiss, Augusto A. Litonjua
Journal: Journal of Allergy and Clinical Immunology (2019)
Flow-dependent epigenetic regulation of IGFBP5 expression by H3K27me3 contributes to endothelial anti-inflammatory effects
Authors: Suowen Xu, Yanni Xu, Meimei Yin, Shuya Zhang, Peng Liu, Marina Koroleva, Shuyi Si, Peter J. Little, Jaroslav Pelisek, Zheng Gen Jin
Journal: Theranostics (2018)

Rationale:Atherosclerosis is a chronic inflammatory and epigenetic disease that is influenced by different patterns of blood flow.However, the epigenetic mechanism whereby atheroprotective flow controls endothelial gene programming remains elusive.Here, we investigated the possibility that flow alters endothelial gene expression through epigenetic mechanisms.Methods: En face staining and western blot were used to detect protein expression.Real-time PCR was used to determine relative gene expression.RNA-sequencing of human umbilical vein endothelial cells treated with siRNA of enhancer of zeste homolog 2 (EZH2) or laminar flow was used for transcriptional profiling.Results: We found that trimethylation of histone 3 lysine 27 (H3K27me3), a repressive epigenetic mark that orchestrates gene repression, was reduced in laminar flow areas of mouse aorta and flow-treated human endothelial cells.The decrease of H3K27me3 paralleled a reduction in the epigenetic "writer"-EZH2, the catalytic subunit of the polycomb repressive complex 2 (PRC2).Moreover, laminar flow decreased expression of EZH2 via mechanosensitive miR101.Genome-wide transcriptome profiling studies in endothelial cells treated with EZH2 siRNA and flow revealed the upregulation of novel mechanosensitive gene IGFBP5 (insulin-like growth factor-binding protein 5), which is epigenetically silenced by H3K27me3.Functionally, inhibition of H3K27me3 by EZH2 siRNA or GSK126 (a specific EZH2 inhibitor) reduced H3K27me3 levels and monocyte adhesion to endothelial cells.Adenoviral overexpression of IGFBP5 also recapitulated the anti-inflammatory effects of H3K27me3 inhibition.More importantly, we observed EZH2 upregulation, and IGFBP5 downregulation, in advanced atherosclerotic plaques from human patients.Conclusion: Taken together, our findings reveal that atheroprotective flow reduces H3K27me3 as a chromatin-based mechanism to augment the expression of genes that confer an anti-inflammatory response in the endothelium.Our study exemplifies flow-dependent epigenetic regulation of endothelial gene expression, and also suggests that targeting the EZH2/H3K27me3/IGFBP5 pathway may offer novel therapeutics for inflammatory disorders such as atherosclerosis.
Steroid-Refractory Acute Gvhd in Children: Retrospective Analysis of the AIEOP HSCT Registry
Authors: Marco Zecca, Daria Pagliara, Franca Fagioli, Attilio Rovelli, Edoardo Lanino, Arcangelo Prete, Elisabetta Calore, Stella Boghen, Pietro Merli, Francesca Compagno, Mimmo Ripaldi, Fulvio Porta, Franco Locatelli
Journal: Blood (2018)
Abstract MP39: Trends in Diet Quality Among US Adults by Supplemental Nutrition Assistance Program Participation Status: 1999-2014
Authors: Fangfang Zhang, Junxiu Liu, Colin D Rehm, Parke Wilde, Jerold R Mande, Dariush Mozaffarian
Journal: Circulation (2018)

Introduction: Unhealthful diet is one of the top contributors to the chronic disease burden in the U.S. There are growing concerns that socioeconomic disparities exist in Americans’ diets and this disparity may have widened over time. Aim: To characterize trends in dietary intake of key food groups and nutrients among low-income Americans who participated in the Supplemental Nutrition Assistance Program (SNAP), and assess whether disparities in U.S. diets have persisted, improved, or worsened over time. Methods: Nationally representative sample of 6,162 adults aged 20 years or older who participated in SNAP, 6,692 income-eligible nonparticipants, and 25,842 higher-income nonparticipants from 8 National Health and Nutrition Examination Survey (NHANES) cycles (1999-2014). Exposures are calendar year and SNAP participation status. Survey-weighted, energy-adjusted mean scores and proportion meeting the American Heart Association (AHA) 2020 Strategic Impact Diet Goals (5 primary components: fruits/vegetables, whole grains, fish/shellfish, sugar-sweetened beverages (SSBs), sodium; 3 secondary components: nuts/seeds/legumes, processed meats, saturated fat). Intakes of individual food groups and nutrients were also assessed. Results: From 2003-2004 to 2013-2014 among SNAP participants with data on two-day dietary recall, primary diet score (maximum of 50) modestly increased (15.6 to 16.6; P-trend =0.03) while the secondary diet score (maximum of 80 points) did not change (31.5 to 32.1; P-trend =0.11). The proportion of SNAP participants having a poor diet decreased from 74.3% to 68.6%, the proportion having an intermediate-quality diet increased from 25.5% to 31.2%, and the proportion of having an ideal diet remained unchanged (0.2%.). Among primary components, changes were strongest for SSBs (-0.43 servings/d, P-trend=0.001) and whole grains (+0.25 servings/d, P-trend&lt;0.001). Compared to higher-income nonparticipants and income-eligible nonparticipants, SNAP participants had weaker improvements in both primary and secondary diet scores. From 1999-2000 to 2013-2014, disparities persisted for most dietary components, worsened for nuts/seeds and added sugars, and weakened for sodium. Conclusion: Despite some improvements in diet quality, SNAP participants still fall far short of meeting the AHA Goals for a healthful diet, and dietary disparities persisted or worsened for most dietary components.
Prenatal PM exposure combined with skin barrier dysfunction is associated with AD and its persistence in early life: COCOA study
Authors: Eun Lee, So-Yeon Lee, Hwan-Cheol Kim, Jisun Yoon, Hyun-ju Cho, Sungsu Jung, Song-I. Yang, Kangmo Ahn, Youn Ho Sheen, Kyung Won Kim, Dong In Suh, Soo-Jong Hong
Journal: Journal of Allergy and Clinical Immunology (2019)
Systemic Succinate Homeostasis and Local Succinate Signaling Affect Blood Pressure and Modify Risks for Calcium Oxalate Lithogenesis
Authors: Ahlam Khamaysi, Shireen Anbtawee-Jomaa, Moran Fremder, Hadar Eini-Rider, Liana Shimshilashvili, Sara Aharon, Elina Aizenshtein, Tomer Shlomi, Audrey Noguchi, Danielle Springer, Orson W. Moe, Nikolay Shcheynikov, Shmuel Muallem, Ehud Ohana
Journal: Journal of the American Society of Nephrology (2019)

In the kidney, low urinary citrate increases the risk for developing kidney stones, and elevation of luminal succinate in the juxtaglomerular apparatus increases renin secretion, causing hypertension. Although the association between stone formation and hypertension is well established, the molecular mechanism linking these pathophysiologies has been elusive.To investigate the relationship between succinate and citrate/oxalate levels, we assessed blood and urine levels of metabolites, renal protein expression, and BP (using 24-hour telemetric monitoring) in male mice lacking slc26a6 (a transporter that inhibits the succinate transporter NaDC-1 to control citrate absorption from the urinary lumen). We also explored the mechanism underlying this metabolic association, using coimmunoprecipitation, electrophysiologic measurements, and flux assays to study protein interaction and transport activity.Compared with control mice, slc26a6-/- mice (previously shown to have low urinary citrate and to develop calcium oxalate stones) had a 40% decrease in urinary excretion of succinate, a 35% increase in serum succinate, and elevated plasma renin. Slc26a6-/- mice also showed activity-dependent hypertension that was unaffected by dietary salt intake. Structural modeling, confirmed by mutational analysis, identified slc26a6 and NaDC-1 residues that interact and mediate slc26a6's inhibition of NaDC-1. This interaction is regulated by the scaffolding protein IRBIT, which is released by stimulation of the succinate receptor SUCNR1 and interacts with the NaDC-1/slc26a6 complex to inhibit succinate transport by NaDC-1.These findings reveal a succinate/citrate homeostatic pathway regulated by IRBIT that affects BP and biochemical risk of calcium oxalate stone formation, thus providing a potential molecular link between hypertension and lithogenesis.
Potential roles for tenascin in (very) early diagnosis and treatment of rheumatoid arthritis
Authors: Maurizio Cutolo, Stefano Soldano, Sabrina Paolino
Journal: Annals of the Rheumatic Diseases (2019)

We read the interesting article by Aungier et al suggesting that targeting proinflammatory signals from the C-terminal fibrinogen-like globe domain (FBG) of tenascin-C (TNC) might provide a viable strategy to treat rheumatoid arthritis (RA).1 

The present story and possible developments are really interesting and might link to other recent evidences concerning the same argument.

We described for the first time in 1992 the distribution of TNC in normal and pathological synovial tissues from patients with RA and osteoarthritis (OA) by indirect immunofluorescence using specific monoclonal antibodies.2 

Tenascin was found in normal synovium just beneath the whole lining cell layer; however, a higher density and spreading pattern of distribution was observed in RA and OA sections, but the possible meaning was unclear at that time.

Soon after, these early data were confirmed by others, and several investigations added …
Gadoxetic acid-enhanced magnetic resonance imaging: Hepatocellular carcinoma and mimickers
Authors: Yeun-Yoon Kim, Mi-Suk Park, Khalid Suliman Aljoqiman, Jin-Young Choi, Myeong-Jin Kim
Journal: Clinical and Molecular Hepatology (2019)

Gadoxetic acid, a hepatocyte-specific magnetic resonance imaging (MRI) contrast agent, has emerged as an important tool for hepatocellular carcinoma (HCC) diagnosis. Gadoxetic acid-enhanced MRI is useful for the evaluation of earlystage HCC, diagnosis of HCC precursor lesions, and highly sensitive diagnosis of HCC. Furthermore, functional information provided by gadoxetic acid-enhanced MRI can aid in the characterization of focal liver lesions. For example, whereas lesions lack functioning hepatocytes appear hypointense in the hepatobiliary phase, preserved or enhanced expression of organic anion transporting polypeptides in some HCCs as well as focal nodular hyperplasia lead to hyperintensity in the hepatobiliary phase; and a targetoid appearance on transitional phase or hepatobiliary phase imaging can be helpful for identifying the histopathological composition of tumors. While gadoxetic acid-enhanced MRI may improve the sensitivity of HCC diagnosis and provide new insights into the characterization of focal liver lesions, there are many challenges associated with its use. This article reviews the pros and cons of HCC diagnosis with gadoxetic acid-enhanced MRI and discuss some clues in the radiological differentiation of HCC from HCC mimickers.
Dupilumab Consistently Improves Rhinoconjunctivitis-Specific Health-Related Quality of Life in Patients With Uncontrolled, Moderate-to-Severe Asthma and Comorbid Allergic Rhinitis: Results from the Phase 3 LIBERTY ASTHMA QUEST Study
Authors: Jean Bousquet, Jorge F. Maspero, Bradley E. Chipps, Jonathan Corren, J. Mark FitzGerald, Zhen Chen, Yufang Lu, Paul Rowe, Heribert Staudinger, Marcella Ruddy, Neil M.H. Graham, Siddhesh Kamat, Nikhil Amin, Ariel Teper, Asif Khan
Journal: Journal of Allergy and Clinical Immunology (2019)
Improving clinician confidence and practice behavior on the therapeutic management of microsatellite-instability high (MSI-H) gastrointestinal (GI) cancers.
Authors: Hamsa Jaganathan, Anne Roc, Wendy Turell, Russell Broaddus, Michael J. Overman
Journal: Journal of Clinical Oncology (2019)

641 Background: With recent advances of immunotherapy and updates to practice guidelines, clinicians may be challenged in applying and managing the outcomes of new treatment standards for their patients with MSI-H GI cancers. To address this need, a one-hour education session was provided to clinicians and learner responses were evaluated to determine the areas of improvement in the therapeutic management of MSI-H GI cancers. Methods: PlatformQ Health developed and executed a 1-hour online CME program on MSI-H GI cancers, which was broadcast live in March 2018 and offered online for 6 months. The program attracted a total of 439* learners. Survey-based evaluations before (n = 338) and after education (n = 147) targeted self-reported clinician data on confidence, practice behaviors, knowledge, and competence. Results: A self-reported survey (n = 56) conducted 8-12 weeks after education reported that 50% of learners were more confident in managing patients with MSI-H GI cancers, 41% in following NCCN practice guidelines for MMR/MSI testing, and 34% in utilizing checkpoint inhibitors for MSI-H GI tumors. Competence on selecting an appropriate treatment for a patient with MSI-H colon cancer significantly improved between pre- and post-education (52% and 63%, respectively; p &lt; 0.001). Significant improvements in knowledge regarding the latest immunotherapy data (33% at baseline to 54% post-education; p &lt; 0.001) and available methods for determining MMR/MSI-H status (18% at baseline to 41% post-education; p &lt; 0.001) were also observed. Conclusions: Outcomes results from education demonstrate learner improvements on facets of management of MSI-H GI cancers. Based on the analysis, further education is needed, particularly in areas of management of immune-related side effects in line with recent ASCO and NCCN guidelines, tools for determining dMMR/MSI-H status, and deciding on optimal treatment based on tumor status. *As of September 10, 2018, data collection is ongoing.
Quality and Safety in Health Care, Part LI
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2019)

Abstract Engagement has 3 different components, the most important of which are felt by some to be vigor and dedication. The third component is absorption. Engagement is considered by some to be the opposite of burnout, although others consider these terms to be not quite opposite, but nearly so. Engaged physicians have greater job satisfaction and less burnout and are less likely to leave their job than physicians who are not engaged. Those physicians who are engaged in their work tend to render patient care that is not only more efficient but also has a higher degree of quality and safety.