tbuckley/cabot-search huggingface dataset:
Abstract 134: Rigid Microenvironments Promote Cardiac Differentiation Of Mouse And Human Embryonic Stem Cells
Authors: Armin Arshi, Yasuhiro Nakashima, Haruko Nakano, Sarayoot Eaimkhong, Denis Evseenko, Jason Reed, Adam Z Stieg, James K Gimzewski, Atsushi Nakano
Journal: Circulation Research (2013)

While adult heart muscle is the least regenerative of tissues, embryonic cardiomyocytes are proliferative, with embryonic stem (ES) cells providing an endless reservoir. In addition to secreted factors and cell-cell interactions, the extracellular microenvironment has been shown to play an important role in stem cell lineage specification, and understanding how scaffold elasticity influences cardiac differentiation is crucial to cardiac tissue engineering. Though previous studies have analyzed the role of the matrix elasticity on the function of differentiated cardiomyocytes, whether it affects the induction of cardiomyocytes from pluripotent stem cells is poorly understood. Here, we examined the role of matrix rigidity on the cardiac differentiation using mouse and human ES cells. Culture on polydimethylsiloxane (PDMS) substrates of varied monomer-to-crosslinker ratios revealed that rigid extracellular matrices promote a higher yield of de novo cardiomyocytes from undifferentiated ES cells. Using an genetically modified ES system that allows us to purify differentiated cardiomyocytes by drug selection, we demonstrate that rigid environments induce higher cardiac troponin T expression, beating rate of foci, and expression ratio of adult α- to fetal β- myosin heavy chain in a purified cardiac population. M-mode and mechanical interferometry image analyses demonstrate that these ES-derived cardiomyocytes display functional maturity and synchronization of beating when co-cultured with neonatal cardiomyocytes harvested from a developing embryo. Together, these data identify matrix stiffness as an independent factor that instructs not only the maturation of the already differentiated cardiomyocytes but also the induction and proliferation of cardiomyocytes from undifferentiated progenitors. Manipulation of the stiffness will help direct the production of functional cardiomyocytes en masse from stem cells for regenerative medicine purposes.
Insurance status and cancer disparities in adolescents and young adults age 15 to 39: National Cancer Data Base, 1998-2003.
Authors: Anthony Robbins, Catherine C. Lerro, Ronald Barr
Journal: Journal of Clinical Oncology (2012)

6011 Background: Since the mid-1970s there has been little progress in improving cancer survival for adolescents and young adults (AYAs, defined by the National Cancer Institute as individuals 15 to 39 years of age), in contrast to the substantial improvements for children and older adults. The association between insurance status and cancer disparities (stage at diagnosis, survival, and treatment) in AYA patients has not been examined in a national sample. Methods: The National Cancer Data Base, a national hospital-based cancer registry, was used to examine insurance status and cancer disparities in 177,359 AYA cancer patients. Cases were diagnosed during 1998−2003 and followed for vital status through 2008. We examined the association between insurance status and stage at diagnosis, stage-specific survival, and receipt of the most frequently used stage-specific treatments for common AYA sites (thyroid, female breast, non-Hodgkin lymphoma, and acute myeloid leukemia). Results: Insurance status was strongly related to cancer disparities in AYA patients. For example, compared to patients with private insurance, uninsured patients were 1.71 times more likely to be diagnosed at stage IV (95% confidence interval [CI], 1.63−1.79), had higher risk of death within every stage [stage I, hazard ratio (HR) (95% CI), 2.43 (2.13−2.76); stage II, 1.87 (1.70−2.06); stage III, 1.55 (1.43−1.68); stage IV, 1.39 (1.31−1.48); and unstaged (leukemias, CNS tumors, etc.), 1.67 (1.58−1.76), and for the four sites listed above, were less likely to receive the most frequently used stage-specific treatments. Insurance status remained a strong independent predictor for each of these outcomes in multivariate models adjusting for patient, hospital, and tumor factors. Conclusions: In a large national sample, insurance status was a strong independent predictor of cancer disparities in AYA patients. The Affordable Care Act of 2010 should facilitate the acquisition of adequate health insurance by AYA, who are the most under- and uninsured age group in the US population, and should contribute to remediation of such disparities.
Incorporation of bioactive glass nanoparticles in electrospun PCL/chitosan fibers by using benign solvents
Authors: Liliana Liverani, Jonas Lacina, Judith A. Roether, Elena Boccardi, Manuela S. Killian, Patrik Schmuki, Dirk W. Schubert, Aldo R. Boccaccini
Journal: Bioactive Materials (2017)

The use of bioactive glass (BG) particles as a filler for the development of composite electrospun fibers has already been widely reported and investigated. The novelty of the present research work is represented by the use of benign solvents (like acetic acid and formic acid) for electrospinning of composite fibers containing BG particles, by using a blend of PCL and chitosan. In this work, different BG particle sizes were investigated, namely nanosized and micron-sized. A preliminary investigation about the possible alteration of BG particles in the electrospinning solvents was performed using SEM analysis. The obtained composite fibers were investigated in terms of morphological, chemical and mechanical properties. An in vitro mineralization assay in simulated body fluid (SBF) was performed to investigate the capability of the composite electrospun fibers to induce the formation of hydroxycarbonate apatite (HCA).
A novel role for cardiac neural crest in heart development
Authors: Karen Waldo, Marzena Zdanowicz, Jarrett Burch, Donna H. Kumiski, Harriet A. Stadt, Robert E. Godt, Tony L. Creazzo, Margaret L. Kirby
Journal: Journal of Clinical Investigation (1999)

Ablation of premigratory cardiac neural crest results in defective development of the cardiac outflow tract. The purpose of the present study was to correlate the earliest functional and morphological changes in heart development after cardiac neural crest ablation. Within 24 hours after neural crest ablation, the external morphology of the hearts showed straight outflow limbs, tighter heart loops, and variable dilations. Incorporation of bromodeoxyuridine in myocytes, an indication of proliferation, was doubled after cardiac neural crest ablation. The myocardial calcium transients, which are a measure of excitation-contraction coupling, were depressed by 50% in both the inflow and outflow portions of the looped heart tube. The myocardial transients could be rescued by replacing the cardiac neural crest. The cardiac jelly produced by the myocardium was distributed in an uneven, rather than uniform, pattern. An extreme variability in external morphology could be attributed to the uneven distribution of cardiac jelly. In the absence of cardiac neural crest, the myocardium was characterized by somewhat disorganized myofibrils that may be a result of abnormally elevated proliferation. In contrast, endocardial development appeared normal, as evidenced by normal expression of fibrillin-2 protein (JB3 antigen) and normal formation of cushion mesenchyme and trabeculae. The signs of abnormal myocardial development coincident with normal endocardium suggest that the presence of cardiac neural crest cells is necessary for normal differentiation and function of the myocardium during early heart development. These results indicate a novel role for neural crest cells in myocardial maturation.
The clinical pathological characters and prognosis of <i>FGFR1 </i>gene amplification in non-small cell lung cancer: A meta-analysis.
Authors: Xie Fa Jun, Fan Yun
Journal: Journal of Clinical Oncology (2015)

e22188 Background: FGFR1 amplification is recognized as a novel therapy target as non-small cell lung cancer (NSCLC), especially in Squamous cell of lung cancer (SCC). However, the association between FGFR1 amplification and clinicopathological characters of NSCLC is still under controversial. Methods: We performed a meta-analysis by using 18 eligible studies to examine the correlation between FGFR1 gene amplification and clinical pathological characters. Results: FGFR1 amplification was closely related with these clinicopathological features, including Sex (OR 2.05, 95% CI: 1.50-2.80), smoking (OR 3.31, 95% CI: 2.02 – 5.44), histology (OR 3.60, 95% CI: 2.82-4.59). FGFR1 amplification was associated with shorter overall survival (OS) and no severe heterogeneity between studies (I2 = 3.8%). We should point out that the publication bias may partly account for the result, but Results remained significant after trim and fill method (HR 1.22, 95 % CI: 1.06-1.40). However, no significantly correlated with poor disease-free survival (HR 1.43, 95% CI: 0.96-2.12). Conclusions: This study showed that FGFR1 amplification was significantly associated with sex, smoking and histology. FGFR1 amplification patients could be a marker for poor prognosis of NSCLC, especially in SCC.
Association of Implantable Cardioverter Defibrillators With Survival in Patients With and Without Improved Ejection Fraction
Authors: Selcuk Adabag, Kristen K. Patton, Alfred E. Buxton, Thomas S. Rector, Kristine E. Ensrud, Kairav Vakil, Wayne C. Levy, Jeanne E. Poole
Journal: JAMA Cardiology (2017)

<h3>Importance</h3> Improvement in left ventricular ejection fraction (EF) to &gt;35% occurs in many patients with reduced EF at baseline. To our knowledge, whether implantable cardioverter defibrillator (ICD) therapy improves survival for these patients is unknown. <h3>Objective</h3> To examine the efficacy of ICD therapy in reducing risk of all-cause mortality and sudden cardiac death among patients with an EF ≤35% at baseline, with or without an improvement in EF to &gt;35% during follow-up. <h3>Design, Setting, and Participants</h3> This retrospective analysis examined data collected in the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), which randomly assigned 2521 patients to placebo, amiodarone, or ICD between 1997 and 2001. A subset of 1902 participants (75.4%) of the SCD-HeFT had a repeated assessment of EF a mean (SD) of 13.5 (6) months after randomization. We stratified these patients by EF ≤35% and &gt;35% based on the first repeated EF measurement after randomization and compared all-cause mortality in 649 patients randomized to placebo vs 624 patients randomized to ICD. Follow-up started with the repeated EF assessment. Analysis was performed between January 2016 and July 2016. <h3>Exposures</h3> Implantable cardioverter-defibrillator therapy. <h3>Main Outcomes and Measures</h3> All-cause mortality and sudden cardiac death. <h3>Results</h3> Of the included 1273 patients, the mean (SD) age was 59 (12) years, and 977 (76.7%) were male and 1009 (79.3%) were white. Repeated EF was &gt;35% in 186 participants (29.8%) randomized to ICD and 185 participants (28.5%) randomized to placebo. During a median follow-up of 30 months, the all-cause mortality rate was lower in the ICD vs placebo group, both in patients whose EF remained ≤35% (7.7 vs 10.7 per 100 person-year follow-up) and in those whose EF improved to &gt;35% (2.6 vs 4.5 per 100 person-year follow-up). Compared with placebo, the adjusted hazard ratio for the effect of ICD on mortality was 0.64 (95% CI, 0.48-0.85) in patients with a repeated EF of ≤35% and 0.62 (95% CI, 0.29-1.30) in those with a repeated EF &gt;35%. There was no interaction between treatment assignment and repeated EF for predicting mortality. <h3>Conclusions and Relevance</h3> Among participants in the SCD-HeFT who had a repeated EF assessment during the course of follow-up, those who had an improvement in EF to &gt;35% accrued a similar relative reduction in mortality with ICD therapy as those whose EF remained ≤35%. Prospective randomized clinical trials are needed to test ICD efficacy in patients with an EF &gt;35%. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT01114269
Tri-Ponderal Mass Index vs Body Mass Index in Estimating Body Fat During Adolescence
Authors: Courtney M. Peterson, Haiyan Su, Diana M. Thomas, Moonseong Heo, Amir H. Golnabi, Angelo Pietrobelli, Steven B. Heymsfield
Journal: JAMA Pediatrics (2017)

Body mass index (BMI) is used to diagnose obesity in adolescents worldwide, despite evidence that weight does not scale with height squared in adolescents. To account for this, health care providers diagnose obesity using BMI percentiles for each age (BMI z scores), but this does not ensure that BMI is accurate in adolescents.To compare the accuracy of BMI vs other body fat indices of the form body mass divided by heightn in estimating body fat levels in adolescents.Cross-sectional data from the 1999 to 2006 US National Health and Nutrition Examination Survey were analyzed between September 2015 and December 2016.Dual-energy x-ray absorptiometry and anthropometric data were used to determine changes in body fat levels, body proportions, and the scaling relationships among body mass, height, and percent body fat. To assess the merits of each adiposity index, 3 criteria were used: stability with age, accuracy in estimating percent body fat, and accuracy in classifying adolescents as overweight vs normal weight.Participants included 2285 non-Hispanic white participants aged 8 to 29 years. Percent body fat varied with both age and height during adolescence, invalidating the standard weight-to-height regression as the way of finding the optimal body fat index. Because the correct regression model (percent body fat is proportional to mass divided by heightn) suggested that percent body fat scales to height with an exponent closer to 3, we therefore focused on the tri-ponderal mass index (TMI; mass divided by height cubed) as an alternative to BMI z scores. For ages 8 to 17 years, TMI yielded greater stability with age and estimated percent body fat better than BMI (R2 = 0.64 vs 0.38 in boys and R2 = 0.72 vs 0.66 in girls). Moreover, TMI misclassified adolescents as overweight vs normal weight less often than BMI z scores (TMI, 8.4%; 95% CI, 7.3%-9.5% vs BMI, 19.4%; 95% CI, 17.8%-20.0%; P < .001) and performed equally as well as updated BMI percentiles derived from the same data set (TMI, 8.4%; 95% CI, 7.3%-9.5% vs BMI, 8.0%; 95% CI, 6.9%-9.1%; P = .62).The tri-ponderal mass index estimates body fat levels more accurately than BMI in non-Hispanic white adolescents aged 8 to 17 years. Moreover, TMI diagnoses adolescents as overweight more accurately than BMI z scores and equally as well as updated BMI percentiles but is much simpler to use than either because it does not involve complicated percentiles. Taken together, it is worth considering replacing BMI z scores with TMI to estimate body fat levels in adolescents.
HIV-activated human plasmacytoid DCs induce Tregs through an indoleamine 2,3-dioxygenase–dependent mechanism
Authors: Olivier Manches, David Munn, Anahita Fallahi, Jeffrey Lifson, Laurence Chaperot, Joel Plumas, Nina Bhardwaj
Journal: Journal of Clinical Investigation (2008)

Plasmacytoid DCs (pDCs) have been implicated as crucial cells in antiviral immune responses. On recognizing HIV, they become activated, secreting large amounts of IFN-alpha and inflammatory cytokines, thereby potentiating innate and adaptive antiviral immune responses. Here, we have shown that HIV-stimulated human pDCs can also induce the differentiation of naive CD4+ T cells into Tregs with suppressive function. This differentiation was independent of pDC production of IFN-alpha and primarily dependent on pDC expression of indoleamine 2,3-dioxygenase, which was induced through the TLR/MyD88 pathway, following binding of HIV to CD4 and triggering of TLR7 by HIV genomic RNA. Functionally, the Tregs induced by pDCs were shown to inhibit the maturation of bystander conventional DCs. This study therefore reveals what we believe to be a novel mechanism by which pDC may regulate and potentially limit anti-HIV immune responses.
Thyroid Function and Sudden Cardiac Death
Authors: Layal Chaker, Marten E. van den Berg, Maartje N. Niemeijer, Oscar H. Franco, Abbas Dehghan, Albert Hofman, Peter R. Rijnbeek, Jaap W. Deckers, Mark Eijgelsheim, Bruno H.C. Stricker, Robin P. Peeters
Journal: Circulation (2016)

BACKGROUND: The association between thyroid function and cardiovascular disease is well established, but no study to date has assessed whether it is a risk factor for sudden cardiac death (SCD). Therefore, we studied the association of thyroid function with SCD in a prospective population-based cohort. METHODS: Participants from the Rotterdam Study ≥45 years with thyroid-stimulating hormone or free thyroxine (FT4) measurements and clinical follow-up were eligible. We assessed the association of thyroid-stimulating hormone and FT4 with the risk of SCD by using an age- and sex-adjusted Cox proportional-hazards model, in all participants and also after restricting the analysis to euthyroid participants (defined by thyroid-stimulating hormone 0.4–4.0 mIU/L). Additional adjustment included cardiovascular risk factors, notably hypertension, serum cholesterol, and smoking. We stratified by age and sex and performed sensitivity analyses by excluding participants with abnormal FT4 values (reference range of 0.85–1.95 ng/dL) and including only witnessed SCDs as outcome. Absolute risks were calculated in a competing risk model by taking death by other causes into account. RESULTS: We included 10 318 participants with 261 incident SCDs (median follow-up, 9.1 years). Higher levels of FT4 were associated with an increased SCD risk, even in the normal range of thyroid function (hazard ratio, 2.28 per 1 ng/dL FT4; 95% confidence interval, 1.31–3.97). Stratification by age or sex and sensitivity analyses did not change the risk estimates substantially. The absolute 10-year risk of SCD increased in euthyroid participants from 1% to 4% with increasing FT4 levels. Conclusions: Higher FT4 levels are associated with an increased risk of SCD, even in euthyroid participants.
Unusual Presentations of Thoracic Tumors
Authors: Ali Guermazi, Mona El Khoury, Francine Perret, Veronique Meignin, Jean Masson, Mourad Rilli, Jacques Frija, Marc Espie
Journal: Journal of Clinical Oncology (2001)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2001.19.17.3784 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11533104 Unusual Presentations of Thoracic Tumors Case 3. Parenchymal Lipoma of the Lung Ali GuermazixAli GuermaziSearch for articles by this author , Mona El KhouryxMona El KhourySearch for articles by this author , Francine PerretxFrancine PerretSearch for articles by this author , Veronique MeigninxVeronique MeigninSearch for articles by this author , Jean MassonxJean MassonSearch for articles by this author , Mourad RillixMourad RilliSearch for articles by this author , Jacques FrijaxJacques FrijaSearch for articles by this author , Marc EspiexMarc EspieSearch for articles by this author Show More Saint-Louis University Hospital, Paris, France https://doi.org/10.1200/JCO.2001.19.17.3784 First Page Full Text PDF Figures and Tables © 2001 by American Society of Clinical Oncology
Drug-Induced Autoimmune Hepatitis: Response to Corticosteroids and Lack of Relapse After Cessation of Steroids
Authors: Einar Stefan Björnsson, Ottar Bergmann, Jon Gunnlaugur Jonasson, Gerdur Grondal, Björn Gudbjornsson, Sigurdur Olafsson
Journal: Clinical Gastroenterology and Hepatology (2017)
A multi-institutional phase II open-label study of AMG 479 in advanced carcinoid and pancreatic neuroendocrine tumors.
Authors: Matthew Kulke, Jennifer A. Chan, David P. Ryan, Jeffrey A. Meyerhardt, Charles S. Fuchs, Thomas Adam Abrams, Eileen Regan, Rachel Brady, Jill M. Weber, Tiffany Campos, Larry Kvols, Jonathan R. Strosberg
Journal: Journal of Clinical Oncology (2012)

4125 Background: The IGF pathway is thought play an important role in neuroendocrine tumor progression. We therefore investigated AMG 479, a human monocolonal antibody against IGF1-R, in patients with metastatic progressive carcinoid and pancreatic neuroendocrine tumors (NETS). Methods: This open-label phase II study enrolled patients (≥18 yrs) with metastatic low and intermediate-grade carcinoid and pancreatic NETs. Key inclusion criteria included evidence of progressive disease (by RECIST) within 12 months of enrollment, ECOG PS 0-2, and fasting blood sugar &lt;160mg/dL. Prior treatments were allowed, and concurrent somatostatin analog therapy was permitted as long as patients remained on a stable dose. The primary endpoint was objective response rate. Secondary endpoints included overall survival (OS), progression-free survival (PFS), and safety. Results: 60 patients (30 carcinoid, 30 pancreatic NET) were treated with AMG 479 18mg/kg every 3 weeks and 54 patients were evaluable for response. There were no objective responders by RECIST. When best response to therapy was evaluated, 10/27 (37%) evaluable carcinoid patients and 8/26 (31%) evaluable pancreatic NET patients experienced 1-29% tumor shrinkage, while 17/27 (63%) of the carcinoid patients and 15/26 (58%) of the pancreatic NET patients appeared to experience continued tumor growth. Median PFS was 6.3 months (95% CI 4.2-12.6) for the entire cohort; 10.5 months for carcinoid patients and 4.2 months for pancreatic NET patients. The OS rate at 12 months was 70% (55%-81%) for the entire cohort. Median OS has not been reached. Treatment related grade 3/4 AEs were rare and consisted of hyperglycemia (4%), neutropenia (4%), thrombocytopenia (4%) and infusion reaction (1%). Conclusions: While well-tolerated, single-agent AMG 479 was not found to result in major tumor responses among patients with metastatic low-intermediate grade carcinoid or pancreatic NET. Subgroup analysis to identify characteristics of patients who may have benefited from therapy with AMG 479 is ongoing.
Thermocool SFカテーテルは肺静脈隔離術において総洗浄量を減少し,透視時間を短縮する 従来のThermocoolカテーテルとの比較
Authors: Kimura Masaomi, Sasaki Shingo, Ohwada Shingen, Horiuchi Daisuke, Sasaki Kenichi, Itoh Taihei, Ishida Yuji, Okumura Ken
Journal: Circulation (2013)