tbuckley/cabot-search huggingface dataset:
Spiritual well-being in long-term survivors with chronic graft versus host disease after hematopoietic stem cell transplant
Authors: B. A. Harris, A. M. Berger, S. Mitchell, S. M. Steinberg, K. L. Baker, D. L. Handel, J. Bolle, E. G. Bush, D. N. Avila, S. Z. Pavletic
Journal: Journal of Clinical Oncology (2008)

18017 Background: Spiritual well-being (Sp-WB) is noted as a resource to support adaptation and resilience, and strengthen quality of life (QOL) in patients with cancer and other chronic, life-threatening illnesses. However, the relationship between Sp-WB and QOL in patients with cGVHD has not been studied. The purpose of this study was to explore the associations among Sp-WB, QOL, and selected demographic and clinical factors in survivors with cGVHD after allogeneic HSCT for hematologic malignancy. Methods: The 52 participants in this study completed the Functional Assessment of Chronic Illness Therapy - Spiritual Well-Being (FACIT-Sp) as part of a prospective multidisciplinary natural history study of cGVHD. Demographic and clinical characteristics were collected during a comprehensive clinical evaluation. Results: Sp-WB was generally high (M 37.06, SD 9.5) and comparable to that reported by another investigator in a mixed sample of autologous and allogeneic HSCT survivors (M 35.9, SD 8.6, p = 0.25). Those with the lowest Sp-WB had been living with cGVHD significantly longer (p = 0.05) than those with higher levels of Sp-WB. There were no associations between Sp-WB and demographic variables, cGVHD severity or intensity of immunosuppression. Participants with the lowest Sp-WB (N = 11) reported inferior physical (p = .0009), emotional (p = .003), social (p = .027), and functional well-being (p ≤ 0.0001) as well as lower overall QOL (p ≤ 0.0001) compared to those with higher Sp-WB. They also had inferior QOL (M 54.88, S.E. 4.19) relative to population norms (M = 80.1, S.E. 0.55). Differences between those with the lowest and those with better Sp-WB consistently exceeded the minimal clinically significant difference for all subscales and for overall QOL. Controlling for physical, emotional and social well-being, Sp-WB was a significant independent predictor of contentment with QOL. Conclusions: Our results suggest that Sp-WB is an important factor contributing to the relatively preserved quality of life observed in this sample of patients with cGVHD. Research is needed to identify the factors that diminish Sp-WB, and to test interventions designed to strengthen this coping resource in patients managing the late-effects of cancer treatment. No significant financial relationships to disclose.
Abstract 18498: Regulator of Calcineurin 1 (RCAN1): A New Factor in the Control of Mitochondrial Dynamics, Metabolism, and Cardiomyocyte Survival
Authors: Valentina Parra, David Rotter, Zully Pedrozo, Beverly A Rothermel
Journal: Circulation (2013)

Dysregulation of calcium handling and mitochondrial function are hallmarks of heart disease. Furthermore, mitochondrial dynamics and metabolism influence the susceptibility of the heart to ischemia reperfusion (I/R). Regulator of Calcineurin 1 (RCAN1) is an endogenous feedback inhibitor of calcineurin, a calcium-activated phosphatase involved in pathological cardiac remodeling. The hearts of mice with a targeted disruption of Rcan1 are more susceptible to damage from I/R in vivo. Here we have used an in vitro model of simulated I/R (sim-I/R) and advanced mitochondrial imaging techniques to dissect RCAN1’s cardiomyocyte-autonomous role in mitochondrial dynamics and cell survival. SiRNA was used to deplete the RCAN1.4 and RCAN1.1 isoforms from neonatal rat ventricular myocytes (NRVMs). Cultures were subjected to 6 hours of sim-I/R followed by 12 hours of reperfusion. Death, measured as LDH release, was significantly greater in the siRCAN1-depeleted cultures than in si-controls. Si-depleted NRVMs were dyed with Mitotracker-green and three-dimensional images obtained by confocal microscopy. Z-stacks of thresholded images were volume-reconstituted. Our results show that siRCAN1-depleted NRVMs have a decrease in the mean volume of mitochondrial particles and an increase in the total number of these organelles. Consistent with increased mitochondrial fission, the rate of ATP production and the mitochondrial membrane potential were lower in siRCAN1-depleted NRVMs compared to control siRNA treated cells. There was also a profound redistribution of the mitochondrial network, decreasing the functional coupling between mitochondria and endoplasmic reticulum, assayed as a decrease in mitochondrial calcium uptake capacity. In vivo and in vitro ultraestructural EM studies showed increased mitochondrial fragmentation and a loss of the cristae structure. Finally, there was evidence of sarcomeric hypertrophy in NRVMs depleted of RCAN1, correlating with a switch to a more glycolytic metabolism. These studies suggest that RCAN1 helps preserve a functional mitochondrial network, providing new insights into the role of mitochondrial dynamics and calcineurin/RCAN1 regulation in adaptive and pathological cardiac remodeling.
Systemic Inflammatory and Autoimmune Diseases (SAID) Associated with MDS: A French Multicenter Retrospective Study
Authors: Arsene Mekinian, Eric Grignano, Thorsten Braun, Decaux Olivier, Liozon Eric, Costedoat Nathalie, Kahn jean Emmanuel, Mohamed Hamidou, Xavier Puechal, Sophie Park, Eric Toussirot, Geraldine Falgarone, David Launay, Morel Nathalie, Sebastien Trouiller, Mathian Alexis, Gombert Bruno, Yoland Schoindre, Bertrand Lioger, Benoit de Wazieres, Zahir Amoura, Buchdaul anne Laure, Sophie georgin Lavialle, Dion Jeremie, Serge Madaule, Loic Raffray, Pascale Cathebras, Jean Charles Piette, Jean Marc Ziza, Christian Rose, Francois Montestruc, Olivier Lortholary, Mohamed Omouri, Guilllaume Denis, Julien Rossignol, Lionel Ades, Claude Gardin, Pierre Fenaux, Olivier Fain
Journal: Blood (2014)
Gait Speed Predicts 30-Day Mortality After Transcatheter Aortic Valve Replacement
Authors: Joakim Alfredsson, Amanda Stebbins, J. Matthew Brennan, Roland Matsouaka, Jonathan Afilalo, Eric D. Peterson, Sreekanth Vemulapalli, John S. Rumsfeld, David Shahian, Michael J. Mack, Karen P. Alexander
Journal: Circulation (2016)

Surgical risk scores do not include frailty assessments (eg, gait speed), which are of particular importance for patients with severe aortic stenosis considering transcatheter aortic valve replacement.We assessed the association of 5-m gait speed with outcomes in a cohort of 8039 patients who underwent transcatheter aortic valve replacement (November 2011-June 2014) and were included in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. We evaluated the association between continuous and categorical gait speed and 30-day all-cause mortality before and after adjustment for Society of Thoracic Surgeons-predicted risk of mortality score and key variables. Secondary outcomes included in-hospital mortality, bleeding, acute kidney injury, and stroke. The overall median gait speed was 0.63 m/s (25th-75th percentile, 0.47-0.79 m/s), with the slowest walkers (<0.5 m/s) constituting 28%, slow walkers (0.5-0.83 m/s) making up 48%, and normal walkers (>0.83 m/s) constituting 24% of the population. Thirty-day all-cause mortality rates were 8.4%, 6.6%, and 5.4% for the slowest, slow, and normal walkers, respectively (P<0.001). Each 0.2-m/s decrease in gait speed corresponded to an 11% increase in 30-day mortality (adjusted odds ratio, 1.11; 95% confidence interval, 1.01-1.22). The slowest walkers had 35% higher 30-day mortality than normal walkers (adjusted odds ratio, 1.35; 95% confidence interval, 1.01-1.80), significantly longer hospital stays, and a lower probability of being discharged to home.Gait speed is independently associated with 30-day mortality after transcatheter aortic valve replacement. Identification of frail patients with the slowest gait speeds facilitates preprocedural evaluation and anticipation of a higher level of postprocedural care.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01737528.
Effect of Low-Magnitude, High-Frequency Mechanical Stimulation on BMD Among Young Childhood Cancer Survivors
Authors: Rona J. Mogil, Sue C. Kaste, Robert J. Ferry, Melissa M. Hudson, Daniel A. Mulrooney, Carrie R. Howell, Robyn E. Partin, Deo K. Srivastava, Leslie L. Robison, Kirsten K. Ness
Journal: JAMA Oncology (2016)

Bone accrual during youth is critical to establish sufficient strength for lifelong skeletal health. Children with cancer may develop low bone mineral density (BMD) any time before or after diagnosis.To evaluate the ability of low-magnitude, high-frequency mechanical stimulation to enhance BMD among childhood cancer survivors.Double-blind randomized clinical trial conducted at St Jude Children's Research Hospital from June 1, 2010, to January 22, 2013, using cancer survivors, ages 7 to 17 years, who were previously treated at St Jude Children's Research Hospital, were in remission, and at least 5 years from diagnosis, with whole-body or lumbar spine BMD z scores of -1.0 or lower. Participants were randomized (stratified by sex and Tanner stage) to either a placebo device or low-magnitude, high-frequency mechanical stimulation device, which was used at home.Placebo or low-magnitude, high-frequency mechanical stimulation (0.3 g; 32-37 Hz) for 2 sessions lasting 10 minutes each, 7 days per week for 1 year. All participants were prescribed daily cholecalciferol (vitamin D) and calcium.Changes in areal and volumetric BMD and bone biomarkers were compared by analysis of variance, adjusted for strata.Of the 65 participants, 32 were randomized to the intervention group (mean [SD] age was 13.6 [3.7] years, 18 [56.2%] were male, and 27 [84.4%] were white), and 33 were randomized to the placebo group (mean [SD] age was 13.6 [2.9] years, 17 [51.5%] were male, and 26 [78.8%] were white). Forty-eight participants completed the trial, 22 in the intervention group and 26 in the placebo group with median adherence of 70.1% for intervention and 63.7% for placebo groups. With intention-to-treat analysis, mean (SD) whole-body BMD z score by dual x-ray absorptiometry improved by 0.25 (0.78) in the intervention (n = 22), but decreased by -0.19 (0.79) in the placebo group (n = 26, P = .05). Circulating osteocalcin at 12 months correlated with change in total body BMD (r = 0.35, P = .02). Tibial trabecular bone among participants completing 70% or more of the prescribed sessions increased by a mean of 11.2% (95% CI, 5.2 to 17.2%) compared with those completing less than 70% who decreased by a mean of -1.3% (95% CI, -7.3 to 4.7%; P = .02). Change in circulating receptor activator of nuclear factor κ-B ligand was higher in the intervention than in the placebo group (0.06 [0.16] vs -0.04 [0.17] pmol/L) (P = .04).Pediatric cancer survivors with low BMD may benefit from low-magnitude, high-frequency mechanical stimulation as a novel and safe intervention to optimize peak bone mass during youth, alone or in conjunction with other therapies.clinicaltrials.gov Identifier: NCT01010230.
S32 Virtual Bronchoscopic Navigation followed by radial EBUS to biopsy peripheral pulmonary lesions: a pilot study: Abstract S32 Table 1
Authors: N Denny, J Mills, L Brown, SJ Fowler, M Munavvar
Journal: Thorax (2015)

<h3>Introduction</h3> Detection of peripheral pulmonary lesions (PPLs) is on the rise but an accurate means of obtaining a tissue diagnosis without high risk of complications is lacking.<sup>1</sup> Virtual bronchoscopic navigation (VBN) guides the bronchoscope under direct vision and, in combination with radial endobronchial ultrasound (R-EBUS) or ultrathin bronchoscopy, may enhance the diagnostic yield of PPLs with a minimal complication rate.<sup>2</sup> <h3>Aims</h3> To pilot the use of VBN in the diagnosis of PPLs. To identify patient and lesion characteristics that predict successful VBN. <h3>Methods</h3> Images from chest CT (slice width 1–1.25 mm) were acquired from patients, and lesion features, including location and presence of a bronchus sign (bronchus contained within PPL), were recorded. CT images were transferred to a portable workstation and Lungpoint Broncus © was used to create a virtual pathway to the PPL. Bronchoscopy was performed with VBN followed by R-EBUS guidance, under conscious sedation, and biopsies obtained. Pre-procedure characteristics, biopsy adequacy, biopsy outcome, 30-day follow up and complications were recorded. <h3>Results</h3> The median age of our cohort (n = 7) was 79 and all patients had one or more comorbidities. PPL median size was 28 mm and all were located in sub-segmental bronchi. VBN guided the operator to the correct site in six cases. Adequate biopsies were taken from five patients; four had a positive bronchus sign. Three adequate biopsies received a diagnosis of primary lung cancer; those remaining were negative. One patient with inadequate biopsies underwent transthoracic needle biopsy (TTNB) and was diagnosed with primary lung cancer. No complications occurred in spite of the significant co-morbidity of this patient cohort. <h3>Discussion</h3> Our preliminary data suggest that in a selected patient cohort with a bronchus sign, VBN may be a useful and safe adjunct to R-EBUS to obtain a tissue diagnosis from PPLs. In contrast, TTNB has a high diagnostic sensitivity but is tarnished by a high complication rate and is not suitable in patients with significant co-morbidity. Therefore, VBN and R-EBUS are particularly useful where TTNB carries a high risk. <h3>References</h3> 1 Kikuchi E, Yamazaki K, Sukoh N, <i>et al</i>. Endobronchial ultrasonography with guide-sheath for peripheral pulmonary lesions. <i>Eur Respir J</i> 2004;<b>24</b>:533–7 2 Ishida T, Asano F, Yamazaki K, <i>et al</i>. Virtual bronchoscopic navigation combined with endobronchial ultrasound to diagnose small peripheral pulmonary lesions: a randomised trial. <i>Thorax</i> 2011;<b>66</b>:1072–7
Dexamethasone administration in antiemetic therapy - Is it safe?
Authors: D. Borces, K. Munstedt, M. Zygmunt, R. Von Georgi
Journal: Journal of Clinical Oncology (2004)

8217 Background: Use of corticosteroids to enhance efficacy of antiemetic drugs is controversial because of its well established ability to improve patients' quality of life. On the other hand there are reports on impairment of tumor apoptosis and increased frequencies of metastasis in patients receiving corticosteroid treatment. Methods: A retrospective chart review was undertaken to determine the effects of corticosteroid medication as a part of general antiemetic prophylaxis prior to chemotherapy with respect to hematological parameters after administration and overall survival in 244 ovarian cancer patients scheduled to receive at least 6 courses of systemic chemotherapy. In a subset 62 patients received glucocorticoids and 182 did not. Results: Both groups are well balanced with respect to stage and other prognostic factors. Kaplan-Meier analyses on recurrence-free and overall survival revealed no statistically significant differences between both groups. Glucocorticoid pretreatment resulted in significantly higher leucocyte counts during the days after chemotherapy, higher nadir values, and counts prior to subsequent courses (p < 0.01; Levene-test, T-test). The fall of hemoglobin serum levels during the courses of treatment was also less pronounced in the dexamethasone group. Thrombocyte levels were only little positively affected (p < 0.10; Levene-test, T-test). As a result, the initial treatment plans were significantly more frequent achieved in the dexamethasone group (p = 0.007; Chi2-test). Conclusions: This retrospective analysis gives no evidence for the concerns that glucosteroids could negatively influence patient outcome. They may have positive bone marrow protecting properties. No significant financial relationships to disclose.
Sequential versus "ab initio' combined diuretic treatment of moderate ascites in cirrhotic patients: Final results of a randomized controlled multicenter clinical study
Authors: Paolo Angeli, Elena Mazza, Silvano Fasolato, Erika Zola, Alessandra Galioto, Alessia Callegaro, Antonietta Sticca, F Salinas, Stefano Fagiuoli, E Miola, Umberto Cillo, Angelo Gatta, Lajos Okolicsanyi
Journal: Hepatology (2007)
The Diagnostic Testing Accuracy of Urinary Leukotriene E4 in Determining Aspirin Intolerance in Asthma: A Systematic Review and Meta-Analysis
Authors: John B. Hagan, Tanya M. Laidlaw, Rohit D. Divekar, Erin O'Brien, Hirohita Kita, Gerald W. Volcheck, Christina R. Hagan, Devyani Lal, Harry G. Teaford, Patricia J. Erwin, Matthew A. Rank
Journal: Journal of Allergy and Clinical Immunology (2016)
WITHDRAWN: Antiulcerative effect of sacran on indomethacin-induced gastric ulcer in mice
Authors: Tomoya Hayashi, Yuya Abe, Shinichiro Kaneko, Takayuki Otsuka, Kiyoaki Sato, Yoichi Ishitsuka, Yuki Kondo, Tetsumi Irie, Taishi Higashi, Keiichi Motoyama, Hidetoshi Arima
Journal: Asian Journal of Pharmaceutical Sciences (2015)

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
Abstract 18619: Scaffold Protein CARD11 Modulates Receptor Mediated Apoptosis in Cardiomyocytes Following Myocardial Infarction
Authors: Philip Wood, Mark Moon, Liyong Zhang, Fayez Dawood, Youan Liu, Naito Kotaro, Peter Liu
Journal: Circulation (2013)

Background: The CARD scaffold family members, named for containing the common caspase-recruitment domain, are important modulators of inflammatory and apoptotic signalling. CARD11, a membrane bound scaffold, is essential for the production of cytokines in the immune cellular response but is present in heart and lung tissue, where its effects are unknown, and described to associate with apoptotic players such as BCL10 and caspase-8. Due to the complex nature of cardiac response to myocardial infarction (MI), we hypothesize that CARD11 can act as a modulator and integrator of receptor mediated apoptotic pathways following cardiac tissue injury. Methods &amp; Results: CARD11 expression was increased in neonatal cardiomyocytes by general stress induction by H2O2 (25μM) and death receptor activation by Fas agonist Jo2 (1μg/ml) and TNF-alpha (50ng/ml) in isolated neonatal cardiomyocytes. Annexin V (AV) and propidium iodide (PI) double staining demonstrated decreased levels of apoptotic cells (AV+/PI+) following H2O2, Jo2 and TNF-alpha treatments in CARD11-/- cardiomyocytes to that of placebo levels compared to CARD11+/+ cells, as analyzed by flow cytometry. Pretreatment with caspase inhibitor zVAD-FMK (25μM) blocked this increase in apoptosis. Replacement of CARD11 through plasmid transfection restored the apoptotic phenotype in CARD11-/- cells and it was susceptible to zVAD-FMK inhibition. Experimental MI was created in CARD11-deficient mice (CARD11-/-) and wild-type littermate controls (CARD11+/+) by left coronary artery ligation. Survival over 28 days was significantly improved in CARD11-/- mice which exhibited lower rates of rupture and reduced infarct size post MI. TUNEL staining identified a lower percentage of apoptotic cells in the border zone of CARD11-/- hearts post-MI. Western blot analysis displayed decreased levels of cleaved caspase-3, -8 and -9, as well as pro-apoptotic mitochondrial proteins Apaf1, cytochrome-C and Bid. Conclusion: CARD11 up-regulation provides a scaffold for the formation of death receptor signaling through caspase-8 to promote cell death via apoptosis and its removal to increased cardiomyocyte survival in the MI environment.
Antitumor effect and safety profile of systemically delivered oncolytic adenovirus complexed with EGFR-targeted PAMAM-based dendrimer in orthotopic lung tumor model
Authors: A-Rum Yoon, Dayananda Kasala, Yan Li, Jinwoo Hong, Wonsig Lee, Soo-Jung Jung, Chae-Ok Yun
Journal: Journal of Controlled Release (2016)
Technique for Preclinical Evaluation of Continuous Infusion Chemotherapy With the Use of WF Rat Acute Myelogenous&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: W D Ensminger, J S Greenberger, E M Egan, M B Muse, W C Moloney
Journal: JNCI Journal of the National Cancer Institute (1979)

A technique was developed for continuous iv infusion chemotherapy in an inbred rat model of acute myelogenous leukemia. Polyethylene tubing was inserted surgically into the internal jugular vein of adult WF rats, burrowed sc to the base of the tall, and connected to an infusion pump. A flexible spring was sutured at the base of the tall and fastened to the cage wall; It protected the infusion catheter and allowed movement of the rat within the cage. This technique was used to compare bolus with continuous infusion therapy with adriamycin, cytosine arabinoside, and neocarzinostatin. Only small differences were noted in host toxicity and in antitumor effect against tumor grown as a subcutaneous myelobiastoma. Nearly three times more neocarzinostatin was required by continuous infusion for an effect equivalent to that of bolus inJection. In contrast, continuous infusion of methotrexate with concurrent thymidine infusion prevented toxicity, enhanced the antitumor effect, and prolonged survival. This infusion system should facilitate rapid preclinical evaluation of drugs considered for constant iv infusion therapy.
The Genetics of Dyslipidemia — When Less Is More
Authors: Sander Kersten
Journal: New England Journal of Medicine (2016)

An elevated plasma level of low-density lipoprotein (LDL) cholesterol is a major risk factor for coronary heart disease. Whether an elevated plasma triglyceride level and a reduced level of high-density lipoprotein (HDL) cholesterol also carry an increased risk of coronary heart disease has remained a contentious issue.1Two groups of investigators now describe in the Journal important genetic evidence showing a causal role of plasma triglycerides in coronary heart disease. Stitziel and colleagues2 tested 54,003 coding-sequence variants covering 13,715 human genes in more than 72,000 patients with coronary artery disease and 120,000 controls. Dewey and colleagues3 sequenced the exons of . . .
Dietary restriction improves repopulation but impairs lymphoid differentiation capacity of hematopoietic stem cells in early aging
Authors: Duozhuang Tang, Si Tao, Zhiyang Chen, Ievgen Oleksandrovich Koliesnik, Philip Gerald Calmes, Verena Hoerr, Bing Han, Nadja Gebert, Martin Zörnig, Bettina Löffler, Yohei Morita, Karl Lenhard Rudolph
Journal: The Journal of Experimental Medicine (2016)

Dietary restriction (DR) improves health, delays tissue aging, and elongates survival in flies and worms. However, studies on laboratory mice and nonhuman primates revealed ambiguous effects of DR on lifespan despite improvements in health parameters. In this study, we analyzed consequences of adult-onset DR (24 h to 1 yr) on hematopoietic stem cell (HSC) function. DR ameliorated HSC aging phenotypes, such as the increase in number of HSCs and the skewing toward myeloid-biased HSCs during aging. Furthermore, DR increased HSC quiescence and improved the maintenance of the repopulation capacity of HSCs during aging. In contrast to these beneficial effects, DR strongly impaired HSC differentiation into lymphoid lineages and particularly inhibited the proliferation of lymphoid progenitors, resulting in decreased production of peripheral B lymphocytes and impaired immune function. The study shows that DR-dependent suppression of growth factors and interleukins mediates these divergent effects caused by DR. Supplementation of insulin-like growth factor 1 partially reverted the DR-induced quiescence of HSCs, whereas IL-6/IL-7 substitutions rescued the impairment of B lymphopoiesis exposed to DR. Together, these findings delineate positive and negative effects of long-term DR on HSC functionality involving distinct stress and growth signaling pathways.