tbuckley/cabot-search huggingface dataset:
Abstract P175: Maintaining Ideal Cardiovascular Health and Freedom From Coronary Artery Calcification
Authors: Shih-Jen Hwang, Oyere Onuma, Joseph M Massaro, Xiaoling Zhang, Yi-Ping Fu, Emily Manders, Caroline S Fox, Udo Hoffmann, Christopher J O'Donnell
Journal: Circulation (2015)

Introduction: Ideal cardiovascular health (CVH), as defined by American Heart Association (AHA), is associated with low levels of cardiovascular disease (CVD) risk factors and freedom from coronary artery calcium (CAC). Hypothesis: Baseline ideal CVH predicts freedom from CAC progression. Methods: In the Framingham Heart Study (FHS), we evaluated prevalence of ideal CVH and investigated associations between ideal CVH and CAC progression. We included 1969 participants who attended the first and second rounds of the FHS Multi-Detector Computed Tomography study (MDCT-I and MDCT-II). The presence and burden of calcification was defined by a modified Agatston score. We calculated the repeatability of two CAC readings performed during MDCT-I and quantified the uncertainty estimate to define CAC progression. At follow-up, an increase in CAC score of 3.4 or higher was defined as positive CAC progression for those free of CAC at baseline. Using criteria modified from the AHA’s Strategic Impact Goal, we defined the prevalence of poor, intermediate and ideal CVH using five of the seven metrics: blood pressure, total-cholesterol, cigarette smoking, body mass index, and fasting glucose. For each metric of CVH, we assigned a score of 0, 1, and 2 points for poor, intermediate, and ideal CVH, respectively, to quantify CVH and extent of change in ideal CVH. Baseline age, baseline CVH status, and change in CVH category were independent variables for logistic regression models to test significant associations between CAC progression and change in ideal CVH. Results: The prevalence of ideal, intermediate, and poor CVH for 1148 participants who were free of baseline CAC were 15.77%, 43.73%, 40.51%, respectively. After an average 6.1 years of follow-up, the prevalence of ideal, intermediate, and poor CVH changed to 6.5%, 43.4%, and 50.1%, respectively, while the CAC progression rates were 8.0%, 13.1%, and 21.6%, respectively. In logistic regression models, there was a non-significant trend for CAC progression by CVH group. Compared to those with poor CVH at baseline, the presence of ideal CVH at baseline was significantly protective against the occurrence of CAC progression; the hazard ratio (HR) for occurrence of CAC progression was 0.36 (95%C.I. 0.19, 0.66, p&lt;0.001). Compared to those with intermediate CVH, there was potential protection against CAC progression, although the HR 0.66 was not statistically significant (95%C.I. 0.36, 1.21, p=0.62). Conclusions: In a community-based study, we observed significant protection from progression of CAC at follow-up for participants who were free of CAC with ideal CVH at baseline. These findings support continued public health measures to promote ideal CVH.
Abstract B1-29: The effect of higher-order receptor clusters on TRAIL induced apoptotic signaling
Authors: Andreas Raue, Diana Chai, Hannah Hudson, Eric Tam, Birgit Schoeberl
Journal: Cancer Research (2015)

Abstract The trimeric TNF-related apoptosis-inducing ligand (TRAIL) is an endogenous ligand that binds to trimeric death receptors (DR4/5). TRAIL is known to induce apoptosis mainly in malignant cells while normal cells remain unaffected. This makes TRAIL a most interesting target for cancer therapy. We investigate the effects of ligand valency on the degree of Caspase-8 activation and apoptosis induction. As a model system we use the semi-sensitive cell line DU145 and multivalent anti-DR5 fibronectin domains that can potentially form higher-order receptor clusters. In order to disentangle the effects of receptor clusters of different size, a dynamic model of ligand-receptor binding and Caspase-8 activation is coupled to a model of cell growth and cell death. The dynamic model is calibrated using quantitative experimental data of ligand on cell binding, Caspase-8 activity and cell viability. Our results show that higher-order receptor clusters do amplify apoptotic signaling. The model predicts that receptor clusters of size three and six are more abundant than others, indicating the special role of preformed receptor trimers. However, Caspase-8 activation only increases after receptor clusters of size larger than three. On the cell population level, the model can quantitatively predict the induction of apoptosis in this cell line. This work is an important step towards an integrative model of TRAIL induced apoptosis that finally aims at the understanding of heterogeneity both on a single cell level across cell lines. Citation Format: Andreas Raue, Diana Chai, Hannah Hudson, Eric Tam, Birgit Schoeberl. The effect of higher-order receptor clusters on TRAIL induced apoptotic signaling. [abstract]. In: Proceedings of the AACR Special Conference on Computational and Systems Biology of Cancer; Feb 8-11 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 2):Abstract nr B1-29.
Long-term survival after curative resection for pancreatic ductal adenocarcinoma
Authors: B. Sakar, N. F. Aykan, S. Saglam, Z. Ustuner
Journal: Journal of Clinical Oncology (2004)

4227 Background: The aim of the study was to determine prognostic factors of long-term survival after curative surgical treatment for pancreatic cancer. Methods: Between 1994 and 2000, resection with curative intent was performed on 75 patients with pancreatic ductal adenocarcinoma admitted to Department of Surgery, Medical Faculty of Istanbul. Clinical and demographic features, postoperative adjuvant treatment (5-fluorouracil continuous infusion and external beam irradiation concomitantly), and pathologic variables were analyzed. Results: A total of 75 patients was included in the final analysis. The median survival after surgery for all 75 patients was 11.6 months (95% CI: 10,00–13,34). Overall survival was influenced by postoperative adjuvant therapy (p=0.001), T stage of the disease (p=0.001), postoperative high level of CA19–9 (p=0.006) and nodal status (p=0.02). Location of the tumor was not prognostic for survival, although it was close to statistical significance (p=0.058). Multivariate analysis showed that T stage of the disease (p=0.001) and presence of adjuvant therapy (p=0.001) independently correlated with overall survival. Conclusions: Based on the analysis carried out, the authors conclude that the main prognostic factors for long-term survival after pancreatic cancer surgery are related to the tumor itself and adjuvant chemoradiation therapy which significantly improves survival after pancreaticoduodenectomy for ductal adenocarcinoma of the pancreas. No significant financial relationships to disclose.
Tumor response and toxicity after single high-dose versus standard five-day divided-dose dactinomycin in childhood rhabdomyosarcoma.
Authors: M Carli, G Pastore, G Perilongo, P Grotto, B De Bernardi, A Ceci, M Di Tullio, E Madon, C Pianca, G Paolucci
Journal: Journal of Clinical Oncology (1988)

This report deals with a randomized prospective multicentric clinical trial in childhood rhabdomyosarcoma (RMS) conducted to evaluate the toxicity and the effectiveness of dactinomycin (ACT-D) administered as high, single doses v five-day, divided doses administered in combination with vincristine (VCR) and cyclophosphamide (CYC). Fifty-five group III evaluable patients (pts) less than 15 years of age with tumor size greater than 5 cm in diameter, without high-risk features of CNS involvement, and 15 group IV RMS pts were randomized to receive VAC as primary chemotherapy (CT): VCR, 1.5 mg/m2 intravenously (IV) days 1 and 8; CYC, 275 mg/m2 IV days 1 through 5; and ACT-D, 0.45 mg/m2 IV days 1 through 5 every 28 days for three cycles (33 pts), or VAC-M: CYC, 150 mg/m2 intramuscularly (IM) days 1 through 7; VCR, 2.0 mg/m2 IV day 8; and ACT-D, 1.7 mg/m2 IV day 8 every 21 days for four cycles (37 pts). Major responses (complete plus partial responses [PR]) were obtained in 67% of the VAC pts and in 70% of the VAC-M pts. Toxic effects were low, and no increased toxicity was observed in pts treated with high, single-dose ACT-D. These results confirm the effectiveness and feasibility of single, high doses of ACT-D with the advantage of requiring less pt hospitalization.
Immunobullous disease and ulcerative colitis - the need of an accurate diagnosis
Authors: P. Iranzo, M. Alsina-Gibert
Journal: British Journal of Dermatology (2016)

Journal Article Immunobullous disease and ulcerative colitis – the need of an accurate diagnosis Get access P. Iranzo, P. Iranzo Department of Dermatology University of Barcelona Barcelona Spain Search for other works by this author on: Oxford Academic Google Scholar M. Alsina‐Gibert M. Alsina‐Gibert Department of Dermatology University of Barcelona Barcelona Spain Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 174, Issue 4, 1 April 2016, Pages 934–935, https://doi.org/10.1111/bjd.14394 Published: 01 April 2016
Maternal and postnatal vitamin D ingestion influences rat aortic structure, function and elastin content [Cardiovasc. Res. 2002;55:369–374]
Authors: B Boucher
Journal: Cardiovascular Research (2002)

The above mentioned paper [1] makes a valuable contribution to explaining the adverse effects that excessive exposure to dietary vitamin D are known to have on the developing vasculature of rodents, rabbits and probably also in man [2,3]. The authors suggest that the dosages used were not excessive, mean circulating levels of 25-OH vitamin D not rising above 103 mmol/l in any group and the mean levels in sows being 30 ng/ml. If the use of different units for these levels is not in error then the sows had mean levels of about 75 nmol/l, somewhere in the middle of levels reported from the three groups of offspring, rather levels matching those fed control chow. The daily intake of vitamin …
Correlation of the survival of ovarian cancer patients with mRNA expression of the 60-kD heat-shock protein HSP-60.
Authors: E Kimura, R E Enns, J E Alcaraz, J Arboleda, D J Slamon, S B Howell
Journal: Journal of Clinical Oncology (1993)

Ovarian carcinomas express the 60-kD heat-shock protein HSP-60 at widely varying levels in different tumors. The aim of this study was to determine whether there was a relationship between expression of HSP-60 and survival in patients with ovarian carcinoma.Total RNA and DNA were prepared from 51 epithelial ovarian cancer tissue samples. The expression and structure of the HSP-60 gene were examined by Northern and Southern blot analyses using the carboxyl-terminal portion of this gene as a probe (0.89 kilobases [kb]). HSP-60 expression was correlated with overall survival by the Kaplan-Meier method.The 2.3-kb HSP-60 message was detected in all samples, but there was marked variation from tumor to tumor. Patients were classified into two groups on the basis of HSP-60 expression: group 1 (n = 25) included patients with low expression, and group 2 (n = 26) consisted of patients with high expression. There were no significant differences between the groups with respect to age, cell type, pathologic grade, clinical stage, and previous treatment. After a median follow-up period of 17 months, Kaplan-Meier plots demonstrated a much better survival for group 1 (median, 46.8 months; 41% at 4 years) than group 2 (median, 22.1 months; 16% at 3.9 years), a difference that was highly significant by the Mantel-Haenszel test (P = .00183). Southern blot analysis of these samples showed no amplification or rearrangement of the gene.The level of HSP-60 mRNA expression is a valuable prognostic factor in epithelial ovarian cancer. Variation in the level of expression is not due to amplification of this gene.
Glaucoma Structural and Functional Progression in American and Korean Cohorts
Authors: Tigran Kostanyan, Kyung Rim Sung, Joel S. Schuman, Yun Ling, Katie A. Lucy, Richard A. Bilonick, Hiroshi Ishikawa, Larry Kagemann, Jin Y. Lee, Gadi Wollstein
Journal: Ophthalmology (2016)
Abstract P003: Trajectories of Cardiovascular Risk Factors / Outcomes and Atrial Fibrillation in a 25 Year Follow-up: The Atherosclerosis Risk in Communities Study
Authors: Faye L Lopez, Sunil K Agarwal, Elsayed Z Soliman, Lin Y Chen, Lindsay G Smith, Laura R Loehr, Alvaro Alonso
Journal: Circulation (2014)

Background: Little attention has been devoted to the timing of risk factor development in relation to atrial fibrillation (AF) diagnosis. We assessed the long term trajectories of risk factors and cardiovascular (CV) outcomes in the Atherosclerosis Risk in Communities (ARIC) study, a US community-based cohort. Methods: Our analysis included 2134 individuals with incident AF and 5674 controls matched with cases 1:3 on age, sex, race and center, participating in the ARIC study. Information on incident AF and risk factors / CV outcomes (obesity, hypertension, smoking, diabetes, heart failure (HF), myocardial infarction (MI), and stroke) was obtained during 5 study exams between 1987 and 2013, and surveillance of CV events through 2010. The prevalence of risk factors / CV outcomes in the period before and after the diagnosis of AF (and the corresponding index date for controls) was modeled using general estimating equations models. Adjusted odds ratios (OR) of risk factors / CV outcomes were calculated, using the index date ±2.5 years as the reference group. The interaction of time with AF was used to compare differences in trajectories. Results: During a median follow-up of 24 years, we observed diverse trajectories in the prevalence of risk factors and CV outcomes among AF patients, with steep increases in the prevalence of stroke, MI and HF during the period close to AF diagnosis, while trajectories for hypertension and diabetes showed monotonic increases, and those for smoking and obesity suggested decreases in prevalence after AF diagnosis (Figure A). The trajectories over time for hypertension, obesity, HF, stroke and MI were significantly different based on AF status, with lower increments among those without AF (Figure A and B). Conclusion: In this large population-based study, trajectories in the odds of risk factors and CV outcomes were diverse, suggesting they could have different roles in the pathogenesis of AF. The prevalence of CV outcomes increased after AF diagnosis, and trajectories differed by AF status.
Abstract 11273: Caveolae-Specific Phosphorylation of L-type Calcium Channel β2a Subunit Exacerbates Cardiac Hypertrophy
Authors: Shohei Kumagai, Nao Hayamizu, Sachi Matsunami, Wataru Otsuka, Yasushi Sakata, Yasushi Fujio, Hiroyuki Nakayama
Journal: Circulation (2014)

Background: L-type calcium channel (LTCC) localizes at T-tubules and caveolae in cardiomyocytes, and plays major roles in excitation-contraction coupling and cardiac hypertrophy. The expression of β2a subunit of LTCC (β2a) is increased in human failing heart. Recently, it was reported that phosphorylation of β2a by CaMKII enhanced LTCC activity. However, the functional role of β2a phosphorylation in heart failure remains to be elucidated. Objective: To make clear the functional role of β2a phosphorylation in cardiomyocytes. Methods and Results: Adenoviral overexpression of β2a demonstrated its constitutive phosphorylation by CaMKII and induced neonatal cardiomyocyte hypertrophy. Interestingly, phosphorylated β2a was co-localized with caveolin3. To assess caveolae-specific activation of CaMKII, we generated a fusion protein composed of phospholamban and caveolin3 (PLN-Cav3). This protein localized at caveolae, and caveolae-specific activation of CaMKII was detected using phospho-specific antibody for PLN (Thr17). In addition, to inhibit caveolae-specific CaMKII activity, we developed a GFP fusion protein with caveolin binding domain fused to CaMKII inhibitory peptide (CBD-GFP-AIP). We identified that this protein co-localized with caveolin3, and inhibited activation of CaMKII specifically at caveolae using PLN-Cav3 method. Moreover, CBD-GFP-AIP abolished β2a phosphorylation and attenuated β2a-induced cardiac hypertrophy. We found that phenylephrine (PE) stimulation activated caveolae-CaMKII and β2a in vitro and in vivo. Finally, we generated transgenic mice overexpressing wild-type (w-TG) or non-phospho mutant β2a (m-TG) in cardiomyocyte and evaluated cardiac hypertrophy after two weeks of chronic PE stimulation. The expression of β2a in both TG increased approximately 2.5 fold compared to control mice. PE-induced cardiac hypertrophy was attenuated in m-DTG compared to w-DTG mice (heart weight-body weight ratio: control; 4.8±0.2, *w-TG; 5.5±0.3, m-TG; 4.8±0.4, n=5-6, *p&lt;0.05 vs others). Conclusion: We developed novel methods to evaluate and inhibit caveolae-specific activation of CaMKII. Using these methods, we revealed that phosphorylated β2a localized at caveolae, and exaggerates cardiac hypertrophy.
STX11 Acts As a Novel Tumor Suppressor Gene in Peripheral T-Cell Lymphomas
Authors: Noriaki Yoshida, Shinobu Tsuzuki, Kennosuke Karube, Miyuki Katayama, Taishi Takahara, Shigeo Nakamura, Momoko Nishikori, Masanori Shimoyama, Koichi Ohshima, Kunihiro Tsukasaki, Masao Seto
Journal: Blood (2014)
Impact of the algorithm for declaring exact progression date on progression-free survival (PFS) estimates in advanced lung cancer clinical trials.
Authors: S. J. Mandrekar, S. L. Hillman, K. Allen-Ziegler, A. Jatoi, J. R. Jett, S. E. Schild, A. A. Adjei
Journal: Journal of Clinical Oncology (2010)

7629 Background: PFS based endpoints are controversial due to ascertainment bias, missing assessments, and symptomatic (nonradiographic) progression. We evaluated the impact of progression date determination on PFS estimates in advanced non-small cell lung cancer (NSCLC), and extensive stage small cell lung cancer (SCLC). Methods: Individual patient (pt) data from 8 consecutive NSCLC (n=485) and 4 SCLC (n=116) trials conducted through NCCTG were pooled. The disease assessment schedule was every 6 or 8 weeks (6 trials) during treatment, and every 3 or 6 months (6 trials) post treatment. The reported progression date (RPD) was defined as either the scan date for radiographic progression or the clinical deterioration date determined by the treating physician for nonradiographic progression. Disease progression date was determined by using: RPD (method 1), midpoint between last progression-free scan date and RPD (method 2), or one day post last progression-free scan date (method 3). PFS was defined as the earlier of time from registration to progression or death from any cause, using the 3 methods, and estimated using the method of Kaplan-Meier. Results: Within NSCLC (SCLC) 53% (58%) of pts reported progression during treatment, and 12% (7%) of pts died without progression. The median time from the last progression-free scan to progression for NSCLC (SCLC) during and post treatment was 1.4 (1.4) months (mos), and 2.8 (3.0) mos. 51% of pts did not have a progression-free scan post-baseline in SCLC. The median PFS ranged from 2.3-5.6 mos (method 1), 1.6-4.3 mos (method 2), and 0.03-2.9 mos (method 3) within NSCLC. The results were similar for SCLC trials. Conclusions: PFS estimates differed substantially across the 3 methods, with the magnitude of difference large enough to conclude efficacy (observed range: 30% to >100%). A standard for progression date determination should be adopted to ensure accurate comparisons between trials and to guide trial design. Progression date determination method Trial type NSCLC Median (95% CI) months SCLC Median (95% CI) months 1 3.9 (3.6-4.5) 2.7 (1.6–4.2) 2 3.0 (2.6–3.4) 1.8 (0.8–3.3) 3 1.8 (1.6-1.9) 0.03 (0.03–1.4) No significant financial relationships to disclose.
Patterns of care for women with ovarian cancer in the United States.
Authors: K A Muñoz, L C Harlan, E L Trimble
Journal: Journal of Clinical Oncology (1997)

To characterize treatments for ovarian cancer, to determine if recommended staging and treatment were provided, and to determine factors that influence receipt of recommended staging and treatment.A total of 785 women diagnosed with ovarian cancer in 1991 were selected from the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) program. Type and receipt of recommended staging and treatment were examined using data on surgery and physician-verified chemotherapy.Most women with presumptive stage I and II ovarian cancer were treated with surgery alone (58%), while women with stage III or IV disease were treated with surgery plus platinum-based chemotherapy (75% stage III, 56% stage IV). Approximately 10% of women with presumptive stage I and II, 71% with stage III, and 53% with stage IV disease received recommended staging and treatment. The absence of lymphadenectomy and assignment of histologic grade were the primary reasons women with presumptive stage I and II cancer did not receive recommended staging and treatment, whereas for stages III and IV, it was due to older women not receiving surgery plus platinum-based adjuvant chemotherapy. Age, stage, comorbidity, "other" race/ethnicity, and treatment at a facility with an approved residency training program were associated with whether recommended staging and therapy were received.Older women with late-stage disease did not receive recommended treatment. The majority of women with early-stage disease did not receive recommended staging and treatment.
Cut special offers on sugary foods, says delayed review
Authors: Zosia Kmietowicz
Journal: BMJ (2015)

A raft of measures is needed to reduce how much sugar people consume, Public Health England has said in its much delayed review of the evidence.

Reducing special offers and discounts on sugary foods in supermarkets, shops, and restaurants, controlling advertising of high sugar products to children, and reducing the sugar content and portion sizes of processed foods would all help to reduce sugar consumption, it said.1

The government should also consider a tax on high sugar foods, such as 10% to 20% levy on the price of sugar sweetened drinks, it said, though it added that this was likely to be less effective than the other three measures.

The review, which was originally due to be published in July, was finally published on 22 October after the main author told MPs about its main findings two days earlier.2 3

Alison Tedstone, chief nutritionist at Public Health England, said: …
Structural Insights into Polymorphic ABO Glycan Binding by Helicobacter pylori
Authors: Kristof Moonens, Pär Gideonsson, Suresh Subedi, Jeanna Bugaytsova, Ema Romaõ, Melissa Mendez, Jenny Nordén, Mahsa Fallah, Lena Rakhimova, Anna Shevtsova, Martina Lahmann, Gaetano Castaldo, Kristoffer Brännström, Fanny Coppens, Alvin W. Lo, Tor Ny, Jay V. Solnick, Guy Vandenbussche, Stefan Oscarson, Lennart Hammarström, Anna Arnqvist, Douglas E. Berg, Serge Muyldermans, Thomas Borén, Han Remaut
Journal: Cell Host & Microbe (2016)