tbuckley/cabot-search huggingface dataset:
New GOLD 2011 guidelines: Is there an improvement?
Authors: Ana Sofia Santos, Ricardo Coelho, Sofia Granadeiro, Raquel Rosa, Alexandra Borba, Inês Gonçalves, Paula Cravo, Alexandra Mineiro, Salvador Coelho, Maria João Gomes, Joao Cardoso
Journal: European Respiratory Journal (2012)

Background: The 2011 revision of GOLD report establishes a new assessment of COPD based on the patient9s level of symptoms, spirometric classification and exacerbation history.  Aim: To compare and establish the differences between the classification of COPD patients using the guidelines of GOLD report 2010 and 2011.  Methods: A prospective study with a group of consecutive COPD patients from our outpatient clinic was performed. They were assessed according to GOLD 2011 by answering COPD Assessment Test (CAT) and Modified British Medical Research Council (mMRC) Questionnaire; by a spirometric evaluation in the same day and by reviewing the history of exacerbations of the previous year. This data was compared with the GOLD 2010 COPD assessment of the same patients.  Results: 45 patients were included (mean age 62,3 (±9); 73% male). The results are as below:  Conclusions: GOLD 2010 stage 4 patients were the group with greater exacerbation history. With exception for GOLD 2010 stage 1 patients, which were mainly assessed as group A in the 2011 GOLD classification, the remaining patients were mostly placed in the groups with greater symptomatic impact (B and D), which was better assessed by CAT. This shows the burden of disease in patient9s life and the need of a better treatment management, which is one of the goals of the 2011 COPD assessment.
Characterization of the overall survival benefit in ENCORE 301, a randomized placebo-controlled phase II study of exemestane with and without entinostat in ER+ postmenopausal women with metastatic breast cancer.
Authors: Pamela Klein, Peter Ordentlich, William McCulloch, Scott Cruickshank, Miranda Rees, Denise Aysel Yardley
Journal: Journal of Clinical Oncology (2012)

567 Background: Histone deacetylase inhibitors (HDACi) prevent the emergence of drug tolerant clones and sensitize cells to a variety of anti-cancer therapies. We previously reported ENCORE 301, a randomized placebo controlled phase 2 study comparing exemestane with (EE) and without (EP) the HDACi entinostat met its primary endpoint of prolonging progression free survival (PFS) (4.3 months vs 2.3 months) and extending overall survival (OS) benefit (26.9 vs 19.8 months). In order to characterize and better understand the OS benefit, exploratory analyses were conducted. Methods: Hazard ratios (HR) for treatment were estimated from the Cox proportional hazards model, with EP serving as the reference treatment in the calculations. Inferential comparisons between treatment groups were made using the log-rank test. Results: Analysis of OS across multiple subsets of interest demonstrated a consistent benefit in EE group versus EP. Sensitivity analysis of baseline characteristics potentially impacting OS did not identify any factors that influenced the effect of EE on OS. Examination of treatments received during follow-up after discontinuation of EE and EP demonstrated balance between treatment group for patients receiving chemotherapy (48% EE: 44% EP), hormone therapy (37% EE: 35% EP), bisphosphonates (2% EE; 0% EP), radiation (6% EE; 5%EP), and surgery (0% EE: 2% EP). Compared to EP, OS was longer in EE group for patients whose first subsequent treatment was a hormone therapy (EE median not reached vs EP median 20.5 months; HR 0.65 [95% CI 0.26, 1.58]) or chemotherapy (EE median 26.9 months vs EP median 17.6 months; HR 0.51 [95% CI 0.25, 1.04]). Updated PFS and OS data will also be presented along with correlation analysis of PFS and OS. Conclusions: Analyses of baseline characteristics, subsequent treatment and subsets of prognostic factors in ENCORE 301 did not identify any contributing factors that account for the extended OS benefit in the EE treatment group. Long lasting effects of entinostat on progenitor cells, emergence of drug tolerant cells and or priming to subsequent therapies cannot be ruled out.
Bone effects of exemestane versus tamoxifen within the TEAM Trial: Results of a prospective randomized bone substudy
Authors: P. Hadji, M. Ziller, D. G. Kieback, W. Dornoff, H. Tessen, G. Weyer, A. Hasenburg
Journal: Journal of Clinical Oncology (2008)

572 Background: A prospective open label randomized multicenter trial was performed in the German TEAM Trial Group to compare the effects of exemestane (EXE) and tamoxifen (TAM) on bone mineral density (BMD) and markers of bone turnover during adjuvant treatment of postmenopausal women with estrogen receptor-positive breast cancer. Methods: BMD and markers of bone turnover were assessed at baseline, after 6 and 12 months of treatment. BMD was performed using dual x-ray absorptiometry (DXA). Marker of bone formation (PINP), bone specific alkaline phosphatase (BAP) and osteocalcin (OC) as well as bone resorption marker (ICPM) were analysed using standardised methods. Intent-to-treat analysis was performed based on 200 patients. The primary endpoint was to compare exemestane and tamoxifen with regard to changes from baseline to month 12 in spine BMD. Results: 156 patients with a mean age of 61 yr. (± 7.3 yr.) were available for final analysis. Both groups were comparable regarding age, height, tumor grade and stage. Compared to women on tamoxifen, who comprised an BMD increase of +0.9% and +0.9% after 6 and 12 months at the spine, women on EXE showed a decrease of -2.8% and - 3.6%. Conversely, BMD at the FN showed a decrease of -2.1% and -2.2% in women on TAM while women on EXE showed a decrease of -3.4% after 6 and an increase of +1.1% after 12 months, respectively. Bone formation and absorption was modulated in both groups. Details will be presented at the meeting. Conclusions: The results of the 12 months analysis in the TEAM Bone substudy confirm the bone protective effect of TAM at the spine while the results at the FN showed a BMD decrease. Women on EXE showed a decrease at the spine while there was a neutral effect at the FN BMD. Further evaluation of the fracture rate of the TEAM trial is necessary to evaluate the effect of EXE on bone health. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis, Pfizer AstraZeneca, Novartis, Pfizer Pfizer
Abstract P355: Sodium and Potassium 24 Hours Excretion in The Italian Adult Population: Preliminary Results of The MINISAL-GIRCSI Study
Authors: Chiara Donfrancesco, Renato Ippolito, Cinzia Lo Noce, Luigi Palmieri, Roberto Iacone, Ornella Russo, Diego Vanuzzo, Ferruccio Galletti, Simona Giampaoli, Pasquale Strazzullo
Journal: Circulation (2012)

Background: According to the recommendation of the High Level Group of the European Union within the “Gaining health: make healthy choices easy choice” Preventive Program of the Italian Ministry of Health, the agreement with bread makers' associations was signed for the gradual reduction of the salt content in bread. In Italy, information about habitual sodium and potassium intake is scanty. In order to monitor preventive actions of this Preventive Programme the MINISAL-GIRCSI Study is to assess the dietary intake of sodium and potassium in representative samples of the Italian adult population. Methods: Baseline data from 12 different random samples collected within the MINISAL-GIRCSI-Health Examination Survey started in 2008, with completed screening and laboratory determinations, were considered: 1196 men and 1231 women aged 35-79 years. Sodium and potassium daily intakes were assessed through 24-hour urine collection using standardized procedures. Determinations of sodium, potassium and creatinine were assessed in a centralized laboratory. Information on habit of adding salt to food and the consumption of high salt content food were collected through a questionnaire. Results: Mean of sodium chloride per day resulted 11 g in men and 8 g in women with a range of 1-27 g and 2-27 g respectively. Mean of potassium chloride per day resulted 5 g in men and 4 g in women with a range of 1-13 g and 1-9 g respectively. Mean of creatinine per day resulted 1463 mg in men and 942 mg in women. Mean of urine volume per day resulted 1861 ml in men and 1827 ml in women. In both men and women, higher intake of sodium chloride was found in Southern regions; no geographical differences were found for potassium chloride. Sodium and potassium chloride excretions were not found higher with increasing age. Most of persons (72%) eat three slices of bread per day and 22% eat cheese and processed meat more than 4 times per week. Thirteen percent of persons usually add salt during meals and 19% are usually thirsty after meals. Conclusions: Preliminary results show that Italian adult population take more than double of WHO recommended salt intake; this is typical in industrialized countries. Further analyses considering data from other Italian regions are needed to confirm these values. The prevention actions at population level should include recommendations for reducing salt intake.
Abstract 16208: High Salt Inhibits Lymphatic Transport Function Through Regulation Of Na+-K+-ATPase Activity
Authors: Risuke Mizuno, Masashi Isshiki, Mitsuhiro Nishimoto, Toshiro Fujita
Journal: Circulation (2012)

Objective:  Current experimental evidence suggests that the lymphatic system is emerging as a key player in the pathogenesis of salt-sensitive hypertension. In hypertensive animals, accumulation of Na+ in subcutaneous spaces stimulates VEGF-C production in macrophages, and this secretion of VEGF-C promotes hyperplasia of lymphatic capillaries. This increased density of lymphatic capillaries reduces blood pressure in response to high salt conditions. Although collecting lymphatics connected to lymphatic capillaries contribute to the transport of lymph in pathophysiological conditions, collecting lymphatic function in response to high salt levels is not clear. The present study aimed to investigate the effects of high salt on the pumping activity of lymphatics.   Methods:  Afferent lymphatics were isolated from the iliac lymph nodes of Sprague-Dawley rats. The lymphatics were cannulated and pressurized to produce spontaneous lymphatic pumping activity. Changes in the frequency and diameter of lymphatic activity were measured using DVD microscopy. We used physiological salt solution (PSS) containing Na+ (146.2 mM), to which we added NaCl (10, 30, 50, and 70 mM) to increase the extra-cellular Na+ concentration.   Results:  NaCl dose-dependently and significantly reduced the % frequency of lymphatic activity, indicating that NaCl induced negative chronotropic effects on the lymphatic activity. The negative effects were potentiated in the presence of ouabain (an inhibitor of Na+-K+-ATPase). Lidocaine (non-selective Na+ channel blocker) and glibenclamide (ATP-sensitive K+-channels blockers) significantly reversed the high salt-mediated reduction in lymphatic activity.   Conclusion:  These results suggest that lymph containing high salt suppress lymphatic transport by inhibition of pumping, which results in excess accumulation of fluids and electrolytes in tissues. The mechanisms of high salt lymphatic transport suppression involve the regulation of Na+-K+-ATPase activity coupling with Na+ channels, and ATP-sensitive K+ channels in lymphatic smooth muscles.
A Facile Method of Purification of Neocarzinostatin, an Antitumor Protein 2
Authors: T. S. Anantha Samy, Jee-Min Hu, J. Meienhofer, H. Lazarus, Randall K. Johnson
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article A Facile Method of Purification of Neocarzinostatin, an Antitumor Protein Get access T. S. Anantha Samy, T. S. Anantha Samy Search for other works by this author on: Oxford Academic PubMed Google Scholar Jee-Min Hu, Jee-Min Hu Search for other works by this author on: Oxford Academic PubMed Google Scholar J. Meienhofer, J. Meienhofer Search for other works by this author on: Oxford Academic PubMed Google Scholar H. Lazarus, H. Lazarus Search for other works by this author on: Oxford Academic PubMed Google Scholar Randall K. Johnson Randall K. Johnson Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 58, Issue 6, June 1977, Pages 1765–1768, https://doi.org/10.1093/jnci/58.6.1765 Published: 01 June 1977 Article history Received: 28 August 1976 Accepted: 28 December 1976 Published: 01 June 1977
Open-label phase II trial of everolimus monotherapy in patients with recurrent metastatic and/or unresectable renal cell carcinoma (RCC).
Authors: B. Tannir, S. Hardikar
Journal: Journal of Clinical Oncology (2010)

TPS233 Background: Until recently, patients with metastatic renal cell carcinoma (mRCC) had few treatment options given the low response rate associated with chemotherapy and cytokine treatment. An improved understanding of the molecular basis of RCC has led to the development of targeted therapies that have shown clinical benefit in patients with metastatic disease. Everolimus is an oral inhibitor of the mammalian target of rapamycin (mTOR), a key regulator of cell growth and proliferation, cellular metabolism, and angiogenesis that is aberrantly activated in RCC. In the pivotal RECORD-1 study, everolimus monotherapy prolonged progression-free survival (PFS) vs placebo in patients with clear cell mRCC whose disease had progressed on vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy, and everolimus is now approved for this indication. The EVERMORE (Everolimus as Monotherapy Treatment for Patients with Metastatic Recurrent and/or Unresectable Renal Cell Carcinoma) trial will evaluate the efficacy and safety of everolimus monotherapy in patients with metastatic recurrent and/or unresectable RCC without prior systemic therapy other than cytokine therapy. Methods: EVERMORE is an open-label, multicenter, single-arm phase II trial. Up to 80 adult patients with metastatic, recurrent, or unresectable RCC of any MSKCC prognosis and histologic or cytologic confirmation of clear cell or non-clear cell RCC, ≥1 measurable baseline lesion as per RECIST criteria, Karnofsky performance status ≥70%, and adequate liver, renal, and bone marrow function are targeted for enrollment. Patients who have received prior systemic RCC therapy (sunitinib, sorafenib, bevacizumab, sirolimus, temsirolimus, everolimus, deferolimus) other than cytokine therapy are excluded. Everolimus 10 mg/d will be administered orally until disease progression, unacceptable toxicity, or study discontinuation for any other reason. The primary study endpoint is PFS. Overall survival, disease control rate, objective response rate and duration, and safety will also be assessed. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis
MM-151 overcomes acquired resistance to cetuximab and panitumumab in colorectal cancers harboring EGFR extracellular domain mutations
Authors: Sabrina Arena, Giulia Siravegna, Benedetta Mussolin, Jeffrey D. Kearns, Beni B. Wolf, Sandra Misale, Luca Lazzari, Andrea Bertotti, Livio Trusolino, Alex A. Adjei, Clara Montagut, Federica Di Nicolantonio, Rachel Nering, Alberto Bardelli
Journal: Science Translational Medicine (2016)

An oligoclonal antibody overcomes drug resistance in colorectal cancers with EGFR mutations.
Abstract 15323: Increased Incidence of Cerebrovascular Events and Decreased Incidence of Coronary Events in Down Syndrome Individuals
Authors: Christopher G Sobey, Courtney P Judkins, Thanh G Phan, Vijaya Sundararajan, Grant R Drummond, Velandai K Srikanth
Journal: Circulation (2013)

The incidence of major cardiovascular events (CVEs) in Down Syndrome (DS) is unknown. We have performed a population-level cohort comparison of the incidence of major CVEs between individuals with ...
Half of UK hospitals lack essential services for managing acute GI bleeds, inquiry finds
Authors: Susan Mayor
Journal: BMJ (2015)

Patients with acute gastrointestinal (GI) bleeds should be admitted only to hospitals with 24/7 access to endoscopy, interventional radiology, GI bleed surgery, and the critical care facilities needed to optimise their care, a UK inquiry has recommended,1 saying that half of hospitals currently managing these patients lack some of these services.

The National Confidential Enquiry into Patient Outcome and Death (NCEPOD) collected data on the care and outcomes of patients admitted to hospitals in England, Wales, Northern Ireland, the Isle of Man, Guernsey, and Jersey with GI bleeding in the four months from 1 January to 30 April 2013. …
Neural network model for estimating the apnoea-hypopnea index from nocturnal oxygen saturation
Authors: Felix del Campo, Roberto Hornero, Daniel Alvarez, J. Victor Marcos
Journal: European Respiratory Journal (2011)

Background: Nocturnal polysomnography (PSG) is the gold-standard for SAHS diagnosis. However, it is complex, expensive and time-consuming. Thus, simplified diagnostic techniques are desirable.

Aims: This study proposes a novel method to assist in SAHS diagnosis based on automated analysis of oxygen saturation (SaO2) recordings. It is hypothesised that an accurate estimate of the AHI can be obtained from these recordings using signal processing methods.

Methods: A database with 96 subjects (64 SAHS-positive) was available. Multilayer perceptron (MLP) neural networks were used to model SAHS diagnosis as a regression problem. A methodology composed of two stages was designed: 1) feature extraction and 2) regression analysis. In the first one, a set of 14 time-domain and frequency-domain features was defined to reflect the dynamical properties of SaO2 signals with respect to SAHS. In the second stage, the pattern composed of the extracted features was used as input to the MLP regression algorithm. The intraclass correlation coefficient (ICC) and the root mean square error (ERMS) between true and predicted AHI were computed to evaluate the accuracy of the estimation.

Results: The MLP-based approach achieved ICC = 0.92 and ERMS = 9.47, which outperformed conventional oximetry indices and the Delta index. In addition to high ICC, this algorithm achieved small error for all the range of AHI values. The regression model using ODI3 overestimated AHI for small target values. The diagnostic ability of the regression model based on ODI3 was very poor

Conclusions: The proposed method represents a valuable screening tool that could contribute to reduce the number of required PSG tests
Substitution Model Adequacy and Assessing the Reliability of Estimates of Virus Evolutionary Rates and Time Scales
Authors: Sebastián Duchêne, Francesca Di Giallonardo, Edward C. Holmes
Journal: Molecular Biology and Evolution (2015)

Determining the time scale of virus evolution is central to understanding their origins and emergence. The phylogenetic methods commonly used for this purpose can be misleading if the substitution model makes incorrect assumptions about the data. Empirical studies consider a pool of models and select that with the highest statistical fit. However, this does not allow the rejection of all models, even if they poorly describe the data. An alternative is to use model adequacy methods that evaluate the ability of a model to predict hypothetical future observations. This can be done by comparing the empirical data with data generated under the model in question. We conducted simulations to evaluate the sensitivity of such methods with nucleotide, amino acid, and codon data. These effectively detected underparameterized models, but failed to detect mutational saturation and some instances of nonstationary base composition, which can lead to biases in estimates of tree topology and length. To test the applicability of these methods with real data, we analyzed nucleotide and amino acid data sets from the genus Flavivirus of RNA viruses. In most cases these models were inadequate, with the exception of a data set of relatively closely related sequences of Dengue virus, for which the GTR+Γ nucleotide and LG+Γ amino acid substitution models were adequate. Our results partly explain the lack of consensus over estimates of the long-term evolutionary time scale of these viruses, and indicate that assessing the adequacy of substitution models should be routinely used to determine whether estimates are reliable.
Abstract A1-08: Comparative genomics study of FOXA/ER dual regulation in breast cancer and liver cancer
Authors: Zhaoyu Li
Journal: Cancer Research (2015)

Abstract Estrogen, the female dominant hormone, has been found to play critical roles in cancers for over 100 years. In 1896, estrogen was found to promote the tumor growth of breast cancer; and in 1937, estrogen was found to prevent the tumor growth of liver cancer. After the estrogen receptor alpha (ERα) was identified in 1958, ERα-mediated estrogen signaling was found to promote or prevent the growth of breast cancer cells or liver cancer cells, respectively. Recent studies showed that ERα-mediated estrogen signaling in promoting the growth of breast cancer cells was dependent of forkhead box protein A1 (FOXA1). Our recent study showed that ERα-mediated estrogen signaling in preventing the growth of liver cancer cells also depended on FOXA factors (FOXA1 and FOXA2). Thus, FOXA-dependent ERα-mediated estrogen signaling plays opposite roles in the growth of breast cancer and liver cancer cells. Here, we applied genomic approaches to identify 184 FOXA/ER dual target genes that showed opposite expression in response to estrogen-mediated stimulation or suppression of cell growth in breast or liver cancer cells. Gene ontology analysis showed that the majority of these FOXA/ER dual target genes were involved in the processes of cell proliferation and growth, cell death, tissue development, and cancer. Manipulations of the expression of these target genes were able to reverse the growth of breast and liver cancer cells. Thus, these 184 FOXA/ER dual target genes provide us a novel set of potential biomarkers and therapeutic targets for both breast cancer and liver cancer. Note: This abstract was not presented at the conference. Citation Format: Zhaoyu Li. Comparative genomics study of FOXA/ER dual regulation in breast cancer and liver cancer. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A1-08.