tbuckley/cabot-search huggingface dataset:
Abstract IA2: Cancer genomes and their implications for basic and applied research
Authors: Bert Voaelstein
Journal: Cancer Research (2011)

Abstract Human cancer is, in essence, a genetic disease. Though this pivotal fact has been established over the past three decades, only recently has the compendium of genetic alterations in tumors been identified at a genome-wide scale. The basic landscapes of cancer genomes are becoming clear and the implications of this research are evident. These landscapes are populated by a few “mountains” – genes that are mutated at high frequency in specific tumor types – but are dominated by hills, representing genes that are mutated in only a relatively small fraction of the tumors. The vast majority of genetic alterations are point mutations, and most of these are passengers, i.e., provide no selective growth advantage to the tumor cell. Moreover, virtually all of the driver mutations in common solid tumors are in tumor suppressor genes rather than in oncogenes. All the bona fide cancer genes identified to date affect one or more of a dozen pathways that are central to neoplasia. Appreciation of this landscape has profound implications for both understanding the disease and managing patients with cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr IA2.
A Comparison of Immediate Angioplasty with Thrombolytic Therapy for Acute Myocardial Infarction
Authors: Cindy L. Grines, Kevin F. Browne, Jean Marco, Donald Rothbaum, Gregg W. Stone, James O'Keefe, Paul Overlie, Bryan Donohue, Noah Chelliah, Gerald C. Timmis, Ronald E. Vlietstra, Michelle Strzelecki, Sylvia Puchrowicz-Ochocki, William W. O'Neill
Journal: New England Journal of Medicine (1993)

The success of thrombolytic therapy for acute myocardial infarction is limited by bleeding complications, the impossibility of reperfusing all occluded coronary arteries, recurrent myocardial ischemia, and the relatively small number of patients who are appropriate candidates for this therapy. We hypothesized that these problems could be overcome by the use of immediate percutaneous transluminal coronary angioplasty (PTCA), without previous thrombolytic therapy.
Hyperglucagonism Induced by Glucocorticoid Treatment in Man
Authors: José Marco, Consuelo Calle, Dolores Román, Maruxa Díaz-Fierros, Maria L. Villanueva, Isabel Valverde
Journal: New England Journal of Medicine (1973)

To elucidate further the nature of glucocorticoid-induced alteration of carbohydrate metabolism, plasma glucagon levels, both basal and after an arginine stimulus, were studied in normal volunteers before and after glucocorticoid treatment. In one group of 13, after oral administration of prednisolone (40 mg daily, for four days) an increase in fasting glucagon levels (+ 24 pg per milliliter) and a glucagon hyper-response to a high arginine load (+ 133 pg per milliliter at 10 minutes, + 80 pg per milliliter at 20 minutes and + 51 pg per milliliter at 30 minutes) were accompanied by an elevation of glucose, amino nitrogen and insulin concentrations. In another group of eight, after oral administration of prednisolone (60 mg daily for three days) a rise in fasting glucagon levels (+ 17 pg per milliliter) and a greater glucagon response to a low arginine load (+ 68 pg per milliliter at 10 minutes) were observed. In a third group of five, the intravenous injection of prednisolone (100 mg) failed to alter plasma glucagon values, thus suggesting that its effect on the alpha cell is not direct. Glucocorticoid-induced hyperglucagonemia could represent another way in which these hormones exert their diabetogenic effect.
Intensified Antituberculosis Therapy in Adults with Tuberculous Meningitis
Authors: A. Dorothee Heemskerk, Nguyen D. Bang, Nguyen T.H. Mai, Tran T.H. Chau, Nguyen H. Phu, Pham P. Loc, Nguyen V.V. Chau, Tran T. Hien, Nguyen H. Dung, Nguyen T.N. Lan, Nguyen H. Lan, Nguyen N. Lan, Le T. Phong, Nguyen N. Vien, Nguyen Q. Hien, Nguyen T.B. Yen, Dang T.M. Ha, Jeremy N. Day, Maxine Caws, Laura Merson, Tran T.V. Thinh, Marcel Wolbers, Guy E. Thwaites, Jeremy J. Farrar
Journal: New England Journal of Medicine (2016)

Tuberculous meningitis is often lethal. Early antituberculosis treatment and adjunctive treatment with glucocorticoids improve survival, but nearly one third of patients with the condition still die. We hypothesized that intensified antituberculosis treatment would enhance the killing of intracerebral Mycobacterium tuberculosis organisms and decrease the rate of death among patients.We performed a randomized, double-blind, placebo-controlled trial involving human immunodeficiency virus (HIV)-infected adults and HIV-uninfected adults with a clinical diagnosis of tuberculous meningitis who were admitted to one of two Vietnamese hospitals. We compared a standard, 9-month antituberculosis regimen (which included 10 mg of rifampin per kilogram of body weight per day) with an intensified regimen that included higher-dose rifampin (15 mg per kilogram per day) and levofloxacin (20 mg per kilogram per day) for the first 8 weeks of treatment. The primary outcome was death by 9 months after randomization.A total of 817 patients (349 of whom were HIV-infected) were enrolled; 409 were randomly assigned to receive the standard regimen, and 408 were assigned to receive intensified treatment. During the 9 months of follow-up, 113 patients in the intensified-treatment group and 114 patients in the standard-treatment group died (hazard ratio, 0.94; 95% confidence interval, 0.73 to 1.22; P=0.66). There was no evidence of a significant differential effect of intensified treatment in the overall population or in any of the subgroups, with the possible exception of patients infected with isoniazid-resistant M. tuberculosis. There were also no significant differences in secondary outcomes between the treatment groups. The overall number of adverse events leading to treatment interruption did not differ significantly between the treatment groups (64 events in the standard-treatment group and 95 events in the intensified-treatment group, P=0.08).Intensified antituberculosis treatment was not associated with a higher rate of survival among patients with tuberculous meningitis than standard treatment. (Funded by the Wellcome Trust and the Li Ka Shing Foundation; Current Controlled Trials number, ISRCTN61649292.).
Evaluation of the efficacy of a novel three-dimensional (3D) rectal probe with a thinner diameter
Authors: S Itoh, K Hirahata, Y Nemoto, T Kakemura, S Hujinuma
Journal: Endoscopy (2006)

Aims: We have studied a manufactured rigid rectal probe enabling three-dimensional (3D) scanning since Jun 2001. The novel 3D rectal probe (7.5MHz, XRU-75M-DP2, Olympus) has a 15-mm outside diameter, and the form of its tip and the hand-operated swiveling part have been modified. When the rectal probe is used, there may be multiple echoes around its surface that can obscure the image, in which case a standoff produced by the balloon or the acoustic silicone coupler can be useful.
ASSOCIATION OF ARRHYTHMIAS WITH OUTCOMES IN PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY: AN ANALYSIS OF THE NATIONWIDE INPATIENT SAMPLE 2003-2011
Authors: Prakash Harikrishnan, Tanush Gupta, Dhaval Kolte, Chandrasekar Palaniswamy, Sahil Khera, Wilbert Aronow, Marjan Mujib, Nivas Balasubramaniyam, Diwakar Jain, Sachin Sule, Gregg Fonarow, Ali Ahmed, Howard Cooper, Jason Jacobson, Sei Iwai, Julio Panza
Journal: Journal of the American College of Cardiology (2015)
Evaluation of a Ventilation Strategy to Prevent Barotrauma in Patients at High Risk for Acute Respiratory Distress Syndrome
Authors: Thomas E. Stewart, Maureen O. Meade, Deborah J. Cook, John T. Granton, Richard V. Hodder, Stephen E. Lapinsky, C. David Mazer, Richard F. McLean, Ted S. Rogovein, B. Diana Schouten, Thomas R.J. Todd, Arthur S. Slutsky
Journal: New England Journal of Medicine (1998)

A strategy of mechanical ventilation that limits airway pressure and tidal volume while permitting hypercapnia has been recommended for patients with the acute respiratory distress syndrome. The goal is to reduce lung injury due to overdistention. However, the efficacy of this approach has not been established.
NC-16 * PREDICTORS OF POST-SURGICAL QUALITY OF LIFE IN PATIENTS WITH NON-FUNCTIONAL PITUITARY ADENOMA: THE INFLUENCE OF NEUROBEHAVIORAL FUNCTIONS
Authors: C.-Y. Yang, S.-H. Yang, C.-C. Yang
Journal: Neuro-Oncology (2014)

INTRODUCTION: Non-functional pituitary adenoma (NFPA) is one of the commonest subtypes of the pituitary adenomas. Although NFPA was benign, the mass effect of the adenoma would cause hypopituitarism or other complications which may affect the cognitive functions, emotional status or quality of life (QoL). Unfortunately, most of the previous studies were cross-sectional and could not reveal the changes of cognitive functions after surgery. This study thus aims to prospectively evaluate the neurobehavioral functions and related factors in patients with NFPA. METHOD: In this prospective study, 36 subjects with NFPA were recruited. Neurobehavioral functions, which included memory, executive function and speed of information processing, were evaluated. Depression, anxiety and QoL, were also examined by self-reported questionnaires. All participants were evaluated at the time of pre-operation, three and six months after surgery. RESULT: The substantial improvements in the memory, executive function and information processing were found. In respect to the emotional status and the QoL, depression and anxiety decreased significantly, while the physical QoL has a significant improvement. Importantly, the results showed that the pre-surgical psychological QoL was significantly associated with the post-surgical physical and global QoLs. In addition, the post-surgical social QoL was significantly negatively associated with the post-surgical disinhibited symptoms. CONCLUSION: This study not only revealed the post-surgical progression of neurobehavioral functions in patients with NFPA, but showed the principal predictors of post-surgical outcomes in those patients. It thus merits a comprehensive evaluation of neurobehavioral functions when patients with NFPA ready for the surgical treatments.
Abstract LB-414: Variation in base excision repair genes and risk of smoking-related non-small cell lung cancer
Authors: Diergaarde Brenda, Shama Buch, Tomoko Nukui, Roger Day, Jill Siegfried, Joel Weissfeld, Marjorie Romkes
Journal: Cancer Research (2010)

Abstract Base excision repair (BER) is the primary mechanism responsible for the repair of small base lesions in DNA caused by oxidation and alkylation. Given this role, functionally relevant polymorphisms in BER pathway genes may well affect the risk of smoking-related non-small cell lung cancer (NSCLC). We examined the association between 49 single nucleotide polymorphisms (SNPs) located in or near 5 different BER genes (XRCC1, LIG1, PARP1, MPG, and OGG1) and risk of NSCLC among Caucasians in a large case-control study. The study population consisted of 599 cases and 934 controls; all study participants were Caucasian and current or former cigarette smokers who had smoked at least 10.0 pack-years. SNPs were selected using various resources including literature review and data from the International HapMap project, and genotyping was conducted by Illumina Goldengate assay. Deviation from Hardy-Weinberg equilibrium was evaluated with the exact method. Associations between alleles and genotypes and NSCLC risk were examined using a Pearson Chi-square test and a Cochran-Armitage trend test, respectively. Per (minor) allele odds ratios (OR) and corresponding 95% confidence intervals (95% CI) were also calculated for each SNP. Six SNPs (rs3219073, rs747658, rs3219090, rs2048424, rs2666428, and rs8679) in PARP1 were statistically significantly (P&amp;lt;0.01) associated with NSCLC risk in our study population. SNP rs3219073 was in high linkage disequilibrium (r2≥0.8) with rs747658, as were rs3219090 and rs2048424 with rs2666428. The minor alleles of these SNPs were associated with a decreased risk of developing NSCLC (rs747658, OR: 0.7, 95%CI: 0.6-0.9, Ptrend=0.0005; rs2666428, OR: 0.8, 95%CI: 0.7-0.9, Ptrend =0.005). The C allele of SNP rs8679 (3′ UTR) was associated with an increased risk of NSCLC (OR: 1.3, 95%CI: 1.1-1.5, Ptrend =0.005). Additionally, SNPs rs3213255 and rs1799782 (Arg194Trp) in XRCC1 and SNP rs10500298 in LIG1 were also significantly associated with NSCLC risk. The minor alleles of rs3213255 and rs10500298 were associated with an increased risk (OR: 1.3, 95%CI: 1.1-1.5; OR: 1.2, 95%CI: 1.1-1.4, respectively), while the minor allele of rs1799782 was associated with a decreased risk (OR: 0.6, 95%CI: 0.4-0.9). PARP1 polymorphisms have previously been reported associated with other cancers, including breast cancer and colorectal cancer, but this is the first study to report associations with NSCLC risk. To conclude, our results suggest that common variation in PARP1, XRCC1 and LIG1 may be associated with risk of smoking-related NSCLC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-414.
OC-008 Endoscopic Submucosal Dissection Can Transform The Management Of Patients With Upper Gastrointestinal Submucosal Tumours: Results From A Uk Series: Abstract OC-008 Table 1
Authors: R Bhattacharyya, P Bhandari
Journal: Gut (2014)

<h3>Introduction</h3> It is very difficult to establish an accurate diagnosis for upper GI submucosal tumours. Biopsy during endoscopy cannot go deep enough. EUS is unable to give a tissue diagnosis. The risks of surgical resection are higher than the benefits as the lesion may very well be benign. As a result most of these patients keep having endoscopic surveillance as ‘possible’ GISTs. <h3>Methods</h3> A retrospective cohort study of patients undergoing ESD for upper GI submucosal tumours. They were all referred to us as possible GISTs that were found to be growing in size on surveillance. ESD was carried out in all these cases. As these lesions are mostly bulky, gravity and patient positioning were utilised as traction during ESD to achieve deroofing and enucleation of these tumours. Any complications were recorded. Endoscopic follow up was performed to assess for incomplete resection or recurrence. <h3>Results</h3> 21 submucosal lesions were resected by ESD between 2007 and 2013. 7 were oesophageal, 10 gastric and 4 duodenal. Sizes ranged from 10 to 35mm. Endoscopic clearance was achieved in all cases. Histology showed a wide range of diagnoses, mostly benign (table). There was 1 complication; a microperforation which was identified and clipped intraprocedurally, giving a complication rate of 4.7%. On follow up, there was 1 recurrence (recurrence rate 4.7%) which was managed endoscopically. 1 patient had surgery as the ESD specimen showed a synovial sarcoma. Endoscopic cure rate was 95.2%. <h3>Conclusion</h3> ESD is a safe and novel, minimal access therapeutic technique which has the potential to transform management of submucosal tumours. Patients go from the uncertainty of having repeated endoscopies for an unknown diagnosis, to having it completely removed and cured in the vast majority, without the need for continuing endoscopies. In the remaining cases, ESD specimens provide an accurate histological diagnosis based on which definite management plans can be made. <h3>Disclosure of Interest</h3> None Declared.
THU0421 Musculoskeletal Diseases Have the Worst Impact on Physical Health Compared with Other Diseases – Results of A Dutch Epidemiological Study
Authors: A. Van Der Zee-Neuen, P. Putrik, S. Ramiro, A. Keszei, R. de Bie, A. Chorus, A. Boonen
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Musculoskeletal conditions (MSKC) are among the most common chronic conditions. Increasingly, patients suffer from more than one disease. The presence of a co-morbid disease adds to the burden of single diseases worldwide. <h3>Objectives</h3> The aim of this study was to explore 1) the impact of the number of morbidities on health, 2) whether MSKC have a higher impact on health compared with other diseases and 3) whether MSKC have an important impact on health independently of the number of co-morbidities <h3>Methods</h3> In a Dutch cross-sectional study, 8904 subjects (&gt;18 years old, random sample) completed a questionnaire on sociodemographic factors, smoking status, BMI, self-reported physician-diagnosed diseases and the 12-Item Short-Form Health Survey (SF-12). Missing values were handled using multiple imputation. Multivariable linear regression was computed to identify 1) whether multimorbidity in terms of number of diseases was significantly associated with the SF-12 physical (PCS) and mental (MCS) subscales, 2) which diseases contributed the most to changes in health and 3) whether MSKC as co-morbidity were associated with additional decrease in PCS/MCS independently of the number of morbidities. Models were adjusted for age, gender, education, origin and BMI. Multilevel analyses were performed to identify possible differences at the level of postal code. Multilevel analyses were performed to identify possible differences by place of residence (postal code). <h3>Results</h3> Multimorbidity was present in 1722 subjects (19%). MSKC was reported by 1766 (20%) participants. 547 (6%) reported diabetes,1855 (21%) CVD, 270 (3%) cancer, 679 (8%) a respiratory condition, 630 (7%) a skin condition, 526 (6%) a mental disorder, 394 (4%) migraine and 333 (4%) bowel disease. A linear relation between the number of diseases and health was observed. MSKC had the highest negative impact on PCS compared to other diseases (β=-8.37[-8.84;-7.89] (Table 1). In addition, a clinically relevant increase of the effect of each single disease on PCS when co-occurring with MSKC was found. <h3>Conclusions</h3> Multimorbidity is prevalent in the Dutch population (19%). A higher number of morbidities results in worse physical and mental health. MSKC have the worst impact on physical health compared to other diseases when occurring alone or when occurring as co-morbid disease. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1678
Abstract P6-01-05: Enhancement of18F-FDG uptake and glycolysis by epidermal growth factor via PI3K activation in T47D breast cancer cells
Authors: EJ Lee, JW Park, Q Cung, K-H Jung, JH Lee, J-Y Paik, K-H Lee
Journal: Cancer Research (2012)

Abstract It is well known that the binding of epidermal growth factor (EGF) to EGF receptors (EGFR) stimulates proliferation of breast cancer cells via activation of mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signaling pathways. There was a report that glucose consumption and lactate production were increased in MDA-MB-468 breast cancer cells following EGF exposure. However, the effect of EGF in enhancing glucose uptake and signaling pathways that are involved have not been clearly revealed. We thus investigated the role of EGF in stimulation of18F-FDG uptake in T47D breast cancer cells, and further elucidated the molecular mechanisms that are involved. Exposure of T47D cells to 100 ng/mL EGF for 24 h caused a substantial augmentation of18F-FDG uptake to even greater extents to 310.8% ± 30.1% of control cells (P &amp;lt; 0.001), and this effect of EGF showed dose- and time-dependency. Increased glucose uptake by EGF occurred through enhanced membrane GLUT-1 expression as well as hexokinase activity. Inhibition experiments with cycloheximide showed that the metabolic effect by EGF required new protein biosynthesis. Stimulation of glucose uptake by EGF was dependent on sufficient EGFR expression because18F-FDG uptake in MCF-7 cells weakly expressing EGFR was not affected by EGF treatment. Although EGF was also a stimulator of T47D cell proliferation (137.3 ± 7.3% of basal levels at 24 h, P &amp;lt; 0.001), the metabolic effect occurred in a manner that clearly preceded and surpassed the proliferative effect. EGF-stimulated proliferation was significantly inhibited by the EGFR inhibitor BIBX1382, the PI3K inhibitor LY294002 and the specific MAPK inhibitor PD98059. Unlike proliferation, the ability of EGF to augment18F-FDG uptake was found to be dependent on PI3K but not on MAPK activity. These findings yield the insight into our understanding of the role of EGF and the molecular basis that are involved in glucose metabolism of breast cancer cells. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-01-05.
Abstract 5103: Analysis of the role of “ATM” through “omics” analysis
Authors: Amrita K. Cheema, Mira Jung, Olga Timofeeva, Rency Varghese, Habtom Ressom, Anatoly Dritschilo
Journal: Cancer Research (2010)

Abstract The human genetic disease, ataxia-telangiectasia (AT) is characterized by exquisite radiation sensitivity, neurological degeneration, immune deficiencies, genetic instability and predisposition to cancer. Furthermore, cells from patients with AT show disruption of the DNA damage response (DDR), a global signaling network that senses damage and coordinates cellular responses that include cell cycle regulation, transcription, DNA repair processes and apoptosis. Previously, AT5BIVA cells have been was established by SV40 immortalization of fibroblasts derived from an AT group D patient. We derived ATCL8 cells line was then derived by transfecting AT5BIVA with a vector carrying expressing the full- length wild type ATM. ATCL8 cells are and was found to be less sensitive to radiation resistant (D0=1.7 Gy) as compared tothan are the parental cell line AT5BIVA cells (D0=0.7 Gy). We have used a systems approach to understand compare the baseline changes that occur at the genomics, proteomics and metabolomic levels in these two near isogenic cell lines and integrate the information to understand the correlation. The. mMicroarray analysies wereas carried performed out to compare investigate basal level changes in gene expression. between AT5BIVA and ATCL8. The p Proteomics analysies for the same system was donewere performed using a 2-D gels and mass spectrometry approach. Finally, metabolomic profilesing was performed were obtained using UPLC-ESI-TOF mass spectrometry followed by multivariate data analysis using (SIMCA-P and random forest) software. The mMetabolites which were found observed to be significantly different in ATCL8 as compared to AT5BIVA were then subjected to functional pathway analysies using the ingenuity software. The proteomics and the microarray data were then scored for the presence of proteins and genes which were a part of the predominant signaling pathways in the two cell lines as determined by metabolomic analysis. The model system used in this study involves studyingof basal level changes in expression resulting from perturbations in a single gene and our results demonstrate the feasibility of such an the approach to correlate the changes found at all three levels of expression. The findings will be discussed in the context of the “AT” phenotype will be discussed. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5103.
SCAR LOCATION, BUT NOT TOTAL SCAR BURDEN, PREDICTS ARRHYTHMIA FREE SURVIVAL IN HEART FAILURE PATIENTS WITH IMPLANTABLE DEFIBRILLATOR
Authors: Uzma Chaudhry, Robert Jablonowski, Henrik Engblom, Håkan Arheden, Pyotr Platonov, Marcus Carlsson, Rasmus Borgquist
Journal: Journal of the American College of Cardiology (2015)