tbuckley/cabot-search huggingface dataset:
Analysis of clinicopathological characteristics of 982 lung cancer patients and subsequent treatment - Epidemiology study
Authors: Dragana Jovanovic, Nevana Secan, Zafir Murtezani, Milan Rancic, Vesna Kacar-Kukric, Marta Velinovic, Ana Tepavac, Evica Budisin, Zoran Andric, Nevena Vukobradovic Djoric
Journal: European Respiratory Journal (2013)

The purpose of the survey was the analysis of clinicopathological features of lung cancer patients in Serbia and subsequent treatment approach.  Method: the data were collected based on specific questionnaire at 4 major centers in Serbia.  Results. Out of 982 patients (pts), NSCLC was diagnosed in 80% (789), 71.6% (679) in stage IIIb and IV. Most common histological subtype was adenocarcinoma (46%), followed by squamous cell carcinoma (44%). Neodjuvant therapy was applied in 8% (67pts), while 19% (153pts) were operated - 64% (98) of operated patients recieved adjuvant chemotherapy. Among IIIb/IV NSCLC patients, 91% (511) recieved 1st line chemotherapy, platinum/etoposide (51%) and platinum/gemcitabine (45%) most frequently applied regimens. Second line chemotherapy was given to 27% (136) of 1st line treated patients. Third line chemotherapy was applied in 22% (29) of 2nd line treated patients.  Conclusions. This is the largest series of lung cancer patients in Serbia, analized by both, patient characteristics and treatment. Compared to previous similar NSCLC analysis in 2009, the number of NSCLC patients is obviously increasing (1.5% per year). Rate of adenocarcinoma is also increasing (41% in 2009 vs 45% in 2011). Regarding treatment options, there is no significant difference.
Abstract 11085: Agonist-Independent Activation of the Angiotensin II Type 1 Receptor Contributes to Left Ventricular Remodeling in vivo
Authors: Noritaka Yasuda, Hiroshi Akazawa, Kaoru Ito, Yoko kudo, Yukako Ozasa, Issei Komuro
Journal: Circulation (2010)

The angiotensin II (AngII) type 1 (AT1) receptor plays a crucial role in regulating the pathophysiological processes in the cardiovascular system. Recent in vitro studies demonstrated that AT1 receptor inherently shows spontaneous activity even in the absence of AngII. However, it remains unclear whether AngII-independent AT1 receptor activation is implicated in the pathogenesis of cardiovascular remodeling. Therefore, to elucidate the role of AngII-independent AT1 receptor activation in in vivo hearts, we generated transgenic mice overexpressing AT1 receptor under the control of the α-myosin heavy chain promoter in the Angiotensinogen-knockout background (AT1Tg-AgtKO). In spite of systemic deficiency of AngII, the redistribution of Gαq11 subunits into the cytosol was significantly increased in AT1Tg-AgtKO hearts, compared with Angiotensinogen-knockout (AgtKO) hearts. Furthermore, AT1Tg-AgtKO hearts showed a significant increas in the phosphorylation levels of extracellular signal-regulated kinases (ERKs)...
Lung function and respiratory symptoms of Brazilian sugarcane cutters exposed to biomass burning
Authors: Luiz Carlos Carvalho Junior, Ercy Ramos, Alessandra Toledo, Aline Ferreira-Ceccato, Rafaela Cuisse, Nayara Galvão, Mariane Monteschi, Dionei Ramos
Journal: European Respiratory Journal (2012)

Brazil is the largest producer of ethanol from sugarcane in the world and part of this production is still manually harvested and for this, it needs to be burned. This action releases toxic gases to atmosphere and produce large quantities of particulate matter (PM) directly exposing the sugarcane cutters for a prolonged period which can cause important respiratory illness. The objective of this study was to evaluate the lung function and frequency of respiratory symptoms of sugarcane cutters. We evaluated twenty-three male sugarcane cutters (age=25±4,7 years, BMI = 24±3 kg/m2), non-smokers, from Sugar and Ethanol Company located in Brazil. Evaluations were performed in the pre-harvest and harvest. Lung function was assessed by spirometry and respiratory symptoms by questionnaire. Data normality was tested by the Shapiro-Wilk test, and comparison of spirometric values in the two periods was performed using the paired t test. To compare the qualitative variables we used the Goodman test.The level of significance was p≤0,05. In the pre-harvest spirometric values were: FVC (4,4±0,57), FVC% (93,8±14,33), FEV1(3,9± 0,47), FEV1% (96±13,3), FVC/FEV1 (89,4±5,55) FVC/FEV1% (101±6,22). In the harvests of we found the following values: FVC (4,5±0,85), FVC% (94±14), FEV1 (3,9± 0,47), FEV1% (90,3±13,23), FVC FVC / FEV 1 (83,65±7,85) e FVC / FEV 1% (94,4±10,4). There was a statistically significant decrease in FEV1% (p=0.033) and FEV1/FVC (p=0.002) after harvest. The prevalence of difficulty of breathing when there is dust and/or climate change increase after harvest. Our results suggest that six months of harvest leads to airway obstruction and increases respiratory symptoms in these workers.
The prevalence and determinants of COPD in an urban community in Lagos, Nigeria
Authors: Obianuju Ozoh, Bolanle Balogun, Olapeju Oguntunde, Chioma Nwizu, Alero Roberts, Victor Inem, Olarenwaju Bandele
Journal: European Respiratory Journal (2013)

Background: There is limited data on the prevalence of COPD in sub-Saharan Africa. We aimed to determine the prevalence of COPD in an urban community in Lagos, Nigeria and also explore the risk factors associated with COPD.  Methods: Adults 40 years and above were randomly selected from Idi-Araba community in Mushin Local Government Area. Questionnaire of symptoms and risk factors for COPD was completed and pre-bronchodilator spirometry performed on all participants. Those with pre-bronchodilator FEV1/FVC ratio   Results: There were 412 participants (58.3%) females. Mean age was 53.7±11.2 years, 9.7% had >12 years of formal education, 13.8% were ever smokers (1.5% current smokers), 23.1% used biomass fuel for cooking, 24.5% had occupational dust exposure, and 1.5% had tuberculosis previously. The prevalence of COPD was 5.3% (95% confidence interval (CI) 3.4 – 8.0), 7.6% (95% CI 4.1 – 12.6) in males, 3.8% (95% CI 1.7 – 7.0) in females, (X2=2.88, p=0.09). The significant determinants of COPD were ever smoking cigarettes (OR 4.9 95% CI 1.8-13.2, p=0.001) and increasing age, (OR for age ≥60 years 3.6, 95%CI 1.4-9.5 and OR for age >70 years 4.6, 95%CI 1.6-13.0, p=0.004).  Conclusion: The prevalence of COPD in our population is substantial. Tobacco control should be a priority in reducing the prevalence of COPD in our region.
Obesity and respiratory muscle power
Authors: Randa Ibrahim, Amir Bashir, Aamir Magzoub, Omer Musa
Journal: European Respiratory Journal (2011)

Introduction:  In the past few decades obesity has become a global health problem. It could be a predisposing factor to a lot of cardiovascular, metabolic (such as diabetes mellitus) and respiratory problems that may result in pulmonary obstruction or restriction.   Objectives:  The aim of this study was to investigate the effect of obesity on respiratory muscle power and so on lung functions.   Methods:  This was a cross sectional study performed on 52 subjects (35 females and 17 males) in the age range 17-23 years in Khartoum state during the period February to May 2010. The body mass index (BMI) was computed following the standard equation (BMI (kg/m 2 ) = (weight/height2). The percent of body fat was measured using Skinfold Caliber at the back of upper arm. Obesity was defined following the internationally accepted BMI cut-off points and ideal body fat percentages such as these from the American Council on Exercise. Pulmonary function tests (FVC, FEV1, PEFR and FEV1/FVC ratio) were performed using micro-plus spirometer. Maximal expiratory pressure (MEP) was measured using Respiratory pressure meter. Statistical analyses were performed using the SPSS.   Results:  The mean of MEP was significantly higher in obese subjects (p   Conclusion:  Maximum expiratory pressure was significantly higher in healthy obese subjects, compared to non obese control. possibly due to the increased work of breathing. Positive correlation between MEP and BMI and body fat% was observed.
Tablet and Insulin Therapy in Type 2 Diabetes in the Elderly
Authors: A H Barnett
Journal: Journal of the Royal Society of Medicine (1994)

There are a range of therapeutic options available for the management of type 2 diabetes in the elderly. Diet remains the mainstay of treatment although this must be realistic. If diet alone is unsuccessful then, for most patients, short-acting sulphonylurea agents are the treatment of choice. Second line agents include the biguanide, metformin, or an alpha-glucosidase inhibitor. A significant proportion of type 2 diabetic patients will, however, eventually require insulin to alleviate symptoms of poor control and improve glycaemia. In this article I discuss the therapeutic options available for diabetic management in the elderly, with particular emphasis on the pros and cons of insulin treatment.
Sequence-based identification, genotyping and EUCAST antifungal susceptibilities of Trichosporon clinical isolates from Greece
Authors: M. Arabatzis, P. Abel, M. Kanellopoulou, D. Adamou, H. Alexandrou-Athanasoulis, A. Stathi, E. Platsouka, A. Milioni, A. Pangalis, A. Velegraki
Journal: Clinical Microbiology and Infection (2013)
Integrative analysis of a cancer somatic mutome
Authors: Pilar Hernández, Xavier Solé, Joan Valls, Víctor Moreno, Gabriel Capellá, Ander Urruticoechea, Miguel Angel Pujana
Journal: Molecular Cancer (2007)

Abstract Background The consecutive acquisition of genetic alterations characterizes neoplastic processes. As a consequence of these alterations, molecular interactions are reprogrammed in the context of highly connected and regulated cellular networks. The recent identification of the collection of somatically mutated genes in breast tumors (breast cancer somatic "mutome") allows the comprehensive study of its function and organization in complex networks. Results We analyzed functional genomic data (loss of heterozygosity, copy number variation and gene expression in breast tumors) and protein binary interactions from public repositories to identify potential novel components of neoplastic processes, the functional relationships between them, and to examine their coordinated function in breast cancer pathogenesis. This analysis identified candidate tumor suppressors and oncogenes, and new genes whose expression level predicts survival rate in breast cancer patients. Mutome network modeling using different types of pathological and healthy functional relationships unveils functional modules significantly enriched in genes or proteins (genes/proteins) with related biological process Gene Ontology terms and containing known breast cancer-related genes/proteins. Conclusion This study presents a comprehensive analysis of the breast somatic mutome, highlighting those genes with a higher probability of playing a determinant role in tumorigenesis and better defining molecular interactions related to the neoplastic process.
Dual Labeling Biotin Switch Assay to Reduce Bias Derived From Different Cysteine Subpopulations
Authors: Heaseung Sophia Chung, Christopher I. Murray, Vidya Venkatraman, Erin L. Crowgey, Peter P. Rainer, Robert N. Cole, Ryan D. Bomgarden, John C. Rogers, Wayne Balkan, Joshua M. Hare, David A. Kass, Jennifer E. Van Eyk
Journal: Circulation Research (2015)

S-nitrosylation (SNO), an oxidative post-translational modification of cysteine residues, responds to changes in the cardiac redox-environment. Classic biotin-switch assay and its derivatives are the most common methods used for detecting SNO. In this approach, the labile SNO group is selectively replaced with a single stable tag. To date, a variety of thiol-reactive tags have been introduced. However, these methods have not produced a consistent data set, which suggests an incomplete capture by a single tag and potentially the presence of different cysteine subpopulations.To investigate potential labeling bias in the existing methods with a single tag to detect SNO, explore if there are distinct cysteine subpopulations, and then, develop a strategy to maximize the coverage of SNO proteome.We obtained SNO-modified cysteine data sets for wild-type and S-nitrosoglutathione reductase knockout mouse hearts (S-nitrosoglutathione reductase is a negative regulator of S-nitrosoglutathione production) and nitric oxide-induced human embryonic kidney cell using 2 labeling reagents: the cysteine-reactive pyridyldithiol and iodoacetyl based tandem mass tags. Comparison revealed that <30% of the SNO-modified residues were detected by both tags, whereas the remaining SNO sites were only labeled by 1 reagent. Characterization of the 2 distinct subpopulations of SNO residues indicated that pyridyldithiol reagent preferentially labels cysteine residues that are more basic and hydrophobic. On the basis of this observation, we proposed a parallel dual-labeling strategy followed by an optimized proteomics workflow. This enabled the profiling of 493 SNO sites in S-nitrosoglutathione reductase knockout hearts.Using a protocol comprising 2 tags for dual-labeling maximizes overall detection of SNO by reducing the previously unrecognized labeling bias derived from different cysteine subpopulations.
Evaluation of oxaliplatin, 5-FU and leucovorin maintenance treatment in refractory metastatic colon cancer
Authors: C. Headlee, S. Beasley, D. Jackson, C. Teel, B. C. Mirtsching
Journal: Journal of Clinical Oncology (2004)

3635 Background: The response rate in ≥ 2nd-line therapy for Oxaliplatin as salvage therapy after failure of irinotecan (I)- or continuous dosing 5FU-containing regimens is low (8–11% PR) and median time-to-progression is short (3.5–4.5 months). Methods: 40 patients were treated with oxaliplatin, 5FU and leucovorin (OFL), or single-agent oxaliplatin (O). All patients who did not progress were treated continuosly until disease progression. Our observations of a fraction of patients who have protracted disease remission and/or stability are herein reported. Results: Prior treatment was 5FU-containing adjuvant therapy (21), or an I-containing regimen (40), capecitabine (15) or 5FU (bolus or infusion) +/- L (12) for metastatic disease. Baseline characteristics: 31 male (78%), 9 female (22%), 30 white (75%), 5 black (12.5%) and 5 hispanic (12.5%). Treatment was 1st-line in 4 (10%), second-line in 11 (28%), third-line in 20 (50%) or ≥ to fourth-line in 5 (12%). Responses: CR 0 (0%), PR 13 (33%), SD 11 (27%) and PD 16 (40%). The mean number of doses of oxaliplatin was 8 (range: 1–46). Response duration ranged from 109–861d (mean 277 d). SD duration ranged from 17 to 465d (mean 196d). 4 patients (10%) with SD and 6 patients (15%) with response that had non-progression for > than 240d (8 months). CEA was elevated at baseline in 33 (83%), range 15–2283, mean 504. The mean time to maximum CEA reduction was 143d. 50% of SD patients had a stable or reduced CEA. All other stable patients had minor elevations of CEA ≤ 5 units changed. The patients with protracted non-progression had the following characteristics: 3 females, 7 males, 2 hispanics, 8 caucasians and the mean age of 56. 1st-line: 2, 2nd-line: 2, 3rd-line: 4, 4th-line: 2. Conclusions: Oxaliplatin-containing salvage therapy for colorectal cancer benefits patients with response or with stable disease similarly, with delayed progression, which may be substantial (greater than 8 months) in 25% of all patients treated, even though many were heavily pre-treated. Maintaining treatment until progression is important in achieving these results. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen
SPORENKONZENTRATIONEN IN STÄDTEN DER EUROPÄISCHEN GEMEINSCHAFT (EG)
Authors: N. BAGNI, K. R. DAVIES, M. MALLEA, N. NOLARD, F. T. SPIEKSMA, E. STIX
Journal: Allergy (1977)

A comparative account of Alternaria and Cladosporium spore concentrations in four cities in the European Economic Community (EEC), is given for the years 1973 and 1974. Sijilar volumetric air sampling methods were employed in each of the cities, and concentrations of 3000 Cladosporium spores and 100 Alternaria spores/m3 were taken as the threshold concentrations for clinical significance. With Cladosporium, although highest concentrations were observed in Brussels, the differences were less marked at the other stations. Highest Alternaria concentrations were reocrded in Brussels, followed by London, Leiden and Munich. During the 2 years studied, the average number of days with spore concentrations greater than the threshold value for Cladosporium were 59 in Brussels, 36 in Leiden, 38 in London and 46 in Munich and for Alternaria, 48 in Brussels, 13 in Leiden, 33 in London and 5 in Munich.
Codon contexts in enterobacterial and coliphage genes.
Authors: M Gouy
Journal: Molecular Biology and Evolution (1987)

This investigation of the codon context of enterobacteria, plasmid, and phage protein genes was based on a search for correlations between the presence of one base type at codon position III and the presence of another base type at some other position in adjacent codons. Enterobacterial genes were compared with eukaryotic sequences for codon context effects. In enterobacterial genes, base usage at codon position III is correlated with the third position of the upstream adjacent codon and with all three positions of the downstream codon. Plasmid genes are free of context biases. Phage genes are heterogeneous: MS2 codons have no biased context, whereas lambda genes partly follow the trends of the host bacterium, and T7 genes have biased codon contexts that differ from those of the host. It has been reported that two successive third-codon positions tend to be occupied by two purines or two pyrimidines in Escherichia coli genes of low expression level. Here, the extent to which highly expressed protein genes can modulate base usage at two successive codon positions III, given the constraints on codon usage and protein sequence that act on them, was quantified. This demonstrates that the above-mentioned favored patterns are not a characteristic of weakly expressed genes but occur in all genes in which codon context can vary appreciably. The correlation between successive third-codon positions is a distinct feature of enterobacteria and of some phages, one that may result from adaptation of gene structure to translational efficiency. Conversely, codon context in yeast and human genes is biased--but for reasons unrelated to translation.
The Primate Erythrocyte Complement Receptor (CR1) as a Privileged Site: Binding of Immunoglobulin G to Erythrocyte CR1 Does Not Target Erythrocytes for Phagocytosis
Authors: Michele L. Reinagel, Murat Gezen, Polly J. Ferguson, Susan Kuhn, Edward N. Martin, Ronald P. Taylor
Journal: Blood (1997)
Late-breaking abstract: Genomic variation as a predictor of smoking behaviour and smoking cessation treatment toxicity
Authors: Stamatoula Tsikrika, Sofia Vakali, Nantia Flora, Cristiana Pavlidis, Athanassios Vozikis, Theodoros Giannakopoulos, George Patrinos, Christina Gratziou
Journal: European Respiratory Journal (2014)

Introduction: Smoking is a major public health problem and is the single largest cause of preventable death in the world, contributing to >5 million deaths a year. The persistence of smoking can be attributed to multiple diverse causes, the most important being genetic risk factors contributing to smoking behavior.  Aim: It has been demonstrated that genetic factors account for approximately 40–75% of the variation in smoking initiation, 70–80% of the variation in smoking maintenance, about 50% of the variance in cessation success and 30–50% of the variance in risk of withdrawal symptoms.  Methods: We have attempted to shed light into the possible correlation of genomic variants with (a) smoking addiction, and (b) response to smoking cessation treatment with varenicline, a prescription medication used to treat nicotine addiction. Genomic DNA was isolated from saliva, obtained with consent from 80 smokers, 60 non-smokers and 100 ethnically matched control individuals of Hellenic origin. We have subsequently genotyped these individuals for the following markers: rs1329650 and rs1028936 in the CHRNA3 gene, previously correlated with nicotine dependence, rs6265 in the BDNF gene and rs1051730 in the DBH gene, previously correlated with smoking initiation and cessation, respectively, and the rs555018, rs1190449, rs6495309, in the CHRN gene family, which were previously reported as pharmacogenomic biomarkers to predict adverse reactions in varenicline treatment.  Conclusion: Data related to the correlation of these genomic biomarkers with smoking addiction, and response to smoking cessation treatment with varenicline will be presented.
Interferon-λ and interleukin 22 act synergistically for the induction of interferon-stimulated genes and control of rotavirus infection
Authors: Pedro P Hernández, Tanel Mahlakõiv, Ines Yang, Vera Schwierzeck, Nam Nguyen, Fabian Guendel, Konrad Gronke, Bernhard Ryffel, Christoph Hölscher, Laure Dumoutier, Jean-Christophe Renauld, Sebastian Suerbaum, Peter Staeheli, Andreas Diefenbach
Journal: Nature Immunology (2015)
The imidazoacridinone, C-1311 (Symadex™): The first of a potent new class of FLT3 inhibitors
Authors: MyDoanh Chau, Yoko Otake, Jennifer L. Christensen, Daniel J. Fernandes, Alfred M. Ajami
Journal: Clinical Cancer Research (2006)

B35   Background: C-1311 (Symadex™) is the lead compound in clinical development from a new series of agents, the imidazoacridinones. It has been previously thought that C-1311 was solely a topoisomerase II inhibitor and DNA damaging agent. Contemporary analysis, however, points to alternative structural parallelisms between C-1311 and the molecular scaffolds now seen as common motifs in receptor tyrosine kinase (RTK) inhibitors.Since mutations and the over-expression of these RTKs have been commonly found in tumor cells, we initiated a kinase inhibitor screening program, first in silico by molecular similarity matching, and then in vitro against recombinant RTKs. We were surprised to find that C-1311 inhibits FLT3 selectively and at nanomolar concentrations, while retaining much weaker TOP2 inhibition than previously recognized.Materials and Methods: In silico screens were carried out with drug-likeliness and property prediction algorithms (Dragon, Milano Chemometrics, X/ABLE, Xanthus Pharmaceuticals). Molecular seeds were generated by permuting the pharmacophore fragments from all RTKs known to date. Inhibitor assays were performed using the Z9-Lyte™ Kinase Screen (Invitrogen) and kinase enzyme assays (MDS). In vitro TOP2 assays were performed by measuring the inhibition of topoisomerase II decatenation of kDNA.Results: C-1311 clusters with RTK inhibitors, especially when sunitinib is used as a molecular seed for pattern recognition. The statistical similarity coefficients fall in the 0.7-0.8 positive probability range, compared to 0.2-0.4 for the classical TOP2 inhibitors. C-1311 has demonstrated low nanomolar inhibition (8-15 nM IC 50 ) against wild-type FLT3 and its D835Y mutant in vitro. Inhibition of PDGFR, FGFR, VEGFR2, and TRKA at low micromolar levels has also been observed. In contrast, the IC 50  of C-1311 in the TOP2 assay is 44 μM compared to 3 and 12 μM for mitoxantrone and daunorubicin, respectively.Conclusions: TOP2 inhibition studies have shown C-1311 to be 15-fold less potent in inhibiting TOP2 than mitoxantrone. Newly initiated studies by in silico screening and with RTK assays have uncovered C-1311 to be a potent and selective FLT3 inhibitor showing about 5,000-fold greater selectivity in vitro than daunorubicin. This finding may prove to be useful in treating as yet unexplored indications, such as hematological cancers and autoimmune diseases.