tbuckley/cabot-search huggingface dataset:
Abstract 1369: Synthesis of substituted N-[(3-(1H-pyrrol-1yl)methyl]-5,6-dihydropyridin-1(2H)-yl) benzamide/benzene sulfonamide as anticancer agents
Authors: Kinfe Ken Redda, Madhavi Gangapuram, Bereket Mochona, Nelly Mateeva, Tiffany Ardley
Journal: Cancer Research (2011)

Abstract Cancer has proven to be one of the most intractable human diseases, and as yet no anticancer agents that are highly effective and safe are available. Therefore, synthesis of novel, potent, selective and less toxic anticancer agents remains the most pressing goal of many investigators. Tetrahydropyridine (THP) ring moieties have attracted synthetic interests for being essential structures in many agrochemicals as well as medicinal agents. The anti-inflammatory and anticancer activities of compounds consisting of reduced pyridine ring systems were investigated in our laboratory. The pharmacological activities of the (THP) derivatives depended on the nature of the substituents on the THP ring moiety. In the current investigation, we synthesized many analogs maintaining the N-(3-[(1-H-pyrrol-1-yl)methyl]-5,6-dihydropyridin-1(2H)-yl) benzamide/benzene sulfonamides, at which the phenyl ring was substituted with groups having different electronic, steric and lipophilic properties. Mesitylene sulfonyl chloride was added with stirring to a solution of ethylacetohydroxymate and triethylamine in dimethylformamide at 0o C. Hydrolysis of this compound with the mixture of p-dioxane-70% perchloric acid and allowing them to react for 45 min gave a white solid of O-mesitylene sulfonyl hydroxylamine (MSH). MSH was used to prepare the N-amino salt since it served as an aminating agent. 3-[(1H-pyrrol-1-yl)methyl]pyridine was reacted with MSH in dichloromethane to produce 3-[(1H-pyrrol-1-yl)methyl]-1-aminopyridinium mesitylenesulfonate, the N-amino salt. Reaction of the amino salt with substituted benzoyl chloride/benzenesulfonyl chloride in anhydrous tetrahydrofuran containing triethylamine gave stable benzoyl/benzene sulfonyl imino ylides. This was followed by reduction with sodium borohydride in absolute ethanol, which furnished the target compounds substituted N-(3-[(1H-pyrrol-1-yl)methyl]-5,6-dihydropyridin-1(2H)-yl) benzamide/benzene sulfonamides. These compounds were evaluated for their cytotoxic effects on MCF-7 estrogen receptor positive breast cancer cells, MDA-MB-231 estrogen receptor negative breast cancer cell line, and Ishikawa cells, using the CellTiter-Glo (CTG) luminescent cell viability assay. N-(3-[(1H-pyrrol-1-yl)methyl]-5,6-dihydropyridin-1(2H)-yl)-4-methoxybenzene- sulfonamide showed the most potent cytotoxicity with an IC50 values of 47, 28, and 44 µM on MCF-7, Ishikawa and MDA-MB-231 cell lines, respectively. This research was supported by NIH/ RCMI Grant # G12 RR 03020 and Pharmaceutical Research Center NIH/NCRR Grant 1 C06 RR12512-01. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1369. doi:10.1158/1538-7445.AM2011-1369
Prophylactic ibuprofen versus placebo in very premature infants: a randomised, double-blind, placebo-controlled trial
Authors: V Gournay, JC Roze, A Kuster, P Daoud, G Cambonie, JM Hascoet, C Chamboux, T Blanc, C Fichtner, C Savagner, JB Gouyon, V Flurin, G Thiriez
Journal: The Lancet (2004)
A Multicenter Phase II Trial of ZD6474, a Vascular Endothelial Growth Factor Receptor-2 and Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, in Patients with Previously Treated Metastatic Breast Cancer
Authors: Kathy D. Miller, Jose Manuel Trigo, Catherine Wheeler, Alan Barge, Jacqui Rowbottom, George Sledge, Jose Baselga
Journal: Clinical Cancer Research (2005)

Abstract Purpose: To determine the efficacy and safety of ZD6474, an orally available inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase with additional activity against the epidermal growth factor receptor (EGFR) tyrosine kinase, in patients with previously treated metastatic breast cancer. Patients and Methods: Eligible patients had histologically confirmed metastatic breast cancer and had received prior treatment with an anthracycline and taxane; measurable disease was required. Patients were enrolled sequentially into one of two dose cohorts, 100 or 300 mg orally once daily; 28 days defined one cycle. The primary end point was objective response rate; pharmacokinetics and serial pharmacodynamic studies were obtained. Results: Forty-six patients were enrolled between May 2002 and April 2003, and 44 were evaluable for response. Diarrhea was the most commonly reported toxicity and seemed dose related (grade ≥2: 4.5% and 37.5% in the 100 and 300 mg cohorts, respectively). Rash was reported by 26% of patients but was never worse than grade 2. Seven patients in the 300 mg cohort had asymptomatic grade 1 prolongation of the QTc interval. Hypertension requiring treatment was not reported. There were no objective responses; one patient in the 300 mg cohort had stable disease ≥24 weeks. All patients in the 300 mg cohort and 90% of patients in the 100 mg cohort achieved steady-state concentrations exceeding the IC50 for VEGF inhibition in preclinical models. Conclusion: ZD6474 monotherapy was generally well tolerated but had limited monotherapy activity in patients with refractory metastatic breast cancer.
Computed tomography of the lungs in asthma: influence of disease severity and etiology.
Authors: F Paganin, E Séneterre, P Chanez, J P Daurés, J M Bruel, F B Michel, J Bousquet
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Airways remodelling is a feature of longstanding asthma, but may differ in persons with allergic and nonallergic asthma. To assess airways remodelling indirectly, we compared permanent CT-scan abnormalities in 70 subjects with allergic (median age: 30 yr) and 56 with nonallergic asthma (median age: 54.5 yr) who had had asthma of similar duration. None of the subjects were smokers. Asthma severity was assessed by Aas score and FEV1. Permanent high-resolution computed tomographic (HR-CT) scan abnormalities were characterized. In comparison with allergic asthmatic subjects, those with nonallergic asthma had a significantly greater frequency of cylindric (p < 0.0007, Mann-Whitney U test) and varicose (p < 0.004) bronchiectasis, emphysema (p < 0.0003), bronchial recruitment (p < 0.0001), and sequellar linear shadows (p < 0.0001). There was a significant correlation between Aas score and emphysema (p < 0.0001 for nonallergic and p < 0.0005 for allergic asthma; Kendall's test method) or Aas score and sequellar linear shadows (p < 0.007, nonallergic asthma). There was a significant increase in the extent of permanent abnormalities with increasing severity and duration of asthma in both groups. Patients with brittle asthma had few permanent abnormalities. This study confirms that after a similar course of the disease, patients with nonallergic asthma have a more extensive remodelling of the airways than those with allergic asthma.
A phase I study of full-dose gemcitabine and regional arterial infusion of nafamostat mesilate for advanced pancreatic cancer
Authors: T. Uwagawa, T. Misawa, T. Sakamoto, R. Ito, T. Gocho, H. Shiba, S. Wakiyama, S. Hirohara, S. Sadaoka, K. Yanaga
Journal: Annals of Oncology (2008)
Behavioral momentum and the Law of Effect
Authors: John A. Nevin, Randolph C. Grace
Journal: Behavioral and Brain Sciences (2000)

In the metaphor of behavioral momentum, the rate of a free operant in the presence of a discriminative stimulus is analogous to the velocity of a moving body, and resistance to change measures an aspect of behavior that is analogous to its inertial mass. An extension of the metaphor suggests that preference measures an analog to the gravitational mass of that body. The independent functions relating resistance to change and preference to the conditions of reinforcement may be construed as convergent measures of a single construct, analogous to physical mass, that represents the effects of a history of exposure to the signaled conditions of reinforcement and that unifies the traditionally separate notions of the strength of learning and the value of incentives. Research guided by the momentum metaphor encompasses the effects of reinforcement on response rate, resistance to change, and preference and has implications for clinical interventions, drug addiction, and self-control. In addition, its principles can be seen as a modern, quantitative version of Thorndike's (1911) Law of Effect, providing a new perspective on some of the challenges to his postulation of strengthening by reinforcement.
Whole genome de novo assemblies of three divergent strains of rice, Oryza sativa, document novel gene space of aus and indica
Authors: Michael C Schatz, Lyza G Maron, Joshua C Stein, Alejandro Hernandez Wences, James Gurtowski, Eric Biggers, Hayan Lee, Melissa Kramer, Eric Antoniou, Elena Ghiban, Mark H Wright, Jer-ming Chia, Doreen Ware, Susan R McCouch, W Richard McCombie
Journal: Genome biology (2014)

Abstract Background The use of high throughput genome-sequencing technologies has uncovered a large extent of structural variation in eukaryotic genomes that makes important contributions to genomic diversity and phenotypic variation. When the genomes of different strains of a given organism are compared, whole genome resequencing data are typically aligned to an established reference sequence. However, when the reference differs in significant structural ways from the individuals under study, the analysis is often incomplete or inaccurate. Results Here, we use rice as a model to demonstrate how improvements in sequencing and assembly technology allow rapid and inexpensive de novo assembly of next generation sequence data into high-quality assemblies that can be directly compared using whole genome alignment to provide an unbiased assessment. Using this approach, we are able to accurately assess the ‘pan-genome’ of three divergent rice varieties and document several megabases of each genome absent in the other two. Conclusions Many of the genome-specific loci are annotated to contain genes, reflecting the potential for new biological properties that would be missed by standard reference-mapping approaches. We further provide a detailed analysis of several loci associated with agriculturally important traits, including the S5 hybrid sterility locus, the Sub1 submergence tolerance locus, the LRK gene cluster associated with improved yield, and the Pup1 cluster associated with phosphorus deficiency, illustrating the utility of our approach for biological discovery. All of the data and software are openly available to support further breeding and functional studies of rice and other species.
Health effects of coal mining and combustion: carcinogens and cofactors.
Authors: H L Falk, W Jurgelski
Journal: Environmental Health Perspectives (1979)

Some polynuclear aromatics (PNA) have been found to be potent carcinogens for all tissues and organs of experimental animals that have been exposed to them, but different dose levels are needed for these effects. They have been known for decades to cause cancer at the site of application but also at certain sites distant from the area of contact. Although some hydrocarbons are potent and complete carcinogens, the majority of related hydrocarbons was originally found to be inactive. Since they generally appear together, it was important to know more about their interaction, particularly whether they would synergize, or antagonize. The polycyclic hydrocarbons have been studied by subcutaneous injection, where they prove very potent carcinogens. They are also very active on the skin of mice where they produce cancer on prolonged application. Inhalation studies, require larger doses yielded negative results until particulate matter was introduced which facilitated the development of lung tumors. Although iron oxide dust was used initially, other dusts were also capable of enhancing the response of the tissue to benzo(a)pyrene carcinogenesis. This point is of importance, particularly since the inhalation of PNA in situations of air pollution or coal mining involves particulates, although of a different type. Soot is not a homogenous substance and several factors determine its properties. Soots will lose some of the absorbed chemicals during their residence in air, but they retain their PNAs for long periods of time when they reach the soil. The carcinogenicity of PNAs in the adsorbed state may be completely absent, depending on particle size of the soot and availability of eluting capability of the tissues or cells in contact with the soot. Whenever the carcinogenic polynuclear aromatics can be eluted they will be active in producing cancer if their residence is adequate. There seems to be no reason to assume that a large increase in coal combustion in the future will by necessity lead to greater risks of cancer to the coal miners or the general urban dweller, because activities to be started now can take into consideration the requirements necessary for control of air pollution in mines as well as in cities. If new uses of coal will be developed, it will be a completely different situation, and statements about the carcinogenic risk from coal utilization do not apply there. Although some of the same carcinogenic PNAs are involved in the health hazards from those processes, other carcinogens and also cocarcinogens will be present, and the exposed workers will not have the apparent benefits of adsorption of PNAs on soot.
The prevalence of antimicrobial resistance of P. aeruginosa, K. pneumoniae, E. coli, A. baumanii in Ukraine
Authors: Tetyana Pertseva, Tetyana Kireyeva, Olga Shtepa
Journal: European Respiratory Journal (2014)

The aim of study:  To determine the prevalence of antimicrobial resistance among  P. aeruginosa, K. pneumoniae, E. coli, A. baumanii  isolated from patients with respiratory tract infections.   Methods:  Retrospective analysis 52  P. aeruginosa, 19 K. pneumoniae, 13 E. coli, 9 A. baumanii  strains which were isolated from patients with respiratory tract infections during the period 2010 to 2013. Susceptibility testing was conducted using disc diffusion method.   Results:  Our dataare presentedin table 1.  P. aeruginosa  (15 is; 28,8%),  E. coli  (8 is; 61,5%),  K. pneumoniae  (7 is; 36,8%),  A. baumanii  (6 is; 66,7%) had a multiple resistance.  P. aeruginosa  (3 is; 5,8%),  A. baumanii  (3 is; 33,3%) had resistance to all antibacterial drugs.   Conclusion:  Ours data indicate that thehighest concern is the increasing trend of resistance P. aeruginosa  and  A. baumanii  to all antimicrobialdrugs .  Elevated multiple resistance gram negative strains poses a serious threat to current and future treatment of respiratory tract infections.
NEW: Network-Enabled Wisdom in Biology, Medicine, and Health Care
Authors: Eric E. Schadt, Johan L. M. Björkegren
Journal: Science Translational Medicine (2012)

Complete repertoires of molecular activity in and between tissues provided by new high-dimensional "omics" technologies hold great promise for characterizing human physiology at all levels of biological hierarchies. The combined effects of genetic and environmental perturbations at any level of these hierarchies can lead to vicious cycles of pathology and complex systemic diseases. The challenge lies in extracting all relevant information from the rapidly increasing volumes of omics data and translating this information first into knowledge and ultimately into wisdom that can yield clinically actionable results. Here, we discuss how molecular networks are central to the implementation of this new biology in medicine and translation to preventive and personalized health care.
Radiofrequency resection of bronchial tumours in combination with cryotherapy: evaluation of a new technique.
Authors: A Marasso, V Bernardi, R Gai, E Gallo, G M Massaglia, M Onoscuri, S B Cardaci
Journal: Thorax (1998)

BACKGROUND: A number of treatments, including Nd-YAG laser therapy, brachytherapy, cryotherapy, electrocautery, and photodynamic therapy, can re-open the obstructed bronchial lumen in patients with inoperable obstructive bronchial tumours. None of these is considered to be a "gold standard". METHODS: The results of a retrospective study of 98 patients treated by radiofrequency tissue ablation and subsequent cryotherapy between January 1994 and June 1995 are reported. The patients were divided in two groups according to whether they were treated either after (group 1, n = 50) or before (group 2, n = 48) radiotherapy and/or chemotherapy. Bronchoscopic follow up was performed. The intervention was considered successful if the lumen was opened by &gt; 80% and partially successful if it was opened by &gt; 50%. RESULTS: In group 1 treatment was successful in 60%, partially successful in 32%, and unsuccessful in 8%. The median survival time was five months from the time of bronchoscopic surgery. In group 2 treatment was successful in 66%, partially successful in 21.5%, and unsuccessful in 12.5%, with a median survival time of 14 months from the time of bronchoscopic treatment. Forty patients (24 in group 1 and 16 in group 2) received a Dumon stent. CONCLUSIONS: Radiofrequency bronchoscopic surgery with cryotherapy appears to be a useful technique in the treatment of tracheobronchial obstruction.
NGL family PSD-95–interacting adhesion molecules regulate excitatory synapse formation
Authors: Seho Kim, Alain Burette, Hye Sun Chung, Seok-Kyu Kwon, Jooyeon Woo, Hyun Woo Lee, Karam Kim, Hyun Kim, Richard J Weinberg, Eunjoon Kim
Journal: Nature Neuroscience (2006)
Examining pacing profiles in elite female road cyclists using exposure variation analysis
Authors: C R Abbiss, L Straker, M J Quod, D T Martin, P B Laursen
Journal: British Journal of Sports Medicine (2008)

Objective In this study, the amplitude and time distribution of power output in a variety of competitive cycling events through the use of a new mathematical analysis was examined: exposure variation analysis (EVA). Design Descriptive field study. Setting Various professional road cycling events, including; a 5-day—eight-stage tour race, a 1-day World Cup event and the Australian National Individual Time Trial Championships. Participants 9 elite female cyclists (mean (SD), mass = 57.8 (3.4) kg, height = 167.3 (2.8) cm, Vo 2 peak = 63.2 (5.2) ml kg −1 min −1 ). Interventions None. Main outcome measurements The variation in power output and the quantification of the total time and acute time spent at various exercise intensities during competitive professional cycling were examined. Predefined levels of exercise intensity that elicited first ventilation threshold, second ventilation threshold and maximal aerobic power were determined from a graded exercise test performed before the events and compared with power output during each event. Results EVA exposed that power output during the time trial was highly variable (EVA SD = 2.81 (0.33)) but more evenly distributed than the circuit/criterium (4.23 (0.31)) and road race events (4.81 (0.96)). Conclusion EVA may be useful for illustrating variations in the amplitude and time distribution of power output during cycling events. The specific race format influenced not only the overall time spent in various power bands, but also the acute time spent at these exercise intensities.
Pulmonary Complications of Sickle Cell Disease
Authors: Andrew C. Miller, Mark T. Gladwin
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Sickle cell disease (SCD) is a common monogenetic disorder with high associated morbidity and mortality. The pulmonary complications of SCD are of particular importance, as acute chest syndrome and pulmonary hypertension have the highest associated mortality rates within this population. This article reviews the pathophysiology, diagnosis, and treatment of clinically significant pulmonary manifestations of SCD, including acute chest syndrome, asthma, and pulmonary hypertension in adult and pediatric patients. Clinicians should be vigilant in screening and treating such comorbidities to improve patient outcomes.
Effect of caffeinated coffee on running speed, respiratory factors, blood lactate and perceived exertion during 1500-m treadmill running.
Authors: J D Wiles, S R Bird, J Hopkins, M Riley
Journal: British Journal of Sports Medicine (1992)

Using a motorized treadmill the study investigated the effects of the ingestion of 3 g of caffeinated coffee on: the time taken to run 1500 m; the selected speed with which athletes completed a 1-min 'finishing burst' at the end of a high-intensity run; and respiratory factors, perceived exertion and blood lactate levels during a high intensity 1500-m run. In all testing protocols decaffeinated coffee (3 g) was used as a placebo and a double-blind experimental design was used throughout. The participants in the study were middle distance athletes of club, county and national standard. The results showed that ingestion of caffeinated coffee: decreases the time taken to run 1500 m (P less than 0.005); increases the speed of the 'finishing burst' (P less than 0.005); and increases VO2 during the high-intensity 1500-m run (P less than 0.025). The study concluded that under these laboratory conditions, the ingestion of caffeinated coffee could enhance the performance of sustained high-intensity exercise.
How many manoeuvres should be done to measure maximal inspiratory mouth pressure in patients with chronic airflow obstruction?
Authors: J A Fiz, J M Montserrat, C Picado, V Plaza, A Agusti-Vidal
Journal: Thorax (1989)

To determine the number of maximal mouth pressure manoeuvres needed to obtain a reproducible value of maximal inspiratory mouth pressure (MIP), we studied 44 patients with chronic airflow obstruction, with a mean (SD) % predicted FEV1 value of 53.9 (25), who were clinically stable. Maximal inspiratory mouth pressure was determined with an anaeroid manometer during maximal inspiratory efforts in a quasi static condition at residual volume. All patients performed 20 consecutive maximal inspiratory mouth manoeuvres, each one separated by 30-40 seconds. The mean (SD) values of MIP varied from 71.5 (25.5) cm H2O at the first measurement to 80.1 (27) cm H2O at the last measurement. Maximal values of MIP were usually achieved after nine determinations. It is concluded that to obtain a reproducible MIP value in patients with chronic airflow obstruction who are untrained and unexperienced in such manoeuvres a minimum of nine technically acceptable maximal mouth pressure manoeuvres should be performed.
Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), reduction in ulcer complications: randomised controlled trial
Authors: Thomas J Schnitzer, Gerd R Burmester, Eduardo Mysler, Marc C Hochberg, Michael Doherty, Elena Ehrsam, Xavier Gitton, Gerhard Krammer, Bernhard Mellein, Patrice Matchaba, Alberto Gimona, Christopher J Hawkey
Journal: The Lancet (2004)