bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variability among nonsteroidal antiinflammatory drugs in risk of upper gastrointestinal bleeding
Authors: Massó González Elvira L. , Patrignani Paola , Tacconelli Stefania , Rodríguez Luis A. García 
Published: February 2010

AbstractObjectiveTraditional nonsteroidal antiinflammatory drugs (NSAIDs) increase the risk of upper gastrointestinal (GI) bleeding/perforation, but the magnitude of this effect for coxibs in the general population and the degree of variability between individual NSAIDs is still under debate. This study was undertaken to assess the risk of upper GI bleeding/perforation among users of individual NSAIDs and to analyze the correlation between this risk and the degree of inhibition of whole blood cyclooxygenase 1 (COX‐1) and COX‐2 in vitro.MethodsWe conducted a systematic review of observational studies on NSAIDs and upper GI bleeding/perforation published between 2000 and 2008. We calculated pooled relative risk (RR) estimates of upper GI bleeding/perforation for individual NSAIDs. Additionally, we verified whether the degree of inhibition of whole blood COX‐1 and COX‐2 in vitro by average circulating concentrations predicted the RR of upper GI bleeding/perforation.ResultsThe RR of upper GI bleeding/perforation was 4.50 (95% confidence interval [95% CI] 3.82–5.31) for traditional NSAIDs and 1.88 (95% CI 0.96–3.71) for coxibs. RRs lower than that for NSAIDs overall were observed for ibuprofen (2.69 [95% CI 2.17–3.33]), rofecoxib (2.12 [95% CI 1.59–2.84]), aceclofenac (1.44 [95% CI 0.65–3.2]), and celecoxib (1.42 [95% CI 0.85–2.37]), while higher RRs were observed for ketorolac (14.54 [95% CI 5.87–36.04]) and piroxicam (9.94 [95% CI 5.99–16.50). Estimated RRs were 5.63 (95% CI 3.83–8.28) for naproxen, 5.57 (95% CI 3.94–7.87) for ketoprofen, 5.40 (95% CI 4.16–7.00) for indomethacin, 4.15 (95% CI 2.59–6.64) for meloxicam, and 3.98 (95% CI 3.36–4.72) for diclofenac. The degree of inhibition of whole blood COX‐1 did not significantly correlate with RR of upper GI bleeding/perforation associated with individual NSAIDs (r2= 0.34,P= 0.058), but a profound and coincident inhibition (>80%) of both COX isozymes was associated with higher risk. NSAIDs with a long plasma half‐life and with a slow‐release formulation were associated with a greater risk than NSAIDs with a short half‐life.ConclusionThe results of our analysis demonstrate that risk of upper GI bleeding/perforation varies between individual NSAIDs at the doses commonly used in the general population. Drugs that have a long half‐life or slow‐release formulation and/or are associated with profound and coincident inhibition of both COX isozymes are associated with a greater risk of upper GI bleeding/perforation.
Risk factors for development of uveitis differ between girls and boys with juvenile idiopathic arthritis
Authors: Saurenmann R. K. , Levin A. V. , Feldman B. M. , Laxer R. M. , Schneider R. , Silverman E. D. 
Published: February 2010

AbstractObjectiveUveitis is the most common extraarticular manifestation of juvenile idiopathic arthritis (JIA) and is associated with considerable morbidity. The aim of this study was to examine the risk factors associated with uveitis in JIA.MethodsWe conducted a chart review of 1,047 patients with JIA from a single tertiary care pediatric rheumatology center for factors associated with the development of uveitis. Special emphasis was put on the following known risk factors: oligoarthritis, antinuclear antibody (ANA) status, sex, and age at the time of onset of JIA.ResultsThe risk of uveitis developing was age dependent in girls but not in boys. Among girls, the risk was maximal (47%) in those who were ANA positive and were ages 1–2 years at the time of the onset of JIA; this risk decreased to <10% in those in whom the age at onset was >7 years. Only girls had an age‐dependent and ANA‐associated increased risk of uveitis. The time interval from the diagnosis of JIA to the diagnosis of uveitis was statistically significantly longer in patients in whom the onset of JIA occurred at a younger age (P = 0.04). This effect was even more pronounced in ANA‐positive patients (P = 0.004). The JIA subtype did not influence a patient's risk of the development of uveitis.ConclusionAn age‐associated risk of uveitis was observed only in girls who were younger than 7 years of age at the time of the onset of JIA. The duration of time between the diagnosis of JIA and the onset of uveitis was longer in patients in whom JIA was diagnosed at a younger age, especially in those who were ANA positive. We suggest that our findings have implications for uveitis screening in patients with JIA.
Identification and prevention of antibody disulfide bond reduction during cell culture manufacturing
Authors: Trexler‐Schmidt Melody , Sargis Sandy , Chiu Jason , Sze‐Khoo Stefanie , Mun Melissa , Kao Yung‐Hsiang , Laird Michael W. 
Published: February 2010

AbstractIn the biopharmaceutical industry, therapeutic monoclonal antibodies are primarily produced in mammalian cell culture systems. During the scale‐up of a monoclonal antibody production process, we observed excessive mechanical cell shear as well as significant reduction of the antibody's interchain disulfide bonds during harvest operations. This antibody reduction event was catastrophic as the product failed to meet the drug substance specifications and the bulk product was lost. Subsequent laboratory studies have demonstrated that cells subjected to mechanical shear release cellular enzymes that contribute to this antibody reduction phenomenon (manuscript submitted; Kao et al., 2009). Several methods to prevent this antibody reduction event were developed using a lab‐scale model to reproduce the lysis and reduction events. These methods included modifications to the cell culture media with chemicals (e.g., cupric sulfate (CuSO4)), pre‐ and post‐harvest chemical additions to the cell culture fluid (CCF) (e.g., CuSO4, EDTA, L‐cystine), as well as lowering the pH and air sparging of the harvested CCF (HCCF). These methods were evaluated for their effectiveness in preventing disulfide bond reduction and their impact to product quality. Effective prevention methods, which yielded acceptable product quality were evaluated for their potential to be implemented at manufacturing‐scale. The work described here identifies numerous effective reduction prevention measures from lab‐scale studies; several of these methods were then successfully translated into manufacturing processes. Biotechnol. Bioeng. 2010; 106: 452–461. © 2010 Wiley Periodicals, Inc.
Lipid analysis of Neochloris oleoabundans by liquid state NMR
Authors: Beal C.M. , Webber M.E. , Ruoff R.S. , Hebner R.E. 
Published: February 2010

AbstractThis study is an evaluation of liquid state NMR as a tool for analyzing the lipid composition of algal cultures used for biodiesel production. To demonstrate the viability of this approach, 13C NMR was used to analyze the lipid composition of intact cells of the algal species, Neochloris oleoabundans (UTEX #1185). Two cultures were used in this study. One culture was “healthy” and grown in conventional media, whereas the other culture was “nitrogen‐starved” and grown in media that lacked nitrate. Triglyceride was determined to be present in both cultures by comparing the algal NMR spectra with published chemical shifts for a wide range of lipids and with a spectrum obtained from a triglyceride standard (glyceryl trioleate). In addition, it is shown that (1) the signal‐to‐noise ratio of the ∼29.5 ppm methylene peak is indicative of the lipid content and (2) the nitrogen‐starved culture contained a greater lipid content than the healthy culture, as expected. Furthermore, the nitrogen‐starved culture produced spectra that primarily contained the characteristic peaks of triglyceride (at ∼61.8 and ∼68.9 ppm), whereas the healthy culture produced spectra that contained several additional peaks in the glycerol region, likely resulting from the presence of monoglyceride and diglyceride. Finally, potential interferences are evaluated (including the analysis of phospholipids via 31P NMR) to assess the specificity of the acquired spectra to triglyceride. These results indicate that NMR is a useful diagnostic tool for selectively identifying lipids in algae, with particular relevance to biodiesel production. Biotechnol. Bioeng. 2010;106: 573–583. © 2010 Wiley Periodicals, Inc.
Experimental evaluation of decrease in the activities of polyphosphate/glycogen‐accumulating organisms due to cell death and activity decay in activated sludge
Authors: Hao Xiaodi , Wang Qilin , Cao Yali , van Loosdrecht Mark C.M. 
Published: February 2010

AbstractDecrease in bacterial activity (biomass decay) in activated sludge can result from cell death (reduction in the amount of active bacteria) and activity decay (reduction in the specific activity of active bacteria). The goal of this study was to experimentally differentiate between cell death and activity decay as the cause of decrease in bacterial activity. By means of measuring maximal anaerobic phosphate release rates, verifying membrane integrity by live/dead staining and verifying presence of 16S rRNA with fluorescence in situ hybridization (FISH), the decay rates and death rates of polyphosphate‐accumulating organisms (PAOs) in a biological nutrient removal (BNR) system and a laboratory phosphate removing sequencing batch reactor (SBR) system were determined, respectively, under famine conditions. In addition, the decay rate and death rate of glycogen‐accumulating organisms (GAOs) in a SBR system with an enrichment culture of GAOs were also measured under famine conditions. Hereto the maximal anaerobic volatile fatty acid uptake rates, live/dead staining, and FISH were used. The experiments revealed that in the BNR and enriched PAO‐SBR systems, activity decay contributed 58% and 80% to the decreased activities of PAOs, and that cell death was responsible for 42% and 20% of decreases in their respective activities. In the enriched GAOs system, activity decay constituted a proportion of 74% of the decreased activity of GAOs, and cell death only accounted for 26% of the decrease of their activity. Biotechnol. Bioeng. 2010; 106: 399–407. © 2010 Wiley Periodicals, Inc.
Laserfragmentierung von anorganischen und organischen Mikropartikel‐Suspensionen zu Nanopartikel‐Kolloiden
Authors: Schnoor A. , Petersen S. , Barcikowski S. 
Published: February 2010

AbstractEs besteht ein hoher Bedarf an hochreinen, stabilen Nanopartikel‐Kolloiden für medizinische und technische Anwendungen. Das Potenzial des kontaminationsfreien Zerkleinerungsverfahrens des Laserfragmentierens von Mikropartikel‐Suspensionen im Batch‐ und im Durchfluss‐Laserfragmentierungsaggregat wird anhand von magnetischen (Eisenoxid), hartkeramischen (Bornitrid, Wolframcarbid) und bioaktiven (Vitamin C, Capsaicin) Nanopartikeln erstmals demonstriert. Eine erste Wertschöpfungsanalyse beschreibt wirtschaftliche Aspekte.
Anwendungen für Terahertz‐Systeme: Märkte und Perspektiven einer innovativen Technik
Authors: Wietzke S. , Jansen C. , Scheller M. , Krumbholz N. , Peters O. , Jördens C. , Hochrein T. , Jung T. , Chatterjee S. , Koch M. 
Published: February 2010

AbstractDer Terahertz‐Frequenzbereich befindet sich zwischen den Mikrowellen und der Infrarotstrahlung. Damit überbrückt er die Lücke zwischen Elektronik und Optik. Aufgrund dieser exponierten Stellung im elektromagnetischen Spektrum existiert eine Fülle vielversprechender metrologischer Einsatzmöglichkeiten für zahlreiche industrielle Anwendungen. Neueste Fortschritte in der Systementwicklung deuten an, dass die Markteinführung dieser zerstörungsfreien und berührungslosen Messtechnik rasch näher rückt. Ziel dieses Beitrages ist es, einen Einblick in die Möglichkeiten und Perspektiven zu geben. Im Fokus stehen dabei Applikationen, bei denen vorhandene Messmethoden keine befriedigende Lösung liefern können: von der Kunststofftechnik über die Lebensmittelindustrie bis hin zur Sicherheit an Flughäfen oder der Züchtung und Bewässerung von Pflanzen.
Understanding Kinase Selectivity Through Energetic Analysis of Binding Site Waters
Authors: Robinson Daniel D. , Sherman Woody , Farid Ramy 
Published: February 2010

AbstractKinases remain an important drug target class within the pharmaceutical industry; however, the rational design of kinase inhibitors is plagued by the complexity of gaining selectivity for a small number of proteins within a family of more than 500 related enzymes. Herein we show how a computational method for identifying the location and thermodynamic properties of water molecules within a protein binding site can yield insight into previously inexplicable selectivity and structure–activity relationships. Four kinase systems (Src family, Abl/c‐Kit, Syk/ZAP‐70, and CDK2/4) were investigated, and differences in predicted water molecule locations and energetics were able to explain the experimentally observed binding selectivity profiles. The successful predictions across the range of kinases studied here suggest that this methodology could be generally applicable for predicting selectivity profiles in related targets.
Quantitative analysis of dynamic MRI data obtained with a hollow fibre module
Authors: Dimicoli Jean‐Luc 
Published: February 2010

AbstractThis paper presents a model describing the diffusion of water and contrast agent (CA) in hollow fibre modules (HFM), which is able to calculate the contribution of water molecular exchange to the parameters resulting from dynamic R1 relaxation data. To acquire these data, the intra‐fibre volume of the HFM initially filled with pure water was perfused with a CA solution of constant concentration C0. The relaxation rate R1e(t) time course was measured assuming fast water molecular exchange, with a saturation–recovery multi‐gradient‐echo snapshot sequence. These data led to uncorrected (uc) water exchange estimations of the constant kCA_uc characterizing the CA R1e(t) kinetics and of the intra‐fibre volume fraction Vin_uc of the HFM. The model, which assumes diffusion‐controlled process and the absence of interaction of CA with the fibre membrane, led to the corresponding theoretical values for corrected water exchange kCA and Vin. kCA_uc was always slightly larger than kCA and independent of C0. Vin_uc was always much smaller than Vin and depended strongly on C0. Furthermore, Vin was found to be very similar to the real intra‐fibre volume fraction as determined directly from high‐resolution MRI and specifications given by the supplier, thus confirming the validity of our model. It is shown that kCA_uc characterizing every CA diffusing without interaction with the membrane depends linearly on its diffusion coefficient in water Ds_CA. The experimental results suggest that interactions of Dotarem® and P806 with the HFM membrane are not significant. This is also the case for the smaller and neutral molecule water, validating all the calculations involved in this work. For the largest CAs, experiments suggest that sterical effects dominate their permeability and that Ds_CA rather than their molecular weight defines HFM membrane cut‐off. However, if other interactions are also important, a multi‐parameter function rather than a single value is expected to define this cut‐off. Copyright © 2010 John Wiley & Sons, Ltd.
The association of menstrual and reproductive factors with upper gastrointestinal tract cancers in the NIH‐AARP cohort
Authors: Freedman Neal D. , Lacey James V. , Hollenbeck Albert R. , Leitzmann Michael F. , Schatzkin Arthur , Abnet Christian C. 
Published: February 2010

AbstractBACKGROUND:In most populations, incidence rates of upper gastrointestinal (UGI) tract cancers (head and neck, esophagus, and stomach) are higher among men than among women. Established risk factors do not appear to explain these differences, suggesting a possible role for sex hormones.METHODS:201,506 women of the NIH‐AARP Diet and Health cohort completed a questionnaire in 1995‐1996. Hazard ratios and 95% confidence intervals were estimated from Cox proportional hazards models.RESULTS:During follow‐up through 2003, 162 incident adenocarcinomas (ACs; esophagus, N = 25, and stomach, N = 137) and 353 incident squamous cell carcinomas (SCCs; head and neck, n = 297, and esophagus, N = 56) occurred. Among examined exposures, older age at menopause was associated inversely with SCC (Ptrend across categories = .013) but not AC (Ptrend = .501). Use of menopausal hormone therapy (MHT) was significantly associated with lower risk of SCC (hazard ratio [HR] = 0.77, 0.62‐0.96) and nonsignificantly associated with lower risk of AC (HR = 0.81, 0.59‐1.12). A subset (N = 127,386) of the cohort completed a more detailed MHT questionnaire a year after baseline. In 74,372 women with intact uteri, ever use of estrogen‐progestin MHT conferred 0.47 (0.30‐0.75) times the risk for SCC and 0.52 (0.26‐1.07) times the risk for ACC. In 51,515 women with a hysterectomy before baseline, we found no associations between use of estrogen MHT and AC or SCC.CONCLUSIONS:Higher estrogen and progesterone levels may be related inversely to UGI cancers and in this way help explain lower incidence rates in women compared with men. Cancer 2010. © 2010 American Cancer Society.
Immunoglobulin G is present in a wide variety of soft tissue tumors and correlates well with proliferation markers and tumor grades
Authors: Chen Zhengshan , Huang Xinrui , Ye Juxiang , Pan Peng , Cao Qi , Yang Baokai , Li Zhuo , Su Meng , Huang Chen , Gu Jiang 
Published: February 2010

AbstractBACKGROUND:The traditional view that immunoglobulin (Ig) is produced only by B lymphocytes has been challenged, because it has been demonstrated that Ig genes and proteins are expressed in epithelial cancer cells. However, whether Ig expression in nonlymphoid cells is limited to epithelial cells is unclear. Because sarcomas differ distinctly from carcinomas in their biologic and clinical features, the authors investigated the question of nonlymphoid IgG expression in soft tissue lesions.METHODS:Immunohistochemistry, in situ hybridization, and polymerase chain reaction (PCR) were used to demonstrate IgG expression in 80 soft tissue lesions. The correlation between Ig expression and proliferation markers (proliferating cell nuclear antigen [PCNA], Ki‐67, and cyclin D1) in sarcomas was investigated by immunohistochemical and statistical analyses.RESULTS:Igκ was identified in 97.4% of sarcomas and in 31.7% of benign lesions by immunohistochemistry. The difference was statistically significant (P < .01). Messenger RNA from the IgG1 heavy‐chain constant region was also detected by in situ hybridization. Variable‐diversity‐joining recombination sequences of both heavy and light chains were obtained by PCR and sequencing. Moreover, the labeling index of PCNA, Ki‐67, and cyclin D1 was much higher in sarcomas with high Igκ expression than in sarcomas with low Igκ expression (P < .01 for PCNA and cyclin D1; P < .001 for Ki‐67). There were more grade 3 sarcomas with high Igκ expression compared with grade 1 and 2 sarcomas (P < .05).CONCLUSIONS:IgG was identified in a wide variety of soft tissue tumors and correlated well with proliferation markers and tumor grades. IgG may be a useful marker for cell proliferation in sarcomas. Cancer 2010. © 2010 American Cancer Society.
Pulmonary dysfunction in survivors of childhood hematologic malignancies after allogeneic hematopoietic stem cell transplantation
Authors: Inaba Hiroto , Yang Jie , Pan Jianmin , Stokes Dennis C. , Krasin Matthew J. , Srinivasan Ashok , Hartford Christine M. , Pui Ching‐Hon , Leung Wing 
Published: February 2010

AbstractBACKGROUND:The number of long‐term survivors of allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is increasing; however, few studies have addressed their long‐term pulmonary function.METHODS:The authors examined 660 baseline and follow‐up pulmonary function tests in 89 long‐term survivors of pediatric hematologic malignancies and allo‐HSCT.RESULTS:At least 1 abnormal lung parameter was seen in 40.4% of baseline tests and developed in 64% of post–allo‐HSCT tests (median follow‐up: 8.9 years). Abnormal baseline values in ratio of forced expiratory volume in 1 second and forced vital capacity (FEV1/FVC), FEV1, residual volume (RV), functional residual capacity (FRC), and FVC were associated with abnormal post–allo‐HSCT values. The following pulmonary function values declined significantly with time: FEV1/FVC, forced mid‐expiratory flow (FEF25%‐75%), total lung capacity (TLC), diffusion capacity corrected for hemoglobin (DLCOcorr), RV, FRC, and RV/TLC. Older age at the time of allo‐HSCT was associated with lower FEV1/FVC, FEF25%‐75%, and DLCOcorr and higher RV/TLC. Patients who experienced respiratory events within 1 year post–allo‐HSCT had lower FEV1 and FVC values and higher RV/TLC from their baseline pulmonary function tests. Female patients had reduced FVC, TLC, and RV values but higher FEV1/FVC. Pulmonary dysfunction was also associated with high‐risk hematological malignancies and peripheral blood HSC product.CONCLUSIONS:Abnormal pulmonary functions in allo‐HSCT survivors are prevalent, which underscore the need for risk‐adapted continual monitoring and improved preventive and management strategies. Cancer 2010. © 2010 American Cancer Society.
Effect of a minimum lymph node policy in radical cystectomy and pelvic lymphadenectomy on lymph node yields, lymph node positivity rates, lymph node density, and survivorship in patients with bladder cancer
Authors: Fang Andrea C. , Ahmad Ardalan E. , Whitson Jared M. , Ferrell Linda D. , Carroll Peter R. , Konety Badrinath R. 
Published: February 2010

AbstractBACKGROUND:Extended pelvic lymphadenectomy (PLND) during radical cystectomy (RC) reportedly improves bladder cancer‐specific survival. Lymph node counts are often a proxy for the extensiveness of a dissection. In the current study, the impact of an institutional policy requiring a minimum number of lymph nodes was assessed.METHODS:Patients undergoing RC and PLND for invasive bladder cancer between March 2000 and February 2008 were retrospectively reviewed at the study institution. Beginning March 1, 2004, a policy was established that at least 16 lymph nodes had to be examined. Specimens with <16 lymph nodes were resubmitted (including any fat) to detect additional lymph nodes. Lymph node yields, lymph node positivity, lymph node density (LND), and survivorship before and after policy implementation were compared.RESULTS:A total of 147 patients underwent surgery 4 years before policy implementation and 202 underwent surgery 4 years after. The median number of lymph nodes increased from 15 to 20. Percentage of cases with ≥16 lymph nodes increased from 42.9% to 69.3% (P<.01). The lymph node positivity rates did not change significantly, but the proportion of patients with LND <20% increased from 43.9% to 65.5% (P= .04). Overall survival increased from 41.5% to 72.3% (P<.01). Univariate and multivariate regression demonstrated that policy implementation, and subsequent increase in median lymph node yield, decreased mortality risk by 30% (hazards ratio [HR], 0.70;P= .04) and 48% (HR, 0.52;P= .01), respectively.CONCLUSIONS:Thorough evaluation of PLND specimens obtained at RC can be influenced by an institutional policy mandating a minimum number of lymph nodes. This could lead to greater confidence in pathologic staging and reliability of LND as a predictor of prognosis. Survival can improve due to increased awareness to perform a more thorough PLND. Cancer 2010. © 2010 American Cancer Society.