bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regioselective biooxidation of (+)-valencene by recombinant E. coli expressing CYP109B1 from Bacillus subtilis in a two-liquid-phase system
Authors: Girhard Marco , Machida Kazuhiro , Itoh Masashi , Schmid Rolf D , Arisawa Akira , Urlacher Vlada B 
Published: July 2009

Abstract

Background
(+)-Nootkatone (4) is a high added-value compound found in grapefruit juice. Allylic oxidation of the sesquiterpene (+)-valencene (1) provides an attractive route to this sought-after flavoring. So far, chemical methods to produce (+)-nootkatone (4) from (+)-valencene (1) involve unsafe toxic compounds, whereas several biotechnological approaches applied yield large amounts of undesirable byproducts. In the present work 125 cytochrome P450 enzymes from bacteria were tested for regioselective oxidation of (+)-valencene (1) at allylic C2-position to produce (+)-nootkatone (4) via cis- (2) or trans-nootkatol (3). The P450 activity was supported by the co-expression of putidaredoxin reductase (PdR) and putidaredoxin (Pdx) from Pseudomonas putida in Escherichia coli.

Results
Addressing the whole-cell system, the cytochrome CYP109B1 from Bacillus subtilis was found to catalyze the oxidation of (+)-valencene (1) yielding nootkatol (2 and 3) and (+)-nootkatone (4). However, when the in vivo biooxidation of (+)-valencene (1) with CYP109B1 was carried out in an aqueous milieu, a number of undesired multi-oxygenated products has also been observed accounting for approximately 35% of the total product. The formation of these byproducts was significantly reduced when aqueous-organic two-liquid-phase systems with four water immiscible organic solvents – isooctane, n-octane, dodecane or hexadecane – were set up, resulting in accumulation of nootkatol (2 and 3) and (+)-nootkatone (4) of up to 97% of the total product. The best productivity of 120 mg l-1 of desired products was achieved within 8 h in the system comprising 10% dodecane.

Conclusion
This study demonstrates that the identification of new P450s capable of producing valuable compounds can basically be achieved by screening of recombinant P450 libraries. The biphasic reaction system described in this work presents an attractive way for the production of (+)-nootkatone (4), as it is safe and can easily be controlled and scaled up.
A stratified random survey of the proportion of poor quality oral artesunate sold at medicine outlets in the Lao PDR – implications for therapeutic failure and drug resistance
Authors: Sengaloundeth Sivong , Green Michael D , Fernández Facundo M , Manolin Ot , Phommavong Khamlieng , Insixiengmay Vongsavanh , Hampton Christina Y , Nyadong Leonard , Mildenhall Dallas C , Hostetler Dana , Khounsaknalath Lamphet , Vongsack Latsamy , Phompida Samlane , Vanisaveth Viengxay , Syhakhang Lamphone , Newton Paul N 
Published: July 2009

AbstractBackgroundCounterfeit oral artesunate has been a major public health problem in mainland SE Asia, impeding malaria control. A countrywide stratified random survey was performed to determine the availability and quality of oral artesunate in pharmacies and outlets (shops selling medicines) in the Lao PDR (Laos).MethodsIn 2003, 'mystery' shoppers were asked to buy artesunate tablets from 180 outlets in 12 of the 18 Lao provinces. Outlets were selected using stratified random sampling by investigators not involved in sampling. Samples were analysed for packaging characteristics, by the Fast Red Dye test, high-performance liquid chromatography (HPLC), mass spectrometry (MS), X-ray diffractometry and pollen analysis.ResultsOf 180 outlets sampled, 25 (13.9%) sold oral artesunate. Outlets selling artesunate were more commonly found in the more malarious southern Laos. Of the 25 outlets, 22 (88%; 95%CI 68–97%) sold counterfeit artesunate, as defined by packaging and chemistry. No artesunate was detected in the counterfeits by any of the chemical analysis techniques and analysis of the packaging demonstrated seven different counterfeit types. There was complete agreement between the Fast Red dye test, HPLC and MS analysis. A wide variety of wrong active ingredients were found by MS. Of great concern, 4/27 (14.8%) fakes contained detectable amounts of artemisinin (0.26–115.7 mg/tablet).ConclusionThis random survey confirms results from previous convenience surveys that counterfeit artesunate is a severe public health problem. The presence of artemisinin in counterfeits may encourage malaria resistance to artemisinin derivatives. With increasing accessibility of artemisinin-derivative combination therapy (ACT) in Laos, the removal of artesunate monotherapy from pharmacies may be an effective intervention.
Measuring patient's expectation and the perception of quality in LASIK services
Authors: Lin Deng-Juin , Sheu Ing-Cheau , Pai Jar-Yuan , Bair Alex , Hung Che-Yu , Yeh Yuan-Hung , Chou Ming-Jen 
Published: July 2009

Abstract

Background
LASIK is the use of excimer lasers to treat therapeutic and refractive visual disorders, ranging from superficial scars to nearsightedness (myopia), and from astigmatism to farsightedness (hyperopia). The purposes of this study are to checking the applicability and psychometric properties of the SERVQUAL on Lasik surgery population. Second, use SEM methods to investigate the loyalty, perceptions and expectations relationship on LASIK surgery.

Methods
The method with which this study was conducted was questionnaire development. A total of 463 consecutive patients, attending LASIK surgery affiliated with Chung Shan Medical University Eye Center, enrolled in this study. All participants were asked to complete revised SERVQUAL questionnaires. Student t test, correlation test, and ANOVA and factor analyses were used to identify the characters and factors of service quality. Paired t test were used to test the gap between expectation and perception scores and structural equation modeling was used to examine relationships among satisfaction components.

Results
The effective response rate was 97.3%. Validity was verified by several methods and internal reliability Cronbach's alpha was > 0.958. The results from patient's scores were very high with an overall score of 6.41(0.66), expectations at 6.68(0.47), and perceptions at 6.51(0.57). The gap between expectations and perceptions was significant, however, (t = 6.08). Furthermore, there were significant differences in the expectation scores among the different jobs. Also, the results showed that the higher the education of the patient, the lower their perception score (r = -0.10). The factor loading results of factor analysis showed 5 factors of the 22 items of the SERVQUAL model. The 5 factors of perception explained 72.94% of the total variance there; and on expectations it explained 77.12% of the total variance of satisfaction scores.
The goodness-of-fit summary, of structure equation modeling, showed trends in concept on expectations, perceptions, and loyalty.

Conclusion
The results of this research appear to show that the SERVQUAL instrument is a useful measurement tool in assessing and monitoring service quality in LASIK service, and enabling staff to identify where improvements are needed, from the patients' perspective. There were service quality gaps in the reliability, assurance, and empathy. This study suggested that physicians should increase their discussions with patients; which has, of course, already been proven to be an effective way to increase patient's satisfaction with medical care, regardless of the procedure received.
Addressing gaps in surgical skills training by means of low-cost simulation at Muhimbili University in Tanzania
Authors: Taché Stephanie , Mbembati Naboth , Marshall Nell , Tendick Frank , Mkony Charles , O'Sullivan Patricia 
Published: July 2009

Abstract

Background
Providing basic surgical and emergency care in rural settings is essential, particularly in Tanzania, where the mortality burden addressable by emergency and surgical interventions has been estimated at 40%. However, the shortages of teaching faculty and insufficient learning resources have hampered the traditionally intensive surgical training apprenticeships. The Muhimbili University of Health and Allied Sciences consequently has experienced suboptimal preparation for graduates practising surgery in the field and a drop in medical graduates willing to become surgeons. To address the decline in circumstances, the first step was to enhance technical skills in general surgery and emergency procedures for senior medical students by designing and implementing a surgical skills practicum using locally developed simulation models.

Methods
A two-day training course in nine different emergency procedures and surgical skills based on the Canadian Network for International Surgery curriculum was developed. Simulation models for the surgical skills were created with locally available materials. The curriculum was pilot-tested with a cohort of 60 senior medical students who had completed their surgery rotation at Muhimbili University. Two measures were used to evaluate surgical skill performance: Objective Structured Clinical Examinations and surveys of self-perceived performance administered pre- and post-training.

Results
Thirty-six students participated in the study. Prior to the training, no student was able to correctly perform a surgical hand tie, only one student was able to correctly perform adult intubation and three students were able to correctly scrub, gown and glove. Performance improved after training, demonstrated by Objective Structured Clinical Examination scores that rose from 6/30 to 15/30. Students perceived great benefit from practical skills training. The cost of the training using low-tech simulation was four United States dollars per student.

Conclusion
Simulation is valued to gain experience in practising surgical skills prior to working with patients. In the context of resource-limited settings, an additional benefit is that of learning skills not otherwise obtainable. Further testing of this approach will determine its applicability to other resource-limited settings seeking to develop skill-based surgical and emergency procedure apprenticeships. Additionally, skill sustainability and readiness for actual surgical and emergency experiences need to be assessed.
Evaluation of preoperative intra-aortic balloon pump in coronary patients with severe left ventricular dysfunction undergoing OPCAB surgery: early and mid-term outcomes
Authors: Qiu Zhibing , Chen Xin , Xu Ming , Jiang Yingshuo , Xiao Liqiong , Liu LeLe , Wang Liming 
Published: July 2009

Abstract

Background
The purpose of the present study was to evaluate the safety and the cost-effectiveness of using preoperative IABP as support compared with postoperative IABP treatment in coronary patients with severe left ventricular dysfunction (SLVD) who is undergoing off-pump coronary artery bypass surgery (OPCAB), including early outcomes, hospital mortality and morbidity, and mid-term follow-up outcomes.

Methods
Between March 2000 and December 2008, we prospectively and randomly studied the insertion of preoperative IABP in 115 (7.4%) and postoperative IABP in 106 (6.8%) of the 1560 consecutive patients. Group A is preoperative IABP therapy. Group B is postoperative IABP therapy.

Results
There was no significant difference in the number of grafts used between the two groups. Completeness of revascularization did not differ between the two groups. The statistically significant difference was hospital mortality (2.6% in group A vs. 3.8% in group B) (p < 0.05). And there was significant reduction in postoperative low cardiac output, malignant arrhythmia, acute renal failure and length of stay in ICU in group A, compared with group B (p < 0.05). In the two groups, six-, 12-, 24- and 48-month survival rates were similar. In the study the degree of improvement in angina and quality of life did not differ significantly between the two groups.

Conclusion
The use of preoperative IABP in SLVD patients undergoing OPCAB is of safety and effectiveness. The combined use of preoperative IABP and OPCAB allows complete revascularization in SLVD patients with an important reduction in operative mortality and excellent mid-term results.
An integration of complementary strategies for gene-expression analysis to reveal novel therapeutic opportunities for breast cancer
Authors: Bild Andrea H , Parker Joel S , Gustafson Adam M , Acharya Chaitanya R , Hoadley Katherine A , Anders Carey , Marcom P Kelly , Carey Lisa A , Potti Anil , Nevins Joseph R , Perou Charles M 
Published: July 2009

Abstract
Introduction
Perhaps the major challenge in developing more effective therapeutic strategies for the treatment of breast cancer patients is confronting the heterogeneity of the disease, recognizing that breast cancer is not one disease but multiple disorders with distinct underlying mechanisms. Gene-expression profiling studies have been used to dissect this complexity, and our previous studies identified a series of intrinsic subtypes of breast cancer that define distinct populations of patients with respect to survival. Additional work has also used signatures of oncogenic pathway deregulation to dissect breast cancer heterogeneity as well as to suggest therapeutic opportunities linked to pathway activation.

Methods
We used genomic analyses to identify relations between breast cancer subtypes, pathway deregulation, and drug sensitivity. For these studies, we use three independent breast cancer gene-expression data sets to measure an individual tumor phenotype. Correlation between pathway status and subtype are examined and linked to predictions for response to conventional chemotherapies.

Results
We reveal patterns of pathway activation characteristic of each molecular breast cancer subtype, including within the more aggressive subtypes in which novel therapeutic opportunities are critically needed. Whereas some oncogenic pathways have high correlations to breast cancer subtype (RAS, CTNNB1, p53, HER1), others have high variability of activity within a specific subtype (MYC, E2F3, SRC), reflecting biology independent of common clinical factors. Additionally, we combined these analyses with predictions of sensitivity to commonly used cytotoxic chemotherapies to provide additional opportunities for therapeutics specific to the intrinsic subtype that might be better aligned with the characteristics of the individual patient.

Conclusions
Genomic analyses can be used to dissect the heterogeneity of breast cancer. We use an integrated analysis of breast cancer that combines independent methods of genomic analyses to highlight the complexity of signaling pathways underlying different breast cancer phenotypes and to identify optimal therapeutic opportunities.
Prostate Cancer–Specific Mortality After Radical Prostatectomy for Patients Treated in the Prostate-Specific Antigen Era
Authors: Stephenson Andrew J. , Kattan Michael W. , Eastham James A. , Bianco Fernando J. , Yossepowitch Ofer , Vickers Andrew J. , Klein Eric A. , Wood David P. , Scardino Peter T. 
Published: July 2009

Purpose The long-term risk of prostate cancer–specific mortality (PCSM) after radical prostatectomy is poorly defined for patients treated in the era of widespread prostate-specific antigen (PSA) screening. Models that predict the risk of PCSM are needed for patient counseling and clinical trial design. Methods A multi-institutional cohort of 12,677 patients treated with radical prostatectomy between 1987 and 2005 was analyzed for the risk of PCSM. Patient clinical information and treatment outcome was modeled using Fine and Gray competing risk regression analysis to predict PCSM. Results Fifteen-year PCSM and all-cause mortality were 12% and 38%, respectively. The estimated PCSM ranged from 5% to 38% for patients in the lowest and highest quartiles of predicted risk of PSA-defined recurrence, based on a popular nomogram. Biopsy Gleason grade, PSA, and year of surgery were associated with PCSM. A nomogram predicting the 15-year risk of PCSM was developed, and the externally validated concordance index was 0.82. Neither preoperative PSA velocity nor body mass index improved the model's accuracy. Only 4% of contemporary patients had a predicted 15-year PCSM of greater than 5%. Conclusion Few patients will die from prostate cancer within 15 years of radical prostatectomy, despite the presence of adverse clinical features. This favorable prognosis may be related to the effectiveness of radical prostatectomy (with or without secondary therapy) or the low lethality of screen-detected cancers. Given the limited ability to identify contemporary patients at substantially elevated risk of PCSM on the basis of clinical features alone, the need for novel markers specifically associated with the biology of lethal prostate cancer is evident.
Phase I Dose Escalation Study of Telatinib, a Tyrosine Kinase Inhibitor of Vascular Endothelial Growth Factor Receptor 2 and 3, Platelet-Derived Growth Factor Receptor β, and c-Kit, in Patients With Advanced or Metastatic Solid Tumors
Authors: Eskens Ferry A.L.M. , Steeghs Neeltje , Verweij Jaap , Bloem Johan L. , Christensen Olaf , van Doorn Leni , Ouwerkerk Jan , de Jonge Maja J.A. , Nortier Johan W.R. , Kraetzschmar Joern , Rajagopalan Prabhu , Gelderblom Hans 
Published: July 2009

Purpose Telatinib (BAY 57-9352) is an orally available tyrosine kinase inhibitor of vascular endothelial growth factor receptor (VEGFR) -2, VEGFR-3, platelet-derived growth factor receptor-β, and c-Kit. This phase I dose escalation study was conducted to evaluate the safety and tolerability of telatinib, with additional pharmacokinetic, pharmacodynamic, and efficacy assessments. Patients and Methods Patients with solid tumors refractory to standard therapies or with no standard therapy available were enrolled. Doses of continuously administered telatinib were escalated from 20 mg once daily to 1,500 mg twice daily. Results Fifty-three patients were enrolled. Most frequently observed drug-related adverse events were nausea (26.4%; grade ≥ 3, 0%) and hypertension (20.8%; grade 3, 11.3%; grade 4, 0%). Two dose-limiting toxicities were observed: one poorly controlled hypertension (600 mg twice daily), and one grade 2 weight loss, anorexia, and fatigue (1,500 mg twice daily). A formal maximum-tolerated dose was not reached. Telatinib was rapidly absorbed, with median time to peak concentration (tmax) lower than 3 hours after dose. A nearly dose-proportional increase in exposure was observed with substantial variability. Telatinib half-life averaged 5.5 hours. Biomarker analyses showed dose-dependent increase in VEGF levels and decrease in plasma soluble VEGFR-2 levels, with a plateau at 900 mg twice daily. A decrease in tumor blood flow (Ktrans and IAUC60) was observed with dynamic contrast-enhanced magnetic resonance imaging. Best tumor response was stable disease, observed in 50.9% of patients. Conclusion Telatinib was safe and well tolerated up to 1,500 mg twice daily. Based on pharmacodynamic and pharmacokinetic end points, telatinib 900 mg twice daily is the recommended dose for subsequent phase II studies.
Gene Expression Profiles of Tumor Biology Provide a Novel Approach to Prognosis and May Guide the Selection of Therapeutic Targets in Multiple Myeloma
Authors: Anguiano Ariel , Tuchman Sascha A. , Acharya Chaitanya , Salter Kelly , Gasparetto Cristina , Zhan Fenghuang , Dhodapkar Madhav , Nevins Joseph , Barlogie Bart , Shaughnessy John D. , Potti Anil 
Published: July 2009

PurposeMonoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) comprise heterogeneous disorders with incompletely understood molecular defects and variable clinical features. We performed gene expression profiling (GEP) with microarray data to better dissect the molecular phenotypes and prognoses of these diseases.MethodsUsing gene expression and clinical data from 877 patients ranging from normal plasma cells (NPC) to relapsed MM (RMM), we applied gene expression signatures reflecting deregulation of oncogenic pathways and tumor microenvironment to highlight molecular changes that occur as NPCs transition to MM, create a high-risk MGUS gene signature, and subgroup International Staging System (ISS) stages into more prognostically accurate clusters of patients.ResultsMyc upregulation and increasing chromosomal instability (CIN) characterized the evolution from NPC to RMM (P < .0001 for both). Studies of MGUS revealed that some samples shared biologic features with RMM, which comprised the basis for a high-risk MGUS signature. Regarding MM, we subclassified ISS stages into clusters based on shared features of tumor biology. These clusters differentiated themselves based on predictions for prognosis (eg, in ISS stage I, one cluster was characterized by increased CIN and a poor prognosis).ConclusionGEP provides insight into the molecular defects underlying plasma cell dyscrasias that may explain their clinical heterogeneity. GEP also may also refine current prognostic and therapeutic models for MGUS and MM.
Trends in Mastectomy Rates at the Mayo Clinic Rochester: Effect of Surgical Year and Preoperative Magnetic Resonance Imaging
Authors: Katipamula Rajini , Degnim Amy C. , Hoskin Tanya , Boughey Judy C. , Loprinzi Charles , Grant Clive S. , Brandt Kathleen R. , Pruthi Sandhya , Chute Christopher G. , Olson Janet E. , Couch Fergus J. , Ingle James N. , Goetz Matthew P. 
Published: July 2009

Purpose Recent changes have occurred in the presurgical planning for breast cancer, including the introduction of preoperative breast magnetic resonance imaging (MRI). We sought to analyze the trends in mastectomy rates and the relationship to preoperative MRI and surgical year at Mayo Clinic, Rochester, MN. Patients and Methods We identified 5,405 patients who underwent surgery between 1997 and 2006. Patients undergoing MRI were identified from a prospective database. Trends in mastectomy rate and the association of MRI with surgery type were analyzed. Multiple logistic regression was used to assess the effect of surgery year and MRI on surgery type, while adjusting for potential confounding variables. Results Mastectomy rates differed significantly across time (P < .0001), and decreased from 45% in 1997% to 31% in 2003, followed by increasing rates for 2004 to 2006. The use of MRI increased from 10% in 2003% to 23% in 2006 (P < .0001). Patients with MRI were more likely to undergo mastectomy than those without MRI (54% v 36%; P < .0001). However, mastectomy rates increased from 2004 to 2006 predominantly among patients without MRI (29% in 2003% to 41% in 2006; P < .0001). In a multivariable model, both MRI (odds ratio [OR], 1.7; P < .0001) and surgical year (compared to 2003 OR: 1.4 for 2004, 1.8 for 2005, and 1.7 for 2006; P < .0001) were independent predictors of mastectomy. Conclusion After a steady decline, mastectomy rates have increased in recent years with both surgery year and MRI as significant predictors for type of surgery. Further studies are needed to evaluate the role of MRI and other factors influencing surgical planning.