bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and validation of an LC‐MS/MS method for the determination of bullatine A in rat plasma: application to a pharmacokinetic study
Authors: Teng Shi‐Yong , Zhang Si‐Xi , Niu Kai , Zhai Li‐Jie , Wang Shi‐Ji 
Published: May 2015

AbstractBullatine A is a diterpenoid alkaloid of Xue‐Shang‐Yi‐Zhi‐Hao (Aconitum brachypodum), which is widely used in traditional Chinese medicine for the treatment of rheumatism and pain. The plasma levels of bullatine A were measured by a rapid and sensitive LC‐MS/MS method. Samples were prepared using acetonitrile precipitation and the separation of bullatine A was achieved on a Capcell Pak MG‐C18 column by isocratic elution using acetonitrile (phase A) and 0.1% formic acid (phase B, pH 4.0; A:B, 30:70, v/v) as the mobile phase at a flow rate of 0.5 mL/min. Detection was performed on a triple‐quadrupole tandem mass spectrometer by multiple‐reaction monitoring of the transitions at m/z 344.2 → 105.2 for bullatine A and m/z 256.2 → 167.1 for the internal standard. The linearity was found to be within the concentration range of 1.32–440 ng/mL with a lower limit of quantification of 1.32 ng/mL. Only 1.3 min was needed for an each analytical run. This method was successfully applied in the determination of the active component bullatine A in rat plasma after intramuscular administration of A. brachypodum injection. Copyright © 2015 John Wiley & Sons, Ltd.
Clinical predictors of mortality following rotational atherectomy and stent implantation in high‐risk patients: A single center experience
Authors: Édes István F. , Ruzsa Zoltán , Szabó György , Nardai Sándor , Becker Dávid , Benke Kálmán , Szilveszter Bálint , Merkely Béla 
Published: May 2015

ObjectivesOur aim was to assess the procedural success and determine the clinical predictors of postprocedure mortality, following rotational atherectomy (RA) and stenting in high‐risk patients.BackgroundRA is mainly used to facilitate stenting in complex lesions. Outcomes involving RA and stenting have been investigated, yet high‐risk patients have not been adequately described.MethodsData of 218 consecutive patients who underwent RA were evaluated in a prospective register. Primary endpoints were the angiographic success and long‐term mortality. Secondary endpoints were procedural success, consumption of the angioplasty equipment, and periprocedural major adverse cardiac events. The impact of the relevant angiographic and clinical characteristics on long‐term mortality was analyzed using uni‐ and multivariate Cox regression analysis.ResultsMean age of the patients was 70 ± 8.2 years, diabetes was present in 44%, and chronic renal failure in 29%. Prior myocardial infarction and three‐vessel disease amounted to 42.2% and 32.6%, respectively. Altogether, 52.8% of patients underwent RA after a failed, non‐RA intervention attempt, and 30.7% of cases presented as acute coronary syndromes. Angiographic success was 100%, and all patients received stents after RA. Periprocedural major adverse cardiac events occurred in five (2.3%) patients. Postprocedural death was investigated, with a mean follow‐up of 36 months. Mortality amounted to 37.2%. Multivariate analysis revealed that left ventricular ejection fraction < 50%, glomerular filtration rate < 60 ml/min, cardiogenic shock, and diabetes were the only independent mortality predictors.ConclusionsWe have found that RA and stenting is feasible and viable in an elderly high‐risk population, with exceptional procedural success and acceptable long‐term results. © 2015 Wiley Periodicals, Inc.
Impact of Mixed Aortic Valve Stenosis on VARC‐2 Outcomes and Postprocedural Aortic Regurgitation in Patients Undergoing Transcatheter Aortic Valve Implantation
Authors: Chieffo Alaide , Van Mieghem Nicolas M. , Tchetche Didier , Dumonteil Nicolas , Giustino Gennaro , Van der Boon Robert M.A. , Pierri Adele , Marcheix Bertrand , Misuraca Leonardo , Serruys Patrick W. , Millischer Damien , Carrié Didier , de Jaegere Peter P.T. , Colombo Antonio 
Published: May 2015

ObjectivesWe sought to evaluate the impact of mixed aortic stenosis (MAS) on postprocedural aortic regurgitation (PPAR) and clinical outcomes after transcatheter aortic valve implantation (TAVI).BackgroundThe impact of MAS of TAVI outcomes is unknown.Methods and ResultsData from a multicenter registry were retrospectively analysed. Outcomes were compared between patients with pure aortic stenosis (PAS; associated AR < 1+/3+) and MAS (associated AR ≥ 1+/3+). Study objectives were PPAR incidence and short‐ and long‐term mortality. Overall, 1,062 patients were included: 419 (39.4%) with MAS and 643 (60.5%) with PAS. At 30 days, there were no differences in mortality, however, a higher incidence of major bleeding (22.7% vs. 16.8%; P = 0.016), PPAR ≥ 1+/3+ (42.6% vs. 26.5%; P < 0.001) and lower device success (89.3% vs. 93.3%; P = 0.019) was observed in patients with MAS. Of note, MAS was an independent predictor of PPAR ≥ 1+/3+ at multivariable analysis (OR: 2.882; CI: 1.851–4.488; P < 0.001). At 2 years of follow‐up, no survival differences were present between MAS and PAS groups. Similarly, following stratification for PPAR ≥ 1+/3+, MAS had no protective effect on survival as compared with PAS.ConclusionsMAS was associated with lower device success and higher PPAR incidence. However, despite these findings, it had no influence on long‐term postoperative outcomes. © 2015 Wiley Periodicals, Inc.
Assessment of MR compatibility and machinability using the fuzzy comprehensive evaluation method for material selection of MR device
Authors: Jiang Shan , Wu Zhengxing , Ren Zhaowei , Yang Zhiyong 
Published: May 2015

ABSTRACTObjectiveTo develop magnetic resonance (MR) robot used in the magnetic field environment, materials selected for manufacturing robot should have good MR compatibility and machinability. Therefore, it is becoming increasingly urgent to develop an evaluation method considering the above two factors at the same time.MethodsA series of experiments were done to study the interaction between the magnetic field of MR scanner and the material samples, and to determine the samples’ machinability. Four kinds of materials including metal and plastics with different geometric shape were used to test the artifacts, force and torque in magnetic resonance image (MRI) tube according to standard method. Three items including surface roughness, cutting force and chip shape were analyzed to evaluate the machinability of four samples. The fuzzy comprehensive evaluation method was adopted to process these experimental data for choosing the most suitable robot material in MR environment.ResultsThe quantized values of MR compatibility and machinability are achieved, and a new methodology for material selection are developed, which provides systematic guideline for engineer and researcher to choose suitable robot materials used in an MRI tube. Polyformaldehyde of four kinds of material is determined to be the most suitable one for MR robots or devices.ConclusionA thorough examination of four commonly used engineering materials has been discussed and the fuzzy comprehensive evaluation method is suitable for choosing MR compatible robot materials. © 2015 Wiley Periodicals, Inc. Concepts Magn Reson Part B (Magn Reson Engineering) 45B: 1–12, 2015
Chemotoxicity recurrence in older patients: Risk factors and effectiveness of preventive strategies—a prospective study
Authors: Extermann Martine , Reich Richard R. , Sehovic Marina 
Published: May 2015

BACKGROUNDThe National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) and adjustment rules after severe toxicity are derived by consensus, but to the authors’ knowledge little is known regarding the determinants of toxicity recurrence, especially in the elderly.METHODSThe authors prospectively accrued 200 patients (aged ≥65 years) before chemotherapy. For those with CTCAE grade 3 to 4 nonhematologic or CTCAE grade 4 hematologic toxicities (severe toxicity), the duration and functional impact, treatment modifications, and severe toxicity recurrence were recorded. The regimen's toxicity was adjusted with the MAX2 index, the average of the most frequent grade 4 hematologic toxicities and the most frequent grade 3 to 4 nonhematologic toxicities reported in publications of a regimen.RESULTSThe median patient age was 73 years (range, 65‐90 years). Among 163 patients who were evaluable for toxicity after ≥1 treatment cycle (receiving on average 4.73 cycles), 82 had severe toxicity, 10 were discontinued for toxicity, 6 were discontinued for other reasons, and 5 patients had died. Sixty‐one patients received further chemotherapy: 41 without dose modification (16 with secondary prevention measures) and 20 with dose modifications. Without modification, 19 patients (46%) experienced toxicity recurrence (0 deaths). With modification, 7 patients (35%) experienced a toxicity recurrence (1 death). On univariate analysis, treatment intent, hospitalization, duration‐adjusted activities of daily living (ADL), quality of life impact, and fatigue were associated with dose modification. ADL remained associated on multivariate analysis (P = .02). On univariate analysis for toxicity recurrence, Eastern Cooperative Oncology Group performance status and MAX2 score demonstrated an association, with only the latter found to remain statistically significant on multivariate analysis (P = .04).CONCLUSIONSIf a severe toxicity does not have a long duration of impact on ADL, oncologists are less inclined to modify treatment. With proper supportive measures, this leads to recurrence risks similar to those shown in patients with modified treatment, with low risks of toxic deaths overall. Cancer 2015;121:2984–2992. © 2015 American Cancer Society.
Impact of obesity on outcomes after definitive dose‐escalated intensity‐modulated radiotherapy for localized prostate cancer
Authors: Wang Lora S. , Murphy Colin T. , Ruth Karen , Zaorsky Nicholas G. , Smaldone Marc C. , Sobczak Mark L. , Kutikov Alexander , Viterbo Rosalia , Horwitz Eric M. 
Published: May 2015

BACKGROUNDPrevious publications have demonstrated conflicting results regarding body mass index (BMI) and prostate cancer (CaP) outcomes after definitive radiotherapy (RT) before the dose escalation era. The goal of the current study was to determine whether increasing BMI was associated with outcomes in men with localized CaP who were treated with dose‐escalated RT.METHODSThe authors identified patients with localized (T1b‐T4N0M0) CaP who were treated with definitive intensity‐modulated RT and image‐guided RT from 2001 through 2010. BMI was analyzed as a continuous variable. Adjusting for confounders, multivariable competing risk and Cox proportional hazards regression models were used to assess the association between BMI and the risk of biochemical failure (BF), distant metastases (DM), cause‐specific mortality (CSM), and overall mortality.RESULTSOf the 1442 patients identified, approximately 20% had a BMI <25 kg/m2, 48% had a BMI of 25 to 29.9 kg/m2, 23% had a BMI of 30 to 34.9 kg/m2, 6% had a BMI of 35 to 39.9 kg/m2, and 4% had a BMI of ≥40 kg/m2. The median follow‐up was 47.6 months (range, 1‐145 months), with a median age of 68 years (range, 36‐89 years). The median dose was 78 grays (range, 76‐80 grays) and 30% of patients received androgen deprivation therapy. Increasing BMI was found to be inversely associated with age (P<.001) and pretreatment prostate‐specific antigen level (P = .018). On multivariable analysis, increasing BMI was associated with an increased risk of BF (hazard ratio [HR], 1.03; 95% confidence interval [95% CI], 1.00‐1.07 [P = .042]), DM (HR, 1.07; 95% CI, 1.02‐1.11 [P = .004]), CSM (HR, 1.15; 95% CI, 1.07‐1.23 [P<.001]), and overall mortality (HR, 1.05; 95% CI, 1.02‐1.08 [P = .004]).CONCLUSIONSFor patients with CaP receiving dose‐escalated intensity‐modulated RT with daily image‐guidance, increasing BMI appears to be associated with an increased risk of BF, DM, CSM, and overall mortality.Cancer2015;121:3010–3017.©2015 American Cancer Society.
Prognostic significance of acquired copy‐neutral loss of heterozygosity in acute myeloid leukemia
Authors: Gronseth Christine M. , McElhone Scott E. , Storer Barry E. , Kroeger Kathleen A. , Sandhu Vicky , Fero Matthew L. , Appelbaum Frederick R. , Estey Elihu H. , Fang Min 
Published: May 2015

BACKGROUNDChromosomal abnormalities are important in the diagnosis and prognosis of patients with acute myeloid leukemia (AML). Genomic microarray techniques detect recurrent copy‐neutral loss of heterozygosity (cnLOH) in addition to copy number aberrations. However, the clinical utility has not been fully established. Therefore, in the current study, the authors examined the prognostic impact of acquired cnLOH in patients with AML, including complete remission (CR) rate, duration of CR, and overall survival (OS).METHODSA total of 112 consecutive patients with AML who were undergoing chromosome genomic array testing (CGAT) at the Seattle Cancer Care Alliance were included in the current study. DNA from the bone marrow or blood was analyzed with a microarray platform with both single‐nucleotide polymorphism (SNP) probes and non‐SNP probes to identify acquired cnLOH. Results were correlated with cytogenetic, molecular, immunophenotypic, and other clinicopathological findings.RESULTSPatients with cnLOH demonstrated a shorter duration of CR (hazard ratio, 1.87;P=.04) and worse OS (HR, 1.82;P = .03). Multivariate analyses confirmed the independent predictive value of cnLOH for early disease recurrence (P=.02). These results largely reflected those in patients with intermediate and unfavorable cytogenetics. Most strikingly, 13q cnLOH was found to demonstrate a 6.64‐fold higher rate of disease recurrence (P=.006) and 3.45‐fold worse OS (P = .02) and was enriched with theFLT3‐ITD(Fms‐related tyrosine kinase 3‐internal tandem duplication) mutation.CONCLUSIONSCnLOH has important prognostic significance in patients with AML. CGAT can replace imbalance fluorescence in situ hybridization and the authors recommend the routine use of CGAT to detect cnLOH, particularly among patients with intermediate‐risk cytogenetics.Cancer2015;121:2900–2908.©2015 American Cancer Society.
Randomized phase 2 trial of erlotinib in combination with high‐dose celecoxib or placebo in patients with advanced non‐small cell lung cancer
Authors: Reckamp Karen L. , Koczywas Marianna , Cristea Mihaela C. , Dowell Jonathan E. , Wang He‐Jing , Gardner Brian K. , Milne Ginger L. , Figlin Robert A. , Fishbein Michael C. , Elashoff Robert M. , Dubinett Steven M. 
Published: May 2015

BACKGROUNDCyclooxygenase 2 (COX‐2)‐dependent signaling represents a potential mechanism of resistance to therapy with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. This is mediated in part through an EGFR‐independent activation of mitogen‐activated protein kinase (MAPK)/extracellular signal‐regulated kinase (Erk) by prostaglandin E2 (PGE2). PGE2 promotes downregulation of E cadherin and epithelial to mesenchymal transition. The current study investigated EGFR and COX‐2 inhibition in patients with non‐small cell lung cancer (NSCLC) and elevated baseline urinary metabolite of PGE2 (PGEM).METHODSPatients with stage IIIB/IV (AJCC 6th edition) NSCLC who progressed after at least 1 line of therapy or refused standard chemotherapy were randomized to receive erlotinib and celecoxib versus erlotinib and placebo. The primary endpoint was progression‐free survival (PFS) with 80% power to detect a 50% improvement with a 1‐sided significance level of .2 in the intent‐to‐treat and elevated baseline PGEM populations. Secondary endpoints included response rate, overall survival, and evaluation of molecular markers to assess targeting COX‐2–related pathways and evaluate EGFR tyrosine kinase inhibitor resistance.RESULTSA total of 107 patients were enrolled with comparable baseline characteristics. Among the patients treated with celecoxib, those with wild‐type EGFR were found to have an increased PFS (3.2 months vs 1.8 months; P = .03). PFS was numerically improved among patients in the intent‐to‐treat group who received erlotinib and celecoxib compared with those treated with erlotinib and placebo (5.4 months vs 3.5 months; P = .33) and was increased in patients in the erlotinib and celecoxib arm with elevated baseline PGEM (5.4 months vs 2.2 months; P = .15). Adverse events were similar in both treatment arms.CONCLUSIONSThe combination of erlotinib and celecoxib did not appear to improve outcomes in an unselected population, but selection by elevated baseline PGEM led to an increase in PFS with this combination. Patients with EGFR wild‐type status may benefit from the combination of erlotinib and celecoxib. Cancer 2015;121:3298–3306. © 2015 American Cancer Society.
A joint individual‐based model coupling growth and mortality reveals that tree vigor is a key component of tropical forest dynamics
Authors: Aubry‐Kientz Mélaine , Rossi Vivien , Boreux Jean‐Jacques , Hérault Bruno 
Published: May 2015

AbstractTree vigor is often used as a covariate when tree mortality is predicted from tree growth in tropical forest dynamic models, but it is rarely explicitly accounted for in a coherent modeling framework. We quantify tree vigor at the individual tree level, based on the difference between expected and observed growth. The available methods to join nonlinear tree growth and mortality processes are not commonly used by forest ecologists so that we develop an inference methodology based on an MCMC approach, allowing us to sample the parameters of the growth and mortality model according to their posterior distribution using the joint model likelihood. We apply our framework to a set of data on the 20‐year dynamics of a forest in Paracou, French Guiana, taking advantage of functional trait‐based growth and mortality models already developed independently. Our results showed that growth and mortality are intimately linked and that the vigor estimator is an essential predictor of mortality, highlighting that trees growing more than expected have a far lower probability of dying. Our joint model methodology is sufficiently generic to be used to join two longitudinal and punctual linked processes and thus may be applied to a wide range of growth and mortality models. In the context of global changes, such joint models are urgently needed in tropical forests to analyze, and then predict, the effects of the ongoing changes on the tree dynamics in hyperdiverse tropical forests.
Interactions between density, home range behaviors, and contact rates in the Channel Island fox (Urocyon littoralis)
Authors: Sanchez Jessica N. , Hudgens Brian R. 
Published: May 2015

AbstractMany of the mechanisms underlying density‐dependent regulation of populations, including contest competition and disease spread, depend on contact among neighboring animals. Understanding how variation in population density influences the frequency of contact among neighboring animals is therefore an important aspect to understanding the mechanisms underlying, and ecological consequences of, density‐dependent regulation. However, contact rates are difficult to measure in the field and may be influenced by density through multiple pathways. This study explored how local density affects contact rates among Channel Island foxes (Urocyon littoralis) through two pathways: changes in home range size and changes in home range overlap. We tracked 40 radio‐collared foxes at four sites on San Clemente Island, California. Fox densities at the four sites ranged from 2.8 ± 1.28 to 42.8 ± 9.43 foxes/km2. Higher fox densities were correlated with smaller home ranges (R2 = 0.526,F1,38 = 42.19,P < 0.001). Thirty foxes wore collars that also contained proximity loggers, which recorded the time and duration of occasions when collared foxes were within 5 m of one another. Contact rates between neighboring fox dyads were positively correlated with home range overlap (R2 = 0.341,P = 0.008), but not fox density (R2 = 0.012,P = 0.976). Individuals at high densities had more collared neighbors with overlapping home ranges (R2 = 0.123,P = 0.026) but not an increase in the amount of contact between individual neighbors. This study was the first time contact rates were directly measured and compared to density and home range overlap. Results suggest that foxes exhibit a threshold in their degree of tolerance for neighbors, overlap is a reliable index of the amount of direct contact between island foxes, and disease transmission rates will likely scale with fox density.
Grazing intensifies degradation of a Tibetan Plateau alpine meadow through plant–pest interaction
Authors: Cao Hui , Zhao Xinquan , Wang Shiping , Zhao Liang , Duan Jichuang , Zhang Zhenhua , Ge Shidong , Zhu Xiaoxue 
Published: May 2015

AbstractUnderstanding the plant–pest interaction under warming with grazing conditions is critical to predict the response of alpine meadow to future climate change. We investigated the effects of experimental warming and grazing on the interaction between plants and the grassland caterpillar Gynaephora menyuanensis in an alpine meadow on the Tibetan Plateau in 2010 and 2011. Our results showed that grazing significantly increased nitrogen concentration in graminoids and sward openness with a lower sward height, sward coverage, and plant litter mass in the community. Grazing significantly increased G. menyuanensis body size and potential fecundity in 2010. The increases in female body size were about twofold greater than in males. In addition, grazing significantly increased G. menyuanensis density and its negative effects on aboveground biomass and graminoid coverage in 2011. We found that G. menyuanensis body size was significantly positively correlated with nitrogen concentration in graminoids but negatively correlated with plant litter mass. Even though warming did not significantly increased G. menyuanensis performance and the negative effects of G. menyuanensis on alpine meadow, the increases in G. menyuanensis growth rate and its negative effect on aboveground biomass under the warming with grazing treatment were significantly higher than those under the no warming with grazing treatment. The positive effects of grazing on G. menyuanensis performance and its damage were exacerbated by the warming treatment. Our results suggest that the fitness of G. menyuanensis would increase under future warming with grazing conditions, thereby posing a greater risk to alpine meadow and livestock production.