bluuebunny/crossref_metadata_2025_split huggingface dataset:
QbD‐based development of an extraction procedure for simultaneous quantification of telmisartan, amlodipine besylate and chlorthalidone in combination complex matrix formulation
Authors: Palakurthi Ashok Kumar , Dongala Thirupathi , Yalavarthi Ravindra Kumar , Anireddy Jayashree 
Published: November 2019

AbstractThe main objective of this study was to establish an efficient extraction procedure for the estimation of telmisartan, amlodipine and chlorthalidone from their combination in sample matrix using an analytical quality by design approach. Initial screening studies were performed for optimization of a suitable diluent to extract active components from sample matrix. Further, the same study was extended for the identification of critical method attributes and the factors affecting the analytical target profile. This study also explains the rugged and robust quantitative determination of combinations drugs with a shorter run time. The design of experimental studies confirms that the current center point parameters are well suited to recoveries. The chromatographic separation was achieved with an X‐Terra RP8, 150 × 4.6 mm, 3.5 μm column with an isocratic mobile phase (mixture of 20 mmaqueous ammonium acetate and acetonitrile). To demonstrate the stability‐indicating nature of the optimized method, forced degradation studies were conducted and proved. The optimized method was validated according to International Conference on Harmonization guidelines.
Analysis of five active ingredients of Er‐Zhi‐Wan, a traditional Chinese medicine water‐honeyed pill, using the biopharmaceutics classification system
Authors: Cao Xuexiao , Li Huanhuan , Wang Meng , Ren Xiaoliang , Deng Yanru 
Published: November 2019

AbstractEr‐Zhi‐Wan (EZW) is a traditional Chinese medicine with many clinical applications and used as a health product in East Asia. Five active ingredients (salidroside, specnuezhenide, nuezhenoside, luteolin, and oleanolic acid) were screened out from EZW to develop an in vitro rapid evaluation method for the classification of in vivo drug absorption behavior by biopharmaceutics classification system (BCS). Ultra‐performance liquid chromatography was used for quantitative analysis. Solubility and permeability were assayed by equilibrium solubility and multiple models: everted rat intestinal sac model, cultured Caco‐2 cells, octanol–water partition coefficient (LogP) method. The BCS properties of drugs were predicted using software applications, and the correlations of measured and predicted values of factors affecting oral drug absorption were calculated. The results were verified by measuring the absolute bioavailability of the active ingredients. Salidroside, specnuezhenide, and nuezhenoside were classified as BCS class III drugs, and luteolin was classified as a BCS class III/I drug because of the difference in LogP and intestinal permeability. Oleanolic acid was classified as a BCS class II/IV drug in acidic media and BCS class I/III drug in other media. Overall, EZW may be classified as a BCS class III drug, and permeability was identified as the primary factor limiting absorption. The results provide a novel method for the evaluation of the in vivo absorption of oral traditional Chinese medicines.
Similar overall survival with reduced vs. standard dose bevacizumab monotherapy in progressive glioblastoma
Authors: Gleeson Jack Patrick , Keane Fergus , Keegan Niamh M. , Mammadov Emin , Harrold Emily , Alhusaini Abdullah , Harte Jeffrey , Eakin‐Love Austin , O'Halloran Philip J. , MacNally Stephen , Hennessy Bryan T. , Breathnach Oscar S. , Grogan Liam , Morris Patrick G. 
Published: November 2019

AbstractIntroductionBevacizumab has demonstrated activity in glioblastoma (GBM), but the true benefits and optimal dose‐schedule are debated. A lower dose‐schedule than standard‐dose bevacizumab (10 mg/kg 2‐weekly) might offer similar benefits with lower costs. At our Institution, patients are randomly assigned at time of primary diagnosis to Neuro‐Oncologists, who have varying practices in terms of bevacizumab dose‐schedule upon progression.MethodsIn a retrospective analysis we examined overall survival (OS), measured from first administered bevacizumab dose until death, according to dose‐schedule. Patients with de novo WHO Grade IV GBM who received standard‐ or reduced‐dose (5 mg/kg 2‐weekly) bevacizumab were included. MGMT methylation status and time from diagnosis to bevacizumab start were examined as prognostic variables. Clinical benefit and a comparative cost analysis were assessed.ResultsIn total, 1127 bevacizumab doses were administered to 118 patients [Median: 7, Range: 1‐44]. Median OS (mOS) was 5.8 months. 69 (59%) patients received standard‐dose bevacizumab (mOS: 5.97 months) and 49 patients received reduced‐dose (mOS: 5.7 months). No statistically significant difference in OS between dosing schedule was seen (HR: 1.11, P‐value: .584). Patients with MGMT methylated tumors (43%) had improved OS compared to those with unmethylated tumors; 7.03 vs 4.97 months (HR: 0.61, P‐value: .027). If all patients were treated with reduced‐dose bevacizumab, an estimated €2.4M cost reduction would be observed.ConclusionsIn this retrospective study, reduced‐dose bevacizumab schedule resulted in similar OS to standard‐dose bevacizumab monotherapy with substantial cost savings. MGMT methylation appears to convey a survival benefit in the setting of bevacizumab treatment for progressive GBM.
Medulloblastoma has a global impact on health related quality of life: Findings from an international cohort
Authors: de Medeiros Cynthia B. , Moxon‐Emre Iska , Scantlebury Nadia , Malkin David , Ramaswamy Vijay , Decker Alexandra , Law Nicole , Kumabe Toshihiro , Leonard Jeffrey , Rubin Josh , Jung Shin , Kim Seung‐Ki , Gupta Nalin , Weiss William , Faria Claudia C. , Vibhakar Rajeev , Lafay‐Cousin Lucie , Chan Jennifer , Kros Johan M. , Janzen Laura , Taylor Michael D. , Bouffet Eric , Mabbott Donald J. 
Published: November 2019

AbstractBackgroundUnderstanding the global impact of medulloblastoma on health related quality of life (HRQL) is critical to characterizing the broad impact of this disease and realizing the benefits of modern treatments. We evaluated HRQL in an international cohort of pediatric medulloblastoma patients.MethodsSeventy‐six patients were selected from 10 sites across North America, Europe, and Asia, who participated in the Medulloblastoma Advanced Genomics International Consortium (MAGIC). The Health Utilities Index (HUI) was administered to patients and/or parents at each site. Responses were used to determine overall HRQL and attributes (ie specific subdomains). The impact of various demographic and medical variables on HRQL was considered—including molecular subgroup.ResultsThe majority of patients reported having moderate or severe overall burden of morbidity for both the HUI2 and HUI3 (HUI2 = 60%; HUI3 = 72.1%) when proxy‐assessed. Self‐care in the HUI2 was rated as higher (ie better outcome) for patients from Western versus Eastern sites, P = .02. Patients with nonmetastatic status had higher values (ie better outcomes) for the HUI3 hearing, HUI3 pain, and HUI2 pain, all P < .05. Patients treated with a gross total resection also had better outcomes for the HUI3 hearing (P = .04). However, those who underwent a gross total resection reported having worse outcomes on the HUI3 vision (P = .02). No differences in HRQL were evident as a function of subgroup.ConclusionsBy examining an international sample of survivors, we characterized the worldwide impact of medulloblastoma. This is a critical first step in developing global standards for evaluating long‐term outcomes.
Reduced PLCG1 expression is associated with inferior survival for myelodysplastic syndromes
Authors: Shiseki Masayuki , Ishii Mayuko , Miyazaki Mari , Osanai Satoko , Wang Yan‐Hua , Yoshinaga Kentaro , Mori Naoki , Tanaka Junji 
Published: November 2019

AbstractThe PLCG1 gene, which encodes the phospholipase C γ1 isoform, is located within the commonly deleted region of the long arm of chromosome 20 (del(20q)) observed in myelodysplastic syndromes (MDS). Phospholipase C is involved in diverse physiological and pathological cellular processes through inositide signaling. We hypothesized that reduced PLCG1 expression because of haploinsufficiency by del(20q) plays a role in the molecular pathogenesis of MDS. Therefore, we analyzed PLCG1 expression in bone marrow mononuclear cells at diagnosis in 116 MDS patients with or without del(20q) by quantitative RT‐PCR to evaluate its clinical significance. The expression level of PLCG1 was significantly lower not only in MDS patients with del(20q) but also in those without del(20q) compared to that of the controls, which suggests that reduced PLCG1 expression is a common molecular event in MDS. Patients in the lowest quartile (Q4) group for PLCG1 expression had lower overall survival (OS) compared to that of other patients (Q1‐Q3) (log‐rank test, P = .0004) with estimated median OS times of 22 in the Q4 group and 106 months in the Q1‐3 group. Univariate and multivariate analysis indicated reduced PLCG1 expression (Q4) was associated with lower OS (hazard ratio 2.58, 95% CI 1.35‐4.84, P = .0049), which suggests that reduced PLCG1 expression is an independent prognostic factor for OS. In addition, patients were well‐stratified for OS by combining PLCG1 expression level (Q4 vs Q1‐3) and bone marrow blast percentage (5% or more vs less than 5%). Thus, the level of PLCG1 expression at time of diagnosis is a prognostic biomarker for MDS.
Not all missed opportunities cast the same shadow: Voluntary inaction reduces the “sting” of missed sales promotions
Authors: Ford Weixing , Andrews Demetra , Sivaraman Anuradha , Krishnamurthy Parthasarathy 
Published: November 2019

AbstractHow do consumers who miss extremely attractive sales promotions respond to merely attractive opportunities they later encounter when prices return to higher levels? The literature on inaction inertia suggests that the more attractive the missed opportunity, the less likely a consumer is to accept the subsequently encountered inferior opportunity, indicating that consumers may stay undecided. Thus, consumers are believed to be negatively influenced by the shadow of the attractive opportunities they missed. This has adverse consequences for both consumer and firm welfare. Yet, we sometimes do see consumers buying even after missing a sale. We draw from the literature on regret and personal responsibility to hypothesize the conditions that would allow the consumer to remain uninfluenced by the attractiveness of the missed opportunity. In three studies, we find support for the idea that personal responsibility for missing the first opportunity allows consumers to be less influenced by its attractiveness when they see a second inferior opportunity compared to conditions in which they were not personally responsible for missing the first opportunity; this bodes well both for consumer and marketer welfare.
Application of modified alveolar ridge augmentation technique for horizontal bone augmentation in posterior mandibular region: Report of 3 cases
Authors: Chu Shunli , Xu Hongwei , Li Xianjing , Guo Tianqi , Ting Zhu , Zhou Yanmin 
Published: November 2019

AbstractThree cases with severe horizontal bone deficiency on mandibular posterior region were committed by modified alveolar ridge augmentation. The therapeutic outcomes show that it is an effective methodology in cases with compromised horizontal bone.
Ligands with Two Monoanionic N,N‐Binding Sites: Synthesis and Coordination Chemistry
Authors: Kretschmer Robert 
Published: November 2019

AbstractPolytopic ligands have become ubiquitous in coordination chemistry because they grant access to a variety of mono‐ and polynuclear complexes of transition metals as well as rare‐earth and main‐group elements. Nitrogen‐based ditopic ligands, in which two monoanionic N,N‐binding sites are framed within one molecule, are of particular importance and are therefore the primary focus of this review. In detail, bis(amidine)s, bis(guanidine)s, bis(β‐diimine)s, bis(aminotroponimine)s, bis(pyrrolimine)s, and miscellaneous bis(N,N‐chelating) ligands are reviewed. In addition to the general synthetic protocols, the application of these ligands is discussed along with their coordination chemistry, the multifarious binding modes, and the ability of these ligands to bridge two (or more) metal(loids).
A Quadrupolar Bis‐Triarylborane Chromophore as a Fluorimetric and Chirooptic Probe for Simultaneous and Selective Sensing of DNA, RNA and Proteins
Authors: Ban Željka , Griesbeck Stefanie , Tomić Sanja , Nitsch Jörn , Marder Todd B. , Piantanida Ivo 
Published: November 2019

AbstractA water‐soluble tetracationic quadrupolar bis‐triarylborane chromophore showed strong binding to ds‐DNA, ds‐RNA, ss‐RNA, as well as to the naturally most abundant protein, BSA. The novel dye can distinguish between DNA/RNA and BSA by fluorescence emission separated by Δ=3600 cm−1, allowing for the simultaneous quantification of DNA/RNA and protein (BSA) in a mixture. The applicability of such fluorimetric differentiation in vitro was demonstrated, strongly supporting a protein‐like target as a dominant binding site of1in cells. Moreover, our dye also bound strongly to ss‐RNA, with the unusual rod‐like structure of the dye, decorated by four positive charges at its termini and having a hydrophobic core, acting as a spindle for wrapping A, C and U ss‐RNAs, but not poly G, the latter preserving its secondary structure. To the best of our knowledge, such unmatched, multifaceted binding activity of a small molecule toward DNA, RNA, and proteins and the selectivity of its fluorimetric and chirooptic response makes the quadrupolar bis‐triarylborane a novel chromophore/fluorophore moiety for biochemical applications.
Highest and Fastest Removal Rate of PbII Ions through Rational Functionalized Decoration of a Metal–Organic Framework Cavity
Authors: Afshariazar Farzaneh , Morsali Ali , Wang Jun , Junk Peter C. 
Published: November 2019

AbstractTo overcome the challenge of developing a multipurpose adsorbent for effective removal of toxic and carcinogenic PbII ions from aqueous solutions, a made‐for‐purpose functional group (N1,N2‐di(pyridine‐4‐yl)oxalamide) was rationally designed and incorporated into the cavities of a Zn metal–organic framework (MOF), namely, TMU‐56. Large enough pore size along with high densities of strong metal chelating sites lead not only to the highest uptake capacity for PbII ions, but also the fastest removal rate that has ever been reported for functionalized MOFs, occurring in just 20 s. Moreover, high concentrations of lead ions favor the ion exchange reaction, resulting in a high degree of metal exchange. In addition, TMU‐56 can be a practical adsorbent because of its notable performance in the simultaneous removal of several toxic and carcinogenic heavy metals from wastewater, which has rare precedence.
Identifying models of trait‐mediated community assembly using random forests and approximate Bayesian computation
Authors: Ruffley Megan , Peterson Katie , Week Bob , Tank David C. , Harmon Luke J. 
Published: November 2019

AbstractEcologists often use dispersion metrics and statistical hypothesis testing to infer processes of community formation such as environmental filtering, competitive exclusion, and neutral species assembly. These metrics have limited power in inferring assembly models because they rely on often‐violated assumptions. Here, we adapt a model of phenotypic similarity and repulsion to simulate the process of community assembly via environmental filtering and competitive exclusion, all while parameterizing the strength of the respective ecological processes. We then use random forests and approximate Bayesian computation to distinguish between these models given the simulated data. We find that our approach is more accurate than using dispersion metrics and accounts for uncertainty in model selection. We also demonstrate that the parameter determining the strength of the assembly processes can be accurately estimated. This approach is available in the R package CAMI; Community Assembly Model Inference. We demonstrate the effectiveness of CAMI using an example of plant communities living on lava flow islands.
Nest attendance by tropical and temperate passerine birds: Same constancy, different strategy
Authors: Austin Suzanne H. , Robinson William Douglas , Ellis Vincenzo A. , Rodden Robinson Tara , Ricklefs Robert E. 
Published: November 2019

AbstractParental care in birds varies among species and geographic regions. Incubation behavior influences embryonic development rate and varies substantially among species.We studied attendance at the nest by videoing nests or collecting data from the literature for 112 species in north temperate and lowland tropical sites, then associated patterns of incubation on‐ and off‐bouts with species and environmental traits.Songbirds nesting at low elevations incubate their eggs for an average of 74.1% (±12.9 SD,n = 60 species) of the time in temperate regions and 71.0% (±12.2 SD,n = 52 species) in tropical regions during daylight hours, and 84.3% (±8.2 SD) and 85.3% (±6.2 SD), respectively, of each 24‐hr cycle.While these attendance percentages do not differ significantly between latitudes, our data also show that lowland tropical songbirds make fewer visits to the nest and, consequently, have longer on‐bouts and off‐bouts during incubation. This pattern in attendance reflects a latitudinal contrast in parental care strategy, where lowland tropical birds reduce visits to the nest by increasing on‐ and off‐bout lengths while maintaining the same proportion of time spent incubating their eggs (constancy).Similar constancy across latitude suggests that tropical and temperate birds may be similarly constrained to maintain elevated egg temperatures for normal embryo growth.The different attendance strategies adopted in each region may reflect differences in ambient temperature, adult foraging time, and nest predation rate. Consistently warm ambient temperatures likely allow tropical birds to take longer off‐bouts, and thereby to reduce activity around the nest, compared to temperate birds.
Mitogenomic phylogenetic analyses of Leptogorgia virgulata and Leptogorgia hebes (Anthozoa: Octocorallia) from the Gulf of Mexico provides insight on Gorgoniidae divergence between Pacific and Atlantic lineages
Authors: Silvestri Samantha , Figueroa Diego F. , Hicks David , Figueroa Nicole J. 
Published: November 2019

AbstractThe use of genetics in recent years has brought to light the need to reevaluate the classification of many gorgonian octocorals. This study focuses on two Leptogorgia species—Leptogorgia virgulata and Leptogorgia hebes—from the northwestern Gulf of Mexico (GOM). We target complete mitochondrial genomes and mtMutS sequences, and integrate this data with previous genetic research of gorgonian corals to resolve phylogenetic relationships and estimate divergence times. This study contributes the first complete mitochondrial genomes for L. ptogorgia virgulata and L. hebes. Our resulting phylogenies stress the need to redefine the taxonomy of the genus Leptogorgia in its entirety. The fossil‐calibrated divergence times for Eastern Pacific and Western Atlantic Leptogorgia species based on complete mitochondrial genomes shows that the use of multiple genes results in estimates of more recent speciation events than previous research based on single genes. These more recent divergence times are in agreement with geologic data pertaining to the formation of the Isthmus of Panama.
The combined use of raw and phylogenetically independent methods of outlier detection uncovers genome‐wide dynamics of local adaptation in a lizard
Authors: Llanos‐Garrido Alejandro , Pérez‐Tris Javier , Díaz José A. 
Published: November 2019

AbstractLocal adaptation is a dynamic process by which different allele combinations are selected in different populations at different times, and whose genetic signature can be inferred by genome‐wide outlier analyses. We combined gene flow estimates with two methods of outlier detection, one of them independent of population coancestry (CIOA) and the other one not (ROA), to identify genetic variants favored when ecology promotes phenotypic convergence. We analyzed genotyping‐by‐sequencing data from five populations of a lizard distributed over an environmentally heterogeneous range that has been changing since the split of eastern and western lineages ca. 3 mya. Overall, western lizards inhabit forest habitat and are unstriped, whereas eastern ones inhabit shrublands and are striped. However, one population (Lerma) has unstriped phenotype despite its eastern ancestry. The analysis of 73,291 SNPs confirmed the east–west division and identified nonoverlapping sets of outliers (12 identified by ROA and 9 by CIOA). ROA revealed ancestral adaptive variation in the uncovered outliers that were subject to divergent selection and differently fixed for eastern and western populations at the extremes of the environmental gradient. Interestingly, such variation was maintained in Lerma, where we found high levels of heterozygosity for ROA outliers, whereas CIOA uncovered innovative variants that were selected only there. Overall, it seems that both the maintenance of ancestral variation and asymmetric migration have counterbalanced adaptive lineage splitting in our model species. This scenario, which is likely promoted by a changing and heterogeneous environment, could hamper ecological speciation of locally adapted populations despite strong genetic structure between lineages.
Effect of altitude and soil properties on biomass and plant richness in the grasslands of Tibet, China, and Manang District, Nepal
Authors: Bhandari Jyoti , Zhang Yangjian 
Published: November 2019

AbstractA positive relationship between plant species richness and biomass has often documented in temperate grassland systems but is still largely lacking in the Himalayan region. Considering altitude and soil properties as major factors influencing species richness and biomass in the Himalayan grasslands, we tested the hypothesis that peak aboveground biomass and species richness increase with higher levels of soil nutrients and decrease with altitude. Our study was conducted in the grasslands of Tibet, China, and Manang District, Nepal, which represent, respectively, the northern and southern slopes of the central Himalayan grasslands. During the growing seasons, we measured vegetation aboveground biomass and soil properties along an altitudinal gradient on the northern slope in 2011 and 2012, and on the grasslands of the southern slope in 2017. Data were analyzed with a Spearman correlation analysis, classification and regression tree model, and the structural equation modeling (SEM) to identify the key factors determining aboveground biomass and species richness. The results demonstrated that aboveground biomass and species richness on the southern slope were significantly greater at the lowest altitude zone compared to middle and higher zones, whereas on the northern slope, aboveground biomass and species richness were not significantly different at three altitudinal zones. There was a significant positive correlation between aboveground biomass and species richness on both northern and southern slopes. However, the slope was found higher in grasslands of southern slope compared to the grasslands of northern slope. Classification and regression tree analysis and SEM indicated that altitude is most closely associated with large‐scale variations in aboveground biomass and species richness. The Spearman correlation analysis revealed that altitude and soil pH were negatively related to aboveground biomass in these grasslands. This study demonstrates that on northern and southern slopes of the Himalayan Range, a positive relation between plant species richness and biomass is determined more by altitude than soil nutrients.