bluuebunny/crossref_metadata_2025_split huggingface dataset:
ChemInform Abstract: Enantioselective Synthesis of Azaflavanones Using Organocatalytic 6‐endo Aza‐Michael Addition.
Authors: Cheng Shuanghua , Zhao Lili , Yu Shouyun 
Published: August 2014

AbstractThe optimized conditions allow the highly enantioselective conversion of 2‐aminochalcones into 2‐substituted azaflavanones via intramolecular 6‐endo aza‐Michael addition.
ChemInform Abstract: Direct sp3 C—H Acroleination of N‐Aryl‐tetrahydroisoquinolines by Merging Photoredox Catalysis with Nucleophilic Catalysis.
Authors: Feng Zhu‐Jia , Xuan Jun , Xia Xu‐Dong , Ding Wei , Guo Wei , Chen Jia‐Rong , Zou You‐Quan , Lu Liang‐Qiu , Xiao Wen‐Jing 
Published: August 2014

AbstractThe first example of sequence catalysis by merging visible light photoredox catalysis and nucleophilic catalysis is reported.
ChemInform Abstract: Sesquiterpenoids from the Fruits of Alpinia oxyphylla and Their anti‐Acetylcholinesterase Activity
Authors: Chen Ping , Wang Pei‐Pei , Jiao Ze‐Zhao , Xiang Lan 
Published: August 2014

Abstractisolation and structure elucidation of fourteen sesquiterpenoids including the novel terpenoids (I) and (II) and in vitro effects of twenty sesquiterpenoids on AChE activity
ChemInform Abstract: Cinanthrenol A, an Estrogenic Steroid Containing Phenanthrene Nucleus, from a Marine Sponge Cinachyrella sp.
Authors: Machida Koshi , Abe Takahiro , Arai Daisuke , Okamoto Mayumi , Shimizu Isao , de Voogd Nicole J. , Fusetani Nobuhiro , Nakao Yoichi 
Published: August 2014

AbstractThe isolation, structure elucidation and determination of the absolute configuration of the title compound (I) is described.
ChemInform Abstract: Stereoisomers of Ieodoglucomides A and B: Synthesis and Evaluation of Anticancer Activity.
Authors: Reddy Chada Raji , Jithender Enukonda , Singh Ashita , Ummanni Ramesh 
Published: August 2014

AbstractThe alpha‐isomers (Ia) and (Ib) of ieodoglucosamides A and B as well as their C14‐epimers (II) are prepared from glucose and tested on their anticancer activity (prostate cancer DU145, human lung carcinoma A549, breast cancer MCF‐7, human epithelial cervical cancer HeLa cells).
CFD modelling of continuous protein extraction process using liquid‐solid circulating fluidized beds
Authors: Dadashi Abbas , Zhu Jingxu , Zhang Chao 
Published: August 2014

AbstractA computational fluid dynamics (CFD) model was developed to describe the hydrodynamics and mass transfer in the process of continuous protein extraction from broth using a liquid‐solid circulating fluidized bed (LSCFB) ion exchange system. The CFD model took into account both the adsorption and desorption processes. The quantitative predictions for the protein concentration were compared favourably with the experimental data from a lab‐scale system. The model was used to investigate the effects of hydrodynamic and kinetic parameters on the performance of the LSCFB ion exchange system. It was demonstrated that the model is a robust tool to simulate, scale up, and optimize the LSCFB ion exchange systems for protein extraction process.
Aptamers as Drug Delivery Vehicles
Authors: Kruspe Sven , Mittelberger Florian , Szameit Kristina , Hahn Ulrich 
Published: August 2014

AbstractThe benefits of directed and selective therapy for systemic treatment are reasons for increased interest in exploiting aptamers for cell‐specific drug delivery. Nucleic acid based pharmaceuticals represent an interesting and novel tool to counter human diseases. Combining inhibitory potential and cargo transfer upon internalization, nanocarriers as well as various therapeutics including siRNAs, chemotherapeutics, photosensitizers, or proteins can be imported via these synthetic nucleic acids. However, widespread clinical application is still hampered by obstacles that must be overcome. In this review, we give an overview of applications and recent advances in aptamer‐mediated drug delivery. We also introduce prominent selection methods as well as useful approaches in choice of drug and conjugation method. We discuss the challenges that need to be considered and present strategies that have been applied to achieve intracellular delivery of effectors transported by readily internalized aptamers.
Design and Characterization of a Twin Ribozyme for Potential Repair of a Deletion Mutation within the Oncogenic CTNNB1‐ΔS45 mRNA
Authors: Balke Darko , Zieten Irene , Strahl Anne , Müller Oliver , Müller Sabine 
Published: August 2014

AbstractRNA repair is an emerging strategy for gene therapy. Conventional gene therapy typically relies on the addition of the corrected DNA sequence of a defective gene to restore gene function. As an additional option, RNA repair allows alteration of the sequence of endogenous messenger RNAs (mRNAs). mRNA sequence alteration is either facilitated by intracellular spliceosome machinery or by the intrinsic catalytic activity of trans‐acting ribozymes. Previously we developed twin ribozymes, derived from the hairpin ribozyme, by tandem duplication and demonstrated their potential for patchwise RNA repair. Herein we describe the development of such a twin ribozyme for potential repair of a deletion mutation in the oncogenic CTNNB1‐ΔS45 mRNA. We demonstrate that hairpin ribozyme units within the twin ribozyme can be adapted to efficiently cleave/ligate non‐consensus substrates by introduction of compensatory mutations in the ribozyme. Thus, we show the twin ribozyme mediated repair of truncated CTNNB1 transcripts (up to 1000 nt length). Repair of the entire CTNNB1‐ΔS45 mRNA, although apparently possible in general, is hampered in vitro by the secondary structure of the transcript.
Poor outcome and death among youth, young adults, and midlife adults with eating disorders: An investigation of risk factors by age at assessment
Authors: Ackard Diann M. , Richter Sara , Egan Amber , Cronemeyer Catherine 
Published: August 2014

ABSTRACTObjectiveEating disorders (EDs) present across a broad age range, yet little is known about the characteristics and outcome of midlife patients compared to younger patients. Among patients seeking ED treatment who were stratified by age at initial assessment (IA), this study aimed to (1) discern sociodemographic and clinical differences, (2) determine outcome rates, and (3) identify predictors of poor outcome including death.MethodParticipants [219 females (12 years or older, 94.1% Caucasian) who completed outcome assessment and 31 known decedents] were stratified by age at IA (<18 as youth, 18–39 as young adult, and ≥40 years as midlife adult). Analyses of variance and chi‐square tests identified group differences; ordered logistic regression with stepwise selection identified factors predicting outcome.ResultsMidlife adults were more significantly compromised at follow‐up compared to youths and young adults, including psychological and physical quality of life, ineffectiveness, interpersonal concerns, and general psychological maladjustment. Midlife adults had the highest rates of poor outcome or death; good outcome was achieved by only 5.9% of midlife adult compared to 14.0% of young adult and 27.5% of youth patients. Older age at IA, alcohol and/or drug misuse, endocrine concerns, and absence of family ED history predicted poor outcome or death.DiscussionMidlife adults seeking ED treatment have more complex medical and psychological concerns and poorer outcomes than youths and young adults; further exploration is needed to improve treatment outcome. Specialized treatment focusing on quality of life, comorbid medical concerns, interpersonal connection, and emotion regulation is encouraged. © 2014 Wiley Periodicals, Inc. Int J Eat Disord 2014; 47:825–835
Coronary artery disease and 10‐year outcome after hospital admission for heart failure with preserved and with reduced ejection fraction
Authors: Rusinaru Dan , Houpe David , Szymanski Catherine , Lévy Franck , Maréchaux Sylvestre , Tribouilloy Christophe 
Published: August 2014

AbstractAimsThe prognostic impact of coronary artery disease (CAD) in heart failure is debated. Whereas causes of death have been well described in patients with cardiomyopathy, little is known about how CAD influences causes of death in heart failure with preserved ejection fraction (HFPEF). We undertook a 10‐year study and analysed causes of death in relation with CAD in HFPEF and in heart failure with reduced ejection fraction (HFREF).Methods and ResultsOur prospective analysis included 591 consecutive patients (320 HFPEF and 271 HFREF) hospitalized for the first time for heart failure during 2000 and followed for 10 years. History of CAD was documented in 25% of HFPEF and 39% of HFREF patients (P < 0.001). Overall, CAD was independently predictive of all‐cause and cardiovascular death. CAD had powerful prognostic impact in HFREF [adjusted hazard ratio (HR) 1.60 (1.19–2.15) for all‐cause death, and adjusted HR 2.01 (1.38–2.92) for cardiovascular death]. In HFPEF, the association between CAD and cardiovascular death was no longer observed after adjustment [adjusted HR 1.01 (0.69–1.50)]. In HFREF, CAD was associated with increased risk of heart failure‐related (adjusted HR 2.03 (1.21–3.43)] and myocardial infarction‐related fatal events [adjusted HR 3.84 (1.16–12.7)], while HFPEF patients with CAD appeared at greater risk of sudden death [adjusted HR 2.22 (1.05–4.95)].ConclusionThe prognostic impact of CAD is different in HFPEF compared with HFREF. Patients with HFPEF and CAD are at high risk of cardiovascular death, especially sudden death.
Drinking From the Holy Grail: Analysis of Whole‐Genome Sequencing From the Genetic Analysis Workshop 18
Authors: Paterson Andrew D. 
Published: August 2014

ABSTRACTThe Genetic Analysis Workshops distribute real and simulated human genetic data to allow the development and comparison of methods to detect genetic variants and genes related to biological traits; the results are then presented and discussed at a biennial meeting. The data made available for Genetic Analysis Workshop 18 (GAW18) included whole‐genome sequence data for odd‐numbered autosomes from 20 large Mexican American pedigrees selected through probands with type 2 diabetes. Real and simulated blood pressure phenotype data were provided to allow the comparison of methods to detect variants and genes associated with blood pressure. Some of the complexity present in the data includes related individuals, repeated quantitative trait outcomes, covariates, medication effects, pharmacokinetic effects, missing data, admixed population, and imputed genotypes. A wide range of analytic approaches were applied to the data. Contributions that focused only on a subset of up to 155 unrelated subjects from the pedigrees were faced with low power. One recommendation for future analysis is the use of the provided null phenotype to allow comparison of type I error across methods. Collaboration between statistical geneticists and molecular biologists or bioinformaticians would provide helpful input to place variants in genes for gene‐based association tests.
Methods for Collapsing Multiple Rare Variants in Whole‐Genome Sequence Data
Authors: Sung Yun Ju , Korthauer Keegan D. , Swartz Michael D. , Engelman Corinne D. 
Published: August 2014

ABSTRACTGenetic Analysis Workshop 18 provided whole‐genome sequence data in a pedigree‐based sample and longitudinal phenotype data for hypertension and related traits, presenting an excellent opportunity for evaluating analysis choices. We summarize the nine contributions to the working group on collapsing methods, which evaluated various approaches for the analysis of multiple rare variants. One contributor defined a variant prioritization scheme, whereas the remaining eight contributors evaluated statistical methods for association analysis. Six contributors chose the gene as the genomic region for collapsing variants, whereas three contributors chose nonoverlapping sliding windows across the entire genome. Statistical methods spanned most of the published methods, including well‐established burden tests, variance‐components‐type tests, and recently developed hybrid approaches. Lesser known methods, such as functional principal components analysis, higher criticism, and homozygosity association, and some newly introduced methods were also used. We found that performance of these methods depended on the characteristics of the genomic region, such as effect size and direction of variants under consideration. Except for MAP4 and FLT3, the performance of all statistical methods to identify rare casual variants was disappointingly poor, providing overall power almost identical to the type I error. This poor performance may have arisen from a combination of (1) small sample size, (2) small effects of most of the causal variants, explaining a small fraction of variance, (3) use of incomplete annotation information, and (4) linkage disequilibrium between causal variants in a gene and noncausal variants in nearby genes. Our findings demonstrate challenges in analyzing rare variants identified from sequence data.
Summary of Results and Discussions From the Gene‐Based Tests Group at Genetic Analysis Workshop 18
Authors: Cordell Heather J. 
Published: August 2014

ABSTRACTI present a summary of the results and discussions held within the working group on gene‐based tests at Genetic Analysis Workshop 18 (GAW18). The main focus of interest in our working group was modeling the action of combinations or “groups” of genetic variants, with a group of variants most often defined as a set of single‐nucleotide polymorphisms lying within a known gene. Some contributions investigated the performance of previously proposed methods (particularly rare variant collapsing or burden‐type methods) for addressing this question, applied to the GAW18 data, and other contributions developed novel approaches and addressed novel questions. Most approaches were successful in detecting significant effects at MAP4 in the simulated data. No other genetic effects were consistently detected across different analyses. Low power was noted, particularly for those methods that restricted analysis to purely the subset of unrelated individuals.
Longitudinal Data Analysis in Genome‐Wide Association Studies
Authors: Beyene Joseph , Hamid Jemila S. 
Published: August 2014

ABSTRACTGenome‐wide association studies have led to the discovery of thousands of susceptibility genetic variants (typically single‐nucleotide polymorphisms [SNPs]) for a wide range of complex diseases and traits commonly measured at a single point in time. Although many novel genotype‐phenotype associations have been identified and successfully replicated using cross‐sectionally measured phenotypes, there is growing interest in the study of longitudinally measured phenotypes because these allow for the study of the natural trajectory of traits and disease progression. However, there are several challenges with analysis and interpretation of longitudinal data. Here, we summarize the methods and strategies proposed and applied in genome‐wide association studies of blood pressure related phenotypes made available through Genetic Analysis Workshop 18 (GAW18). The investigators considered methods that incorporated correlation across time points and familial relatedness among the individuals into their studies and compared their approaches with single‐time‐point analysis using baseline data. Some of the studies used unrelated individuals; some also used the simulated data provided by the GAW18 organizers to assess type I error and power of their approach in detecting true associations.
Longitudinal Data Analysis for Genetic Studies in the Whole‐Genome Sequencing Era
Authors: Wu Zheyang , Hu Yijuan , Melton Phillip E. 
Published: August 2014

ABSTRACTThe analysis of whole‐genome sequence (WGS) data using longitudinal phenotypes offers a potentially rich resource for the examination of the genetic variants and their covariates that affect complex phenotypes over time. We summarize eight contributions to the Genetic Analysis Workshop 18, which applied a diverse array of statistical genetic methods to analyze WGS data in combination with data from genome‐wide association studies (GWAS) from up to four different time points on blood pressure phenotypes. The common goal of these analyses was to develop and apply appropriate methods that utilize longitudinal repeated measures to potentially increase the analytic efficiency of WGS and GWAS data. These diverse methods can be grouped into two categories, based on the way they model dependence structures: (1) linear mixed‐effects (LME) models, where the random effect terms in the linear models are used to capture the dependence structures; and (2) variance‐components models, where the dependence structures are constructed directly based on multiple components of variance‐covariance matrices for the multivariate Gaussian responses. Despite the heterogeneous nature of these analytical methods, the group came to the following conclusions: (1) the use of repeat measurements can gain power to identify variants associated with the phenotype; (2) the inclusion of family data may correct genotyping errors and allow for more accurate detection of rare variants than using unrelated individuals only; and (3) fitting mixed‐effects and variance‐components models for longitudinal data presents computational challenges. The challenges and computational burden demanded by WGS data were addressed in the eight contributions.
Antagonism of D1/D5 receptors prevents long‐term depression (LTD) and learning‐facilitated LTD at the perforant path–dentate gyrus synapse in freely behaving rats
Authors: Wiescholleck Valentina , Manahan‐Vaughan Denise 
Published: August 2014

ABSTRACTHippocampal synaptic plasticity, in the form of long‐term potentiation (LTP) and long‐term depression (LTD), enables spatial memory formation, whereby LTP and LTD are likely to contribute different elements to the resulting spatial representation. Dopamine, released from the ventral tegmental area particularly under conditions of reward, acts on the hippocampus, and may specifically influence the encoding of information into long‐term memory. The dentate gyrus (DG), as the “gateway” to the hippocampus is likely to play an important role in this process. D1/D5 dopamine receptors are importantly involved in the regulation of synaptic plasticity thresholds in the CA1 region of the hippocampus and determine the direction of change in synaptic strength that occurs during novel spatial learning. Here, we explored whether D1/D5‐receptors influence LTD that is induced in the DG following patterned afferent stimulation of the perforant path of freely behaving adult rats, or influence LTD that occurs in association with spatial learning. We found that LTD that is induced by afferent stimulation, and LTD that is facilitated by learning about novel landmark configurations, were both prevented by D1/D5‐receptor antagonism, whereas agonist activation of the D1/D5‐receptor had no effect on basal tonus or short‐term depression. Other studies have reported that in the DG, D1/D5‐receptor agonism or antagonism do not affect LTP, but agonism prevents depotentiation. These findings suggest that the dopaminergic system, acting via D1/D5‐receptors, influences information gating by the DG and modulates the direction of change in synaptic strength that underlies information storage in this hippocampal substructure. Information encoded by robust forms of LTD is especially dependent on D1/D5‐receptor activation. Thus, dopamine acting on D1/D5‐receptors is likely to support specific experience‐dependent encoding, and may influence the content of hippocampal representations of experience. © 2014 The Authors. Hippocampus Published by Wiley Periodicals, Inc.
Pharmacokinetic profile and first preliminary clinical evaluation of bendamustine in Taiwanese patients with heavily pretreated indolent B‐cell non‐Hodgkin lymphoma and mantle cell lymphoma
Authors: Hsiao Liang‐Tsai , Tien Hwei‐Fang , Kuo Ching‐Yuan , Wu Jin‐Hou , Hou Hsin‐An , Wang Ming‐Chung , Liu Chun‐Yu , Chen Po‐Min , Chiou Tzeon‐Jye 
Published: August 2014

AbstractPrior studies found bendamustine is efficacious in patients with indolent B‐cell non‐Hodgkin lymphoma (NHL). To date, no studies have reported the efficacy of bendamustine in a Chinese population. This multicentre phase II trial evaluated the pharmacokinetics (PK), safety and efficacy of bendamustine monotherapy in Chinese patients in Taiwan with pretreated indolent B‐cell NHL or mantle cell lymphoma (MCL). For PK assessments, patients were randomized (n = 16; 11 with indolent B‐cell NHL and five with MCL) to 90 or 120 mg/m2 of bendamustine for the first cycle. Plasma levels of bendamustine and its two metabolites were analyzed. For efficacy and safety evaluations, bendamustine 120 mg/m2 was given to all patients every 3 weeks starting at cycle 2 for a minimum of a total of six cycles. The median age of patients was 61.7 years, and the majority were men (75%). The median number of prior treatments was 4 (range, 1–9 regimens), and all patients were previously treated with rituximab. Bendamustine plasma concentration peaked near the end of infusion and was rapidly eliminated with a mean elimination half‐life (t1/2) of 0.67–0.8 h. Of the evaluable patients (n = 14), the overall response rate was 78.6%, including 7.2% of patients having a complete response. Mean progression‐free survival was 27.5 weeks. The most common grade 3–4 adverse events were leucopenia (56.3%), neutropenia (56.3%) and thrombocytopenia (25%). In conclusion, bendamustine was efficacious and well tolerated in Taiwanese patients with indolent NHL and MCL with a similar PK profile to that of other populations. Copyright © 2014 John Wiley & Sons, Ltd.
How do supply‐side factors influence informal payments for healthcare? The case of HIV patients in Cameroon
Authors: Kankeu Hyacinthe Tchewonpi , Boyer Sylvie , Fodjo Toukam Raoul , Abu‐Zaineh Mohammad 
Published: August 2014

SummaryDirect out‐of‐pocket payments for healthcare continue to be a major source of health financing in low‐income and middle‐income countries. Some of these direct payments take the form of informal charges paid by patients to access the needed healthcare services. Remarkably, however, little is known about the extent to which these payments are exercised and their determinants in the context of Sub‐Saharan Africa. This study attempts therefore to shed light on the role of supply‐side factors in the occurrence of informal payments while accounting for the demand‐side factors. The study relies on data taken from a nationally representative survey conducted among people living with HIV/AIDS in Cameroon. A multilevel mixed‐effect logistic model is employed to identify the factors associated with the incidence of informal payments. Results reveal that circa 3.05% of the surveyed patients incurred informal payments for the consultations made on the day of the survey. The amount paid informally represents up to four times the official tariff. Factors related to the following: (i) human resource management of the health facilities (e.g., task shifting); (ii) health professionals' perceptions vis‐à‐vis the remunerations of HIV care provision; and (iii) reception of patients (e.g., waiting time) significantly influence the probability of incurring informal payments. Also of note, the type of healthcare facilities is found to play a role: informal payments appear to be significantly lower in private non‐profit facilities compared with those belonging to public sector. Our findings allude to some policy recommendations that can help reduce the incidence of informal payments. Copyright © 2014 John Wiley & Sons, Ltd.