bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacological characterization of ZYDPLA1, a novel long‐acting dipeptidyl peptidase‐4 inhibitor
Authors: Jain Mukul R. , Joharapurkar Amit A. , Bahekar Rajesh H. , Patel Harilal , Jadav Pradip , Kshirsagar Samadhan G. , Patel Vishal J. , Patel Kartikkumar N. , Ramanathan Vikram K. , Patel Pankaj R. , Desai Ranjit C. 
Published: October 2014

AbstractObjectiveDipeptidyl peptidase‐4 (DPP‐4) is responsible for degradation of glucagon‐like peptide 1 (GLP‐1) and gastric inhibitory polypeptide (GIP), the endogenous incretins that stimulate glucose‐dependent insulin secretion. The objective was to evaluate preclinical profile of a novel DPP‐4 inhibitor ZYDPLA1.MethodsIn vitro inhibition potency and selectivity were assessed using recombinant enzymes and/or plasma. In vivo efficacy was determined in oral glucose tolerance test or mixed meal tolerance test in C57BL/6J mice, db/db mice and Zucker fatty rats. Pharmacokinetics/pharmacodynamics was studied in mice, rats, dogs, and non‐human primates.ResultsZYDPLA1 is a potent, competitive and long acting inhibitor of DPP‐4 (Ki 0.0027 μM; Koff 2.3 × 10–4 s–1). ZYDPLA1 was more than 7000‐fold selective for recombinant DPP‐4 relative to DPP‐8 and DPP‐9, and more than 60 000‐fold selective relative to fibroblast activation protein (FAP) in vitro. DPP‐4 inhibition was comparable across species. In vivo, oral ZYDPLA1 elevated circulating GLP‐1 and insulin levels in mice and rats and showed dose‐dependent anti‐hyperglycemic effect. Anti‐hyperglycemic effect was also observed in db/db mice and Zucker fatty rats. ZYDPLA1 showed low clearance, large volume of distribution, and a long half‐life with excellent oral bioavailability in all species. It significantly inhibited plasma DPP‐4 activity in mice and rats for more than 48 h, and for up to 168 h in dogs and non‐human primates. Allometric scaling predicted a half‐life in humans of 53 to 166 h.ConclusionZYDPLA1 is a potent, selective, long‐acting oral DPP‐4 inhibitor with potential to become once‐a‐week therapy for treatment of type 2 diabetes mellitus.
Replication levels, false presences and the estimation of the presence/absence from eDNA metabarcoding data
Authors: Ficetola Gentile F. , Pansu Johan , Bonin Aurélie , Coissac Eric , Giguet‐Covex Charline , De Barba Marta , Gielly Ludovic , Lopes Carla M. , Boyer Frédéric , Pompanon François , Rayé Gilles , Taberlet Pierre 
Published: October 2014

AbstractEnvironmental DNA (eDNA) metabarcoding is increasingly used to study the present and past biodiversity. eDNA analyses often rely on amplification of very small quantities or degraded DNA. To avoid missing detection of taxa that are actually present (false negatives), multiple extractions and amplifications of the same samples are often performed. However, the level of replication needed for reliable estimates of the presence/absence patterns remains an unaddressed topic. Furthermore, degraded DNA and PCR/sequencing errors might produce false positives. We used simulations and empirical data to evaluate the level of replication required for accurate detection of targeted taxa in different contexts and to assess the performance of methods used to reduce the risk of false detections. Furthermore, we evaluated whether statistical approaches developed to estimate occupancy in the presence of observational errors can successfully estimate true prevalence, detection probability and false‐positive rates. Replications reduced the rate of false negatives; the optimal level of replication was strongly dependent on the detection probability of taxa. Occupancy models successfully estimated true prevalence, detection probability and false‐positive rates, but their performance increased with the number of replicates. At least eight PCR replicates should be performed if detection probability is not high, such as in ancient DNA studies. Multiple DNA extractions from the same sample yielded consistent results; in some cases, collecting multiple samples from the same locality allowed detecting more species. The optimal level of replication for accurate species detection strongly varies among studies and could be explicitly estimated to improve the reliability of results.
Nucleotide variability and gene expression reveal new putative genes related to seed shattering in weedy rice
Authors: Nunes A.L. , Markus C. , Delatorre C.A. , Merotto A. 
Published: October 2014

AbstractSeed shattering is one of the main traits related with the domestication of cultivated rice and with the invasiveness and persistence of weedy rice. Two independent studies in 2006 have indicated that qSH1 in Japonica and Sh4 in Indica rice are major genes governing this trait. However, a wide variation of seed shattering occurs in weedy rice ecotypes from the same geographic region and even within the same ecotype. The aim of this study was to evaluate the nucleotide variability of known and putative genes related to seed shattering in cultivated rice and to identify and validate new genes related to this trait in weedy rice. The qSH1 gene was not associated with seed shattering in the evaluated genotypes. The nucleotide variability of the genes Os01g0849100 and Os08g0512400, previously identified based on a genome‐wide resequencing study, was related to seed shattering in rice. The nucleotide variability of three single nucleotide polymorphisms (SNPs) of the OsXTH8 gene, which is related to cell wall biosynthesis, was not associated with seed shattering. However, the high expression of this gene was related to the occurrence of this trait. This study evaluated jointly a series of genes involved in rice seed shattering and indicated that the genes OsXTH8, Os08g0512400 and Os01g0849100 are important for the regulation of this trait in weedy rice in addition to previously described genes. Seed shattering in weedy rice has a more complex regulation than in cultivated rice where few major genes were identified.
Prospection and molecular analysis of CpGV isolates infecting Cydia pomonella at different geographical locations in Argentina
Authors: Arneodo J.D. , De Anna J. , Salvador R. , Farinon M. , Quintana G. , Sciocco‐Cap A. 
Published: October 2014

AbstractThe occurrence and genetic diversity of Cydia pomonella granulovirus infecting C. pomonella across Argentina were investigated. Larvae were collected from fruit orchards in regions where CpGV‐based biopesticides have been extensively used and then discontinued (Catamarca) or are still being used (Alto Valle). The survey was also extended to regions where few occasional (i.e. Mendoza) or no virus treatments (various locations) have been made. PCR analysis showed an unexpectedly high proportion of infected larvae (31.3–50%) at most sampling sites in Catamarca. Phylogenetic analysis of these samples, based on gran and lef‐8 genes partial sequences, revealed a previously unreported CpGV variant which could not be assigned to any of the known CpGV genome types and formed a well‐defined new cluster. Instead, samples from Alto Valle were genetically similar to isolate CpGV‐M (the active ingredient in commercial formulations). There, the percentage of infected individuals was considerably lower (1.8–21.9%). The virus was not detected in Mendoza or the other sampling regions. Implications of these results on the epidemiology and current classification of CpGV isolates are discussed.
Differential functional role of purinergic and nitrergic inhibitory cotransmitters in human colonic relaxation
Authors: Mañé N. , Gil V. , Martínez‐Cutillas M. , Clavé P. , Gallego D. , Jiménez M. 
Published: October 2014

AbstractAimATP and nitric oxide (NO) are released from enteric inhibitory motor neurones and are responsible for colonic smooth muscle relaxation. However, how frequency of neural stimulation affects this cotransmission process and the post‐junctional responses has not been systematically characterized in the human colon.MethodsThe dynamics of inhibitory cotransmission were studied using different protocols of electrical field stimulation (EFS) to characterize the inhibitory junction potentials (IJP) and the corresponding relaxation in colonic strips obtained from 36 patients.ResultsSingle pulses elicited a fast IJP (IJPfMAX = −27.6 ± 1.6 mV), sensitive to the P2Y1 antagonist MRS2500 1 μm, that ran down with frequency increase leaving a residual hyperpolarization at high frequencies (IJPf∞ = −3.7 ± 0.6 mV). Accordingly, low frequencies of EFS caused purinergic transient relaxations that cannot be maintained at high frequencies. Addition of the P2Y1 agonist MRS2365 10 μm during the purinergic rundown did not cause any hyperpolarization. Protein kinase C (PKC), a putative P2Y1 desensitizator, was able to reduce the amplitude of the IJPf when activated, but the rundown was not modified by PKC inhibitors. Frequencies higher than 0.60 ± 0.15 Hz were needed to evoke a sustained nitrergic hyperpolarization that progressively increased reaching IJPs∞ = −13 ± 0.4 mV at high frequencies and leading to a sustained inhibition of spontaneous motility.ConclusionChanges in frequency of stimulation possibly mimicking neuronal firing will post‐junctionally determine purinergic vs. nitrergic responses underlying different functional roles. NO will be responsible for sustained relaxations needed in physiological processes such as storage, while purinergic neurotransmission evoking sharp transient relaxations will be dominant in processes such as propulsion.
Dynamic changes of the inflammation‐based index predict mortality following chemoembolisation for hepatocellular carcinoma: a prospective study
Authors: Pinato D. J. , Karamanakos G. , Arizumi T. , Adjogatse D. , Kim Y. W. , Stebbing J. , Kudo M. , Jang J. W. , Sharma R. 
Published: October 2014

SummaryBackgroundTransarterial chemoembolisation (TACE) is a standard treatment for unresectable, intermediate stage hepatocellular carcinoma (HCC). Survival after TACE, however, can be highly variable, with no suitable biomarker predicting therapeutic outcome. The inflammation‐based index (IBI) has previously been shown to independently predict overall survival (OS) in all stages of HCC.AimTo explore the prognostic ability of IBI as a predictor of survival after TACE.MethodsBaseline staging, biochemical and clinicopathological features including IBI were studied in a derivation set of 64 patients undergoing TACE for intermediate stage HCC. Dynamic changes in IBI before and after TACE were studied as predictors of survival using both a univariate and multivariate Cox regression model and further validated in two independent patient cohorts from Korea (n = 76) and Japan (n = 577).ResultsPre‐treatment IBI predicted for OS in the derivation set (P = 0.001). Other univariate predictors of OS included radiological response to TACE (P < 0.001), pre‐TACE CLIP score (P < 0.01), tumour diameter >5 cm (P = 0.05) and AFP ≥400 (P < 0.001). Normalisation of IBI post‐TACE was associated with radiological response by mRECIST criteria and improved OS (P < 0.001). Normalisation of IBI remained a significant multivariate predictor of OS in both the derivation and validation sets (P < 0.001).ConclusionsNormalisation of IBI after TACE is shown to be an independent predictor of survival and may be integrated into the retreatment criteria for repeat TACE in intermediate stage HCC. IBI and its dynamic changes after treatment are validated as a biomarker allowing the stratification of patients with a significant survival advantage following initial TACE.
Structured Functional Principal Component Analysis
Authors: Shou Haochang , Zipunnikov Vadim , Crainiceanu Ciprian M. , Greven Sonja 
Published: October 2014

Summary
Motivated by modern observational studies, we introduce a class of functional models that expand nested and crossed designs. These models account for the natural inheritance of the correlation structures from sampling designs in studies where the fundamental unit is a function or image. Inference is based on functional quadratics and their relationship with the underlying covariance structure of the latent processes. A computationally fast and scalable estimation procedure is developed for high-dimensional data. Methods are used in applications including high-frequency accelerometer data for daily activity, pitch linguistic data for phonetic analysis, and EEG data for studying electrical brain activity during sleep.
Adverse effects of androgen‐deprivation therapy in prostate cancer and their management
Authors: Rhee Handoo , Gunter Jennifer H. , Heathcote Peter , Ho Ken , Stricker Phillip , Corcoran Niall M. , Nelson Colleen C. 
Published: October 2014

ObjectiveTo provide an up‐to‐date summary of current literature on the management of adverse effects of androgen‐deprivation therapy (ADT).Patients and MethodsAll relevant medical literature on men with prostate cancer treated with ADT from 2005 to 2014, and older relevant papers, were reviewed. Recent health advisory statements from the Australian government, societies and advocacy groups have been incorporated to the document.ResultsThere are numerous adverse effects of ADT that require pro‐active prevention and treatment. Ranging from cardiovascular disease, diabetes and osteoporosis, to depression, cognitive decline and sexual dysfunction, the range of adverse effects is wide. Baseline assessment, monitoring, prevention and consultation from a multidisciplinary team are important in minimising the harm from ADT.ConclusionsThis review provides a series of practical recommendations to assist with managing the adverse effects of ADT.
Diacylglycerol kinase κ (DGKK) variants and hypospadias in Han Chinese: association and meta‐analysis
Authors: Ma Qichao , Tang Yunman , Lin Houwei , Xu Maosheng , Xu Guofeng , Fang Xiaoliang , Chen Jianhua , Song Zhijian , Li Zhiqiang , Shi Yongyong , Geng Hongquan 
Published: October 2014

ObjectiveTo investigate whether diacylglycerol kinase κ (DGKK) is a susceptibility gene for hypospadias in the Han Chinese population as has been suggested by previous publications.Patients Subjects and MethodsA case‐control study involving 466 patients with hypospadias and 402 healthy subjects was conducted to assess the relationship between DGKK single nucleotide polymorphisms (SNPs) and hypospadias risk in the Han Chinese population. The 466 hypospadias patients were further divided into mild, moderate and severe subgroups for analysis.ResultsSix SNPs (rs1934179, rs4143304, rs9969978, rs1934188, rs4826632 and rs4599945) were marginally associated with mild and moderate hypospadias [odds ratios (ORs) > 1, P = 0.05 to P < 0.1), whereas no significant relationship was seen with the severe cases (ORs >1, P > 0.1). After correcting for multiple testing, it was determined that neither individual SNPs nor individual haplotypes were associated with hypospadias. To evaluate this relationship in multiple populations, we performed a meta‐analysis on six SNPs, using combined data from our present results and those of previous studies of different races (including 1966 patients and 2492 controls). Six SNPs (rs1934179, rs4143304, rs9969978, rs1934188, rs7063116 and rs1934190) were significantly associated with mild/moderate hypospadias (ORs >1, P < 0.05), and rs1934179 was significantly associated with severe hypospadias (OR > 1, P < 0.05).ConclusionsDGKK gene variants do not appear to play a major role in hypospadias susceptibility in the Chinese Han population. Our meta‐analysis supports the hypothesis that DGKK is a common risk gene for hypospadias, particularly in cases of mild or moderate hypospadias in Caucasian populations.
International multicentre psychometric evaluation of patient‐reported outcome data for the treatment of Peyronie's disease
Authors: Kueronya Verena , Miernik Arkadius , Stupar Slavisa , Kojovic Vladimir , Hatzichristodoulou Georgios , Egydio Paulo H. , Tosev Georgi , Falcone Marco , De Luca Francesco , Mulalic Demir , Djordjevic Miroslav , Schoenthaler Martin , Fahr Christian , Kuehhas Franklin E. 
Published: October 2014

ObjectiveTo compare patient‐reported outcomes (PROs) of surgical correction of Peyronie's disease (PD) with the Nesbit procedure, plaque incision and grafting, and the insertion of a malleable penile implant after surgical correction of penile curvature.Patients and MethodsWe performed a retrospective review of men who underwent surgical correction of PD between January 2010 and December 2012 at six international centres. Treatment‐related PROs and satisfaction were evaluated with a non‐validated questionnaire.ResultsThe response rate to the questionnaire was 70.9%, resulting in a study cohort of 206 patients. The Nesbit procedure, plaque incision with grafting, or implantation of a malleable penile prosthesis was performed in 50, 48, and 108 patients, respectively. Overall, 79.1% reported a subjective loss of penile length due to PD preoperatively (range 2.1–3.2 cm). Those patients treated with a malleable penile implant reported the greatest subjective penile length loss, due to PD. A subjective loss of penile length of >2.5 cm resulted in reduced preoperative sex ability. Postoperatively, 78.0%, 29.2% and 24.1% patients in the Nesbit, grafting, and implant groups reported a postoperative, subjective loss of penile length (range 0.4–1.2 cm), with 86.3%, 78.6%, and 82.1% of the patients in each group, respectively, being bothered by the loss of length.ConclusionsPenile length loss due to PD affects most patients. Further penile length loss due to the surgical correction leads to bother among the affected patients, irrespective of the magnitude of the loss. The Nesbit procedure was associated with the highest losses in penile length. In patients with PD and severe erectile dysfunction, a concomitant lengthening procedure may be offered to patients to help overcome the psychological burden caused by the loss of penile length.
Academic Risk and Resilience in the Context of Homelessness
Authors: Masten Ann S. , Cutuli J. J. , Herbers Janette E. , Hinz Elizabeth , Obradović Jelena , Wenzel Amanda J. 
Published: October 2014

AbstractFamily homelessness in the United States has increased over the past two decades, raising concerns about associated risks for child development. In this article, we describe a translational research program focused on academic risk and resilience in homeless and highly mobile children. We find that although these children share many risk factors with other disadvantaged children, they are higher on an underlying continuum of risk. Additionally, marked variability has been observed among children who experience homelessness, both in risk level and achievement, with many children manifesting resilience. We discuss implications for research and efforts to address disparities in achievement.
Teachers' Daily Interactions With Children: An Essential Ingredient in Effective Early Childhood Programs
Authors: Hamre Bridget K. 
Published: October 2014

AbstractTo ensure that investments in expanding early childhood programs are effective in supporting children's school readiness, early childhood settings must include responsive and cognitively stimulating daily interactions between teachers and children. Few young children are exposed to the types of teacher–child interactions needed to help ensure that they are prepared to start kindergarten. In this article, I review studies identifying teacher–child interactions that promote children's development and documenting how systematic professional development enhances these areas of teachers' practice. I also address the limits to research and the policy implications of this work.
“Everything Happens for a Reason”: Children's Beliefs About Purpose in Life Events
Authors: Banerjee Konika , Bloom Paul 
Published: October 2014

Do children believe that “everything happens for a reason?” That is, do children endorse purpose‐based, teleological explanations for significant life events, as they do for social behavior, artifacts, biological properties, and natural kinds? Across three experiments, 5‐ to 7‐year‐olds (N = 80), 8‐ to 10‐year‐olds (N = 72), and adults (N = 91) chose between teleological and nonteleological accounts of significant life events and judged how helpful those accounts were for understanding an event's cause. Five‐ to 7‐year‐olds favored teleological explanations, but this preference diminished with age. Five‐ to 7‐year‐olds and 8‐ to 10‐year‐olds also found teleological explanations more helpful than did adults. Perceiving purpose in life events may therefore have roots in childhood, potentially reflecting a more general sensitivity to purpose in the social and natural worlds.
Phylogeny and historical biogeography of the cocosoid palms (Arecaceae, Arecoideae, Cocoseae) inferred from sequences of six WRKY gene family loci
Authors: Meerow Alan W. , Noblick Larry , Salas‐Leiva Dayana E. , Sanchez Vanessa , Francisco‐Ortega Javier , Jestrow Brett , Nakamura Kyoko 
Published: October 2014

AbstractArecaceae tribe Cocoseae is the most economically important tribe of palms, including both coconut and African oil palm. It is mostly represented in the Neotropics, with one and two genera endemic to South Africa and Madagascar, respectively. Using primers for six single copy WRKY gene family loci, we amplified DNA from 96 samples representing all genera of the palm tribe Cocoseae as well as outgroup tribes Reinhardtieae and Roystoneae. We compared parsimony (MP), maximum likelihood (ML), and Bayesian (B) analysis of the supermatrix with three species‐tree estimation approaches. Subtribe Elaeidinae is sister to the Bactridinae in all analyses. Within subtribe Attaleinae, Lytocaryum, previously nested in Syagrus, is now positioned by MP and ML as sister to the former, with high support; B maintains Lytocaryum embedded within Syagrus. Both MP and ML resolve Cocos as sister to Syagrus; B positions Cocos as sister to Attalea. Bactridineae is composed of two sister clades, Bactris and Desmoncus in one, for which there is morphological support, and a second comprising Acrocomia, Astrocaryum, and Aiphanes. Two B and one ML gene tree‐species estimation approaches are incongruent with the supermatrix in a few critical intergeneric clades, but resolve the same infrageneric relationships. The biogeographic history of the Cocoseae is dominated by dispersal events. The tribe originated in the late Cretaceous in South America. Evaluated together, the supermatrix and species tree analyses presented in this paper provide the most accurate picture of the evolutionary history of the tribe to date, with more congruence than incongruence among the various methodologies.