bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reproducibility of pyrosequencing data for biodiversity assessment in complex communities
Authors: Zhan Aibin , He Song , Brown Emily A. , Chain Frédéric J.J. , Therriault Thomas W. , Abbott Cathryn L. , Heath Daniel D. , Cristescu Melania E. , MacIsaac Hugh J. 
Published: July 2014

Summary

High‐throughput sequencing is rapidly becoming a popular method to profile complex communities and has generated deep insights into community biodiversity. However, the reproducibility of this method for biodiversity assessment remains largely unexplored.

Here we evaluated reproducibility by analysing 454 pyrosequenced biological replicates of two complex plankton communities collected from one freshwater port and one marine port. We also tested whether reproducibility potentially influences biodiversity estimates, notably α‐ and β‐diversity.

Our evaluation of reproducibility revealed a complex scenario, having both technical and biological significance. At the Operational Taxonomic Unit (OTU) level, reproducibility was 100% for high‐abundance OTUs (>100 sequences), although it was lower for low‐abundance OTUs, and sometimes <25% for singletons. BLAST searches showed that >88% of irreproducible OTUs had high sequence similarity to existing records, suggesting that some singletons may reflect rare lineages/genotypes in communities. However, spurious amplification of distantly related taxonomic groups generated mainly low‐abundance OTUs that were characterized by low reproducibility. At a broad taxonomic level (i.e. order level), reproducibility decreased as the abundance of OTUs decreased and was particularly low for distantly related taxonomic groups such as algae and protists that were not the targets of our zooplankton biodiversity survey. At a lower taxonomical level (i.e. family‐level), overall reproducibility was high (>80%) for crustaceans, the dominant group in zooplankton samples. Therefore, we suggest that random variation during both sample collection and sequencing processes can be responsible for low reproducibility. Our analyses also suggest that random sampling processes may influence both α‐ and β‐diversity estimates.

Our results add to growing evidence that caution needs to be applied when designing and interpreting experiments utilizing high‐throughput sequencing data for biodiversity assessments. Technical replicates are needed to statistically correct intra‐sample variation, while field‐based replicate samples are desirable to substantiate results. An overestimation of species diversity can occur when OTUs are uniquely characterized by spuriously amplified sequences and errors/artifacts. Therefore, careful management of low‐abundance OTUs is required to reveal unique/rare lineages. Our results suggest that further studies are needed to determine the ecological significance of low‐abundance OTUs in complex communities.
The pharmacokinetics, pharmacodynamics and safety of oral doses of ilaprazole 10, 20 and 40 mg and esomeprazole 40 mg in healthy subjects: a randomised, open‐label crossover study
Authors: Shin J. S. , Lee J. Y. , Cho K. H. , Park H. L. , Kukulka M. , Wu J.‐T. , Kim D. Y. , Park S.‐H. 
Published: July 2014

SummaryBackgroundIlaprazole, a proton pump inhibitor (PPI) currently in clinical use, may provide improved acid suppression vs. other PPIs.AimTo compare the pharmacodynamic and pharmacokinetic profiles of ilaprazole and esomeprazole.MethodsA phase 1, randomised, open‐label, single‐centre, 4‐period crossover study was conducted in 40 healthy volunteers. Ilaprazole 10, 20 or 40 mg or esomeprazole 40 mg was administered once daily for 5 days with ≥5‐day washout intervals. Pharmacokinetic blood samples and intragastric pH measurements were collected at scheduled timepoints for 24 h after dosing on Days 1 and 5.ResultsEsomeprazole 40 mg provided significantly better pH control during the initial hours (0–4 h) after a single dose, but ilaprazole (particularly 20 and 40 mg) provided significantly better pH control for the entire 24‐h period and during evening and overnight hours after single and multiple doses. Increasing ilaprazole doses resulted in dose‐proportional increases in peak plasma concentration and area under the plasma concentration vs. time curve following single and multiple doses. Ilaprazole was safe and generally well tolerated; an unexpectedly high incidence of allergic eye and skin reactions were observed but were not specific to any dosing regimen. Plasma gastrin concentrations did not increase proportionately with increasing ilaprazole dose.ConclusionsIlaprazole provided significantly better pH control over 24 h and during evening and overnight hours compared with esomeprazole in healthy volunteers, which may translate to greater relief of night‐time heartburn in the clinical setting for patients with gastric acid‐related disorders.
Escalation to weekly dosing recaptures response in adalimumab‐treated patients with moderately to severely active ulcerative colitis
Authors: Wolf D. , D'Haens G. , Sandborn W. J. , Colombel J.‐F. , Van Assche G. , Robinson A. M. , Lazar A. , Zhou Q. , Petersson J. , Thakkar R. B. 
Published: July 2014

SummaryBackgroundPatients with moderately to severely active ulcerative colitis occasionally do not respond to or lose initial response to maintenance dosing of anti‐TNF therapy.AimTo report the efficacy of escalation from every other week (EOW) to weekly adalimumab dosing in patients from the clinical trial ULTRA 2 (NCT00408629), by week 8 response (i.e. response after adalimumab induction therapy).MethodsWeek 52 remission, response, and mucosal healing rates were assessed in ULTRA 2 adalimumab‐randomised patients who escalated to weekly dosing. Patients were stratified by week 8 response per partial Mayo score. Kaplan–Meier and logistic regression analyses estimated time to weekly dosing and defined predictors of escalation to weekly dosing, respectively. Adverse events were reported for patients receiving open‐label adalimumab.ResultsThe rate of escalation to weekly dosing was 16.3% (20/123) for week 8 responders and 38.4% (48/125) for week 8 nonresponders. Week 52 remission, response and mucosal healing rates with weekly dosing were 20%, 45%, and 45% for week 8 responders and 2.1%, 25% and 29.2% for nonresponders, respectively (NRI). The median time to weekly dosing was 288 days for week 8 nonresponders and not estimable for responders. Prior anti‐TNF use was a significant predictor of escalation to weekly dosing. Treatment‐emergent adverse event rates were similar for patients receiving open‐label EOW or weekly adalimumab.ConclusionsEscalation to weekly adalimumab dosing demonstrated clinical benefits for patients who lost response to therapy and may be beneficial for patients not initially responding to induction therapy. No new safety risks were identified with weekly dosing.
Adalimumab drug and antibody levels as predictors of clinical and laboratory response in patients with Crohn's disease
Authors: Mazor Y. , Almog R. , Kopylov U. , Ben Hur D. , Blatt A. , Dahan A. , Waterman M. , Ben‐Horin S. , Chowers Y. 
Published: July 2014

SummaryBackgroundAdalimumab is an effective treatment for Crohn's disease (CD). Anti‐adalimumab antibodies (AAA) and low trough serum drug concentrations have been implicated as pre‐disposing factors for treatment failure.AimsTo assess adalimumab and AAA serum levels, and to examine their association and discriminatory ability with clinical response and serum C‐reactive protein (CRP).MethodsWe performed a cross‐sectional study using trough sera from adalimumab‐treated CD patients. Demographical data, Montreal classification, treatment regimen and clinical status were recorded. Serum adalimumab, AAA and CRP were measured. Receiver operating characteristic analysis and a multivariate regression model were performed to find drug and antibody thresholds for predicting disease activity at time of serum sampling.ResultsOne hundred and eighteen trough serum samples were included from 71 patients. High adalimumab trough serum concentration was associated with disease remission (Area Under Curve 0.748, P < 0.001). A cut‐off drug level of 5.85 μg/mL yielded optimal sensitivity, specificity and positive likelihood ratio for remission prediction (68%, 70.6% and 2.3, respectively). AAA were inversely related with adalimumab drug levels (Spearman's r = −0.411, P < 0.001) and when subdivided into categorical values, positively related with disease activity (P < 0.001). High drug levels and stricturing vs. penetrating or inflammatory phenotype, but not AAA levels, independently predicted disease remission in a multivariate logistic regression model.ConclusionsAdalimumab drug levels were inversely related to disease activity. High levels of anti‐adalimumab antibodies were positively associated with disease activity, but this association was mediated mostly by adalimumab drug levels.
The incidence rate of colectomy for medically refractory ulcerative colitis has declined in parallel with increasing anti‐TNF use: a time‐trend study
Authors: Reich K. M. , Chang H.‐J. , Rezaie A. , Wang H. , Goodman K. J. , Kaplan G. G. , Svenson L. W. , Lees G. , Fedorak R. N. , Kroeker K. I. 
Published: July 2014

SummaryBackgroundMedical therapy is standard treatment for ulcerative colitis with colectomy reserved for medically refractory disease or malignancy. The introductions of ciclosporin in 1994 and anti‐TNF therapy in 2005 have extended medical management options.AimTo determine whether the colectomy incidence rate for medically refractory ulcerative colitis has changed since the introduction of anti‐TNF therapy.MethodsAdult patients with a diagnosis of ulcerative colitis and who subsequently underwent an urgent or elective colectomy for medically refractory disease in Edmonton, Canada between 1 January 1998 and 31 December 2011 were identified. Log‐linear regression was used to estimate the annual percent change in the total colectomy incidence rate (urgent and elective combined) and the urgent and elective incidence rates individually, before and after 2005, the year infliximab was approved for use in ulcerative colitis. Temporal trends of drug utilisation in this study population were also described.ResultsDuring 1998–2011, 481 patients with ulcerative colitis underwent a colectomy for medically refractory disease. There was negligible change in the total colectomy incidence rate from 1998 to 2005, with an annual percent change of 4.4% (95% confidence interval (CI): −1.12% to 10.16%). From 2005‐2011, following the approval and increasing use of anti‐TNF therapy, the total colectomy incidence rate decreased by 16.1% (95% CI: −21.32% to −10.54%) every year to 0.9 per 100 ulcerative colitis patients in 2011.ConclusionThe total incidence rate of colectomy for medically refractory ulcerative colitis has declined substantially since 2005, paralleling the increased use of anti‐TNF therapy in this patient population.
Metabolic syndrome delays HBeAg seroclearance in Chinese patients with hepatitis B
Authors: Hsiang J. C. , Wong G. L.‐H. , Chan H. L.‐Y. , Chan A. W.‐H. , Chim A. M.‐L. , Wong V. W.‐S. 
Published: July 2014

SummaryBackgroundDelayed hepatitis B e antigen (HBeAg) seroclearance increases the risk of cirrhosis and hepatocellular carcinoma (HCC). The effect of metabolic syndrome (MetS) on HBeAg seroclearance in chronic hepatitis B (CHB) patients remains unclear.AimsTo examine the effect of MetS on HBeAg seroclearance.MethodsA prospective cohort of 413 treatment‐naïve HBeAg‐positive CHB patients from 2005 to 2012 was studied. Clinical, virological and histological parameters were evaluated. The patients were classified into three groups according to the metabolic characteristics; normal, pre‐MetS and MetS based on the International Diabetes Federation criteria. The primary outcome was age at HBeAg seroclearance.ResultsThe overall HBeAg seroclearance rate was 11.4% per annum during 19 351 patient‐months of follow‐up with no difference in HBeAg seroclearance rates between 162 treatment‐free and 251 patients receiving nucleos(t)ide analogues. Patients with pre‐MetS and MetS were older when HBeAg seroclearance occurred (44 ± 12 and 53 ± 7 years, respectively) than the normal patients (37 ± 9 years, all P < 0.01). Patients with pre‐MetS and MetS had more advanced liver fibrosis (33.0% and 53.1%, respectively) than the normal patients (18.4%, all P < 0.05). By the age of 50, 59.3% of the metabolic normal patients, 42.1% of the pre‐MetS and 18.7% of the MetS patients had achieved HBeAg seroclearance (all P < 0.05, except P = 0.07 for pre‐MetS vs. MetS). In multivariate analysis, MetS and type II diabetes at baseline were predictors of delayed HBeAg seroclearance after adjusting for viral load, anti‐viral therapy and necroinflammatiom.ConclusionChinese patients with chronic hepatitis B and with pre‐metabolic syndrome or metabolic syndrome have delayed HBeAg seroclearance.
Predictors of either rapid healing or refractory reflux oesophagitis during treatment with potent acid suppression
Authors: Kahrilas P. J. , Persson T. , Denison H. , Wernersson B. , Hughes N. , Howden C. W. 
Published: July 2014

SummaryBackgroundLittle is known regarding patient characteristics that influence the speed of reflux oesophagitis (RO) healing.AimTo investigate patient characteristics that may influence RO healing rates.MethodsA post hoc analysis of clinical trial data for potent acid suppression treatment of RO (esomeprazole or AZD0865) was conducted. Group A underwent endoscopy at baseline, week 2 and 4, and group B at baseline, week 4 and 8. Group A patients were sub‐grouped as ‘rapid’ (healed at 2 weeks) or unhealed at 2 weeks. Group B patients were sub‐grouped as ‘slow’ (healed at 8 weeks, not at 4 weeks) or ‘refractory’ (not healed at 8 weeks). Logistic regression analysis was performed only for comparisons within group A.ResultsAt 2, 4 and 8 weeks, RO had healed in 68%, 65% and 61% of patients unhealed at previous endoscopy, respectively. Low‐grade [vs. high‐grade (C or D)] RO was the only independent predictor of rapid healing in group A after logistic regression analysis. Significantly more rapid healers had low grade RO (A or B) at baseline than patients with refractory RO (84% vs. 49%; P < 0.001), and significantly more refractory patients had frequent regurgitation at baseline than slow healers (80% vs. 63%; P = 0.039).ConclusionsLow‐ (vs. high‐) grade RO determines the most rapid benefit from acid suppression. Roughly two‐thirds of patients healed with each time increment of potent acid suppression therapy. This suggests that some unhealed patients may still heal with continued therapy and that truly refractory RO is rare. (ClinicalTrials.gov: NCT00206245).
Persistent effect of broody hens on behaviour of chickens
Authors: Shimmura Tsuyoshi , Maruyama Yuji , Fujino Saori , Kamimura Eriko , Uetake Katsuji , Tanaka Toshio 
Published: July 2014

AbstractWe reported previously that behavioral development of chicks was promoted remarkably by the presence of a broody hen. Here we report that these effects at an early age persist after maturity. A total of 60 female chicks were randomly assigned to one of two treatment groups: six pens with five chicks (brooded group) each were reared by a broody hen and six pens with five chicks (non‐brooded group) each were provided with an infrared heating lamp. We evaluated the persistent effects of broody hens by measures of behavior, physical condition and production at 9, 16, 35 and 55 weeks of age. The numbers of threatening, aggressive pecking, fighting and severe feather pecking behaviors were higher in non‐brooded than in brooded chickens (all P < 0.05). Egg production was lower in brooded than in non‐brooded chickens (P < 0.05), while the number of brooding chickens was higher in the brooded than in the non‐brooded group (P < 0.05). In conclusion, the presence of broody hens at an early stage of chicks' lives has a persistent effect on behavior. Although brooded chickens showed more brooding and lower egg production than non‐brooded chickens, feather pecking and aggressive interaction were decreased in brooded hens.
Regeneration in chalk grassland during 150 years in a military area
Authors: Bakker Jan P. 
Published: July 2014

AbstractThe long‐term regeneration of calcareous grassland after agricultural intensification is elucidated in Redhead et al. 2014 (Applied Vegetation Science 17: 408–418). The paper generates thoughts about the impact of different pre‐purchase agricultural practices. It makes the reader think about the seeming contradiction of reducing soil fertility, grazing and atmospheric deposition. And what is it that prevents some characteristic species from re‐establishing even after 150 yrs of regeneration?
Effects of factor Xa on the expression of proteins in femoral arteries from type 2 diabetic patients
Authors: López‐Farré Antonio J. , Rodriguez‐Sierra Pablo , Modrego Javier , Segura Antonio , Martín‐Palacios Naiara , Saiz Ana M. , Zamorano‐León José J. , Duarte Juan , Serrano Javier , Moñux Guillermo 
Published: July 2014

AimFurther to its pivotal role in haemostasis, factor Xa (FXa) promotes effects on the vascular wall. The purpose of the study was to evaluate if FXa modifies the expression level of energy metabolism and oxidative stress‐related proteins in femoral arteries obtained from type 2 diabetic patients with end‐stage vasculopathy.MethodsFemoral arteries were obtained from 12 type 2 diabetic patients who underwent leg amputation. Segments from the femoral arteries were incubated in vitro alone and in the presence of 25 nmol l−1 FXa and 25 nmol l−1 FXa + 50 nmol l−1 rivaroxaban.ResultsIn the femoral arteries, FXa increased triosephosphate isomerase and glyceraldehyde‐3‐phosphate dehydrogenase isotype 1 expression but decreased pyruvate dehydrogenase expression. These facts were accompanied by an increased content of acetyl‐CoA. Aconitase activity was reduced in FXa‐incubated femoral arteries as compared with control. Moreover, FXa increased the protein expression level of oxidative stress‐related proteins which was accompanied by an increased malonyldialdehyde arterial content. The FXa inhibitor, rivaroxaban, failed to prevent the reduced expression of pyruvate dehydrogenase induced by FXa but reduced acetyl‐CoA content and reverted the decreased aconitase activity observed with FXa alone. Rivaroxaban + FXa but not FXa alone increased the expression level of carnitine palmitoyltransferase I and II, two mitochondrial long chain fatty acid transporters. Rivaroxaban also prevented the increased expression of oxidative stress‐related proteins induced by FXa alone.ConclusionsIn femoral isolated arteries from type 2 diabetic patients with end‐stage vasculopathy, FXa promoted disruption of the aerobic mitochondrial metabolism. Rivaroxaban prevented such effects and even seemed to favour long chain fatty acid transport into mitochondria.
Novel coumarin modified GLP‐1 derivatives with enhanced plasma stability and prolonged in vivo glucose‐lowering ability
Authors: Han Jing , Sun Lidan , Huang Xun , Li Zheng , Zhang Chenyu , Qian Hai , Huang Wenlong 
Published: July 2014

Background and PurposeThe short biological half‐life limits the therapeutic use of glucagon‐like peptide‐1 (GLP‐1) and chemical modification to improve the interaction of peptides with serum albumin represents an effective strategy to develop long‐acting peptide analogues. Coumarin, a natural product, is known to bind tightly to plasma proteins and possesses many biological activities. Therefore, we designed and synthesized a series of coumarin‐modified GLP‐1 derivatives, hypothesizing that conjugation with coumarin would retain the therapeutic effects and prolong the biological half‐life of the conjugates.Experimental ApproachFour cysteine‐modified GLP‐1 analogues (1–4) were prepared using Gly8‐GLP‐1(7–36)‐NH2 peptide as a starting point. These analogues were conjugated with two coumarin maleimides to yield eight compounds (conjugates 6–13) for testing. Activation of human GLP‐1 receptors, stability to enzymic inactivation in plasma and binding to human albumin were assessed in vitro. In vivo, effects on oral glucose tolerance tests (OGTT) in rats and on blood glucose levels in db/db mice were studied.Key ResultsMost conjugates showed well preserved receptor activation efficacy, enhanced albumin‐binding properties and improved in vitro plasma stability and conjugate 7 was selected to undergo further assessment. In rats, conjugate 7 had a longer circulating t1/2 than exendin‐4 or liraglutide. A prolonged antidiabetic effect of conjugate 7 was observed after OGTT in rats and a prolonged hypoglycaemic effect in db/db mice.Conclusions and ImplicationsCysteine‐specific coumarin conjugation with GLP‐1 offers a useful approach to the development of long‐acting incretin‐based antidiabetic agents. Conjugate 7 is a promising long‐lasting GLP‐1 derivative deserving further investigation.
Where Culture Takes Hold: “Overimitation” and Its Flexible Deployment in Western, Aboriginal, and Bushmen Children
Authors: Nielsen Mark , Mushin Ilana , Tomaselli Keyan , Whiten Andrew 
Published: July 2014

Children often “overimitate,” comprehensively copying others' actions despite manifest perceptual cues to their causal ineffectuality. The inflexibility of this behavior renders its adaptive significance difficult to apprehend. This study explored the boundaries of overimitation in 3‐ to 6‐year‐old children of three distinct cultures: Westernized, urban Australians (N = 64 in Experiment 1; N = 19 in Experiment 2) and remote communities of South African Bushmen (N = 64) and Australian Aborigines (N = 19). Children overimitated at high frequency in all communities and generalized what they had learned about techniques and object affordances from one object to another. Overimitation thus provides a powerful means of acquiring and flexibly deploying cultural knowledge. The potency of such social learning was also documented compared to opportunities for exploration and practice.
Social oral epidemi(olog)2y where next: one small step or one giant leap?
Authors: Baker Sarah R. , Gibson Barry G. 
Published: July 2014

AbstractSince the early 1990s, there has been heated debate critically reflecting on social epidemiology. Yet, very little of this debate has reached oral epidemiology. This is no more noticeable than in the field of oral health inequalities. One of the significant achievements of social oral epidemiology has been the persistent documentation of social patterning of oral disease. Nevertheless, where social oral epidemiology has fallen down is going beyond description to explaining these patterns. Thinking how and in what way things happen, not just in relation to oral health inequalities but also more broadly, requires a more creative approach which links to scholarship outside of dentistry, including the work from critical epidemiologists to that within the social sciences. The aim of this review study is to provide a critical commentary on key aspects of more general epidemiological debates in order to inform and develop social oral epidemiology theory and methodology. In the first section, ‘Where are we now?’, six key debates are reflected upon: (i) analysis of variance versus analysis of causes, (ii) the fallacy of independent effects, (iii) black box thinking, (iv) theory and the understanding of mechanisms, (v) individualization of risk and (vi) the meaning of ‘social’. In the second section, ‘Where to next?’ we draw on a number of fundamental issues from within the social science literature in order to highlight possible channels of future inquiry. Our overriding goal throughout is to facilitate a critical engagement in order to improve understanding and generate knowledge in relation to population oral health.