bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lower rates of dislocation with increased femoral head size after primary total hip replacement
Authors: Jameson S. S. , Lees D. , James P. , Serrano-Pedraza I. , Partington P. F. , Muller S. D. , Meek R. M. D. , Reed M. R. 
Published: June 2011

Increased femoral head size may reduce dislocation rates following total hip replacement. The National Joint Registry for England and Wales has highlighted a statistically significant increase in the use of femoral heads ≥ 36 mm in diameter from 5% in 2005 to 26% in 2009, together with an increase in the use of the posterior approach. The aim of this study was to determine whether rates of dislocation have fallen over the same period. National data for England for 247 546 procedures were analysed in order to determine trends in the rate of dislocation at three, six, 12 and 18 months after operation during this time. The 18-month revision rates were also examined. Between 2005 and 2009 there were significant decreases in cumulative dislocations at three months (1.12% to 0.86%), six months (1.25% to 0.96%) and 12 months (1.42% to 1.11%) (all p < 0.001), and at 18 months (1.56% to 1.31%) for the period 2005 to 2008 (p < 0.001). The 18-month revision rates did not significantly change during the study period (1.26% to 1.39%, odds ratio 1.10 (95% confidence interval 0.98 to 1.24), p = 0.118). There was no evidence of changes in the coding of dislocations during this time. These data have revealed a significant reduction in dislocations associated with the use of large femoral head sizes, with no change in the 18-month revision rate.
Genetic Drift Widens the Expected Cline but Narrows the Expected Cline Width
Authors: Polechová Jitka , Barton Nick 
Published: June 2011

AbstractRandom genetic drift shifts clines in space, alters their width, and distorts their shape. Such random fluctuations complicate inferences from cline width and position. Notably, the effect of genetic drift on the expected shape of the cline is opposite to the naive (but quite common) misinterpretation of classic results on the expected cline. While random drift on average broadens the overall cline in expected allele frequency, it narrows the width of any particular cline. The opposing effects arise because locally, drift drives alleles to fixation—but fluctuations in position widen the expected cline. The effect of genetic drift can be predicted from standardized variance in allele frequencies, averaged across the habitat: 〈F〉. A cline maintained by spatially varying selection (step change) is expected to be narrower by a factor of 1−〈F〉 relative to the cline in the absence of drift. The expected cline is broader by the inverse of this factor. In a tension zone maintained by underdominance, the expected cline width is narrower by about 1 – 〈F〉 relative to the width in the absence of drift. Individual clines can differ substantially from the expectation, and we give quantitative predictions for the variance in cline position and width. The predictions apply to clines in almost one-dimensional circumstances such as hybrid zones in rivers, deep valleys, or along a coast line and give a guide to what patterns to expect in two dimensions.
Ectopic Gene Expression and Organogenesis in Arabidopsis Mutants Missing BRU1 Required for Genome Maintenance
Authors: Ohno Yusuke , Narangajavana Jarunya , Yamamoto Akiko , Hattori Tsukaho , Kagaya Yasuaki , Paszkowski Jerzy , Gruissem Wilhelm , Hennig Lars , Takeda Shin 
Published: June 2011

Abstract
Chromatin reconstitution after DNA replication and repair is essential for the inheritance of epigenetic information, but mechanisms underlying such a process are still poorly understood. Previously, we proposed that Arabidopsis BRU1 functions to ensure the chromatin reconstitution. Loss-of-function mutants of BRU1 are hypersensitive to genotoxic stresses and cause release of transcriptional gene silencing of heterochromatic genes. In this study, we show that BRU1 also plays roles in gene regulation in euchromatic regions. bru1 mutations caused sporadic ectopic expression of genes, including those that encode master regulators of developmental programs such as stem cell maintenance and embryogenesis. bru1 mutants exhibited adventitious organogenesis, probably due to the misexpression of such developmental regulators. The key regulatory genes misregulated in bru1 alleles were often targets of PcG SET-domain proteins, although the overlap between the bru1-misregulated and PcG SET-domain-regulated genes was limited at a genome-wide level. Surprisingly, a considerable fraction of the genes activated in bru1 were located in several subchromosomal regions ranging from 174 to 944 kb in size. Our results suggest that BRU1 has a function related to the stability of subchromosomal gene regulation in the euchromatic regions, in addition to the maintenance of chromatin states coupled with heritable epigenetic marks.
A Survey for Novel Imprinted Genes in the Mouse Placenta by mRNA-seq
Authors: Wang Xu , Soloway Paul D , Clark Andrew G 
Published: June 2011

Abstract
Many questions about the regulation, functional specialization, computational prediction, and evolution of genomic imprinting would be better addressed by having an exhaustive genome-wide catalog of genes that display parent-of-origin differential expression. As a first-pass scan for novel imprinted genes, we performed mRNA-seq experiments on embryonic day 17.5 (E17.5) mouse placenta cDNA samples from reciprocal cross F1 progeny of AKR and PWD mouse strains and quantified the allele-specific expression and the degree of parent-of-origin allelic imbalance. We confirmed the imprinting status of 23 known imprinted genes in the placenta and found that 12 genes reported previously to be imprinted in other tissues are also imprinted in mouse placenta. Through a well-replicated design using an orthogonal allelic-expression technology, we verified 5 novel imprinted genes that were not previously known to be imprinted in mouse (Pde10, Phf17, Phactr2, Zfp64, and Htra3). Our data suggest that most of the strongly imprinted genes have already been identified, at least in the placenta, and that evidence supports perhaps 100 additional weakly imprinted genes. Despite previous appearance that the placenta tends to display an excess of maternally expressed imprinted genes, with the addition of our validated set of placenta-imprinted genes, this maternal bias has disappeared.
Pathways of Resistance to Thymineless Death in Escherichia coli and the Function of UvrD
Authors: Fonville Natalie C , Vaksman Zalman , DeNapoli Jessica , Hastings P J , Rosenberg Susan M 
Published: June 2011

Abstract
Thymineless death (TLD) is the rapid loss of viability in bacterial, yeast, and human cells starved of thymine. TLD is the mode of action of common anticancer drugs and some antibiotics. TLD in Escherichia coli is accompanied by blocked replication and chromosomal DNA loss and recent work identified activities of recombination protein RecA and the SOS DNA-damage response as causes of TLD. Here, we examine the basis of hypersensitivity to thymine deprivation (hyper-TLD) in mutants that lack the UvrD helicase, which opposes RecA action and participates in some DNA repair mechanisms, RecBCD exonuclease, which degrades double-stranded linear DNA and works with RecA in double-strand-break repair and SOS induction, and RuvABC Holliday-junction resolvase. We report that hyper-TLD in ∆uvrD cells is partly RecA dependent and cannot be attributed to accumulation of intermediates in mismatch repair or nucleotide-excision repair. These data imply that both its known role in opposing RecA and an additional as-yet-unknown function of UvrD promote TLD resistance. The hyper-TLD of ∆ruvABC cells requires RecA but not RecQ or RecJ. The hyper-TLD of recB cells requires neither RecA nor RecQ, implying that neither recombination nor SOS induction causes hyper-TLD in recB cells, and RecQ is not the sole source of double-strand ends (DSEs) during TLD, as previously proposed; models are suggested. These results define pathways by which cells resist TLD and suggest strategies for combating TLD resistance during chemotherapies.
Novel Rank-Based Approaches for Discovery and Replication in Genome-Wide Association Studies
Authors: Kuo Chia-Ling , Zaykin Dmitri V 
Published: June 2011

AbstractIn recent years, genome-wide association studies (GWAS) have uncovered a large number of susceptibility variants. Nevertheless, GWAS findings provide only tentative evidence of association, and replication studies are required to establish their validity. Due to this uncertainty, researchers often focus on top-ranking SNPs, instead of considering strict significance thresholds to guide replication efforts. The number of SNPs for replication is often determined ad hoc. We show how the rank-based approach can be used for sample size allocation in GWAS as well as for deciding on a number of SNPs for replication. The basis of this approach is the “ranking probability”: chances that at least j true associations will rank among top u SNPs, when SNPs are sorted by P-value. By employing simple but accurate approximations for ranking probabilities, we accommodate linkage disequilibrium (LD) and evaluate consequences of ignoring LD. Further, we relate ranking probabilities to the proportion of false discoveries among top u SNPs. A study-specific proportion can be estimated from P-values, and its expected value can be predicted for study design applications.
CLAVATA Signaling Pathway Receptors of Arabidopsis Regulate Cell Proliferation in Fruit Organ Formation as well as in Meristems
Authors: Durbak Amanda R , Tax Frans E 
Published: June 2011

Abstract
The CLAVATA1 (CLV1), CLV2, and CORYNE (CRN) receptors in Arabidopsis thaliana maintain cell proliferation in shoot apical meristems by restricting expression of the transcription factor WUSCHEL (WUS). Previously characterized receptor mutants generate extra fruit and floral organs that are proposed to arise from enlarged floral meristems (FMs). We identified new alleles in clv1, clv2, and crn and found that most mutants produce only extra fruit organs and generate FMs of similar dimensions as wild type. Characterization of gynoecium development in receptor mutants revealed increased cell proliferation and ectopic fruit organ initiation after FM termination. These regions of increased cell division also display expanded expression of the cell proliferation-promoting transcription factor SHOOTMERISTEMLESS (STM), similar to the expansion of WUS expression in the shoot apical meristems of strong clv1 mutants. We also examined genetic interactions between the ERECTA (ER) and BARELY ANY MERISTEM 1 (BAM1) receptor-like kinases and CLV pathway receptors. Our results suggest a model in which CLV1/BAM1 and CLV2/CRN complexes act in separate, parallel pathways in shoot meristems, while the CLV1, CLV2, and CRN receptors function together in a linear pathway during fruit development. These results demonstrate the importance of regulating cell proliferation in plants that undergo organogenesis throughout their life cycle.
ELAV-Mediated 3′-End Processing of ewg Transcripts Is Evolutionarily Conserved Despite Sequence Degeneration of the ELAV-Binding Site
Authors: Haussmann Irmgard U , Li Min , Soller Matthias 
Published: June 2011

Abstract
Regulation of alternative mRNA processing by ELAV (embryonic lethal abnormal visual system)/Hu proteins is mediated by binding to AU-rich elements of low complexity. Since such sequences diverge very rapidly during evolution, it has not been clear if ELAV regulation is maintained over extended phylogenetic distances. The transcription factor Erect wing (Ewg) is a major target of ELAV in Drosophila melanogaster and coordinates metabolic gene expression with regulation of synaptic plasticity. Here, we demonstrate evolutionary conservation of ELAV regulation of ewg despite massive degeneration of its binding site and of associated elements in the regulated intronic 3′-end processing site in distantly related Drosophila virilis. In this species, the RNA-binding part of ELAV protein is identical to D. melanogaster. ELAV expression as well as expression and regulation of ewg are also conserved. Using in vitro binding assays and in vivo transgene analysis, we demonstrate, however, that the ELAV-binding site of D. virilis is fully functional in regulating alternative splicing of ewg intron 6 in D. melanogaster. Known features of the ELAV-binding site, such as the requirement of multiple poly(U) motifs spread over an extended binding site of ∼150 nt and a higher affinity to the 3′ part of the binding site, are conserved. We further show that the 135-bp ELAV-binding site from D. melanogaster is sufficient for ELAV recruitment in vivo. Hence, our data suggest that ELAV/Hu protein-regulated alternative RNA processing is more conserved than anticipated from the alignment of degenerate low-complexity sequences.
Effects of Paroxetine on the Pharmacokinetics and Pharmacodynamics of Immediate‐Release and Extended‐Release Metoprolol
Authors: Parker Robert B. , Soberman Judith E. 
Published: June 2011

Study Objective. To compare the effects of paroxetine on the pharmacokinetics and pharmacodynamics of the immediate‐release (IR) and extended‐release (ER) formulations of metoprolol.Design. Prospective, randomized, open‐label, 3‐way crossover study.Setting. General clinical research center.Subjects. Fifteen healthy volunteers with at least one active cytochrome P450 (CYP) CYP2D6 allele (CYP2D6*1 or CYP2D6*2).Intervention. In each of three phases conducted in random sequence, subjects received one of three metoprolol formulations administered on day 1: a single dose of metoprolol ER 100 mg, a single dose of metoprolol ER 200 mg, or two 100‐mg doses of metoprolol IR administered 12 hours apart. Oral paroxetine 20 mg/day was then given alone on days 2–7 and coadministered with the same metoprolol formulation on day 8. Subjects received each of the other two formulations during the next two phases, with a 14‐day washout period between each phase.Measurements and Main Results. After receiving metoprolol on days 1 (before paroxetine) and 8 (after paroxetine), S‐ and R‐metoprolol pharmacokinetic parameters and exercise heart rate and blood pressure responses were measured. The mean area under the plasma concentration‐time curve values of both S‐ and R‐metoprolol for each formulation were increased approximately 3‐ and 4‐fold, respectively, by paroxetine. Paroxetine significantly increased the S‐ and R‐metoprolol maximum concentration (Cmax) of each formulation and increased the elimination half‐life of both isomers approximately 2‐fold. When metoprolol IR was given with paroxetine, the S‐metoprolol Cmax was significantly greater than that of either the 100‐mg or 200‐mg ER products. The maximum effect of metoprolol IR on heart rate was significantly greater than that of metoprolol ER 200 mg, independent of whether the agents were administered alone or with paroxetine. Both the heart rate and systolic blood pressure area under the effect‐time curve values were significantly decreased by paroxetine.Conclusion. Paroxetine significantly inhibits the metabolism of both metoprolol IR and ER, resulting in an increase in the magnitude and duration of β‐blockade. The potential risk of adverse effects from excessive β‐blockade may be greater with metoprolol IR than with metoprolol ER because of the significantly higher peak S‐metoprolol plasma concentrations achieved with the IR formulation. Thus, if paroxetine treatment is indicated in patients receiving metoprolol, use of the ER formulation may reduce the risk of adverse effects.
Otoacoustic Emission Screen Results in Critically Ill Neonates Who Received Gentamicin in the First Week of Life
Authors: Cooper Aaron C. , Commers Amy R. , Finkelstein Marsha , Lipnik Polina G. , Tollefson Lisa M. , Wilcox Roger A. , Hoff David S. 
Published: June 2011

Study Objective. To characterize the extent that serum gentamicin concentrations are associated with hearing loss indicated by otoacoustic emission (OAE) screen failure in critically ill neonates receiving gentamicin in accordance with a high‐dose, extended‐interval dosing protocol.Design. Retrospective medical record review.Setting. Two neonatal intensive care units in a pediatric tertiary care system.Patients. Sequential sample of 528 critically ill neonates who were admitted between February 2003 and January 2008 and who received a gentamicin pharmacokinetic consultation during the first week of life and an OAE hearing screen before hospital discharge. Neonates were stratified into two groups: very low birth weight (VLBW [≤ 1500 g]) and non‐VLBW (> 1500 g).Measurements and Main Results. Gentamicin was dosed intravenously to achieve a target calculated gentamicin peak serum concentration (Cmax) of 7–10 μg/ml and a target trough serum concentration (Cmin) of less than 2 μg/ml. The dosage administered was 4 mg/kg/dose every 48 hours if the neonate's birth weight was less than 1250 g or if the neonate was receiving indomethacin. Otherwise, the dosing interval was every 24 hours. Initial OAE screen results were obtained from the medical records, and follow‐up results were collected for neonates who failed the initial OAE screen. The overall rate of OAE screen failure was 13.1% (69/528 patients). The rate of OAE screen failure was 34.1% (29/85 patients) in the VLBW neonates, which was significantly higher than the failure rate in non‐VLBW neonates (9.0% [40/443 patients], p=0.001). Multivariate analysis of non‐VLBW neonates determined that each 1–μg/ml increase in gentamicin Cmax was associated with an increased risk of OAE screen failure (odds ratio [OR] 1.4, 95% confidence interval (CI) 1.1–1.7, p=0.003). Further, the non‐VLBW neonate subpopulation had an increased rate of OAE screen failure if the gentamicin Cmax exceeded 10 μg/ml (OR 2.2, 95% CI 1.1–4.2, p=0.022) compared with neonates whose Cmax was 10 μg/ml or lower. No association between serum gentamicin concentration and OAE screen failure could be determined among the VLBW neonates.Conclusion. Neonates weighing more than 1500 g at birth and whose gentamicin Cmax exceeded 10 μg/ml were at an increased risk for OAE screen failure. Monitoring and maintaining gentamicin Cmax at or below 10 μg/ml may minimize hearing impairment; however, further studies are necessary.
Safety of Daptomycin in Patients Receiving Hemodialysis
Authors: Mueller Bruce A. , Crompton Jason A. , Donovan Brian J. , Yankalev Sara , Lamp Kenneth C. 
Published: June 2011

Study Objective. To determine the safety of daptomycin administered using a variety of doses and dosing frequencies in patients receiving intermittent hemodialysis who had probable or confirmed gram‐positive infections.Design. Analysis of data from the Cubicin Outcomes Registry and Experience (CORE), a multicenter, retrospective, observational registry.Setting. Fifty‐four study sites, mostly (46%) large teaching hospitals.Patients. Three hundred ninety‐three adults in the CORE registry who received intermittent hemodialysis between 2005 and 2008.Measurements and Main Results. The CORE registry is noninterventional and collects standard‐of‐care data on daptomycin treatment from health care institutions. Of the 393 patients, 370 (94%) could be categorized by daptomycin dosing frequency: every 48 hours (251 patients [64%]), 3 times/week (87 [22%]), and every 24 hours (32 [8%]); the remaining 23 (6%) had unreported dosing frequencies or received a single dose of daptomycin. Three hundred eighty‐four patients (98%) received part of their daptomycin therapy as an inpatient and 129 patients (33%) received part of their daptomycin therapy in an intensive care setting. The primary infection type was bacteremia (224 patients [57%]), and the most common pathogen was Staphylococcus aureus (155 patients [39%]). Thirty‐eight adverse events possibly related to daptomycin occurred in 28 patients (7%); increased blood creatine kinase level (7 patients [1.8%]) was the most common adverse event. Adverse‐event rates were similar across all dosing regimens.Conclusion. In these patients undergoing hemodialysis, daptomycin was a well‐tolerated treatment for gram‐positive infections across several doses and dosing frequencies. Further study in prospective trials is warranted.
TOP2A Amplification in the Absence of That of HER-2/neu: Toward Individualization of Chemotherapeutic Practice in Breast Cancer
Authors: Glynn Ronan W. , Mahon Sarah , Curran Catherine , Callagy Grace , Miller Nicola , Kerin Michael J. 
Published: June 2011

AbstractPrimary objective.To investigate the relationship between human epidermal growth factor receptor (HER)-2/neu and the gene encoding topoisomerase IIα (TOP2A) in breast cancer, while elucidating their association with clinicopathological variables.Methods.Real-time quantitative polymerase chain reaction (RQ-PCR) was performed on a 96-patient study group to assess gene amplification, and levels were determined using the comparative cycle threshold approach and Taqman assays. An immunohistochemistry (IHC) microarray (n = 76) was then employed to check for correlation between gene amplification and protein expression levels.Results.Amplification levels of TOP2A did not differ significantly according to HER-2/neu status by either RQ-PCR or IHC microarray. Of the HER-2/neu− patients, 29.1% demonstrated levels of TOP2A above the third quartile, whereas 22.9% of the HER-2/neu+ patients had values in the first quartile (log TOP2A &lt;0.62), thereby indicating low-level amplification. Of the 60 patients characterized as HER-2/neu− using IHC and fluorescence in situ hybridization (FISH), 22.9% were classified as TOP2A+ on the IHC microarray. Of the 14 patients deemed HER-2/neu+ using IHC and FISH, meanwhile, the majority (n = 10) were classified as TOP2A+.Conclusions.Our results indicate that amplification of TOP2A in breast cancer is not confined to those who are concomitantly HER-2/neu+, and suggest that a significant proportion of HER-2/neu− patients exhibit high levels of TOP2A.
Long-term Outcome of Renal Transplantation Patients with Henoch-Schönlein Purpura
Authors: Samuel Joyce P. , Bell Cynthia S. , Molony Donald A. , Braun Michael C. 
Published: June 2011

Summary

Background and objectives
Although Henoch-Schönlein purpura (HSP) is the most common form of renal vasculitis in childhood, progression to ESRD is rare, and there are few data on outcomes of renal transplantation in patients with HSP.

Design, setting, participants, & measurements
This is a matched retrospective cohort study of renal allografts using the United Network of Organ Sharing database (1987 to 2005). Of the 189,211 primary renal allografts, there were 339 with a diagnosis of HSP. The primary end point was allograft survival.

Results
Compared with the remainder of the database, the HSP population was younger (25 years versus 46 years), and had a higher proportion of women (47% versus 40%), live donors (50% versus 35%), and Caucasians (77% versus 60%). Controlling for age, gender, donor source, ethnicity, and year of transplantation, death-censored graft survival for patients with HSP was 80.0% at 5 years and 58.8% at 10 years compared with 79.0% at 5 years and 55.4% at 10 years in the non-HSP population. Among patients with reported causes of graft loss, failure from recurrent disease occurred in 13.6% of patients with HSP, compared with 6.6% in the non-HSP population. When analyzing allograft survival in recipients with HSP compared with those with IgA nephropathy, there was no difference in 10-year allograft survival (58.4% and 59.3%, respectively).

Conclusions
These data indicate that although there is an increased risk of graft failure attributable to recurrent disease in patients with HSP, a diagnosis of HSP has little effect on overall renal allograft survival.