bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tyrosinase Is the Modifier of Retinoschisis in Mice
Authors: Johnson Britt A , Cole Brian S , Geisert Eldon E , Ikeda Sakae , Ikeda Akihiro 
Published: September 2010

AbstractX-linked retinoschisis (XLRS) is a form of macular degeneration with a juvenile onset. This disease is caused by mutations in the retinoschisin (RS1) gene. The major clinical pathologies of this disease include splitting of the retina (schisis) and a loss in synaptic transmission. Human XLRS patients display a broad range in phenotypic severity, even among family members with the same mutation. This variation suggests the existence of genetic modifiers that may contribute to disease severity. Previously, we reported the identification of a modifier locus, named Mor1, which affects severity of schisis in a mouse model of XLRS (the Rs1tmgc1 mouse). Homozygosity for the protective AKR allele of Mor1 restores cell adhesion in Rs1tmgc1 mice. Here, we report our study to identify the Mor1 gene. Through collecting recombinant mice followed by progeny testing, we have localized Mor1 to a 4.4-Mb region on chromosome 7. In this genetic region, the AKR strain is known to carry a mutation in the tyrosinase (Tyr) gene. We observed that the schisis phenotype caused by the Rs1 mutation is rescued by a Tyr mutation in the C57BL/6J genetic background, strongly suggesting that Tyr is the Mor1 gene.
A Molecularly Defined Duplication Set for the X Chromosome of Drosophila melanogaster
Authors: Venken Koen J T , Popodi Ellen , Holtzman Stacy L , Schulze Karen L , Park Soo , Carlson Joseph W , Hoskins Roger A , Bellen Hugo J , Kaufman Thomas C 
Published: September 2010

Abstract
We describe a molecularly defined duplication kit for the X chromosome of Drosophila melanogaster. A set of 408 overlapping P[acman] BAC clones was used to create small duplications (average length 88 kb) covering the 22-Mb sequenced portion of the chromosome. The BAC clones were inserted into an attP docking site on chromosome 3L using ΦC31 integrase, allowing direct comparison of different transgenes. The insertions complement 92% of the essential and viable mutations and deletions tested, demonstrating that almost all Drosophila genes are compact and that the current annotations of the genome are reasonably accurate. Moreover, almost all genes are tolerated at twice the normal dosage. Finally, we more precisely mapped two regions at which duplications cause diplo-lethality in males. This collection comprises the first molecularly defined duplication set to cover a whole chromosome in a multicellular organism. The work presented removes a long-standing barrier to genetic analysis of the Drosophila X chromosome, will greatly facilitate functional assays of X-linked genes in vivo, and provides a model for functional analyses of entire chromosomes in other species.
Diminishing Returns From Beneficial Mutations and Pervasive Epistasis Shape the Fitness Landscape for Rifampicin Resistance in Pseudomonas aeruginosa
Authors: MacLean R C , Perron G G , Gardner A 
Published: September 2010

Abstract
Because adaptation depends upon the fixation of novel beneficial mutations, the fitness effects of beneficial mutations that are substituted by selection are key to our understanding of the process of adaptation. In this study, we experimentally investigated the fitness effects of beneficial mutations that are substituted when populations of the pathogenic bacterium Pseudomonas aeruginosa adapt to the antibiotic rifampicin. Specifically, we isolated the first beneficial mutation to be fixed by selection when 96 populations of three different genotypes of P. aeruginosa that vary considerably in fitness in the presence of rifampicin were challenged with adapting to a high dose of this antibiotic. The simple genetics of rifampicin resistance allowed us to determine the genetic basis of adaptation in the majority of our populations. We show that the average fitness effects of fixed beneficial mutations show a simple and clear pattern of diminishing returns, such that selection tends to fix mutations with progressively smaller effects as populations approach a peak on the adaptive landscape. The fitness effects of individual mutations, on the other hand, are highly idiosyncratic across genetic backgrounds, revealing pervasive epistasis. In spite of this complexity of genetic interactions in this system, there is an overall tendency toward diminishing-returns epistasis. We argue that a simple overall pattern of diminishing-returns adaptation emerges, despite pervasive epistasis between beneficial mutations, because many beneficial mutations are available, and while the fitness landscape is rugged at the fine scale, it is smooth and regular when we consider the average over possible routes to adaptation. In the context of antibiotic resistance, these results show that acquiring mutations that confer low levels of antibiotic resistance does not impose any constraint on the ability to evolve high levels of resistance.
Neonatal Candidiasis: Epidemiology, Risk Factors, and Clinical Judgment
Authors: Benjamin Daniel K. , Stoll Barbara J. , Gantz Marie G. , Walsh Michele C. , Sánchez Pablo J. , Das Abhik , Shankaran Seetha , Higgins Rosemary D. , Auten Kathy J. , Miller Nancy A. , Walsh Thomas J. , Laptook Abbot R. , Carlo Waldemar A. , Kennedy Kathleen A. , Finer Neil N. , Duara Shahnaz , Schibler Kurt , Chapman Rachel L. , Van Meurs Krisa P. , Frantz Ivan D. , Phelps Dale L. , Poindexter Brenda B. , Bell Edward F. , O'Shea T. Michael , Watterberg Kristi L. , Goldberg Ronald N. ,   for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network
Published: September 2010

OBJECTIVE:
Invasive candidiasis is a leading cause of infection-related morbidity and mortality in extremely low birth weight (&lt;1000-g) infants. We quantified risk factors that predict infection in premature infants at high risk and compared clinical judgment with a prediction model of invasive candidiasis.

METHODS:
The study involved a prospective observational cohort of infants ≤1000 g birth weight at 19 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. At each sepsis evaluation, clinical information was recorded, cultures were obtained, and clinicians prospectively recorded their estimate of the probability of invasive candidiasis. Two models were generated with invasive candidiasis as their outcome: (1) potentially modifiable risk factors; and (2) a clinical model at time of blood culture to predict candidiasis.

RESULTS:
Invasive candidiasis occurred in 137 of 1515 (9.0%) infants and was documented by positive culture from ≥1 of these sources: blood (n = 96); cerebrospinal fluid (n = 9); urine obtained by catheterization (n = 52); or other sterile body fluid (n = 10). Mortality rate was not different for infants who had positive blood culture compared with those with isolated positive urine culture. Incidence of candida varied from 2% to 28% at the 13 centers that enrolled ≥50 infants. Potentially modifiable risk factors included central catheter, broad-spectrum antibiotics (eg, third-generation cephalosporins), intravenous lipid emulsion, endotracheal tube, and antenatal antibiotics. The clinical prediction model had an area under the receiver operating characteristic curve of 0.79 and was superior to clinician judgment (0.70) in predicting subsequent invasive candidiasis.

CONCLUSION:
Previous antibiotics, presence of a central catheter or endotracheal tube, and center were strongly associated with invasive candidiasis. Modeling was more accurate in predicting invasive candidiasis than clinical judgment.
Day Care Increases the Risk of Respiratory Morbidity in Chronic Lung Disease of Prematurity
Authors: McGrath-Morrow Sharon A. , Lee Grace , Stewart Beth H. , McGinley Brian M. , Lefton-Greif Maureen A. , Okelo Sande O. , Collaco J. Michael 
Published: September 2010

OBJECTIVES:Infants and children with chronic lung disease of prematurity (CLDP) are at increased risk for morbidity and mortality from respiratory viral infections. Exposure to respiratory viruses may be increased in the day care environment. The risk of respiratory morbidity from day care attendance in the CLDP population is unknown. We therefore sought to determine if day care attendance is a significant risk factor for increased respiratory morbidity and symptoms in infants and children with CLDP.METHODS:Between January 2008 and October 2009, parents of infants and children with CLDP were surveyed. Information on perinatal history, sociodemographic information, day care attendance, and indicators of respiratory morbidity, including emergency department (ED) visits, hospitalizations, systemic corticosteroid use, antibiotic use, and respiratory symptoms, was collected on children &lt;3 years of age. Logistic regression models were constructed to examine associations between exposure to day care and respiratory morbidities.RESULTS:Data were collected from 111 patients with CLDP. The average gestational age was 26.2 ± 2.0 weeks. Day care attendance was associated with significantly higher adjusted odds for ED visits (odds ratio [OR]: 3.74 [95% confidence interval (CI): 1.41–9.91]; P &lt; .008), systemic corticosteroid use (OR: 2.22 [CI: 1.10–4.49]; P &lt; .026), antibiotic use (OR: 2.40 [CI: 1.08–5.30]; P &lt; .031), and days with trouble breathing (OR: 2.72 [CI: 1.30–5.69]; P &lt; .008). Although there was an increased OR for hospitalization (OR: 3.22 [CI: 0.97–10.72]; P &lt; .057), this did not reach statistical significance.CONCLUSIONS:We found that day care attendance is associated with increased respiratory morbidities in young children with CLDP. Physicians should consider screening for and educating caregivers about the risks of day care attendance by young children with CLDP.
Improving the Quality of Discharge Communication With an Educational Intervention
Authors: Key-Solle Mikelle , Paulk Elizabeth , Bradford Kathleen , Skinner Asheley Cockrell , Lewis Matthew C. , Shomaker Kyrie 
Published: September 2010

BACKGROUND:
Communication between hospital providers and primary care physicians at the time of hospital discharge is necessary for optimal patient care and safety. Content of the inpatient discharge summary (DS) is not uniformly addressed by residency programs.

OBJECTIVE:
To improve DSs quality through a brief educational intervention.

METHODS:
We prospectively enrolled interns (first-year pediatric residents [PL1s]) in an educational intervention that consisted of a group session in which components of a high-quality DS were taught and a subsequent brief small-group session in which key components with distribution of a reminder card were reiterated. Six key components were identified: diagnosis; timely completion; pending laboratory work/studies; medications; length ≤3 pages; and discharge weight. DSs prepared by PL1s before and after the small-group session were objectively scored by blinded reviewers on the basis of how many DS components they contained (maximum score: 6). Scores were compared with historical controls of PL1s from the previous year. Audit scores were analyzed by using a mixed-effects linear regression model.

RESULTS:
Sixty-four PL1s were enrolled in the study; 477 DSs were scored. Mean score before the small-group reminder session was 3.6 in both groups. In mixed-effects models, scores in the intervention group increased by 0.56 points (P = .002) and DSs incorporating at least 5 of 6 components increased from 22% to 41% (P &lt; .001) after the small-group session, whereas the control group's scores were unchanged.

CONCLUSION:
A brief, low-intensity educational intervention can improve quality of discharge communication and be incorporated into residency training. Electronic templates should incorporate prompts for key components of a DS.
Gender, Attention-Deficit/Hyperactivity Disorder, and Reading Disability in a Population-Based Birth Cohort
Authors: Yoshimasu Kouichi , Barbaresi William J. , Colligan Robert C. , Killian Jill M. , Voigt Robert G. , Weaver Amy L. , Katusic Slavica K. 
Published: September 2010

OBJECTIVE:
To determine the incidence of reading disability (RD) among children with and without research-identified attention-deficit/hyperactivity disorder (ADHD), separately according to gender, in a population-based birth cohort.

METHOD:
Subjects included all children born in 1976–1982 remaining in Rochester, Minnesota, after 5 years of age (n = 5718). Information from medical, school, and private tutorial records was abstracted. Cumulative incidence of RD, by any of 3 RD formulas, in children with and without ADHD and corresponding hazard ratios (HRs) were calculated separately according to gender.

RESULTS:
Cumulative incidence of RD by the age of 19 years was significantly higher in children with ADHD (51% in boys, 46.7% in girls) compared with those without ADHD (14.5% in boys, 7.7% in girls). Among children with ADHD, the risk for RD was similar in boys versus girls (HR: 1.0). However, among children without ADHD, boys were 2.0 times more likely than girls to meet RD criteria. Among girls, the HR for the risk for RD associated with ADHD (versus those without ADHD) was 8.1 (95% confidence interval: 5.7–11.5), which was significantly higher than the corresponding HR among boys (3.9 [95% confidence interval: 3.2–4.9]).

CONCLUSIONS:
The risk for RD is significantly greater among children with ADHD compared with those without ADHD. Among children with ADHD, the risk for RD is the same for boys and girls. However, among children without ADHD, boys are more at risk for RD than girls. Among girls, the magnitude of increased risk for RD associated with ADHD is nearly twice that among boys, because girls without ADHD are less likely to have RD than boys without ADHD.
Dietary and Activity Correlates of Sugar-Sweetened Beverage Consumption Among Adolescents
Authors: Ranjit Nalini , Evans Martin H. , Byrd-Williams Courtney , Evans Alexandra E. , Hoelscher Deanna M. 
Published: September 2010

OBJECTIVE:
To examine the dietary and activity correlates of sugar-sweetened beverage consumption by children in middle and high school.

METHODS:
Data were obtained from a cross-sectional survey of 15 283 children in middle and high schools in Texas. Consumption of sodas and noncarbonated flavored and sports beverages (FSBs) were examined separately for their associations with the level of (1) unhealthy food (fried meats, French fries, desserts) consumption, (2) healthy food (vegetables, fruit, and milk) consumption, (3) physical activity including usual vigorous physical activity and participation in organized physical activity, and (4) sedentary activity, including hours spent watching television, using the computer, and playing video games.

RESULTS:
For both genders, consumption of soda and FSBs was systematically associated with a number of unhealthy dietary practices and with sedentary behaviors. However, consumption of FSBs showed significant positive graded associations with several healthy dietary practices and level of physical activity, whereas soda consumption showed no such associations with healthy behaviors.

CONCLUSIONS:
Consumption of FSBs coexists with healthy dietary and physical activity behaviors, which suggests popular misperception of these beverages as being consistent with a healthy lifestyle. Assessment and obesity-prevention efforts that target sugar-sweetened beverages need to distinguish between FSBs and sodas.
Organic Thin-film Transistors for pH Detection
Authors: Demelas Monia , Caboni Alessandra , Barbaro Massimo , Bonfiglio Annalisa 
Published: September 2010

AbstractA novel, flexible and ductile organic field-effect transistor (OFET) able to detect pH changes in chemical solutions has been realized and successfully tested. With respect to other organic pH sensors, based on an ISFET-like structure, in our approach the organic transistor is completely separated from the sensing active area and its gate is left floating. The device is biased with a fourth electrode (control-gate) capacitively coupled to the floating-gate. The floating-gate is functionalized by deposition of a layer of thio-amines able to protonize proportionally to the pH value of the solution thus modulating the drain current. The structure does not need an Ag/AgCl counter-electrode since the control-gate is not in contact with the solution. Moreover, the sensing mechanism does not depend on the choice of the dielectric and semiconductor material since the working principle is based on charge separation in the metal induced by the electric field. This structure also simplifies the realization of the fluidics since all the contactable electrodes (drain, source and control-gate) are on the same side of the substrate. A differential measurement approach was adopted in order to get rid of device aging and process-related fluctuations. With the same structure, other chemical species may be detected provided that a proper functionalization procedure is adopted.
Preparation and characterization of LiFePO4/graphene-oxide composites
Authors: Yu Hongming , Pan Ruijun , Chen Xuefei , Song Wentao , Xie Jian , Zhao Xinbing 
Published: September 2010

AbstractLiFePO4/graphene-oxide (GNO) composites were prepared by co-precipitation method. Their structure and morphology were investigated by X-ray diffraction, Fourier transform infrared spectra, field emission scanning electron microscopy, and transmission electron microscopy. A low content of GNO can be uniformly dispersed in the matrix of LiFePO4 nano particles, while at a higher content, GNO will aggregate severely and has a negative effect on the electrochemical performance of LiFePO4. Further heat treatment can improve the crystallinity of LiFePO4, and improve the electrochemical performance of LiFePO4 with a relatively low content of GNO.
Significant Ultra-low Percolation Threshold, Enhanced Positive Temperature Coefficient Effect and Dielectric Permittivity in Polymer-based Composites with Immiscible Polymers
Authors: Xu Haiping , Bing Naici , Wu Yihua , Yang Dandan , Dang Zhimin 
Published: September 2010

AbstractSignificant conductive polymer-based composites consisting of immiscible semi-crystalline polymers PP and PVDF, at different volume ratios loaded with a certain concentration of CB were prepared by blending and sequent hot-pressing technology. The distributing status of CB in the polymers was evaluated through the micrographs of the composite. The percolation threshold of this kind of composite is much lower than those of the individual polymers. Even more, the composite at 1/1 volume ratio of PP and PVDF displays the best conductivity among different ratios at a certain concentration of CB, and it displays an outstanding PTC effect more than five orders of magnitude, and synchronously an enhanced dielectric permittivity about 24.9 at 100 Hz. These inimitable properties may owe to the formation of PP/PVDF co-continuous phases and a double-percolation effect in the composite. The novel polymer-based composite with ultra-low percolation threshold, enhanced PTC effect, as well as the significant dielectric permittivity is promising a potential application.
Bardet-Biedl Syndrome
Authors: Imhoff Olivier , Marion Vincent , Stoetzel Corinne , Durand Myriam , Holder Muriel , Sigaudy Sabine , Sarda Pierre , Hamel Christian P. , Brandt Christian , Dollfus Hélène , Moulin Bruno 
Published: September 2010

Summary

Background and Objectives
Bardet-Biedl Syndrome (BBS) is a rare autosomal recessive ciliopathy with a wide spectrum of clinical features including obesity, retinitis pigmentosa, polydactyly, mental retardation, hypogonadism, and renal abnormalities. The molecular genetic profile of BBS is currently being investigated after the recent identification of 14 BBS genes involved in primary cilia-linked disease. This study aims to characterize the renal and cardiovascular presentations and to analyze possible relationships between genotypes and clinical phenotypes.

Design, setting, participants & measurements
This clinical study was performed in a national cohort of 33 BBS patients, 22 men and 11 women, all aged >16 years (mean age 26.3 years).

Results
Renal abnormalities, including impairment of renal function and signs of chronic interstitial nephropathy of dysplastic nature, were documented in 82% of the patients. Cardiovascular evaluations revealed that this group of young patients had significant cardiovascular risk factors. Hypertension was found in >30% of the patients and hyperlipidemia in >60%, and almost 50% had other metabolic abnormalities. Overt diabetes was present in only 6%. With regard to genotype-phenotype correlation, patients with a mutation in the BBS6, BBS10, or BBS12 gene (10 of 33 patients) had more severe renal disease.

Conclusions
Our study results confirm the frequent occurrence of renal involvement in patients with BBS, underscore the high risk of cardiovascular disease in these patients, and provide new information on a possible genotype-phenotype correlation.
Indoxyl Sulfate–Induced Endothelial Dysfunction in Patients with Chronic Kidney Disease via an Induction of Oxidative Stress
Authors: Yu Mina , Kim Young Ju , Kang Duk-Hee 
Published: September 2010

Summary

Background and objectives
Recent data suggest indoxyl sulfate (IS), one of the uremic toxins that accelerate the progression of chronic kidney disease (CKD), may also be responsible for vascular disease via an induction of oxidative stress. The role of IS in endothelial dysfunction in CKD and potential mechanisms of IS-induced endothelial dysfunction were investigated.

Design, setting, participants, & measurements
A prospective observational study in 40 CKD patients was performed. Flow-mediated endothelium-dependent vasodilatation (FMD) and its reaction time before and 24 weeks after an oral adsorbent of IS were evaluated. Plasma levels of IS and markers of oxidative stress were also measured. The proliferation, senescence, and production of nitric oxide and reactive oxygen species from human umbilical vein endothelial cells (HUVEC) were evaluated and the effect of antioxidants, N-acetylcysteine, rotenone, and apocynin was examined to explore the mechanism of IS-induced endothelial dysfunction.

Results
AST-120 treatment for 24 weeks resulted in a significant increase in FMD with a decrease in IS and oxidized/reduced glutathione ratio. The presence of diabetes and high-sensitivity C-reactive protein were the independent predictors for an improved FMD. IS induced a production of reactive oxygen species in HUVEC, and pretreatment with antioxidants ameliorated IS-induced inhibition of proliferation and nitric oxide production and inhibited a senescence of HUVEC.

Conclusions
IS may play an important role in endothelial dysfunction via generation of oxidative stress with an induction of endothelial senescence. AST-120 improved endothelial dysfunction in patients with CKD associated with a decrease in IS and a restoration of antioxidant reserve.