bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deletions of the PRKAR1A Locus at 17q24.2-q24.3 in Carney Complex: Genotype-Phenotype Correlations and Implications for Genetic Testing
Authors: Salpea Paraskevi , Horvath Anelia , London Edra , Faucz Fabio R. , Vetro Annalisa , Levy Isaac , Gourgari Evgenia , Dauber Andrew , Holm Ingrid A. , Morrison Patrick J. , Keil Margaret F. , Lyssikatos Charalampos , Smith Eric D. , Sanidad Marc A. , Kelly JoAnn C. , Dai Zunyan , Mowrey Philip , Forlino Antonella , Zuffardi Orsetta , Stratakis Constantine A. 
Published: October 2013

Background:
Carney complex (CNC) is a multiple neoplasia syndrome caused by PRKAR1A-inactivating mutations. One-third of the patients, however, have no detectable PRKAR1A coding sequence defects. Small deletions of the gene were previously reported in few patients, but large deletions of the chromosomal PRKAR1A locus have not been studied systematically in a large cohort of patients with CNC.

Setting:
A tertiary care referral center was the setting for analysis of an international cohort of patients with CNC.

Methods:
Methods included genome-wide array analysis followed by fluorescent in situ hybridization, mRNA, and other studies as well as a retrospective analysis of clinical information and phenotype-genotype correlation.

Results:
We detected 17q24.2-q24.3 deletions of varying size that included the PRKAR1A gene in 11 CNC patients (of 51 tested). Quantitative PCR showed that these patients had significantly lower PRKAR1A mRNA levels. Phenotype varied but was generally severe and included manifestations that are not commonly associated with CNC, presumably due to haploinsufficiency of other genes in addition to PRKAR1A.

Conclusions:
A significant number (21.6%) of patients with CNC that are negative in currently available testing may have PRKAR1A haploinsufficiency due to genomic defects that are not detected by Sanger sequencing. Array-based studies are necessary for diagnostic confirmation of these defects and should be done in patients with unusual and severe phenotypes who are PRKAR1A mutation-negative.
Biomarkers of Brain Injury in Cerebral Infections
Authors: Rohlwink Ursula K , Figaji Anthony A 
Published: October 2013

Abstract

BACKGROUND
Central nervous system (CNS) infections present a major burden of disease worldwide and are associated with high rates of mortality and morbidity. Swift diagnosis and initiation of appropriate treatment are vital to minimize the risk of poor outcome; however, tools are lacking to accurately diagnose infection, assess injury severity, and predict outcome. Biomarkers of structural neurological injury could provide valuable information in addressing some of these challenges.

CONTENT
In this review, we summarize experimental and clinical research on biomarkers of neurological injury in a range of CNS infectious diseases. Data suggest that in both adults and children, the biomarkers S100B and neuron-specific enlose (NSE), among others, can provide insight into the pathophysiology of CNS infection and injury severity, evolution, and response to treatment. Research into the added utility of combining a panel of biomarkers and in assessing biomarker association with clinical and radiological outcomes warrants further work. Various factors, including age, the establishment of normative values, and comparison of biomarker concentrations across different testing platforms still present challenges in biomarker application.

SUMMARY
Research regarding the value of biomarkers in CNS infections is still in its infancy. However, early evidence supports their utility in diagnosis and prognosis, and potentially as effective surrogate end points in the assessment of novel interventions.
The long road to recognition: New musical theatre development in Britain
Authors: Lundskaer-Nielsen Miranda 
Published: October 2013

Abstract
In the wake of the ‘megamusicals’ at the end of the twentieth century, this article explores the current state of new British musical development. The article outlines the challenges faced by producers, venues and writers engaged with new musicals that do not conform to the demands of the West End and examines recent developments that have started to address these hurdles. The article draws on interviews conducted by the author in 2012 with thirteen contemporary practitioners (including producers, writers, teachers and theatre programmers) to create a snapshot of the current and potential future state of new British musical theatre development.
Fading Signatures of Critical Brain Dynamics during Sustained Wakefulness in Humans
Authors: Meisel Christian , Olbrich Eckehard , Shriki Oren , Achermann Peter 
Published: October 2013

Sleep encompasses approximately a third of our lifetime, yet its purpose and biological function are not well understood. Without sleep optimal brain functioning such as responsiveness to stimuli, information processing, or learning may be impaired. Such observations suggest that sleep plays a crucial role in organizing or reorganizing neuronal networks of the brain toward states where information processing is optimized.Increasing evidence suggests that cortical neuronal networks operate near a critical state characterized by balanced activity patterns, which supports optimal information processing. However, it remains unknown whether critical dynamics is affected in the course of wake and sleep, which would also impact information processing. Here, we show that signatures of criticality are progressively disturbed during wake and restored by sleep. We demonstrate that the precise power-laws governing the cascading activity of neuronal avalanches and the distribution of phase-lock intervals in human electroencephalographic recordings are increasingly disarranged during sustained wakefulness. These changes are accompanied by a decrease in variability of synchronization. Interpreted in the context of a critical branching process, these seemingly different findings indicate a decline of balanced activity and progressive distance from criticality toward states characterized by an imbalance toward excitation where larger events prevail dynamics. Conversely, sleep restores the critical state resulting in recovered power-law characteristics in activity and variability of synchronization. These findings support the intriguing hypothesis that sleep may be important to reorganize cortical network dynamics to a critical state thereby assuring optimal computational capabilities for the following time awake.
Effect of Processing on the Microstructure and Electrical Conductivity of Hot Pressed PMMA/ITO Bulk Nanocomposites
Authors: Capozzi Charles J. , Gerhardt Rosario A. 
Published: October 2013

AbstractThere are few studies that discuss the effect of the fabrication conditions and bulk thickness on the electrical conductivity of hot pressed polymer-matrix composites. For polymer-matrix composites that possess a segregated-network microstructure, the processing parameters can significantly impact the electrical properties and microstructure of the composite material. Our group has recently fabricated novel polymer-matrix nanocomposites, which possess a segregated network microstructure containing regular, polyhedral-shaped polymer matrix particles1-2. This paper investigates the effect of processing pressure and specimen thickness on the electrical properties and microstructure of hot pressed poly(methyl methacrylate) (PMMA) containing segregated networks of indium tin oxide (ITO) nanopowders.
Proteomic Analyses of Human Gingival and Periodontal Ligament Fibroblasts
Authors: McKnight Holly , Kelsey W. Patrick , Hooper Deborah A. , Hart Thomas C. , Mariotti Angelo 
Published: October 2013

Background: Although human gingival fibroblasts (hGFs) and human periodontal ligament fibroblasts (hPDLFs) exhibit numerous phenotypic similarities, it has been suggested that the secretory and behavioral differences, which exist between these cell types, are a result of the membrane protein composition of these cells.Methods: Four matched pairs of hGFs and hPDLFs were cultured. Before confluence, membrane‐bound and ‐associated proteins from cells of the fourth passage were extracted. The processed protein samples were evaluated using capillary‐liquid chromatography‐nanospray tandem mass spectrometry. Global protein identification was performed on an orbitrap mass spectrometer equipped with a microspray source operated in positive ion mode. Proteome software was used to validate protein identifications derived from tandem mass spectrometry sequencing results.Results: Four hundred fifty proteins were common to both hGFs and hPDLFs. Of the proteins identified, 214 were known membrane‐bound or ‐associated proteins, and 165 proteins were known nuclear‐associated proteins. Twenty‐seven proteins, identified from the 450 proteins, common to both hGFs and hPDLFs, were detected in statistically significant greater quantities in either hGFs or hPDLFs. More specifically, 13 proteins were detected in significantly greater quantities in hGFs, whereas 14 proteins were detected in significantly greater quantities in hPDLFs.Conclusions: Distinct differences in the cellular protein catalog may reflect the dynamic role and high energy requirements of hGFs in extracellular matrix remodeling and response to inflammatory challenge as well as the role of hPDLFs in monitoring mechanical stress and maintaining tissue homeostasis during regeneration and remineralization.
Initiation and Gradual Intensification of Premixed Insulin Lispro Therapy Versus Basal ± Mealtime Insulin in Patients With Type 2 Diabetes Eating Light Breakfasts
Authors: Giugliano Dario , Tracz Mariusz , Shah Sanjiv , Calle-Pascual Alfonso , Mistodie Cristina , Duarte Rui , Sari Ramazan , Woo Vincent , Jiletcovici Alina O. , Deinhard Jürgen , Wille Simone A. , Kiljański Jacek 
Published: October 2013

OBJECTIVEWe compared two strategies initiating and intensifying insulin treatment and tested for noninferiority of premixed insulin to basal ± mealtime insulin analog in patients eating light breakfasts.RESEARCH DESIGN AND METHODSThis randomized, open-label, 48-week study compared two algorithms. Up to three injections of insulin lispro mix 25 and/or insulin lispro mix 50 (premix; premixed insulin lispro) or basal insulin glargine plus up to three injections of insulin lispro (basal+; glargine + insulin lispro) were used in type 2 diabetic patients uncontrolled with oral antihyperglycemic medication and consuming &lt;15% daily calories at breakfast. The hypothesis was to test noninferiority of premix to basal+ for glycemic control measured by HbA1c after 48 weeks, assessed using ANCOVA with a 0.4% margin.RESULTSPatients (n = 344; 176 [51%] females; mean [SD] age 54.3 [8.8] years; BMI 29.4 [4.6] kg/m2; baseline HbA1c 9.02 [0.97]%) were randomized to premix (n = 171) or basal+ (n = 173). In the per-protocol analysis (n = 230), least squares means (95% CI) end point HbA1c were 7.40% (7.15–7.65) and 7.55% (7.27–7.82) in respective arms. Between-treatment difference was −0.14% (−0.42 to 0.13), with noninferiority met. Significantly more patients in premix achieved HbA1c targets of &lt;7.0% compared with basal+ (48.2 vs. 36.2%; P = 0.024). Self-monitored blood glucose profiles, body weight changes, total insulin doses, and overall hypoglycemia (65 vs. 60%) were similar in premix and basal+ (P = 0.494), except nocturnal episodes (34.3 vs. 23.7%; P = 0.018) were more common in premix.CONCLUSIONSBoth intensive insulin strategies improved glycemic control; however, final HbA1c levels were seen above those achieved in previous treat-to-target trials, likely due to the inadequate insulin titrations and probably due to the complexity of tested insulin regimens. A higher percentage of patients achieved target HbA1c &lt;7% with multiple premixed insulins, but this treatment resulted in more nocturnal hypoglycemia than a basal–bolus regimen.
Changing Impact of Modifiable Risk Factors on the Incidence of Major Outcomes of Type 1 Diabetes
Authors: Miller Rachel G. , Secrest Aaron M. , Ellis Demetrius , Becker Dorothy J. , Orchard Trevor J. 
Published: October 2013

OBJECTIVE
The incidence of type 1 diabetes complications appears to be decreasing, but relative contributions of risk factors are unclear. We thus estimated the effect of modifiable risk factors on the incidence of a composite end point, major outcomes of diabetes (MOD).

RESEARCH DESIGN AND METHODS
The Pittsburgh Epidemiology of Diabetes Complications (EDC) Study was used to derive two cohorts based on diabetes diagnosis year (1960–1969 and 1970–1980). Baseline exam data in the current analysis for the 1960s group were collected in 1986–1988 and for the 1970s in 1996–1998. Each group was followed for 8 years for MOD incidence (diabetes-related death, myocardial infarction, revascularization procedure/blockage ≥50%, stroke, end-stage renal disease, blindness, and amputation). Assessed risk factors include the following: HbA1c, hypertension, microalbuminuria, BMI, hypercholesterolemia, and smoking. Accelerated failure time models were used to estimate the acceleration factor.

RESULTS
MOD incidence decreased in the 1970s cohort (15.8% [95% CI 11.6–21.4]) compared with the 1960s (22.6% [17.0–29.1]) over the 8-year follow-up (P = 0.06). Hypertension and microalbuminuria were associated with significantly accelerated MOD incidence in both cohorts (P &lt; 0.01 for both). High HbA1c (P = 0.0005), hypercholesterolemia (P = 0.01), and current smoking (P = 0.003) significantly accelerated the incidence of MOD in the 1960s but not 1970s cohort. BMI was not associated with MOD in either cohort.

CONCLUSIONS
These results suggest that hypertension and microalbuminuria remain important predictors of complications that are not being adequately addressed.
Health-Related Quality of Life Predicts Major Amputation and Death, but Not Healing, in People With Diabetes Presenting With Foot Ulcers: The Eurodiale Study
Authors: Siersma Volkert , Thorsen Hanne , Holstein Per E. , Kars Marleen , Apelqvist Jan , Jude Edward B. , Piaggesi Alberto , Bakker Karel , Edmonds Michael , Jirkovská Alexandra , Mauricio Didac , Ragnarson Tennvall Gunnel , Reike Heinrich , Spraul Maximilian , Uccioli Luigi , Urbancic Vilma , van Acker Kristien , van Baal Jeff , Schaper Nicolaas C. 
Published: October 2013

OBJECTIVE
Low health-related quality of life (HRQoL) has been consistently reported to be associated with poor prognosis for a variety of health outcomes in various settings. We aimed to evaluate whether HRQoL in patients presenting with new diabetic foot ulcers (DFUs) has prognostic significance for ulcer healing, major amputation, and death.

RESEARCH DESIGN AND METHODS
We followed 1,088 patients with new DFUs presenting for treatment at one of the 14 centers in 10 European countries participating in the Eurodiale (European Study Group on Diabetes and the Lower Extremity) study, prospectively until healing (76.9%), major amputation (4.6%), or death (6.4%) up to a maximum of 1 year. At baseline, patient and ulcer characteristics were recorded as well as EQ-5D, a standardized instrument consisting of five domains and a visual analog scale for use as a measure of HRQoL. The prognostic influence of the EQ-5D domains was evaluated in multivariable Cox regression analyses on the time-to-event data, adjusting for baseline clinical characteristics of the ulcer and comorbidities.

RESULTS
While predictive effects of HRQoL, adjusted for possible confounders, were absent for healing, decreased HRQoL, especially in the physical domains, was statistically significant for major amputation (mobility, self-care, usual activities) and death (self-care, usual activities, pain/discomfort).

CONCLUSIONS
Low HRQoL appears to be predictive for major amputation and death, but high HRQoL does not increase healing. Future studies into the influence of HRQoL on ulcer outcome are important in attempts to decrease treatment failure and mortality.
Diagnosis of chronic small bowel disease in cats: 100 cases (2008–2012)
Authors: Norsworthy Gary D. , Scot Estep J. , Kiupel Matti , Olson Jennifer C. , Gassler Loren N. 
Published: October 2013

Abstract
Objective—To determine whether a diagnosis of chronic small bowel disease could be established in a subset of cats that had clinical signs of chronic vomiting, chronic small bowel diarrhea, weight loss, or a combination of these, combined with ultrasonographically determined thickening of the small bowel.
Design—Retrospective case series.
Animals—100 client-owned domestic cats.
Procedures—Medical records of cats with clinical signs of chronic vomiting, chronic small bowel diarrhea, weight loss, or a combination of these, combined with ultrasonographically determined small bowel thickening, that underwent laparotomy and multiple small bowel biopsies between 2008 and 2012 were examined. Biopsy specimens were submitted for histologic evaluation, immunohistochemical evaluation, and, when findings were ambiguous, PCR assay for antigen receptor rearrangement.
Results—Chronic small bowel disease was diagnosed in 99 of the 100 cats. The most common diagnoses were chronic enteritis and intestinal lymphoma.
Conclusions and Clinical Relevance—Results suggested that cats with clinical signs of chronic small bowel disease should undergo detailed diagnostic testing because they are likely to have clinically important, diagnosable, treatable disease. Clinical signs of small bowel disease, especially weight loss and chronic or recurrent vomiting, are extremely common in cats. These signs should not be considered a normal condition and should not be ignored, regardless of common explanations given by owners, and cats with these signs should undergo appropriate diagnostic testing.
Arthritis Self-Efficacy Scale Scores in Knee Osteoarthritis: A Systematic Review and Meta-analysis Comparing Arthritis Self-Management Education With or Without Exercise
Authors: Brand Emily , Nyland John , Henzman Cameron , Mcginnis Mark 
Published: October 2013

Study Design Systematic literature review and meta-analysis. Objective To evaluate studies that used arthritis self-management education alone or with exercise to improve Arthritis Self-Efficacy Scale scores of patients with knee osteoarthritis. Background Increasing self-efficacy may improve patient knee osteoarthritis symptom management and function. Methods MEDLINE (1946–March 2013), CINAHL (1981–March 2013), and PsycINFO (1967–March 2013) databases were searched. Results Twenty-four studies, including 3163 subjects (women, n = 2547 [80.5%]; mean ± SD age, 65.3 ± 6.5 years), met the inclusion criteria. A meta-analysis was performed to compare the standardized mean difference effect sizes (Cohen d) of randomized controlled studies that used the Arthritis Self-Efficacy Scale pain (13 studies, n = 1906), other symptoms (13 studies, n = 1957), and function (5 studies, n = 399) subscales. Cohen d effect sizes were also calculated for cohort studies that used the Arthritis Self-Efficacy Scale pain (10 studies, n = 1035), other symptoms (9 studies, n = 913), and function (3 studies, n = 141) subscales. Both randomized controlled studies and cohort studies were grouped by intervention type (intervention 1, arthritis self-management education alone; intervention 2, arthritis self-management education with exercise), and effect sizes were compared (Mann-Whitney U tests, P<.05). Interventions that used arthritis self-management education with exercise displayed higher methodological quality scale scores (76.8 ± 13.1 versus 61.6 ± 19.6, P = .03). Statistically significant standardized effect-size differences between intervention 1 and intervention 2 were not observed. Conclusion Small to moderate effect sizes were observed regardless of whether the intervention included exercise. Exercise interventions used in conjunction with arthritis self-management education programs need to be developed to better enhance the self-efficacy of patients with knee osteoarthritis. Level of Evidence Therapy, level 2b-. J Orthop Sports Phys Ther 2013;43(12):895–910. Epub 30 October 2013. doi:10.2519/jospt.2013.4471
A Callixylon (Archaeopteridales, Progymnospermopsida) trunk with preserved secondary phloem from the Late Devonian of Morocco
Authors: Decombeix Anne‐Laure , Meyer‐Berthaud Brigitte 
Published: October 2013

• Premise of the study: During the Devonian, the evolution of secondary phloem produced by a bifacial vascular cambium was a key innovation that increased the ability of plants within the lignophyte clade to redistribute photosynthates and other organic compounds throughout their body. Unraveling the secondary phloem anatomy of the first arborescent lignophytes is crucial to understand the evolution of this tissue and the physiology of early trees.• Methods: A 10 cm wide stem of Callixylon with preserved secondary phloem from the Famennian of Morocco is described using thin‐sections.• Key results: The secondary phloem of this Callixylon zalesskyi‐type of stem is composed of fibers, sclereids, rays, axial parenchyma, and putative sieve cells. Fibers differentiate early and are relatively abundant in the inner phloem. In the older phloem, fibers are arranged in tangential bands alternating with extensive layers of axial parenchyma. Changes between the young and old phloem involve the periclinal division and radial elongation of the axial parenchyma cells. The presence of fibers in the inner, presumably functional phloem, combined with evidence for rhythmicity in the production of different phloem cell types are documented for the first time in detail in an archaeopteridalean progymnosperm. No periderm was observed within the preserved seven millimeters of bark tissues.• Conclusions: The secondary phloem anatomy supports a close affinity of archaeopteridalean progymnosperms with both aneurophytalean progymnosperms and seed plants. The production of secondary phloem might have provided an advantage to these first arborescent lignophytes over other types of Devonian early trees, especially in dry conditions.
L'évolution du manager : un pilote de communauté de pratique entre l'expert et l'intrapreneur
Authors: Bootz Jean-Philippe 
Published: October 2013

Malgré leur caractère récent, les communautés de pratique pilotées connaissent, avec l’avènement d’une économie fondée sur les connaissances, un développement significatif et rapide au sein des organisations. Elles constituent à ce titre un véritable « germe de changement » structurant pour l’évolution du management. Ces communautés pilotées ont par ailleurs la particularité d’être des structures hybrides qui conservent pour partie leur dimension auto-organisée tout en étant articulées à l’organisation formelle. L’objet de cet article est, à travers une investigation structurée de la littérature, de déterminer l’impact de ces structures hybrides, sur l’avenir du management et des managers. Nos réflexions portent en particulier sur les défis que constituent pour le management, le pilotage de ces communautés afin de parvenir à concilier deux éléments a priori antagonistes : l’auto-organisation et le pilotage. Elles portent également sur les conséquences de la multiplication de ces communautés pilotées sur l’évolution du profil des managers. Une synthèse des principales études empiriques récentes nous conduit à opérer une distinction entre communautés stratégiques d’exploration et communautés opérationnelles d’exploitation. Nous en déduisons deux figures de manager correspondants : l’intrapreneur et l’expert.