bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low‐Density Lipoprotein Receptor Gene Familial Hypercholesterolemia Variant Database: Update and Pathological Assessment
Authors: Usifo Ebele , Leigh Sarah E. A. , Whittall Ros A. , Lench Nicholas , Taylor Alison , Yeats Corin , Orengo Christine A. , Martin Andrew C. R. , Celli Jacopo , Humphries Steve E. 
Published: August 2012

SummaryFamilial hypercholesterolemia (FH) is caused predominately by variants in the low‐density lipoprotein receptor gene (LDLR). We report here an update of the UCL LDLR variant database to include variants reported in the literature and in‐house between 2008 and 2010, transfer of the database to LOVDv.2.0 platform (https://grenada.lumc.nl/LOVD2/UCL‐Heart/home.php?select_db=LDLR) and pathogenicity analysis. The database now contains over 1288 different variants reported in FH patients: 55% exonic substitutions, 22% exonic small rearrangements (<100 bp), 11% large rearrangements (>100 bp), 2% promoter variants, 10% intronic variants and 1 variant in the 3' untranslated sequence. The distribution and type of newly reported variants closely matches that of the 2008 database, and we have used these variants (n= 223) as a representative sample to assess the utility of standard open access software (PolyPhen, SIFT, refined SIFT, Neural Network Splice Site Prediction Tool, SplicePort and NetGene2) and additional analyses (Single Amino Acid Polymorphism database, analysis of conservation and structure and Mutation Taster) for pathogenicity prediction. In combination, these techniques have enabled us to assign with confidence pathogenic predictions to 8/8 in‐frame small rearrangements and 8/9 missense substitutions with previously discordant results from PolyPhen and SIFT analysis. Overall, we conclude that 79% of the reported variants are likely to be disease causing.
Analysis of Secondary Phenotype Involving the Interactive Effect of the Secondary Phenotype and Genetic Variants on the Primary Disease
Authors: Wang Jian , Shete Sanjay 
Published: August 2012

SummaryA genome‐wide association (GWA) study is usually designed as a case‐control study, where the presence and absence of the primary disease define the cases and controls, respectively. Using the existing data from GWA studies, investigators are also trying to identify the association between genetic variants and secondary phenotypes, which are defined as traits associated with the primary disease. However, recent studies have shown that bias arises in the estimation of marker‐secondary phenotype association using originally collected data. We recently proposed a bias correction approach to accurately estimate the odds ratio (OR) for marker‐secondary phenotype association. In this communication, we further investigated whether our bias correction approach is robust for a scenario involving the interactive effect of the secondary phenotype and genetic variants on the primary disease. We found that in such a scenario, our bias correction approach also provides an accurate estimation of OR for marker‐secondary phenotype association. We investigated accuracy of our approach using simulation studies and showed that the approach better controlled for type I errors than the existing approaches. We also applied our bias correction approach to the real data analysis of association between an N‐acetyltransferase gene, NAT2, and smoking on the basis of colorectal adenoma data.
Histochemical identification of sialylated glycans in Xenopus laevis testis
Authors: Valbuena Galder , Alonso Edurne , de Ubago María Martínez , Madrid Juan Francisco , Díaz‐Flores Lucio , Sáez Francisco José 
Published: August 2012

AbstractCarbohydrate chains of glycoprotein and glycosphingolipids are highly diverse molecules involved in many cell functions, including cell recognition, adhesion and signalling. Sialylated glycans are of special interest because the terminal position of sialic acid (NeuAc) in glycans linked by different ways to subterminal monosaccharides has been shown to be involved in several biological processes, as occurs with gangliosides, which have been reported as being essential in spermatogenesis in mammals. Some glycan‐binding proteins, the lectins, which specifically recognize glycan sequences, have been extensively used to characterize tissue and cell carbohydrates by means of cytochemical techniques. The aim of the present work was to determine the presence of NeuAc by means of histochemical techniques in the testis of Xenopus laevis, an animal model widely used in cell and molecular biology research. However, considering that some NeuAc‐binding lectins are capable of binding to N‐acetylglucosamine (GlcNAc), other GlcNAc‐binding lectins were also assayed. The results showed that NeuAc is mainly expressed in the interstitium, and only a weak labelling in the male germ cells was observed. Most NeuAc was located in O‐linked oligosaccharides, but some masked NeuAc in N‐glycans were identified in primary and secondary spermatogonia and spermatocytes. By contrast, GlcNAc was widely expressed in all germ cell types. Deglycosylative pre‐treatments suggest that both N‐ and O‐glycans and/or glycolipids could be responsible for this labelling. In addition, GlcNAc in O‐linked oligosaccharides has been identified in spermatogonial cells. The acrosome of spermatids was always negative. Variations of glycan expression have been found in different cell types, suggesting that glycosylation is modified during spermatogenetic development.
The adverse influence of attention‐deficit disorder with or without hyperactivity on cognition in neurofibromatosis type 1
Authors: LIDZBA KAREN , GRANSTRÖM SOFIA , LINDENAU JORGE , MAUTNER VICTOR‐FELIX 
Published: August 2012

Aim  A substantial proportion of patients with neurofibromatosis type 1 (NF1) have attention‐deficit disorder with or without hyperactivity (AD[H]D). This study explored the influence of AD(H)D symptoms on the intellectual profile of patients with NF1.Method  We retrospectively analysed neuropsychological data from 114 children (66 males, 48 females; age range 6–16y; mean age 9y 3mo [SE 3mo]) with NF1 from an NF1 outpatients department. Assessment included psychiatric diagnosis of AD(H)D (DSM‐IV‐TR criteria) and intelligence testing (Wechsler Intelligence Scale for Children, German version). Magnetic resonance images were available for all patients, intracranial findings being an exclusion criterion. The effects of AD(H)D symptoms on intelligence and on the cognitive profile were tested by analyses of variance.Results  Patients with AD(H)D symptoms performed significantly worse than those without AD(H)D symptoms on all intelligence measures (main effects for Full‐scale, Verbal, and Performance IQ; p<0.005). Subtests typically impaired in patients with NF1 (visuospatial skills and arithmetic) were not specifically influenced by AD(H)D symptoms. There were no differences between AD(H)D subtypes.Interpretation  AD(H)D symptoms have a negative impact on the intellectual development of children with NF1. This impact seems to be of an unspecific nature, with a general attenuation of the cognitive profile.
Unregulated brain iron deposition in transgenic mice over‐expressing HMOX1 in the astrocytic compartment
Authors: Song Wei , Zukor Hillel , Lin Shih‐Hsiung , Liberman Adrienne , Tavitian Ayda , Mui Jeannie , Vali Hojatollah , Fillebeen Carine , Pantopoulos Kostas , Wu Ting‐Di , Guerquin‐Kern Jean‐Luc , Schipper Hyman M. 
Published: August 2012

AbstractThe mechanisms responsible for pathological iron deposition in the aging and degenerating mammalian CNS remain poorly understood. The stress protein, HO‐1 mediates the degradation of cellular heme to biliverdin/bilirubin, free iron, and CO and is up‐regulated in the brains of persons with Alzheimer's disease and Parkinson's disease. HO‐1 induction in primary astroglial cultures promotes deposition of non‐transferrin iron, mitochondrial damage and macroautophagy, and predisposes cocultured neuronal elements to oxidative injury. To gain a better appreciation of the role of glial HO‐1 in vivo, we probed for aberrant brain iron deposition using Perls' method and dynamic secondary ion mass spectrometry in novel, conditional GFAP.HMOX1 transgenic mice that selectively over‐express human HO‐1 in the astrocytic compartment. At 48 weeks, the GFAP.HMOX1 mice exhibited increased deposits of glial iron in hippocampus and other subcortical regions without overt changes in iron‐regulatory and iron‐binding proteins relative to age‐matched wild‐type animals. Dynamic secondary ion mass spectrometry revealed abundant FeO− signals in the transgenic, but not wild‐type, mouse brain that colocalized to degenerate mitochondria and osmiophilic cytoplasmic inclusions (macroautophagy) documented by TEM. Sustained up‐regulation of HO‐1 in astrocytes promotes pathological brain iron deposition and oxidative mitochondrial damage characteristic of Alzheimer's disease‐affected neural tissues. Curtailment of glial HO‐1 hyperactivity may limit iron‐mediated cytotoxicity in aging and degenerating neural tissues.
Holothuria grisea agglutinin (HGA): the first invertebrate lectin with anti‐inflammatory effects
Authors: Moura Raniere da M. , Aragão Karoline S. , de Melo Arthur A. , Carneiro Rômulo F. , Osório César B. H. , Luz Patricia B. , de Queiroz Alexandre F. S. , dos Santos Elizeu A. , de Alencar Nylane M. N. , Cavada Benildo S. 
Published: August 2012

AbstractHolothuria grisea agglutinin (HGA) is a dimeric lectin of molecular mass 228 kDa by gel filtration with monomers of 105 kDa by SDS‐PAGE. The lectin is highly thermostable as it retains full activity for 1 h at 70 °C. Unlike other lectins purified from marine invertebrates, the hemagglutination activity of HGA does not require any divalent metal ions. The affinity analysis of HGA showed that only mucin was able to inhibit the hemagglutinating activity. HGA administered intravenously was tested in classical models of nociception and inflammation. HGA was able to inhibit neutrophil migration into the peritoneal cavity induced by carrageenan. This inhibitory effect was 68% at a dose of 1 mg/kg. In acetic acid‐induced writhing tests, a significant antinociceptive effect was observed by treatment with HGA (0.1; 1 or 10 mg/kg) reducing constrictions by 27, 90 and 84%, respectively. In formalin tests, HGA at a dose of 10 mg/kg showed antinociceptive effect only in the inflammatory phase (phase 2). Nevertheless, in hot‐plate tests, HGA did not show any nociceptive effect. In rota‐rod and open‐field tests, HGA did not alter the animals' behavior. The treatment with HGA 10 mg/kg presented diminished myeloperoxidase activity activity (81.6% inhibition) and raised the circulating levels of NO by 50.4% when compared with the carrageenan group. HGA has demonstrated the ability to modulate the inflammatory response in models of inflammation in vivo. HGA is the first marine invertebrate lectin that showed an anti‐inflammatory effect. This finding opens a new perspective on the potential of lectins from the marine environment.
The Impact of Obstetric Unit Closures on Maternal and Infant Pregnancy Outcomes
Authors: Lorch Scott A. , Srinivas Sindhu K. , Ahlberg Corinne , Small Dylan S. 
Published: August 2012

ObjectiveTo define the association between large‐scale obstetric unit closures and relative changes in maternal and neonatal outcomes.Data Sources/Study SettingBirth and death certificates were linked to maternal and neonatal hospital discharge records for all births between January 1, 1995 and June 30, 2005 in Philadelphia, which experienced the closure of 9 of 19 obstetric units between 1997 and 2005, and five surrounding counties and eight urban counties that did not experience a similar reduction in obstetric units.DesignA before‐and‐after study design with an untreated control group compared changes in perinatal outcomes in Philadelphia to five surrounding control counties and eight urban control counties after controlling for case mix differences and secular trends (N = 3,140,782).ResultsRelative to the preclosure years, the difference in neonatal mortality (odds ratio (OR) 1.49, 95 percent CI 1.12–2.00) and all perinatal mortality (OR 1.53, 95 percent CI 1.14–2.04) increased for Philadelphia residents compared with both control groups between 1997 and 1999. After 2000, there was no statistically significant change in any outcome in Philadelphia county compared with the preclosure epoch.ConclusionsObstetric unit closures were initially associated with adverse changes in perinatal outcomes, but these outcomes ameliorated over time.
Receptor tyrosine kinase inhibitors: molecularly targeted drugs for veterinary cancer therapy
Authors: Bavcar S. , Argyle D. J. 
Published: August 2012

AbstractTyrosine kinases (TKs) are key mediators of signalling pathways in cells. Located at the surface of the cell, within the cytoplasm or in the nucleous, TKs have been showed to be involved in regulation of normal cellular processes and also play an important role in the development, progression and spread of several types of cancer. Seventy percent of TK's are Receptor Tyrosine Kinases and these have become key targets for cancer therapy. This short synopsis is intended to give the reader an introduction to this area of targeted therapy for cancer as a prelude to this special edition of Veterinary and Comparative Oncology.
Mental Disorders and Cigarette Use among Adults in the United States
Authors: Goodwin Renee D. , Zvolensky Michael J. , Keyes Katherine M. , Hasin Deborah S. 
Published: August 2012

Background:
The goal of this study was to determine the association between mental disorders and cigarette consumption and nicotine dependence.
Methods: Data were drawn from the National Epidemiologic Survey of Alcohol and Related Conditions (NESARC), a nationally representative survey of adults (N = 43,093) aged 18 and older. Relationships between specific anxiety disorders, mood disorders, nondependent cigarette use, nicotine dependence among the whole sample, and nicotine dependence among cigarette users were examined.
Results: After adjusting for demographics and comorbid mental disorders, generalized anxiety disorder (OR = 1.16 (1.29–1.51)), specific phobia (OR = 1.35 (1.21–1.51)), panic disorder (PD) (OR = 1.90 (1.62–2.23)), major depression (MDD) (OR = 1.31 (1.16–1.48)), and bipolar disorder (OR = 1.30 (1.09–1.54)) were associated with increased likelihood of nondependent cigarette use. Specific phobia (OR = 1.69 (1.49–1.91)), PD (OR = 1.82 (1.50–2.21)), MDD (OR = 1.59 (1.38–1.84)), and bipolar disorder (OR = 1.71 (1.39–2.09)) were associated with increased odds of nicotine dependence among the whole sample; social phobia (OR = 1.69 (1.19–2.40)), specific phobia (OR = 1.69 (1.43–2.01)), MDD (OR = 1.65 (1.34–2.02)), and bipolar disorder (OR = 2.38 (1.74–3.24)) were associated with increased risk of nicotine dependence among cigarette users.
Conclusions: Specific anxiety disorders and mood disorders were uniquely associated with nondependent cigarette use, nicotine dependence among the whole sample, and the risk of nicotine dependence among cigarette users in the United States. Findings suggest that demographic differences, comorbid mood, anxiety, substance, and personality disorders all contributed to previously observed associations between mental disorders and nicotine dependence, explaining these links in some but not all cases. (Am J Addict 2012;21:416–423)
Effects of platelet‐rich plasma (PRP) on the healing of Achilles tendons of rats
Authors: Kaux Jean‐François , Drion Pierre V. , Colige Alain , Pascon Frédéric , Libertiaux Vincent , Hoffmann Audrey , Janssen Lauriane , Heyers Antoine , Nusgens Betty V. , Le Goff Caroline , Gothot André , Cescotto Serge , Defraigne Jean‐Olivier , Rickert Markus , Crielaard Jean‐Michel 
Published: August 2012

AbstractPlatelet‐rich plasma (PRP) contains growth factors involved in the tissular healing process. The aim of the study was to determine if an injection of PRP could improve the healing of sectioned Achilles tendons of rats. After surgery, rats received an injection of PRP (n = 60) or a physiological solution (n = 60) in situ. After 5, 15, and 30 days, 20 rats of both groups were euthanized and 15 collected tendons were submitted to a biomechanical test using cryo‐jaws before performing transcriptomic analyses. Histological and biochemical analyses were performed on the five remaining tendons in each group. Tendons in the PRP group were more resistant to rupture at 15 and 30 days. The mechanical stress was significantly increased in tendons of the PRP group at day 30. Histological analysis showed a precocious deposition of fibrillar collagen at day 5 confirmed by a biochemical measurement. The expression of tenomodulin was significantly higher at day 5. The messenger RNA levels of type III collagen, matrix metalloproteinases 2, 3, and 9, were similar in the two groups at all time points, whereas type I collagen was significantly increased at day 30 in the PRP group. In conclusion, an injection of PRP in sectioned rat Achilles tendon influences the early phase of tendon healing and results in an ultimately stronger mechanical resistance.
Recombination Signals In The rpoC1 Gene Indicate Gene‐Flow Between Planktothrix (Cyanoprokaryota) Species
Authors: D'Alelio Domenico , Gandolfi Andrea 
Published: August 2012

The delineation of species boundaries in the potentially harmful cyanobacterium Planktothrix Anagnostidis et Komárek 1988 is particularly tangled. Genetic recombination has been invoked to explain the occurrence of overlapping biological traits among recognized species. Although horizontal gene transfer is shown as a driver of diversification in this genus, clear evidence for homologous recombination at the single gene level is still lacking. Several Planktothrix strains (n = 244) sampled in eight fresh water lakes in north Italy were characterized by sequencing the rpoC1 gene, a molecular marker previously proposed to discriminate between species. Six haplotypes were detected, four of which are newly described. A relevant number of rpoC1 sequences (n = 54) showed evidence of homologous recombination. By comparing the sequences produced in the work presented here to those available on GenBank for the genus, multiple recombination events were tracked between haplotypes associated to P. rubescens, P. suspensa and P. agardhii, the latter being a species not found in our survey. Recombination signals were in form of (i) a vast mosaic structure present in the alignment of rpoC1 haplotypes, (ii) multiple and statistically significant paths in the split decomposition network connecting these haplotypes and (iii) many individual crossing‐over events detected by means of recombination detection tests. Data suggest that the molecular evolution of the rpoC1 gene in the genus Planktothrix appears as strongly influenced by homologous recombination. In addition, rpoC1 diversity effectively tracks recombinational processes among species in the complex made up by P. rubescens, P. agardhii and P. suspensa, which are not isolated in terms of gene‐flow.
Chapter 3: Cohort Life Tables by Smoking Status, Removing Lung Cancer as a Cause of Death
Authors: Rosenberg Marjorie A. , Feuer Eric J. , Yu Binbing , Sun Jiafeng , Henley S. Jane , Shanks Thomas G , Anderson Christy M. , McMahon Pamela M. , Thun Michael J. , Burns David M. 
Published: August 2012

The purpose of this study was to develop life tables by smoking status removing lung cancer as a cause of death. These life tables are inputs to studies that compare the effectiveness of lung cancer treatments or interventions, and provide a way to quantify time until death from causes other than lung cancer. The study combined actuarial and statistical smoothing methods, as well as data from multiple sources, to develop separate life tables by smoking status, birth cohort, by single year of age, and by sex. For current smokers, separate life tables by smoking quintiles were developed based on the average number of cigarettes smoked per day by birth cohort. The end product is the creation of six non‐lung‐cancer life tables for males and six tables for females: five current smoker quintiles and one for never smokers. Tables for former smokers are linear combinations of the appropriate table based on the current smoker quintile before quitting smoking and the never smoker probabilities, plus added covariates for the smoking quit age and time since quitting.
Feasibility of Defibrillation and Automatic Arrhythmia Detection Using an Exclusively Subcutaneous Defibrillator System in Canines
Authors: CAPPATO RICCARDO , CASTELVECCHIO SERENELLA , ERLINGER PAUL , SANGHERA RICK , SCHECK DONALD , OSTROFF ALAN , RISSMANN WILLIAM , GROPPER CHARLES , BARDY GUST H. 
Published: August 2012

Subcutaneous Defibrillation in Canines. Introduction: This study reports the experimental process leading to development of an automatic totally subcutaneous implantable cardioverter defibrillator (SICD) system engineered for human use.Methods and Results: Two studies were conducted to test defibrillation and detection feasibility of an SICD system located in the left chest. In the first study, 2 pockets were created in 15 canines for placement of an anterior electrode adjacent to the left edge of the sternum and a lateral electrode at the site along the axillary line between the 4th and 6th intercostal space. Stainless steel flat electrodes with active surface areas of 5, 10, 20, and 25 cm2 or rod electrodes were subsequently positioned and the defibrillation threshold (DFT) was measured for multiple combinations. In the second study, the ability to induce, detect, and provide shock delivery in response to ventricular fibrillation (VF) using an SICD system engineered for clinical use was tested in 5 canines. One hundred and three DFT tests with 11 different dual electrode combinations were performed. All combinations terminated VF with a DFT of 35 ± 16 J (range: 9–79 J). Nineteen VF episodes were induced and recognized by the chronic SICD, leading to automatic capacitor charge and shock delivery in all cases.Conclusions: Subcutaneous defibrillation using different electrode combinations with shock energies less than 80 J terminated all induced VFs. An automatic SICD proved effective in detecting and activating shock delivery in all cases. (J Cardiovasc Electrophysiol, Vol. 24, pp. 77‐82, January 2013)
Cognizance and Consultation of Randomized Controlled Trials among Ministerial Policy Analysts
Authors: Bédard Pierre‐Olivier , Ouimet Mathieu 
Published: August 2012

AbstractConsultation of scientific evidence by policy actors has been the foci of attention of knowledge utilization scholars for decades. The present study questioned the extent to which randomized controlled trials (RCTs)—generally seen as the gold standard of scientific research—are known and consulted by policy analysts in ministerial settings. Using cross‐sectional data collected in 17 ministries inQuébec (Canada), our study showed that fairly high levels of policy analysts report never having heard ofRCTs, thus possibly hindering effective communication of scientific results to relevant policy makers. Statistical analyses reveal the importance of cognitive factors in explaining both phenomena.