bluuebunny/crossref_metadata_2025_split huggingface dataset:
Buried in the Middle but Guilty: Intronic Mutations in the TCIRG1 Gene Cause Human Autosomal Recessive Osteopetrosis
Authors: Palagano Eleonora , Blair Harry C , Pangrazio Alessandra , Tourkova Irina , Strina Dario , Angius Andrea , Cuccuru Gianmauro , Oppo Manuela , Uva Paolo , Van Hul Wim , Boudin Eveline , Superti-Furga Andrea , Faletra Flavio , Nocerino Agostino , Ferrari Matteo C , Grappiolo Guido , Monari Marta , Montanelli Alessandro , Vezzoni Paolo , Villa Anna , Sobacchi Cristina 
Published: April 2015

Abstract

Autosomal recessive osteopetrosis (ARO) is a rare genetic bone disease with genotypic and phenotypic heterogeneity, sometimes translating into delayed diagnosis and treatment. In particular, cases of intermediate severity often constitute a diagnostic challenge and represent good candidates for exome sequencing. Here, we describe the tortuous path to identification of the molecular defect in two siblings, in which osteopetrosis diagnosed in early childhood followed a milder course, allowing them to reach the adult age in relatively good conditions with no specific therapy. No clearly pathogenic mutation was identified either with standard amplification and resequencing protocols or with exome sequencing analysis. While evaluating the possible impact of a 3'UTR variant on the TCIRG1 expression, we found a novel single nucleotide change buried in the middle of intron 15 of the TCIRG1 gene, about 150 nucleotides away from the closest canonical splice site. By sequencing a number of independent cDNA clones covering exons 14 to 17, we demonstrated that this mutation reduced splicing efficiency but did not completely abrogate the production of the normal transcript. Prompted by this finding, we sequenced the same genomic region in 33 patients from our unresolved ARO cohort and found three additional novel single nucleotide changes in a similar location and with a predicted disruptive effect on splicing, further confirmed in one of them at the transcript level. Overall, we identified an intronic region in TCIRG1 that seems to be particularly prone to splicing mutations, allowing the production of a small amount of protein sufficient to reduce the severity of the phenotype usually associated with TCIRG1 defects. On this basis, we would recommend including TCIRG1 not only in the molecular work-up of severe infantile osteopetrosis but also in intermediate cases and carefully evaluating the possible effects of intronic changes. © 2015 American Society for Bone and Mineral Research.
Differences in food intake of tumour‐bearing cachectic mice are associated with hypothalamic serotonin signalling
Authors: Dwarkasing Jvalini T. , Boekschoten Mark V. , Argilès Joseph M. , van Dijk Miriam , Busquets Silvia , Penna Fabio , Toledo Miriam , Laviano Alessandro , Witkamp R. F. , van Norren Klaske 
Published: April 2015

AbstractBackgroundAnorexia is a common symptom among cancer patients and contributes to malnutrition and strongly impinges on quality of life. Cancer‐induced anorexia is thought to be caused by an inability of food intake‐regulating systems in the hypothalamus to respond adequately to negative energy balance during tumour growth. Here, we show that this impaired response of food‐intake control is likely to be mediated by altered serotonin signalling and by failure in post‐transcriptional neuropeptide Y (NPY) regulation.MethodsTwo tumour cachectic mouse models with different food intake behaviours were used: a C26‐colon adenocarcinoma model with increased food intake and a Lewis lung carcinoma model with decreased food intake. This contrast in food intake behaviour between tumour‐bearing (TB) mice in response to growth of the two different tumours was used to distinguish between processes involved in cachexia and mechanisms that might be important in food intake regulation. The hypothalamus was used for transcriptomics (affymetrix chips).ResultsIn both models, hypothalamic expression of orexigenic NPY was significantly higher compared with controls, suggesting that this change does not directly reflect food intake status but might be linked to negative energy balance in cachexia. Expression of genes involved in serotonin signalling showed to be different between C26‐TB mice and Lewis lung carcinoma‐TB mice and was inversely associated with food intake. In vitro, using hypothalamic cell lines, serotonin repressed neuronal hypothalamic NPY secretion while not affecting messenger NPY expression, suggesting that serotonin signalling can interfere with NPY synthesis, transport, or secretion.ConclusionsAltered serotonin signalling is associated with changes in food intake behaviour in cachectic TB mice. Serotonins' inhibitory effect on food intake under cancer cachectic conditions is probably via affecting the NPY system. Therefore, serotonin regulation might be a therapeutic target to prevent the development of cancer‐induced eating disorders.
The delayed recovery of the remobilized rat tibialis anterior muscle reflects a defect in proliferative and terminal differentiation that impairs early regenerative processes
Authors: Slimani Lamia , Vazeille Emilie , Deval Christiane , Meunier Bruno , Polge Cécile , Dardevet Dominique , Béchet Daniel , Taillandier Daniel , Micol Didier , Listrat Anne , Attaix Didier , Combaret Lydie 
Published: April 2015

AbstractBackgroundThe immobilization‐induced tibialis anterior (TA) muscle atrophy worsens after cast removal and is associated with altered extracellular matrix (ECM) composition. The secreted protein acidic and rich in cysteine (Sparc) is an ECM component involved in Akt activation and in β‐catenin stabilization, which controls protein turnover and induces muscle regulatory factors (MRFs), respectively. We hypothesized that ECM alterations may influence these intracellular signalling pathways controlling TA muscle mass.MethodsSix‐month‐old Wistar rats were subjected to hindlimb cast immobilization for 8 days (I8) or not (I0) and allowed to recover for 1 to 10 days (R1–10).ResultsThe TA atrophy during remobilization correlated with reduced fibre cross‐sectional area and thickening of endomysium. mRNA levels for Sparc increased during remobilization until R10 and for integrin‐α7 and ‐β1 at I8 and R1. Integrin‐linked kinase protein levels increased during immobilization and remobilization until R10. This was inversely correlated with changes in Akt phosphorylation. β‐Catenin protein levels increased in the remobilized TA at R1 and R10. mRNA levels of the proliferative MRFs (Myf5 and MyoD) increased at I8 and R1, respectively, without changes in Myf5 protein levels. In contrast, myogenin mRNA levels (a terminal differentiation MRF) decreased at R1, but only increased at R10 in remobilized muscles, as for protein levels.ConclusionsAltogether, this suggests that the TA inefficiently attempted to preserve regeneration during immobilization by increasing transcription of proliferative MRFs, and that the TA could engage recovery during remobilization only when the terminal differentiation step of regeneration is enhanced.
The july effect: An analysis of never events in the nationwide inpatient sample
Authors: Wen Timothy , Attenello Frank J. , Wu Brian , Ng Alvin , Cen Steven Y. , Mack William J. 
Published: April 2015

BACKGROUNDPrior studies examining the impact of the “July effect” on in‐hospital mortality rates have generated variable results. In 2008, the Centers for Medicare & Medicaid Services published a series of high‐cost, high‐volume, nonreimbursable hospital‐acquired complications (HACs). These events were believed to be preventable and indicate deficiencies in healthcare delivery.OBJECTIVEThe present study aims to investigate the impact of July admissions on patient safety in a national sample using the HACs as a metric.DESIGN/SETTING/PATIENTSDischarge data were collected from all admissions recorded in the Nationwide Inpatient Sample database from 2008 to 2011. HAC incidence was evaluated as a function of admission month, adjusting for demographic and hospital factors in multivariable analysis.MEASURESThe outcome measures were HAC occurrence, prolonged length of stay (LOS), and higher inpatient costs.RESULTSA total of 143,019,381 inpatient admissions were recorded, with an overall HAC occurrence of 4.7%. July admissions accounted for 7.6% of the total number of inpatient admissions. July admissions experienced a 6% increase in likelihood of HAC occurrence (odds ratio = 1.06, 95% confidence interval: 1.06–1.07, P < 0.001) when compared to those admitted during all other months. Patients with HAC occurrence had almost 2 times increased likelihood of prolonged LOS (P < 0.001) and higher inpatient costs (P < 0.001).CONCLUSIONSJuly admissions are associated with increased likelihood of HAC occurrence. This trend may represent breakdowns in organization structure distinct from traditional quality measures, requiring novel transition protocols dedicated to improving HACs. Journal of Hospital Medicine 2015;10:432–438. © 2015 Society of Hospital Medicine
Comparison of Aggregate Stability Measurement Methods for Clay‐rich Soils in Asartepe Catchment of Turkey
Authors: Saygin Selen D. , Erpul Gunay , Basaran Mustafa 
Published: April 2015

AbstractThere are many methods and approaches of determining the structural status of soils as a quality indicator. But there is no common method for aggregate stability measurement that can be used for all soil types and circumstances affecting aggregate disruption. This study aimed to compare different aggregate stability methods for clay‐rich soil systems of semi‐arid lands, where desertification is a significant threat to land resources. The study area is located in the Asartepe catchment of Ankara, Turkey, mainly including land use types of secondary forest, grassland and rainfed arable land. Four research methods were tested: (1) fast wetting (FW); (2) slow wetting (SW); (3) mechanical breakdown (MB) and (4) multiple sieve separation process (MSSP). For clay rich soils (C% ≥ 38) with different land use types in the semiarid region, it was found that MSSP has a greater potential for soil aggregate stability differences to statistically reflect slight variations in SOC than FW, SW and MB. Although the research specifically includes the results from certain land uses and soil types, it is not limited to those but should provide useful findings to help interpret the impairment of soil structural stability differences under various management systems and the processes that each methodology tries to reproduce in a close linkage to given soil properties. Copyright © 2015 John Wiley & Sons, Ltd.
Runoff Trends Driven by Climate and Afforestation in a Pyrenean Basin
Authors: Buendia Cristina , Batalla Ramon J. , Sabater Sergi , Palau Antoni , Marcé Rafael 
Published: April 2015

AbstractThe abandonment of traditional rural life in mountain areas has favoured the expansion of forest in the headwaters of Pyrenean rivers. In this paper, we (i) analyse hydro‐climatic trends at the annual and monthly scales in three nested sub‐catchments in a central Pyrenean basin and (ii) quantify the relative contribution of climate change and forest cover on the observed changes in runoff. Land use maps indicate an increase in the forest cover in all sub‐basins for the period 1987–2009. Non‐parametric Mann–Kendall statistic on annual and monthly hydro‐climatic data from 1965 to 2009 was used to identify trends in climate and runoff data. To assess the potential influence of the period length, trends were also examined for the 1941–2009 stretch. Upward trends were detected for temperature and potential evapotranspiration, particularly during summer and winter months. Precipitation trends and their significance depended on the length of the period considered, although overall results indicated a decrease, particularly for February and July. The effects of climate change and land cover change on annual runoff were identified by means of a change point analysis. Results indicated that a change in annual runoff took place in the 1980s, suggesting the non‐linearity in the relationship between precipitation and runoff, and thus the influence of land use factors. The influence of forest cover was confirmed by comparing observed runoff trends with those resulting from a hydro‐climatic model that does not take into account land use changes. Divergence between both trends revealed that forest cover can account for ~40% of the observed decrease in annual runoff. Copyright © 2015 John Wiley & Sons, Ltd.
Abnormal sonographic appearance of posterior brain at 11–14 weeks and fetal outcome
Authors: Volpe P. , Muto B. , Passamonti U. , Rembouskos G. , De Robertis V. , Campobasso G. , Tempesta A. , Volpe G. , Fanelli T. 
Published: April 2015

AbstractObjectiveThe aim of this retrospective study was to describe the sonographic appearance of the posterior brain anatomy in normal fetuses at 11 to 14 weeks of pregnancy and to determine the fetal outcome when one of the posterior brain anatomical space is not recognized.MethodsTwo groups of patients were included in the study: a control group of consecutive 311 healthy fetuses with a normal sonogram and a study group of 21 fetuses with absence of one of the three posterior brain spaces. In each fetus, images of the mid‐sagittal view of the fetal face and brain at 11 to 14 weeks of gestation were obtained.ResultsIn all fetuses with absence of one of the three posterior brain spaces, a severe anomaly, including open spina bifida, cephalocele, Dandy–Walker complex, and chromosomal aberrations, was associated.ConclusionOur study indicates that the sonographic finding characterized by the absence of one of the three posterior brain spaces seems to facilitate not only the detection of open spina bifida, as previously reported, but also of other neural tube defects, such as cephalocele, and is an important risk factor for cystic posterior brain anomalies, and/or chromosomal abnormalities. Thus it seems a poor prognostic finding for major fetal abnormalities. © 2015 John Wiley & Sons, Ltd.
Gene expression during the first 28 days of axolotl limb regeneration I: Experimental design and global analysis of gene expression
Authors: Voss S. Randal , Palumbo Alex , Nagarajan Radha , Gardiner David M. , Muneoka Ken , Stromberg Arnold J. , Athippozhy Antony T. 
Published: April 2015

AbstractWhile it is appreciated that global gene expression analyses can provide novel insights about complex biological processes, experiments are generally insufficiently powered to achieve this goal. Here we report the results of a robust microarray experiment of axolotl forelimb regeneration. At each of 20 post‐amputation time points, we estimated gene expression for 10 replicate RNA samples that were isolated from 1 mm of heterogeneous tissue collected from the distal limb tip. We show that the limb transcription program diverges progressively with time from the non‐injured state, and divergence among time adjacent samples is mostly gradual. However, punctuated episodes of transcription were identified for five intervals of time, with four of these coinciding with well‐described stages of limb regeneration—amputation, early bud, late bud, and pallet. The results suggest that regeneration is highly temporally structured and regulated by mechanisms that function within narrow windows of time to coordinate transcription within and across cell types of the regenerating limb. Our results provide an integrative framework for hypothesis generation using this complex and highly informative data set.
Bayesian model selection using the median probability model
Authors: Ghosh Joyee 
Published: April 2015

In the Bayesian approach to model selection, models and model specific parameters are treated as unknown quantities and uncertainty about them are expressed through prior distributions. Given the observed data, updating of the prior distribution to the posterior distribution occurs via Bayes' theorem. The posterior probability of a given model may be interpreted as the support it gets based on the observed data. The highest probability model (HPM) that receives the maximum support from the data is a possible choice for model selection. For large model spaces, Markov chain Monte Carlo (MCMC) algorithms are commonly used to estimate the posterior distribution over models. However, estimates of posterior probabilities of individual models based on MCMC output are not reliable because the number of MCMC samples is typically far smaller than the size of the model space. Thus, the HPM is difficult to estimate and for large model spaces it often has a very small posterior probability. An alternative to the HPM is the median probability model (MPM) of Barbieri and Berger, which has been shown to be the optimal model for prediction using a squared error loss function, under certain conditions. In this article we review some of the conditions for which the MPM is optimal, and provide real data examples to evaluate the performance of the MPM under small and large model spaces. We also discuss the behavior of the MPM under collinearity. WIREs Comput Stat 2015, 7:185–193. doi: 10.1002/wics.1352This article is categorized under:

Statistical and Graphical Methods of Data Analysis > Bayesian Methods and Theory
Statistical and Graphical Methods of Data Analysis > Markov Chain Monte Carlo (MCMC)
Synthesis, Structure and Thermal Decomposition of the Bismuth Silyltellurolate Bi(TeSitBu2Ph)3
Authors: Traut Stephan , Stahl Sven , Eichhöfer Andreas , von Hänisch Carsten 
Published: April 2015

AbstractThe compound Bi(TeSitBu2Ph)3 (1) was obtained from the reaction of BiCl3 with tBu2PhSiTeSiMe3 in diethyl ether. The single crystal structure analysis revealed a trigonal pyramidal structure of the BiTe3 core and weak Bi···C(arene) contacts. Compound 1 was characterized by multinuclear NMR spectroscopy, IR spectroscopy and elemental analysis. Thermogravimetric experiments show that compound 1 decomposes with formation of Bi2Te3 or a mixture of elemental bismuth and Bi4Te3, depending on the pressure conditions.
Disaster Education in Australian Schools
Authors: Boon Helen J. , Pagliano Paul J. 
Published: April 2015

AbstractAustralia regularly suffers floods, droughts, bushfires and cyclones, which are predicted to increase and/or intensify in the future due to climate change. While school-aged children are among the most vulnerable to natural disasters, they can be empowered through education to prepare for and respond to disasters. School disaster education is essential to raise awareness among students and their communities and to encourage preparedness action. However, evaluation of Australian school-based disaster education programs has been limited. This article presents the results of a critical literature review of peer-reviewed publications on disaster education programs in Australian schools conducted through Scopus, A Plus, PsycINFO and the Education Resources Information Center (ERIC) databases. Results highlight a significant dearth of studies examining disaster education programs in Australian schools. Recommendations for future research are proposed to bridge knowledge gaps and establish disaster preparedness resources that support children's knowledge and preparedness for disasters.
Canadian Emergency Medicine Residents’ Perspectives on Pediatric Pain Management
Authors: Ali Huma , Kircher Janeva , Meyers Christine , MacLellan Joseph , Ali Samina 
Published: April 2015

AbstractBackgroundUnder-treatment of children’s pain in the emergency department (ED) can have many detrimental effects. Emergency medicine (EM) residents often manage pediatric pain, but their educational needs and perspectives have not been studied.MethodsA novel online survey was administered from May to June 2013 to 122 EM residents at three Canadian universities using a modified Dillman methodology. The survey instrument captured information on training received in pediatric acute pain management, approach to common painful presentations, level of comfort, perceived facilitators, and barriers and attitudes towards pediatric pain.Results56 residents participated (46%), 25 of whom (45%) indicated they had not received any training in pediatric pain assessment. All levels of residents reported they were uncomfortable with pain assessment in 0-2 year olds (p=0.07); level of comfort with assessment increased with years of training for patients aged 2-12 years (p=0.02). When assessing children with disabilities, 83% of respondents (45/54) indicated they were ‘extremely’ or ‘somewhat’ uncomfortable. Sixty-nine percent (38/55) had received training on how to treat pediatric pain. All residents reported they were more comfortable using pain medication for a 9 year old, as compared to a 1 year old (oral oxycodone p<0.001, oral morphine p<0.001, IV morphine p=0.004). The preferred methods to learn about children’s pain management were role-modeling (61%) and lectures (57%). The top challenges in pain management were with non-verbal, younger, or developmentally delayed patients.ConclusionCanadian EM residents report receiving inadequate training in pediatric pain management, and are particularly uneasy with younger or developmentally disabled children. Post-graduate curricula should be adjusted to correct these self-identified weaknesses in children’s pain management.
Short- and long-term reliability of adult recall of vegetarian dietary patterns in the Adventist Health Study-2 (AHS-2)
Authors: Teixeira Martins Marcia C. , Jaceldo-Siegl Karen , Fan Jing , Singh Pramil , Fraser Gary E. 
Published: April 2015

AbstractPast dietary patterns may be more important than recent dietary patterns in the aetiology of chronic diseases because of the long latency in their development. We developed an instrument to recall vegetarian dietary patterns during the lifetime and examined its reliability of recall over 5·3 and 32·6 years on average. The short-term/5-year recall ability study (5-RAS) was done using 24 690 participants from the cohort of the Adventist Health Study-2 (mean age 62·2 years). The long-term/33-year recall ability study (33-RAS) included an overlap population of 1721 individuals who joined the Adventist Health Study-1 and Adventist Health Study-2 (mean age 72·5 years). Spearman correlation coefficients for recall of vegetarian status were 0·78 and 0·72 for the 5-RAS and 33-RAS, respectively, when compared with ‘reference’ data. For both time periods sensitivity and positive predictive values were highest for the lacto-ovo-vegetarian and non-vegetarian patterns (vegans, lacto-ovo-vegetarians, pesco-vegetarians, semi-vegetarians and non-vegetarians). In the 5-RAS analyses, male, non-black, younger, and more educated participants, lifetime Adventists, and those with more stability of consumption of animal products generally showed higher recall ability. Somewhat similar tendencies were shown for the 33-RAS analyses. Our findings show that the instrument has higher reliability for recalled lacto-ovo-vegetarian and non-vegetarian than for vegan, semi- and pesco-vegetarian dietary patterns in both short- and long-term recalls. This is in part because these last dietary patterns were greatly contaminated by recalls that correctly would have belonged in the adjoining category that consumed more animal products.