bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emerging roles of pulmonary macrophages in driving the development of severe asthma
Authors: Yang Ming , Kumar Rakesh K , Hansbro Philip M , Foster Paul S 
Published: February 2012

ABSTRACTAsthma is recognized as a heterogeneous disorder, although in most patients, the clinical manifestations are effectively managed with established combination therapies. However, 5–10% of asthmatics have severe asthma, which does not respond to treatment, and these patients account for &gt;50% of asthma-related healthcare costs. New investigations into the pathogenesis of glucocorticoid resistance in severe asthma indicate that pulmonary macrophages may play central roles in promoting airway inflammation, particularly in asthma that is resistant to steroid therapy. Importantly, factors that are linked to the activation of pulmonary macrophages may contribute to glucocorticoid resistance and severe asthma. Here, we review recent advances in understanding the roles of pulmonary macrophages in the mechanisms of glucocorticoid resistance and the pathogenesis of severe asthma. We discuss the role of macrophage phenotype, infection, IFN-γ, LPS, associated signaling pathways, TNF-α, MIF, and other macrophage-associated factors. Understanding the pathogenesis of steroid-resistant severe asthma will contribute to the identification of optimal therapeutic strategies for the effective management of the disease.
Moderating role of the MAOA genotype in antisocial behaviour
Authors: Fergusson David M. , Boden Joseph M. , Horwood L. John , Miller Allison , Kennedy Martin A. 
Published: February 2012

BackgroundRecent studies have examined gene×environment (G×E) interactions involving the monoamine oxidase A (MAOA) gene in moderating the associations between exposure to adversity and antisocial behaviour. The present study examined a novel method for assessing interactions between a single gene and multiple risk factors related to environmental and personal adversity.AimsTo test the hypothesis that the presence of the low-activity MAOA genotype was associated with an increased response to a series of risk factors.MethodParticipants were 399 males from the Christchurch Health and Development Study who had complete data on: (a) MAOA promoter region variable number tandem repeat genotype; (b) antisocial behaviour (criminal offending) to age 30 and convictions to age 21; and (c) maternal smoking during pregnancy, IQ, childhood maltreatment and school failure.ResultsPoisson regression models were fitted to three antisocial behaviour outcomes (property/violent offending ages 15–30; and convictions ages 17–21), using measures of exposure to adverse childhood circumstances. The analyses revealed consistent evidence of G x E interactions, such that those with the low-activity MAOA variant who were exposed to adversity in childhood were significantly more likely to report offending in late adolescence and early adulthood.ConclusionsThe present findings add to the evidence suggesting that there is a stable G x E interaction involving MAOA, a range of adverse environmental and personal factors, and antisocial behaviour across the life course. These analyses also demonstrate the utility of using multiple environmental/personal exposures to test G×E interactions.
Should registrars be reporting after-hours CT scans? A calculation of error rate and the influencing factors in South Africa
Authors: Terreblanche Owen D , Andronikou Savvas , Hlabangana Linda T , Brown Taryn , Boshoff Pieter E 
Published: February 2012

BackgroundThere is a heavy reliance on registrars for after-hours CT reporting with a resultant unavoidable error rate.PurposeTo determine the after-hours CT reporting error rate by radiology registrars and influencing factors on this error rate.Material and MethodsA 2-month prospective study was undertaken at two tertiary, level 1 trauma centers in Johannesburg, South Africa. Provisional CT reports issued by the registrar on call were reviewed by a qualified radiologist the following morning and information relating to the number, time and type of reporting errors made as well as the body region scanned, indication for the scan, year of training of the registrar, and workload during the call were recorded and analyzed.ResultsA total of 1477 CT scans were performed with an overall error rate of 17.1% and a major error rate of 7.7%. The error rate for 2nd, 3rd, and 4th year registrars was 19.4%, 15.1%, and 14.5%, respectively. A significant difference was found between the error rate in reporting trauma scans (15.8%) compared to non-trauma scans (19.2%) although the difference between emergency scans (16.9%) and elective scans (22.6%) was found to be not significant, a finding likely due to the low number of elective scans performed. Abdominopelvic scans elicited the highest number of errors (33.9%) compared to the other body regions such as head (16.5%) and cervical, thoracic, or lumbar spine (11.7%). Increasing workload resulted in a significant increase in error rate when analyzed with a generalized linear model. There was also a significant difference noted in the time of scan groups which we attributed to a workload effect. Missed findings were the most frequent errors seen (57.3%).ConclusionWe found an increasing error rate associated with increasing workload and marked increase in errors with the reporting of abdominopelvic scans. There was a decrease in the error rate when looking an increasing year of training although this there was only found to be significant difference between the 2nd and 3rd year registrars.
Microfluidic Amplification as a Tool for Massive Parallel Sequencing of the Familial Hypercholesterolemia Genes
Authors: Hollants Silke , Redeker Egbert J W , Matthijs Gert 
Published: February 2012

Abstract

BACKGROUND
Familial hypercholesterolemia (FH) is an autosomal dominant disorder that affects cholesterol metabolism and is an important risk factor for heart disease. Three different genes were causally linked to this disorder: LDLR (low density lipoprotein receptor), APOB [apolipoprotein B (including Ag(x) antigen)], and PCSK9 (proprotein convertase subtilisin/kexin type 9). We evaluated a new amplicon preparation tool for resequencing these genes on next generation sequencing (NGS) platforms.

METHODS
For the 3 genes, 38 primer pairs were designed and loaded on the Fluidigm Access Array, a microfluidic array in which a PCR was performed. We amplified 144 DNA samples (73 positive controls and 71 patient samples) and performed 3 sequencing runs on a GS FLX Titanium system from Roche 454, using pyrosequencing. Data were analyzed with the SeqNext module of the Sequence Pilot software.

RESULT
From the 38 amplicons, 37 were amplified successfully, without any further optimization. Sequencing resulted in a mean coverage of the individual amplicons of 71-fold, 74-fold, and 117-fold for the 3 runs, respectively. In the positive controls, all known mutations were identified. In 29% of the patient samples, a pathogenic point mutation or small deletion/insertion was found. Large rearrangements were not detectable with NGS, but were picked up by multiplex ligation-dependent probe amplification.

CONCLUSIONS
Combining a microfluidic amplification system with massive parallel sequencing is an effective method for mutation scanning in FH patients, which can be implemented in diagnostics. For data analysis, we propose a minimum variant frequency threshold of 20% and a minimum coverage of 25-fold.
Neural Correlates of Humor Detection and Appreciation in Children
Authors: Neely Michelle N. , Walter Elizabeth , Black Jessica M. , Reiss Allan L. 
Published: February 2012

Humor is a vital component of human well-being. Neuroimaging studies conducted with adults indicate that humor activates specific brain regions, including the temporo-occipito-parietal junction (TOPJ), involved in incongruity resolution, and mesolimbic regions, involved in reward processing. However, no study to date has used neuroimaging to examine humor in typically developing children. Here, we illuminate the neural network involved in the detection and appreciation of humor in childhood.Fifteen typically developing children (ages, 6–12 years) were invited to watch and respond to video clips while neural activity was imaged with a 3T GE Discovery MR750 scanner. Before presentation during functional imaging, the clips were evaluated by age-matched controls and were representative of three categories: Funny, Positive (enjoyable but not funny), and Neutral (not intended to evoke any emotional response). We found TOPJ and mesolimbic activation in children's response to humor, suggesting these regions may form a humor-essential neural network already present in childhood. Furthermore, in a novel comparison of Funny to Positive stimuli, we found that bilateral TOPJ activation may be specific to humor processing and not part of a general constellation of neural activity in response to reward. Finally, we observed greater activation in the inferior frontal gyrus and nucleus accumbens in younger participants, indicating humor activation intensity changes during development.By providing a crucial link in studying the neurodevelopment of humor processing across the lifespan, our findings contribute valuable information about the evolution of how children understand their world.
Tissue Architecture in the Caenorhabditis elegans Gonad Depends on Interactions Among Fibulin-1, Type IV Collagen and the ADAMTS Extracellular Protease
Authors: Kubota Yukihiko , Nagata Kayo , Sugimoto Asako , Nishiwaki Kiyoji 
Published: February 2012

Abstract
Molecules in the extracellular matrix (ECM) regulate cellular behavior in both development and pathology. Fibulin-1 is a conserved ECM protein. The Caenorhabditis elegans ortholog, FBL-1, regulates gonad-arm elongation and expansion by acting antagonistically to GON-1, an ADAMTS (adisintegrin and metalloprotease with thrombospondin motifs) family protease. The elongation of gonad arms is directed by gonadal distal tip cells (DTCs). Here we report that a dominant mutation in the EMB-9/type IV collagen α1 subunit can compensate for loss of FBL-1 activity in gonadogenesis. A specific amino acid substitution in the noncollagenous 1 (NC1) domain of EMB-9 suppressed the fbl-1 null mutant. FBL-1 was required to maintain wild-type EMB-9 in the basement membrane (BM), whereas mutant EMB-9 was retained in the absence of FBL-1. EMB-9 (either wild type or mutant) localization in the BM enhanced PAT-3/β-integrin expression in DTCs. In addition, overexpression of PAT-3 partially rescued the DTC migration defects in fbl-1 mutants, suggesting that EMB-9 acts in part through PAT-3 to control DTC migration. In contrast to the suppression of fbl-1(tk45), mutant EMB-9 enhanced the gonadal defects of gon-1(e1254), suggesting that it gained a function similar to that of wild-type FBL-1, which promotes DTC migration by inhibiting GON-1. We propose that FBL-1 and GON-1 control EMB-9 accumulation in the BM and promote PAT-3 expression to control DTC migration.
Roles for Receptors, Pheromones, G Proteins, and Mating Type Genes During Sexual Reproduction in Neurospora crassa
Authors: Kim Hyojeong , Wright Sara J , Park Gyungsoon , Ouyang Shouqiang , Krystofova Svetlana , Borkovich Katherine A 
Published: February 2012

Abstract
Here we characterize the relationship between the PRE-2 pheromone receptor and its ligand, CCG-4, and the general requirements for receptors, pheromones, G proteins, and mating type genes during fusion of opposite mating-type cells and sexual sporulation in the multicellular fungus Neurospora crassa. PRE-2 is highly expressed in mat a cells and is localized in male and female reproductive structures. Δpre-2 mat a females do not respond chemotropically to mat A males (conidia) or form mature fruiting bodies (perithecia) or meiotic progeny (ascospores). Strains with swapped identity due to heterologous expression of pre-2 or ccg-4 behave normally in crosses with opposite mating-type strains. Coexpression of pre-2 and ccg-4 in the mat A background leads to self-attraction and development of barren perithecia without ascospores. Further perithecial development is achieved by inactivation of Sad-1, a gene required for meiotic gene silencing. Findings from studies involving forced heterokaryons of opposite mating-type strains show that presence of one receptor and its compatible pheromone is necessary and sufficient for perithecial development and ascospore production. Taken together, the results demonstrate that although receptors and pheromones control sexual identity, the mating-type genes (mat A and mat a) must be in two different nuclei to allow meiosis and sexual sporulation to occur.
A General Population Genetic Framework for Antagonistic Selection That Accounts for Demography and Recurrent Mutation
Authors: Connallon Tim , Clark Andrew G 
Published: February 2012

Abstract
Antagonistic selection—where alleles at a locus have opposing effects on male and female fitness (“sexual antagonism”) or between components of fitness (“antagonistic pleiotropy”)—might play an important role in maintaining population genetic variation and in driving phylogenetic and genomic patterns of sexual dimorphism and life-history evolution. While prior theory has thoroughly characterized the conditions necessary for antagonistic balancing selection to operate, we currently know little about the evolutionary interactions between antagonistic selection, recurrent mutation, and genetic drift, which should collectively shape empirical patterns of genetic variation. To fill this void, we developed and analyzed a series of population genetic models that simultaneously incorporate these processes. Our models identify two general properties of antagonistically selected loci. First, antagonistic selection inflates heterozygosity and fitness variance across a broad parameter range—a result that applies to alleles maintained by balancing selection and by recurrent mutation. Second, effective population size and genetic drift profoundly affect the statistical frequency distributions of antagonistically selected alleles. The “efficacy” of antagonistic selection (i.e., its tendency to dominate over genetic drift) is extremely weak relative to classical models, such as directional selection and overdominance. Alleles meeting traditional criteria for strong selection (Nes &gt;&gt; 1, where Ne is the effective population size, and s is a selection coefficient for a given sex or fitness component) may nevertheless evolve as if neutral. The effects of mutation and demography may generate population differences in overall levels of antagonistic fitness variation, as well as molecular population genetic signatures of balancing selection.
Rapid and Robust Resampling-Based Multiple-Testing Correction with Application in a Genome-Wide Expression Quantitative Trait Loci Study
Authors: Zhang Xiang , Huang Shunping , Sun Wei , Wang Wei 
Published: February 2012

AbstractGenome-wide expression quantitative trait loci (eQTL) studies have emerged as a powerful tool to understand the genetic basis of gene expression and complex traits. In a typical eQTL study, the huge number of genetic markers and expression traits and their complicated correlations present a challenging multiple-testing correction problem. The resampling-based test using permutation or bootstrap procedures is a standard approach to address the multiple-testing problem in eQTL studies. A brute force application of the resampling-based test to large-scale eQTL data sets is often computationally infeasible. Several computationally efficient methods have been proposed to calculate approximate resampling-based P-values. However, these methods rely on certain assumptions about the correlation structure of the genetic markers, which may not be valid for certain studies. We propose a novel algorithm, rapid and exact multiple testing correction by resampling (REM), to address this challenge. REM calculates the exact resampling-based P-values in a computationally efficient manner. The computational advantage of REM lies in its strategy of pruning the search space by skipping genetic markers whose upper bounds on test statistics are small. REM does not rely on any assumption about the correlation structure of the genetic markers. It can be applied to a variety of resampling-based multiple-testing correction methods including permutation and bootstrap methods. We evaluate REM on three eQTL data sets (yeast, inbred mouse, and human rare variants) and show that it achieves accurate resampling-based P-value estimation with much less computational cost than existing methods. The software is available at http://csbio.unc.edu/eQTL.
Studies of Archaeological Bone Structure by Different Analytical Methods
Authors: Rudovica V. , Viksna A. , Katkevich J. , Zarina G. , Bitenieks J. , Zicans J. , Leito I. , Vahur S. 
Published: February 2012

Studies of Archaeological Bone Structure by Different Analytical Methods
Preservation of the structure of archaeological bones was studied by examining their physicochemical properties. The mechanical properties, and conductivity porosity, crystallinity and content of organic material were evaluated. These parameters were established to be suitable for characterizing changes in the course of time of archaeological bone structure. The obtained results revealed that the elastic modulus and conductivity changes depended on the porosity of bones; and the increase in crystallinity was correlated with a loss of organic matter.
Posterior fossa epidural hematomas in children: clinical experience with 40 cases
Authors: Sencer Altay , Aras Yavuz , Akcakaya Mehmet Osman , Goker Burcu , Kırıs Talat , Canbolat Ali Tuncay 
Published: February 2012

Object
Traumatic posterior fossa epidural hematoma (PFEDH) is rare, but among children it may have a slightly higher incidence. With the widespread use of CT scanning, the diagnosis of PFEDH can be established more accurately, leading to an increased incidence of the lesion and possibly to a better patient prognosis. This study presents 40 pediatric cases with PFEDH.

Methods
The authors assessed the type of trauma, clinical findings on admission, Glasgow Coma Scale scores, CT findings (thickness of the hematoma, bone fracture, compression of the fourth ventricle, and ventricle enlargement), type of treatment, clinical course, and prognosis. Early postoperative CT scans (within the first 6 hours) were obtained and reviewed in all surgical cases.

Results
Twenty-nine patients underwent surgery and 11 patients received conservative therapy and close follow-up. All patients fared well, and there was no surgical mortality or morbidity.

Conclusions
Based on the data in this large series, the authors conclude that PFEDH in children can be treated in experienced centers with excellent outcome, and there is no need to avoid surgery when it is indicated.
Metastasis of soft-tissue myoepithelial carcinoma to clivus
Authors: Bohnstedt Bradley N. , Tomcik Matthew , Eads Todd , Hagen Matthew C. , Shah Mitesh 
Published: February 2012

The differential diagnosis for masses involving the clivus is broad. The authors present a case of myoepithelial carcinoma metastatic to the clivus, a lesion that has not been reported to their knowledge. This 14-year-old girl with a history of myoepithelial carcinoma originating in the soft tissues of the left hip and metastatic to the lung presented with left lateral gaze palsy. Imaging demonstrated a 3 × 3–cm osteolytic mass in the clivus. Microscopic transsphenoidal resection with endoscopic assistance was performed. Pathological findings were consistent with the previously diagnosed myoepithelial carcinoma. Within 4 weeks postoperatively and 2 weeks into a chemotherapeutic regimen, the tumor exhibited progression. Radiation therapy was started and growth of the tumor was halted.
Myoepithelial carcinoma should be included in the differential diagnosis for clival masses, especially in patients with previously diagnosed myoepithelial carcinoma. The primary management of this tumor should be with chemotherapy and radiation, with surgery serving only for decompression.
Histological analysis of the third ventricle floor in hydrocephalic and nonhydrocephalic brains: application to neuroendocrine complications following third ventriculostomy procedures
Authors: Tubbs R. Shane , Hattab Eyas M. , Loukas Marios , Chern Joshua J. , Wellons Melissa , Wellons John C. , Iskandar Bermans J. , Cohen-Gadol Aaron A. 
Published: February 2012

Object
Endocrine dysfunction following endoscopic third ventriculostomy (ETV) is rare, but it has been reported. In the present study the authors sought to determine the histological nature of the floor of the third ventricle in hydrocephalic brains to better elucidate this potential association.

Methods
Five adult cadaveric brains with hydrocephalus were examined. Specifically, the floors of the third ventricle of these specimens were studied histologically. Age-matched controls without hydrocephalus were used for comparison.

Results
Although it was thinned in the hydrocephalic brains, the floor of the third ventricle had no significant difference between the numbers of neuronal cell bodies versus nonhydrocephalic brains.

Conclusions
Although uncommon following ETV, endocrine dysfunction has been reported. Based on the present study, this is most likely to be due to the injury of normal neuronal cell bodies found in this location, even in very thinned-out tissue.
Natural history and imaging prevalence of cavernous malformations in children and young adults
Authors: Al-Holou Wajd N. , O'Lynnger Thomas M. , Pandey Aditya S. , Gemmete Joseph J. , Thompson B. Gregory , Muraszko Karin M. , Garton Hugh J. L. , Maher Cormac O. 
Published: February 2012

Object
This study was undertaken to define the age-related prevalence of cavernous malformations (CMs) in children and young adults undergoing intracranial imaging. In addition, the authors aim to clarify the natural history of CMs in young people, especially in those with incidentally discovered lesions.

Methods
To identify those patients with CMs, the authors retrospectively reviewed the electronic medical records of 14,936 consecutive patients 25 years of age or younger who had undergone brain MR imaging. In patients with a CM, clinical and imaging data were collected. Patients with untreated cavernomas who had more than 6 months of clinical and MR imaging follow-up were included in a natural history analysis. The natural history analysis included 110 CMs in 56 patients with a 3.5-year mean clinical follow-up interval (199 patient-years and 361 cavernoma-years).

Results
In 92 patients (0.6%), 164 CMs were identified. The imaging prevalence of cavernomas increased with advancing age (p = 0.002). Multiple CMs occurred in 28 patients (30%), and 8 patients (9%) had a family history of multiple CMs. Fifty patients (54%) presented with symptoms related to the cavernoma, of whom 30 presented with hemorrhage (33%). Of the 164 cavernomas identified, 103 (63%) were considered incidental, asymptomatic lesions. Larger size was associated with acute symptomatic presentation (p = 0.0001). During the follow-up interval, 6 patients with 8 cavernomas developed 11 symptomatic hemorrhages after initial identification. Five of the patients who had a hemorrhage during the follow-up interval had initially presented with hemorrhage, while only 1 had presented incidentally. The hemorrhage rate for all patients in the natural history group was 1.6% per patient-year and 0.9% per cavernoma-year. The hemorrhage rate was 8.0% per patient-year in the symptomatic group versus 0.2% in the incidental group. Symptomatic hemorrhage after long-term follow-up was associated with initial acute presentation (p = 0.02).

Conclusions
The imaging prevalence of CM increases with advancing age during childhood. Patients presenting without hemorrhage have a significantly lower risk of bleeding compared with those who present with acute neurological symptoms. Comparing this series of children to prior analyses of CM natural history in adults, the authors' data do not suggest a higher bleeding risk in younger patients.