bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantifying uncertainty in genotype calls
Authors: Carvalho Benilton S. , Louis Thomas A. , Irizarry Rafael A. 
Published: November 2009

AbstractMotivation: Genome-wide association studies (GWAS) are used to discover genes underlying complex, heritable disorders for which less powerful study designs have failed in the past. The number of GWAS has skyrocketed recently with findings reported in top journals and the mainstream media. Microarrays are the genotype calling technology of choice in GWAS as they permit exploration of more than a million single nucleotide polymorphisms (SNPs) simultaneously. The starting point for the statistical analyses used by GWAS to determine association between loci and disease is making genotype calls (AA, AB or BB). However, the raw data, microarray probe intensities, are heavily processed before arriving at these calls. Various sophisticated statistical procedures have been proposed for transforming raw data into genotype calls. We find that variability in microarray output quality across different SNPs, different arrays and different sample batches have substantial influence on the accuracy of genotype calls made by existing algorithms. Failure to account for these sources of variability can adversely affect the quality of findings reported by the GWAS.Results: We developed a method based on an enhanced version of the multi-level model used by CRLMM version 1. Two key differences are that we now account for variability across batches and improve the call-specific assessment of each call. The new model permits the development of quality metrics for SNPs, samples and batches of samples. Using three independent datasets, we demonstrate that the CRLMM version 2 outperforms CRLMM version 1 and the algorithm provided by Affymetrix, Birdseed. The main advantage of the new approach is that it enables the identification of low-quality SNPs, samples and batches.Availability: Software implementing of the method described in this article is available as free and open source code in the crlmm R/BioConductor package.Contact: rafa@jhu.eduSupplementary information: Supplementary data are available at Bioinformatics online.
Folic Acid, Iron, and Zinc Contents in Chosen Food Products Prepared with Fortified Flours
Authors: Boen Thaís Rezende , Lima Pallone Juliana A. 
Published: November 2009

ABSTRACTIn 2002, Brazil issued a regulation requiring that corn and wheat flours be fortified by the addition of folic acid and iron. The aim of the present work was to evaluate the levels of folic acid, iron, and zinc in macaroni, pizza, and bread prepared with fortified flour. The methodologies used for the mineral (FAAS) and vitamin (HPLC) determinations were validated and considered adequate. For macaroni, the folic acid content range was 50.0–182.4 μg/100 g. The iron and zinc levels were 1.6–5.4 mg/100 g and 0.7–1.0 mg/100 g, respectively. The pizza and bread samples contained 14.8–271.3 μg/100 g and 47.4–481.4 μg/100 g of folic acid, respectively. The iron and zinc levels were 2.6–7.3 mg/100 g and 0.4–0.9 mg/100 g, respectively, for pizza, and 3.0–12.4 mg/100 g and 0.4–0.8 mg/100 g for bread. The results indicated that the distribution of folic acid and iron in the majority of the samples tested was heterogeneous. This study could be of use to governmental authorities in their food fortification evaluation programs. Moreover, the average iron contents observed in the products could result in problems with zinc absorption, and it is important to consider that iron can induce oxidative stress in cells.
CD44+ slow‐cycling tumor cell expansion is triggered by cooperative actions of Wnt and prostaglandin E2 in gastric tumorigenesis
Authors: Ishimoto Takatsugu , Oshima Hiroko , Oshima Masanobu , Kai Kazuharu , Torii Ryota , Masuko Takashi , Baba Hideo , Saya Hideyuki , Nagano Osamu 
Published: November 2009

(Cancer Sci 2010; 101: 673–678)Similar to normal tissue stem cells, cancer stem cells (CSCs) are thought to be quiescent or slow‐cycling and, thereby, insensitive to chemo‐ and radiotherapies. CD44, a cell surface component that interacts with the extracellular matrix, has been found to be highly expressed in CSCs of several solid tumors. However, the relevancy between CD44+ cells and slow‐cycling cells and the underlying mechanisms for the emergence of CD44+ CSCs during tumorigenesis have not been elucidated. Here we show that a gastric gland residing at the squamo‐columnar junction (SCJ) in normal mouse stomach contains CD44+ stem cell‐like slow‐cycling cells and that this characteristic CD44+ gland was expanded by prostaglandin E2 (PGE2) and Wnt signaling in K19‐Wnt1/C2mE mouse, a genetic mouse model for gastric tumorigenesis. The analysis of three transgenic mouse lines, K19‐Wnt1, K19‐C2mE and K19‐Wnt1/C2mE, revealed that the expansion of CD44+ SCJ cells is triggered by PGE2‐mediated signaling and is prominently enhanced by the addition of Wnt activation. Furthermore, each expanded CD44+ gland in gastric tumor of K19‐Wnt1/C2mE mouse contains a few BrdU label‐retaining quiescent or slow‐cycling cells, suggesting that the CD44+ SCJ cells in normal mouse are candidates for the cell‐of‐origin of gastric CSCs. These observations suggest that PGE2‐mediated inflammatory signaling and Wnt signaling cooperatively trigger the expansion of CD44+ slow‐cycling stem‐like cells in SCJ, leading to development of lethal gastric tumors in mice.
Bmi‐1 gene is upregulated in early‐stage hepatocellular carcinoma and correlates with ATP‐binding cassette transporter B1 expression
Authors: Effendi Kathryn , Mori Taisuke , Komuta Mina , Masugi Yohei , Du Wenlin , Sakamoto Michiie 
Published: November 2009

(Cancer Sci 2010; 101: 666–672)Overexpression of “stemness gene”Bmi‐1 has been identified in some solid tumors. We investigated Bmi‐1 expression in hepatocellular carcinoma (HCC) and ATP‐binding cassette transporter B1 (ABCB1) as a new potential target for Bmi‐1. Bmi‐1 was highly expressed in HCC cell lines and the most well differentiated cell line, KIM‐1, showed the highest expression. Immunohistochemical, immunocytochemical, and immunoelectron microscopic analysis showed the Bmi‐1 protein as having a high intensity of small dots within the nucleus which reflected concentrated sites of Bmi‐1 repressive activity. Clear “dot‐pattern” staining was observed in 24 of 37 (65%) well differentiated HCC (including 13 of 21 early nodules [62%]), in 32 of 71 (45%) moderately differentiated HCC, and 7 of 14 (50%) poorly differentiated HCC. A similar expression was not observed in non‐cancerous background regions. High Bmi‐1 expression was observed in the early and well differentiated HCC. Furthermore, overexpression and suppression of Bmi‐1 was followed by a respective increase and decrease in ABCB1 expression. As with Bmi‐1, high ABCB1 expression was also observed in the early and well differentiated HCC. A strong correlation between ABCB1 and Bmi‐1 mRNA expression was seen in HCC cell lines and clinical samples (Pearson’s correlation coefficient 0.95 and 0.90, respectively). The Bmi‐1 gene is upregulated in HCC, and in particular is highly expressed in early and well differentiated HCC. The fact that this expression correlated with that of ABCB1 suggests a new regulation target for Bmi‐1, and gives new insight into early hepatocarcinogenesis mechanisms and potential targets for future HCC treatment.
A review on the vascular features of the hyperimmunoglobulin E syndrome
Authors: Yavuz H , Chee R 
Published: November 2009

Summary
Autosomal recessive, autosomal dominant and the sporadic forms of hyperimmunoglobulin E syndrome (HIES) are multi-system disorders. Although HIES patients may present with cold abscesses, the vascular features of HIES are not well recognized. The objective of this review is to characterize the nature and spectrum of vascular abnormalities in HIES patients. Vascular abnormalities in HIES patients were reviewed with Medline and Google Scholar-based searches. In brief, the searches combined terms related to HIES with the terms related to vasculature. Furthermore, reference lists from the original studies and review papers identified were screened. There were vascular abnormalities in 25 patients with HIES. These abnormalities were identified as aneurysms (coronary, aortic, carotid and cerebral), pseudoaneurysms, congenital patent ductus venosus, superior vena cava syndrome, vasculitides, vascular ectasia, thrombosis and others. They may be congenital or acquired, in the veins and arteries, affecting both sexes. These abnormalities can be seen in all subtypes of HIES. They could be also fatal in children and adults. Limited pathological investigations revealed the presence of vasculitis. Three of the patients were found to have overlap diseases. In this review, the spectrum of vascular abnormalities in HIES are documented and discussed in detail for the first time. They highlight a previously under-recognized and potentially devastating complication of these disorders. These vascular abnormalities constitute one of the major clinical characteristics in HIES. The presence of hypereosinophilia, vasculitis and defective angiogenesis in HIES may contribute to the formation of vascular abnormalities in HIES.
Differential effects of glucocorticoids in the establishment and maintenance of endotoxin tolerance
Authors: Rearte B , Landoni V , Laborde E , Fernández G , Isturiz M 
Published: November 2009

Summary
Gram-negative infections can result in endotoxic shock, which is the most common cause of death in intensive care units. Most of the undesirable effects in sepsis and septic shock have been ascribed to lipopolysaccharide (LPS), a normal constituent of the bacterial wall. The response to LPS involves rapid secretion of proinflammatory cytokines [tumour necrosis factor-α, interleukin (IL)-1, IL-6, IL-8, interferon-γ] and the concomitant induction of anti-inflammatory mediators such as IL-10 and transforming growth factor-β and glucocorticoids (GC), which render the host temporarily refractory to subsequent lethal doses of LPS challenge in a process known as LPS or endotoxin tolerance. Although protective from the development of sepsis or systemic inflammation, endotoxin tolerance has also been pointed out as the principal cause of the non-specific immunosuppression described in these patients. In this report we demonstrate, using a mouse model, that while the maintenance of tolerance is dependent upon GC, the establishment of tolerance by LPS could be inhibited by dexamethasone (Dex), a synthetic GC. Conversely, we demonstrated that mifepristone (RU486), a known GC receptor antagonist, was capable of inducing a transient and reversible disruption of endotoxin tolerance, also permitting partial restoration of the humoral immune response in LPS tolerant/immunosuppressed mice. These results are encouraging for the management of immunosuppression in sepsis and/or non-infectious shock, and deserve further investigation in the future.
The acute effect of smoking in healthy and asthmatic smokers
Authors: Papaioannou A. I. , Koutsokera A. , Tanou K. , Kiropoulos T. S. , Tsilioni I. , Oikonomidi S. , Liadaki K. , Pournaras S. , Gourgoulianis K. I. , Kostikas K. 
Published: November 2009

Eur J Clin Invest 2010; 40 (2): 103–109ABSTRACTBackground  Acute exposure to cigarette smoke is related to airway and systemic inflammation and oxidative stress. Little is known about the acute effect of cigarette smoking in smoking asthmatics. The aim of this study was to evaluate the acute effect of smoking in airway and systemic inflammation and oxidative stress in normal smokers and patients with properly treated well‐controlled persistent asthma.Materials and methods  Ten normal smokers and 10 smokers with moderate persistent asthma controlled with LABA and ICS were recruited. Subjects refrained from smoking for at least 12 h prior to their inclusion. We compared the effects of smoking of two cigarettes on airway obstruction, airway inflammation and oxidative stress [by measuring fraction of exhaled nitric oxide (FeNO), plus pH and 8‐isoprostane in exhaled breath condensate (EBC)] before and 30, 90 and 180 min after smoking. Furthermore, we evaluated systemic oxidative stress, C‐reactive protein (CRP) and serum amyloid A (SAA) and urine leukotriene E4 (LTE4) before and 180 min after smoking.Results  No differences were observed in EBC pH and 8‐isoprostane, FeNO and systemic oxidative stress between the groups at baseline. In asthmatics, EBC pH decreased 30 min and EBC 8‐isoprostane increased 90 min after smoking (P = 0·039 and P = 0·029 respectively), which was not evident in smoking controls. Serum oxidative stress increased only in asthmatic smokers at 180 min (P = 0·001). No differences were observed in SAA, CRP and urine LTE4 levels before and after smoking.Conclusion  Acute smoking has more deleterious effects in well‐controlled properly treated asthmatic smokers compared with matched normal smokers.
Cellular components of probiotics control Yersinia ruckeri infection in rainbow trout, Oncorhynchus mykiss (Walbaum)
Authors: Abbass A , Sharifuzzaman S M , Austin B 
Published: November 2009

AbstractSubcellular components of the probiotics Aeromonas sobria GC2 and Bacillus subtilis JB‐1, when administered to rainbow trout, Oncorhynchus mykiss, conferred protection against a new biogroup of Yersinia ruckeri. Thus, intraperitoneal or intramuscular injection of rainbow trout with cell wall proteins (CWPs), outer membrane proteins (OMPs), lipopolysaccharides (LPS), whole cell proteins (WCPs) and live cells followed by challenge on day 8 with Y. ruckeri led to 80–100% survival compared with 10% survival in the controls. Sodium dodecyl sulphate‐polyacrylamide gel electrophoresis (SDS‐PAGE) profiles of WCPs and OMPs from GC2 had 10 and 5 variable protein bands in comparison to 11 and 5 bands in the WCPs and CWPs from JB‐1. Proteomic analyses were employed following SDS‐PAGE to categorize one dominant protein of 104.7 kDa from the CWPs of JB‐1 and equated it with ‘Bacillus spp. endoglucanase’ with a Mascot score >69. These results point to the potential of using cellular components of probiotics for protection of fish against bacterial diseases.
A sensitive FRET probe assay for the selective detection of Mycobacterium marinum in fish
Authors: Salati F , Meloni M , Fenza A , Angelucci G , Colorni A , Orrù G 
Published: November 2009

Abstract Mycobacterium marinum is the causative agent of mycobacteriosis in wild and cultured fish and of atypical infection in humans. For the diagnosis of M. marinum, cultural and traditional polymerase chain reaction (PCR) methods are currently used. However, these protocols, although able to discriminate within Mycobacterium spp., have proved to be time‐consuming or difficult to carry out. For this reason, the aim of this study was to obtain a rapid and specific diagnostic tool to quantify fish Mycobacterium spp. or to discriminate M. marinum from other mycobacteria. A primary PCR amplification with SYBR Green had a detection limit (dl) of 102Mycobacterium DNA copies with a log‐linear quantification range up to 104 (R2 = 0.99). The second PCR using FRET probes, flanking a region containing species specific nucleotide variations, was designed and validated with synthetic erp gene fragments corresponding to different mycobacterial species, different whole mycobacteria suspensions, experimentally infected fish tissues, tissues from experimentally infected fish, and samples of cultured fish. The results show that the FRET probes demonstrate a high specificity as the melting curve analysis allowed efficient discrimination of M. marinum from Mycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium pseudoshottsii, Mycobacterium shottsii and Mycobacterium ulcerans. The kidney is the organ with the strongest detection signal and using fish tissues the method has a mean sensitivity of 50 DNA copies/PCR.
Complete sequencing of Tunisian redspotted grouper nervous necrosis virus betanodavirus capsid gene and RNA‐dependent RNA polymerase gene
Authors: Chérif N , Gagné N , Groman D , Kibenge F , Iwamoto T , Yason C , Hammami S 
Published: November 2009

AbstractFinfish nodaviruses (betanodaviruses) can cause highly destructive infections in numerous species of farmed marine fish larvae and juveniles worldwide. The betanodavirus genome consists of two single‐stranded positive‐sense RNA molecules (RNA1 and RNA2). The virus can be classified into four genotypes based on the partial sequences of the coat protein (CP) gene (T2 and T4 regions). Currently, genomic sequence information for RNA1 regions of RNA2 outside of T2 and T4 is less well documented. This study reports on the characterization of the full RNA2 sequence of a Tunisian betanodavirus with a length of 1433 nt, containing a 339 amino acid open‐reading frame encoding the CP, and typing to the redspotted grouper nervous necrosis virus Ia genotype following phylogenetic analysis. The homology of the capsid protein to other betanodaviruses or alphanodaviruses was compared. In addition, a full length RNA1 sequence of 3104 nt encoding a 982 amino acid RNA‐dependent RNA polymerase was obtained.
A comparative molecular study of the presence of “Candidatus arthromitus” in the digestive system of rainbow trout, Oncorhynchus mykiss (Walbaum), healthy and affected with rainbow trout gastroenteritis
Authors: Del‐Pozo J , Turnbull J , Ferguson H , Crumlish M 
Published: November 2009

AbstractObservations were made using histopathological techniques in conjunction with a nested polymerase chain reaction (PCR) protocol for the specific detection of “Candidatus arthromitus” on DNA extracted from wax‐embedded tissues and fresh digestive contents of rainbow trout. Samples positive for “Candidatus arthromitus” DNA included fish with rainbow trout gastroenteritis (RTGE), clinically normal cohabiting fish, and apparently healthy controls from RTGE positive and RTGE negative sites. The results obtained from the PCR were confirmed by nucleotide sequencing. “Candidatus arthromitus” DNA was found in distal intestine as well as in sections of pyloric caeca, suggesting that both these locations are appropriate for molecular detection of “Candidatus arthromitus” DNA in trout. Furthermore, rainbow trout fry distal intestinal samples from two different hatcheries where RTGE had not been reported were also positive. Differences in “Candidatus arthromitus” DNA detection between paraffin wax‐embedded and fresh digestive content samples from the same fish suggested that it may be predominantly epithelium‐associated in healthy trout. Parallel histopathological observations indicated that pyloric caeca are the preferred site for visualizing segmented filamentous bacteria (SFB) in trout with RTGE. The results of this study showed that the presence of SFB was not invariably associated with clinical disease and that more information is required to understand the role of these organisms.
The incidence and temporal patterning of insomnia: a pilot study
Authors: PERLIS MICHAEL L. , SWINKELS CINDY M. , GEHRMAN PHILIP R. , PIGEON WILFRED R. , MATTESON‐RUSBY SARA E. , JUNGQUIST CARLA R. 
Published: November 2009

SummaryTo date very little research has been conducted on night‐to‐night variability in the incidence of insomnia. It is unclear from prior research whether subjects with primary insomnia (PI) exhibit good sleep (or better than average sleep) on some interval basis. In the present study, pilot data are provided on: (1) the frequency with which ‘good sleep’ occurs in subjects with PI; and (2) whether these events occur in a non‐random manner. Ten subjects with PI participated in this ‘naturalistic’ study. All subjects completed daily sleep diaries for a minimum of 20 days. None of the subjects received treatment for their insomnia during the monitoring period. The night‐to‐night data were evaluated by typing each night’s sleep as ‘Good’ or ‘Bad’, and then by determining the number of bad nights that occurred prior to a good night for each subject. Good and bad nights were typed in two ways: (1) using a ≥85% cut‐off and (2) using a better than the individual’s mean sleep efficiency (idiographic cut‐off). Subjects exhibited good sleep on between 29% (>85% criteria) and 55% (idiographic criteria) of the nights evaluated. The temporal patterning analysis (based on an idiographic cut‐off) revealed that better than average sleep most frequently occurred (>89% of instances) following one to three nights of poor sleep. These data suggest that insomnia severity may be mediated/moderated by sleep homeostasis and that the homeostat, or input to the homeostat, may be abnormal in patients with PI.
A cohort study of the prevalence of sleep problems in adults with intellectual disabilities
Authors: BOYLE AINSLIE , MELVILLE CRAIG A. , MORRISON JILL , ALLAN LINDA , SMILEY ELITA , ESPIE COLIN A. , COOPER SALLY‐ANN 
Published: November 2009

SummaryPrevious studies of the prevalence of sleep problems in adults with intellectual disabilities (ID) are affected by small, potentially biased samples and other limitations. This study aims to determine the prevalence and associations of sleep problems in the adult population with ID. The 4‐week period prevalence of sleep problems was determined in a cross‐sectional study of all adults with ID in a defined geographical area. Sleep problems were identified using the Psychiatric Assessment Scale for Adults with Developmental Disabilities (PAS‐ADD) checklist and categorized as initial insomnia, early morning wakening and broken sleep. A fourth, composite, variable of significant sleep problem was also derived. Of the 1023 adults with ID who participated, 9.2% had experienced a significant sleep problem, during the 1‐month period. Individuals with a significant sleep problem are more likely to have mental ill‐health [odds ratio (OR) = 5.53, 95% confidence interval (CI) 3.52–8.69], problem behaviours (OR = 2.06, 95% CI: 1.25–3.41) and respiratory disease (OR = 2.03, 95% CI: 1.27–3.26). There is a positive association between visual impairment and initial insomnia (OR = 1.91, 95% CI: 1.21–3.04). Although a diagnosis of epilepsy is not associated with sleep problems, the finding that individuals taking antiepileptic medication are more likely to experience broken sleep (OR = 1.73, 95% CI: 1.13–2.66) suggests that medication side effects may impact on sleep of individuals with ID. The results suggest that there is a need to further examine the relationship between sleep problems and co‐morbid health problems, which would inform the development of interventions, and trials of their efficacy.