bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical spectrum and severity of hemolytic anemia in glucose 6-phosphate dehydrogenase–deficient children receiving dapsone
Authors: Pamba Allan , Richardson Naomi D. , Carter Nick , Duparc Stephan , Premji Zul , Tiono Alfred B. , Luzzatto Lucio 
Published: September 2012

AbstractDrug-induced acute hemolytic anemia led to the discovery of G6PD deficiency. However, most clinical data are from isolated case reports. In 2 clinical trials of antimalarial preparations containing dapsone (4,4′-diaminodiphenylsulfone; 2.5 mg/kg once daily for 3 days), 95 G6PD-deficient hemizygous boys, 24 G6PD-deficient homozygous girls, and 200 girls heterozygous for G6PD deficiency received this agent. In the first 2 groups, there was a maximum decrease in hemoglobin averaging −2.64 g/dL (range −6.70 to +0.30 g/dL), which was significantly greater than for the comparator group receiving artemether-lumefantrine (adjusted difference −1.46 g/dL; 95% confidence interval −1.76, −1.15). Hemoglobin concentrations were decreased by ≥ 40% versus pretreatment in 24/119 (20.2%) of the G6PD-deficient children; 13/119 (10.9%) required blood transfusion. In the heterozygous girls, the mean maximum decrease in hemoglobin was −1.83 g/dL (range +0.90 to −5.20 g/dL); 1 in 200 (0.5%) required blood transfusion. All children eventually recovered. All the G6PD-deficient children had the G6PD A− variant, ie, mutations V68M and N126D. Drug-induced acute hemolytic anemia in G6PD A− subjects can be life-threatening, depending on the nature and dosage of the drug trigger. Therefore, contrary to current perception, in clinical terms the A− type of G6PD deficiency cannot be regarded as mild. This study is registered at http://www.clinicaltrials.gov as NCT00344006 and NCT00371735.
Use of 111-Indium–labeled autologous eosinophils to establish the in vivo kinetics of human eosinophils in healthy subjects
Authors: Farahi Neda , Singh Nanak R. , Heard Sarah , Loutsios Chrystalla , Summers Charlotte , Solanki Chandra K. , Solanki Kishor , Balan Kottekkattu K. , Ruparelia Prina , Peters A. Michael , Condliffe Alison M. , Chilvers Edwin R. 
Published: September 2012

AbstractEosinophils are the major cellular effectors of allergic inflammation and represent an important therapeutic target. Although the genesis and activation of eosinophils have been extensively explored, little is known about their intravascular kinetics or physiological fate. This study was designed to determine the intravascular life span of eosinophils, their partitioning between circulating and marginated pools, and sites of disposal in healthy persons. Using autologous, minimally manipulated 111-Indium–labeled leukocytes with blood sampling, we measured the eosinophil intravascular residence time as 25.2 hours (compared with 10.3 hours for neutrophils) and demonstrated a substantial marginated eosinophil pool. γ camera imaging studies using purified eosinophils demonstrated initial retention in the lungs, with early redistribution to the liver and spleen, and evidence of recirculation from a hepatic pool. This work provides the first in vivo measurements of eosinophil kinetics in healthy volunteers and shows that 111-Indium–labeled eosinophils can be used to monitor the fate of eosinophils noninvasively.
Whole transcriptome analysis of the silicon response of the diatom Thalassiosira pseudonana
Authors: Shrestha Roshan Prakash , Tesson Benoit , Norden-Krichmar Trina , Federowicz Stephen , Hildebrand Mark , Allen Andrew E 
Published: September 2012

AbstractBackgroundSilicon plays important biological roles, but the mechanisms of cellular responses to silicon are poorly understood. We report the first analysis of cell cycle arrest and recovery from silicon starvation in the diatomThalassiosira pseudonanausing whole genome microarrays.ResultsThree known responses to silicon were examined, 1) silicified cell wall synthesis, 2) recovery from silicon starvation, and 3) co-regulation with silicon transporter (SIT) genes. In terms of diatom cell wall formation, thus far only cell surface proteins and proteins tightly associated with silica have been characterized. Our analysis has identified new genes potentially involved in silica formation, and other genes potentially involved in signaling, trafficking, protein degradation, glycosylation and transport, which provides a larger-scale picture of the processes involved. During silicon starvation, an overrepresentation of transcription and translation related genes were up-regulated, indicating thatT. pseudonanais poised to rapidly recover from silicon starvation and resume cell cycle progression upon silicon replenishment. This is in contrast to other types of limitation, and provides the first molecular data explaining the well-established environmental response of diatoms to grow as blooms and to out-compete other classes of microalgae for growth. Comparison of our data with a previous diatom cell cycle analysis indicates that assignment of the cell cycle specific stage of particular cyclins and cyclin dependent kinases should be re-evaluated. Finally, genes co-varying in expression with the SITs enabled identification of a new class of diatom-specific proteins containing a unique domain, and a putative silicon efflux protein.ConclusionsAnalysis of theT. pseudonanamicroarray data has provided a wealth of new genes to investigate previously uncharacterized cellular phenomenon related to silicon metabolism, silicon’s interaction with cellular components, and environmental responses to silicon.
Role of tight junction proteins in gastroesophageal reflux disease
Authors: Mönkemüller Klaus , Wex Thomas , Kuester Doerthe , Fry Lucia C , Kandulski Arne , Kropf Siegfried , Roessner Albert , Malfertheiner Peter 
Published: September 2012

Abstract

Background
Gastroesophageal reflux disease (GERD) is associated with impaired epithelial barrier function that is regulated by cell-cell contacts. The aim of the study was to investigate the expression pattern of selected components involved in the formation of tight junctions in relation to GERD.

Methods
Eighty-four patients with GERD-related symptoms with endoscopic signs (erosive: n = 47) or without them (non-erosive: n = 37) as well as 26 patients lacking GERD-specific symptoms as controls were included. Endoscopic and histological characterization of esophagitis was performed according to the Los Angeles and adapted Ismeil-Beigi criteria, respectively. Mucosal biopsies from distal esophagus were taken for analysis by histopathology, immunohistochemistry and quantitative reverse-transcription polymerase chain reaction (RT-PCR) of five genes encoding tight junction components [Occludin, Claudin-1, -2, Zona occludens (ZO-1, -2)].

Results
Histopathology confirmed GERD-specific alterations as dilated intercellular spaces in the esophageal mucosa of patients with GERD compared to controls (P < 0.05). Claudin-1 and −2 were 2- to 6-fold upregulation on transcript (P < 0.01) and in part on protein level (P < 0.015) in GERD, while subgroup analysis of revealed this upregulation for ERD only. In both erosive and non-erosive reflux disease, expression levels of Occludin and ZO-1,-2 were not significantly affected. Notably, the induced expression of both claudins did not correlate with histopathological parameters (basal cell hyperplasia, dilated intercellular spaces) in patients with GERD.

Conclusions
Taken together, the missing correlation between the expression of tight junction-related components and histomorphological GERD-specific alterations does not support a major role of the five proteins studied in the pathogenesis of GERD.
Subtle mutations in the SMN1 gene in Chinese patients with SMA: p.Arg288Met mutation causing SMN1 transcript exclusion of exon7
Authors: Yu-jin Qu , Juan Du , Er-zhen Li , Jin-li Bai , Yu-wei Jin , Hong Wang , Fang Song 
Published: September 2012

Abstract

Background
Proximal spinal muscular atrophy (SMA) is a common neuromuscular disorder resulting in death during childhood. Around 81 ~ 95% of SMA cases are a result of homozygous deletions of survival motor neuron gene 1 (SMN1) gene or gene conversions from SMN1 to SMN2. Less than 5% of cases showed rare subtle mutations in SMN1. Our aim was to identify subtle mutations in Chinese SMA patients carrying a single SMN1 copy.

Methods
We examined 14 patients from 13 unrelated families. Multiplex ligation-dependent probe amplification analysis was carried out to determine the copy numbers of SMN1 and SMN2. Reverse transcription polymerase chain reaction (RT-PCR) and clone sequencing were used to detect subtle mutations in SMN1. SMN transcript levels were determined using quantitative RT-PCR.

Results
Six subtle mutations (p.Ser8LysfsX23, p.Glu134Lys, p.Leu228X, p.Ser230Leu, p.Tyr277Cys, and p.Arg288Met) were identified in 12 patients. The p.Tyr277Cys mutation has not been reported previously. The p.Ser8LysfsX23, p.Leu228X, and p.Tyr277Cys mutations have only been reported in Chinese SMA patients and the first two mutations seem to be the common ones. Levels of full length SMN1 (fl-SMN1) transcripts were very low in patients carrying p.Ser8LysfsX23, p.Leu228X or p.Arg288Met compared with healthy carriers. In patients carrying p.Glu134Lys or p.Ser230Leu, levels of fl-SMN1 transcripts were reduced but not significant. The SMN1 transcript almost skipped exon 7 entirely in patients with the p.Arg288Met mutation.

Conclusions
Our study reveals a distinct spectrum of subtle mutations in SMN1 of Chinese SMA patients from that of other ethnicities. The p.Arg288Met missense mutation possibly influences the correct splicing of exon 7 in SMN1. Mutation analysis of the SMN1 gene in Chinese patients may contribute to the identification of potential ethnic differences and enrich the SMN1 subtle mutation database.
microRNA-146a inhibits G protein-coupled receptor-mediated activation of NF-κB by targeting CARD10 and COPS8 in gastric cancer
Authors: Crone Stephanie Geisler , Jacobsen Anders , Federspiel Birgitte , Bardram Linda , Krogh Anders , Lund Anders H , Friis-Hansen Lennart 
Published: September 2012

Abstract

Background
Gastric cancer is the second most common cause of cancer-related death in the world. Inflammatory signals originating from gastric cancer cells are important for recruiting inflammatory cells and regulation of metastasis of gastric cancer. Several microRNAs (miRNA) have been shown to be involved in development and progression of gastric cancer. miRNA-146a (miR-146a) is a modulator of inflammatory signals, but little is known about its importance in gastric cancer. We therefore wanted to identify targets of miR-146a in gastric cancer and examine its biological roles.

Results
The expression of miR-146a was evaluated by quantitative PCR (qPCR) and found up-regulated in the gastrin knockout mice, a mouse model of gastric cancer, and in 73% of investigated human gastric adenocarcinomas. Expression of miR-146a by gastric cancer cells was confirmed by in situ hybridization. Global analysis of changes in mRNA levels after miR-146a transfection identified two transcripts, caspase recruitment domain-containing protein 10 (CARD10) and COP9 signalosome complex subunit 8 (COPS8), as new miR-146a targets. qPCR, Western blotting and luciferase assays confirmed these transcripts as direct miR-146a targets. CARD10 and COPS8 were shown to be part of the G protein-coupled receptor (GPCR) pathway of nuclear factor-kappaB (NF-kappaB) activation. Lysophosphatidic acid (LPA) induces NF-kappaB activation via this pathway and over-expression of miR-146a inhibited LPA-induced NF-kappaB activation, reduced LPA-induced expression of tumor-promoting cytokines and growth factors and inhibited monocyte attraction.

Conclusions
miR-146a expression is up-regulated in a majority of gastric cancers where it targets CARD10 and COPS8, inhibiting GPCR-mediated activation of NF-kappaB, thus reducing expression of NF-kappaB-regulated tumor-promoting cytokines and growth factors. By targeting components of several NF-kappaB-activating pathways, miR-146a is a key component in the regulation of NF-kappaB activity.
Wnt/beta-catenin signaling in embryonic stem cell converted tumor cells
Authors: Peng Xinrong , Liu Tao , Wang Ying , Yan Qiaoling , Jin Huajun , Li Linfang , Qian Qijun , Wu Mengchao 
Published: September 2012

Abstract

Background
Embryonic stem cells (ESCs) are pluripotent stem cells and can form tumors containing cells from all three germ layers. Similarities between pluripotent stem cells and malignant tumor cells have been identified. The purpose of this study was to obtain ESCs-converted tumor cell lines and to investigate the mechanism of malignancy in pluripotent stem cells.

Methods
Mouse ESCs were subcutaneously injected into nude mice to obtain tumors from which a tumor-like cell line (ECCs1) was established by culturing the cells in chemical-defined N2B27 medium supplied with two small molecular inhibitors CHIR99021 and PD0325901 (2i). The ECCs1 were then subcutaneously injected into nude mice again to obtain tumors from which another tumor-like cells line (ECCs2) was established in the same 2i medium. The malignant degree of ESCs, ECCs1 and ECCs2 was compared and the underlying mechanism involved in the malignancy development of ESCs was examined.

Results
The three ESCs, ECCs1 and ECCs2 cell lines were cultured in the same 2i condition and showed some likeness such as Oct4-expression and long-term expansion ability. However, the morphology and the tumor-formation ability of the cell lines were different. We identified that ECCs1 and ECCs2 gradually acquired malignancy. Moreover, Wnt signaling-related genes such as CD133 and β-catenin expression were up-regulated and Frizzled related protein (FRP) was down-regulated during the tumor development of ESCs.

Conclusions
The two tumor-like cell lines ECCs1 and ECCs2 stand for early malignant development stage of ESCs and the ECCs2 was more malignant than the ECCs1. Moreover, we identified that Wnt/β-catenin signaling played an important role in the malignancy process of ESCs.
The Drosophila Arf1 homologue Arf79F is essential for lamellipodium formation
Authors: Humphreys Daniel , Liu Tao , Davidson Anthony C. , Hume Peter J. , Koronakis Vassilis 
Published: September 2012

Summary
The WAVE regulatory complex (WRC) drives the polymerisation of actin filaments located beneath the plasma membrane to generate lamellipodia that are pivotal to cell architecture and movement. By reconstituting WRC-dependent actin assembly at the membrane, we recently discovered that several classes of Arf family GTPases directly recruit and activate WRC in cell extracts, and that Arf cooperates with Rac1 to trigger actin polymerisation. Here, we demonstrate that the Class 1 Arf1 homologue Arf79F colocalises with the WRC at dynamic lamellipodia. We report that Arf79F is required for lamellipodium formation in Drosophila S2R+ cells, which only express one Arf isoform for each class. Impeding Arf function either by dominant-negative Arf expression or by Arf double-stranded RNA interference (dsRNAi)-mediated knockdown uncovered that Arf-dependent lamellipodium formation was specific to Arf79F, establishing that Class 1 Arfs, but not Class 2 or Class 3 Arfs, are crucial for lamellipodia. Lamellipodium formation in Arf79F-silenced cells was restored by expressing mammalian Arf1, but not by constitutively active Rac1, showing that Arf79F does not act via Rac1. Abolition of lamellipodium formation in Arf79F-silenced cells was not due to Golgi disruption. Blocking Arf79F activation with guanine nucleotide exchange factor inhibitors impaired WRC localisation to the plasma membrane and concomitant generation of lamellipodia. Our data indicate that the Class I Arf GTPase is a central component in WRC-driven lamellipodium formation.
A method for quantifying intervertebral disc signal intensity on T2-weighted imaging
Authors: Nagashima Masaki , Abe Hitoshi , Amaya Kenji , Matsumoto Hideo , Yanaihara Hisashi , Nishiwaki Yuji , Toyama Yoshiaki , Matsumoto Morio 
Published: September 2012

Background Quantification of intervertebral disc degeneration based on intensity of the nucleus pulposus in magnetic resonance imaging (MRI) often uses the mean intensity of the region of interest (ROI) within the nucleus pulposus. However, the location and size of ROI have varied in different reports, and none of the reported methods can be considered fully objective. Purpose To develop a more objective method of establishing ROIs for quantitative evaluation of signal intensity in the nucleus pulposus using T2-weighted MRI. Material and Methods A 1.5-T scanner was used to obtain T2-weighted mid-sagittal images. A total of 288 intervertebral discs from 48 patients (25 men, 23 women) were analyzed. Mean age was 47.4 years (range, 17-69 years). All discs were classified into five grades according to Pfirrmann et al. Discs in grades I and II were defined as bright discs, and discs in grades IV and V were defined as dark discs. Eight candidate methods of ROI determination were devised. The method offering the highest degree of discrimination between bright and dark discs was investigated among these eight methods. Results The method with the greatest degree of discrimination was as follows. The quadrangle formed by anterior and posterior edges of the upper and lower end plates in contact with the intervertebral disc to be measured was defined as the intervertebral area. A shape similar to the intervertebral area but with one-quarter the area was drawn. The geometrical center of the shape was matched to the center of intensity, and this shape was then used as the ROI. Satisfactory validity and reproducibility were obtained using this method. Conclusion The present method offers adequate discrimination and could be useful for longitudinal tracking of intervertebral disc degeneration with sufficient reproducibility.
MDCT has the potential to predict percutaneous coronary intervention outcome in swine model: microscopic validation
Authors: Saeed Maythem , Hetts Steven W , Do Loi , Sullivan Sammir , Wilson Mark W 
Published: September 2012

Background Volumes and sizes of dislodged coronary microemboli vary during PCI so their effects at the left ventricular (LV) and cellular levels cannot be quantified. Furthermore, biopsy for tissue characterization is not an option in PCI patients. Purpose To characterize and validate microinfarct size, LAD territory where microinfarct were found using multidetector computed tomography (MDCT), histochemical staining and microscopy as a function of microemboli volumes and to scale the effects of microemboli volumes on LV function. Material and Methods Under X-ray guidance, a 3F catheter was inserted into LAD coronary artery of 14 pigs for delivering 16 mm3 or 32 mm3 of 40-120 μm microemboli. MDCT imaging/histochemical staining/ microscopy were performed 3 days later and used to characterize regional and global structural and functional changes in LV by threshold/planimetric methods. Results MDCT and ex-vivo methods were able to quantify microinfarct size and LAD territory where microinfarct was found as a function of volumes. However, MDCT and histochemical staining significantly underestimated microinfarct size and territory where microinfarct was found compared with microscopy. MDCT demonstrated the functional changes and showed a moderate correlation between LV ejection fraction and microinfarct size (r = 0.53). Microscopy provided higher spatial resolution for measuring islands of necrotic cells, which explains the difference in measuring structural changes. Conclusion MDCT showed the difference in microinfarct size and LAD territory as a function of microemboli volumes and scaled the changes in LV function. This experimental study gives clinicians a reference for the effects of defined microemboli volumes on myocardial viability and LV function and the under-estimation of microinfarct on MDCT.
Capitalism and the Ivory Tower: The Gordian Knot Between Money and Science
Authors: Messer-Yaron Hagit 
Published: September 2012

Transferring knowledge and technology from academia to industry requires bridging the natural gap between the two sectors: industry, which is fueled by profit to the shareholders; and academia, whose currency is knowledge. The technology transfer process is an essential component of contemporary academic life in most modern countries. However, despite the common argument, it is not necessarily a win-win process.
In this paper we shall detail who wins and who loses in this process. In particular, we will study the role of governments, which, on the one hand, finance research and are the only source for supporting basic science, and, on the other hand, dictate and impose policy
We will specify some guidelines for responsible technology transfer policy, which contributes to reconciliation of money and science.
Relationship between Palate-Vomer Development and Maxillary Growth in Submucous Cleft Palate Patients
Authors: Ren Shuxin , Ma Lian , Sun Zhipeng , Qian Jing 
Published: September 2012

Objective Experimental and clinical findings suggest that the vomer is involved in facial development and might contribute to the short and retrusive maxilla in cleft patients. The aim of this study was to investigate the relationship between vomer development and maxillary growth in unoperated submucous cleft palate (SMCP) patients. Design Retrospective cohort study. Participants Thirty unoperated SMCP patients were included. The criteria for clinical diagnosis were: bifid uvula, a translucent zone in the midline of the soft palate, and a touchable “V” notch on the posterior border of the bony palate. There were 19 female and 11 male patients, with an age range from 3 to 25 years. Interventions All patients were imaged using spiral computed tomography (CT) while in centric occlusion before the surgeries. Main Outcome Measures Three-dimensional (3D) reconstruction models were created, and dentoalveolar relationships were rated by three experienced doctors according to the GOSLON score principles. The patients then were divided into three groups: 1 - normal occlusion, 2 - edge-to-edge bite, and 3 - crossbite. The vomer-palate fusion rate was calculated on 3D CT images and represented the vomer development. Results The sagittal extent of the palatal cleft and the malformation of vomer in SMCP were greatly varied. The vomer-palate fusion rate in the crossbite group (occlusal score = 3) was significantly lower than that in the normal occlusion group ( P .027). Conclusions Our findings suggest that correlation exists between vomer development and sagittal maxillary growth in unoperated SMCP patients.
State Cigarette Excise Tax, Secondhand Smoke Exposure, and Periodontitis in US Nonsmokers
Authors: Sanders Anne , Slade Gary 
Published: September 2012

Objectives. We assessed the relationship of state cigarette excise tax with cigarette sales, secondhand smoke (SHS) exposure, and periodontitis among US lifetime nonsmokers. Methods. Cigarette excise tax and per capita sales data from 1983 to 1998 were obtained for 50 states and the District of Columbia. Periodontal data were analyzed for 3137 adults in 28 states from 3 National Health and Nutrition Examination Survey cycles (1999–2004). Measures of periodontal pocket depth and attachment level were used to classify people with moderate or severe periodontitis. SHS exposure was classified according to gender- or race/ethnicity–specific thresholds of serum cotinine concentration. Statistical analysis adjusted for the complex survey design. Results. For each additional $0.10 in excise tax, predicted sales decreased by 0.74 packs per person per month and adjusted odds of moderate or severe periodontitis decreased 22% (odds ratio [OR] = 0.78; 95% confidence interval [CI] = 0.62, 0.97). For each pack sold per person per month, adjusted odds of SHS exposure increased 28% (95% CI = 1.17, 1.40) and adjusted odds of periodontitis increased 15% (95% CI = 1.03, 1.29). Odds of periodontitis for those exposed to SHS were elevated 2-fold relative to those who were unexposed (OR = 2.03; 95% CI = 1.30, 3.20). Conclusions. Cigarette excise tax may protect nonsmokers against periodontitis.