bluuebunny/crossref_metadata_2025_split huggingface dataset:
An 8‐week, randomized, controlled, clinical study of the use of a 0.1% chlorhexidine mouthwash by chronic periodontitis patients
Authors: Tenenbaum Henri , Luc Jöelle , Schaaf Jean‐François , Federlin‐Ducani Marie , Cotton Christine , Elkaim René , Cuisinier Frédéric J.G. , Roques Christine 
Published: November 2010

AbstractAim:  To evaluate the efficacy of a 2‐week administration of a 0.1% chlorhexidine mouthwash in the short‐term treatment of chronic periodontitis patients and the impact of this product when administered twice by pocket irrigation.Methods:  Sixty patients were enrolled in a single‐centre, placebo‐controlled, randomized study with the blind allocation of product to two parallel groups. Clinical assessments were performed, and samples from six selected subgingival sites were collected for microbial analysis by culture at baseline, D15 and D56. Three of the six sites were randomly selected and were treated by subgingival irrigation with the same 0.1% chlorhexidine product at D0 and D7. A subsequent statistical analysis was performed using the paired Student’s t‐test and Wilcoxon rank sum test for within‐group analyses; analysis of variance and the Kruskall–Wallis test were used for between‐group analyses.Results:  Two‐week treatment with a 0.1% chlorhexidine mouthwash slightly reduced the gingival inflammation associated with periodontitis. We observed a significant decrease in Gram‐negative, facultative anaerobes and micro‐aerophiles, and a significant increase in Gram‐positive cocci. No increase in the treatment effect was demonstrated by irrigation of the periodontal pockets.Conclusion:  The 0.1% chlorhexidine mouthwash showed limited beneficial effects in the treatment of periodontitis patients.
Genetic dissection of ion currents underlying all‐or‐none action potentials in C. elegans body‐wall muscle cells
Authors: Liu Ping , Ge Qian , Chen Bojun , Salkoff Lawrence , Kotlikoff Michael I. , Wang Zhao‐Wen 
Published: November 2010

Non‐technical summaryMammalian skeletal muscle contractions are initiated by all‐or‐none action potentials (APs) triggered by motoneurons. In C. elegans locomotory muscle, however, the characteristics of APs, the underlying ion channels, and their role in Ca2+ release are poorly understood. Here we show that C. elegans locomotory muscle fires spontaneous, all‐or‐none APs, which appear to be modulated by motoneuron activity. The upstroke of muscle APs requires Ca2+ entry through a voltage‐gated Ca2+ channel (EGL‐19), whereas the downstroke of the APs relies on a voltage‐gated potassium channel as well as a Ca2+‐ and Cl−‐activated potassium channel. AP‐elicited elevations of intracellular Ca2+ concentration require both EGL‐19 in the plasma membrane and the ryanodine receptor in the sarcoplasmic reticulum membrane. The discovery of all‐or‐none action potentials in C. elegans body‐wall muscle brings the physiology of C. elegans much closer to that of other metazoans, and strengthens its utility as a model organism.
Use of historical data and a novel metric in the evaluation of the effectiveness of hearing conservation program components
Authors: Heyer Nicholas , Morata Thais C , Pinkerton Lynne E , Brueck Scott E , Stancescu Daniel , Panaccio Mary Prince , Kim Hyoshin , Sinclair J Stephen , Waters Martha A , Estill Cherie F , Franks John R 
Published: November 2010

ObjectivesTo evaluate the effectiveness of hearing conservation programs (HCP) and their specific components in reducing noise-induced hearing loss (NIHL).MethodsThis retrospective cohort study was conducted at one food-processing plant and two automotive plants. Audiometric and work-history databases were combined with historical noise monitoring data to develop a time-dependent exposure matrix for each plant. Historical changes in production and HCP implementation were collected from company records, employee interviews and focus groups. These data were used to develop time-dependent quality assessments for various HCP components. 5478 male (30 427 observations) and 1005 female (5816 observations) subjects were included in the analysis.ResultsAnalyses were conducted separately for males and females. Females tended to have less NIHL at given exposure levels than males. Duration of noise exposure stratified by intensity (dBA) was a better predictor of NIHL than the standard equivalent continuous noise level (Leq) based upon a 3-dBA exchange. Within this cohort, efficient dBA strata for males were <95 versus ≥95, and for females <90 versus ≥90. The reported enforced use of hearing protection devices (HPDs) significantly reduced NIHL. The data did not have sufficient within-plant variation to determine the effectiveness of noise monitoring or worker training. An association between increased audiometric testing and NIHL was believed to be an artifact of increased participation in screening.ConclusionsHistorical audiometric data combined with noise monitoring data can be used to better understand the effectiveness of HCPs. Regular collection and maintenance of quality data should be encouraged and used to monitor the effectiveness of these interventions.
Novel Interaction of MUC4 and Galectin: Potential Pathobiological Implications for Metastasis in Lethal Pancreatic Cancer
Authors: Senapati Shantibhusan , Chaturvedi Pallavi , Chaney William G. , Chakraborty Subhankar , Gnanapragassam Vinayaga S. , Sasson Aaron R. , Batra Surinder K. 
Published: November 2010

Abstract
Purpose: Several studies have reported aberrant expression of MUC4 in pancreatic cancer (PC), which is associated with tumorigenicity and metastasis. Mechanisms through which MUC4 promote metastasis of PC cells to distant organs are poorly defined.
Experimental Design: Identification of MUC4–galectin-3 interaction and its effect on the adhesion of cancer cells to endothelial cells were done by immunoprecipitation and cell–cell adhesion assays, respectively. Serum galectin-3 level for normal and PC patients were evaluated through ELISA.
Results: In the present study, we have provided clinical evidence that the level of galectin-3 is significantly elevated in the sera of PC patients with metastatic disease compared with patients without metastasis (P = 0.04) and healthy controls (P = 0.00001). Importantly, for the first time, we demonstrate that MUC4 present on the surface of circulating PC cells plays a significant role in the transient and reversible attachment (docking) of circulating tumor cells to the surface of endothelial cells. Further, exogenous galectin-3 at concentrations similar to that found in the sera of PC patients interacts with MUC4 via surface glycans such as T antigens, which results in the clustering of MUC4 on the cell surface and a stronger attachment (locking) of circulating tumor cells to the endothelium.
Conclusions: Altogether, these findings suggest that PC cell-associated MUC4 helps in the docking of tumor cells on the endothelial surface. During cancer progression, MUC4–galectin-3 interaction–mediated clustering of MUC4 may expose the surface adhesion molecules, which in turn promotes a stronger attachment (locking) of tumor cells to the endothelial surface. Clin Cancer Res; 17(2); 267–74. ©2010 AACR. Clin Cancer Res; 17(2); 267–74. ©2010 AACR.
Analyses and interpretation of whole-genome gene expression from formalin-fixed paraffin-embedded tissue: an illustration with breast cancer tissues
Authors: Kibriya Muhammad G , Jasmine Farzana , Roy Shantanu , Paul-Brutus Rachelle M , Argos Maria , Ahsan Habibul 
Published: November 2010

Abstract

Background
We evaluated (a) the feasibility of whole genome cDNA-mediated Annealing, Selection, extension and Ligation (DASL) assay on formalin-fixed paraffin-embedded (FFPE) tissue and (b) whether similar conclusions can be drawn by examining FFPE samples as proxies for fresh frozen (FF) tissues. We used a whole genome DASL assay (addressing 18,391 genes) on a total of 72 samples from paired breast tumor and surrounding healthy tissues from both FF and FFPE samples.

Results
Gene detection was very good with comparable success between the FFPE and FF samples. Reproducibility was also high (r2 = 0.98); however, concordance between the two types of samples was low. Only one-third of the differentially expressed genes in tumor tissues (compared to corresponding normal) from FF samples could be detected in FFPE samples and conversely only one-fourth of the differentially expressed genes from FFPE samples could be detected in FF samples. GO-enrichment analysis, gene set enrichment analysis (GSEA) and GO-ANOVA analyses also suggested small overlap between the lead functional groups that were differentially expressed in tumor detectable by examining FFPE and FF samples. In other words, FFPE samples may not be ideal for picking individual target gene(s), but may be used to identify some of the lead functional group(s) of genes that are differentially expressed in tumor. The differentially expressed genes in breast cancer found in our study were biologically meaningful. The "cell cycle" & "cell division" related genes were up-regulated and genes related to "regulation of epithelial cell proliferation" were down-regulated.

Conclusions
Gene expression experiments using the DASL assay can efficiently handle fragmentation issues in the FFPE tissues. However, formalin fixation seems to change RNA and consequently significantly alters gene expression in a number of genes which may not be uniform between tumor and normal tissues. Therefore, considerable caution needs to be taken when interpreting gene expression data from FFPE tissues, especially in relation to specific genes.
Alternative splicing and nonsense-mediated decay regulate telomerase reverse transcriptase (TERT) expression during virus-induced lymphomagenesis in vivo
Authors: Amor Souheila , Remy Sylvie , Dambrine Ginette , Le Vern Yves , Rasschaert Denis , Laurent Sylvie 
Published: November 2010

Abstract

Background
Telomerase activation, a critical step in cell immortalization and oncogenesis, is partly regulated by alternative splicing. In this study, we aimed to use the Marek's disease virus (MDV) T-cell lymphoma model to evaluate TERT regulation by splicing during lymphomagenesis in vivo, from the start point to tumor establishment.

Results
We first screened cDNA libraries from the chicken MDV lymphoma-derived MSB-1 T- cell line, which we compared with B (DT40) and hepatocyte (LMH) cell lines. The chTERT splicing pattern was cell line-specific, despite similar high levels of telomerase activity. We identified 27 alternative transcripts of chicken TERT (chTERT). Five were in-frame alternative transcripts without in vitro telomerase activity in the presence of viral or chicken telomerase RNA (vTR or chTR), unlike the full-length transcript. Nineteen of the 22 transcripts with a premature termination codon (PTC) harbored a PTC more than 50 nucleotides upstream from the 3' splice junction, and were therefore predicted targets for nonsense-mediated decay (NMD). The major PTC-containing alternatively spliced form identified in MSB1 (ie10) was targeted to the NMD pathway, as demonstrated by UPF1 silencing. We then studied three splicing events separately, and the balance between in-frame alternative splice variants (d5f and d10f) plus the NMD target i10ec and constitutively spliced chTERT transcripts during lymphomagenesis induced by MDV indicated that basal telomerase activity in normal T cells was associated with a high proportion of in-frame non functional isoforms and a low proportion of constitutively spliced chTERT. Telomerase upregulation depended on an increase in active constitutively spliced chTERT levels and coincided with a switch in alternative splicing from an in-frame variant to NMD-targeted variants.

Conclusions
TERT regulation by splicing plays a key role in telomerase upregulation during lymphomagenesis, through the sophisticated control of constitutive and alternative splicing. Using the MDV T-cell lymphoma model, we identified a chTERT splice variant as a new NMD target.
Comparison between amniotomy, oxytocin or both for augmentation of labor in prolonged latent phase: a randomized controlled trial
Authors: Nachum Zohar , Garmi Gali , Kadan Yfat , Zafran Noah , Shalev Eliezer , Salim Raed 
Published: November 2010

Abstract

Background
A prolonged latent phase is independently associated with an increased incidence of subsequent labor abnormalities. We aimed to compare between oxytocin augmentation, amniotomy and a combination of both on the duration of labor among women with a prolonged latent phase.

Methods
Women with a singleton fetus in cephalic presentation who have a prolonged latent phase, were randomly allocated to amniotomy (group 1), oxytocin (group 2) or both (group 3). A group of women who progressed spontaneously without intervention composed the control group (group 4). The primary outcome was the duration of time from initiation of augmentation until delivery.

Results
A total of 213 women were consented and randomized to group 1 (70 women), group 2 (72 women) and group 3 (71 women). Group 4 was composed from additional 70 women. A mean reduction of 120 minutes in labor duration was observed among group 3 compared to group 1 (p = 0.08) and 180 minutes compared to group 2 and 4 (p = 0.001). Women in group 3 had a shorter length of time from augmentation until the beginning of the active phase and a shorter first stage of labor than group 1 (p = 0.03), group 2 (p = 0.001) and group 4 (p = 0.001). Satisfaction was greater among group 3 and 4. Mode of delivery and neonatal outcome were comparable between the groups.

Conclusion
Labor augmentation by combined amniotomy and oxytocin among women with a prolonged latent phase at term seems superior compared to either of them alone.
IL-2 as a therapeutic target for the restoration of Foxp3+ regulatory T cell function in organ-specific autoimmunity: implications in pathophysiology and translation to human disease
Authors: d'Hennezel Eva , Kornete Mara , Piccirillo Ciriaco A 
Published: November 2010

Abstract
Peripheral immune tolerance requires a finely controlled balance between tolerance to self-antigens and protective immunity against enteric and invading pathogens. Self-reactive T cells sometimes escape thymic clonal deletion, and can subsequently provoke autoimmune diseases such as type 1 diabetes (T1D) unless they are controlled by a network of tolerance mechanisms in the periphery, including CD4+ regulatory T cells (Treg) cells. CD4+ Treg cells are characterized by the constitutive expression of the IL-2Rα chain (CD25) and preferentially express the forkhead winged helix transcriptional regulator Foxp3. These cells have been shown to possess immunosuppressive properties towards various immune cell subsets and their defects are thought to contribute to many autoimmune disorders. Strong evidence shows that IL-2 is one of the important stimulatory signals for the development, function and fitness of Treg cells. The non-obese diabetic (NOD) mouse model, a prototypic model of spontaneous autoimmunity, mimics many features of human T1 D. Using this model, the contribution of the IL-2-IL-2R pathway to the development of T1 D and other autoimmune disorders has been extensively studied. In the past years, strong genetic and molecular evidence has indicated an essential role for the IL-2/IL-2R pathway in autoimmune disorders. Thus, the major role of IL-2 is to maintain immune tolerance by promoting Treg cell development, functional fitness and stability. Here we first summarize the genetic and experimental evidence demonstrating a role for IL-2 in autoimmunity, mainly through the study of the NOD mouse model, and analyze the cellular and molecular mechanisms of its action on Treg cells. We then move on to describe how this data can be translated to applications for human autoimmune diseases by using IL-2 as a therapeutic agent to restore Treg cell fitness, numbers and functions.
Prediabetes as a Therapeutic Target
Authors: Pour Omid Rad , Dagogo-Jack Samuel 
Published: November 2010

BACKGROUND
The term “prediabetes” is used to describe a condition that involves impaired glucose tolerance (IGT) or impaired fasting glucose (IFG). IGT is defined by a 2-h oral glucose tolerance test plasma glucose concentration &gt;140 mg/dL (7.8 mmol/L) but &lt;200 mg/dL (11.1 mmol/L), and IFG is defined by a fasting plasma glucose concentration ≥100 mg/dL (5.6 mmol/L), but &lt;126 mg/dL (7.0 mmol/L). Studies have shown that people with prediabetes tend to develop type 2 diabetes within 10 years and are at increased risk for cardiovascular disease and death even before the development of diabetes.

CONTENT
In this minireview we discusses the epidemiology, pathophysiology, and clinical implications of prediabetes. The rationale for therapeutic intervention in people with prediabetes, the goals of intervention, and the specific tools for intervention are presented. Emphasis is placed on data from randomized controlled clinical trials, whenever such data are available.

SUMMARY
Approximately 57 million Americans have prediabetes and are consequently at risk for cardiometabolic complications. Lifestyle modifications (dietary restriction and exercise) and certain medications can prevent the development of diabetes in persons with prediabetes. Lifestyle intervention also has been demonstrated to decrease cardiovascular disease risk markers, although data on clinical events are lacking.
Intracellular and Extracellular MicroRNAs in Breast Cancer
Authors: Corcoran Claire , Friel Anne M , Duffy Michael J , Crown John , O'Driscoll Lorraine 
Published: November 2010

BACKGROUNDSuccessful treatment of breast cancer is enhanced by early detection and, if possible, subsequent patient-tailored therapy. Toward this goal, it is essential to identify and understand the most relevant panels of biomarkers, some of which may also have relevance as therapeutic targets.METHODSWe critically reviewed published literature on microRNAs (miRNAs) as relevant to breast cancer.SUMMARYSince the initial recognition of the association of miRNAs with breast cancer in 2005, studies involving cell lines, in vivo models, and clinical specimens have implicated several functions for miRNAs, including suppressing oncogenesis and tumors, promoting or inhibiting metastasis, and increasing sensitivity or resistance to chemotherapy and targeted agents in breast cancer. For example, miR-21 is overexpressed in both male and female breast tumors compared with normal breast tissue and has been associated with advanced stage, lymph node positivity, and reduced survival time. miR-21 knock-down in cell-line models has been associated with increased sensitivity to topotecan and taxol in vitro and the limitation of lung metastasis in vivo. Furthermore, the discovery of extracellular miRNAs (including miR-21), existing either freely or in exosomes in the systemic circulation, has led to the possibility that such molecules may serve as biomarkers for ongoing patient monitoring. Although additional investigations are necessary to fully exploit the use of miRNAs in breast cancer, there is increasing evidence that miRNAs have potential not only to facilitate the determination of diagnosis and prognosis and the prediction of response to treatment, but also to act as therapeutic targets and replacement therapies.
Association of a MTNR1B gene variant with fasting glucose and HOMA-B in children and adolescents with high BMI-SDS
Authors: Holzapfel Christina , Siegrist Monika , Rank Melanie , Langhof Helmut , Grallert Harald , Baumert Jens , Irimie Corinna , Klopp Norman , Wolfarth Bernd , Illig Thomas , Hauner Hans , Halle Martin 
Published: November 2010

ContextGenome-wide association studies have shown that the melatonin receptor 1B (MTNR1B) gene locus is strongly associated with fasting glucose and β-cell function. However, data are rather limited to the adult population and normal-weight children. So far, little is known whether similar associations are present in overweight and obese children and adolescents.ObjectiveThe aim is to investigate an MTNR1B polymorphism in a sample of 310 overweight and obese children and adolescents (mean body mass index standard deviation score (BMI-SDS)): 2.74 (±0.55), mean age: 14 (±2) years), who participated in a short-term weight-loss program based on energy reduction, physical activity, and behavior therapy.MethodsWe investigated an association between genotype and fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and of β-cell function (HOMA-B), and anthropometric parameters and their change during intervention.ResultsThe minor G allele of polymorphism rs10830963 was significantly associated with increased fasting glucose (0.205 mmol/l, P<0.0001) and decreased HOMA-B (−0.353, P<0.0001). Categorizing the sample into BMI-SDS groups, these significant associations were abolished in children with BMI-SDS below 2.5 but remained in those with higher BMI-SDS values with stronger β-estimates. The P value for the genotype×BMI-SDS category interaction was 0.012 for fasting glucose and 0.083 for HOMA-B. There was no significant association between genotype and anthropometric parameters and their change during intervention.ConclusionsThis is the first single study, replicating the association between the MTNR1B locus and diabetes-related traits in overweight and obese children and adolescents. The effect sizes in children and adolescents seem to be stronger than in adults and differed among BMI-SDS categories.
Insulin enhances ACTH-stimulated androgen and glucocorticoid metabolism in hyperandrogenic women
Authors: Tosi Flavia , Negri Carlo , Brun Elisabetta , Castello Roberto , Faccini Giovanni , Bonora Enzo , Muggeo Michele , Toscano Vincenzo , Moghetti Paolo 
Published: November 2010

ObjectiveIn hyperandrogenic women, hyperinsulinaemia amplifies 17α-hydroxycorticosteroid intermediate response to ACTH, without alterations in serum cortisol or androgen response to stimulation. The aim of the study is to assess whether acute hyperinsulinaemia determines absolute changes in either basal or ACTH-stimulated adrenal steroidogenesis in these subjects.Design and methodsTwelve young hyperandrogenic women were submitted in two separate days to an 8 h hyperinsulinaemic (80 mU/m2×min) euglycaemic clamp, and to an 8 h saline infusion. In the second half of both the protocols, a 4 h ACTH infusion (62.5 μg/h) was carried out. Serum cortisol, progesterone, 17α-hydroxyprogesterone (17-OHP), 17α-hydroxypregnenolone (17-OHPREG), DHEA and androstenedione were measured at basal level and during the protocols. Absolute adrenal hormone secretion was quantified by measuring C19 and C21 steroid metabolites in urine collected after the first 4 h of insulin or saline infusion, and subsequently after 4 h of concurrent ACTH infusion.ResultsDuring insulin infusion, ACTH-stimulated 17-OHPREG and 17-OHP were significantly higher than during saline infusion. No significant differences in cortisol and androgens response to ACTH were found between the protocols. Nevertheless, urinary excretion of ACTH-stimulated C19 and C21 steroid metabolites was significantly higher during hyperinsulinaemia than at basal insulin levels (both P<0.005). Changes in steroid metabolites molar ratios suggested stimulation by insulin of 5α-reductase activity.ConclusionsThese in vivo data support the hypothesis that insulin acutely enhances ACTH effects on both the androgen and glucocorticoid pathways.