tbuckley/cabot-search huggingface dataset:
A cross-sectional study using the Children’s Dermatology Life Quality Index (CDLQI) in childhood psoriasis: negative effect on quality of life and moderate correlation of CDLQI with severity scores
Authors: M.E.A. De Jager, P.C.M. Van De Kerkhof, E.M.G.J. De Jong, M.M.B. Seyger
Journal: British Journal of Dermatology (2010)

Journal Article A cross‐sectional study using the Children’s Dermatology Life Quality Index (CDLQI) in childhood psoriasis: negative effect on quality of life and moderate correlation of CDLQI with severity scores Get access M.E.A. De Jager, M.E.A. De Jager Department of Dermatology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, the Netherlands Correspondence: Michelle E.A. de Jager. E‐mail: M.deJager@derma.umcn.nl Search for other works by this author on: Oxford Academic Google Scholar P.C.M. Van De Kerkhof, P.C.M. Van De Kerkhof Department of Dermatology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar E.M.G.J. De Jong, E.M.G.J. De Jong Department of Dermatology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar M.M.B. Seyger M.M.B. Seyger Department of Dermatology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 163, Issue 5, 1 November 2010, Pages 1099–1101, https://doi.org/10.1111/j.1365-2133.2010.09993.x Published: 01 November 2010
Pregnancy Complications and Neonatal Outcomes in Women With Eating Disorders
Authors: D L Franko, M A Blais, A E Becker, S S Delinsky, D N Greenwood, A T Flores, E R Ekeblad, K T Eddy, D B Herzog
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: This study reported pregnancy complications and neonatal outcomes for 49 live births in a group of women with eating disorders who were prospectively followed. METHOD: Subjects were recruited from 246 women participating in a longitudinal study of anorexia nervosa and bulimia nervosa, now in its 12th year. Subjects were interviewed by trained assistants and completed a brief self-report instrument that assessed both birth statistics and birth-related complications. Medical records and/or self-report data describing the neonates' birth status were obtained. RESULTS: The majority of the women with eating disorders had normal pregnancies, resulting in healthy babies. Across the group, the mean length of pregnancy was 38.7 weeks, the mean birth weight was 7.6 lb, and mean Apgar scores at 1 and 5 minutes after birth were 8.2 and 9.0, respectively. Most outcomes were positive; however, three babies (6.1%) had birth defects, and 17 (34.7%) of the women experienced postpartum depression. The mean number of obstetric complications in the group was 1.3, and 13 (26.5%) of the women delivered by cesarean section. Women who showed symptoms of either anorexia nervosa or bulimia nervosa during pregnancy had a higher frequency of birth by cesarean section and postpartum depression than did nonsymptomatic women. CONCLUSIONS: Pregnant women with active eating disorders appear to be at greater risk for delivery by cesarean section and for postpartum depression. Pregnant women with past or current eating disorders should be viewed as being at high risk and monitored closely both during and after pregnancy to optimize maternal and fetal outcomes.
Macrolide Resistance Among Invasive &lt;EMPH TYPE="ITAL"&gt;Streptococcus pneumoniae&lt;/EMPH&gt; Isolates
Authors: T B Hyde, K Gay, D S Stephens, D J Vugia, M Pass, S Johnson, N L Barrett, W Schaffner, P R Cieslak, P S Maupin, E R Zell, J H Jorgensen, R R Facklam, C G Whitney
Journal: JAMA (2001)

ContextMacrolide antibiotics, including erythromycin, clarithromycin, and azithromycin, are the mainstays of empirical pneumonia therapy. Macrolide resistance among Streptococcus pneumoniae, the most common cause of community-acquired pneumonia, is increasing in the United States. Whether resistance is a significant problem or whether macrolides remain useful for treatment of most resistant strains is unknown.ObjectiveTo examine the epidemiology of macrolide-resistant pneumococci in the United States.Design and SettingAnalysis of 15 481 invasive isolates from 1995 to 1999 collected by the Centers for Disease Control and Prevention's Active Bacterial Core surveillance system in 8 states.Main Outcome MeasuresTrends in macrolide use (1993-1999) and resistance and factors associated with resistance, including examination of 2 subtypes, the M phenotype, associated with moderate minimum inhibitory concentrations (MICs), and the MLSB phenotype, associated with high MICs and clindamycin resistance.ResultsFrom 1993 to 1999, macrolide use increased 13%; macrolide use increased 320% among children younger than 5 years. Macrolide resistance increased from 10.6% in 1995 to 20.4% in 1999. M phenotype isolates increased from 7.4% to 16.5% (P<.001), while the proportion with the MLSB phenotype was stable (3%-4%). The median erythromycin MIC (MIC50) of M phenotype isolates increased from 4 µg/mL to 8 µg/mL. In 1999, M phenotype strains were more often from children than persons 5 years or older (25.2% vs 12.6%; P<.001) and from whites than blacks (19.3% vs 11.2%; P<.001).ConclusionsIn the setting of increasing macrolide use, pneumococcal resistance has become common. Most resistant strains have MICs in the range in which treatment failures have been reported. Further study and surveillance are critical to understanding the clinical implications of our findings.
The Control of Mesenchymal Stem Cell Differentiation Using Dynamically Tunable Surface Microgrooves
Authors: Tao Gong, Kun Zhao, Guang Yang, Jinrong Li, Hongmei Chen, Yuping Chen, Shaobing Zhou
Journal: Advanced Healthcare Materials (2014)

Many studies have demonstrated the potential to modulate stem cell differentiation by using static material substrate surfaces. However, cells actually grow in a dynamically diverse microenvironment in vivo. The regulated signals to the differentiation provided by these materials should not be passive or static but be active and dynamic. To mimic the endogenous cell culture microenvironment, a novel system is designed to realize the dynamic change of the surface geometries as well as a resultant mechanical force using a thermally activated four‐stage shape memory polymer. The parallel microgroove surface patterns are fabricated via thermal embossing lithography on the polymer substrate surface. The dynamic microgroove surfaces accompanying with the mechanical force can effectively and significantly regulate the shape and the cytoskeletal arrangement of rBMSC compared with the static patterned and non‐patterned surfaces. Cellular and molecular analyses reveal that the spatiotemporally programmed regulation of cell shape is more viable to coax lineage‐specific differentiation of stem cell in contrast to the general reports with the static surfaces. Therefore, this study provides a facile strategy in designing and manufacturing an artificial substrate with a mimic natural cellular environment to precisely direct the cell differentiation.
Protective effects of tiotropium bromide in the progression of airway smooth muscle remodeling
Authors: Mariana Kulynych-Miskiv, Mykola Ostrovskyy, Oleksandr Varunkiv, Iryna Savelikhina
Journal: European Respiratory Journal (2013)

OBJECTIVE: We investigated the effects of treatment with the long-acting muscarinic receptor antagonist tiotropium on airway smooth muscle changes in patient with COPD II stages.  RESULTS: To observe the effect on airway inflammation, we analyzed total and differential cell counts in bronchoalveolar lavage fluid and there is little difference between COPD group and tiotropium- treated group, regardless of the concentration of tiotropium. In the preliminary study of COPD, we also observed that tiotropium administration does not decrease the counts of airway inflammatory cells compared with COPD group. However, the tiotropium-treated group inhibited airway hyperresponsiveness to methacholine in comparision with control group and showed the hyperplasia of goblet cells more decreased than in COPD group. The area of α-smooth muscle actin, as an indicator of remodeling in airway smooth muscle by immun histochemical staining significantly decreased in tiotropium-treated group.  CONCLUSIONS: These results indicate a prominent role for acetylcholine in airway smooth muscle remodeling, a process that was thus far considered to be primarily caused by growth factors and other mediators of inflammation. Therefore, muscarinic receptor antagonists like the long-acting anticholinergic tiotropium bromide could be beneficial in preventing chronic airway hyperresponsiveness and decline in lung function in COPD.
Role of DNA Methylation and Epigenetic Silencing of HAND2 in Endometrial Cancer Development
Authors: Allison Jones, Andrew E. Teschendorff, Quanxi Li, Jane D. Hayward, Athilakshmi Kannan, Tim Mould, James West, Michal Zikan, David Cibula, Heidi Fiegl, Shih-Han Lee, Elisabeth Wik, Richard Hadwin, Rupali Arora, Charlotte Lemech, Henna Turunen, Päivi Pakarinen, Ian J. Jacobs, Helga B. Salvesen, Milan K. Bagchi, Indrani C. Bagchi, Martin Widschwendter
Journal: PLoS Medicine (2013)

Background Endometrial cancer incidence is continuing to rise in the wake of the current ageing and obesity epidemics. Much of the risk for endometrial cancer development is influenced by the environment and lifestyle. Accumulating evidence suggests that the epigenome serves as the interface between the genome and the environment and that hypermethylation of stem cell polycomb group target genes is an epigenetic hallmark of cancer. The objective of this study was to determine the functional role of epigenetic factors in endometrial cancer development. Methods and Findings Epigenome-wide methylation analysis of >27,000 CpG sites in endometrial cancer tissue samples (n = 64) and control samples (n = 23) revealed that HAND2 (a gene encoding a transcription factor expressed in the endometrial stroma) is one of the most commonly hypermethylated and silenced genes in endometrial cancer. A novel integrative epigenome-transcriptome-interactome analysis further revealed that HAND2 is the hub of the most highly ranked differential methylation hotspot in endometrial cancer. These findings were validated using candidate gene methylation analysis in multiple clinical sample sets of tissue samples from a total of 272 additional women. Increased HAND2 methylation was a feature of premalignant endometrial lesions and was seen to parallel a decrease in RNA and protein levels. Furthermore, women with high endometrial HAND2 methylation in their premalignant lesions were less likely to respond to progesterone treatment. HAND2 methylation analysis of endometrial secretions collected using high vaginal swabs taken from women with postmenopausal bleeding specifically identified those patients with early stage endometrial cancer with both high sensitivity and high specificity (receiver operating characteristics area under the curve = 0.91 for stage 1A and 0.97 for higher than stage 1A). Finally, mice harbouring a Hand2 knock-out specifically in their endometrium were shown to develop precancerous endometrial lesions with increasing age, and these lesions also demonstrated a lack of PTEN expression. Conclusions HAND2 methylation is a common and crucial molecular alteration in endometrial cancer that could potentially be employed as a biomarker for early detection of endometrial cancer and as a predictor of treatment response. The true clinical utility of HAND2 DNA methylation, however, requires further validation in prospective studies. Please see later in the article for the Editors' Summary
Aerosol Delivery of Glucosylated Polyethylenimine/Phosphatase and Tensin Homologue Deleted on Chromosome 10 Complex Suppresses Akt Downstream Pathways in the Lung of K-<b> <i>ras</i> </b> Null Mice
Authors: Hyun Woo Kim, In Kyu Park, Chong Su Cho, Kee Ho Lee, George R. Beck, Nancy H. Colburn, Myung Haing Cho
Journal: Cancer Research (2004)

Abstract Difficulties in achieving long-term survival of lung cancer patients treated with conventional therapies suggest that novel approaches are required. Although several genes have been investigated for antitumor activities using gene delivery, problems surrounding the methods used such as efficiency, specificity, and toxicity hinder its application as an effective therapy. This has lead to the re-emergence of aerosol gene delivery as a noninvasive approach to lung cancer therapy. In this study, glucosylated conjugated polyethylenimine (glucosylated PEI) was used as carrier. After confirming the efficiency of glucosylated PEI carriers in lungs, the potential effects of the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) tumor suppressor gene on Akt downstream pathways were investigated. Aerosol containing glucosylated PEI and recombinant plasmid pcDNA3.0-PTEN complex was delivered into K-ras null lung cancer model mice through a nose-only inhalation system. Investigation of proteins in the phosphatidylinositol 3′-kinase/Akt signaling pathway in PTEN-delivered mouse lung revealed that the PTEN protein was highly expressed, whereas the protein levels of PDK1, total Akt1, phospho-(Thr-308)-Akt, phospho-(Ser-2448)-mTOR, p70S6K, and 4E-BP1 were decreased to varying degrees. Additionally, the kinase activities of both Akt and mTOR were suppressed. Finally, apoptosis was detected in PTEN-delivered mouse lung by terminal deoxynucleotidyltransferase-mediated nick end labeling assay, suggesting that our aerosol PTEN delivery is capable of functionally altering cell phenotype in vivo. In summary, Western blot analysis, kinase assays, immunohistochemistry, and terminal deoxynucleotidyltransferase-mediated nick end labeling assays suggest that our aerosol gene delivery technique is compatible with in vivo gene delivery and can be applied as a noninvasive gene therapy.
Circulating TNF Receptors 1 and 2 Predict Stage 3 CKD in Type 1 Diabetes
Authors: Tomohito Gohda, Monika A. Niewczas, Linda H. Ficociello, William H. Walker, Jan Skupien, Florencia Rosetti, Xavier Cullere, Amanda C. Johnson, Gordon Crabtree, Adam M. Smiles, Tanya N. Mayadas, James H. Warram, Andrzej S. Krolewski
Journal: Journal of the American Society of Nephrology (2012)

Elevated plasma concentrations of TNF receptors 1 and 2 (TNFR1 and TNFR2) predict development of ESRD in patients with type 2 diabetes without proteinuria, suggesting these markers may contribute to the pathogenesis of renal decline. We investigated whether circulating markers of the TNF pathway determine GFR loss among patients with type 1 diabetes. We followed two cohorts comprising 628 patients with type 1 diabetes, normal renal function, and no proteinuria. Over 12 years, 69 patients developed estimated GFR less than 60 mL/min per 1.73 m2 (16 per 1000 person-years). Concentrations of TNFR1 and TNFR2 were strongly associated with risk for early renal decline. Renal decline was associated only modestly with total TNFα concentration and appeared unrelated to free TNFα. The cumulative incidence of estimated GFR less than 60 mL/min per 1.73 m2 for patients in the highest TNFR2 quartile was 60% after 12 years compared with 5%–19% in the remaining quartiles. In Cox proportional hazards analysis, patients with TNFR2 values in the highest quartile were threefold more likely to experience renal decline than patients in the other quartiles (hazard ratio, 3.0; 95% confidence interval, 1.7–5.5). The risk associated with high TNFR1 values was slightly less than that associated with high TNFR2 values. TNFR levels were unrelated to baseline free TNFα level and remained stable over long periods within an individual. In conclusion, early GFR loss in patients with type 1 diabetes without proteinuria is strongly associated with circulating TNF receptor levels but not TNFα levels (free or total).
Clinical outcome after infection with <i>Helicobacter pylori</i> does not appear to be reliably predicted by the presence of any of the genes of the <i>cag</i> pathogenicity island
Authors: P J Jenks, F Mégraud, A Labigne
Journal: Gut (1998)

Background —The development of clinical disease after infection with Helicobacter pylori has been reported to be associated with expression of the cagA gene. Recently, it has been shown that cagA is part of a multigene locus, described as the cag pathogenicity island (PAI). The role of this region in determining clinical outcome remains to be established. Aims —To investigate whether the presence of cagA is always associated with the presence of the complete cag PAI and to evaluate the distribution of selected cag genes in 73 H pylori strains isolated from patients in France. Methods —Clinical strains of H pylori were screened for selected genes of the cag PAI by polymerase chain reaction and colony hybridisation. Results —Of 64 strains that harboured the cagA gene, 57 (89%) also contained the entire cag PAI. The entire cag PAI was found in 85% (48/56) and 53% (9/17) of duodenal ulcer and non-ulcer dyspepsia isolates, respectively. Eight strains had deletions within the cag PAI, including deletion of the cagA gene in one isolate; the deletions were not associated with the insertion sequence IS605. Of eight strains lacking the cag PAI, four were isolated from patients with duodenal ulcer. Conclusion —The cag PAI is not a uniform, conserved entity. Although the presence of the cag PAI is highly associated with duodenal ulcer, the clinical outcome of infection with H pylori is not reliably predicted by any gene of the cag PAI.
GC3 of Genes Can Be Used as a Proxy for Isochore Base Composition: A Reply to Elhaik et al.
Authors: O. K. Clay, G. Bernardi
Journal: Molecular Biology and Evolution (2010)

In an article published in these pages, Elhaik et al. (Elhaik E, Landan G, Graur D. 2009. Can GC content at third-codon positions be used as a proxy for isochore composition? Mol Biol Evol. 26:1829–1833) asked if GC3, the GC level of the third-codon positions in protein-coding genes, can be used as a "proxy" to estimate the GC level of the surrounding isochore. We use available data to directly answer this simple question in the affirmative and show how the use of indirect methods can lead to apparently conflicting conclusions. The answer reasserts that in human and other vertebrates, genes have a strong tendency to reside in compositionally corresponding isochores, which has far-reaching implications for genome structure and evolution.
Integrative Analysis of Cyclin Protein Levels Identifies Cyclin B1 as a Classifier and Predictor of Outcomes in Breast Cancer
Authors: Roshan Agarwal, Ana-Maria Gonzalez-Angulo, Simen Myhre, Mark Carey, Ju-Seog Lee, Jens Overgaard, Jan Alsner, Katherine Stemke-Hale, Ana Lluch, Richard M. Neve, Wen Lin Kuo, Therese Sorlie, Aysegul Sahin, Vicente Valero, Khandan Keyomarsi, Joe W. Gray, Anne-Lise Borresen-Dale, Gordon B. Mills, Bryan T. Hennessy
Journal: Clinical Cancer Research (2009)

We studied the expression levels of cyclins B1, D1, and E1 and the implications of cyclin overexpression for patient outcomes in distinct breast cancer subtypes defined by clinical variables and transcriptional profiling.The expression levels of cyclins B1, D1, and E1 were quantified in 779 breast tumors and 53 cell lines using reverse phase protein arrays and/or transcriptional profiling.Whereas cyclin E1 overexpression was a specific marker of triple-negative and basal-like tumors, cyclin B1 overexpression occurred in poor prognosis hormone receptor-positive, luminal B and basal-like breast cancers. Cyclin D1 overexpression occurred in luminal and normal-like cancers. Breast cancer subgroups defined by integrated expression of cyclins B1, D1, and E1 correlated significantly (P < 0.000001) with tumor subtypes defined by transcriptional profiling and clinical criteria. Across three hormone receptor-positive data sets, cyclin B1 was the dominant cyclin associated with poor prognosis in univariate and multivariate analyses. Although CCNE1 was present in significantly higher copy numbers in basal-like versus other subtypes (ANOVA P < 0.001), CCNB1 gene copy number did not show gain in breast cancer. Instead, cyclin B1 expression was increased in tumors with co-occurrence of TP53 mutations and MYC amplification, a combination that seems to characterize basal-like and luminal B tumors. CCNB1 gene expression was significantly correlated with PLK, CENPE, and AURKB gene expression.Cyclins B1, D1, and E1 have distinct expressions in different breast cancer subtypes. Novel PLK, CENPE, and AURKB inhibitors should be assessed for therapeutic utility in poor prognosis cyclin B1-overexpressing breast cancers.
BORIS Binding to the Promoters of Cancer Testis Antigens, <i>MAGEA2</i>, <i>MAGEA3</i>, and <i>MAGEA4</i>, Is Associated with Their Transcriptional Activation in Lung Cancer
Authors: Sheetal Bhan, Sandeep S. Negi, Chunbo Shao, Chad A. Glazer, Alice Chuang, Daria A. Gaykalova, Wenyue Sun, David Sidransky, Patrick K. Ha, Joseph A. Califano
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Aim of this study was to determine whether BORIS (Brother of the Regulator of Imprinted Sites) is a regulator of MAGEA2, MAGEA3, and MAGEA4 genes in lung cancer. Experimental Design: Changes in expression of MAGEA genes upon BORIS induction/knockdown were studied. Recruitment of BORIS and changes in histone modifications at their promoters upon BORIS induction were analyzed. Luciferase assays were used to study their activation by BORIS. Changes in methylation at these promoters upon BORIS induction were evaluated. Results: Alteration of BORIS expression by induction/knockdown directly correlated with expression of MAGEA genes. BORIS was enriched at their promoters in H1299 cells, which show high expression of these cancer testis antigens (CTA), compared with normal human bronchial epithelial (NHBE) cells which show low expression of the target CTAs. BORIS induction in A549 cells resulted in increased amounts of BORIS and activating histone modifications at their promoters along with a corresponding increase in their expression. Similarly, BORIS binding at these promoters in H1299 correlates with enrichment of activating modifications, whereas absence of BORIS binding in NHBE is associated with enrichment of repressive marks. BORIS induction of MAGEA3 was associated with promoter demethylation, but no methylation changes were noted with activation of MAGEA2 and MAGEA4. Conclusions: These data suggest that BORIS positively regulates these CTAs by binding and inducing a shift to a more open chromatin conformation with promoter demethylation for MAGEA3 or independent of promoter demethylation in case of MAGEA2 and MAGEA4 and may be a key effector involved in their derepression in lung cancer. Clin Cancer Res; 17(13); 4267–76. ©2011 AACR.