bluuebunny/crossref_metadata_2025_split huggingface dataset:
May duration of untreated illness influence the long-term course of major depressive disorder?
Authors: Altamura A. Carlo , Dell'Osso Bernardo , Vismara Serena , Mundo Emanuela 
Published: January 2008

AbstractThe aim of this naturalistic study was to investigate the possible influence of the duration of untreated illness (DUI) on the long-term course of Major Depressive Disorder (MDD). One hundred and thirteen patients with recurrent MDD, according to DSM-IV-TR criteria, followed up for 5 years, were selected, interviewed and their clinical charts were reviewed. The DUI was defined as the interval between the onset of the first depressive episode and the first adequate antidepressant treatment. The sample was divided into two groups according to the DUI: one group with a DUI ≤ 12 months (n = 75), and the other with a DUI > 12 months (n = 38). The main demographic and clinical course variables were compared between the two groups using Student's t-tests or chi-square tests. Patients with a longer DUI showed an earlier age at onset (t = 2.82, p = 0.006) and a longer duration of illness (t = 3.20, p = 0.002) compared to patients with a shorter DUI. In addition, the total number of depressive episodes occurring before the first antidepressant treatment was higher in the group with a longer DUI (t = −2.223, p < 0.03). Even though limited by the retrospective nature of the study, these preliminary findings would suggest that a longer DUI may negatively influence the course of MDD. Larger prospective studies are warranted to further investigate the role of the DUI within MDD.
BARRIERS TO THE USE OF MODERN CONTRACEPTIVES AND IMPLICATIONS FOR WOMAN-CONTROLLED PREVENTION OF SEXUALLY TRANSMITTED INFECTIONS IN MADAGASCAR
Authors: RANDRIANASOLO BODO , SWEZEY TERESA , VAN DAMME KATHLEEN , KHAN MARIA R. , RAVELOMANANA NORO , LOVANIAINA RABENJA NY , RAHARINIVO MBOLATIANA , BELL APRIL J. , JAMIESON DENISE ,   THE MAD STI PREVENTION GROUP, BEHETS FRIEDA 
Published: January 2008

SummaryGlobally, unplanned pregnancies and sexually transmitted infections (STIs) persist as significant threats to women’s reproductive health. Barriers to the use of modern contraceptives by women might inhibit uptake of novel woman-controlled methods for preventing STIs/HIV. Use of modern contraceptives and perceptions and attitudes towards contraceptive use were investigated among women in Antananarivo, Madagascar, using qualitative research. The hypothetical acceptability of the diaphragm – a woman-controlled barrier contraceptive device that also holds promise of protecting against STIs/HIV – was assessed. Women consecutively seeking care for vaginal discharge at a public health clinic were recruited for participation in a semi-structured interview (SSI) or focus group discussion (FGD). Audiotaped SSIs and FGDs were transcribed, translated and coded for predetermined and emerging themes. Of 46 participating women, 70% reported occasional use of male condoms, mostly for preventing pregnancy during their fertile days. Although women could name effective contraceptive methods, only 14% reported using hormonal contraception. Three barriers to use of modern contraceptives emerged: gaps in knowledge about the range of available contraceptive methods; misinformation and negative perceptions about some methods; and concern about social opposition to contraceptive use, mainly from male partners. These results demonstrate the need for programmes in both family planning and STI prevention to improve women’s knowledge of modern contraceptives and methods to prevent STI and to dispel misinformation and negative perceptions of methods. In addition, involvement of men will probably be a critical component of increased uptake of woman-controlled pregnancy and STI/HIV prevention methods and improved health.
Successful Control of Aggregation and Folding Rates during Refolding of Denatured Lysozyme by Adding N‐Methylimidazolium Cations with Various N′‐Substituents
Authors: Yamaguchi Satoshi , Yamamoto Etsushi , Tsukiji Shinya , Nagamune Teruyuki 
Published: January 2008

AbstractThe present study aimed to obtain more effective refolding agents and to understand the influence of their chemical structures on their function as refolding agents. To achieve these aims, we investigated the effects of a large variety of N′‐substituted N‐methylimidazolium chlorides on the oxidative refolding of lysozyme in a high throughput manner. Among the molecules examined, N‐methylimidazolium cations with a short N′‐alkyl chain, such as an N′‐ethyl or N′‐butyl chain, significantly enhanced the refolding yield compared to conventional refolding additives such as arginine hydrochloride and Triton X‐100. Detailed kinetic analyses revealed that the effective cations selectively decreased the aggregation rate constant ( kA) without any large decreases in the folding rate constant ( kN). However, when the hydrophobicity of the N′‐substituent of the cations was increased, the desirable properties of the short N′‐alkyl chain‐type cations for protein refolding were diminished. Furthermore, increases in the N′‐alkyl chain length to an N′‐octyl or N′‐dodecyl chain drastically decreased the kA values, thereby increasing the ratio of kN to kA, despite the very small kN values and resulting in enhanced refolding yields. Thus, by tuning the chemical structure of the N′‐substituents of N‐methylimidazolium chloride, five effective refolding agents ( N′‐ethyl‐, N′‐propyl‐, N′‐butyl‐, N′‐pentyl‐ and N′‐isobutyl‐ N‐methylimidazolium chlorides) were successfully obtained, and the kinetic parameters of folding and aggregation during the refolding process could be controlled using three different modes.
Temporal Patterns of Recovery Across Eating Disorder Subtypes
Authors: Von Holle Ann , Poyastro Pinheiro Andréa , Thornton Laura M. , Klump Kelly L. , Berrettini Wade H. , Brandt Harry , Crawford Steven , Crow Scott , Fichter Manfred M. , Halmi Katherine A. , Johnson Craig , Kaplan Allan S. , Keel Pamela , La Via Maria , Mitchell James , Strober Michael , Blake Woodside D. , Kaye Walter H. , Bulik Cynthia M. 
Published: January 2008

Objective: To compare patterns of recovery in individuals with index episodes of anorexia nervosa (AN) and bulimia nervosa (BN). Method: Using Kaplan–Meier methods and Cox proportional hazards models, comparisons were conducted that were conditional on duration of eating disorder from onset and included a conservative recovery criterion of 3 asymptomatic years. Data collection was retrospective and from two of the international Price Foundation genetic studies on 901 individuals with eating disorders. Results: Using Kaplan–Meier methods, 11% of those with index AN and 10% of those with index BN met recovery criteria at 10 years. At 15 years, 16% of those with index AN and 25% of those with index BN met recovery criteria. In a Cox proportional hazards model the index BN group had three times the rate of recovery at 10–14 years (p=0.01) than the index AN group. Conclusions: Initially the probability of recovery was greater for those with index AN, but as the duration of the eating disorder lengthened those with BN had higher probabilities of recovery. Replication of these results with prospective data using similarly stringent recovery criteria and methods is required to confirm trends.
Antenatal pulmonary embolism: risk factors, management and outcomes
Authors: Knight M ,   UKOSS
Published: January 2008

Objectives  To estimate the incidence of antenatal pulmonary embolism and describe the risk factors, management and outcomes.Design  A national matched case–control study using the UK Obstetric Surveillance System (UKOSS).Setting  All hospitals with consultant‐led maternity units in the UK.Participants  A total of 143 women who had an antenatal pulmonary embolism between February 2005 and August 2006. Two hundred and fifty nine matched control women.Methods  Prospective case and control identification through the UKOSS monthly mailing.Main outcome measures  Incidence and case fatality rates with 95% CIs. Adjusted odds ratio estimates.Results  One hundred per cent of UK consultant‐led obstetric units contributed data to UKOSS. A total of 143 antenatal pulmonary embolisms were reported, representing an estimated incidence of 1.3 per 10 000 maternities (95% CI 1.1–1.5). Seventy per cent of women had identifiable classical risk factors for thromboembolic disease. The main risk factors for pulmonary embolism were multiparity (adjusted odds ratio [aOR] 4.03, 95% CI 1.60–9.84) and body mass index ≥ 30 kg/m2 (aOR 2.65, 95% CI 1.09–6.45). Nine women who had a pulmonary embolism should have received antenatal thromboprophylaxis with low‐molecular‐weight heparin (LMWH) according to national guidelines; only three (33%) of them did. Six women (4%) had a pulmonary embolism following antenatal prophylaxis with LMWH; three of these women (50%) were receiving lower than recommended doses. Two women had recurrent pulmonary emboli (1.4%, 95% CI 0.2–5.1%). Five women died (case fatality 3.5%, 95% CI 1.1–8.0%).Conclusions  Significant severe morbidity from thromboembolic disease underlies the maternal deaths from pulmonary embolism in the UK. This study has shown some cases where thromboprophylaxis was not provided according to national guidelines, and there may be scope for further work on guideline implementation.
Geographic variation in ecophysiological traits of black cottonwood (Populus trichocarpa)This article is one of a selection of papers published in the Special Issue on Poplar Research in Canada.
Authors: Gornall Jemma L. , Guy Robert D. 
Published: January 2008

Variation in traits related to photosynthesis and water-use were examined within and between geographic sources (provenances) of black cottonwood in two range-wide common garden experiments in British Columbia, Canada. In the first experiment, CO2 assimilation (A), stomatal conductance (gs), instantaneous intrinsic water use efficiency (WUEi), stomatal density, specific leaf area, growth height, and foliar N were measured on five 2-year-old trees of 20 clones from five widely separated provenances (i.e., 4 clones per source). Leaf disks were analysed for stable carbon isotope composition (δ13C) to provide a more long-term measure of WUE. Photosynthetic rate per unit leaf nitrogen was used as a measure of nitrogen use efficiency (NUE). A differed between (p < 0.001), but not within provenances, and increased with latitude of origin (R2 = 0.70). NUE and WUEi also varied between (p = 0.034 and p = 0.039, respectively), but not within provenances. In contrast, no variation among provenances was detected for δ13C, but there were strong differences between clones within provenances (p < 0.001). Variation in A was well correlated with foliar nitrogen, gs, and stomatal density and adaxial:abaxial distribution ratio; hence, WUEi, δ13C and NUE were mostly unrelated to latitude or associated climate variables. Species-wide patterns in stomatal density and distribution were confirmed in the second experiment which utilized 140 clones. Stomatal density on the adaxial (but not the abaxial) leaf surface was strongly correlated with latitude (p <0.001). We speculate that northern provenances may have inherently higher A and gs to compensate for shorter growing seasons.
HARMONIC OSCILLATOR IN NONCOMMUTING TWO-DIMENSIONAL SPACE
Authors: STREKLAS ANTONY 
Published: January 2008

In the present paper, we study a two-dimensional harmonic oscillator in a constant magnetic field in noncommuting space. We use the following Hamiltonian [Formula: see text] with commutation relations [Formula: see text] and [Formula: see text].The parameter λ expresses the presence of the magnetic field. We find the exact propagator of the system and the time evolution of the basic operators. We prove that the system is equivalent to a two-dimensional system where the operators of momentum and coordinates of the second dimension satisfy a deformed commutation relation [Formula: see text]. The deformation parameter, μ, depends on λ and θ, and is independent of the Hamiltonian. Finally, we investigate the thermodynamic properties of the system in Boltzmann statistics. We find the statistical density matrix and the partition function, which is equivalent to that of a two-dimensional harmonic oscillator with two deformed frequencies Ω1and Ω2.
Regulation of Angiogenic Factors by HDM2 in Renal Cell Carcinoma
Authors: Carroll Veronica A. , Ashcroft Margaret 
Published: January 2008

Abstract
The oncogene HDM2 has been implicated in the regulation of the transcription factor, hypoxia inducible factor (HIF). We show in von Hippel-Lindau (VHL)-defective renal carcinoma cells that express constitutively high levels of HIF-1α and HIF-2α that down-regulation of HDM2 by siRNA leads to decreased levels of both HIF-1α and HIF-2α protein levels. However, we show a differential regulation of HDM2 on the HIF angiogenic targets, vascular endothelial growth factor (VEGF), plasminogen activator inhibitor-1 (PAI-1), and endothelin-1 (ET-1): siRNA to HDM2 leads to increased expression of VEGF and PAI-1 proteins but decreased levels of ET-1. We show that HDM2-mediated regulation of these proteins is independent of VHL and p53 but dependent on a novel action of HDM2. Ablation of HDM2 leads to phosphorylation of extracellular-regulated kinase (ERK)1/2 in renal carcinoma cells. We show that regulation of these angiogenic factors is dependent on ERK1/2 phosphorylation, which can be reversed by addition of the MAP/ERK1/2 kinase inhibitors PD98059 and PD184352. This study identifies a novel role for the HDM2 oncoprotein in the regulation of angiogenic factors in renal cell carcinoma. [Cancer Res 2008;68(2):545–52]
Regulation of Gastric Carcinogenesis by Helicobacter pylori Virulence Factors
Authors: Franco Aime T. , Johnston Elizabeth , Krishna Uma , Yamaoka Yoshio , Israel Dawn A. , Nagy Toni A. , Wroblewski Lydia E. , Piazuelo Maria Blanca , Correa Pelayo , Peek Richard M. 
Published: January 2008

Abstract
Helicobacter pylori is the strongest known risk factor for gastric adenocarcinoma, and strains that possess the cag secretion system, which translocates the bacterial effector CagA into host cells, augment cancer risk. H. pylori strains that express the vacuolating cytotoxin or the outer membrane protein OipA are similarly associated with severe pathologic outcomes. We previously reported that an in vivo adapted H. pylori strain, 7.13, induces gastric adenocarcinoma in rodent models of gastritis. In the current study, we used carcinogenic strain 7.13 as a prototype to define the role of virulence constituents in H. pylori–mediated carcinogenesis. Mongolian gerbils were infected with wild-type strain 7.13 or cagA−, vacA−, or oipA− mutants for 12 to 52 weeks. All infected gerbils developed gastritis; however, inflammation was significantly attenuated in animals infected with the cagA− but not the vacA− or oipA− strains. Gastric dysplasia and cancer developed in &gt;50% of gerbils infected with either the wild-type or vacA− strain but in none of the animals infected with the cagA− strain. Inactivation of oipA decreased β-catenin nuclear localization in vitro and reduced the incidence of cancer in gerbils. OipA expression was detected significantly more frequently among H. pylori strains isolated from human subjects with gastric cancer precursor lesions versus persons with gastritis alone. These results indicate that loss of CagA prevents the development of cancer in this model. Inactivation of oipA attenuates β-catenin nuclear translocation and also decreases the incidence of carcinoma. In addition to defining factors that mediate H. pylori–induced cancer, these results provide insight into mechanisms that may regulate the development of other malignancies arising within the context of inflammatory states. [Cancer Res 2008;68(2):379–87]
α2-6–Linked Sialic Acids on N-Glycans Modulate Carcinoma Differentiation In vivo
Authors: Hedlund Maria , Ng Elisa , Varki Ajit , Varki Nissi M. 
Published: January 2008

Abstract
Sialic acids on vertebrate cell surfaces mediate many biological roles. Altered expression of certain sialic acid types or their linkages can have prognostic significance in human cancer. A classic but unexplained example is enhanced α2-6-sialylation on N-glycans resulting from overexpression of the Golgi enzyme β-galactoside:α2-6-sialyltransferase (ST6Gal-I). Previous data supporting a role for the resulting Siaα2-3Galβ1-4GlcNAc (Sia6LacNAc) structure in tumor biology were based on in vitro studies in transfected carcinoma cells, in which increased Sia6LacNAc on β1-integrins enhanced their binding to ligands, and stimulated cell motility. Here, we examine for the first time the in vivo role of the ST6Gal-I enzyme in the growth and differentiation of spontaneous mammary cancers in mice transgenic for a mouse mammary tumor virus promoter–driven polyomavirus middle T antigen, a tumor in which β1-integrin function is important for tumorigenesis and in maintaining the proliferative state of tumor cells. Tumors induced in St6gal1-null animals were more differentiated compared with those in the wild-type background, both by histologic analysis and by protein expression profiles. Furthermore, we show the St6gal1-null tumors have selectively altered expression of genes associated with focal adhesion signaling and have decreased phosphorylation of focal adhesion kinase, a downstream target of β1-integrins. This first in vivo evidence for a role of ST6Gal-I in tumor progression was confirmed using a novel approach, which conditionally restored St6gal1 in cell lines derived from the null tumors. These findings indicate a role for ST6Gal-I as a mediator of tumor progression, with its expression causing a less differentiated phenotype, via enhanced β1-integrin function. [Cancer Res 2008;68(2):388–94]
Inhibition of Hsp90 Down-regulates Mutant Epidermal Growth Factor Receptor (EGFR) Expression and Sensitizes EGFR Mutant Tumors to Paclitaxel
Authors: Sawai Ayana , Chandarlapaty Sarat , Greulich Heidi , Gonen Mithat , Ye Qing , Arteaga Carlos L. , Sellers William , Rosen Neal , Solit David B. 
Published: January 2008

Abstract
Mutations in the kinase domain of the epidermal growth factor receptor (EGFR) are found in a subset of patients with lung cancer and correlate with response to EGFR tyrosine kinase inhibitors (TKI). Resistance to these agents invariably develops, and current treatment strategies have limited efficacy in this setting. Hsp90 inhibitors, such as 17-allylamino-17-demethoxygeldanamycin (17-AAG), induce the degradation of EGFR and other Hsp90 interacting proteins and may thus have utility in tumors dependent upon sensitive Hsp90 clients. We find that the EGFR mutations found most commonly in patients with lung adenocarcinoma who respond to EGFR TKIs are potently degraded by 17-AAG. Although the expression of wild-type EGFR was also down-regulated by 17-AAG, its degradation required higher concentrations of drug and a longer duration of drug exposure. In animal models, a single dose of 17-AAG was sufficient to induce degradation of mutant EGFR and inhibit downstream signaling. 17-AAG treatment, at its maximal tolerated dose, caused a significant delay in H3255 (L858R EGFR) xenograft growth but was less effective than the EGFR TKI gefitinib. 17-AAG alone delayed, but did not completely inhibit, the growth of H1650 and H1975 xenografts, two EGFR mutant models which show intermediate and high levels of gefitinib resistance. 17-AAG could be safely coadministered with paclitaxel, and the combination was significantly more effective than either drug alone. These data suggest that Hsp90 inhibition in combination with chemotherapy may represent an effective treatment strategy for patients whose tumors express EGFR kinase domain mutations, including those with de novo and acquired resistance to EGFR TKIs. [Cancer Res 2008;68(2):589–96]
t-Darpp Promotes Cancer Cell Survival by Up-regulation of Bcl2 through Akt-Dependent Mechanism
Authors: Belkhiri Abbes , Dar Altaf A. , Zaika Alexander , Kelley Mark , El-Rifai Wael 
Published: January 2008

Abstractt-Darpp is a cancer-related truncated isoform of Darpp-32 (dopamine and cyclic-AMP–regulated phosphoprotein of Mr 32,000). We detected overexpression of t-Darpp mRNA in two thirds of gastric cancers compared with normal samples (P = 0.004). Using 20 μmol/L ceramide treatment as a model for induction of apoptosis in AGS cancer cells, we found that expression of t-Darpp led to an increase in Bcl2 protein levels and blocked the activation of caspase-3 and caspase-9. The MitoCapture mitochondrial apoptosis and cytochrome c release assays indicated that t-Darpp expression enforces the mitochondrial transmembrane potential and protects against ceramide-induced apoptosis. Interestingly, the expression of t-Darpp in AGS cells led to ≥2-fold increase in Akt kinase activity with an increase in protein levels of p-Ser473 Akt and p-Ser9 GSK3β. These findings were further confirmed using tetracycline-inducible AGS cells stably expressing t-Darpp. We also showed transcriptional up-regulation of Bcl2 using the luciferase assay with Bcl2 reporter containing P1 full promoter, quantitative reverse transcription-PCR, and t-Darpp small interfering RNA. The Bcl2 promoter contains binding sites for cyclic AMP–responsive element binding protein CREB/ATF1 transcription factors and using the electrophoretic mobility shift assay with a CREB response element, we detected a stronger binding in t-Darpp–expressing cells. The t-Darpp expression led to an increase in expression and phosphorylation of CREB and ATF-1 transcription factors that were required for up-regulating Bcl2 levels. Indeed, knockdown of Akt, CREB, or ATF1 in t-Darpp–expressing cells reduced Bcl2 protein levels. In conclusion, the t-Darpp/Akt axis underscores a novel oncogenic potential of t-Darpp in gastric carcinogenesis and resistance to drug-induced apoptosis. [Cancer Res 2008;68(2):395–403]
Integrating Global Gene Expression and Radiation Survival Parameters across the 60 Cell Lines of the National Cancer Institute Anticancer Drug Screen
Authors: Amundson Sally A. , Do Khanh T. , Vinikoor Lisa C. , Lee R. Anthony , Koch-Paiz Christine A. , Ahn Jaeyong , Reimers Mark , Chen Yidong , Scudiero Dominic A. , Weinstein John N. , Trent Jeffrey M. , Bittner Michael L. , Meltzer Paul S. , Fornace Albert J. 
Published: January 2008

Abstract
The 60 cell lines of the National Cancer Institute Anticancer Drug Screen (NCI-60) constitute the most extensively characterized in vitro cancer cell model. They have been tested for sensitivity to more than 100,000 potential chemotherapy agents and have been profiled extensively at the DNA, RNA, protein, functional, and pharmacologic levels. We have used the NCI-60 cell lines and three additional lines to develop a database of responses of cancer cells to ionizing radiation. We compared clonogenic survival, apoptosis, and gene expression response by microarray. Although several studies have profiled relative basal gene expression in the NCI-60, this is the first comparison of large-scale gene expression changes in response to genotoxic stress. Twenty-two genes were differentially regulated in cells with low survival after 2-Gy γ-rays; 14 genes identified lines more sensitive to 8 Gy. Unlike reported basal gene expression patterns, changes in expression in response to radiation showed little tissue-of-origin effect, except for differentiating the lymphoblastoid cell lines from other cell types. Basal expression patterns, however, discriminated well between radiosensitive and more resistant lines, possibly being more informative than radiation response signatures. The most striking patterns in the radiation data were a set of genes up-regulated preferentially in the p53 wild-type lines and a set of cell cycle regulatory genes down-regulated across the entire NCI-60 panel. The response of those genes to γ-rays seems to be unaffected by the myriad of genetic differences across this diverse cell set; it represents the most penetrant gene expression response to ionizing radiation yet observed. [Cancer Res 2008;68(2):415–24]