bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of new cancer biomarkers based on aberrant mucin glycoforms by in situ proximity ligation
Authors: Pinto Rita , Carvalho Ana S. , Conze Tim , Magalhães Ana , Picco Gianfranco , Burchell Joy M. , Taylor‐Papadimitriou Joyce , Reis Celso A. , Almeida Raquel , Mandel Ulla , Clausen Henrik , Söderberg Ola , David Leonor 
Published: September 2011

AbstractMucin glycoproteins are major secreted or membrane‐bound molecules that, in cancer, show modifications in both the mucin proteins expression and in the O‐glycosylation profile, generating some of the most relevant tumour markers in clinical use for decades. Thus far, the identification of these biomarkers has been based on the detection of either the protein or the O‐glycan modifications. We therefore aimed to identify the combined mucin and O‐glycan features, that is, specific glycoforms, in an attempt to increase specificity of these cancer biomarkers. Using in situ proximity ligation assays (PLA) based on existing monoclonal antibodies directed to MUC1, MUC2, MUC5AC and MUC6 mucins and to cancer‐associated carbohydrate antigens Tn, Sialyl‐Tn (STn), T, Sialyl‐Lea (SLea) and Sialyl‐Lex (SLex) we screened a series of 28 mucinous adenocarcinomas from different locations (stomach, ampulla of Vater, colon, lung, breast and ovary) to detect specific mucin glycoforms. We detected Tn/STn/SLea/SLex‐MUC1 and STn/SLea/SLex‐MUC2 glycoforms in $50% of the cases, with a variable distribution among organs. Some new glycoforms‐T/SLea‐MUC2, STn/T/SLea/SLex‐MUC5AC and STn/T/SLea/SLex‐MUC6‐were identified for the first time in the present study in a variable percentage of cases from different organs. In conclusion, application of the PLA technique allowed sensitive detection of specific aberrant mucin glycoforms in cancer, increasing specificity to the use of antibodies either to the mucin protein backbone or to the O‐glycan haptens alone.
Use of an antispasmodic (rociverine) to shorten the length of labor: a randomized, placebo‐controlled trial
Authors: CROMI ANTONELLA , GHEZZI FABIO , AGOSTI MASSIMO , UCCELLA STEFANO , PIAZZA NICOLETTA , SERATI MAURIZIO , BOLIS PIERFRANCESCO 
Published: September 2011

AbstractObjective. To determine the effectiveness of rociverine, an antispasmodic drug, for reducing the duration of labor among nulliparous women managed according to a standard intrapartum protocol. Design. Randomized controlled trial. Setting. An academic tertiary care hospital. Population. Nulliparae in spontaneous active labor, with cervical dilatation between 3 and 5cm. Methods. Participants were randomly assigned to receive either an intramuscular injection of 20mg rociverine (n=55) or the same volume of saline (n=56). Main Outcome Measure. Cervical dilatation rate (from administration of study drug to full dilatation). Results. Laboring women who received rociverine had faster cervical dilatation than those assigned to placebo (2.43±1.84 vs. 1.85±1.38cm/hour, p=0.03). The time interval from treatment administration to full cervical dilatation was shorter in the rociverine group than in the placebo group (220±125 vs. 278±129min, p=0.04). No difference was found in any other obstetric outcome. No adverse effects have been recorded from rociverine administration. Conclusions. Intrapartum administration of rociverine to nulliparous women may help to reduce the duration of the first stage of labor in a context of uniform labor management.
Hydration measurements of the stratum corneum: comparison between the capacitance method (digital version of the Corneometer CM 825®) and the impedance method (Skicon‐200EX®)
Authors: Clarys Peter , Clijsen Ron , Taeymans Jan , Barel André O. 
Published: September 2011

BackgroundMeasurement of stratum corneum (SC) hydration often involves the use of commercial instruments. The aim of this study was to compare and validate two recent instruments: the Corneometer 825® (digital probe) and the Skicon‐200 EX®.MethodsIn vitro calibration was carried out on filter pads using different solvents, measurements over different layers of plastic foils, and evaluation of desorption kinetics. In vivo measurements were carried out on skin sites covering a range of very dry to well‐hydrated skin areas.ResultsConductance measurements are influenced by electrolytes while capacitance measurements are not. Dielectric constant of the solvents influences the values of both instruments (r respectively 0.92 and 0.99). The capacitance method carries information from deeper layers (up to 45 μm) compared with the conductance instrument (up to 15 μm). Desorption experiments show a strong relation between the amount of water and respectively the capacitance and the conductance values. The in vivo experiments revealed a strong relation between the two methods (r = 0.97). Sensitivity of the capacitance method is limited for the highest hydration values.ConclusionsBoth instruments allow a certain calibration and both give good estimates of the SC hydration.
Satisfying Sexual Events as Outcome Measures in Clinical Trial of Female Sexual Dysfunction
Authors: Kingsberg Sheryl A. , Althof Stanley E. 
Published: September 2011

ABSTRACT

Introduction
Assessing the sexual response in women with female sexual dysfunctions (FSDs) in clinical trials remains difficult. Part of the challenge is the development of meaningful and valid end points that capture the complexity of women’s sexual response.

Aim
The purpose of this review is to highlight the shortcomings of daily diaries and the limitations of satisfying sexual events (SSEs) as primary end points in clinical trials of women with hypoactive sexual desire disorder (HSDD) as recommended by the Food and Drug Administration (FDA) in their draft guidance on standards for clinical trials in women with FSD.

Methods
Clinical trials in women with HSDD using SSEs as primary end points were reviewed.

Main Outcome Measures
The agreement between three outcome measures (SSEs, desire, and distress) was assessed to illustrate to what degree improvements in SSEs were in agreement with improvements in sexual desire and/or personal distress.

Results
Nine placebo-controlled randomized trials in women with HSDD were reviewed: seven with transdermal testosterone and two with flibanserin. In four trials, all using transdermal testosterone 300 µg/day had agreement between changes in SSEs, desire, and distress. In five studies (testosterone 300 µg/day, n = 2; testosterone 150 µg/day, n = 1; flibanserin n = 2), changes in SSEs did not correlate with changes in desire and/or distress and vice versa. It should be noted that in the flibanserin trials, SSEs did correlate with desire assessed using the Female Sexual Function Index but not when it was assessed using the eDiary.

Conclusions
Findings in the literature do not uniformly support the recommendations from the FDA draft guidance to use diary measures in clinical trials of HSDD as primary end points. Patient-reported outcomes appear to be better suited to capture the multidimensional and more subjective information collected in trials of FSD.
DNA barcoding meets molecular scatology: short mtDNA sequences for standardized species assignment of carnivore noninvasive samples
Authors: CHAVES PAULO B. , GRAEFF VANESSA G. , LION MARÍLIA B. , OLIVEIRA LARISSA R. , EIZIRIK EDUARDO 
Published: September 2011

AbstractAlthough species assignment of scats is important to study carnivore biology, there is still no standardized assay for the identification of carnivores worldwide, which would allow large‐scale routine assessments and reliable cross‐comparison of results. Here, we evaluate the potential of two short mtDNA fragments [ATP6 (126 bp) and cytochrome oxidase I gene (COI) (187 bp)] to serve as standard markers for the Carnivora. Samples of 66 species were sequenced for one or both of these segments. Alignments were complemented with archival sequences and analysed with three approaches (tree‐based, distance‐based and character‐based). Intraspecific genetic distances were generally lower than between‐species distances, resulting in diagnosable clusters for 86% (ATP6) and 85% (COI) of the species. Notable exceptions were recently diverged species, most of which could still be identified using diagnostic characters and uniqueness of haplotypes or by reducing the geographic scope of the comparison. In silico analyses were also performed for a 110‐bp cytochrome b (cytb) segment, whose identification success was lower (70%), possibly due to the smaller number of informative sites and/or the influence of misidentified sequences obtained from GenBank. Finally, we performed case studies with faecal samples, which supported the suitability of our two focal markers for poor‐quality DNA and allowed an assessment of prey DNA co‐amplification. No evidence of prey DNA contamination was found for ATP6, while some cases were observed for COI and subsequently eliminated by the design of more specific primers. Overall, our results indicate that these segments hold good potential as standard markers for accurate species‐level identification in the Carnivora.
Involvement of poly(3‐hydroxybutyrate) synthesis in catabolite repression of tetralin biodegradation genes in Sphingomonas macrogolitabida strain TFA
Authors: Martín‐Cabello Guadalupe , Moreno‐Ruiz Emilia , Morales Valle , Floriano Belén , Santero Eduardo 
Published: August 2011

SummaryThe tetralin biodegradation genes of Sphingomonas macrogolitabida strain TFA are repressed by catabolite. Insertion mutants in which thn genes are transcribed in the presence of a preferential carbon source and tetralin, bear the insertion in phaC, encoding a poly(3‐hydroxybutyrate) (PHB) synthase, a key enzyme in PHB synthesis. Mutant complementation with phaC genes from either Ralstonia euthropha or TFA restored PHB accumulation and the wild‐type regulatory pattern of thn genes, thus indicating that this accumulation is a signal for carbon sufficient conditions that prevents expression of thn catabolic genes in this α‐proteobacteria.
Characterization of hepatocellular adenoma based on the phenotypic classification: The Kanazawa experience
Authors: Sasaki Motoko , Yoneda Norihide , Kitamura Seiko , Sato Yasunori , Nakanuma Yasuni 
Published: September 2011

Aim:  Hepatocellular adenoma (HCA) represents a heterogeneous entity, and recently four major subgroups were identified based on genotype and phenotype classification from Europe. HCA is rare in Asian countries including Japan and there has been no study regarding the subgroups of HCA in Japan.Methods:  We took advantage of the reported genotype/phenotype classification to analyze 14 HCA (seven women) in Japan.Results:  We identified one hepatocyte nuclear factor (HNF)1α‐inactivated HCA (one woman), two β‐catenin‐activated HCA (one woman), seven inflammatory HCA (IHCA, two women); four additional cases (three women) had no known phenotypic marker (unclassified HCA). The use of oral contraceptives was found only in two unclassified HCA (29%) cases. Fatty change of the background liver was seen in one β‐catenin‐activated HCA cases, four IHCA (57%) and two unclassified HCA (50%). Hepatic fibrosis was seen in five IHCA (71%) and two unclassified HCA (50%) cases. Four IHCA patients (one woman) were alcohol drinkers and one had alcoholic steatofibrosis and three had alcoholic cirrhosis. Eight HCA (57%) were multiple; one HNF1α‐inactivated HCA (100%), four IHCA (57%) and three unclassified HCA (75%). The tumor was significantly larger in β‐catenin‐activated HCA than in other subgroups. The association of hepatocellular carcinoma was seen only in one case of unclassified HCA.Conclusion:  This study suggests that IHCA arising in men with alcoholic liver disease may be a major subtype of HCA in Japan.
IQ as a predictor of clinician‐rated mental health problems in children and adolescents
Authors: Mathiassen Børge , Brøndbo Per Håkan , Waterloo Knut , Martinussen Monica , Eriksen Mads , Hanssen‐Bauer Ketil , Kvernmo Siv 
Published: September 2011

Objective. Previous studies indicate that low IQ is a substantial risk factor for developing mental health problems. Based on these results, we hypothesized that IQ may predict some of the variance in clinician‐rated severity of children's mental health problems measured with the Children's Global Assessment Scale (CGAS) and Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA). The other aims of this study were to examine if there was any difference in the predictive ability of the different IQ scores of the Wechsler Intelligence Scale for Children, Third edition (WISC‐III) and to examine if parent‐rated measure of child mental health problems could predict the scores on CGAS and HoNOSCA after controlling for IQ, age, and gender.Methods. In this study, 132 patients at three outpatient clinics in North Norway were assessed with the parent version of the Strength and Difficulties Questionnaire (SDQ), HoNOSCA, CGAS, and with the WISC‐III.Results. Hierarchical regression analyses were conducted with HoNOSCA and CGAS as dependent variables. Demographics, WISC‐III IQ scores, and SDQ were entered as independent variables. The model with HoNOSCA as the dependent variable predicted 25% of the total variance. The WISC‐III full‐scale IQ predicted an additional 6% of the variance. The analyses with CGAS as the dependent variable gave no significant results.Conclusion. When a patient has a high HoNOSCA score, an intelligence test in addition to an evaluation of symptoms on mental health should be considered. Future research ought to examine whether HoNOSCA's ability to detect change might be affected by patients IQ.
Stabilité de l’holonomie sur les variétés quasi-projectives
Authors: Caro Daniel 
Published: August 2011

AbstractLet 𝒱 be a mixed characteristic complete discrete valuation ring with perfect residue field k. We solve Berthelot’s conjectures on the stability of the holonomicity over smooth projective formal 𝒱-schemes. Then we build a category of F-complexes of arithmetic 𝒟-modules over quasi-projective k-varieties with bounded and holonomic cohomology. We obtain its stability under Grothendieck’s six operations.
Compensatory Mutations Restore the Replication Defects Caused by Cytotoxic T Lymphocyte Escape Mutations in Hepatitis C Virus Polymerase
Authors: Oniangue-Ndza Cesar , Kuntzen Thomas , Kemper Michael , Berical Andrew , Wang Yaoyu E. , Neumann-Haefelin Christoph , Foote Peter Kristian , Hills-Evans Kelsey , Reyor Laura L. , Kane Katherine , Gladden Adrianne D. , Bloom Allyson K. , Power Karen A. , Thimme Robert , Lauer Georg M. , Henn Matthew R. , Kim Arthur Y. , Allen Todd M. 
Published: September 2011

ABSTRACT

While human leukocyte antigen B57 (HLA-B57) is associated with the spontaneous clearance of hepatitis C virus (HCV), the mechanisms behind this control remain unclear. Immunodominant CD8
+
T cell responses against the B57-restricted epitopes comprised of residues 2629 to 2637 of nonstructural protein 5B (NS5B
2629–2637
) (KSKKTPMGF) and E2
541–549
(NTRPPLGNW) were recently shown to be crucial in the control of HCV infection. Here, we investigated whether the selection of deleterious cytotoxic T lymphocyte (CTL) escape mutations in the NS5B KSKKTPMGF epitope might impair viral replication and contribute to the B57-mediated control of HCV. Common CTL escape mutations in this epitope were identified from a cohort of 374 HCV genotype 1a-infected subjects, and their impact on HCV replication assessed using a transient HCV replicon system. We demonstrate that while escape mutations at residue 2633 (position 5) of the epitope had little or no impact on HCV replication
in vitro
, mutations at residue 2629 (position 1) substantially impaired replication. Notably, the deleterious mutations at position 2629 were tightly linked
in vivo
to upstream mutations at residue 2626, which functioned to restore the replicative defects imparted by the deleterious escape mutations. These data suggest that the selection of costly escape mutations within the immunodominant NS5B KSKKTPMGF epitope may contribute in part to the control of HCV replication in B57-positive individuals and that persistence of HCV in B57-positive individuals may involve the development of specific secondary compensatory mutations. These findings are reminiscent of the selection of deleterious CTL escape and compensatory mutations by HLA-B57 in HIV-1 infection and, thus, may suggest a common mechanism by which alleles like HLA-B57 mediate protection against these highly variable pathogens.
Direct Sequencing and Characterization of a Clinical Isolate of Epstein-Barr Virus from Nasopharyngeal Carcinoma Tissue by Using Next-Generation Sequencing Technology
Authors: Liu Pan , Fang Xiaodong , Feng Zizhen , Guo Yun-Miao , Peng Rou-Jun , Liu Tengfei , Huang Zhiyong , Feng Yue , Sun Xiaoqing , Xiong Zhiqiang , Guo Xiaosen , Pang Sha-Sha , Wang Bo , Lv Xiaojuan , Feng Fu-Tuo , Li Da-Jiang , Chen Li-Zhen , Feng Qi-Sheng , Huang Wen-Lin , Zeng Mu-Sheng , Bei Jin-Xin , Zhang Yong , Zeng Yi-Xin 
Published: September 2011

ABSTRACT

Epstein-Barr virus (EBV)-encoded molecules have been detected in the tumor tissues of several cancers, including nasopharyngeal carcinoma (NPC), suggesting that EBV plays an important role in tumorigenesis. However, the nature of EBV with respect to genome width
in vivo
and whether EBV undergoes clonal expansion in the tumor tissues are still poorly understood. In this study, next-generation sequencing (NGS) was used to sequence DNA extracted directly from the tumor tissue of a patient with NPC. Apart from the human sequences, a clinically isolated EBV genome 164.7 kb in size was successfully assembled and named GD2 (GenBank accession number
HQ020558
). Sequence and phylogenetic analyses showed that GD2 was closely related to GD1, a previously assembled variant derived from a patient with NPC. GD2 contains the most prevalent EBV variants reported in Cantonese patients with NPC, suggesting that it might be the prevalent strain in this population. Furthermore, GD2 could be grouped into a single subtype according to common classification criteria and contains only 6 heterozygous point mutations, suggesting the monoclonal expansion of GD2 in NPC. This study represents the first genome-wide analysis of a clinical isolate of EBV directly extracted from NPC tissue. Our study reveals that NGS allows the characterization of genome-wide variations of EBV in clinical tumors and provides evidence of monoclonal expansion of EBV
in vivo
. The pipeline could also be applied to the study of other pathogen-related malignancies. With additional NGS studies of NPC, it might be possible to uncover the potential causative EBV variant involved in NPC.
Annual Vaccination against Influenza Virus Hampers Development of Virus-Specific CD8+T Cell Immunity in Children
Authors: Bodewes Rogier , Fraaij Pieter L. A. , Geelhoed-Mieras Martina M. , van Baalen Carel A. , Tiddens Harm A. W. M. , van Rossum Annemarie M. C. , van der Klis Fiona R. , Fouchier Ron A. M. , Osterhaus Albert D. M. E. , Rimmelzwaan Guus F. 
Published: September 2011

ABSTRACTInfection with seasonal influenza A viruses induces immunity to potentially pandemic influenza A viruses of other subtypes (heterosubtypic immunity). We recently demonstrated that vaccination against seasonal influenza prevented the induction of heterosubtypic immunity against influenza A/H5N1 virus induced by infection with seasonal influenza in animal models, which correlated with the absence of virus-specific CD8+T cell responses. Annual vaccination of all healthy children against influenza has been recommended, but the impact of vaccination on the development of the virus-specific CD8+T cell immunity in children is currently unknown. Here we compared the virus-specific CD8+T cell immunity in children vaccinated annually with that in unvaccinated children. In the present study, we compared influenza A virus-specific cellular and humoral responses of unvaccinated healthy control children with those of children with cystic fibrosis (CF) who were vaccinated annually. Similar virus-specific CD4+T cell and antibody responses were observed, while an age-dependent increase of the virus-specific CD8+T cell response that was absent in vaccinated CF children was observed in unvaccinated healthy control children. Our results indicate that annual influenza vaccination is effective against seasonal influenza but hampers the development of virus-specific CD8+T cell responses. The consequences of these findings are discussed in the light of the development of protective immunity to seasonal and future pandemic influenza viruses.
A Fusion-Loop Antibody Enhances the Infectious Properties of Immature Flavivirus Particles
Authors: Rodenhuis-Zybert Izabela A. , Moesker Bastiaan , da Silva Voorham Júlia M. , van der Ende-Metselaar Heidi , Diamond Michael S. , Wilschut Jan , Smit Jolanda M. 
Published: September 2011

ABSTRACT
Flavivirus-infected cells secrete a mixture of mature, partially immature, and fully immature particles into the extracellular space. Although mature virions are highly infectious, prM-containing fully immature virions are noninfectious largely because the prM protein inhibits the cell attachment and fusogenic properties of the virus. If, however, cell attachment and entry are facilitated by anti-prM antibodies, immature flavivirus becomes infectious after efficient processing of the prM protein by the endosomal protease furin. A recent study demonstrated that E53, a cross-reactive monoclonal antibody (MAb) that engages the highly conserved fusion-loop peptide within the flavivirus envelope glycoprotein, preferentially binds to immature flavivirus particles. We investigated here the infectious potential of fully immature West Nile virus (WNV) and dengue virus (DENV) particles opsonized with E53 MAb and observed that, like anti-prM antibodies, this anti-E antibody also has the capacity to render fully immature flaviviruses infectious. E53-mediated enhancement of both immature WNV and DENV depended on efficient cell entry and the enzymatic activity of the endosomal furin. Furthermore, we also observed that E53-opsonized immature DENV particles but not WNV particles required a more acidic pH for efficient cleavage of prM by furin, adding greater complexity to the dynamics of antibody-mediated infection of immature flavivirus virions.
Potential adverse effects of oseltamivir in rats: males are more vulnerable than females
Authors: El-Sayed Wael M. , Al-Kahtani Mohamed Ali 
Published: August 2011

Oseltamivir is the most widely used antiviral drug for the treatment and prophylaxis of influenza. However, not much is known about its adverse effects. The potential side effects were investigated in male and female rats (140–170 g). Oseltamivir was administered at 2.2 mg·kg–1·day–1for 5 days. For both genders, treatment with oseltamivir resulted in significant reductions in the hepatic activities of glutathione reductase, glutathione peroxidase, and glutathione S-transferase. Also for both genders, oseltamivir produced modest reductions in the hepatic activities of UDP-glucuronosyltransferase, quinone oxidoreductase, thioredoxin reductase, CYP1A1/2, and CYP3A, as well as hepatic glutathione content. For both genders, neither the kidney functions nor protein profile was affected by oseltamivir. Oseltamivir also caused significant elevation in serum levels of both triacylglycerols and LDL-cholesterol and in the activity of γ-glutamyl transpeptidase, in both genders. For male animals only, oseltamivir treatment elevated the serum level of total cholesterol as well as the activity of serum alanine aminotransferase, and reduced the hepatic activities of superoxide dismutase and catalase. Oseltamivir caused oxidative stress and acute toxicity in the liver, and disrupted the cholesterol and lipid metabolism but was less likely to cause serious drug interactions. There was a sexual differentiation in these adverse effects, with adverse effects being more evident in male rats.