bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors and protective factors for adolescent Internet victimization: results from a 2008 nationwide Danish youth survey
Authors: Helweg‐Larsen Karin , Schütt Nina , Larsen Helmer B 
Published: December 2011

AbstractAim:  To examine the rate of Internet victimization in a nationally representative sample of adolescents aged 14–17 and to analyze predictors and protective factors for victimization.Methods:  Data were collected for 3707 pupils in Danish schools in 2008, using a multimedia computer‐based self‐interviewing programme. Family characteristics, alcohol and drug abuse, exposure to physical/sexual abuse, emotional problems, social conduct and own risky Internet behaviour were included in the analyses.Results: Any online victimization was reported by 27% of the adolescents, most frequently a rumour spread online (9% of boys and 15% of girls) and sexual solicitation (5% of boys and 16% of girls). Parental surveillance of adolescents’ Internet use significantly reduced their risk of online victimization. Roughly half of the adolescents had met Internet acquaintances face to face, with few instances resulting in forced sex (five boys and nine girls). Female gender, parental physical violence, previous exposure to sexual abuse, alcohol abuse in the family, self‐reported emotional problems and antisocial behaviour and high Internet use were all weakly and risky online behaviour strongly associated with online victimization.Conclusions:  Danish adolescents are generally aware of the principles of ‘safe chatting’; however, online harassment is relatively frequent, but offline victimization based on Internet acquaintances is rare.
Bioenergy? Yes, we can! But at what cost? And what else?  Bioénergies ? Oui, nous avons la capacité! Mais à quel coût ? Et après?  Bioenergie? Na klar! Aber zu welchem Preis? Und was kommt als nächstes?
Authors: Burrell Alison 
Published: December 2011

SummaryBioenergy? Yes, we can! But at what cost? And what else?Global energy demand is increasing, as is the environmental damage due to fossil fuel use. In this context bioenergy looks attractive. Waste biomass and crops with high energy yields that do not compete for prime cropland are more promising bioenergy feedstocks than food crops. Still, constrained land capacity relative to potential demands means that bioenergy can only be part of the solution. A more level playing field is needed for technologies that capture renewable energy more directly, particularly wind and solar voltaic power. Conventional arguments against these options – intermittent supply, high cost – are rapidly being overturned or are based on invalid cost accounting. A broader, more integrated approach is needed to energy policy, embracing all renewable energies that reduce GHG emissions without serious side‐effects and that have potential for longer‐term viability in a non‐distorted energy market, whilst also encouraging energy‐saving on the demand side. Governments should refrain from trying to pick renewable energy winners or creating new vested interests through unbalanced use of subsidies. Instead, they should promote the institutional and market conditions conducive to greener energy use, and should maximise their efforts to reach global consensus on emissions targets and reduction of fossil fuel subsidies.
Mineralogy and Mineral Chemistry of the Cretaceous Duolong Gold‐Rich Porphyry Copper Deposit in the Bangongco Arc, Northern Tibet
Authors: LI Jinxiang , LI Guangming , QIN Kezhang , XIAO Bo , CHEN Lei , ZHAO Junxing 
Published: December 2011

AbstractThe Early Cretaceous Duolong gold‐rich porphyry copper deposit is a newly discovered deposit with proven 5.38 Mt Cu resources of 0.72% Cu and 41 t gold of 0.23 g t−1 in northern Tibet. Granodiorite porphyry and quartz diorite porphyrite are the main ore‐bearing porphyries. A wide range of hydrothermal alteration associated with these porphyries is divided into potassic, argillic and propylitic zones from the ore‐bearing porphyry center outward and upward. In the hydrothermal alteration zones, secondary albite (91.5–99.7% Ab) occurs along the rim of plagioclase phenocryst and fissures. Secondary K‐feldspar (75.1–96.9% Or) replaces plagioclase phenocryst and matrix or occurs in veinlets. Biotite occurs mainly as matrix and veinlet in addition to phenocryst in the potassic zone. The biotite are Mg‐rich and formed under a highly oxidized condition at temperatures ranging from 400°C to 430°C. All the biotites are absent in F, and have high Cl content (0.19–0.26%), with log (XCl/XOH) values of −2.74 to −2.88 and IV (Cl) values of −3.48 to −3.35, suggesting a significant role of chloride complexes (CuCl2‐ and AuCl2‐) in transporting and precipitating copper and gold. Chlorites are present in all alteration zones and correspond mainly to pycnochlorite. They have similar Fe/(Fe+Mg), Mn/(Mn+Mg) ratios, and a formation temperature range of 280–360°C. However, the formation temperature of chlorite in the quartz‐gypsum‐carbonate‐chlorite vein is between 190°C and 220°C, indicating that it may have resulted from a later stage of hydrothermal activity. Fe3+/Fe2+ ratios of chlorites have negative correlation with AlIV, suggesting oxygen fugacity of fluids increases with decreasing temperature. Apatite mineral inclusions in the biotite phenocrysts show high SO3 content (0.44–0.82%) and high Cl content (1–1.37%), indicating the host magma had a high oxidation state and was enriched in S and Cl. The highest Cl content of apatite in the propylitic zone may have resulted from pressure decrease, and the lowest Cl content of apatite in the argillic zone may have been caused by a low Cl content in the fluids. The low concentration of SO3 content in the hydrothermal apatite compared to the magmatic one may have resulted from the decrease of oxygen fugacity and S content in the hydrothermal fluid, which are caused by the abundant precipitation of magnetite.
Molecular and genetic features of myelodysplastic syndromes
Authors: GREENBERG P. L. 
Published: December 2011

SummaryMultifactorial pathogenetic features underlying myelodysplastic syndromes (MDS) relate to inherent abnormalities within the hematopoietic precursor cell population. The predominant final common pathogenetic pathway causing ineffective hematopoiesis in MDS has been the varying degrees of apoptosis of the hematopoietic precursors and their progeny. A variety of molecular abnormalities have been demonstrated in MDS. These lesions are attributable to nonrandom cytogenetic and oncogenic mutations, indicative of chromosomal and genetic instability, transcriptional RNA splicing abnormalities, and epigenetic changes. Evolutionary cytogenetic changes may occur during the course of the disorder, which are associated with disease progression. These genetic derangements reflect a multistep process believed to underlie the transformation of MDS to acute myeloid leukemia. Recent findings provide molecular insights into specific gene mutations playing major roles for the development and clinical outcome of MDS and their propensity to progress to a more aggressive stage. Use of more comprehensive and sensitive methods for molecular profiling using ‘next‐generation’ sequencing techniques for MDS marrow cells will likely further define critical biologic lesions underlying this spectrum of diseases.
Reshuffling of Aspergillus fumigatus Cell Wall Components Chitin and β-Glucan under the Influence of Caspofungin or Nikkomycin Z Alone or in Combination
Authors: Verwer Patricia E. B. , van Duijn M. L. , Tavakol M. , Bakker-Woudenberg Irma A. J. M. , van de Sande Wendy W. J. 
Published: December 2011

ABSTRACT

Chitin and β-glucan are major cell wall components of
Aspergillus
spp. We investigated the antifungal activity of chitin synthesis inhibitors nikkomycin Z, polyoxin D, flufenoxuron, lufenuron, and teflubenzuron, alone and combined with the β-glucan synthesis inhibitor caspofungin. Only nikkomycin Z and caspofungin were found to act synergistically. The nikkomycin Z-induced chitin decrease corresponded with a β-glucan increase, while with the caspofungin-induced β-glucan decrease, an increase in chitin was found. This could explain the synergistic activity of this combination of drugs.
Antistaphylococcal Activity of TD-1792, a Multivalent Glycopeptide-Cephalosporin Antibiotic
Authors: Blais Johanne , Lewis Stacey R. , Krause Kevin M. , Benton Bret M. 
Published: December 2011

ABSTRACT

TD-1792 is a new multivalent glycopeptide-cephalosporin antibiotic with potent activity against Gram-positive bacteria. The
in vitro
activity of TD-1792 was tested against 527
Staphylococcus aureus
isolates, including multidrug-resistant isolates. TD-1792 was highly active against methicillin-susceptible
S. aureus
(MIC
90
, 0.015 μg/ml), methicillin-resistant
S. aureus
, and heterogeneous vancomycin-intermediate
S. aureus
(MIC
90
, 0.03 μg/ml). Time-kill studies demonstrated the potent bactericidal activity of TD-1792 at concentrations of ≤0.12 μg/ml. A postantibiotic effect of >2 h was observed after exposure to TD-1792.
Characterization of Resistance to the Nonnucleoside NS5B Inhibitor Filibuvir in Hepatitis C Virus-Infected Patients
Authors: Troke Philip J. F. , Lewis Marilyn , Simpson Paul , Gore Katrina , Hammond Jennifer , Craig Charles , Westby Mike 
Published: December 2011

ABSTRACT

Filibuvir (PF-00868554) is an investigational nonnucleoside inhibitor of the hepatitis C virus (HCV) nonstructural 5B (NS5B) RNA-dependent RNA polymerase currently in development for treating chronic HCV infection. The aim of this study was to characterize the selection of filibuvir-resistant variants in HCV-infected individuals receiving filibuvir as short (3- to 10-day) monotherapy. We identified amino acid M423 as the primary site of mutation arising upon filibuvir dosing. Through bulk cloning of clinical NS5B sequences into a transient-replicon system, and supported by site-directed mutagenesis of the Con1 replicon, we confirmed that mutations M423I/T/V mediate phenotypic resistance. Selection in patients of an NS5B mutation at M423 was associated with a reduced replicative capacity
in vitro
relative to the pretherapy sequence; consistent with this, reversion to wild-type M423 was observed in the majority of patients following therapy cessation. Mutations at NS5B residues R422 and M426 were detected in a small number of patients at baseline or the end of therapy and also mediate reductions in filibuvir susceptibility, suggesting these are rare but clinically relevant alternative resistance pathways. Amino acid variants at position M423 in HCV NS5B polymerase are the preferred pathway for selection of viral resistance to filibuvir
in vivo
.
Comparative Effects of Micafungin, Caspofungin, and Anidulafungin against a Difficult-To-Treat Fungal Opportunistic Pathogen, Candida glabrata
Authors: Spreghini Elisabetta , Orlando Fiorenza , Sanguinetti Maurizio , Posteraro Brunella , Giannini Daniele , Manso Esther , Barchiesi Francesco 
Published: December 2011

ABSTRACT

The aim of this study was to compare the
in vitro
and
in vivo
activities of micafungin, caspofungin, and anidulafungin against
Candida glabrata
. The MICs against 28 clinical isolates showed that the overall susceptibilities to caspofungin and to micafungin were not statistically different in the absence of human serum, whereas the isolates were less susceptible to micafungin than to caspofungin in its presence. Minimum fungicidal concentrations, as well as time-kill experiments, showed that caspofungin was more active than anidulafungin, while micafungin was superior to either caspofungin or anidulafungin without serum; its addition rendered caspofungin and micafungin equally effective. A murine model of systemic candidiasis against a
C. glabrata
-susceptible isolate was performed to study the effects of all three echinocandins, and kidney burden counts showed that caspofungin, micafungin, and anidulafungin were active starting from 0.25, 1, and 5 mg/kg of body weight/day, respectively. Two echinocandin-resistant strains of
C. glabrata
were selected:
C. glabrata
30, a laboratory strain harboring the mutation Fks2p-P667T, and
C. glabrata
51, a clinical isolate harboring the mutation Fks2p-D666G. Micafungin activity was shown to be as effective as or more effective than that of caspofungin or anidulafungin in terms of MICs.
In vivo
studies against these resistant strains showed that micafungin was active starting from 1 mg/kg/day, while caspofungin was effective only when administrated at higher doses of 5 or 10 mg/kg/day. Although a trend toward colony reduction was observed with the highest doses of anidulafungin, a significant statistical difference was never reached.
Impact of Mutations at Residue I223 of the Neuraminidase Protein on the Resistance Profile, Replication Level, and Virulence of the 2009 Pandemic Influenza Virus
Authors: Pizzorno Andrés , Abed Yacine , Bouhy Xavier , Beaulieu Édith , Mallett Corey , Russell Rupert , Boivin Guy 
Published: December 2011

ABSTRACTAmino acid substitutions at residue I223 of the neuraminidase (NA) protein have been identified in 2009 pandemic influenza (pH1N1) variants with altered susceptibilities to NA inhibitors (NAIs). We used reverse genetics and site-directed mutagenesis to generate the recombinant A/Québec/144147/09 pH1N1 wild-type virus (WT) and five (I223R, I223V, H275Y, I223V-H275Y, and I223R-H275Y) NA mutants. A fluorimetry-based assay was used to determine 50% inhibitory concentrations (IC50s) of oseltamivir, zanamivir, and peramivir. Replicative capacity was analyzed by viral yield assays in ST6GalI-MDCK cells. Infectivity and transmission of the WT, H275Y, and I223V-H275Y recombinant viruses were evaluated in ferrets. As expected, the H275Y mutation conferred resistance to oseltamivir (982-fold) and peramivir (661-fold) compared to the drug-susceptible recombinant WT. The single I223R mutant was associated with reduced susceptibility to oseltamivir (53-fold), zanamivir (7-fold) and peramivir (10-fold), whereas the I223V virus had reduced susceptibility to oseltamivir (6-fold) only. Interestingly, enhanced levels of resistance to oseltamivir and peramivir and reduced susceptibility to zanamivir (1,647-, 17,347-, and 16-fold increases in IC50s, respectively) were observed for the I223R-H275Y recombinant, while the I223V-H275Y mutant exhibited 1,733-, 2,707-, and 2-fold increases in respective IC50s. The I223R and I223V changes were associated with equivalent or higher viral titersin vitrocompared to the recombinant WT. Infectivity and transmissibility in ferrets were comparable between the recombinant WT and the H275Y or I223V-H275Y recombinants. In conclusion, amino acid changes at residue I223 may alter the NAI susceptibilities of pH1N1 variants without compromising fitness. Consequently, I223R and I223V mutations, alone or with H275Y, need to be thoroughly monitored.
First Report of the Multidrug Resistance Gene
cfr
in Enterococcus faecalis of Animal Origin
Authors: Liu Yang , Wang Yang , Wu Congming , Shen Zhangqi , Schwarz Stefan , Du Xiang-Dang , Dai Lei , Zhang Wanjiang , Zhang Qijing , Shen Jianzhong 
Published: December 2011

ABSTRACT

The multiresistance gene
cfr
was identified for the first time in an
Enterococcus faecalis
isolate of animal origin. The 32,388-bp plasmid pEF-01, which carried the
cfr
gene, was sequenced completely. Three copies of the insertion sequence IS
1216
were identified in pEF-01, and the detection of a
cfr
- and IS
1216
-containing amplicon by inverse PCR suggests that IS
1216
may play a role in the dissemination of
cfr
by a recombination process.
Identification of Human Regulatory T Cells in the Setting of T-Cell Activation and Anti–CTLA-4 Immunotherapy on the Basis of Expression of Latency-Associated Peptide
Authors: Sun Jingjing , Tang Derek Ng , Fu Tihui , Sharma Padmanee 
Published: December 2011

AbstractEffector and regulatory T cells (Treg) share multiple markers that make it difficult to discern differences in these populations in humans. The transcription factor FoxP3 has been shown to identify Tregs. However, the detection of FoxP3 requires cell permeabilization, thereby preventing isolation of viable Tregs. Subsequently, the extracellular marker CD127 was established for the identification of Tregs. However, these studies were not conducted in the setting of immunotherapy. Here, we conducted studies to analyze CD127 and FoxP3 expression on T cells before and after in vitro activation as well as in the setting of patients treated with antibodies directed against cytotoxic T-lymphocyte antigen-4 (CTLA-4). We show that latency-associated peptide (LAP), as opposed to CD127, was capable of identifying Tregs after in vitro activation as well as after treatment with anti–CTLA-4. Therefore, we propose that LAP should be used as a marker of Tregs for immune monitoring studies in patients treated with active immunotherapy such as anti–CTLA-4.Significance: Tregs play an important role in human diseases, including cancer and autoimmunity; however, it has been difficult to study these cells because of a lack of an appropriate marker. Here, we propose LAP as a marker that can be used to identify Tregs in patients treated with immunotherapy, thereby permitting isolation of these cells for functional studies and for ex vivo expansion. Cancer Discovery; 2(2); 122–30. © 2011 AACR.Read the Commentary on this article by Lee and Yee, p. 107.This article is highlighted in the In This Issue feature, p. 95.
Identification of a Monocyte-Predisposed Hierarchy of Hematopoietic Progenitor Cells in the Adventitia of Postnatal Murine Aorta
Authors: Psaltis Peter J. , Harbuzariu Adriana , Delacroix Sinny , Witt Tyra A. , Holroyd Eric W. , Spoon Daniel B. , Hoffman Scott J. , Pan Shuchong , Kleppe Laurel S. , Mueske Cheryl S. , Gulati Rajiv , Sandhu Gurpreet S. , Simari Robert D. 
Published: December 2011

Background—
Hematopoiesis originates from the dorsal aorta during embryogenesis. Although adult blood vessels harbor progenitor populations for endothelial and smooth muscle cells, it is not known if they contain hematopoietic progenitor or stem cells. Here, we hypothesized that the arterial wall is a source of hematopoietic progenitor and stem cells in postnatal life.

Methods and Results—

Single-cell aortic disaggregates were prepared from adult chow-fed C57BL/6 and apolipoprotein E–null
(ApoE
−/−
) mice. In short- and long-term methylcellulose-based culture, aortic cells generated a broad spectrum of multipotent and lineage-specific hematopoietic colony-forming units, with a preponderance of macrophage colony-forming units. This clonogenicity was higher in lesion-free
ApoE
−/−
mice and localized primarily to stem cell antigen-1–positive cells in the adventitia. Expression of stem cell antigen-1 in the aorta colocalized with canonical hematopoietic stem cell markers, as well as CD45 and mature leukocyte antigens. Adoptive transfer of labeled aortic cells from green fluorescent protein transgenic donors to irradiated C57BL/6 recipients confirmed the content of rare hematopoietic stem cells (1 per 4 000 000 cells) capable of self-renewal and durable, low-level reconstitution of leukocytes. Moreover, the predominance of long-term macrophage precursors was evident by late recovery of green fluorescent protein–positive colonies from recipient bone marrow and spleen that were exclusively macrophage colony-forming units. Although trafficking from bone marrow was shown to replenish some of the hematopoietic potential of the aorta after irradiation, the majority of macrophage precursors appeared to arise locally, suggesting long-term residence in the vessel wall.

Conclusions—
The postnatal murine aorta contains rare multipotent hematopoietic progenitor/stem cells and is selectively enriched with stem cell antigen-1–positive monocyte/macrophage precursors. These populations may represent novel, local vascular sources of inflammatory cells.
Targeted 'Next-Generation' sequencing in anophthalmia and microphthalmia patients confirms SOX2, OTX2 and FOXE3 mutations
Authors: Lopez Jimenez Nelson , Flannick Jason , Yahyavi Mani , Li Jiang , Bardakjian Tanya , Tonkin Leath , Schneider Adele , Sherr Elliott H , Slavotinek Anne M 
Published: December 2011

Abstract

Background
Anophthalmia/microphthalmia (A/M) is caused by mutations in several different transcription factors, but mutations in each causative gene are relatively rare, emphasizing the need for a testing approach that screens multiple genes simultaneously. We used next-generation sequencing to screen 15 A/M patients for mutations in 9 pathogenic genes to evaluate this technology for screening in A/M.

Methods
We used a pooled sequencing design, together with custom single nucleotide polymorphism (SNP) calling software. We verified predicted sequence alterations using Sanger sequencing.

Results
We verified three mutations - c.542delC in SOX2, resulting in p.Pro181Argfs*22, p.Glu105X in OTX2 and p.Cys240X in FOXE3. We found several novel sequence alterations and SNPs that were likely to be non-pathogenic - p.Glu42Lys in CRYBA4, p.Val201Met in FOXE3 and p.Asp291Asn in VSX2. Our analysis methodology gave one false positive result comprising a mutation in PAX6 (c.1268A > T, predicting p.X423LeuextX*15) that was not verified by Sanger sequencing. We also failed to detect one 20 base pair (bp) deletion and one 3 bp duplication in SOX2.

Conclusions
Our results demonstrated the power of next-generation sequencing with pooled sample groups for the rapid screening of candidate genes for A/M as we were correctly able to identify disease-causing mutations. However, next-generation sequencing was less useful for small, intragenic deletions and duplications. We did not find mutations in 10/15 patients and conclude that there is a need for further gene discovery in A/M.
Phase II, Open-Label, Randomized, Multicenter Study Comparing the Efficacy and Safety of Olaparib, a Poly (ADP-Ribose) Polymerase Inhibitor, and Pegylated Liposomal Doxorubicin in Patients With BRCA1 or BRCA2 Mutations and Recurrent Ovarian Cancer
Authors: Kaye Stan B. , Lubinski Jan , Matulonis Ursula , Ang Joo Ern , Gourley Charlie , Karlan Beth Y. , Amnon Amit , Bell-McGuinn Katherine M. , Chen Lee-May , Friedlander Michael , Safra Tamar , Vergote Ignace , Wickens Mark , Lowe Elizabeth S. , Carmichael James , Kaufman Bella 
Published: December 2011

Purpose Olaparib (AZD2281), an orally active poly (ADP-ribose) polymerase inhibitor that induces synthetic lethality in BRCA1- or BRCA2-deficient cells, has shown promising clinical efficacy in nonrandomized phase II trials in patients with ovarian cancer with BRCA1 or BRCA2 deficiency. We assessed the comparative efficacy and safety of olaparib and pegylated liposomal doxorubicin (PLD) in this patient population. Patients and Methods In this multicenter, open-label, randomized, phase II study, patients with ovarian cancer that recurred within 12 months of prior platinum therapy and with confirmed germline BRCA1 or BRCA2 mutations were enrolled. Patients were assigned in a 1:1:1 ratio to olaparib 200 mg twice per day or 400 mg twice per day continuously or PLD 50 mg/m2 intravenously every 28 days. The primary efficacy end point was Response Evaluation Criteria in Solid Tumors (RECIST) –assessed progression-free survival (PFS). Secondary end points included objective response rate (ORR) and safety. Results Ninety-seven patients were randomly assigned. Median PFS was 6.5 months (95% CI, 5.5 to 10.1 months), 8.8 months (95% CI, 5.4 to 9.2 months), and 7.1 months (95% CI, 3.7 to 10.7 months) for the olaparib 200 mg, olaparib 400 mg, and PLD groups, respectively. There was no statistically significant difference in PFS (hazard ratio, 0.88; 95% CI, 0.51 to 1.56; P = .66) for combined olaparib doses versus PLD. RECIST-assessed ORRs were 25%, 31%, and 18% for olaparib 200 mg, olaparib 400 mg, and PLD, respectively; differences were not statistically significant. Tolerability of both treatments was as expected based on previous trials. Conclusion The efficacy of olaparib was consistent with previous studies. However, the efficacy of PLD was greater than expected. Olaparib 400 mg twice per day is a suitable dose to explore in further studies in this patient population.