bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does the ‘2012 IUSTI ECCG report on the diagnosis and management of Neisseria gonorrhoeae infections in Europe’ depict the situation in Europe?
Authors: Unemo M , Brooks B , Cole M , Ross J D C , White J A , Patel R 
Published: July 2013

Summary Gonorrhoea is a major public health concern globally. Of particular grave concern is that resistance to the third generation cephalosporins has been identified during recent years. This paper summarises and discusses the results of the ‘2012 IUSTI European Collaborative Clinical Group (ECCG) report on the diagnosis and management of Neisseria gonorrhoeae infections in Europe’. Although high quality care was reported in many settings, in several other countries the testing, diagnostics, antimicrobial treatment and follow-up of gonorrhoea patients need to be optimized. This, together with increased access to and use of antimicrobial susceptibility testing, is crucial in controlling the emergent spread of cephalosporin-resistant and multidrug-resistant gonorrhoea.
Interferon beta-1b reduces black holes in a randomised trial of clinically isolated syndrome
Authors: Nagtegaal Gijsbert JA , Pohl Christoph , Wattjes Mike P , Hulst Hanneke E , Freedman Mark S , Hartung Hans-Peter , Miller David , Montalban Xavier , Kappos Ludwig , Edan Gilles , Pleimes Dirk , Beckman Karola , Stemper Brigitte , Polman Christoph H , Sandbrink Rupert , Barkhof Frederik 
Published: July 2013

Background: Multiple sclerosis (MS) is characterised by inflammatory lesions of the central nervous system. Interferon beta-1b (IFNB-1b) has been shown to improve clinical and magnetic resonance imaging (MRI) measures for patients with MS. Objective: To evaluate whether IFNB-1b in patients presenting with clinically isolated syndromes (CIS) prevented persisting T1 hypointensities on MRI (persistent black holes (PBHs)). Methods: In the placebo-controlled phase, patients ( n = 468) were initially randomised to IFNB-1b ( n = 292) or placebo ( n = 176) for two years or clinically definite MS (CDMS). In the open-label phase ( n = 418), both groups were offered IFNB-1b for up to five years. Lesions were classified as PBHs if T1 hypointensity persisted throughout the last available scan (minimum time one year). Results: A total of 435 patients were evaluable for analysis. The number of PBHs/patient was lower in the early rather than the delayed treatment arm during both phases (.42 vs .71, p = .0102 and .70 vs 1.17, p = .0121). Exploratory analyses identified baseline characteristics that affected rate of conversion. Conclusions: Although the rate of lesions that converted to PBH showed no significant differences between groups, the numbers of PBHs per patient out of new lesions was significantly lower in IFNB-1b patients compared to patients on placebo. Trial registration number: NCT00544037.
Maternal consumption: A view from the past
Authors: Rose Clare 
Published: July 2013

Children’s clothes are an appropriate topic for examining maternal consumption, as they are among the first items provided for infants and must be frequently replaced to accommodate growth, requiring repeated consumption decisions. For contemporary mothers, decisions about clothing may act as a way of defining their parenting practice both to their children and to adult peers, and anxieties about this role may be heightened by the characterization of commercial interests as corrupters of childhood innocence. As Dan Cook has noted, the disjuncture between theories of consumption and the historiography of childhood is a major problem, with the origins of contemporary practices largely unexamined. Thus there is scope for examining maternal consumption in the past in order to illuminate parallels and disjunctures with contemporary practices and issues around maternal consumption. This article examines the role of mothers in providing children’s clothing in Britain from 1890–1914, in a society that was both fixated on consumption as a sign of social status and increasingly concerned about correct methods of mothering. It is framed by a review of some of the main themes and anxieties raised by contemporary studies of maternal consumption. It then examines 19th-century texts addressed to mothers to establish how maternal provision of clothing was conceptualized. These reveal a divergence between the promotion of the pleasures of consumption in dressmaking magazines such as Letts’s Illustrated Household Magazine, Madame Schild’s Shilling Dress Patterns and Myra’s Mid-Monthly Journal and Children’s Fashions and the counsels of restraint in childrearing manuals and wardrobe management guides. Texts addressing the needs of working-class families, such as school textbooks, linked clothing consumption with improving child health and rationalizing scarce resources of time and money. The extent to which consumption practices reflected these competing sources of advice is evaluated through an analysis of school group photographs. A case study of the pinafores commonly worn by young schoolgirls draws out the ways in which this garment embodied social meanings. This leads to reflections on the relevance of these findings for contemporary investigations of maternal consumption.
Showtime’s ‘female problem’: Cancer, quality and motherhood
Authors: Bradshaw Lara 
Published: July 2013

Since the debut of the TV series Weeds in 2005, the cable network Showtime has developed a reputation for programming content based on the anti-heroine mother protagonist. This programming trend – which also includes The United States of Tara, Nurse Jackie and, most recently, The Big C – demonstrates the network’s success. In this way, Showtime pushes against the dominant trends of ‘quality television’s’ preference for male-centered programs ( The Sopranos, The Wire, etc.) with narratives featuring middle-aged females and the contemporary issues that they face as women and mothers. I use theorist Diane Negra’s notion of ‘time-anxiety’ trope in postfeminist representations of women, motherhood, consumerism and time. For Negra, the ‘time-anxiety’ trope is a marketing tool based on the biological categorization of essential female experiences, which include themes of motherhood, marriage and anti-aging. Turing to trade and magazine publications, I use the term ‘female problem’ to investigate Showtime’s programming and marketing based on female mental and physical illness and its relevance to a broader, postmodern female experience. Using The Big C as a case study, I am interested in the show’s depiction of cancer as a larger cultural metaphor for the failures of motherhood and anxieties around consumerism. At the same time, the show’s investment in female experience fails to account for female bodies that differ from the white, middle-class and youthful protagonist.
Maternofetal transplacental transport of recombinant IgG antibodies lacking effector functions
Authors: Mathiesen Line , Nielsen Leif K. , Andersen Jan Terje , Grevys Algirdas , Sandlie Inger , Michaelsen Terje E. , Hedegaard Morten , Knudsen Lisbeth E. , Dziegiel Morten Hanefeld 
Published: July 2013

Key PointsRetained FcRn binding of an IgG3 antibody devoid of FcgR and C1q binding, cellular cytotoxicity and complement activation. Inhibition of pathogenic polyclonal anti-D in antibody-dependent cellular toxicity by a hinge region deleted anti-D IgG3 antibody with efficient transplacental transport capacity.
Plaque vulnerability of coronary artery lesions is related to left ventricular dilatation as determined by optical coherence tomography and cardiac magnetic resonance imaging in patients with type 2 diabetes
Authors: Burgmaier Mathias , Frick Michael , Liberman Ana , Battermann Simone , Hellmich Martin , Lehmacher Walter , Jaskolka Agnes , Marx Nikolaus , Reith Sebastian 
Published: July 2013

Abstract

Background
Patients with type 2 diabetes are at increased risk for both, left ventricular (LV)-dilatation and myocardial infarction (MI) following the rupture of a vulnerable plaque. This study investigated the to date incompletely understood relationship between plaque vulnerability and LV-dilatation using optical coherence tomography (OCT) and cardiac magnetic resonance imaging (CMR) in patients with type 2 diabetes and stable coronary artery disease.

Methods
CMR was performed in 58 patients with type 2 diabetes, in which 81 coronary lesions were investigated using OCT.

Results
A decreased minimal fibrous cap thickness (FCT) of coronary lesions was associated with an increase of several CMR-derived parameters including LV-end diastolic volume (LVEDV, r = 0.521, p < 0.001), LV-end diastolic diameter (r = 0.502, p < 0.001) and LV-end systolic volume (r = 0.467, p = 0.001). Similar results were obtained for mean FCT.
Furthermore, patients with dilated versus non-dilated LV differed significantly in several cardiovascular risk factors including previous MI (47.1% vs. 14.6%, p = 0.009), HDL-cholesterol (40.35 ± 5.57 mg/dl vs. 45.20 ± 10.79 mg/dl, p = 0.029) and smoking (82.4% vs. 51.2%, p = 0.027). However, minimal FCT is associated to LV-dilatation independent of previous MIs (odds ratio 0.679, p = 0.022).
Receiver-operating curve analysis demonstrated that CMR-derived LVEDV predicts plaque vulnerability with low-moderate diagnostic efficiency (area under the curve 0.699) and considerate specificity (83.3%) at the optimal cut-off value (159.0 ml).

Conclusion
These data suggest that vulnerability of coronary lesions is associated with LV-dilatation in high risk patients with type 2 diabetes. CMR may be a useful adjunct to the risk-stratification in this population. Future studies are warranted to investigate potential mechanisms linking plaque vulnerability and LV-dilatation.
Distinct single cell signal transduction signatures in leukocyte subsets stimulated with khat extract, amphetamine-like cathinone, cathine or norephedrine
Authors: Bredholt Therese , Ersvær Elisabeth , Erikstein Bjarte Skoe , Sulen André , Reikvam Håkon , Aarstad Hans Jørgen , Johannessen Anne Christine , Vintermyr Olav Karsten , Bruserud Øystein , Gjertsen Bjørn Tore 
Published: July 2013

Abstract

Background
Amphetamine and amphetamine derivatives are suggested to induce an immunosuppressive effect. However, knowledge of how amphetamines modulate intracellular signaling pathways in cells of the immune system is limited. We have studied phosphorylation of signal transduction proteins (Akt, CREB, ERK1/2, NF-κB, c-Cbl, STAT1/3/5/6) and stress sensors (p38 MAPK, p53) in human leukocyte subsets following in vitro treatment with the natural amphetamine cathinone, the cathinone derivatives cathine and norephedrine, in comparison with a defined extract of the psychostimulating herb khat (Catha edulis Forsk.). Intracellular protein modifications in single cells were studied using immunostaining and flow cytometry, cell viability was determined by Annexin V-FITC/Propidium Iodide staining, and T-lymphocyte proliferation was measured by 3H-thymidine incorporation.

Results
Cathinone, cathine and norephedrine generally reduced post-translational modifications of intracellular signal transducers in T-lymphocytes, B-lymphocytes, natural killer cells and monocytes, most prominently affecting c-Cbl (pTyr700), ERK1/2 (p-Thr202/p-Tyr204), p38 MAPK (p-Thr180/p-Tyr182) and p53 (both total p53 protein and p-Ser15). In contrast, the botanical khat-extract induced protein phosphorylation of STAT1 (p-Tyr701), STAT6 (p-Tyr641), c-Cbl (pTyr700), ERK1/2 (p-Thr202/p-Tyr204), NF-κB (p-Ser529), Akt (p-Ser473), p38 MAPK (p-Thr180/p-Tyr182), p53 (Ser15) as well as total p53 protein. Cathinone, cathine and norephedrine resulted in unique signaling profiles, with B-lymphocytes and natural killer cells more responsive compared to T-lymphocytes and monocytes. Treatment with norephedrine resulted in significantly increased T-lymphocyte proliferation, whereas khat-extract reduced proliferation and induced cell death.

Conclusions
Single-cell signal transduction analyses of leukocytes distinctively discriminated between stimulation with cathinone and the structurally similar derivatives cathine and norephedrine. Cathinone, cathine and norephedrine reduced phosphorylation of c-Cbl, ERK1/2, p38 MAPK and p53(Ser15), and norephedrine induced T-lymphocyte proliferation. Khat-extract induced protein phosphorylation of signal transducers, p38 MAPK and p53, followed by reduced cell proliferation and cell death. This study suggests that protein modification-specific single-cell analysis of immune cells could unravel pharmacologic effects of amphetamines and amphetamine-like agents, and further could represent a valuable tool in elucidation of mechanism(s) of action of complex botanical extracts.
Identification of a neuronal transcription factor network involved in
medulloblastoma development
Authors: Łastowska Maria , Al-Afghani Hani , Al-Balool Haya H , Sheth Harsh , Mercer Emma , Coxhead Jonathan M , Redfern Chris PF , Peters Heiko , Burt Alastair D , Santibanez-Koref Mauro , Bacon Chris M , Chesler Louis , Rust Alistair G , Adams David J , Williamson Daniel , Clifford Steven C , Jackson Michael S 
Published: July 2013

Abstract

Background
Medulloblastomas, the most frequent malignant brain tumours affecting
children, comprise at least 4 distinct clinicogenetic subgroups. Aberrant
sonic hedgehog (SHH) signalling is observed in approximately 25% of tumours
and defines one subgroup. Although alterations in SHH pathway genes (e.g.
PTCH1, SUFU) are observed in many of these tumours,
high throughput genomic analyses have identified few other recurring
mutations. Here, we have mutagenised the Ptch
+/- murine tumour model using the Sleeping Beauty transposon
system to identify additional genes and pathways involved in SHH subgroup
medulloblastoma development.

Results
Mutagenesis significantly increased medulloblastoma frequency and identified
17 candidate cancer genes, including orthologs of genes somatically mutated
(PTEN, CREBBP) or associated with poor outcome (PTEN,
MYT1L) in the human disease. Strikingly, these candidate genes were
enriched for transcription factors (p= 2x10-5), the
majority of which (6/7; Crebbp, Myt1L, Nfia, Nfib,
Tead1 and Tgif2) were linked within a single regulatory
network enriched for genes associated with a differentiated neuronal
phenotype. Furthermore, activity of this network varied significantly
between the human subgroups, was associated with metastatic disease, and
predicted poor survival specifically within the SHH subgroup of tumours.
Igf2, previously implicated in medulloblastoma, was the most
differentially expressed gene in murine tumours with network perturbation,
and network activity in both mouse and human tumours was characterised by
enrichment for multiple gene-sets indicating increased cell proliferation,
IGF signalling, MYC target upregulation, and decreased neuronal
differentiation.

Conclusions
Collectively, our data support a model of medulloblastoma development in
SB-mutagenised Ptch
+/- mice which involves disruption of a novel transcription
factor network leading to Igf2 upregulation, proliferation of GNPs,
and tumour formation. Moreover, our results identify rational therapeutic
targets for SHH subgroup tumours, alongside prognostic biomarkers for the
identification of poor-risk SHH patients.
Autocrine IGF-I/insulin receptor axis compensates for inhibition of AKT in ER-positive breast cancer cells with resistance to estrogen deprivation
Authors: Fox Emily M , Kuba María Gabriela , Miller Todd W , Davies Barry R , Arteaga Carlos L 
Published: July 2013

Abstract
Introduction
Estrogen receptor α-positive (ER+) breast cancers adapt to hormone deprivation and acquire resistance to antiestrogen therapies. Upon acquisition of hormone independence, ER+ breast cancer cells increase their dependence on the phosphatidylinositol-3 kinase (PI3K)/AKT pathway. We examined the effects of AKT inhibition and its compensatory upregulation of insulin-like growth factor (IGF)-I/InsR signaling in ER+ breast cancer cells with acquired resistance to estrogen deprivation.

Methods
Inhibition of AKT using the catalytic inhibitor AZD5363 was examined in four ER+ breast cancer cell lines resistant to long-term estrogen deprivation (LTED) by western blotting and proliferation assays. Feedback upregulation and activation of receptor tyrosine kinases (RTKs) was examined by western blotting, real-time qPCR, ELISAs, membrane localization of AKT PH-GFP by immunofluorescence and phospho-RTK arrays. For studies in vivo, athymic mice with MCF-7 xenografts were treated with AZD5363 and fulvestrant with either the ATP-competitive IGF-IR/InsR inhibitor AZD9362 or the fibroblast growth factor receptor (FGFR) inhibitor AZD4547.

Results
Treatment with AZD5363 reduced phosphorylation of the AKT/mTOR substrates PRAS40, GSK3α/β and S6K while inducing hyperphosphorylation of AKT at T308 and S473. Inhibition of AKT with AZD5363 suppressed growth of three of four ER+ LTED lines and prevented emergence of hormone-independent MCF-7, ZR75-1 and MDA-361 cells. AZD5363 suppressed growth of MCF-7 xenografts in ovariectomized mice and a patient-derived luminal B xenograft unresponsive to tamoxifen or fulvestrant. Combined treatment with AZD5363 and fulvestrant suppressed MCF-7 xenograft growth better than either drug alone. Inhibition of AKT with AZD5363 resulted in upregulation and activation of RTKs, including IGF-IR and InsR, upregulation of FoxO3a and ERα mRNAs as well as FoxO- and ER-dependent transcription of IGF-I and IGF-II ligands. Inhibition of IGF-IR/InsR or PI3K abrogated AKT PH-GFP membrane localization and T308 P-AKT following treatment with AZD5363. Treatment with IGFBP-3 blocked AZD5363-induced P-IGF-IR/InsR and T308 P-AKT, suggesting that receptor phosphorylation was dependent on increased autocrine ligands. Finally, treatment with the dual IGF-IR/InsR inhibitor AZD9362 enhanced the anti-tumor effect of AZD5363 in MCF-7/LTED cells and MCF-7 xenografts in ovariectomized mice devoid of estrogen supplementation.

Conclusions
These data suggest combinations of AKT and IGF-IR/InsR inhibitors would be an effective treatment strategy against hormone-independent ER+ breast cancer.
jMOSAiCS: joint analysis of multiple ChIP-seq datasets
Authors: Zeng Xin , Sanalkumar Rajendran , Bresnick Emery H , Li Hongda , Chang Qiang , Keleş Sündüz 
Published: July 2013

AbstractThe ChIP-seq technique enables genome-wide mapping of in vivo protein-DNA interactions and chromatin states. Current analytical approaches for ChIP-seq analysis are largely geared towards single-sample investigations, and have limited applicability in comparative settings that aim to identify combinatorial patterns of enrichment across multiple datasets. We describe a novel probabilistic method, jMOSAiCS, for jointly analyzing multiple ChIP-seq datasets. We demonstrate its usefulness with a wide range of data-driven computational experiments and with a case study of histone modifications on GATA1-occupied segments during erythroid differentiation. jMOSAiCS is open source software and can be downloaded from Bioconductor [1].
Isolation method and xeno-free culture conditions influence multipotent differentiation capacity of human Wharton’s jelly-derived mesenchymal stem cells
Authors: Corotchi Maria Cristina , Popa Mirel Adrian , Remes Anca , Sima Livia Elena , Gussi Ilinca , Lupu Plesu Marilena 
Published: July 2013

Abstract
Introduction
Human Wharton’s jelly (WJ) has become a preferred source of mesenchymal stem cells (MSCs) whose clinical applications are limited by the use of adequate xeno-free (XF), in vitro manipulation conditions. Therefore, the objective of our study was to characterize WJ-derived MSCs (WJ-MSCs), isolated by different methods and cultured in a commercially available, MSC XF medium, not least of all by investigating their endothelial differentiation capacity.

Methods
WJ explants and enzymatically dissociated WJ cells were cultured in a defined, XF medium for MSCs. Adherent cells at passages 2 and 5 were characterized as MSCs by flow cytometry, MTT, real-time quantitative reverse transcription PCR, and functional multipotent differentiation assays. The endothelial differentiation capacity of MSCs isolated and expanded until passage 2 in the MSC XF medium, and then subcultured for five passages in a commercially available endothelial growth medium (group A), was assessed over serial passages, as compared to adherent WJ-derived cells isolated and expanded for five consecutive passages in the endothelial medium (group B).

Results
The MSC phenotype of WJ explant- and pellet-derived cells, isolated and expanded in the MSC XF medium, was proven based on the expression of CD44/CD73/CD90/CD105 surface markers and osteo-/adipo-/chondrogenic multipotent differentiation potential, which differed according to the isolation method and/or passage number. Upon exposure to endothelial differentiation cues, cells belonging to group A did not exhibit endothelial cell characteristics over serial passages; by contrast, WJ pellet-derived cells belonging to group B expressed endothelial characteristics at gene, protein and functional levels, potentially due to culture conditions favoring the isolation of other stem/progenitor cell types than MSCs, able to give rise to an endothelial progeny.

Conclusions
The use of defined, MSC XF media for isolation and expansion of human WJ-MSCs is a prerequisite for the establishment of their real endothelial differentiation capacity, as candidates for clinical therapy applications. Thus, the standardization of WJ-MSCs isolation and culture expansion techniques in defined, MSC XF media, for their accurate characterization, would be a priority in the stem cell research field.
Soluble Urokinase Plasminogen Activator Receptor for Risk Prediction in Patients Admitted with Acute Chest Pain
Authors: Lyngbæk Stig , Andersson Charlotte , Marott Jacob L , Møller Daniél V , Christiansen Michael , Iversen Kasper K , Clemmensen Peter , Eugen-Olsen Jesper , Hansen Peter R , Jeppesen Jørgen L 
Published: July 2013

BACKGROUNDPlasma concentrations of soluble urokinase plasminogen activator receptor (suPAR) predict mortality in several clinical settings, but the long-term prognostic importance of suPAR in chest pain patients admitted on suspicion of non–ST-segment elevation acute coronary syndrome (NSTEACS) is uncertain.METHODSsuPAR concentrations were measured on admission in 449 consecutive chest pain patients in a single center between January 3, 2005, and February 14, 2006. Patients were followed for all-cause mortality from discharge until July 28, 2011.RESULTSThe diagnoses at discharge comprised high-risk NSTEACS [non–ST elevation myocardial infarction or unstable angina with electrocardiogram (ECG) abnormalities] in 77 patients (17.2%) and low-risk NSTEACS without evidence of myocardial ischemia in 257 (57.2%) of patients. Another 115 (25.6%) of patients received other diagnoses. During a median follow-up of 5.7 years (range, 0.01–6.6 years) there were 162 (36.1%) deaths. suPAR was predictive of mortality independent of age, sex, smoking, final diagnosis for the hospitalization, comorbidities (diabetes, hypertension, previous myocardial infarction, and heart failure), and variables measured on the day of admission (renal function, inflammatory markers, and markers of myocardial ischemia) with a hazard ratio (95% CI) of 1.93 (1.48–2.51) per SD increase in log-transformed suPAR, P &lt; 0.0001. The use of suPAR improved the predictive accuracy of abnormal ECG findings and increased troponin concentrations regarding all-cause mortality (c statistics, 0.751–0.805; P &lt; 0.0001).CONCLUSIONSsuPAR is a strong predictor of adverse long-term outcomes and improves risk stratification beyond traditional risk variables in chest pain patients admitted with suspected NSTEACS.