bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple primary syphilis on the lip, nipple–areola and penis: An immunohistochemical examination of Treponema pallidum localization using an anti‐T. pallidum antibody
Authors: Fukuda Hidetsugu , Takahashi Misaki , Kato Keiichi , Oharaseki Toshiaki , Mukai Hideki 
Published: February 2015

AbstractPrimary syphilis caused by Treponema pallidum usually develops after sexual contact as an initial solitary sclerosis or hard chancre in the genital region. We describe a case of primary syphilis at three sites in genital and extragenital regions of a man who had sex with men. A 29‐year‐old man visited our hospital for skin lesions on his lower lip, nipple–areola and penis. A positive syphilis serological test for rapid plasma reagin had a titer of 1:16; the patient also tested positive for specific antibodies against T. pallidum, with a cut‐off index of 39.0. Histopathological examination of a nipple–areola biopsy specimen revealed a thickened epidermis and dense infiltration of inflammatory cells extending from the upper dermal layers to the deep dermis. The inflammatory cells were composed of abundant lymphocytes, plasma cells, histiocytes and neutrophils. Immunohistochemical staining for T. pallidum using an anti‐T. pallidum antibody showed numerous spirochetes in the lower portion of the epidermis, scattered inside inflammatory cell infiltrate and perivascular sites throughout the dermis. Based on these findings, the patient was diagnosed with primary syphilis. Treatment with oral amoxicillin hydrate was started. Five days after starting treatment, a diffuse maculopapular rash (syphilitic roseola) occurred on his trunk and extremities. Perivascular cuffing due to T. pallidum was present throughout the dermis in the biopsy specimen of a localized lesion of primary syphilis. Moreover, syphilitic roseola, which indicates generalized dissemination of T. pallidum, developed during the course of treatment for primary syphilis. Therefore, we considered perivascular cuffing to be indicative of the dissemination phase.
Artemisinin inhibits tumour necrosis factor‐α‐induced vascular smooth muscle cell proliferation in vitro and attenuates balloon injury‐induced neointima formation in rats
Authors: Cao Qian , Jiang Yan , Shi Jin , Liu Xue , Chen Jie , Niu Tiesheng , Li Xiaodong 
Published: February 2015

SummaryThe aim of this study was to evaluate the effect of artemisinin (ART) on rat vascular smooth muscle cell (VSMC) proliferation induced by tumour necrosis factor (TNF)‐α, cell cycle arrest, and apoptosis, and its effect on neointima formation after balloon injury of rat carotid artery. Primary rat VSMC were identified by immunofluorescence assay. The proliferation of VSMC induced by TNF‐α was significantly inhibited by ART treatment in a dose‐dependent manner. Treatment with 100‐μM ART significantly reduced the expression of proliferating cell nuclear antigen. In contrast, the same treatment arrested the cell cycle in G0/G1 phase. Western blot analysis showed that the cell cycle‐related proteins cyclin D1, cyclin E, cyclin‐dependent kinase 2, and cyclin‐dependent kinase 4 were downregulated by ART in TNF‐α‐stimulated VSMC. For apoptosis induced by ART, cleaved caspase‐3/‐9 was detected, and the pro‐apoptotic protein Bcl‐2‐associated X protein was upregulated while the anti‐apoptotic protein Bcl‐2 was downregulated. The results suggest that ART can effectively inhibit the proliferation of VSMC induced by TNF‐α through the apoptotic induction pathway and cell cycle arrest. Also, balloon injury indicated that ART significantly inhibited neointima formation in the rat carotid arteries.
Can experts judge elections? Testing the validity of expert judgments for measuring election integrity
Authors: Martínez i Coma Ferran , van Ham Carolien 
Published: February 2015

AbstractExpert surveys have been used to measure a wide variety of phenomena in political science, ranging from party positions, to corruption, to the quality of democracy and elections. However, expert judgments raise important validity concerns, both about the object being measured as well as the experts. It is argued in this article that the context of evaluation is also important to consider when assessing the validity of expert surveys. This is even more important for expert surveys with a comprehensive, worldwide scope, such as democracy or corruption indices. This article tests the validity of expert judgments about election integrity – a topic of increasing concern to both the international community and academics. Evaluating expert judgments of election integrity provides an important contribution to the literature evaluating the validity of expert surveys as instruments of measurement as: (1) the object under study is particularly complex to define and multifaceted; and (2) election integrity is measured in widely varying institutional contexts, ranging from electoral autocracies to liberal democracies. Three potential sources of bias are analysed (the object, the experts and the context), using a unique new dataset on election integrity entitled the ‘Perceptions of Electoral Integrity’ dataset. The data include over 800 experts in 66 parliamentary and presidential elections worldwide. It is found that validity of expert judgments about election integrity is increased if experts are asked to provide factual information (rather than evaluative judgments), and if they are asked to evaluate election day (rather than pre‐election) integrity. It is also found that ideologically polarised elections and elections of lower integrity increase expert disagreement about election integrity. The article concludes with suggestions for researchers using the expert survey data on election integrity on how to check the validity of their data and adjust their analyses accordingly, and outlines some remaining challenges for future data collection using expert surveys.
Application of AJCC/UICC and WHO‐2010 classifications for GEP‐NEN in Chinese patients
Authors: Ye Bi Xing , Heng Ding , Jiang Liu Qin , Wang Yun , Zhang Hong Jie , Lin Lin 
Published: February 2015

ObjectiveTo assess the prognostic value in Chinese patients of two new systems, the World Health Organization (WHO)‐2010 and the American Joint Committee on Cancer and the Union for International Cancer Control (AJCC/UICC) systems, for the classification of gastroenteropancreatic neuroendocrine neoplasms (GEP‐NEN).MethodsOne hundred and three patients with GEP‐NEN treated at the First Affiliated Hospital of Nanjing Medical University from January 2003 to December 2011 were included in the study. All patients were diagnosed pathologically and had complete follow‐up data. Univariate and multivariate analyses of their clinicopathological characteristics were performed.ResultsThe 5‐year survival rates were 95%, 74%, 24% and 15% based on the AJCC/UICC stages I to IV, and 92%, 62% and 29% according to WHO‐2010 grades 1 to 3, respectively, in patients with GEP‐NEN. A higher mortality was observed in patients with AJCC/UICC stage III and IV tumors compared with those at stage I–II, and patients with stage II compared with those with stage I, whereas there was no difference in survival between stage IV and III patients. Based on the WHO‐2010 grading classification, patients with grade 3 tumors had the lowest survival rate than those with grade 1 and 2 tumors, followed by patients with grade 2 tumors.ConclusionThe WHO‐2010 and AJCC/UICC staging systems can effectively evaluate the prognosis of patients with GEP‐NEN, although the latter might not accurately discriminate the prognosis of patients with local metastasis from those having distant metastasis.
Clinical efficacy of collagenase Clostridium histolyticum in the treatment of Peyronie's disease by subgroup: results from two large, double‐blind, randomized, placebo‐controlled, phase III studies
Authors: Lipshultz Larry I. , Goldstein Irwin , Seftel Allen D. , Kaufman Gregory J. , Smith Ted M. , Tursi James P. , Burnett Arthur L. 
Published: February 2015

ObjectivesTo examine the efficacy of intralesional collagenase Clostridium histolyticum (CCH) in defined subgroups of patients with Peyronie's disease (PD).Patients and MethodsThe efficacy of CCH compared with placebo, assessed from baseline to week 52, was examined in subgroups of participants from the Investigation for Maximal Peyronie's Reduction Efficacy and Safety Studies (IMPRESS) I and II. The subgroups were defined according to: severity of penile curvature deformity at baseline (30–60° [n = 492] and 61–90° [n = 120]); PD duration (1 to ≤2 [n = 201], >2 to ≤4 [n = 212] and >4 years [n = 199]); degree of plaque calcification (no calcification [n = 447], non‐contiguous stippling [n = 103] and contiguous calcification that did not interfere with injection of CCH [n = 62]); and baseline erectile function (International Index of Erectile Function [IIEF] scores 1–5 [n = 22], 6–16 [n = 106] and ≥17 [n = 480]).ResultsReductions in penile curvature deformity and PD symptom bother were observed in all subgroups. Penile curvature deformity reductions were significantly greater with CCH than with placebo for the following subgroups: baseline penile curvature 30–60° and 61–90°; disease duration >2 to ≤4 years and >4 years; no calcification; and IIEF score ≥17 (high IIEF‐erectile function score; P < 0.05 for all). PD symptom bother reductions were significantly greater in the CCH group for: penile curvature 30–60°; disease duration >4 years; no calcification; and IIEF score 1–5 (no sexual activity) and ≥17 (P < 0.05 for all).ConclusionsIn this analysis, clinical efficacy of CCH treatment for reducing penile curvature deformity and PD symptom bother was found across subgroups. In the IMPRESS I and II overall, adverse events (AEs) were typically mild or moderate, although treatment‐related serious AEs, including corporal rupture or penile haematoma, occurred. Future studies could be considered to directly assess the efficacy and safety of CCH treatment in defined subgroups of PD patients, with the goal of identifying predictors of optimum treatment success.
Collapse‐induced fluidization structures in the Lower Cretaceous Athabasca Oil Sands Deposit, Western Canada
Authors: Broughton Paul L. 
Published: February 2015

AbstractUnique vertical fluidization structures from the Lower Cretaceous Athabasca Oil Sands Deposit in Western Canada are described. The multi‐metre long structures resulted from ascending Devonian karst aquifer waters injected into the overlying unconsolidated sands of the McMurray Formation (Aptian). The dissolution removal of 100–200 m of Middle Devonian salt beds caused the collapse and fragmentation of the 200 m of Upper Devonian limestones underlying the Cretaceous sands. Hypogene karst aquifer waters fingered upwards along the faults and fractures. Disintegrated muddy wall rock sourced hydroplastic mud flows along fractures in the limestone beds below the floor of the central Bitumount Trough. These dykes widened and lengthened collapse‐induced Upper Devonian fault blocks that differentially subsided due to salt dissolution. Conduits plugged by these mud flows diverted over‐pressured aquifer waters upwards along remaining open pipes, some of which vented on the trough floor. Aquifer waters injected into the McMurray sand and mud beds accumulated on the trough floor generated several types of collapse‐induced fluidization structures: (1) stronger aquifer flows mobilized sands into tens‐of‐metres high sand dykes consisting of multiple vertical pipes of fluidized sand contorted around and intertwined with fragmented muddy wall rock; (2) smaller aquifer jets resulted in 1–2 m high sand‐rich pillars on the trough floor; and (3) narrower high‐pressure jets flowed muddy waters along multi‐metre long, 3–5 cm wide, vertical pipes that cross‐cut and wrapped around fragmented in situ beds. The velocity gradient between these narrow but multi‐metre long water pipe flows and the ambient velocity in the surrounding sediments caused water infiltration to radiate outwards. This plugged porosity along the outer wall of the pipe, diminished drainage into the wall rock, and stabilized concentric growth ring depositions along the length of the pipe. These pipe fills appear as unique striped ribbon fabrics when viewed in longitudinal section.
Synthesis and Evaluation of 3‐(furo[2,3‐b]pyridin‐3‐yl)‐4‐(1H‐indol‐3‐yl)‐maleimides as Novel GSK‐3β Inhibitors and Anti‐Ischemic Agents
Authors: Ye Qing , Li Qiu , Zhou Yubo , Xu Lei , Mao Weili , Gao Yuanxue , Li Chenhui , Xu Yuan , Xu Yazhou , Liao Hong , Zhang Luyong , Gao Jianrong , Li Jia , Pang Tao 
Published: February 2015

A series of novel 3‐(furo[2,3‐b]pyridin‐3‐yl)‐4‐(1H‐indol‐3‐yl)‐maleimides were designed, synthesized, and biologically evaluated for their GSK‐3β inhibitory activities. Most compounds showed favorable inhibitory activities against GSK‐3β protein. Among them, compounds 5n, 5o, and 5p significantly reduced GSK‐3β substrate tau phosphorylation at Ser396 in primary neurons, indicating inhibition of cellular GSK‐3β activity. In the in vitro neuronal injury models, compounds 5n, 5o, and 5p prevented neuronal death against glutamate, oxygen–glucose deprivation, and nutrient serum deprivation which are closely associated with cerebral ischemic stroke. In the in vivo cerebral ischemia animal model, compound 5o reduced infarct size by 10% and improved the neurological deficit. The results may provide new insights into the development of novel GSK‐3β inhibitors with potential neuroprotective activity against brain ischemic stroke.
Mapping area variability in social and behavioural difficulties among Glasgow pre‐schoolers: linkage of a survey of pre‐school staff with routine monitoring data
Authors: Barry S. J. E. , Marryat L. , Thompson L. , Ellaway A. , White J. , McClung M. , Wilson P. 
Published: February 2015

AbstractBackgroundSocial, emotional and behavioural development in early to middle childhood impact upon many outcomes in future life and are influenced by home, neighbourhood and school environments. We used linked data to investigate differences between areas in Glasgow City in level of difficulties in pre‐school age children, after consideration of demographics, including area‐level deprivation.MethodsPre‐school education staff completed Strengths and Difficulties Questionnaires (SDQ) on all children progressing to school from a local authority or partnership (local authority‐funded private) pre‐school in Glasgow City between 2010 and 2012. These data were linked to individual (age, gender) and area‐level (deprivation) demographics from the City Council Education Services Department. Statistical models were fitted to the SDQ scores, adjusting for age, gender, area deprivation, year of school entry, pre‐school establishment attended and electoral ward of residence. Correlation between neighbouring wards was incorporated to allow for clustering of scores.ResultsBoys and those living in more deprived areas had higher levels of difficulties. Children aged 5.0–5.5 years had fewest difficulties, while the oldest and youngest children had similar levels of difficulties. There were no significant secular trends by year of school entry. There remained differences among areas after adjusting for these variables, with children living in some areas having fewer difficulties than would be expected based on their socio‐demographic characteristics.ConclusionsThere remained differences in children's levels of difficulties between areas after adjusting for age, gender, area deprivation and year of school entry. Children in some very deprived areas had fewer difficulties than might be expected, while those in relatively affluent areas had more difficulties than expected based on their deprivation level. There may be other, unmeasured, individual‐ and area‐level reasons for children's level of difficulties, and these require further exploration.
Flow cytometry detection of vitamin D receptor changes during vitamin D treatment in Crohn's disease
Authors: Bendix M , Dige A , Deleuran B , Dahlerup J F , Jørgensen S P , Bartels L E , Husted L B , Harsløf T , Langdahl B , Agnholt J 
Published: February 2015

Summary
Crohn's disease (CD) is a chronic inflammatory disease associated with a dysregulated T cell response towards intestinal microflora. Vitamin D has immune modulatory effects on T cells through the nuclear vitamin D receptor (VDR) in vitro. It is unclear how oral vitamin D treatment affects VDR expression. The aim of this study was to establish a flow cytometry protocol, including nuclear and cytoplasmic VDR expression, and to investigate the effects of vitamin D treatment on T cell VDR expression in CD patients. The flow cytometry protocol for VDR staining was developed using the human acute monocytic leukaemia cell line (THP-1). The protocol was evaluated in anti-CD3/CD28-stimulated peripheral blood mononuclear cells (PBMCs) from vitamin D3- (n = 9) and placebo-treated (n = 9) CD patients. Anti-VDR-stained PBMCs were examined by flow cytometry, and their cytokine production was determined by cytokine bead array. VDR, CYP27B1 and RXRα mRNA expression levels in CD4+ T cells were measured by quantitative reverse transcriptase polymerase chain reaction. The flow cytometry protocol enabled detection of cytoplasmic and nuclear VDR expression. The results were confirmed by confocal microscopy and supported by correlation with VDR mRNA expression. VDR expression in CD4+ T cells increased following stimulation. This VDR up-regulation was inhibited with 30% by vitamin D treatment compared to placebo in CD patients (P = 0·027). VDR expression was correlated with in-vitro interferon-γ production in stimulated PBMCs (P = 0·01). Flow cytometry is a useful method with which to measure intracellular VDR expression. Vitamin D treatment in CD patients reduces T cell receptor-mediated VDR up-regulation.
Distinct invasion strategies operating within a natural annual plant system
Authors: Lai Hao Ran , Mayfield Margaret M. , Gay‐des‐combes Justine M. , Spiegelberger Thomas , Dwyer John M. 
Published: February 2015

AbstractAlien plant species are known to have a wide range of impacts on recipient communities, from resident species’ exclusions to coexistence with resident species. It remains unclear; however, if this variety of impacts is due to different invader strategies, features of recipient communities or both. To test this, we examined multiple plant invasions of a single ecosystem in southwestern Australia. We used extensive community data to calculate pairwise segregation between target alien species and many co‐occurring species. We related segregation to species’ positions along community trait hierarchies and identified at least two distinct invasion strategies: ‘exploiters’ which occupy high positions along key trait hierarchies and reduce local native species diversity (particularly in nutrient‐enriched situations), and ‘coexisters’ who occupy intermediate trait positions and have no discernable impact on native diversity. We conclude that trait hierarchies, linked to measures of competition, can provide valuable insights about the processes driving different invasion outcomes.
Climate‐dependent costs of reproduction: Survival and fecundity costs decline with length of the growing season and summer temperature
Authors: Sletvold Nina , Ågren Jon 
Published: February 2015

AbstractCosts of reproduction are expected to vary with environmental conditions thus influencing selection on life‐history traits. Yet, the effects of habitat conditions and climate on trade‐offs among fitness components remain poorly understood. For 2–5 years, we quantified costs of experimentally increased reproduction in two populations (coastal long‐season vs. inland short‐season) of two long‐lived orchids that differ in natural reproductive effort (RE; 30 vs. 75% fruit set). In both species, survival costs were found only at the short‐season site, whereas growth and fecundity costs were evident at both sites, and both survival and fecundity costs declined with increasing growing season length and/or summer temperature. The results suggest that the expression of costs of reproduction depend on the local climate, and that climate warming could result in selection favouring increased RE in both study species.
Solar‐simulated ultraviolet radiation induces histone 3 methylation changes in the gene promoters of matrix metalloproteinases 1 and 3 in primary human dermal fibroblasts
Authors: Gesumaria Lisa , Matsui Mary S. , Kluz Thomas , Costa Max 
Published: February 2015

AbstractMolecular signalling pathways delineating the induction of matrix metalloproteinases (MMPs) by ultraviolet radiation (UVR) are currently well‐defined; however, the effects of UVR on epigenetic mechanisms of MMP induction are not as well understood. In this study, we examined solar‐simulated UVR (ssUVR)‐induced gene expression changes and alterations to histone methylation in the promoters of MMP1 and MMP3 in primary human dermal fibroblasts (HDF). Gene expression changes, including the increased expression of MMP1 and MMP3, were observed using Affymetrix GeneChip arrays and confirmed by qRT‐PCR. Using ChIP‐PCR, we showed for the first time that in HDF irradiated with 12 J/cm2 ssUVR, the H3K4me3 transcriptional activating mark increased and the H3K9me2 transcriptional silencing mark decreased in abundance in promoters, correlating with the observed elevation of MMP1 and MMP3 mRNA levels following ssUVR exposure. Changes in mRNA levels due to a single exposure were transient and decreased 5 days after exposure.
A longitudinal evaluation of anti‐FVIII antibodies demonstrated IgG4 subclass is mainly correlated with high‐titre inhibitor in haemophilia A patients
Authors: Montalvão S. A. L. , Tucunduva A. C. , Siqueira L. H. , Sambo A. L. A. , Medina S. S. , Ozelo M. C. 
Published: February 2015

SummaryThe development of inhibitory antibodies against factor VIII (FVIII) (inhibitor) is the major complication in haemophilia A patients. The FVIII‐binding antibodies development comprises a polyclonal immunoglobulin (Ig) G response. Recent studies showed strong correlation between the presence of neutralizing anti‐FVIII antibodies (inhibitors) and IgG4 subclass. The aim of this study was to evaluate anti‐FVIII IgG subclasses in haemophilia A patients with inhibitor both in a cross‐sectional and in a longitudinal analysis. Inhibitors were determined by Nijmegen–Bethesda assay. Anti‐FVIII IgG subclasses were performed by ELISA, and samples from 20 healthy individuals were used to validate the test. We studied 25 haemophilia A patients with inhibitor, previously treated exclusively with plasma‐derived FVIII concentrates or bypassing agents. The IgG subclasses distributions were evaluated in two groups of patients classified according to inhibitor response. IgG1 and IgG4 antibodies were most prominent in haemophilia A patients with inhibitors when compared with IgG2 and IgG3. This study reports for the first time the behaviour of FVIII‐binding IgG1 and IgG4 subclasses in a longitudinal analysis, in a clinical setting, of high‐response inhibitor haemophilia A patients, showing the correlation of IgG4 and the inhibitor titres. In spite of being considered a non‐pathologic antibody subclass with anti‐inflammatory properties in other situations, IgG4 is correlated with the presence of high‐titre inhibitor in the haemophilia setting. The comprehension of the IgG4 role in immune response may be crucial to establish the process for designing specific tolerance to FVIII.