bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of a novel acetamidobenzoxazolone‐based PET ligand for translocator protein (18 kDa) imaging of neuroinflammation in the brain
Authors: Tiwari Anjani K. , Yui Joji , Fujinaga Masayuki , Kumata Katsushi , Shimoda Yoko , Yamasaki Tomoteru , Xie Lin , Hatori Akiko , Maeda Jun , Nengaki Nobuki , Zhang Ming‐Rong 
Published: February 2014

AbstractWe developed the novel positron emission tomography (PET) ligand 2‐[5‐(4‐[11C]methoxyphenyl)‐2‐oxo‐1,3‐benzoxazol‐3(2H)‐yl]‐N‐methyl‐N‐phenylacetamide ([11C]MBMP) for translocator protein (18 kDa, TSPO) imaging and evaluated its efficacy in ischemic rat brains. [11C]MBMP was synthesized by reacting desmethyl precursor (1) with [11C]CH3I in radiochemical purity of ≥ 98% and specific activity of 85 ± 30 GBq/μmol (n = 18) at the end of synthesis. Biodistribution study on mice showed high accumulation of radioactivity in the TSPO‐rich organs, e.g., the lungs, heart, kidneys, and adrenal glands. The metabolite analysis in mice brain homogenate showed 80.1 ± 2.7% intact [11C]MBMP at 60 min after injection. To determine the specific binding of [11C]MBMP with TSPO in the brain, in vitro autoradiography and PET studies were performed in an ischemic rat model. In vitro autoradiography indicated significantly increased binding on the ipsilateral side compared with that on the contralateral side of ischemic rat brains. This result was supported firmly by the contrast of radioactivity between the ipsilateral and contralateral sides in PET images. Displacement experiments with unlabelled MBMP or PK11195 minimized the difference in uptake between the two sides. In summary, [11C]MBMP is a potential PET imaging agent for TSPO and, consequently, for the up‐regulation of microglia during neuroinflammation.
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We developed 2‐[5‐(4‐[11C]methoxyphenyl)‐2‐oxo‐1,3‐benzoxazol‐3(2H)‐yl]‐N‐methyl‐N‐phenylacetamide ([11C]MBMP) as a novel positron emission tomography ligand for imaging of translocator protein (18 kDa, TSPO) in the brain. [11C]MBMP exhibited high in vitro and in vivo specific binding with TSPO in the ischemic rat brain.
Factors associated with pain induced by orthodontic separators
Authors: Beck V. J. , Farella M. , Chandler N. P. , Kieser J. A. , Thomson W. M. 
Published: February 2014

SummaryPain resulting from the application of orthodontic forces varies markedly across individuals. The reasons of this variability are still largely unknown. To investigate factors that may be associated with orthodontic pain following the application of orthodontic separators. One hundred and seven participants were screened for pain response over 48 h following placement of orthodontic elastomeric separators. The highest (n = 10) and lowest (n = 10) pain responders were identified, and data collected on tooth pain sensitivity to electrical stimulation in conjunction with using the Pain Catastrophising Scale (PCS), Dental Anxiety Scale (DAS) and cold pressor test (CPT). There were statistically significant differences between high‐ and low‐pain responders in catastrophising score (P ≤ 0·023). For every PCS magnification score of 1 unit higher, the relative risk of being a high‐pain responder was 1·6 (P = 0·002); those scoring higher on helplessness had a lower risk of being so. DAS scores of high‐pain responders were twice as high as those of low‐pain responder (P = 0·043). During the first 2 min of CPT, the high‐pain responders experienced more pain than the low‐pain responders (P ≤ 0·029). Tooth pain thresholds did not differ between the two different pain responder groups. Pain catastrophising, dental anxiety and cold sensitivity appear to modify the pain experienced following placement of orthodontic separators. Further research is needed to determine the validity of screening questions to identify at‐risk patients prior to commencing orthodontic treatment.
Calcifying Cystic Odontogenic Tumour: immunohistochemical expression of matrix metalloproteinases, their inhibitors (TIMPs and RECK) and inducer (EMMPRIN)
Authors: Prosdócimi Fábio C. , Rodini Camila O. , Sogayar Mari C. , Sousa Suzana C. O. M. , Xavier Flávia C. A. , Paiva Katiúcia B. S. 
Published: February 2014

BackgroundCalcifying cyst odontogenic tumour (CCOT) is a rare benign cystic neoplasm of odontogenic origin. MMPs are responsible for extracellular matrix remodelling and, together their inhibitors and inducer, determinate the level of its turnover in pathological processes, leading to an auspicious microenvironment for tumour development. Thus, our goal was to evaluate matrix metalloproteinases (MMPs‐2, ‐7, ‐9 and ‐14), their inhibitors (TIMPs‐2, ‐3, ‐4 and RECK) and its inductor (EMMPRIN) expression in CCOT.Materials and MethodsWe used 18 cases of CCOT submitted to immunolocalization of the target proteins and analysed in both neoplastic odontogenic epithelial and stromal compartments.ResultsAll molecules evaluated were expressed in both compartments in CCOT. In epithelial layer, immunostaining for MMPs, TIMPs, RECK and EMMPRIN was found in basal, suprabasal spindle and stellate cells surrounding ghost cells and ghost cells themselves, except for MMP‐9 and TIMP‐2 which were only expressed by ghost cells. In stromal compartment, extracellular matrix, mesenchymal (MC) and endothelial cells (EC) were positive for MMP‐2, ‐7, TIMP‐3 and ‐4, while MMP‐9, TIMP‐2 and RECK were positive only in MC and MMP‐14 only in EC. Statistical significance difference was found between both compartments for MMP‐9 (P < 0.001), RECK (P = 0.004) and EMMPRIN (P < 0.001), being more expressed in epithelium than in stroma. Positive correlation between both stromal EMMPRIN and RECK expression was found (R = 0.661, P = 0.003).ConclusionsWe concluded that these proteins/enzymes are differentially expressed in both epithelium and stroma of CCOT, suggesting an imbalance between MMPs and their inducer/inhibitors may contribute on the tumour behaviour.
Panax notoginseng saponins inhibit areca nut extract‐induced oral submucous fibrosis in vitro
Authors: Dai Jian‐Ping , Chen Xiao‐Xuan , Zhu Dan‐Xia , Wan Qian‐Ying , Chen Cheng , Wang Ge‐Fei , Li Wei‐Zhong , Li Kang‐Sheng 
Published: February 2014

BackgroundOral submucous fibrosis (OSF) is a premalignant and fibrosing disease, which is closely associated with the habit of chewing areca nut. Panax notoginseng Buck F. H. Chen is an often used antifibrotic and antitumor agent. To treat areca nut‐induced OSF, we have developed a chewable tablet, in which one of the major medicines is total Panax notoginseng saponins (PNS). In this study, we have investigated the antifibrotic effect and mechanism of PNS on areca nut‐induced OSF in vitro.MethodsThrough human procollagen gene promoter luciferase reporter plasmid, hydroxyproline assay, gelatin zymography, qRT‐PCR, ELISA, and Western blot, the influences of PNS on areca nut extract (ANE)‐induced cell growth, collagen accumulation, procollagen gene transcription, MMP‐2/‐9 activity, MMP‐1/‐13 and TIMP‐1/‐2 expression, cytokine secretion, and the activation of PI3K/AKT, ERK/JNK/p38 MAPK, and TGFβ/Smads pathways were detected.ResultsPanax notoginseng saponins could inhibit the ANE‐induced abnormal growth and collagen accumulation of oral mucosal fibroblasts in a concentration‐dependent manner. PNS (25 μg/ml) could significantly inhibit the ANE‐induced expression of Col1A1 and Col3A1, augment the ANE‐induced decrease of MMP‐2/‐9 activity, inhibit the ANE‐induced increase of TIMP‐1/‐2 expression, and decrease the ANE‐induced transcription and release of CTGF, TGFβ1, IL‐6, and TNFα. PNS (25 μg/ml) also significantly inhibited the ANE‐induced activation of AKT and ERK/JNK/p38 MAPK pathways in oral mucosal fibroblasts and the ANE‐induced activation of TGFβ/smad pathway in HaCaT cells.ConclusionPanax notoginseng saponins possess excellent anti‐OSF activity, and its mechanism may be related to its ability to inhibit the ANE‐induced activation of PI3K/AKT, ERK/JNK/p38 MAPK, and TGFβ/smad pathways.
The axis inhibition protein 2 polymorphisms and non‐syndromic orofacial clefts susceptibility in a Chinese Han population
Authors: Han Yue , Zhou Lian , Ma Lan , Li Dandan , Xu Min , Yuan Hua , Ma Junqing , Zhang Weibing , Jiang Hongbing , Wu Yunong , Wang Lin , Pan Yongchu 
Published: February 2014

BackgroundThe axis inhibition protein 2 (AXIN2) is an important regulator of β‐catenin degradation in the Wnt pathway, which plays a key role in craniofacial morphogenesis. The goal of this study was to investigate the potential relationship between AXIN2 polymorphisms and the risks of non‐syndromic orofacial clefts (NSOC) in a Chinese Han population.MethodsFour polymorphisms of AXIN2 (rs2240307, rs11867417, rs2240308, and rs7591) were selected to perform a case–control study with 599 NSOC cases and 602 healthy individuals from a Chinese Han population. The single nucleotide polymorphisms (SNPs) were genotyped on basis of double ligation and multiplex fluorescence PCR.ResultsWeak associations were found between these four SNPs and the risk of NSOC. Further stratified analysis showed that the overall genotype frequencies of rs2240307 were different between the cleft palate only (CPO) group and the control group (P = 0.048), and GG genotype markedly contributed to the susceptibility to CPO (OR = 3.22, 95% CI = 1.13–9.18). The similar effect was also observed on GA/AA genotype compared with GG homozygote (OR = 0.30, 95% CI = 0.11–0.84). The results of LD analysis between each pair of SNPs revealed that two SNPs (rs11867417 and rs7591) were in a LD block (r2 > 0.8). But no statistically significant was found between cases and controls from haplotype analysis in these two loci.ConclusionsThe borderline results gave us a hint that rs2240307 contributed to the susceptibility to CPO in a Chinese Han population, which was conductive to improving our awareness of the causes of NSOC.
16S rDNA‐based metagenomic analysis of dental plaque and lung bacteria in patients with severe acute exacerbations of chronic obstructive pulmonary disease
Authors: Tan L. , Wang H. , Li C. , Pan Y. 
Published: February 2014

Background and ObjectiveAcute exacerbations of chronic obstructive pulmonary disease (AE‐COPD) are leading causes of mortality in hospital intensive care units. We sought to determine whether dental plaque biofilms might harbor pathogenic bacteria that can eventually cause lung infections in patients with severe AE‐COPD.Material and MethodsPaired samples of subgingival plaque biofilm and tracheal aspirate were collected from 53 patients with severe AE‐COPD. Total bacterial DNA was extracted from each sample individually for polymerase chain reaction amplification and/or generation of bacterial 16S rDNA sequences and cDNA libraries. We used a metagenomic approach, based on bacterial 16S rDNA sequences, to compare the distribution of species present in dental plaque and lung.ResultsAnalysis of 1060 sequences (20 clones per patient) revealed a wide range of aerobic, anaerobic, pathogenic, opportunistic, novel and uncultivable bacterial species. Species indistinguishable between the paired subgingival plaque and tracheal aspirate samples (97–100% similarity in 16S rDNA sequence) were dental plaque pathogens (Aggregatibacter actinomycetemcomitans, Capnocytophaga sputigena, Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola) and lung pathogens (Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa and Streptococcus pneumoniae). Real‐time polymerase chain reaction of 16S rDNA indicated lower levels of Pseudomonas aeruginosa and Porphyromonas gingivalis colonizing the dental plaques compared with the paired tracheal aspirate samples.ConclusionThese results support the hypothesis that dental bacteria may contribute to the pathology of severe AE‐COPD.
Birth Volume and the Quality of Obstetric Care in Rural Hospitals
Authors: Kozhimannil Katy B. , Hung Peiyin , Prasad Shailendra , Casey Michelle , McClellan Maeve , Moscovice Ira S. 
Published: February 2014

AbstractBackgroundChildbirth is the most common reason for hospitalization in the United States. Assessing obstetric care quality is critically important for patients, clinicians, and hospitals in rural areas.MethodsThe study used hospital discharge data from the Statewide Inpatient Databases, Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality, for 9 states (Colorado, Iowa, Kentucky, New York, North Carolina, Oregon, Vermont, Washington, and Wisconsin) to identify all births in rural hospitals with 10 or more births/year in 2002 (N = 94,356) and 2010 (N = 103,880). Multivariate logistic regression was used to assess the relationship between hospital annual birth volume, measured as low (10‐110), medium (111‐240), medium‐high (241‐460) or high (>460), and 3 measures of obstetric care quality (low‐risk cesarean rates for term, vertex, and singleton pregnancies with no prior cesarean; nonindicated cesarean; and nonindicated induction) and 2 patient safety measures (episiotomy and perineal laceration).ResultsThe odds of low‐risk and nonindicated cesarean were lower in medium‐high and high‐volume rural hospitals compared with low‐volume hospitals after controlling for maternal demographic and clinical factors. In low‐volume hospitals, odds of labor induction without medical indication were higher than in medium‐volume hospitals, but not significantly different from medium‐high or high‐volume hospitals. Odds of episiotomy were greater in medium‐high or high‐volume hospitals than in low‐volume hospitals. The likelihood of perineal laceration did not differ significantly by birth volume.ConclusionsObstetric quality and safety outcomes vary significantly across rural hospitals by birth volume. Better performance is not consistently associated with either lower or higher volume facilities.
Access to Medical and Supportive Care for Rural and Remote Cancer Survivors in Northern British Columbia
Authors: Fuchsia Howard A. , Smillie Kirsten , Turnbull Kristin , Zirul Chelan , Munroe Dana , Ward Amanda , Tobin Pam , Kazanjian Arminee , Olson Rob 
Published: February 2014

AbstractBackgroundRural cancer survivors (RCS) potentially have unique medical and supportive care experiences when they return to their communities posttreatment because of the availability and accessibility of health services. However, there is a limited understanding of cancer survivorship in rural communities.PurposeThe purpose of this study is to describe RCS experiences accessing medical and supportive care postcancer treatment.MethodsInterviews and focus groups were conducted with 52 RCS residing in northern British Columbia, Canada. The data were analyzed using qualitative content analysis methods.ResultsGeneral Population RCS and First Nations RCS experienced challenges accessing timely medical care close to home, resulting in unmet medical needs. Emotional support services were rarely available, and, if they did exist, were difficult to access or not tailored to cancer survivors. Travel and distance were barriers to medical and psychological support and services, not only in terms of the cost of travel, but also the toll this took on family members. Many of the RCS lacked access to trusted and useful information. Financial assistance, for follow‐up care and rehabilitation services, was rarely available, as was appropriate employment assistance.ConclusionMedical and supportive care can be inaccessible, unavailable, and unaffordable for cancer survivors living in rural northern communities.
Histological subclassification of cirrhosis can predict recurrence after curative resection of hepatocellular carcinoma
Authors: Kim Seung Up , Jung Kyu Sik , Lee Sarah , Park Jun Yong , Kim Do Young , Ahn Sang Hoon , Choi Gi Hong , Kim Kyung Sik , Choi Jin Sub , Han Kwang‐Hyub , Park Young Nyun 
Published: February 2014

AbstractBackgroundRecurrence of hepatocellular carcinoma (HCC) after curative resection continues to be a major cause of death. This prospective study is designed to investigate whether histological subclassification of cirrhosis using the Laennec system could predict recurrence in patients with hepatitis B virus (HBV)‐related HCC after curative resection.MethodsPatients with HBV‐related HCC who underwent curative resection and showed Laennec stage 3 to 4 were enrolled and the cases with stage 4 were subclassified histologically into three groups (stages 4A, 4B and 4C) according to the Laennec system. Between February 2006 and August 2009, 92 patients were recruited.ResultsStage 3, 4A, 4B and 4C were identified in 24 (26.1%), 15 (16.3%), 43 (46.7%) and 10 (10.9%) patients respectively. The cumulative incidence rates of recurrence at 1, 2 and 3 years were 24.2%, 40.5% and 55.1% respectively. On multivariate analysis, serum albumin [hazard ratio (HR), 0.528; 95% confidence interval (CI), 0.312–0.891; P = 0.017] and Edmondson–Steiner grade III–IV (HR, 3.456; 95% CI, 1.123–10.517; P = 0.031) were significantly correlated with early recurrence (<1 year), whereas stage 4C (HR, 5.426; 95% CI, 1.030–28.598; P = 0.046) was the only independent risk factor for late recurrence (≥1 year).ConclusionsHistological subclassification of cirrhosis using the Laennec system is a significant predictor of late recurrence in patients with HBV‐related HCC after curative resection.
Metabolomic tissue signature in human non‐alcoholic fatty liver disease identifies protective candidate metabolites
Authors: von Schönfels Witigo , Patsenker Eleonora , Fahrner René , Itzel Timo , Hinrichsen Holger , Brosch Mario , Erhart Wiebke , Gruodyte Auste , Vollnberg Bernd , Richter Klaus , Landrock Andreas , Schreiber Stefan , Brückner Stephan , Beldi Guido , Sipos Bence , Becker Thomas , Röcken Christoph , Teufel Andreas , Stickel Felix , Schafmayer Clemens , Hampe Jochen 
Published: February 2014

AbstractBackgroundNon‐alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in industrialized countries, yet its pathophysiology is incompletely understood. Small‐molecule metabolite screens may offer new insights into disease mechanisms and reveal new treatment targets.MethodsDiscovery (N = 33) and replication (N = 66) of liver biopsies spanning the range from normal liver histology to non‐alcoholic steatohepatitis (NASH) were ascertained ensuring rapid freezing under 30 s in patients. 252 metabolites were assessed using GC/MS. Replicated metabolites were evaluated in a murine high‐fat diet model of NAFLD.ResultsIn a two‐stage metabolic screening, hydroquinone (HQ, pcombined = 3.0 × 10−4) and nicotinic acid (NA, pcombined = 3.9 × 10−9) were inversely correlated with histological NAFLD severity. A murine high‐fat diet model of NAFLD demonstrated a protective effect of these two substances against NAFLD: Supplementation with 1% HQ reduced only liver steatosis, whereas 0.6% NA reduced both liver fat content and serum transaminase levels and induced a complex regulatory network of genes linked to NALFD pathogenesis in a global expression pathway analysis. Human nutritional intake of NA equivalent was also consistent with a protective effect of NA against NASH progression.ConclusionThis first small‐molecular screen of human liver tissue identified two replicated protective metabolites. Either the use of NA or targeting its regulatory pathways might be explored to treat or prevent human NAFLD.
Fetuin‐A negatively correlates with liver and vascular fibrosis in nonalcoholic fatty liver disease subjects
Authors: Sato Motoya , Kamada Yoshihiro , Takeda Yuri , Kida Sachiho , Ohara Yuka , Fujii Hironobu , Akita Maaya , Mizutani Kayo , Yoshida Yuichi , Yamada Makoto , Hougaku Hidetaka , Takehara Tetsuo , Miyoshi Eiji 
Published: February 2014

AbstractBackground & AimsFetuin‐A (α2HS‐glycoprotein), a liver secretory glycoprotein, is known as a transforming growth factor (TGF)‐β1 signalling inhibitor. Serum fetuin‐A concentration is associated with nonalcoholic fatty liver disease (NAFLD) and cardiovascular disease. However, the usefulness of serum fetuin‐A as a predictive fibrosis biomarker in NAFLD patients remains unclear. In this study, we investigated the relationship between circulating fetuin‐A levels and fibrosis‐related markers [platelet count, NAFLD fibrosis score and carotid intima media thickness (IMT)] in subjects with NAFLD.MethodsA total of 295 subjects (male, 164; female, 131) who received medical health check‐ups were enrolled in this study. NAFLD was diagnosed using abdominal ultrasonography. Serum fetuin‐A was measured by ELISA. IMT was assessed using a high‐resolution ultrasound scanner. Using recombinant human fetuin‐A, we investigated the effects of fetuin‐A on hepatic stellate cells, which play a pivotal role in the process of hepatic fibrosis.ResultsSerum fetuin‐A concentration was significantly correlated with platelet count (R = 0.19, P < 0.01), NAFLD fibrosis score (R = −0.25, P < 0.01) and mean IMT (R = −0.22, P < 0.01). Multivariate analyses revealed that the fetuin‐A concentration is a significant and independent determinant of platelet count, NAFLD fibrosis score and mean IMT. Recombinant fetuin‐A suppressed TGF‐β1 signalling and fibrosis‐related gene expression and increased the expression of TGF‐β1 pseudoreceptor bone morphogenic protein and activin membrane‐bound inhibitor (BAMBI).ConclusionsSerum fetuin‐A level is associated with liver/vessel fibrosis‐related markers in NAFLD patients. Circulating fetuin‐A could be a useful serum biomarker for predicting liver and vascular fibrosis progression in NAFLD patients.
Skin toxins in coral‐associated Gobiodon species (Teleostei: Gobiidae) affect predator preference and prey survival
Authors: Gratzer Barbara , Millesi Eva , Walzl Manfred , Herler Juergen 
Published: February 2014

AbstractPredation risk is high for the many small coral reef fishes, requiring successful sheltering or other predator defence mechanisms. Coral‐dwelling gobies of the genus Gobiodon live in close association with scleractinian corals of the genus Acropora. Earlier studies indicated that the low movement frequency of adult fishes and the development of skin toxins (crinotoxicity) are predation avoidance mechanisms. Although past experiments showed that predators refuse food prepared with goby skin mucus, direct predator–prey interactions have not been studied. The present study compares the toxicity levels of two crinotoxic coral gobies – Gobiodon histrio, representative of a conspicuously coloured species, and Gobiodon sp.3 with cryptic coloration – using a standard bioassay method. The results show that toxin levels of both species differ significantly shortly after mucus release but become similar over time. Predator preferences were tested experimentally in an aquarium in which the two gobies and a juvenile damselfish Chromis viridis were exposed to the small grouper Epinephelus fasciatus. Video‐analysis revealed that although coral gobies are potential prey, E. fasciatus clearly preferred the non‐toxic control fish (C. viridis) over Gobiodon. When targeting a goby, the predator did not prefer one species over the other. Contrary to our expectations that toxic gobies are generally avoided, gobies were often captured, but they were expelled quickly, repeatedly and alive. This unusual post‐capture avoidance confirms that these gobies have a very good chance of surviving attacks in the field due to their skin toxins. Nonetheless, some gobies were consumed: the coral shelter may therefore also provide additional protection, with toxins protecting them mainly during movement between corals. In summary, chemical deterrence by crinotoxic fishes seems to be far more efficient in predation avoidance than in physical deterrence involving body squamation and/or strong fin spines.