bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Role of Urotensin Receptors in the Paracetamol‐Induced Hepatotoxicity Model in Mice: Ameliorative Potential of Urotensin II Antagonist
Authors: Palabiyik Saziye S. , Karakus Emre , Akpinar Erol , Halici Zekai , Bayir Yasin , Yayla Muhammed , Kose Duygu 
Published: July 2015

AbstractWe aimed to evaluate the possible protective effect of a UTR antagonist and to determine the effect of the antagonist on ALT and AST levels in serum, the mRNA expression level of UTR, tumour necrosis factor‐alpha (TNF‐α) and IL‐1β and SOD activity, GSH and MDA levels in liver tissues, which are important mediators or markers for the hepatotoxicity animal model in mice. Animals fasted overnight and were divided into seven equal groups (n = 12). The first group was the healthy group (administered 0.1% DMSO intraperitoneally). Group 2 received only paracetamol (PARA) (administered orally at a dosage of 300 mg/kg). Groups 3 and 4 were treated with only AGO (AC7954, UTR agonist) 15 and 30 mg/kg intraperitoneally, respectively. Groups 5 and 6 were treated with only ANTA (SB657510, UTR antagonist) 30 and 60 mg/kg intraperitoneally, respectively. Group 7 was treated with AGO 30 mg/kg and ANTA 60 mg/kg intraperitoneally. One hour after the pre‐treatment drugs were administered, groups 3 through 7 were given PARA. After the experimental period, the mice were killed 6 and 24 hr after PARA was administered. Antagonist administration significantly decreased the ALT and AST levels, while agonist administration did not. In addition, SOD activity and GSH levels increased, and the MDA level decreased with the pre‐treatment of two antagonist doses. The increased UTR gene expression through PARA was significantly lower in both doses of the antagonist groups at 24 hr when compared with the agonist and PARA groups. This study showed that UTR antagonists have hepatoprotective and anti‐inflammatory effects on high‐dose PARA‐induced hepatotoxicity in mice.
Predictors of prostate cancer specific mortality after radical prostatectomy: 10 year oncologic outcomes from the Victorian Radical Prostatectomy Registry
Authors: Bolton Damien M. , Papa Nathan , Ta Anthony D. , Millar Jeremy , Davidson Adee‐Jonathan , Pedersen John , Syme Rodney , Patel Manish I. , Giles Graham G. 
Published: July 2015

PurposeTo identify the ability of multiple variables to predict prostate cancer specific mortality (PCSM) in a whole of population series of all radical prostatectomies (RP) performed in Victoria, Australia.Materials & MethodsA total of 2154 open RPs were performed in Victoria between July 1995 and December 2000. Subjects without follow up data, Gleason grade, pathological stage were excluded as were those who had pT4 disease or received neoadjuvant treatment. 1967 cases (91.3% of total) met the inclusion criteria for this study. Tumour characteristics were collated via a central registry. We used competing hazards regression models to investigate associations.ResultsAt median follow up of 10.3 years pT stage of RP (P < 0.001) and high Gleason score of the RP specimen (P < 0.001 for ≥8 [Subhazard ratio (SHR) 11.19] and 4 + 3 = 7 [SHR 7.10]) compared with Gleason score 6 disease were strong predictors of progression to PCSM. Gleason score 3 + 4 = 7 was not at this time a significant predictor of PCSM (P = 0.08, SHR 1.84). Predictors of PCSM, independent of stage and grade, included rural residency (P = 0.003), primary surgeon contributing less than 40 cases (low‐volume) to the VRPR (P = 0.025) and the involvement of a trainee surgeon in the operation (P = 0.031).ConclusionThe significant prediction of PCSM by pT cancer stage, Gleason score and primary Gleason pattern at RP in this whole of population study suggests a need to avoid understaging/grading in the process of cancer diagnosis and active surveillance protocols. Multi‐modality therapy is likely to have a greater impact on PCSM in higher stage and Gleason grade disease. Identification of increased PCSM with rural residency and with involvement of a trainee urologist, and reduction in PCSM with higher surgeon volume all suggest potential for improved PC outcomes to be achieved with changes to surgical training and service delivery.
The effectiveness of BCG and interferon against non‐muscle invasive bladder cancer: a New Zealand perspective
Authors: O'Regan Toni , Tatton Michael , Lyon Maryanne , Masters Jonathan 
Published: July 2015

ObjectiveTo ascertain whether the current practice at Auckland City Hospital of adding interferon to BCG in patients with high risk or recurrent non‐muscle invasive bladder cancer (NMIBC) unable or unwilling to undergo radical cystectomy is effective.Subjects and MethodThis study examined all institutional cases where BCG alone had not been effective or tolerated as primary treatment for NMIBC and the next guideline agreed step of radical cystectomy was unable to be performed. We identified all patients unwilling or unable to undergo radical cystectomy due to patient co‐morbidities or preference for whom ongoing treatment and care was required and included 45 in the data analysis. Current practice at Auckland City Hospital is adding interferon α‐2b to BCG for this population group and all patients that were given this therapy with at least three years of follow up data from diagnosis were included into the study. Patients were either on maintenance BCG or single dosing. Several secondary outcomes were also assessed concurrently to the primary objective.ResultsThis observational study showed that adding interferon to BCG proved to be an effective therapy for both treatment and salvage therapy in this patient group with 56% of the patients disease (and recurrence) free at the time of audit. 8/45 patients died whilst undergoing treatment with two of these as a direct result of bladder cancer due to disease progression.ConclusionThis therapy has improved outcomes at our institution and has a place as a treatment of choice in this difficult to manage patient group.
Eicosapentaenoic acid prevents TCDD‐induced oxidative stress and inflammatory response by modulating MAP kinases and redox‐sensitive transcription factors
Authors: Palanisamy Kalaiselvi , Krishnaswamy Rajashree , Paramasivan Poornima , Chih‐Yang Huang , Vishwanadha Vijaya Padma 
Published: July 2015

Background and PurposeOxidative stress and subsequent activation of inflammatory responses is a widely accepted consequence of exposure to environmental toxins. TCDD (2,3,7,8‐tetrachlorodibenzo‐p‐dioxin), a well‐known environmental toxin, exerts its toxicity through many signalling mechanisms, with liver being the principal organ affected. However, an effective antidote to TCDD‐induced toxicity is unknown. The present study evaluated the effect of eicosapentaenoic acid (EPA), an n3 fatty acid, on TCDD‐induced toxicity.Experimental ApproachIn cultures of HepG2 cells, the EPA/AA ratio was determined using gas chromatography, oxidative stress and inflammatory responses through reactive oxygen species (ROS) levels, antioxidant status, [Ca2+]i, nuclear migration of two redox‐sensitive transcription factors, NF‐κB p65 and Nrf‐2, expression of MAP kinase (p‐Erk, p‐p38), NF‐κB p65, COX‐2 and Nrf‐2. Cellular changes in ΔΨm, acidic vesicular organelle formation, cell cycle analysis and scanning electron microscopy analysis were performed.Key ResultsEPA offered significant cytoprotection by increasing EPA/AA ratios in cell membranes, inhibiting ROS generation, enhancing antioxidant status and modulating nuclear translocation of redox‐sensitive transcription factors (NF‐κB p65 and Nrf‐2) and expression of NF‐κB p65, COX‐2 and Nrf‐2. Furthermore, TCDD‐induced upstream events of MAPK phosphorylation, the increase in [Ca2+]i levels and cell surface changes in microvilli were significantly inhibited by EPA. EPA treatment maintained ΔΨm and prevented formation of acidic vesicular organelles.Conclusion and ImplicationsThe present study demonstrates for the first time some underlying molecular mechanisms of cytoprotection exerted by EPA against TCDD‐induced oxidative stress and inflammatory responses.
Activating mitochondrial function and haemoglobin expression with EH‐201, an inducer of erythropoietin in neuronal cells, reverses memory impairment
Authors: Horng Lin‐Yea , Hsu Pei‐Lun , Chen Li‐Wen , Tseng Wang‐Zou , Hsu Kai‐Tin , Wu Chia‐Ling , Wu Rong‐Tsun 
Published: July 2015

Background and PurposeMemory impairment can be progressive in neurodegenerative diseases, and physiological ageing or brain injury, mitochondrial dysfunction and oxidative stress are critical components of these issues. An early clinical study has demonstrated cognitive improvement during erythropoietin treatment in patients with chronic renal failure. As erythropoietin cannot freely cross the blood–brain barrier, we tested EH‐201 (2,3,5,4′‐tetrahydroxystilbene‐2‐O‐β‐d‐glucoside, also known as TSG), a low MW inducer of erythropoietin, for its therapeutic effects on memory impairment in models of neurodegenerative diseases, physiological ageing or brain injury.Experimental ApproachThe effects of EH‐201 were investigated in astrocytes and PC12 neuronal‐like cells. In vivo, we used sleep‐deprived (SD) mice as a stress model, amyloid‐β (Aβ)‐injected mice as a physiological ageing model and kainic acid (KA)‐injected mice as a brain damage model to assess the therapeutic effects of EH‐201.Key ResultsEH‐201 induced expression of erythropoietin, PPAR‐γ coactivator 1α (PGC‐1α) and haemoglobin in astrocytes and PC12 neuronal‐like cells. In vivo, EH‐201 treatment restored memory impairment, as assessed by the passive avoidance test, in SD, Aβ and KA mouse models. In the hippocampus of mice given EH‐201 in their diet, levels of erythropoietin, PGC‐1α and haemoglobin were increasedConclusions and ImplicationsThe induction of endogenous erythropoietin in neuronal cells by inducers such as EH‐201 might be a therapeutic strategy for memory impairment in neurodegenerative disease, physiological ageing or traumatic brain injury.
Geological structure and kinematics of normal faults in the Otway Basin, Australia, based on quantitative analysis of 3‐D seismic reflection data
Authors: Ziesch Jennifer , Aruffo Chiara M. , Tanner David C. , Beilecke Thies , Dance Tess , Henk Andreas , Weber Bastian , Tenthorey Eric , Lippmann Andrea , Krawczyk Charlotte M. 
Published: July 2015

AbstractThe Otway Basin in the south of Victoria, Australia underwent three phases of deformation during breakup of the southern Australian margin. We assess the geometry and kinematics of faulting in the basin by analysing a 3‐D reflection seismic volume. Eight stratigraphic horizons and 24 SW‐dipping normal faults as well as subordinate antithetic faults were interpreted. This resulted in a high‐resolution geological 3‐D model (ca. 8 km × 7 km × 4 km depth) that we present as a supplementary 3‐D PDF (Data S1). We identified hard‐ and soft‐linking fault connections over the entire area, such as antithetic faults and relay ramps, respectively. Most major faults were continuously active from Early to Late Cretaceous, with two faults in the northern part of the study area active until at least the Oligocene. Allan maps of faults show tectonic activity continuously waned over this time period. Isopach maps of stratigraphic volumes quantify the amount of syn‐sedimentary movement that is characteristic of passive margins, such as the Otway Basin. We show that the faults possess strong corrugations (with amplitudes above the seismic resolution), which we illustrated by novel techniques, such as cylindricity and curvature. We argue that the corrugations are produced by sutures between sub‐vertical fault segments and this morphology was maintained during fault growth. Thus, they can be used to indicate the kinematics vector of the fault movement. This evidences, together with left‐stepping relay ramps, that 40% of the faults had a small component (up to 25°) of dextral oblique slip as well as normal (dip‐slip) movement.
Interdisciplinarity to reconstruct historical introductions: solving the status of cryptogenic crayfish
Authors: Clavero Miguel , Nores Carlos , Kubersky‐Piredda Susanne , Centeno‐Cuadros Alejandro 
Published: July 2015

ABSTRACTAnciently introduced species can be confounded with native species because introduction pre‐dates the first species inventories or because of the loss of the collective memory of the introductions. The term ‘cryptogenic species’ denotes species of unknown or unclear status (nativeversusnon‐native) in a given territory, and disciplinary approaches are often insufficient for solving their true status. Here, we follow an integrative, multidisciplinary approach to solve the status of a cryptogenic species, proposing that building on evidence from multiple disciplines can produce robust and clarifying insights. We undertook an exhaustive review of information on a putatively native crayfish (Austropotamobius italicus) inSpain. The reviewed information included taxonomy, genetics and phylogeography, history, archaeology, linguistics, biogeography, ecology, symbiotic organisms and even gastronomy and pharmacy. The knowledge produced by different scientific disciplines converges to indicate thatA. italicusis a non‐native species inSpain. Historical documents even identify the first introduction event: crayfish were shipped fromItaly toSpain in 1588 as a diplomatic gift fromFrancescoIde'Medici toKingPhilipIIofSpain. Previous discussions on the status ofA. italicusfocussed on inconclusive and often confusing genetic results and excluded the rich and clarifying evidence available from other approaches and disciplines. Interdisciplinarity is an often‐invoked but rarely implemented practice in an academic environment that increasingly promotes narrow‐focussed specialization. Our review shows that the integration of disciplines can surpass disciplinary approaches in solving scientific controversies. Our results have straightforward implications for strategies to conserve biological diversity inSpain andEurope, urging a debate on the appropriateness of devoting conservation efforts to non‐native species.
Changes in Patterns of Species Co‐occurrence across Two Tropical Cloud Forests Differing in Soil Nutrients and Air Temperature
Authors: Long Wenxing , Xiong Menghui , Zang Runguo , Schamp Brandon S. , Yang Xiaobo , Ding Yi , Huang Yunfeng , Xiang Yangzhou 
Published: July 2015

AbstractPatterns of co‐occurrence of species are increasingly used to examine the contribution of biotic interactions to community assembly. We assessed patterns of co‐occurrence at four scales, in two types of tropical cloud forests in Hainan Island, China (tropical montane evergreen forests, TMEF and tropical dwarf forests, TDF) that varied significantly in soil nutrients and temperature. We tested if the patterns of co‐occurrence changed when we sorted species into classes by abundance and diameter at breast height (dbh). Co‐occurrence differed by forest type and with plot size, with significant species aggregation observed across larger plots in TDF and patterns of species segregation observed in smaller plots in TMEF. Analyses of differential abundance and dbh classes also showed that smaller plots in TMEF tend to have negative co‐occurrence patterns, but larger plots in TDF tend to show patterns of aggregation, suggesting competitive and facilitative interactions. This underscores the scale‐dependence of the processes contributing to community assembly. Furthermore, it is consistent with predictions of the stress gradient hypothesis that facilitation will be most important in biological systems subject to abiotic stress, while competition will be more important in less abiotically stressful habitats. Our results clearly demonstrate that these two types of tropical cloud forest exhibit different co‐occurrence patterns, and that these patterns are scale‐dependent, though independent of plant abundance and size class.
Impact of KRAS mutation on response and outcome of patients with stage III non‐squamous non‐small cell lung cancer
Authors: Yagishita Shigehiro , Horinouchi Hidehito , Sunami Kuniko S. , Kanda Shintaro , Fujiwara Yutaka , Nokihara Hiroshi , Yamamoto Noboru , Sumi Minako , Shiraishi Kouya , Kohno Takashi , Furuta Koh , Tsuta Koji , Tamura Tomohide , Ohe Yuichiro 
Published: July 2015

The frequency and clinical profile of patients with stage III non‐small cell lung cancer harboring KRAS mutations have not yet been well documented. Here, we analyzed hotspot KRAS mutations using high‐resolution melting analyses in tumor specimens from patients who received chemoradiotherapy between January 2001 and December 2010 at the National Cancer Center Hospital. The associations between the presence of KRAS mutations and the response rate, relapse‐free survival, first relapse sites, survival post‐progression and overall survival were investigated. A total of 274 non‐squamous non‐small cell lung cancer patients received chemoradiotherapy at our hospital. After excluding 121 patients for whom tumor specimens were not available and 34 patients with EGFR mutations, the remaining 119 patients were included in the analysis. KRAS mutations were found at a frequency of 13%. Patients with KRAS mutations had a shorter median relapse‐free survival (6.1 vs 10.9 months) and a lower response rate (63% vs 81%). As for the first relapse site, patients with KRAS mutations had fewer local relapses (8% vs 23%) and more brain metastases (46% vs 12%). After disease progression, patients with KRAS mutations had a significantly shorter median survival post‐progression (2.5 vs 7.3 months, P = 0.028) and median overall survival (15.1 vs 29.1 months, P = 0.022). Our results suggested that KRAS mutation could be associated with a reduced efficacy of chemoradiotherapy and a shortened survival time.
Telling children their mother is seriously ill or dying: mapping French people's views
Authors: Muñoz Sastre M. T. , Sorum P. C. , Mullet E. 
Published: July 2015

AbstractBackgroundWhat to tell children when their mother's life is seriously endangered is a largely unstudied issue.MethodsWe had 255 lay persons in France judge the appropriateness of the parents' behaviour in 48 scenarios of parents dealing with this problem. The scenarios comprised according to a four within‐subject orthogonal design: child's age (4, 6, 8 or 10 years), severity of disease (lethal or worrisome but curable), child's concern or not about his or her mother's illness and parents' decision about how much to tell (tell nothing, minimize or tell the full truth).ResultsCluster analysis revealed four clusters, labelled ‘always tell the truth’ (33%), ‘tell the truth or minimize’ (16%), ‘tell nothing or minimize’ (22%) and ‘depends on child's age and level of concern’ (29%). Women and participants who had already faced breaking bad news like this to children were more frequently members of the two ‘tell the truth’ clusters than other participants.ConclusionsPeople who have already experienced a situation of having to tell a child about their mother's bad health tend to think, more than others, that telling the truth is the best policy.
Postoperative biochemical remission of serum calcitonin is the best predictive factor for recurrence‐free survival of medullary thyroid cancer: a large‐scale retrospective analysis over 30 years
Authors: Jung Kyong Yeun , Kim Seok‐Mo , Yoo Won Sang , Kim Bup‐Woo , Lee Yong Sang , Kim Kyung Won , Lee Kyu Eun , Jeong Jong Ju , Nam Kee‐Hyun , Lee Se Hoon , Hah Jeong Hun , Chung Woong Youn , Yi Ka Hee , Park Do Joon , Youn Yeo‐Kyu , Sung Myung‐Whun , Cho Bo Youn , Park Cheong Soo , Park Young Joo , Chang Hang‐Seok 
Published: July 2015

SummaryContextThe increase in thyroid screening in the general population may lead to earlier detection of medullary thyroid carcinoma (MTC).ObjectiveWe aimed to evaluate secular trends in clinicopathological characteristics and long‐term prognosis of MTC and its prognostic factors.DesignThis was a retrospective analysis from 1982 to 2012.PatientsThree hundred and thirty‐one patients with MTC were included and grouped based on the year of diagnosis (1982–2000, 2001–2005, 2006–2010 and 2011–2012).MeasurementsThese included recurrence and mortality as well as biochemical remission (BCR) of serum calcitonin.ResultsMean tumour size (from 2·5 cm to 1·7 cm, P < 0·001) and percentage of extrathyroidal extension (from 52·0% to 26·0%, P = 0·026) decreased. The percentage of patients achieving BCR within six postoperative months (po‐BCR) increased with time (from 39·6% to 76·1%, P < 0·001). The 5‐year overall recurrence rate significantly decreased in 2006–2012 compared to 1982–2005 (10% vs 18%, respectively, P = 0·031), although the 5‐year survival rate did not improve (92% vs 92%, P = 0·929). Failure to achieve po‐BCR was the strongest predictive factor associated with recurrence (hazard ratio [HR] = 58·04, 95% CI 7·14–472·11; P < 0·001). Male gender (HR = 3·18, 95% CI 1·18–8·56; P = 0·022), tumour size >2 cm (HR = 18·33, 95% CI 2·35–143·06; P = 0·006) and distant metastasis (HR = 4·00, 95% CI 1·31–12·21; P = 0·015) were significant prognostic factors for mortality.ConclusionsClinicopathological characteristics and recurrence of MTC improved with time. Po‐BCR was the best predictive factor for recurrence‐free survival.
Accelerated Osteogenic Differentiation and Bone Formation on Zirconia with Surface Grooves Created with Fiber Laser Irradiation
Authors: Taniguchi Yusuke , Kakura Kae , Yamamoto Katsuki , Kido Hirofumi , Yamazaki Jun 
Published: July 2015

AbstractBackgroundModification of the surface topography of biomaterials is a critical factor for the proliferation and differentiation of osteoblasts. Elucidating the biological response to surface roughening is necessary for clinical application of zirconia implants.PurposeTo investigate the effects of fiber laser‐induced zirconia surface roughening on cultured osteoblast‐like cell morphology, proliferation, differentiation, and calcification, and on in vivo bone formation.Materials and MethodsSixty‐six machine‐surfaced yttria‐tetragonal zirconia polycrystal plates (S‐Zr) and 16 machine‐surfaced implants were used as controls. We prepared 66 rough plates (R‐Zr) and 16 rough implants by surface treatment using a fiber laser.ResultsMC3T3‐E1 cells spread well in all directions on S‐Zr, whereas elongated cells with poorly organized actin stress fibers were observed on R‐Zr. Cell proliferation was significantly greater on R‐Zr than on S‐Zr. The Runx2 mRNA level increased time dependently in osteogenic culture condition. Alkaline phosphatase activity and osteocalcin mRNA levels were higher on R‐Zr compared with S‐Zr. Alizarin red S staining revealed greater calcification on R‐Zr than on S‐Zr. Laser treatment of zirconia implant bodies placed in rat tibiae increased the bone‐implant contact ratio and removal torque considerably.ConclusionsOur results suggest that fiber laser irradiation produces adequate surface roughening of zirconia ceramics to support osseointegration.