bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypoxic conditions stimulate the release of B‐type natriuretic peptide from human retinal pigment epithelium cell culture
Authors: Aaltonen Vesa , Kinnunen Kati , Jouhilahti Eeva‐Mari , Peltonen Juha , Nikinmaa Mikko , Kaarniranta Kai , Arjamaa Olli 
Published: April 2014

AbstractPurposeA‐type peptide, a natriuretic peptide belonging to the natriuretic peptide family, has been shown to be increased in the vitreous of patients suffering from diabetic retinopathy and that human retina has a well‐developed natriuretic peptide system. The stimulus to which the synthesis of natriuretic peptides responded in these patients has, however, remained unknown. As the natriuretic peptides have recently been shown to respond to hypoxic conditions, the genes of both A‐type and B‐type have a hypoxia‐response element (HRE) in their promoter sequence, we therefore hypothesized that hypoxia in the human retinal pigment epithelium will increase the secretion of NT‐proBNP, the most common natriuretic peptide monitored in clinical medicine.MethodsWe used cultured human retinal pigment epithelium cell line (ARPE‐19) which was exposed either to normoxia or to hypoxia for 2 hr, 4 hr, 6 hr and 24 hr. NT‐proBNP was measured with enzyme immunoassay, VEGF with ELISA and HIF‐1α with Western blotting.ResultsHypoxia induced VEGF 165 release in culture medium and HIF‐1α expression in cultured ARPE‐19 cells. Time‐dependent NT‐proBNP release was detected when the ARPE‐19 cells were cultured under normoxia. When hypoxia was induced, a statistically significant increase in NT‐proBNP release was demonstrated in the culture medium.ConclusionsHypoxic conditions increase the release of a natriuretic peptide from retinal pigment epithelium (RPE) cells. The secretion of VEGF was also enhanced. The responses were associated with the up‐regulation of the HIF‐1α transcription factor. These results explain the previous findings from patients with diabetes, which also suggest that hypoxia is a ubiquitous stimulus for the secretion of natriuretic peptides in human body.
Idarubicin‐loaded beads for chemoembolisation of hepatocellular carcinoma: results of the IDASPHERE phase I trial
Authors: Boulin M. , Hillon P. , Cercueil J. P. , Bonnetain F. , Dabakuyo S. , Minello A. , Jouve J. L. , Lepage C. , Bardou M. , Wendremaire M. , Guerard P. , Denys A. , Grandvuillemin A. , Chauffert B. , Bedenne L. , Guiu B. 
Published: April 2014

SummaryBackgroundA phase I dose‐escalation trial of transarterial chemoembolisation (TACE) with idarubicin‐loaded beads was performed in cirrhotic patients with hepatocellular carcinoma (HCC).AimTo estimate the maximum‐tolerated dose (MTD) and to assess safety, efficacy, pharmacokinetics and quality of life.MethodsPatients received a single TACE session with injection of 2 mL drug‐eluting beads (DEBs; DC Bead 300–500 μm) loaded with idarubicin. The idarubicin dose was escalated according to a modified continuous reassessment method. MTD was defined as the dose level closest to that causing dose‐limiting toxicity (DLT) in 20% of patients.ResultsTwenty‐one patients were enrolled, including nine patients at 5 mg, six patients at 10 mg, and six patients at 15 mg. One patient at each dose level experienced DLT (acute myocardial infarction, hyperbilirubinaemia and elevated aspartate aminotransferase (AST) at 5‐, 10‐ and 15‐mg, respectively). The calculated MTD of idarubicin was 10 mg. The most frequent grade ≥3 adverse events were pain, elevated AST, elevated γ‐glutamyltranspeptidase and thrombocytopenia. At 2 months, the objective response rate was 52% (complete response, 28%, and partial response, 24%) by modified Response Evaluation Criteria in Solid Tumours. The median time to progression was 12.1 months (95% CI 7.4 months – not reached); the median overall survival was 24.5 months (95% CI 14.7 months – not reached). Pharmacokinetic analysis demonstrated the ability of DEBs to release idarubicin slowly.ConclusionsUsing drug‐eluting beads, the maximum‐tolerated dose of idarubicin was 10 mg per TACE session. Encouraging responses and median time to progression were observed. Further clinical investigations are warranted (NCT01040559).
Systematic review: the safety and efficacy of hyperbaric oxygen therapy for inflammatory bowel disease
Authors: Dulai P. S. , Gleeson M. W. , Taylor D. , Holubar S. D. , Buckey J. C. , Siegel C. A. 
Published: April 2014

SummaryBackgroundHyperbaric oxygen therapy (HBOT) provides 100% oxygen under pressure, which increases tissue oxygen levels, relieves hypoxia and alters inflammatory pathways. Although there is experience using HBOT in Crohn's disease and ulcerative colitis, the safety and overall efficacy of HBOT in inflammatory bowel disease (IBD) is unknown.AimTo quantify the safety and efficacy of HBOT for Crohn's disease (CD) and ulcerative colitis (UC). The rate of adverse events with HBOT for IBD was compared to the expected rate of adverse events with HBOT.MethodsMEDLINE, EMBASE, Cochrane Collaboration and Web of Knowledge were systematically searched using the PRISMA standards for systematic reviews. Seventeen studies involving 613 patients (286 CD, 327 UC) were included.ResultsThe overall response rate was 86% (85% CD, 88% UC). The overall response rate for perineal CD was 88% (18/40 complete healing, 17/40 partial healing). Of the 40 UC patients with endoscopic follow‐up reported, the overall response rate to HBOT was 100%. During the 8924 treatments, there were a total of nine adverse events, six of which were serious. The rate of adverse events with HBOT in IBD is lower than that seen when utilising HBOT for other indications (P < 0.01). The risk of bias across studies was high.ConclusionsHyperbaric oxygen therapy is a relatively safe and potentially efficacious treatment option for IBD patients. To understand the true benefit of HBOT in IBD, well‐controlled, blinded, randomised trials are needed for both Crohn's disease and ulcerative colitis.
Current status of endoscopic retrograde cholangiopancreatography in patients with surgically altered anatomy in Japan: Questionnaire survey and important discussion points at Endoscopic Forum Japan 2013
Authors: Katanuma Akio , Isayama Hiroyuki 
Published: April 2014

Background and AimEndoscopic retrograde cholangiopancreatography (ERCP) in patients with surgically altered anatomy is still challenging. We aimed to clarify the current status of ERCP in Japan in patients with surgically altered anatomy.MethodsQuestionnaire survey was conducted in 2012 at 11 participating facilities regarding ERCP in patients with surgically altered anatomy.ResultsA total of 490 ERCP procedures were carried out in 273 patients with surgically altered anatomy. The breakdown of surgical procedures was as follows: Roux‐en‐Y (R‐Y) reconstruction (n = 154 [31.4%]), pancreaticoduodenectomy (PD) (n = 136 [27.8%]), hepaticojejunostomy (n = 103 [21.0%]), liver transplantation (n = 20 [4.1%]), Billroth II reconstruction (n = 69 [14.1%]), and interposition after total gastrectomy (n = 8 [1.6%]). The overall success rate of reaching the target site was 91.8% (450 of 490 ERCP procedures). According to reconstructive surgical procedures, the target site was reached in 138 of 154 procedures (89.6%) for R‐Y reconstruction, 129 of 136 procedures (94.8%) for PD, 89 of 103 procedures (86.4%) for hepaticojejunostomy, 18 of 20 procedures (90.0%) for liver transplantation, 68 of 69 procedures (98.6%) for Billroth II reconstruction, and eight of eight procedures (100%) for interposition after total gastrectomy.ConclusionsThe success rate of reaching the target site was high in patients with Billroth II reconstruction and low in patients with hepaticojejunostomy. Although the success rate of endoscopic insertion for ERCP in patients with surgically altered anatomy was high, there are still cases in which it is difficult to achieve technical success.
Endoscopic diagnosis of superficial non‐ampullary duodenal epithelial tumors in Japan: Multicenter case series
Authors: Goda Kenichi , Kikuchi Daisuke , Yamamoto Yorimasa , Takimoto Kengo , Kakushima Naomi , Morita Yoshinori , Doyama Hisashi , Gotoda Takuji , Maehata Yuji , Abe Noritsugu 
Published: April 2014

Background and AimTo verify the current status in Japan on endoscopic diagnosis of superficial non‐ampullary duodenal epithelial tumors (SNADET) by a multicenter case series through a questionnaire survey.MethodsNine endoscopists and a surgeon responded to a questionnaire on endoscopic diagnosis of SNADET. The subjects of this survey were histologically confirmed SNADET that were endoscopically or surgically resected from 2007 to 2012. This survey collected data of 364 patients with 396 SNADET.ResultsOf the 396 SNADET, 121 were histologically diagnosed as low‐grade dysplasia (LGD), 112 as high‐grade dysplasia (HGD), and 163 as superficial adenocarcinoma (SAC) including 153 mucosal carcinomas and 10 submucosal carcinomas. Total number of SNADET increased from 125 in the first half to 271 in the second half of the survey period. Compared to LGD, a significantly greater number of HGD or SAC was found in the tumors having a diameter >5 mm as well as solitary or predominantly red color. Preoperative endoscopic diagnosis indicated significantly higher sensitivity and accuracy and significantly lower specificity for HGD or SAC of final histology than preoperative biopsy. Ten submucosal carcinomas had 0‐I or 0‐IIa+IIc macroscopic‐type tumors with red color.ConclusionsThis multicenter case series study suggested that the number of resected SNADET is dramatically increasing in Japan. Tumor diameter >5 mm and red color seemed to be signs for tumors of HGD or SAC. Preoperative endoscopy may provide a more reliable diagnosis of final histology of HGD or SAC than preoperative biopsy. Further studies are warranted for establishing endoscopic features of submucosal carcinoma.
Early intervention for first‐episode psychosis: broadening the scope of economic estimates
Authors: Park A‐La , McCrone Paul , Knapp Martin 
Published: April 2014

AbstractAimTo explore the economic impacts of early intervention in England on outcomes and costs for people with first‐episode psychosis.MethodsThree decision analytical models were constructed to compare treatment by early intervention for first‐episode psychosis with standard care in relation to employment, education, homicide and suicide. Data on effectiveness and costs were taken from previous studies and expert opinion. Sensitivity analyses tested the robustness of assumptions.ResultsOur models indicate that early intervention demonstrates savings of £2087 per person over 3 years from improved employment and education outcomes. In addition, the annual costs over 10 years related to homicide after early intervention were £80 lower than for standard care. There were also annual savings of £957 per person for early intervention over 4 years compared to standard care as a result of suicides averted.ConclusionsNot only can investment in early intervention help reduce some of the long‐term costs and consequences of mental disorders to the health‐care system. In addition, there are broader economic benefits that strengthen the potential cost savings to society.
Characterisation of the inflammatory cytokine response to anthelmintic treatment in ponies
Authors: Betancourt A. , Lyons E. T. , Horohov D. W. 
Published: April 2014

SummaryReasons for performing studyAnthelmintic treatments have been associated with local inflammatory reactions. Since each class of anthelmintic has unique mechanisms of action affecting different subpopulations of parasites, we hypothesised that they will also induce characteristic proinflammatory responses.ObjectivesTo determine the effect of anthelmintic class on the proinflammatory response post treatment.Study designPonies naturally infected with cyathostomins and other parasites after pasture grazing were left untreated or treated with representatives of 3 different classes of anthelmintics: fenbendazole (benzimidazole); pyrantel tartrate (pyrimidine); and moxidectin (macrocyclic lactone). All were monitored for the expression of proinflammatory genes in the peripheral blood using real‐time PCR.MethodsThe ponies were divided into 4 treatment groups: Group 1 (n = 4) were untreated controls; Group 2 (n = 5) received 5 daily doses of fenbendazole (10 mg/kg bwt); Group 3 (n = 4) received daily treatment of pyrantel tartrate 2× (2.65 mg/kg bwt); and Group 4 (n = 5) received a single dose of moxidectin (400 μg/kg bwt). Blood samples were collected daily for 2 weeks to determine the effect of deworming on proinflammatory gene expression. Faecal egg counts were used to evaluate the efficacy of each drug.ResultsWhile treatment with the benzimidazole significantly reduced egg counts up to 14 days post treatment, it also stimulated proinflammatory gene expression. Treatment with pyrantel salt also reduced faecal egg counts with less of a proinflammatory response. Treatment with the macrocyclic lactone was the most successful in reducing faecal egg counts and produced no signs of increased proinflammatory cytokine expression.ConclusionsThis study revealed pronounced differences in the cytokine responses to anthelmintic treatment. This inflammatory reaction may play a role in the development of parasitic disease post anthelmintic treatment.
Allosteric regulation of phosphofructokinase controls the emergence of glycolytic oscillations in isolated yeast cells
Authors: Gustavsson Anna‐Karin , van Niekerk David D. , Adiels Caroline B. , Kooi Bob , Goksör Mattias , Snoep Jacky L. 
Published: April 2014

Oscillations are widely distributed in nature and synchronization of oscillators has been described at the cellular level (e.g. heart cells) and at the population level (e.g. fireflies). Yeast glycolysis is the best known oscillatory system, although it has been studied almost exclusively at the population level (i.e. limited to observations of average behaviour in synchronized cultures). We studied individual yeast cells that were positioned with optical tweezers in a microfluidic chamber to determine the precise conditions for autonomous glycolytic oscillations. Hopf bifurcation points were determined experimentally in individual cells as a function of glucose and cyanide concentrations. The experiments were analyzed in a detailed mathematical model and could be interpreted in terms of an oscillatory manifold in a three‐dimensional state‐space; crossing the boundaries of the manifold coincides with the onset of oscillations and positioning along the longitudinal axis of the volume sets the period. The oscillatory manifold could be approximated by allosteric control values of phosphofructokinase for ATP and AMP.DatabaseThe mathematical models described here have been submitted to the JWS Online Cellular Systems Modelling Database and can be accessed at http://jjj.mib.ac.uk/webMathematica/UItester.jsp?modelName=gustavsson5.[Database section added 14 May 2014 after original online publication]
ILEI: a novel marker for epithelial–mesenchymal transition and poor prognosis in colorectal cancer
Authors: Gao Zhao‐Hua , Lu Chong , Wang Zhen‐Ning , Song Yong‐Xi , Zhu Jin‐Liang , Gao Peng , Sun Jing‐Xu , Chen Xiao‐Wan , Wang Mei‐Xian , Dong Yu‐Lan , Xu Hui‐Mian 
Published: April 2014

AimsAccumulating evidence over the past decade has shown that abnormal activation of epithelial to mesenchymal transition (EMT) contributes to tumour progression and metastasis in colorectal cancer (CRC). In this study, we investigated the expression of interleukin‐like EMT inducer (ILEI) and EMT‐associated markers (E‐cadherin, vimentin) in CRC tissues and determined the correlations between ILEI expression and clinicopathological characteristics, prognosis and EMT in CRC.Methods and resultsIn total, 194 patients diagnosed with CRC based on histopathological evaluation and those subjected to surgical resection at the First Hospital of China Medical University between 2003 and 2005 were examined. Immunohistochemical staining for ILEI, vimentin and E‐cadherin was performed for each specimen. Cytoplasmic overexpression of ILEI usually accompanied down‐regulation of E‐cadherin and positive expression of vimentin. Conversely, ILEI was simultaneously down‐regulated with overexpression of E‐cadherin and negative expression of vimentin. ILEI overexpression was associated significantly with T‐stage, N‐stage, TNM stage and EMT phenotype (P = 0.024, <0.001, <0.001 and <0.001, respectively). Multivariate analysis revealed that ILEI expression was an independent prognostic factor for patient survival.ConclusionsOur findings indicate that cytoplasmic ILEI expression is a potential marker of EMT and tumour progression in CRC. ILEI is an independent predictive factor associated with poor prognosis in CRC.
“SEEING” THE PAST: TEXT AND QUESTIONS OF HISTORY IN THE RĀJATARAṄGIṆĪ
Authors: KAUL SHONALEEKA 
Published: April 2014

ABSTRACTTraditional scholarly opinion has regarded Kalhaṇa's Rājataraṅgiṇī, the twelfth‐century Sanskrit chronicle of Kashmiri kings, as a work of history. This essay proposes a reinvestigation of the nature of the iconic text from outside the shadow of that label. It first closely critiques the positivist “history hypothesis,” exposing its internal contradictions over questions of chronology, causality, and objectivity as attributed to the text. It then argues that more than an empiricist historical account that modern historians like to believe it is—in the process bracketing out integral rhetorical, mythic, and didactic parts of the text—the Rājataraṅgiṇī should be viewed in totality for the kāvya (epic poem) that it is, which is to say, as representing a specific language practice that sought to produce meaning and articulated the poet's vision of the land and its lineages. The essay thus urges momentarily reclaiming the text from the hegemonic but troubled understanding of it as history—only to restore it ultimately to a more cohesive notion of historicality that is consistent with its contents. Toward this end, it highlights the concrete claim to epistemic authority that is asserted both by the genre of Sanskrit kāvya generally and by the Rājataraṅgiṇī in particular, and their conception of the poetic “production” of the past that bears a striking resonance with constructivist historiography. It then traces the intensely intertextual and value‐laden nature of the epistemology that frames the Rājataraṅgiṇī into a narrative discourse on power and ethical governance. It is in its narrativity and discursivity—its meaningful representation of what constitutes “true” knowledge of time and human action—that the salience of the Rājataraṅgiṇī may lie.
THE VERTIGO OF HISTORICAL ANALYSES IN A GLOBALIZING WORLD
Authors: Epple Angelika 
Published: April 2014

ABSTRACTIn this anthology, Joan Scott reconfigures her understanding of feminist history and thus contributes to a long overdue theoretical discussion on how we can write feminist history in a globalizing world. She traces both the history of gender history and the history of feminist movements. Scott's main source of inspiration is the French version of psychoanalysis following Lacan. In a further development of her pioneering 1986 article, “Gender: A Useful Category of Historical Analysis,” she points out that gender is neither a mere social construction nor a somehow biological referent (such as “sex”). Integrating the constructive criticism of her approach elaborated prominently by Judith Butler during the 1990s, Scott argues instead that gender is a historically and culturally specific attempt to resolve the dilemma of sexual difference. Sexual difference, for its part, is also far from referring simply to physically different male/female bodies. Sexual difference is, for Scott, a permanent quandary for modern subjects, a puzzle to which every society or culture finds specific answers.My reading of her book concentrates on two main questions that run like a thread through her considerations: First, how can we bridge the gap between a subject and a group? Second, how can we overcome binary oppositions and/or fixed categories and entities—a challenge that becomes even more important every day in a rapidly globalizing world. I broadly discuss the benefits and shortcomings of the pivotal role Scott ascribes to fantasy. Although the concept of fantasy is powerful and striking, particularly with reference to the concepts of “imagined communities” and “invented traditions,” coined by Eric Hobsbawm and Benedict Anderson, I find the Lacanian tone to be less convincing.
THE WORDS OF HISTORY
Authors: Froeyman Anton 
Published: April 2014

ABSTRACTIn From History to Theory, Kerwin Lee Klein writes a history of the central terms of the discipline of theory of history, such as “historiography,” “philosophy of history,” “theory of history,” and “memory.” Klein tells us when and how these terms were used, how the usage of some (“historiography” and “philosophy of history”) declined during the twentieth century, and how other terms (“theory” and “memory”) became increasingly popular. More important, Klein also shows that the use of these words is not innocent. Using words such as “theory” or “historiography” implies certain specific ideas about what the writing of history should be like, and how theoretical reflection on the nature of history and its writing relates to the practical issues of the discipline.In the second half of his book, Klein focuses more on the concept of memory and the memory boom since the later part of the 1980s. He observes that “memory” came to be seen as a kind of “counterhistory,” a postcolonial, fragmented, and personal alternative to the traditional mainstream discourse of history. Klein does not necessarily disagree with this view, but he does warn us about unwanted side effects. More specifically, he argues that the discourse of memory is surprisingly compatible with that of extremist right‐wing groups, and should be treated with suspicion. Although Klein certainly has a point, he presents it in a rather dogmatic fashion. However, a more nuanced version of Klein's criticism of memory can be developed by building on Klein's suggestion that there is an intimate connection between memory and identity.
OPACITY AND TRANSPARENCY IN HISTORICAL REPRESENTATIONS
Authors: Mitrović Branko 
Published: April 2014

ABSTRACTIn his latest book Frank Ankersmit develops a comprehensive philosophical perspective on the problem of the truth and reference of historical representations. The approach and the wider perspective of the book largely belong to what could be called the postmodernist paradigm, in spite of some recent attempts to interpret Ankersmit's recent work differently. Since his 1983 Narrative Logic Ankersmit has propounded the view that individual statements that constitute historical representations may have reference, but that representations themselves do not. His most recent book remains faithful to this position and elaborates it further. This essay examines Ankersmit's arguments as well as the assumptions and implications of this view.
DARWINIAN WE ARE NOT: COUNTERFACTUALISM AS THE NATURAL COURSE OF HISTORY
Authors: Hesketh Ian 
Published: April 2014

ABSTRACTThis article considers Peter Bowler's recent contribution to the genre of counterfactual history as exemplifying a “restrained” counterfactual framework, one that must downplay the role of contingency in the historical process in order to present what Bowler calls a more “natural course” of historical development. This restrained counterfactual methodology is discussed with reference to analogous debates within evolutionary science about the competing roles of contingency and convergence in the history of life, along with recent work done within the humanities about the more subtle nuances of counterfactual reasoning. Although there is little doubt that Bowler's study will help legitimize the genre of counterfactual history, it is argued that the role of contingency—once thought to be integral to the counterfactual—has been necessarily minimized in order to construct a narrative that is a plausible counterfactual history of science. It is in this way that Bowler's world without Darwin sheds light on our historiographical preconceptions about what makes for a plausible historical narrative.