bluuebunny/crossref_metadata_2025_split huggingface dataset:
(4‐[6‐(4‐isopropoxyphenyl)pyrazolo [1,5‐a]pyrimidin‐3‐yl] quinoline) is a novel inhibitor of autophagy
Authors: Sheng Yue , Sun Bo , Guo Wen‐Ting , Liu Xiao , Wang Yu‐Chun , Xie Xin , Xiao Xiao‐Lin , Li Na , Dong De‐Li 
Published: June 2014

Background and PurposeAutophagy is an important intracellular degradation system, which is related to various diseases. In preliminary experiments we found that D4‐[6‐(4‐isopropoxyphenyl)pyrazolo [1,5‐a]pyrimidin‐3‐yl] quinoline (DMH1) inhibited autophagy responses. However DMH1 also inhibits the signalling pathway activated by bone morphogenetic protein‐4 (BMP4). The aim of the present study was to elucidate the inhibitory effects of DMH1 on autophagy and the underlying mechanisms.Experimental ApproachThe effects of DMH1 on autophagy responses were evaluated in cultures of different cell types and with different stimuli to induce autophagy, using Western blots, transmission electron microscopy and fluorescent microscopy.Key ResultsDMH1 inhibited starvation‐induced autophagy in cardiomyocytes, HeLa and MCF‐7 cells, without involving the signalling pathway of BMP4. DMH1 inhibited aminoimidazole carboxamide ribonucleotide (AICAR)‐ and rapamycin‐induced autophagy in HeLa and MCF‐7 cells. DMH1 reversed starvation‐ and AICAR‐induced inhibition of Akt, mammalian target of rapamycin (mTOR) and p70S6 kinase (S6K), and reversed rapamycin‐induced inhibition of mTOR and S6K. DMH1 reversed starvation‐induced decrease of the phosphorylated form of glycogen synthase kinase‐3 in MCF‐7 and HT29 cells. Activation of Akt and inhibition of autophagy induced by DMH1 were antagonized by an Akt specific inhibitor or by small interfering RNA for Akt in HeLa cells.Conclusion and ImplicationsDMH1 inhibited cellular autophagy responses in a range of cell types and the underlying mechanisms include activation of the Akt pathway.
Anti‐IL‐31 receptor antibody is shown to be a potential therapeutic option for treating itch and dermatitis in mice
Authors: Kasutani K , Fujii E , Ohyama S , Adachi H , Hasegawa M , Kitamura H , Yamashita N 
Published: June 2014

Background and PurposeIL‐31, which is described as a pruritogenic cytokine, is linked to the itching that is associated with allergic and non‐allergic eczema, but the precise pruritogenic mechanism of IL‐31 and its potential as a therapeutic target for atopic dermatitis (AD) have not been determined.Experimental ApproachWe investigated the effects of existing drugs on the scratching behaviour induced by an i.v. injection of IL‐31 to clarify whether IL‐31 induced pruritus indirectly. In addition, we studied the effects of an anti‐IL‐31 receptor α subunit (anti‐IL‐31 receptor α) neutralizing antibody on chronic pruritus‐inducing dermatitis in an AD‐like model to determine whether IL‐31 not only induces scratching behaviour, but is also the causative factor in an AD phenotype.Key ResultsThe scratching behaviour induced by an i.v. injection of IL‐31 was inhibited by pretreatment with an anti‐IL‐31 receptor α‐neutralizing antibody. In contrast, it was not inhibited significantly by a non‐sedative antihistamine (terfenadine), immunosuppressants (dexamethasone and tacrolimus), or a μ‐opioid receptor antagonist (naloxone). The anti‐IL‐31 receptor α‐neutralizing antibody reduced the ear swelling and dermatitis score in a chronic pruritus‐inducing AD‐like model. Moreover, treatment with the anti‐IL‐31 receptor α‐neutralizing antibody showed therapeutic effects on the dermatitis even if it was injected after the disease had developed.Conclusions and ImplicationsAnti‐IL‐31 receptor α is a potential novel therapeutic approach for escaping from the itch–scratch cycle and also a treatment for dermatitis in AD.
Ten‐year follow up after laparoscopic suture rectopexy for full‐thickness rectal prolapse
Authors: Foppa C. , Martinek L. , Arnaud J. P. , Bergamaschi R. 
Published: June 2014

AbstractAimStudies have shown that recurrence rates of full‐thickness rectal prolapse (FTRP) 5 years after surgery can quadruple at 10 years. This study aimed to evaluate the impact of laparoscopic suture rectopexy for FTRP on recurrence rates and functional outcome at a median follow up of 10 years.MethodProspectively collected data for patients who underwent laparoscopic suture rectopexy for FTRP between 1993 and 2006 were analysed. Laparoscopic rectopexy consisted of circumferential mobilization of the rectum down to the levator followed by suture suspension to promontory. Patients with preexisting constipation or who were unfit for general anaesthesia were not included. Incontinence, quality of life and constipation were assessed by validated scores. Recurrence‐free curves were generated using the Kaplan–Meier method.ResultsOne hundred and seventy‐nine patients with a median age of 62 (15–93) years including 174 women and five men underwent laparoscopic suture rectopexy. There was no mortality. The 30‐day complication rate was 4% (partial transection of the left ureter, pneumonia, urinary tract infection, urinary retention, superficial surgical site infection). Data on 172 patients (96%) were available at follow up. There were 10 recurrences of FTRP at 5‐year follow up giving a crude recurrence rate of 6%. The actuarial 10‐year recurrence rate was 20% (95% CI, 10.8–20.1). Follow‐up continence (P < 0.0001) and quality of life were better than preoperatively: lifestyle (P < 0.001), coping (P < 0.001), self‐perception (P < 0.005), embarrassment (P < 0.06). Constipation was unchanged.ConclusionLaparoscopic suture rectopexy led to few complications, a recurrence rate of 20%, improved continence and quality of life with no worsening of constipation at 10 years.
Heidegger the Metaphysician: Modes‐of‐Being andGrundbegriffe
Authors: Kelly Howard D. 
Published: June 2014

AbstractModes‐of‐being (Seinsarten) figure centrally inHeidegger's masterworkBeing and Time. Testimony to this isHeidegger's characterisation of two of his most celebrated enquiries—the Existential analytic and theZeuganalysis—as investigations into the respective modes‐of‐being of the entities concerned. Yet despite the importance of this concept, commentators disagree widely about what a mode‐of‐being is. In this paper,Isystematically outline and defend a novel and exegetically grounded interpretation of this concept. Strongly opposed to Kantian readings, such as those advocated byTaylorCarman andCristinaLafont,Iinterpret a mode‐of‐being as a universal that defines a district (Bezirk)—that is, a natural class of entities that ought to be conceptualised in a special way. As such, every mode‐of‐being plays an important metaphysical and epistemic role: serving both to unify a natural class of a high degree of generality and as theinterpretandumof an act yielding the basic‐concepts (Grundbegriffe) pertaining to the entities therein. In explicating and arguing for this interpretation,Iattribute a characteristically Aristotelian philosophical position to the earlyHeidegger, encompassing both metaphysical and epistemological realism and a conceptualist theory of universals.
Detecting past changes of effective population size
Authors: Nikolic Natacha , Chevalet Claude 
Published: June 2014

AbstractUnderstanding and predicting population abundance is a major challenge confronting scientists. Several genetic models have been developed using microsatellite markers to estimate the present and ancestral effective population sizes. However, to get an overview on the evolution of population requires that past fluctuation of population size be traceable. To address the question, we developed a new model estimating the past changes of effective population size from microsatellite by resolving coalescence theory and using approximate likelihoods in a Monte Carlo Markov Chain approach. The efficiency of the model and its sensitivity to gene flow and to assumptions on the mutational process were checked using simulated data and analysis. The model was found especially useful to provide evidence of transient changes of population size in the past. The times at which some past demographic events cannot be detected because they are too ancient and the risk that gene flow may suggest the false detection of a bottleneck are discussed considering the distribution of coalescence times. The method was applied on real data sets from several Atlantic salmon populations. The method called VarEff (Variation of Effective size) was implemented in the R package VarEff and is made available at https://qgsp.jouy.inra.fr and at http://cran.r-project.org/web/packages/VarEff.
Age‐specific reference range of prostate‐specific antigen and prostate cancer detection in population‐based screening cohort in Japan: Verification of Japanese Urological Association Guideline for prostate cancer
Authors: Kitagawa Yasuhide , Izumi Kouji , Sawada Kiyoshi , Mizokami Atsushi , Nakashima Kazuyoshi , Koshida Kiyoshi , Nakashima Takao , Miyazaki Kimiomi , Namiki Mikio 
Published: June 2014

ObjectivesTo investigate the age‐specific reference range of prostate‐specific antigen and clinical characteristics of screening‐detected cancer in prostate‐specific antigen‐based screening, and to verify the age‐specific prostate‐specific antigen cut‐offs in the Japanese Urological Association Guidelines.MethodsProstate‐specific antigen distributions were estimated in a total of 69 028 screening tests according to the age of the participants in population screening from 2000 to 2013. The age‐specific reference range of prostate‐specific antigen for detection of cancer was investigated by analyzing the receiver operating characteristic curves. Furthermore, the clinicopathological features of screening‐detected cancer with serum prostate‐specific antigen levels below the age‐specific prostate‐specific antigen cut‐off in the Japanese Urological Association Guidelines were also investigated.ResultsOf all 69 028 screens, 2053 prostate biopsies (2.97%) were carried out and 549 cases of cancer (0.79%) were diagnosed. The 95th percentiles in all participants aged 54–59, 60–64, 65–69 and 70–75 years old were 2.90, 3.60, 4.10, and 4.70 ng/mL, respectively. The optimal prostate‐specific antigen cut‐offs for cancer detection determined from the receiver operating characteristic curves were 2.3 and 2.6 for the age ranges 54–69 and 70–75 years, respectively. These values were lower than the age‐specific cut‐offs in the Japanese Urological Association Guidelines. Of all 137 patients with prostate‐specific antigen levels below the age‐specific cut‐offs in the Japanese Urological Association Guidelines, 80 (58.4%) had unfavorable clinicopathological features as active surveillance criteria.ConclusionsThe age‐specific reference range of prostate‐specific antigen might be lower than that recommended in the Japanese Urological Association Guidelines. An individualized and natural history‐adjusted screening system should be established for screening participants with low prostate‐specific antigen level.
Immunity to intestinal pathogens: lessons learned from Salmonella
Authors: McSorley Stephen J. 
Published: June 2014

SummarySalmonella are a common source of food‐ or water‐borne infection and cause a wide range of clinical disease in human and animal hosts. Salmonella are relatively easy to culture and manipulate in a laboratory setting, and the infection of laboratory animals induces robust innate and adaptive immune responses. Thus, immunologists have frequently turned to Salmonella infection models to expand understanding of host immunity to intestinal pathogens. In this review, I summarize current knowledge of innate and adaptive immunity to Salmonella and highlight features of this response that have emerged from recent studies. These include the heterogeneity of the antigen‐specific T‐cell response to intestinal infection, the prominence of microbial mechanisms to impede T‐ and B‐cell responses, and the contribution of non‐cognate pathways for elicitation of T‐cell effector functions. Together, these different issues challenge an overly simplistic view of host–pathogen interaction during mucosal infection, but also allow deeper insight into the real‐world dynamic of protective immunity to intestinal pathogens.
Cellular and molecular mechanisms underlying NOD2 risk‐associated polymorphisms in Crohn's disease
Authors: Strober Warren , Asano Naoki , Fuss Ivan , Kitani Atsushi , Watanabe Tomohiro 
Published: June 2014

SummaryThe discovery that polymorphisms in the NOD2 (nucleotide‐binding oligomerization domain containing 2) gene are associated with a greatly increased risk for the development of Crohn's disease has provided a means to achieve a deeper understanding of the dysregulation of mucosal immune responses to the commensal intestinal organisms that is thought to underlie this disease. NOD2 is a NOD‐like receptor (NLR) family member that senses and responds to bacterial wall peptides; thus, the most widely held view of the relation of the NOD2 polymorphisms with Crohn's disease is that these polymorphisms lead to deficient immune responses to gut bacteria, and these, in turn, lead to quantitative or qualitative changes in the bacterial population in the gut lumen or lamina propria that cause inflammation at this site. Initially, this view was based mainly on the observation that defective NOD2 function can result in reduced α‐defensin production by intestinal Paneth cells and that such impairment leads to loss of host defense against gut bacteria. In this review, we reconsider this possibility and marshal evidence that it is not in fact likely to be a prime element of Crohn's disease causation. More recently, evidence has been accumulating that the NOD2 dysfunction leads to Crohn's inflammation by inducing changes in the gut microbiome that influence immune effector or regulatory function. We review the strengths and weaknesses of this emerging hypothesis. Finally, we consider the possibility that NOD2 dysfunction can lead to inflammation because of a second and somewhat overlooked aspect of its function, that as an immunoregulator of innate immune responses. In particular, we review the body of evidence that NOD2 stimulation activates a cross‐tolerance response that downregulates and thus prevents excessive TLR responses that cause Crohn's inflammation.
In Defence of State Directed Enhancement
Authors: Fowler Tim 
Published: June 2014

AbstractThis article considers the ways in which a liberal society ought to view the potential to cognitively or physically enhance children. At present, the dominant approach in the literature is to leave this decision to parents. I suggest that the parental choice approach is often inadequate and fails to account properly for the interests of children and wider society in enhancement decisions. Instead I suggest that the state should play a greater role in determining when, and how, to enhance. To make this case, I compare the case of enhancement with existing practices of education, an area in which the state already plays a significant role. Finally I suggest that some concerns with a statist approach are not as serious as has been argued.
Periodontitis in coronary heart disease patients: strong association between bleeding on probing and systemic biomarkers
Authors: Bokhari Syed Akhtar H. , Khan Ayyaz A. , Butt Arshad K. , Hanif Mohammad , Izhar Mateen , Tatakis Dimitris N. , Ashfaq Mohammad 
Published: June 2014

AbstractAimFew studies have examined the relationship of individual periodontal parameters with individual systemic biomarkers. This study assessed the possible association between specific clinical parameters of periodontitis and systemic biomarkers of coronary heart disease risk in coronary heart disease patients with periodontitis.Materials and MethodsAngiographically proven coronary heart disease patients with periodontitis (n = 317), aged >30 years and without other systemic illness were examined. Periodontal clinical parameters of bleeding on probing (BOP), probing depth (PD), and clinical attachment level (CAL) and systemic levels of high‐sensitivity C‐reactive protein (CRP), fibrinogen (FIB) and white blood cells (WBC) were noted and analyzed to identify associations through linear and stepwise multiple regression analyses.ResultsUnadjusted linear regression showed significant associations between periodontal and systemic parameters; the strongest association (r = 0.629; p < 0.001) was found between BOP and CRP levels, the periodontal and systemic inflammation marker, respectively. Stepwise regression analysis models revealed that BOP was a predictor of systemic CRP levels (p < 0.0001). BOP was the only periodontal parameter significantly associated with each systemic parameter (CRP, FIB, and WBC).ConclusionIn coronary heart disease patients with periodontitis, BOP is strongly associated with systemic CRP levels; this association possibly reflects the potential significance of the local periodontal inflammatory burden for systemic inflammation.
Turnover and Knowledge Loss: An Examination of the Differential Impact of Production Manager and Worker Turnover in Service and Manufacturing Firms
Authors: Eckardt Rory , Skaggs Bruce C. , Youndt Mark 
Published: June 2014

AbstractThis research examines the comparative effects of production manager and worker turnover in service and manufacturing settings. We suggest that, due to the centrality of human action in services and the ability of manufacturers to insulate the technical core, service and manufacturing companies are differentially dependent on and impacted by the loss of production manager and worker knowledge. The results from a survey of 150 service and manufacturing firms provide partial support for this notion and show that turnover impacts these organizations differently. More specifically, we find that: (1) the negative impact of production worker turnover on firm performance is greater in service settings than in manufacturing settings; and (2) the negative impact of production worker turnover on firm performance is greater than the impact of production manager turnover in service firms. In addition, our findings show that organizational capital moderates the turnover–performance relationship for production workers in service firms.
Ear, nose and throat foreign bodies: The experience of the Pediatric Hospital of Turin
Authors: Pecorari Giancarlo , Tavormina Paolo , Riva Giuseppe , Landolfo Vincenzo , Raimondo Luca , Garzaro Massimiliano 
Published: June 2014

AimEar, nose and throat (ENT) foreign body (FB) injuries represent an emerging problem in the paediatric population because of their human and social costs. The aim of the study is the site‐specific evaluation of FB injuries in the paediatric population referred to the emergency department of the Pediatric Hospital of Turin.MethodsThis retrospective analysis was carried out sifting medical reports between 2002 and 2011. We collected information about 338 patients’ FB characteristics, complications and hospitalisation.ResultsThe mean age was 4.2 ± 2.9 years. Nose and ear are the most involved anatomical sites, followed by pharynx, oesophagus and trachea‐bronchi. The most common FBs are balls, beads and toys parts (29.6%), followed by fishbones (13.6%). A lower mean age is observed in tracheo‐bronchial and oesophageal FBs. The 9.2% of cases reported complications.ConclusionsA quick and proper diagnosis followed by an effective treatment of FB injuries and their complication is mandatory. Surveillance registries have a key role in prevention and management of FB injuries; useful information can be obtained also for nurse and ENT specialist training in order to create professionals ready to recognise and manage FB injuries in the most effective way.
Discriminating four temperate lakes using phytoplankton absorption spectra
Authors: Kalenak David 
Published: June 2014

AbstractPhotosynthetic algal particles are integral to the ecology and optical quality of lake water. Their absorption properties (photopigments, often >20 per species) are modified in response to drivers that affect the intensity and spectral distribution of incident solar energy, including the plankton itself, water, and chromophoric dissolved and suspended particulate matter. The present study was based on the hypothesis that this complex interaction imparts a distinguishing optical signature in lakes. A multivariate discriminant model was applied to in situ phytoplankton spectra from four temperate lakes of different trophy to test this hypothesis. The analysis identified a small set of wavelengths with significant discriminatory power that permitted near‐perfect lake classification solely on the basis of the aggregate spectral features in the absorption coefficient of phytoplankton. Furthermore, weighting the sample spectra by the corresponding standard deviation increased model robustness considerably, as shown in both unsupervised and supervised classification. Also presented are additional multivariate techniques that allow for the visualization of the data structure to help explain contributing factors. The results support the possibility of utilizing the optical properties of the phytoplankton to monitor ecological change in lakes.
The state as a symbol or a means to an end: internal border changes in multinational federations
Authors: Basta Karlo 
Published: June 2014

AbstractFederalism is an important institutional option for the management of difference in multinational states. A number of scholars have argued that the internal boundaries of such states should divide each constituent group into several federal units. In theory, boundary engineering of this type should activate cross‐cutting cleavages, subvert secessionist movements and, ultimately, foster political integration and stability. This article, by contrast, demonstrates the conditions under which the subdivision of territorial units can destabilise polities. Where statehood is a central symbol in nationalist narratives of constituent groups, the fragmentation of the sub‐state unit will be perceived as a threat to national identity of the group in question. The article compares formerYugoslavia andNigeria, two cases in which such processes led to divergent outcomes.
Reconstructed nationalism inTaiwan: a politicised and economically driven identity
Authors: Chen Rou‐lan 
Published: June 2014

AbstractSince the late 1980s,Taiwan has been engulfed in waves of both democratisation and integration with mainlandChina. These two waves have pulled identity reconstruction inTaiwan in two different directions. In the process of democratisation, a shift to a majoritarian system encouraged aTaiwanese renaissance on the political platform and consequently led to the deconstruction ofChinese identity. On the other hand, in the 1990s, with the high mobility of capital and people across theTaiwanStrait, close economic ties could have put the brakes onTaiwan independence movements. Hence, this paper uses random coefficient models to explore how the democratic transition and increasing cross‐strait relations brought about psychological and structural mechanisms that motivated people to opt for identity change inTaiwan. It also attempts to investigate how people dealt with the dissonance between rising Taiwanese nationalism and the economic interests that deterred a radical Taiwanese identity.