bluuebunny/crossref_metadata_2025_split huggingface dataset:
Management of immune thrombocytopenia in adults: a population‐based analysis of the French hospital discharge database from 2009 to 2012
Authors: Michel Marc , Suzan Florence , Adoue Daniel , Bordessoule Dominique , Marolleau Jean‐Pierre , Viallard Jean‐François , Godeau Bertrand 
Published: April 2015

SummaryThe present study describes the current clinical practice and hospital management of adults with immune thrombocytopenia (ITP) between 2009 and 2012 in France, based on the national discharge hospital database. Adult ITP patients were managed almost exclusively in public hospitals. A relatively stable number of patients, around 3200 per year, were hospitalized for ITP annually over the 4‐year period, about two‐thirds of whom were newly‐diagnosed ITP. Re‐hospitalizations tended to decrease over the study period. Intravenous immunoglobulin administration, concerning half of ITP hospitalized patients, and rituximab administration were stable over time, whereas a slight decrease of splenectomies was observed.
Aspirin‐induced histone acetylation in endothelial cells enhances synthesis of the secreted isoform of netrin‐1 thus inhibiting monocyte vascular infiltration
Authors: Passacquale Gabriella , Phinikaridou Alkystis , Warboys Christina , Cooper Margaret , Lavin Begona , Alfieri Alessio , Andia Marcelo E , Botnar Rene M , Ferro Albert 
Published: April 2015

Background and PurposeThere are conflicting data regarding whether netrin‐1 retards or accelerates atherosclerosis progression, as it can lead either to monocyte repulsion from or retention within plaques depending on its cellular source. We investigated the effect of aspirin, which is widely used in cardiovascular prophylaxis, on the synthesis of different isoforms of netrin‐1 by endothelial cells under pro‐inflammatory conditions, and defined the net effect of aspirin‐dependent systemic modulation of netrin‐1 on atherosclerosis progression.Experimental ApproachNetrin‐1 synthesis was studied in vitro using human endothelial cells stimulated with TNF‐α, with or without aspirin treatment. In vivo experiments were conducted in ApoE−/− mice fed with a high‐fat diet (HFD), receiving either aspirin or clopidogrel.Key ResultsTNF‐α‐induced NF‐κB activation up‐regulated the nuclear isoform of netrin‐1, while simultaneously reducing secreted netrin‐1. Down‐regulation of the secreted isoform compromised the chemorepellent action of the endothelium against monocyte chemotaxis. Aspirin counteracted TNF‐α‐mediated effects on netrin‐1 synthesis by endothelial cells through COX‐dependent inhibition of NF‐κB and concomitant histone hyperacetylation. Administration of aspirin to ApoE−/− mice on HFD increased blood and arterial wall levels of netrin‐1 independently of its effects on platelets, accompanied by reduced plaque size and content of monocytes/macrophages, compared with untreated or clopidogrel‐treated mice. In vivo blockade of netrin‐1 enhanced monocyte plaque infiltration in aspirin‐treated ApoE−/− mice.Conclusions and ImplicationsAspirin counteracts down‐regulation of secreted netrin‐1 induced by pro‐inflammatory stimuli in endothelial cells. The aspirin‐dependent increase of netrin‐1 in ApoE−/− mice exerts anti‐atherogenic effects by preventing arterial accumulation of monocytes.
A derivative of epigallocatechin‐3‐gallate induces apoptosis via SHP‐1‐mediated suppression of BCR‐ABL and STAT3 signalling in chronic myelogenous leukaemia
Authors: Jung Ji Hoon , Yun Miyong , Choo Eun‐Jeong , Kim Sun‐Hee , Jeong Myoung‐Seok , Jung Deok‐Beom , Lee Hyemin , Kim Eun‐Ok , Kato Nobuo , Kim Bonglee , Srivastava Sanjay K , Kaihatsu Kunihiro , Kim Sung‐Hoon 
Published: April 2015

Background and PurposeEpigallocatechin‐3‐gallate (EGCG) is a component of green tea known to have chemo‐preventative effects on several cancers. However, EGCG has limited clinical application, which necessitates the development of a more effective EGCG prodrug as an anticancer agent.Experimental ApproachDerivatives of EGCG were evaluated for their stability and anti‐tumour activity in human chronic myeloid leukaemia (CML) K562 and KBM5 cells.Key ResultsEGCG‐mono‐palmitate (EGCG‐MP) showed most prolonged stability compared with other EGCG derivatives. EGCG‐MP exerted greater cytotoxicity and apoptosis in K562 and KBM5 cells than the other EGCG derivatives. EGCG‐MP induced Src‐homology 2 domain‐containing tyrosine phosphatase 1 (SHP‐1) leading decreased oncogenic protein BCR‐ABL and STAT3 phosphorylation in CML cells, compared with treatment with EGCG. Furthermore, EGCG‐MP reduced phosphorylation of STAT3 and survival genes in K562 cells, compared with EGCG. Conversely, depletion of SHP‐1 or application of the tyrosine phosphatase inhibitor pervanadate blocked the ability of EGCG‐MP to suppress phosphorylation of BCR‐ABL and STAT3, and the expression of survival genes downstream of STAT3. In addition, EGCG‐MP treatment more effectively suppressed tumour growth in BALB/c athymic nude mice compared with untreated controls or EGCG treatment. Immunohistochemistry revealed increased caspase 3 and SHP‐1 activity and decreased phosphorylation of BCR‐ABL in the EGCG‐MP‐treated group relative to that in the EGCG‐treated group.Conclusions and ImplicationsEGCG‐MP induced SHP‐1‐mediated inhibition of BCR‐ABL and STAT3 signalling in vitro and in vivo more effectively than EGCG. This derivative may be a potent chemotherapeutic agent for CML treatment.
Spinal antinociceptive effects of the novel NOP receptor agonist PWT2‐nociceptin/orphanin FQ in mice and monkeys
Authors: Rizzi A , Sukhtankar D D , Ding H , Hayashida K , Ruzza C , Guerrini R , Calò G , Ko M C 
Published: April 2015

Background and purposeUsing an innovative chemical approach, peptide welding technology (PWT), a tetrabranched derivative of nociceptin/orphanin FQ (N/OFQ) has been generated and pharmacologically characterized. Both in vitro and in vivo PWT2‐N/OFQ displayed the same pharmacological profile to the natural ligand. It was more potent and produced longer‐lasting effects. The aim of the present study was to investigate the spinal effects of PWT2‐N/OFQ in nociceptive and neuropathic pain models in mice and non‐human primates.Experimental ApproachTail withdrawal assay in mice and monkeys was used as a nociceptive pain model and mechanical threshold in mice subjected to chronic constriction injury was used as a neuropathic pain model. The antinociceptive effects of spinally administered N/OFQ and PWT2‐N/OFQ were assessed in these models.Key ResultsPWT2‐N/OFQ mimicked the spinal antinociceptive effects of N/OFQ both in nociceptive and neuropathic pain models in mice as well as in non‐human primates displaying 40‐fold higher potency and a markedly prolonged duration of action. The effects of N/OFQ and PWT2‐N/OFQ were sensitive to the N/OFQ receptor (NOP) antagonist SB‐612111, but not to opioid receptor antagonists.Conclusions and ImplicationsThe present study has demonstrated that PWT2‐N/OFQ mimicked the antinociceptive effects of the natural peptide in rodents and non‐human primates acting as a potent and longer‐lasting NOP‐selective agonist. More generally, PWT derivatives of biologically active peptides can be viewed as innovative pharmacological tools for investigating those conditions and states in which selective and prolonged receptor stimulation promotes beneficial effects.
PKPD modelling to predict altered disposition of 1α,25‐dihydroxyvitamin D3 in mice due to dose‐dependent regulation of CYP27B1 on synthesis and CYP24A1 on degradation
Authors: Quach Holly P , Yang Qi J , Chow Edwin C , Mager Donald E , Hoi Stacie Y , Pang K Sandy 
Published: April 2015

Background and PurposeConcentrations of 1α,25‐dihydroxyvitamin D3 [1,25(OH)2D3], the active ligand of the vitamin D receptor, are tightly regulated by CYP27B1 for synthesis and CYP24A1 for degradation. However, the dose‐dependent pharmacokinetic (PK)‐pharmacodynamic (PD) relationship between these enzymes and 1,25(OH)2D3 concentrations has not been characterized.Experimental ApproachThe pharmacokinetics of 1,25(OH)2D3 were evaluated after administration of single (2, 60 and 120 pmol) and repeated (2 and 120 pmol q2d ×3) i.v. doses to male C57BL/6 mice. mRNA expression of CYP27B1 and CYP24A1 was examined by quantitative PCR and 1,25(OH)2D3 concentrations were determined by enzyme immunoassay.Key ResultsCYP27B1 and CYP24A1 changes were absent for the 2 pmol dose and biexponential decay profiles showed progressively shorter terminal half‐lives with increasing doses. Fitting with a two‐compartment model revealed decreasing net synthesis rates and increasing total clearances with dose, consistent with a dose‐dependent down‐regulation of renal CYP27B1 and the induction of renal/intestinal CYP24A1 mRNA expression. Upon incorporation of PD parameters for inhibition of CYP27B1 and induction of CYP24A1 to the simple two‐compartment model, fitting was significantly improved. Moreover, fitted estimates for the 2 pmol dose, together with the PD parameters as modifiers, were able to predict profiles reasonably well for the higher (60 and 120 pmol) doses. Lastly, an indirect response model, which considered the synthesis and degradation of enzymes, adequately described the PK and PD profiles.Conclusions and ImplicationsThe unique PK of exogenously administered 1,25(OH)2D3 led to changes in PD of CYP27B1 and CYP24A1, which hastened the clearance of 1,25(OH)2D3.
Inflammation in acute CNS injury: a focus on the role of substance P
Authors: Corrigan F , Vink R , Turner R J 
Published: April 2015

Recently, a number of reports have shown that neurogenic inflammation may play a role in the secondary injury response following acute injury to the CNS, including traumatic brain injury (TBI) and stroke. In particular substance P (SP) release appears to be critically involved. Specifically, the expression of the neuropeptide SP is increased in acute CNS injury, with the magnitude of SP release being related to both the frequency and magnitude of the insult. SP release is associated with an increase in blood–brain barrier permeability and the development of vasogenic oedema as well as neuronal injury and worse functional outcome. Moreover, inhibiting the actions of SP through use of a NK1 receptor antagonist is highly beneficial in both focal and diffuse models of TBI, as well as in ischaemic stroke, with a therapeutic window of up to 12 h. We propose that NK1 receptor antagonists represent a novel therapeutic option for treatment of neurogenic inflammation following acute CNS injury.Linked ArticlesThis article is part of a themed section on Inflammation: maladies, models, mechanisms and molecules. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2016.173.issue-4
Recovery of Amphibian and Reptile Assemblages During Old‐Field Succession of Tropical Rain Forests
Authors: Hernández‐Ordóñez Omar , Urbina‐Cardona Nicolas , Martínez‐Ramos Miguel 
Published: April 2015

AbstractConversion of tropical forests to agriculture affects vertebrate assemblages, but we do not know how fast or to what extent these assemblages recover after field abandonment. We addressed this question by examining amphibians and reptiles in secondary forests in southeastern Mexico. We used chronosequence data (12 secondary forests fallow for 1–23 yr and 3 old‐growth forest sites) to analyze successional trajectories and estimate recovery times of assemblage attributes for amphibians and reptiles. We conducted 6 surveys at each site over 14 mo (1200 person‐hours) and recorded 1552 individuals, including 25 species of amphibians and 36 of reptiles, representing 96 and 74 percent of the expected regional number of species, respectively. Abundance, species richness, and species diversity of amphibians increased rapidly with successional age, approaching old‐growth forest values in < 30 yr. Species richness and species diversity of reptiles reached old‐growth forest values in < 20 yr. By contrast, the abundance of reptiles and the assemblage composition of amphibians and reptiles recovered more slowly. Along the chronosequence, we observed more species replacement in reptile assemblages than in amphibian assemblages. Several species in the old‐growth forest were absent from secondary forests. Dispersal limitation and harsh conditions prevailing in open sites and early successional environments appear to preclude colonization by old‐growth forest species. Furthermore, short fallow periods and isolation of forest remnants lead to the formation of new assemblages dominated by species favored by human disturbances.
Inflammatory features of pancreatic cancer highlighted by monocytes/macrophages and CD4+ T cells with clinical impact
Authors: Komura Takuya , Sakai Yoshio , Harada Kenichi , Kawaguchi Kazunori , Takabatake Hisashi , Kitagawa Hirohisa , Wada Takashi , Honda Masao , Ohta Tetsuo , Nakanuma Yasuni , Kaneko Shuichi 
Published: April 2015

Pancreatic ductal adenocarcinoma (PDAC) is among the most fatal of malignancies with an extremely poor prognosis. The objectives of this study were to provide a detailed understanding of PDAC pathophysiology in view of the host immune response. We examined the PDAC tissues, sera, and peripheral blood cells of PDAC patients using immunohistochemical staining, the measurement of cytokine/chemokine concentrations, gene expression analysis, and flow cytometry. The PDAC tissues were infiltrated by macrophages, especially CD33+CD163+ M2 macrophages and CD4+ T cells that concomitantly express programmed cell death‐1 (PD‐1). Concentrations of interleukin (IL)‐6, IL‐7, IL‐15, monocyte chemotactic protein‐1, and interferon‐γ‐inducible protein‐1 in the sera of PDAC patients were significantly elevated. The gene expression profile of CD14+ monocytes and CD4+ T cells was discernible between PDAC patients and healthy volunteers, and the differentially expressed genes were related to activated inflammation. Intriguingly, PD‐1 was significantly upregulated in the peripheral blood CD4+ T cells of PDAC patients. Correspondingly, the frequency of CD4+PD‐1+ T cells was increased in the peripheral blood cells of PDAC patients, and this increase correlated to chemotherapy resistance. In conclusion, inflammatory conditions in both PDAC tissue and peripheral blood cells in PDAC patients were prominent, highlighting monocytes/macrophages as well as CD4+ T cells with influence of the clinical prognosis.
ADIPOQ polymorphism rs182052 is associated with clear cell renal cell carcinoma
Authors: Zhang Guiming , Gu Chengyuan , Zhu Yao , Luo Lei , Dong Dahai , Wan Fangning , Zhang Hailiang , Shi Guohai , Sun Lijiang , Ye Dingwei 
Published: April 2015

Recent studies have indicated that low circulating adiponectin concentrations are associated with a higher risk of several cancers, including renal cell carcinoma. In this case–control study, we examined the frequency of single nucleotide polymorphisms (rs182052G>A, rs266729C>G, and rs3774262G>A) in the adiponectin gene (ADIPOQ) in 1004 patients with clear cell renal cell carcinoma (ccRCC) compared with a group of healthy subjects (n = 1108). Fasting serum adiponectin concentrations were also examined. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). The association of serum adiponectin concentration with genetic variants was calculated using a multivariate linear regression model. A significantly higher ccRCC risk was associated with the rs182052 variant A allele (adjusted OR, 1.36 and 95% CI, 1.07–1.74 for AA vs GG, P = 0.013; adjusted OR, 1.27 and 95% CI, 1.04–1.56 for AA vs GG+AG, P = 0.019), and this positive association was more evident in overweight subjects. Fasting serum adiponectin was lower in subjects carrying A alleles of rs182052 in both ccRCC patients (β = −0.399, P = 0.018) and healthy controls (β = −0.371, P = 0.024). These results suggest that ADIPOQ rs182052 is significantly associated with ccRCC risk.
The potential role of benefit and burden finding in school engagement of young leukaemia survivors: an exploratory study
Authors: Tougas A.‐M. , Jutras S. , Bigras M. , Tourigny M. 
Published: April 2015

AbstractBackgroundChildhood cancer may radically change the daily lives of young survivors, particularly in school. Depending on the sense they derive from the experience of illness, survivors may go through profound transformations in the way they approach life.MethodsThis exploratory study reports on school engagement of cancer survivors by examining their perceptions of benefits and burdens in relation to their illness. Forty‐nine young Quebecers, previously diagnosed and treated for leukaemia, completed a questionnaire measuring their school engagement and participated in an interview focusing on the impact of cancer on their lives. Perceptions with regard to the presence and types of benefits and burdens were described and examined in light of participants' characteristics. An analysis of variance explored whether the presence/absence of benefits and burdens were associated with participants' scores regarding school engagement.ResultsMost participants mentioned benefits from having had cancer, and in particular benefits at an interpersonal level. Half of the participants mentioned burdens, mainly of a physical and psychological nature. Significant correlations indicated that (i) the older the survivors were, the more likely they were to report benefits in terms of qualities and strengths of character; (ii) the more time had elapsed since their diagnosis, the more survivors were likely to report psychological types of burdens; and (iii) children from single‐parent families reported more frequently having appreciated social or recreational activities compared with children from two‐parent families. One main effect indicated that school engagement was greater for survivors who perceived the presence of benefits. An interaction effect revealed that the perception of both benefits and burdens predicts the highest scores of school engagement.ConclusionsWhile the results reveal the promising potential that an optimistic yet realistic disposition has in regard to school engagement, more research is necessary to further our understanding of such a disposition.
The value of postoperative anticoagulants to improve flap survival in the free radial forearm flap: a systematic review and retrospective multicentre analysis
Authors: Swartz J.E. , Aarts M.C.J. , Swart K.M.A. , Disa J.J. , Gerressen M. , Kuo Y.‐R. , Wax M.K. , Grolman W. , Braunius W.W. 
Published: April 2015

BackgroundFree radial forearm flap (FRFF) reconstruction is a valuable technique in head and neck surgery, which allows closure of large defects while striving to maintain functionality. Anticoagulative drugs are often administered to improve flap survival, although evidence regarding effectiveness is lacking.Objective of reviewTo investigate the effectiveness of postoperative anticoagulants to improve survival of the FRFF in head and neck reconstruction.Type of reviewSystematic review and multicentre, individual patient data meta‐analysis.Search strategyMEDLINE, EMBASE, Web of Science and CINAHL were searched for synonyms of ‘anticoagulants’ and ‘free flap reconstruction’.Evaluation methodStudies were critically appraised for directness of evidence and risk of bias. Authors of the highest quality publications were invited to submit their original data for meta‐analysis.ResultsFive studies were of adequate quality, and data from four studies (80%) were available for meta‐analysis, describing 759 FRFF procedures. Anticoagulants used were as follows: aspirin (12%), low molecular weight dextran (18.3%), unfractioned heparin (28.1%), low molecular weight heparin (49%) and prostaglandin‐E1 (2.1%). Thirty‐one per cent did not receive anticoagulants. Flap failure occurred in 40 of 759 patients (5.3%) On univariate analysis, use of unfractioned heparin was associated with a higher rate of flap failure. However, these regimens were often administered to patients who had revision surgery of the anastomosis. In multivariate logistic regression analysis, anticoagulant use was not associated with improved flap survival or flap‐related complications.ConclusionsThe studied anticoagulative drugs did not improve FRFF survival or lower the rate of flap‐related complications. In addition, some anticoagulants may cause systemic complications.
Utility of biological sensor tags in animal conservation
Authors: Wilson A.D.M. , Wikelski M. , Wilson R.P. , Cooke S.J. 
Published: April 2015

AbstractElectronic tags (both biotelemetry and biologging platforms) have informed conservation and resource management policy and practice by providing vital information on the spatial ecology of animals and their environments. However, the extent of the contribution of biological sensors (within electronic tags) that measure an animal's state (e.g., heart rate, body temperature, and details of locomotion and energetics) is less clear. A literature review revealed that, despite a growing number of commercially available state sensor tags and enormous application potential for such devices in animal biology, there are relatively few examples of their application to conservation. Existing applications fell under 4 main themes: quantifying disturbance (e.g., ecotourism, vehicular and aircraft traffic), examining the effects of environmental change (e.g., climate change), understanding the consequences of habitat use and selection, and estimating energy expenditure. We also identified several other ways in which sensor tags could benefit conservation, such as determining the potential efficacy of management interventions. With increasing sensor diversity of commercially available platforms, less invasive attachment techniques, smaller device sizes, and more researchers embracing such technology, we suggest that biological sensor tags be considered a part of the necessary toolbox for conservation. This approach can measure (in real time) the state of free‐ranging animals and thus provide managers with objective, timely, relevant, and accurate data to inform policy and decision making.
Kidney transplant complications from undiagnosed benign prostatic hypertrophy
Authors: Lubetzky Michelle , Ajaimy Maria , Kamal Layla , de Boccardo Graciela , Akalin Enver , Kayler Liise 
Published: April 2015

AbstractBackgroundIt is estimated that approximately 50% of males over 50 have benign prostatic hypertrophy (BPH). BPH is underappreciated in anuric patients with end stage renal disease, and failure of diagnosis in this population can lead to complications after kidney transplantation.MethodsA single‐center retrospective review of male patients over 50 yr of age transplanted from January 1, 2010, until September 30, 2013, was performed. Outcomes assessed were as follows: graft survival, urinary retention, discharge with Foley catheter, and urinary tract infection (UTI).ResultsOf 147 patients, 17.0% were diagnosed with BPH before transplant, 19.0% received a BPH diagnosis after transplant, and 64% did not have BPH. Compared to those without BPH, a post‐transplant BPH diagnosis was associated with urinary retention during the transplant admission (0% vs. 46.4%, p < 0.01), discharge with Foley catheter (0% vs. 21.4%, p < 0.01), readmission related to urinary retention (0% vs. 46.4%, p < 0.01), and UTI (18.0% vs. 64.3%, p < 0.01). Patients with prior diagnosis of BPH and on therapy had similar outcomes to those without BPH.ConclusionsFollowing kidney transplant, urinary tract complications are more common in patients with BPH; however, being on medical therapy prior to transplantation diminishes the incidence of these complications significantly.