bluuebunny/crossref_metadata_2025_split huggingface dataset:
OBESICA study: relationship between BMI and acute heart failure outcome
Authors: Miró Òscar , A. Rizzi Miguel , Herrero Pablo , Jacob Javier , Martín-Sánchez Francisco J. , Gil Víctor , Alquezar Aitor , Escoda Rosa , Llorens Pere 
Published: January 2016

Objective
The objective of this study was to investigate the relationship between BMI and outcome of acute heart failure (AHF).

Methods
We carried out a secondary analysis of the Epidemiology of Acute Heart Failure in Emergency department Registry (prospective, multicenter registry following a cohort of AHF patients from 34 Spanish emergency departments). Follow-up was at 3 months and 1 year after enrolment over the telephone and included medical history review. We analyzed revisits to the emergency department and death in relation to BMI. Significant differences were analyzed using proportional risk models including data on demographic variables, basal status, the acute episode, and patient outcome.

Results
We included 1562 patients: low weight 1.3%, normal weight 26.1%, overweight 45.3%, obese 24.3%, and morbidly obese 3.1%. BMI was inversely associated with mortality (P<0.001) but not with revisit (P=0.70). Compared with patients with normal weight, the proportional risk of death among patients with low weight was increased [hazard ratio (HR) 1.75, 95% confidence interval (CI) 0.95–3.23], being reduced in overweight, obese and morbidly obese patients (HR 0.72, 95% CI 0.59–0.89; HR 0.75, 95% CI 0.58–0.96; and HR 0.42, 95% CI 0.20–0.85, respectively). These differences disappeared after adjusting the model for confounding factors and other predictive variables of mortality.

Conclusion
BMI seems to be related to AHF and death, although this relationship disappeared on considering other prognostic factors and confounding variables. This finding limits the use of BMI by emergency physicians when estimating the risk of emergency department reconsultation or death in AHF patients.
Multifaceted ability of naturally occurring polyphenols against metastatic cancer
Authors: Zhou Qingyu , Bennett Lunawati L , Zhou Shufeng 
Published: January 2016

SummaryAlthough cancer metastases are known to be the main cause of cancer‐related deaths, truly effective antimetastatic therapeutics remain scarce in clinical practice. Naturally occurring polyphenols are the most abundant antioxidants in human diets. Many of them possess chemopreventive and chemotherapeutic properties against various types of cancer. Recent advances in understanding the molecular pathways that mediate cancer development and progression have led to an increase of interest in preclinical investigations on the mechanisms underlying anticancer activity of polyphenols. In particular, an increasing number of preclinical studies using cultured cells and animal models have demonstrated the inhibitory effects of polyphenols on tumour cell invasion and metastasis, thereby highlighting the potential of polyphenols against metastatic cancer. This review specifically addresses growing evidence of the capability of polyphenols to impair the invasion and migration of tumour cells through a diverse set of mechanisms, including downregulation of expression of matrix metalloproteinases, modulation of regulators of epithelial‐mesenchymal transition, interference with Met signalling, inhibition of nuclear factor‐kappa B mediated transcription, and so on. Given that metastasis occurs through a multistep process in which each step is regulated by a complex network of signalling pathways, the multi‐function and multi‐target characteristics of polyphenols render those promising candidates for effective adjuvant therapy against metastatic cancer.
Late spontaneous resolution of persistent molar pregnancy
Authors: Taylor F , Short D , Harvey R , Winter MC , Tidy J , Hancock BW , Savage PM , Sarwar N , Seckl MJ , Coleman RE 
Published: January 2016

ObjectiveTo determine the outcome of women with persistently raised but falling human chorionic gonadotrophin (hCG) levels 6 months after surgical evacuation of a molar pregnancy.DesignAn 11‐year retrospective review.SettingThe United Kingdom supra‐regional trophoblastic disease treatment centres at Weston Park Hospital (Sheffield) and Charing Cross Hospital (London).PopulationWomen with raised but falling serum human chorionic gonadotrophin (hCG) levels 6 months after evacuation of a molar pregnancy.MethodsRetrospective case note review of eligible women identified by the electronic databases held at each supra‐regional centre.Main outcome measuresThe proportion of women that attain normal hCG levels spontaneously without chemotherapy. In addition, rates of gestational trophoblastic neoplasia (GTN), drug resistance, disease relapse and overall survival are reported.ResultsThirty‐five women with molar pregnancy and raised but falling serum hCG levels continued surveillance 6 months after evacuation. Levels of hCG in 30 of the patients (86%) fell to normal levels spontaneously. One woman defaulted follow up prior to hCG normalisation (3%) and the remaining four women (11%) were treated with chemotherapy due to a plateau or rise in serum hCG levels indicating GTN. All treated women were successfully salvaged by either first (n = 1) or second line (n = 2) chemotherapy or found to have persistently raised low level hCG of uncertain clinical relevance (n = 1). No women developed relapsed disease and overall survival was 100%.ConclusionsWomen with a molar pregnancy and a raised but falling hCG level beyond 6 months from uterine evacuation can be safely observed with regular hCG monitoring and can usually avoid potentially toxic chemotherapy.Tweetable abstractWomen with treated molar pregnancy may avoid chemotherapy if 6‐month hCG levels are raised but falling.
Factors associated with disallowance of compulsory mental healthcare referrals
Authors: Fuglseth N. L. D. , Gjestad R. , Mellesdal L. , Hunskaar S. , Oedegaard K. J. , Johansen I. H. 
Published: January 2016

ObjectiveNorwegian studies report that a substantial amount of referrals for compulsory mental health care are disallowed at specialist assessment, at a rate that varies with referring agent. Knowledge on factors associated with disallowance could improve the practice of compulsory mental health care. This study aims to examine such factors, placing particular emphasis on the impact of referring agents.MethodThis study utilized data from the prospective, longitudinal cohort study ‘Suicidality in Psychiatric Emergency Admissions’ conducted at a Norwegian psychiatric emergency unit which served approximately 400 000 inhabitants. Data on referral, admission and patient characteristics were retrieved on compulsory admissions conducted between 1 May 2005 and 30 April 2008. Bivariate and logistic regression analyses and structural multilevel modelling were performed.ResultsAmong 2813 compulsory admissions, 764 were disallowed. Low competence in the referring agent, high GAF S score, observed alcohol or drug intoxication, reported suicide risk, and the presence of neurotic, stress‐related and somatoform disorders, personality disorders and other non‐specified diagnoses were associated with above average disallowance frequency. Non‐Norwegian ethnicity and schizophrenia spectrum disorders were associated with below average disallowance rates.ConclusionAmong several factors associated with disallowance, low symptom load was the strongest, whilst referring agent competence modestly affected disallowance rate.
Frontal cortex gray matter volume alterations in pathological gambling occur independently from substance use disorder
Authors: Zois Evangelos , Kiefer Falk , Lemenager Tagrid , Vollstädt‐Klein Sabine , Mann Karl , Fauth‐Bühler Mira 
Published: January 2016

AbstractNeuroimaging in pathological gambling (PG) allows studying brain structure independent of pharmacological/neurotoxic effects occurring in substance addiction. Because of high comorbidity of PG with substance use disorder (SUD), first results on structural deficits in PG are controversial. The current investigation is the first to examine gray matter (GM) volume alterations in PG controlling for the impact of SUD by comparing non‐comorbid (PGPURE) and two comorbid (PGALCOHOL and PGPOLY) groups. Two hundred and five individuals were included in the analysis: 107 patients diagnosed with PG and 98 healthy controls (HCs). We employed voxel‐based morphometry to look for GM volume differences between the groups controlling for age, smoking and depression. GM decreases in the superior medial and orbital frontal cortex occur independently of substance use in PGPURE compared with HCs. The frontal pattern of GM decrease was comparable with PGALCOHOL group where additionally GM volume was decreased in the anterior cingulate but increased in the amygdala. Moreover, regions in PGALCOHOL + POLY with reduced GM volume were the medial frontal, anterior cingulate and occipital lobe regions. PGALCOHOL + POLY not only exhibited structural deficits in comparison with HCs but also relative to PGPURE in the precuneus and post‐central gyrus. We demonstrated specific frontal cortex GM deficits in PG without SUD comorbidities. Whereas some target regions reported in earlier studies might result from comorbid substance abuse, there seems to be a core set of frontal alterations associated with addicted gambling behaviour independent of toxic substance effects.
No Compromise: Political Consequences of Moralized Attitudes
Authors: Ryan Timothy J. 
Published: January 2016

AbstractEvolutionary, neuroscientific, and cognitive perspectives in psychology have converged on the idea that some attitudes are moralized—a distinctive characteristic. Moralized attitudes reorient behavior from maximizing gains to adhering to rules. Here, I examine a political consequence of this tendency. In three studies, I measure attitude moralization and examine how it relates to approval of political compromise. I find that moralized attitudes lead citizens to oppose compromises, punish compromising politicians, and forsake material gains. These patterns emerge on economic and noneconomic issues alike and identify a psychological phenomenon that contributes to intractable political disputes.
“I found the truth in Foot Locker”: London 2011, Urban Culture, and the Post‐Political City
Authors: Millington Gareth 
Published: January 2016

AbstractThe article begins with an overview of what is implied in the notion of the “post‐political” before looking closely at post‐political interpretations of the 2011 London riots. It presents a critique of the restricted sense of political subjectivity in such accounts. It demonstrates how participation in the riots and their aftermath may be seen as indicative of an embryonic form of urban politics that works with and against the post‐political city. This discussion is illuminated by an analysis of the discursive space of London hip‐hop which reveals an ironic, complex and reflexive dialogue about identity, justice and politics that is far removed from the caricature offered by “strong” interpretations of the post‐political subject. This is then linked to readings of the post‐political city that place a welcome stress not only on the evacuation of the political dimension from the city, but also on the opportunities for the re‐emergence of the proto‐political.
Reregulating for Freshwater Enclosure: A State of Exception in Canterbury, Aotearoa New Zealand
Authors: Thomas Amanda C. , Bond Sophie 
Published: January 2016

AbstractIn this paper, we argue that democracy is increasingly indistinguishable from authoritarianism, in a process that is entangled with neoliberalisms. To build this argument, we examine a case study of central government intervention in regional environmental decision making in Aotearoa New Zealand through the lens of Agamben's “state of exception”. The intervention—unprecedented and unconstitutional—squeezed democratic spaces for decision making about freshwater and sought to smooth the way for capital accumulation. The audacity of government actions indicate, we argue, an abandonment of efforts to disguise neoliberal encroachments on democracy, known as the double truth tactic. Yet we also argue that in identifying this as a state of exception, we can examine it as part of a process and therefore demonstrate the possibilities for counter‐hegemonic actions to emerge.
Absence of ethnic differences in the pharmacokinetics of moxifloxacin, simvastatin, and meloxicam among three East Asian populations and Caucasians
Authors: Hasunuma Tomoko , Tohkin Masahiro , Kaniwa Nahoko , Jang In‐Jin , Yimin Cui , Kaneko Masaru , Saito Yoshiro , Takeuchi Masahiro , Watanabe Hiroshi , Yamazoe Yasushi , Uyama Yoshiaki , Kawai Shinichi 
Published: January 2016

AimTo examine whether strict control of clinical trial conditions could reduce apparent differences of pharmacokinetic (PK) parameters among ethnic groups.MethodsOpen‐label, single dose PK studies of moxifloxacin, simvastatin and meloxicam were conducted in healthy male subjects from three East Asian populations (Japanese, Chinese and Koreans) and one Caucasian population as a control. These three drugs were selected because differences in PK parameters have been reported, even though the backgrounds of these East Asian populations are similar. Moxifloxacin (400 mg) was administered orally to 20 subjects, and plasma and urine levels of moxifloxacin and its metabolite (M2) were measured. Simvastatin (20 mg) was given to 40 subjects, and plasma levels of simvastatin and simvastatin acid were measured. Meloxicam (7.5 mg) was given to 30 subjects and its plasma concentration was determined. Intrinsic factors (polymorphism of UGT1A1 for moxifloxacin, SLCO1B1 for simvastatin, and CYP2C9 for meloxicam) were also examined.ResultsAUCinf values for moxifloxacin, simvastatin and meloxicam showed no significant differences among the East Asian groups. Cmax values of moxifloxacin and simvastatin, but not meloxicam, showed significant differences. There were no significant differences of data for M2 or simvastatin acid. Genetic analysis identified significant differences in the frequencies of relevant polymorphisms, but these differences did not affect the PK parameters observed.ConclusionsAlthough there were some differences in PK parameters among the three East Asian groups, the present study performed under strictly controlled conditions did not reproduce the major ethnic differences observed in previous studies.
Prolonged clot lysis time increases the risk of a first but not recurrent venous thrombosis
Authors: Karasu Alev , Baglin Trevor P. , Luddington Roger , Baglin Caroline A. , van Hylckama Vlieg Astrid 
Published: January 2016

SummaryThe role of the fibrinolytic system in the development of venous thrombosis (VT) is unclear. We studied the risk of first and recurrent VT associated with reduced fibrinolysis, as measured by clot lysis time (CLT). We also studied the relationship between CLT and thrombin generation to determine if any relationship between CLT and VT was affected by thrombin generation. Analyses were performed in the Thrombophilia Hypercoagulability Environmental risk for Venous Thromboembolism Study, a two‐centre population‐based case‐control study, including 579 patients and 338 controls, with patients followed from the event to determine incidence of recurrent VT. Hypofibrinolysis was associated with a 1·8‐fold increased risk of a first VT [95% confidence interval (CI) 1·2–2·7]. Adjustment for sex, age, study location and Endogenous Thrombin Potential (ETP) did not change the result. The risk of VT was 2·9‐fold increased when the 90th percentiles of prolonged CLT and high ETP were combined, with the highest risk for unprovoked first events (Odds Ratio = 4·2, 95% CI 1·3–13·5). In the follow‐up study the Hazard Ratio for a recurrent VT associated with hypofibrinolysis was 1·5 (95% CI 0·9–2·6). A weak dose response effect was observed in relation to prolongation of CLT and recurrent VT. Although hypofibrinolysis constitutes a risk factor for a first VT, an association with recurrence is, at best, weak.
Hemin induces mitophagy in a leukemic erythroblast cell line
Authors: Fader Claudio Marcelo , Salassa Betiana Nebaí , Grosso Rubén Adrián , Vergara Agustín Nicolás , Colombo María Isabel 
Published: January 2016

Background InformationIn eukaryotic cells, autophagy is considered a lysosomal catabolic process which participates in the degradation of intracellular components in a vacuolar structure termed autolysosome. This pathway plays a significant role in the erythropoiesis process, contributing to the clearance of some organelles (such as mitochondria) that are not necessary in the mature red blood cells. Nevertheless, the role of autophagy in erythrocyte maturation has not been fully established.ResultsHere, we have demonstrated that hemin (a physiological erythroid maturation stimulator) is able to induce the expression of critical autophagic genes (i.e., Map1a1b (LC3), Beclin‐1 gen, Atg5) in an erythroleukemia cell type. We have also shown that hemin increased the size of autophagic vacuoles which were labelled with LC3 and the degradative lysosomal marker dye quenched‐bovine serum albumin. In addition, we have determined by Western blot a rise in the lipidated form of the autophagic protein LC3 (i.e., LC3‐II) upon hemin treatment. Moreover, we provide evidence that hemin induces mitochondrial membrane depolarisation and that mitochondria sequestration by autophagy requires the active form of the NIX protein.ConclusionsWe have found that the physiological erythroid maturation stimulator hemin is able to induce mitophagy in K562 cells, and that the autophagy adaptor NIX is necessary for mitophagy progression. K562 cells have been used as a relevant model to determine the possible therapeutic role of new differentiating compounds.SignificanceIt has been proposed that autophagy induction is a feasible new therapeutic key in fighting cancer. Our results suggest that hemin is favoring erythroid maturation by inducing an autophagic response in K562 cells, being a possible therapeutic candidate that may help in the chronic myelogenous leukemia (CML) treatment.
Effects of new‐generation inhibitors of the calcium‐activated chloride channel anoctamin 1 on slow waves in the gastrointestinal tract
Authors: Hwang Sung Jin , Basma Naseer , Sanders Kenton M , Ward Sean M 
Published: January 2016

Background and PurposeHigh‐throughput screening of compound libraries using genetically encoded fluorescent biosensors has identified several second‐generation. low MW inhibitors of the calcium‐activated chloride channel anoctamin 1 (CaCC/Ano1). Here we have (i) examined the effects of these Ano1 inhibitors on gastric and intestinal pacemaker activity; (ii) compared the effects of these inhibitors with those of the more classical CaCC inhibitor, 5‐nitro‐2‐(3‐phenylpropylalanine) benzoate (NPPB); (ii) examined the mode of action of these compounds on the waveform of pacemaker activity; and (iii) compared differences in the sensitivity between gastric and intestinal pacemaker activity to the Ano1 inhibitors.Experimental ApproachUsing intracellular microelectrode recordings of gastric and intestinal muscle preparations from C57BL/6 mice, the dose‐dependent effects of Ano1 inhibitors were examined on spontaneous electrical slow waves.Key ResultsThe efficacy of second‐generation Ano1 inhibitors on gastric and intestinal pacemaker activity differed significantly. Antral slow waves were more sensitive to these inhibitors than intestinal slow waves. CaCCinh‐A01 and benzbromarone were the most potent at inhibiting slow waves in both muscle preparations and more potent than NPPB. Dichlorophene and hexachlorophene were equally potent at inhibiting slow waves. Surprisingly, slow waves were relatively insensitive to T16Ainh‐A01 in both preparations.Conclusions and ImplicationsWe have identified several second‐generation Ano1 inhibitors, blocking gastric and intestinal pacemaker activity. Different sensitivities to Ano1 inhibitors between stomach and intestine suggest the possibility of different splice variants in these two organs or the involvement of other conductances in the generation and propagation of pacemaker activity in these tissues.
Hippocampal 5‐HT7 receptors signal phosphorylation of the GluA1 subunit to facilitate AMPA receptor mediated‐neurotransmission in vitro and in vivo
Authors: Andreetta Filippo , Carboni Lucia , Grafton Gillian , Jeggo Ross , Whyment Andrew D , van den Top Marco , Hoyer Daniel , Spanswick David , Barnes Nicholas M 
Published: January 2016

Background and PurposeThe 5‐HT7 receptor is a GPCR that is the target of a broad range of antidepressant and antipsychotic drugs. Various studies have demonstrated an ability of the 5‐HT7 receptor to modulate glutamatergic neurotransmission and cognitive processes although the potential impact upon AMPA receptors has not been investigated directly. The purposes of the present study were to investigate a direct modulation of the GluA1 AMPA receptor subunit and determine how this might influence AMPA receptor function.Experimental ApproachThe influence of pharmacological manipulation of the 5‐HT7 receptor system upon phosphorylation of GluA1 subunits was assessed by Western blotting of fractionated proteins from hippocampal neurones in culture (or proteins resident at the neurone surface) and the functional impact assessed by electrophysiological recordings in rat hippocampus in vitro and in vivo.Key Results5‐HT7 receptor activation increased cAMP and relative pCREB levels in cultures of rat hippocampal neurones along with an increase in phosphorylation (Ser845) of the GluA1 AMPA receptor subunit evident in whole neurone extracts and within the neurone surface compartment. Electrophysiological recordings in rat hippocampus demonstrated a 5‐HT7 receptor‐mediated increase in AMPA receptor‐mediated neurotransmission in vitro and in vivo.Conclusions and ImplicationsThe 5‐HT7 receptor‐mediated phosphorylation of the GluA1 AMPA receptor provides a molecular mechanism consistent with the 5‐HT7 receptor‐mediated increase in AMPA receptor‐mediated neurotransmission.
Safety, pharmacokinetics and pharmacodynamics of the anti‐hepcidin Spiegelmer lexaptepid pegol in healthy subjects
Authors: Boyce M , Warrington S , Cortezi B , Zöllner S , Vauléon S , Swinkels D W , Summo L , Schwoebel F , Riecke K 
Published: January 2016

Background and PurposeAnaemia of chronic disease is characterized by impaired erythropoiesis due to functional iron deficiency, often caused by excessive hepcidin. Lexaptepid pegol, a pegylated structured l‐oligoribonucleotide, binds and inactivates hepcidin.Experimental ApproachWe conducted a placebo‐controlled study on the safety, pharmacokinetics and pharmacodynamics of lexaptepid after single and repeated i.v. and s.c. administration to 64 healthy subjects at doses from 0.3 to 4.8 mg·kg−1.Key ResultsAfter treatment with lexaptepid, serum iron concentration and transferrin increased dose‐dependently. Iron increased from approximately 20 μmol·L−1 at baseline by 67% at 8 h after i.v. infusion of 1.2 mg·kg−1 lexaptepid. The pharmacokinetics showed dose‐proportional increases in peak plasma concentrations and moderately over‐proportional increases in systemic exposure. Lexaptepid had no effect on hepcidin production or anti‐drug antibodies. Treatment with lexaptepid was generally safe and well tolerated, with mild and transient transaminase increases at doses ≥2.4 mg·kg−1 and with local injection site reactions after s.c. but not after i.v. administration.Conclusions and ImplicationsLexaptepid pegol inhibited hepcidin and dose‐dependently raised serum iron and transferrin saturation. The compound is being further developed to treat anaemia of chronic disease.