bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact on oncological outcomes after radical prostatectomy for prostate cancer of converting soft tissue margins at the apex and bladder neck from tumour‐positive to ‐negative
Authors: Pak Sahyun , Park Sejun , Kim Myong , Go Heounjeong , Cho Yong Mee , Ahn Hanjong 
Published: July 2018

ObjectivesTo assess the impact of conversion from histologically positive to negative soft tissue margins at the apex and bladder neck on biochemical recurrence‐free survival (BCRFS) and distant metastasis‐free survival (DMFS) after radical prostatectomy (RP) for prostate cancer.Materials and MethodsThe records of 2 013 patients who underwent RP and intra‐operative frozen section (IFS) analysis between July 2007 and June 2016 were reviewed. IFS analysis of the urethra and bladder neck was performed, and if malignant or atypical cells remained, further resection with the aim of achieving histological negativity was carried out. Patients were divided into three groups according to the findings: those with a negative surgical margin (NSM), a positive surgical margin converted to negative (NCSM) and a persistent positive surgical margin (PSM).ResultsAmong the 2 013 patients, rates of NSMs, NCSMs and PSMs were 75.1%, 4.9%, and 20.0%, respectively. The 5‐year BCRFS rates of patients with NSMs, NCSMs and PSMs were 89.6%, 85.1% and 57.1%, respectively (P < 0.001). In both pathological (p)T2 and pT3 cancers, the 5‐year BCRFS rate for patients with NCSMs was similar to that for patients with NSMs, and higher than for patients with PSMs. The 7‐year DMFS rates of patients with NSMs, NCSMs and PSMs were 97.8%, 99.1% and 89.4%, respectively (P < 0.001). Among patients with pT3 cancers, the 7‐year DMFS rate was significantly higher in the NCSM group than in the PSM group (98.0% vs 86.7%; P = 0.023), but not among those with pT2 cancers (100% vs 96.9%; P = 0.616). The 5‐year BCRFS rate for the NCSM group was not significantly different from that of the NSM group among the patients with low‐ (96.3% vs 95.8%) and intermediate‐risk disease (91.1% vs 82.8%), but was lower than that of the NSM group among patients in the high‐risk group (73.2% vs 54.7%).ConclusionsConversion of the soft tissue margin at the prostate apex and bladder neck from histologically positive to negative improved the BCRFS and DMFS after RP for prostate cancer; however, the benefit of conversion was not apparent in patients in the high‐risk group.
β3‐Adrenoceptor stimulation of perivascular adipocytes leads to increased fat cell‐derived NO and vascular relaxation in small arteries
Authors: Bussey Charlotte E , Withers Sarah B , Saxton Sophie N , Bodagh Neil , Aldous Robert G , Heagerty Anthony M 
Published: July 2018

Background and PurposeIn response to noradrenaline, healthy perivascular adipose tissue (PVAT) exerts an anticontractile effect on adjacent small arterial tissue. Organ bath solution transfer experiments have demonstrated the release of PVAT‐derived relaxing factors that mediate this function. The present studies were designed to investigate the mechanism responsible for the noradrenaline‐induced PVAT anticontractile effect.Experimental ApproachIn vitro rat small arterial contractile function was assessed using wire myography in the presence and absence of PVAT and the effects of sympathomimetic stimulation on the PVAT environment explored using Western blotting and assays of organ bath buffer.Key ResultsPVAT elicited an anticontractile effect in response to noradrenaline but not phenylephrine stimulation. In arteries surrounded by intact PVAT, the β3‐adrenoceptor agonist, CL‐316243, reduced the vasoconstrictor effect of phenylephrine but not noradrenaline. Kv7 channel inhibition using XE 991 reversed the noradrenaline‐induced anticontractile effect in exogenously applied PVAT studies. Adrenergic stimulation of PVAT with noradrenaline and CL‐316243, but not phenylephrine, was associated with increased adipocyte‐derived NO production, and the contractile response to noradrenaline was augmented following incubation of exogenous PVAT with L‐NMMA. PVAT from eNOS−/− mice had no anticontractile effect. Assays of adipocyte cAMP demonstrated an increase with noradrenaline stimulation implicating Gαs signalling in this process.Conclusions and ImplicationsWe have shown that adipocyte‐located β3‐adrenoceptor stimulation leads to activation of Gαs signalling pathways with increased cAMP and the release of adipocyte‐derived NO. This process is dependent upon Kv7 channel function. We conclude that adipocyte‐derived NO plays a central role in anticontractile activity when rodent PVAT is stimulated by noradrenaline.
MGCD0103, a selective histone deacetylase inhibitor, coameliorates oligomeric Aβ25‐35‐induced anxiety and cognitive deficits in a mouse model
Authors: Huang Hei‐Jen , Huang Hsin‐Yu , Hsieh‐Li Hsiu Mei 
Published: July 2018

SummaryAimsRecently, histone deacetylase (HDAC) inhibitors are considered a possible therapeutic strategy in Alzheimer's disease (AD). However,HDACi treatments exhibit diverse functions with unfavorable effects inAD. Thus, the development of selectiveHDACi without side effects is urgently needed.MethodsHDACi, namely,BML210,MGCD0103,PXD101, and Droxinostat, were screened in mouse hippocampal primary cultures incubated with oligomeric Aβ25‐35(50 μmol/L).MGCD0103 was chosen for in vivo tests and was intraperitoneally injected into C57BL/6J mice (0.5 mg/kg, once per day) for 4 weeks following an intrahippocampalCA1 injection of oligomeric Aβ25‐35. Brain samples were collected for pathological analyses after the behavioral analyses including open‐ field test (OFT), elevated plus maze (EPM), Y‐maze, and Morris water maze (MWM).ResultsAmong theHDACi,MGCD0103 exhibited significant neuroprotection against the Aβ toxicity in primary cultures.MGCD0103 coattenuated cognitive deficits and anxiety against Aβ damage in mice.MGCD0103 further ameliorated pathological features such as the levels of acetylated histone 3 at Lys 9 site (H3K9) and α‐tubulin, synaptophysin, Aβ, tau protein phosphorylation, and serotonergic neuron loss against Aβ toxicity. Furthermore, chronicMGCD0103 treatment did not show liver or kidney toxicity in mice.ConclusionsThese results revealMGCD0103 could be a potential therapeutic agent againstAD.
Worth the wait: Children trade off delay and reward in self‐ and other‐benefiting decisions
Authors: Liu Shari , Gonzalez Gorana , Warneken Felix 
Published: July 2018

AbstractHuman prosocial behaviors are supported by early‐emerging psychological processes that detect and fulfill the needs of others. However, little is known about the mechanisms that enable children to deliver benefits to others at costs to the self, which requires weighing other‐regarding and self‐serving preferences. We used an intertemporal choice paradigm to systematically study and compare these behaviors in 5‐year‐old children. Our results show that other‐benefiting and self‐benefiting behavior share a common decision‐making process that integrates delay and reward. Specifically, we found that children sought to minimize delay and maximize reward, and traded off delays against rewards, regardless of whether these rewards were for the children themselves or another child. However, we found that children were more willing to invest their time to benefit themselves than someone else. Together, these findings show that from childhood, other‐ and self‐serving decisions are supported by a general mechanism that flexibly integrates information about the magnitude of rewards, and the opportunity costs of pursuing them. A video abstract of this article can be viewed at: https://youtu.be/r8S0DGe7f8Q
Differences in health outcomes associated with initial adherence to oral antidiabetes medications among veterans with uncomplicated Type 2 diabetes: a 5‐year survival analysis
Authors: Gatwood J. D. , Chisholm‐Burns M. , Davis R. , Thomas F. , Potukuchi P. , Hung A. , Kovesdy C. P. 
Published: July 2018

AbstractAimTo determine the association of adherence to oral antidiabetes medication with macrovascular and microvascular complications, time to insulin therapy, revascularization, admissions, and death among veterans with uncomplicated diabetes.MethodsThis was a retrospective cohort study using the Veterans Affairs Corporate Data Warehouse to examine 159 032 veterans diagnosed with uncomplicated diabetes during 2002–2014 and starting oral antidiabetes therapy for the first time. The first uncomplicated diabetes diagnosis was identified and confirmed by subsequent oral antidiabetes therapy initiation. Adherence was calculated from outpatient pharmacy records using the proportion of days covered over the first year of therapy. Health outcomes were observed up to 5 years beyond the first oral antidiabetes agent fill, and compared according to adherence status using Cox proportional hazards models adjusted for baseline demographic and clinical characteristics.ResultsDuring the first 5 years of oral antidiabetes treatment, people initially non‐adherent to oral antidiabetes therapy were more likely to experience myocardial infarction (hazard ratio 1.14, 95% CI 1.03–1.27) and ischaemic stroke (hazard ratio 1.22, 95% CI 1.05–0.1.42), or to die (hazard ratio 1.21; 95% CI 1.15–1.28). Veterans with <20% adherence to oral antidiabetes therapy in the first year had particularly high hazards for ischaemic stroke (hazard ratio 1.78, 95% CI 1.27–2.49) and all‐cause death (hazard ratio 1.33, 95% CI 1.17–151). Adherent people were more likely to be diagnosed with a microvascular complication or chronic kidney disease.ConclusionsPeople who are non‐adherent to treatment were more likely to experience detrimental health outcomes within the first 5 years of antidiabetes therapy. Adherence is paramount to disease management and this should be stressed from the time at which treatment is initiated.
Spared CA1 pyramidal neuron function and hippocampal performance following antisense knockdown of microRNA‐134
Authors: Morris Gareth , Brennan Gary P. , Reschke Cristina R. , Henshall David C. , Schorge Stephanie 
Published: July 2018

SummaryObjectiveInhibition of microRNA‐134 by an oligonucleotide antagomir (ant‐134) has been shown to produce powerful antiseizure effects in multiple models of epilepsy. However, to successfully translate the treatment to the clinic, it is important to assess what potential adverse effects it may have on naive brain tissue.MethodsTo investigate this, adult male Sprague‐Dawley rats were treated with either ant‐134 or a scrambled control sequence. Animals were later assessed for spatial navigation, before ex vivo slices were taken to assess the effects of microRNA‐134 knockdown on well‐defined measures of intrinsic and synaptic properties.ResultsHippocampal field potential recordings determined that silencing of microRNA‐134 by ant‐134 injection was associated with a reduction in epileptiform activity following application of 9 mmol/L K+. Nevertheless, rats performed normally in the novel object location test. Action potential waveforms and miniature excitatory synaptic currents recorded in CA1 pyramidal neurons were unaffected by ant‐134.SignificanceThese results demonstrate that ant‐134 confers a seizure‐protective effect without obvious interference with hippocampal neuronal properties or network function. These findings support further development of this novel approach to epilepsy treatment.
Combination of 5‐aminolevulinic acid and iron prevents skin fibrosis in murine sclerodermatous graft‐versus‐host disease
Authors: Liu Chi , Yang Xue , Zhu Ping , Fujino Masayuki , Ito Hidenori , Takahashi Kiwamu , Nakajima Motowo , Tanaka Tohru , Wang Jiucun , Zhuang Jian , Zou Hejian , Li Xiao‐Kang 
Published: July 2018

AbstractScleroderma or systemic sclerosis (SSc) is a clinically heterogeneous rheumatological autoimmune disease affecting the skin, internal organs and blood vessels. There is at present no effective treatment for this condition. Our study investigated the effects of 5‐aminolevulinic acid (5‐ALA), which is a precursor of haem synthesis, on graft‐vs‐host disease (GvHD)‐induced SSc murine model. Lymphocytes were intravenously injected from donor mice (B10.D2) into recipient BALB/c mice (recombination‐activating gene 2 (Rag‐2)‐null mice) deficient in mature T and B cells to induce sclerodermatous GvHD (scl‐GvHD). To investigate the effect of 5‐ALA on scl‐GvHD, combination of 5‐ALA and sodium ferrous citrate (SFC) was orally administered to the recipient mice for 9 weeks. 5‐ALA/SFC treatment significantly reduced progressive inflammation and fibrosis in the skin and ears. Furthermore, 5‐ALA/SFC suppressed mRNA expression of transforming growth factor‐β, type I collagen and inflammatory cytokines. These results indicate that the 5‐ALA/SFC combination treatment has a protective effect against tissue fibrosis and inflammation in a murine scl‐GvHD‐induced skin and ear inflammation and fibrosis. Furthermore, the efficacy of 5‐ALA/SFC suggests important implications of HO‐1 protective activity in autoimmune diseases, and therefore, 5‐ALA/SFC may have promising clinical applications. These findings suggested that the 5‐ALA/SFC treatment may be the potential strategies for SSc.
“Celebrated, not just endured:” Rethinking Winter Cities
Authors: Stout Madeleine , Collins Damian , Stadler Sophie L. , Soans Ranon , Sanborn Emma , Summers Robert J. 
Published: July 2018

AbstractA winter city is any urban centre that experiences a long, dark, cold, and/or snowy winter. The Winter Cities movement is a more precise concept, referring to cities taking an active role in becoming more appealing and functional in winter, primarily through physical interventions. The movement also has a social purpose, seeking to counter reclusion and “hibernation” in winter through greater use of the public realm. The movement is increasingly influential in policy, as part of a broader shift towards promoting livability and sustainability in cities. However, it has yet to receive sustained scholarly attention. This article brings the Winter City movement more fully into the academic sphere, describing its emergence, purpose, and key attributes, while also examining it critically for silences. Drawing on English‐ and German‐language publications, it places particular emphasis on the range of interventions and design approaches intended to promote greater use of outdoor public spaces, and an associated problematization of quasi‐public indoor environments.
Advantages, disadvantages and optimization of one‐stage and chromogenic factor activity assays in haemophilia A and B
Authors: Adcock D. M. , Strandberg K. , Shima M. , Marlar R. A. 
Published: July 2018

AbstractHaemophilia A and B diagnosis and disease severity classification are determined on the basis of results from factor VIII (FVIII) and factor FIX (FIX) activity assays, respectively. These assays are also used for potency labelling, postinfusion monitoring of factor replacement products and testing for FVIII/FIX inhibitors. This review focuses on activated partial thromboplastin time (APTT)‐based one‐stage assays (OSAs) and two‐stage chromogenic substrate assays (CSAs). Currently, there is considerable inter‐laboratory variability in the results obtained using OSAs, which can be intensified in a reagent‐specific manner by the presence of the new modified recombinant factor replacement products that are entering the market. Furthermore, the use of CSAs, which tend to show less variability, especially with the new modified products, is recommended in a number of clinical scenarios. Clinical laboratories may, therefore, need to establish CSAs for routine use. In this review, we aim to improve understanding and help establish best practices by describing the methodology behind OSAs and CSAs and highlighting assay advantages and limitations. We argue that there can be value in offering both assay methodologies in clinical laboratories that contribute to the care of patients with haemophilia A or B. Educating both laboratory scientists and clinicians about the strengths and weaknesses of each type of assay will help to establish the necessary dialogue that is key to ensuring not only that the appropriate assays are used in the right clinical situations, but also that the results are interpreted correctly.
IPO underpricing in the second and main markets: The case of the London Stock Exchange
Authors: Acedo‐Ramírez Miguel Á. , Díaz‐Mendoza Ana C. , Ruiz‐Cabestre Francisco J. 
Published: July 2018

AbstractThis study contributes to a broader knowledge of initial public offerings (IPOs) underpricing in second and main markets. We analyse the particular case of the London Stock Exchange. In the second market, we distinguish between those companies that do not meet the main market listing requirements and those companies that, even though they meet the main market listing requirements, decide to float on the second market. The results show that there is less underpricing for firms that float on the main market than for companies listed on the second market regardless of whether those companies meet the main market listing requirements. Moreover, behind the underpricing, we find several variables related to firm and/or offering characteristics and market information and observe different behaviours in the explanatory variables for underpricing depending on the group to which the company belongs.
Effectiveness of high rate and delayed detection ICD programming by race: A MADIT‐RIT substudy
Authors: Jackson Larry R. , Thomas Kevin L. , Polonsky Bronislava , Zareba Wojciech , Lahiri Marc , Saba Samir , McNitt Scott , Schuger Claudio , Daubert James P. , Moss Arthur J. , Kutyifa Valentina 
Published: July 2018

AbstractIntroductionData on inappropriate and appropriate ICD therapy, and efficacy of ICD programing strategies by race are limited.MethodsIn MADIT‐RIT, we evaluated the risk of ICD therapy by race, and the efficacy of high rate cut‐off ventricular tachycardia (VT) zone ≥200 beats per minute (bpm) (Arm B), or 60 seconds delay in VT zone 170–199 bpm (Arm C), compared to 2.5 seconds delay at 170 bpm (Arm A) among black and white patients.ResultsMADIT‐RIT enrolled 272 (20%) black and 1119 (80%) white patients. The risk of inappropriate therapy was similar among blacks and whites, HR 1.25, 95% CI (0.82–1.93), P = 0.30. High rate cut‐off or delayed VT therapy was associated with significant reductions in inappropriate therapy among whites, Arm B versus Arm A, HR 0.15, 95% CI (0.08–0.29), P < 0.0001, Arm C versus Arm A, HR 0.19, 95% CI (0.11–0.33), P < 0.001, and black individuals Arm B versus Arm A, HR 0.24, 95% CI (0.01–0.56), P = 0.0001, Arm C versus Arm A, HR 0.30, 95% CI (0.13–0.68), P = 0.004, P interaction > 0.10). However, delayed VT therapy was associated with a trend toward greater reduction in appropriate therapy in black individuals, HR 0.08, 95% CI (0.03–0.27), P < 0.0001 relative to white individuals, HR 0.27, 95% CI (0.16–0.43), P < 0.0001, P interaction = 0.077.ConclusionIn MADIT‐RIT, high rate and delayed detection ICD programming provided similar benefit with reductions in both inappropriate therapy and unnecessary appropriate therapy among black and white individuals.Clinicaltrials.gov identifierNCT00947310
EU Investors versus EU States: International Arbitration of Investment Disputes
Authors: Donaubauer Julian , Nunnenkamp Peter 
Published: July 2018

AbstractRecent information on investor‐state dispute settlement, collected by UNCTAD, suggests that European investors are more litigious than non‐European investors. Most of the intra‐EU claims for financial compensation are directed at relatively poor respondent states in Central Europe. However, private investors win surprisingly few intra‐EU disputes. The appointment bias of arbitrators and the composition of tribunals appear to matter for the outcome of investor‐state dispute settlement.
Pain in labor assessed from two discomfort aspects: Physical pain intensity and psychological stress state
Authors: Iizuka Yukie , Masaoka Naoki , Ohashi Kazutomo 
Published: July 2018

AbstractAimTo assess two discomfort aspects of pain in labor, physical pain intensity and psychological stress state, we analyzed the association between the two parameters.MethodsTwenty‐nine pregnant Japanese women with a singleton in 37–40 weeks of gestation were analyzed. Physical pain intensity was examined by the Numeric Rating Scale (NRS). Psychological stress state was measured by chromogranin A (CgA) in saliva. Data were collected thrice during labor (at 4–6 cm and 10 cm of cervical dilatation and immediately after delivery) and were accumulated from 4–6 cm and 10 cm of cervical dilatation. The study was approved by the Ethics Committees of Osaka University and Tokyo Women's Medical University.ResultsThe median NRS score (10, IQR = 10–18) and the median CgA in saliva (8.0, IQR = 4.3–12.0) pmol/mg at 10 cm of cervical dilatation were significantly higher than those at the other two time points (P < 0.05). Although there were no correlations between NRS scores and concentrations of CgA in saliva at the three time points, there was a significant correlation between accumulated NRS and accumulated CgA in saliva (r = 0.68, P = 0.000). There was a significant difference in the accumulated NRS scores (P = 0.005) but not in the accumulated concentrations of CgA between primiparae and multiparae.ConclusionWomen in labor perceived severe pain and psychological stress with similar patterns during labor. However, these parameters were independent and need to be measured to evaluate these two discomfort aspects.
Pain management of surgical abortion using transcutaneous acupoint electrical stimulation: An orthogonal prospective study
Authors: Wang Zedong , Chen Yong , Chen Chong , Zhao Liang , Chen Pinjie , Zeng Linchai , Xie Wenxia 
Published: July 2018

AbstractAimThis study aimed to evaluate the optimal combination of parameters for the management of pain during surgical abortion using transcutaneous acupoint electrical stimulation (TEAS).MethodsThis study recruited patients scheduled for surgical abortion between October 2014 and August 2015. The treatment protocol was created using three levels for each factor (stimulating time, acupoints, age, and parity). The primary outcomes were intraoperative visual analog scale (VAS), postoperative VAS, cervical relaxation degree and intraoperative blood loss. The secondary outcomes were the vital signs.ResultsStimulation time was associated with intraoperative VAS scores (P < 0.001), acupoints were associated with postoperative VAS scores (P = 0.037), and age was associated with postoperative VAS scores (P < 0.043). Parity (P = 0.025) was associated with heart rate. A comprehensive analysis of the parameters revealed the best levels for each (stimulation time: from 15 min before operation to immediate postoperative; acupoints: SP 6 and LR 3; patient age 25.1–30.0 years; and parity: G≥2P0A≥1). Seven patients did not complete follow‐up. The remaining 135 subjects did not show continuous vaginal bleeding, abdominal pain, fever or any other adverse effect.ConclusionDuring surgical abortion, TEAS stimulation from 15 min before operation to immediate postoperative, SP 6 and LR 3, age 25.1–30.0 years and G≥2P0A≥1 were associated with the best analgesic effect.