bluuebunny/crossref_metadata_2025_split huggingface dataset:
Noradrenergic signaling in the VTA modulates cocaine craving
Authors: Solecki Wojciech Barnaba , Szklarczyk Klaudia , Pradel Kamil , Kwiatkowska Krystyna , Dobrzański Grzegorz , Przewłocki Ryszard 
Published: June 2017

AbstractExposure to drug‐associated cues evokes drug‐seeking behavior and is regarded as a major cause of relapse. Conditional stimulus upregulates noradrenaline (NA) system activity, but the drug‐seeking behavior depends particularly on phasic dopamine signaling downstream from the ventral tegmental area (VTA). The VTA dopamine‐ergic activity is regulated via the signaling of alpha1‐adrenergic and alpha2‐adrenergic receptors (α1‐ARs and α2‐ARs); thus, the impact of the conditional stimulus on drug‐seeking behavior might involve NAergic signaling in the VTA. To date, the role of VTA ARs in regulating cocaine seeking was not studied. We found that cocaine seeking under extinction conditions in male Sprague–Dawley rats was attenuated by intra‐VTA prazosin or terazosin—two selective α1‐AR antagonists. In contrast, cocaine seeking was facilitated by intra‐VTA administration of the selective α1‐AR agonist phenylephrine as well as α2‐AR antagonist RX 821002, whereas the selective β‐AR antagonist propranolol had no effects. In addition, blockade of α1‐AR in the VTA prevented α2‐AR antagonist‐induced enhancement of cocaine seeking. Importantly, the potential non‐specific effects of the VTA AR blockade on cocaine seeking could be excluded, because none of the AR antagonists influenced sucrose seeking under extinction conditions or locomotor activity in the open field test. These results demonstrate that NAergic signaling potently and selectively regulates cocaine seeking during early cocaine withdrawal via VTA α1‐AR and α2‐AR but not β‐AR. Our findings provide new insight into the NAergic mechanisms that underlie cocaine craving.
Novel role and regulation of HDAC4 in cocaine‐related behaviors
Authors: Penrod Rachel D. , Carreira Maria B. , Taniguchi Makoto , Kumar Jaswinder , Maddox Stephanie A. , Cowan Christopher W. 
Published: June 2017

AbstractEpigenetic mechanisms have been proposed to contribute to persistent aspects of addiction‐related behaviors. One family of epigenetic molecules that may regulate maladaptive behavioral changes produced by cocaine use are the histone deacetylases (HDACs)—key regulators of chromatin and gene expression. In particular, the class IIa HDACs (HDAC4, HDAC5, HDAC7 and HDAC9) respond to changes in neuronal activity by modulating their distribution between the nucleus and cytoplasm—a process controlled in large part by changes in phosphorylation of conserved residues. Cocaine triggers a transient nuclear accumulation of HDAC5 that functions to limit the development of cocaine reward behavior. However, the role and regulation of the close family member, HDAC4, in cocaine behaviors remain largely unknown. In this study, we report that cocaine and cAMP signaling in striatum produced differential phosphorylation and subcellular localization of HDAC4 and HDAC5. Unlike HDAC5, cocaine exposure induced a modest hyperphosphorylation and nuclear export of HDAC4. Genetic deletion of HDAC4 in the nucleus accumbens reduced acute cocaine‐produced locomotion, maximum locomotor sensitization and cocaine reward‐related behavior. Interestingly, overexpression of an HDAC4 cytoplasm‐concentrated mutant (S266E) increased cocaine reward behavior in the cocaine conditioned place preference assay, suggesting that cocaine‐induced nuclear export of HDAC4 might function to facilitate the development of cocaine reward behaviors through a role in the cell cytoplasm. Together, our findings suggest that, despite high sequence homology, HDAC4 and HDAC5 are oppositely regulated by cocaine‐induced signaling in vivo and have distinct roles in regulating cocaine behaviors.
Locomotor sensitization is expressed by ghrelin and D1 dopamine receptor agonist in the nucleus accumbens core in amphetamine pre‐exposed rat
Authors: Jang Ju Kyong , Kim Wha Young , Cho Bo Ram , Lee Jung Won , Kim Jeong‐Hoon 
Published: June 2017

AbstractGhrelin modulates mesolimbic dopaminergic pathways in the brain in addition to its role in feeding. We investigated what roles ghrelin in the nucleus accumbens (NAcc) core may play in mediating locomotor activating effects of amphetamine (AMPH). First, when rats were administered with AMPH (1 mg/kg, i.p.) following a bilateral microinjection of ghrelin (0.1 or 0.5 μg/side) into the NAcc core, their locomotor activity was significantly enhanced, while these effects were blocked by co‐microinjection of ghrelin receptor antagonist (0.5 μg/side) into this site. Second, we pre‐exposed rats to saline or amphetamine (1 mg/kg, i.p.) every 2 to 3 days for a total of four times. After 2 weeks of drug‐free withdrawal period, we examined the effect of saline, ghrelin (0.5 μg/side), D1 dopamine receptor agonist, SKF81297 (0.5 μg/side) or ghrelin (0.5 μg/side) + SKF81297 (0.5 μg/side) directly microinjected into the NAcc core on locomotor activity. When we measured rats' locomotor activity for 1 hour immediately following microinjections, only ghrelin + SKF81297 produces sensitized locomotor activity, while all others have no effects. These results suggest that ghrelin may have a distinct role in the NAcc core to provoke the sensitized locomotor activity induced by psychomotor stimulants, and further, it may produce these effects by interaction with D1 dopamine receptors.
How Does CEO Age Affect Firm Risk?
Authors: Chowdhury Jaideep , Fink Jason 
Published: June 2017

AbstractPrevious research demonstrates that older CEOs are associated with lower firm equity risk and fewer R&D expenditures. We examine the risk‐taking behavior of CEOs and find that not only do older CEOs invest in less R&D, they do so sub‐optimally, in the sense that CEO age distorts the effect of q on R&D investment decisions. We find that it is specifically through the channel of R&D investment that CEO age is associated with the reduction in firm equity risk. Consistent with the sub‐optimality of these distortions, firms with more effective corporate governance do not exhibit these associations.
Who's Leaving Money on the Table? Evidence from IPOs within Business Groups
Authors: Kim Woojin , Lim Chan , Yoon Tae Jun 
Published: June 2017

AbstractThis paper examines how controlling shareholders of business groups may pass on the cost of IPO underpricing to minority shareholders. Based on a sample of IPOs made in Korea, we find that sale of secondary shares in Korea in general does not reduce underpricing as it does in the US. However, we do find less underpricing or even overpricing when the offered shares are directly sold by the controlling shareholders. On the other hand, sale of secondary shares held by affiliated firms leads to a negative market reaction for the selling firms, implying a direct wealth transfer from shareholders of affiliated firms to IPO subscribers. These findings suggest that minority shareholders in certain affiliated firms, or scapegoats, may bear the cost of underpricing while controlling shareholders of the business group remain effectively protected instead.
Sperm DNA damage measured by sperm chromatin structure assay in men with a history of undescended testes
Authors: van Brakel J. , Dinkelman‐Smit M. , de Muinck Keizer‐Schrama S. M. P. F. , Hazebroek F. W. J. , Dohle G. R. 
Published: June 2017

SummaryThe aim of this study was to compare sperm DNA damage between men with a history of congenital undescended testis (UDT) and men with a history of acquired UDT. A long‐term follow‐up study of men with previous UDT was performed. Fifty men with congenital UDT who had undergone orchiopexy at childhood age, 49 men with acquired UDT after a ‘wait‐and‐see’‐protocol (e.g. awaiting spontaneous descent until puberty and perform an orchiopexy in case of non‐decent), and 22 healthy proven fertile men were included. The DNA fragmentation index (DFI) using sperm chromatin structure assay (SCSA) was used to express the level of sperm DNA damage. Decreased fertility potential was considered if DFI was above 30%. Sperm DNA damage was not statistically different between cases of congenital and acquired UDT. DFI was significantly more often >30% in the complete group of men with congenital UDT (9/50; 18%) and in the subgroup with bilateral congenital UDT (3/7; 43%) in comparison with the controls (none) (p‐value 0.049 and 0.01, respectively). Age at orchiopexy in congenital UDT had no statistical effect on DNA damage. In men with acquired UDT, DFI did not statistically differ between those having undergone orchiopexy and those experiencing spontaneous descent. This study supports the hypothesis that UDT is a spectrum representing both congenital UDT and acquired UDT. Sperm DNA damage at adult age is not influenced by age at orchiopexy in congenital UDT cases and by orchiopexy or spontaneous descent in acquired UDT cases.
Prediction of sustained fetal toxicity induced by ketoprofen based on PK/PD analysis using human placental perfusion and rat toxicity data
Authors: Tanaka Shingo , Kanagawa Takeshi , Momma Kazuo , Hori Satoko , Satoh Hiroki , Nagamatsu Takeshi , Fujii Tomoyuki , Kimura Tadashi , Sawada Yasufumi 
Published: June 2017

AimWe encountered a case of fetal toxicity due to ductus arteriosus (DA) constriction in a 36‐week pregnant woman who had applied multiple ketoprofen patches. The aim of the present study was to present the case and develop a model to predict quantitatively the fetal toxicity risk of transdermal administration of ketoprofen.MethodsHuman placenta perfusion studies were conducted to estimate transplacental pharmacokinetic (PK) parameters. Using a developed model and these parameters, human fetal plasma concentration profiles of ketoprofen administered to mothers were simulated. Using pregnant rats, DA constriction and fetal plasma drug concentration after ketoprofen administration were measured, fitted to an Emax model, and extrapolated to humans.ResultsTransplacental transfer value at the steady state of ketoprofen was 4.82%, which was approximately half that of antipyrine (passive marker). The model and PK parameters predicted almost equivalent mother and fetus drug concentrations at steady state after transdermal ketoprofen administration in humans. Maximum DA constriction and maximum plasma concentration of ketoprofen after administration to rat dams were observed at different times: 4 h and 1 h, respectively. The model accurately described the delay in DA constriction with respect to the fetal ketoprofen concentration profile. The model with effect compartment and the obtained parameters predicted that use of multiple ketoprofen patches could potentially cause severe DA constriction in the human fetus, and that fetal toxicity might persist after ketoprofen discontinuation by the mother, as observed in our case.ConclusionThe present approach successfully described the sustained fetal toxicity after discontinuing the transdermal administration of ketoprofen.
Covariate Selection with Group Lasso and Doubly Robust Estimation of Causal Effects
Authors: Koch Brandon , Vock David M. , Wolfson Julian 
Published: June 2017

Summary
The efficiency of doubly robust estimators of the average causal effect (ACE) of a treatment can be improved by including in the treatment and outcome models only those covariates which are related to both treatment and outcome (i.e., confounders) or related only to the outcome. However, it is often challenging to identify such covariates among the large number that may be measured in a given study. In this article, we propose GLiDeR (Group Lasso and Doubly Robust Estimation), a novel variable selection technique for identifying confounders and predictors of outcome using an adaptive group lasso approach that simultaneously performs coefficient selection, regularization, and estimation across the treatment and outcome models. The selected variables and corresponding coefficient estimates are used in a standard doubly robust ACE estimator. We provide asymptotic results showing that, for a broad class of data generating mechanisms, GLiDeR yields a consistent estimator of the ACE when either the outcome or treatment model is correctly specified. A comprehensive simulation study shows that GLiDeR is more efficient than doubly robust methods using standard variable selection techniques and has substantial computational advantages over a recently proposed doubly robust Bayesian model averaging method. We illustrate our method by estimating the causal treatment effect of bilateral versus single-lung transplant on forced expiratory volume in one year after transplant using an observational registry.
Clinically distinct trajectories of fatigue and their longitudinal relationship with the disturbance of personal goals following a cancer diagnosis
Authors: Müller Fabiola , Tuinman Marrit A. , Janse Moniek , Almansa Josué , Sprangers Mirjam A. G. , Smink Ans , Ranchor Adelita V. , Fleer Joke , Hagedoorn Mariët 
Published: June 2017

ObjectivesMost studies on fatigue in patients with cancer aggregate its prevalence and severity on a group level, ignoring the possibility that subgroups of patients may differ widely in their development of fatigue. This study aimed to identify subgroups of patients with clinically distinct trajectories of fatigue from diagnosis to 18 months post‐diagnosis. As fatigue might trigger goal disturbance, the study also identified trajectories of concrete and abstract goal disturbance and longitudinally examined their co‐occurrence with fatigue.DesignProspective design with quantitative and qualitative method of data collection.MethodsPatients with colorectal cancer (n = 183) reported on their levels of fatigue and goal disturbance shortly after diagnosis (T1) and at 7 months (T2) and 18 months (T3) post‐diagnosis. Growth mixture model analyses were performed to identify trajectories of fatigue and goal disturbance. Guidelines for the clinical relevance of fatigue were applied.ResultsFour clinically distinct trajectories of fatigue were identified as follows: (1) persistent severe fatigue (25.4%), (2) moderate fatigue (56.1%), (3) no fatigue (13.8%), and (4) rapidly improving fatigue (4.7%). The majority of patients with cancer reported high disturbance of their concrete goals, while high disturbance of abstract goals was less evident. Fatigue and concrete goal disturbance co‐occurred longitudinally.ConclusionsThe fatigue and goal disturbance experienced from diagnosis to 18 months post‐diagnosis differ considerably for subgroups of patients with cancer. Fatigue and concrete goal disturbance are persistent burdens in the majority of patients. Investigating symptom burden beyond average trends can guide clinicians to identify patients most in need for treatment. Targeting goal disturbance might benefit the psychological well‐being in patients suffering from persistent symptoms.
Statement of contribution

What is already known on this subject?

Fatigue is a common and distressing symptom at all stages of the cancer experience.

Earlier studies suggest that many patients recover from fatigue after treatment completion.

Patients with cancer experience disturbance in their personal goals, which is related to poor psychological well‐being.

What does this study add?

Developments of fatigue and goal disturbance differ between subgroups of patients with cancer but co‐occur within these subgroups.

About 30% of the patients experience severe fatigue after diagnosis, of which only few patients recover within 18 months post‐diagnosis.

Targeting goal disturbance might benefit patients with severe and ongoing symptoms.
Improving precision of ability estimation: Getting more from response times
Authors: Bolsinova Maria , Tijmstra Jesper 
Published: June 2017

By considering information about response time (RT) in addition to response accuracy (RA), joint models for RA and RT such as the hierarchical model (van der Linden, 2007) can improve the precision with which ability is estimated over models that only consider RA. The hierarchical model, however, assumes that only the person's speed is informative of ability. This assumption of conditional independence between RT and ability given speed may be violated in practice, and ignores collateral information about ability that may be present in the residual RTs. We propose a posterior predictive check for evaluating the assumption of conditional independence between RT and ability given speed. Furthermore, we propose an extension of the hierarchical model that contains cross‐loadings between ability and RT, which enables one to take additional collateral information about ability into account beyond what is possible in the standard hierarchical model. A Bayesian estimation procedure is proposed for the model. Using simulation studies, the performance of the model is evaluated in terms of parameter recovery, and the possible gain in precision over the standard hierarchical model and an RA‐only model is considered. The model is applied to data from a high‐stakes educational test.
Understanding and improving photo‐control of ion channels in nociceptors with azobenzene photo‐switches
Authors: Mourot Alexandre , Herold Christian , Kienzler Michael A , Kramer Richard H 
Published: June 2017

Background and PurposeThe photo‐isomerizable local anaesthetic, quaternary ammonium–azobenzene–quaternary ammonium (QAQ), provides rapid, optical control over pain signalling without involving genetic modification. In darkness or in green light, trans‐QAQ blocks voltage‐gated K+ and Na+ channels and silences action potentials in pain‐sensing neurons. Upon photo‐isomerization to cis with near UV light, QAQ blockade is rapidly relieved, restoring neuronal activity. However, the molecular mechanism of cis and trans QAQ blockade is not known. Moreover, the absorption spectrum of QAQ requires UV light for photo‐control, precluding use deep inside neural tissue.Experimental ApproachElectrophysiology and molecular modelling were used to characterize the binding of cis and trans QAQ to voltage‐gated K+ channels and to develop quaternary ammonium–ethylamine–azobenzene–quaternary ammonium (QENAQ), a red‐shifted QAQ derivative controlled with visible light.Key Resultstrans QAQ was sixfold more potent than cis QAQ, in blocking current through Shaker K+ channels. Both isomers were use‐dependent, open channel blockers, binding from the cytoplasmic side, but only trans QAQ block was slightly voltage dependent. QENAQ also blocked native K+ and Na+ channels preferentially in the trans state. QENAQ was photo‐isomerized to cis with blue light and spontaneously reverted to trans within seconds in darkness, enabling rapid photo‐control of action potentials in sensory neurons.Conclusions and ImplicationsLight‐switchable local anaesthetics provide a means to non‐invasively photo‐control pain signalling with high selectivity and fast kinetics. Understanding the mode of action of QAQ and related compounds will help to design of drugs with improved photo‐pharmacological properties.Linked ArticlesThis article is part of a themed section on Recent Advances in Targeting Ion Channels to Treat Chronic Pain. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.12/issuetoc
Optimizing outcomes in pancreas transplantation: Impact of organ preservation time
Authors: Rudolph Ehren N. , Dunn Ty B. , Sutherland David E. R. , Kandaswamy Raja , Finger Erik B. 
Published: June 2017

AbstractRecent changes to pancreas graft allocation policy have increased the number of organs available for regional and distant sharing, which results in a corresponding increase in preservation time. We sought to systematically assess the impact of cold ischemia time (CIT) on outcomes post‐transplant. A retrospective review of 1253 pancreas transplants performed at a single transplant center was performed to correlate CIT to transplant outcomes. The rate of technical failure (TF) increased with 20+ hours of CIT, with a 2.7‐fold to 6.2‐fold increased rate of TF for pancreas after kidney (PAK), simultaneous pancreas and kidney (SPK), and pancreas transplants overall. Long‐term graft survival was best with <12 hours of CIT; graft failure increased 1.2‐fold to 1.4‐fold with 12‐24 hours of CIT and 2.2‐fold with 24+ hours. CIT had less influence on the pancreas transplant alone category than either SPK or PAK and had markedly more influence on grafts from older (age >25 years) and overweight (body mass index >25) donors. In the final analysis, grafts with <12 hours of CIT performed the best overall, and strategies that reduce CIT (such as early allocation, pre‐recovery cross‐matching, and chartered flights for organs) should be considered whenever possible.
Socio‐economic status and risk of gestational diabetes mellitus among Chinese women
Authors: Song L. , Shen L. , Li H. , Liu B. , Zheng X. , Zhang L. , Xu S. , Wang Y. 
Published: June 2017

AbstractAimsThe relationship between socio‐economic status and gestational diabetes mellitus has received little attention. The purpose of this study was to investigate the association between socio‐economic status and risk of gestational diabetes.MethodsData were obtained from the ongoing Healthy Baby Cohort study in Hubei Province, China, in 2012–2014. Information on educational level and household income was collected using standard questionnaires during face‐to‐face interviews. Gestational diabetes was defined based on the International Association of Diabetes and Pregnancy Study Group's criteria. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for gestational diabetes in relation to socio‐economic status.ResultsAmong 6886 participants, 1005 (14.6%) pregnant women were diagnosed with gestational diabetes. Higher educational level was inversely associated with risk of gestational diabetes (OR, 0.74; 95% CI, 0.58, 0.95 for high school and OR, 0.62; 95% CI, 0.50, 0.76 for college or above). After adjustment for potential confounders, the ORs for gestational diabetes were 0.77 (95% CI, 0.59, 1.00) and 0.65 (95% CI, 0.51, 0.83) for women with high school and college or above education, respectively, compared with women with less than high school education. No significant association between household income and gestational diabetes was observed after adjustment for potential confounders. Subgroup analysis showed that the reduced risk of gestational diabetes with higher educational level was more evident among women with a pre‐pregnancy BMI < 24 kg/m2 (P for interaction = 0.022).ConclusionsOur findings suggested that educational level was a more robust predictor of gestational diabetes than household income among Chinese women.
Putting promises into practice: The New Aid Architecture in Uganda
Authors: Habraken Rik , Schulpen Lau , Hoebink Paul 
Published: June 2017

AbstractVia the Paris Declaration and the Accra Agenda for Action the international donor community has delivered a set of promises on ownership, harmonization and co‐ordination. Uganda is an interesting case for assessing progress on Paris Principles and seeing the New Aid Architecture in practice. This article provides a historical overview of the implementation of ‘Paris’ in Uganda from the late 1990s up to 2010, showing that implementation is laggardly and, in more recent years, that earlier progress has been reversed. This is due to donors’ perceptions of Uganda's political structure, and particularly its rampant corruption, and also to different views among donors and their internal adaptability in terms of truly measuring up to the Paris Principles.