bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and pharmacological profile of SPP1, a potent, functionally selective and brain penetrant agonist at muscarinic M1 receptors
Authors: Broad Lisa M , Sanger Helen E , Mogg Adrian J , Colvin Ellen M , Zwart Ruud , Evans David A , Pasqui Francesca , Sher Emanuele , Wishart Graham N , Barth Vanessa N , Felder Christian C , Goldsmith Paul J 
Published: October 2018

Background and PurposeWe aimed to identify and develop novel, selective muscarinic M1 receptor agonists as potential therapeutic agents for the symptomatic treatment of Alzheimer's disease.Experimental ApproachWe developed and utilized a novel M1 receptor occupancy assay to drive a structure activity relationship in a relevant brain region while simultaneously tracking drug levels in plasma and brain to optimize for central penetration. Functional activity was tracked in relevant native in vitro assays allowing translational (rat–human) benchmarking of structure–activity relationship molecules to clinical comparators.Key ResultsUsing this paradigm, we identified a series of M1 receptor selective molecules displaying desirable in vitro and in vivo properties and optimized key features, such as central penetration while maintaining selectivity and a partial agonist profile. From these compounds, we selected spiropiperidine 1 (SPP1). In vitro, SPP1 is a potent, partial agonist of cortical and hippocampal M1 receptors with activity conserved across species. SPP1 displays high functional selectivity for M1 receptors over native M2 and M3 receptor anti‐targets and over a panel of other targets. Assessment of central target engagement by receptor occupancy reveals SPP1 significantly and dose‐dependently occupies rodent cortical M1 receptors.Conclusions and ImplicationsWe report the discovery of SPP1, a novel, functionally selective, brain penetrant partial orthosteric agonist at M1 receptors, identified by a novel receptor occupancy assay. SPP1 is amenable to in vitro and in vivo study and provides a valuable research tool to further probe the role of M1 receptors in physiology and disease.
On publication, refereeing and working hard
Authors: Baghestanian Sascha , Popov Sergey V. 
Published: October 2018

AbstractWe present a model for academia with heterogeneous author types and endogenous effort to evaluate recent changes in the publication process in economics. We analyze the implications of these developments on research output. Lowering the precision of refereeing signals lowers the effort choices of intermediate ability authors, but invites more submissions from less able authors. Increasing the number of journals stimulates less able authors to submit their papers. The editor can improve the journal's quality pool of submitted manuscripts by improving the precision of refereeing, but not by lowering acceptance standards. The submission strategy of an author is informative of his ability.
Acupuncture as a multifunctional neuroprotective therapy ameliorates cognitive impairment in a rat model of vascular dementia: A quantitative iTRAQ proteomics study
Authors: Yang Jing‐Wen , Wang Xue‐Rui , Zhang Meng , Xiao Ling‐Yong , Zhu Wen , Ji Cai‐Shuo , Liu Cun‐Zhi 
Published: October 2018

SummaryAimsAcupuncture has been reported to affect vascular dementia through a variety of molecular mechanisms. An isobaric tag for relative and absolute quantification (iTRAQ) with high‐resolution liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) analyses makes it possible to attain a global profile of proteins. Hence, we used an iTRAQ‐LC‐MS/MS strategy to unravel the underlying mechanism of acupuncture.MethodsWistar rats were subjected to vascular dementia with bilateral common carotid occlusion. Acupuncture was intervened for 2 weeks at 3 days after surgery. The Morris water maze was used to assess the cognitive function. Proteins were screened by quantitative proteomics and analyzed by bioinformatic analysis. Four differentially expressed proteins (DEPs) were validated by western blot. The reactive oxygen species (ROS) production, neuron cell loss, and long‐term potentiation (LTP) were determined after western blot.ResultsAcupuncture at proper acupoints significantly improved cognitive function. A total of 31 proteins were considered DEPs. Gene ontology (GO) analysis showed that most of the DEPs were related to oxidative stress, apoptosis, and synaptic function, which were regarded as the major cellular processes related to acupuncture effect. Western blot results confirm the credibility of iTRAQ results. Acupuncture could decrease ROS production, increase neural cell survival, and improve LTP, which verified the three major cellular processes.ConclusionAcupuncture may serve as a promising clinical candidate for the treatment of vascular dementia via regulating oxidative stress, apoptosis, or synaptic functions.
Use of beta‐blocker is associated with lower mortality in patients with coronary artery disease with or without COPD
Authors: Rezaei Safoura Sheikh , Rinner Christoph , Ratajczak Paulina , Grossmann Wilfried , Gall Walter , Wolzt Michael 
Published: October 2018

AbstractIntroductionBeta‐blockers are indicated for secondary prevention of coronary artery disease (CAD). However, in patients with co‐morbidity of chronic obstructive pulmonary disease (COPD) an underuse of beta‐blocker has been reported.Materials and MethodsPrescription and demographic data and information on hospital discharge diagnoses from 13 Austrian health insurance funds for the years 2006‐2007 were analyzed. The primary end point was all‐cause mortality of patients with CAD with or without COPD and its association with use of beta‐blockers.ResultsIn 2006 and 2007, 65717 patients (37% female, 63% male) were discharged with a diagnosis of CAD. Among these patients, 46% had a co‐diagnosis of COPD, 24% had diabetes, and 75% received beta‐blockers. Use of beta‐blockers was comparable in CAD patients with COPD and without COPD with 77% and 74%, respectively.Thousand eight hundred seventy‐two (8.1%) and 1473 (5.6%) patients with and without COPD, who used beta‐blockers died within months in 2006 and 2007. Thousand five hundred fifty‐three (22.0%) and 1862 (22.2%) of patients with and without COPD and without beta‐blockers died during the corresponding time period.DiscussionUse of beta‐blockers was similar in patients with CAD with or without co‐diagnosis of COPD. However, mortality of beta‐blocker users was markedly lower than that of nonusers in patients with CAD with or without COPD.
Inducing Downstream Information Sharing via Manufacturer Information Acquisition and Retailer Subsidy
Authors: Li Guo , Zheng Hong , Sethi Suresh P. , Guan Xu 
Published: October 2018

ABSTRACTWe investigate a manufacturer's information acquisition and subsidization strategies in a supply chain featuring two competing retailers who sell substitutable products and have private demand information. The manufacturer can decide whether to acquire demand information at a cost and further decide whether to offer subsidies simultaneously to retailers to induce their sharing of private demand information. We demonstrate that subsidizing retailers is always in the manufacturer's interest, but direct information acquisition is profitable only if its cost is low. Information acquisition helps the manufacturer gain superior demand information and leverages the retailer's information advantage, thereby reducing the expenditure of subsidization. Compared with the simultaneous subsidy provision scheme, we further investigate the sequential and partial subsidy schemes and find that the simultaneous and sequential subsidy schemes result in an identical equilibrium outcome that dominates the equilibrium outcome in the partial subsidy scheme when three subsidy provision schemes are all feasible. Although the outcomes are the same, we show that the simultaneous subsidy scheme can be applied in a broader range than the sequential subsidy scheme can. Otherwise, if complete information sharing cannot be achieved, the partial subsidy scheme may be the optimal choice for the manufacturer.
The ontogeny of intent‐based normative judgments
Authors: Proft Marina , Rakoczy Hannes 
Published: October 2018

AbstractWhen evaluating norm transgressions, children begin to show some sensitivity to the agent's intentionality around preschool age. However, the specific developmental trajectories of different forms of such intent‐based judgments and their cognitive underpinnings are still largely unclear. The current studies, therefore, systematically investigated the development of intent‐based normative judgments as a function of two crucial factors: (a) the type of the agent's mental state underlying a normative transgression, and (b) the type of norm transgressed (moral versus conventional). In Study 1, 5‐ and 7‐year‐old children as well as adults were presented with vignettes in which an agent transgressed either a moral or a conventional norm. Crucially, she did so either intentionally, accidentally (not intentionally at all) or unknowingly (intentionally, yet based on a false belief regarding the outcome). The results revealed two asymmetries in children's intent‐based judgments. First, all age groups showed greater sensitivity to mental state information for moral compared to conventional transgressions. Second, children's (but not adults') normative judgments were more sensitive to the agent's intention than to her belief. Two subsequent studies investigated this asymmetry in children more closely and found evidence that it is based on performance factors: children are able in principle to take into account an agent's false belief in much the same way as her intentions, yet do not make belief‐based judgments in many existing tasks (like that of Study 1) due to their inferential complexity. Taken together, these findings contribute to a more systematic understanding of the development of intent‐based normative judgment.
Structural and functional neuroimaging in attention‐deficit/hyperactivity disorder
Authors: Albajara Sáenz Ariadna , Villemonteix Thomas , Massat Isabelle 
Published: October 2018

Over the last decade, there has been a dramatic increase in the number of neuroimaging studies in attention‐deficit/hyperactivity disorder (ADHD). In terms of brain structure, magnetic resonance imaging (MRI), and diffusion tensor imaging studies have evidenced differences in volume, surface‐based measures (cortical thickness, surface area, and gyrification), and white matter integrity in different cerebral regions, in children and adults with ADHD compared to population norms. Abnormalities in the basal ganglia, prefrontal structures, and the corpus callosum have been the most consistently reported findings across studies. Hemodynamic (functional MRI, functional near‐infrared spectroscopy, positron emission tomography, single‐photon emission computed tomography) and magnetoencephalography measurements have also shown differences in neural activity during the execution of neuropsychological tasks and during rest, in widespread regions of the brain. Importantly, multimodal studies combining structural and functional methods have shown an intercorrelation between structural and functional abnormalities in ADHD. Further longitudinal studies are needed to clarify the effects of age and medication on brain structure and function in individuals with ADHD.What this paper adds

In attention‐deficit/hyperactivity disorder (ADHD), the brain is characterized by abnormal neural network interplay.

Structural and functional cerebral abnormalities in ADHD are intercorrelated.

Currently there is no neural biomarker that can be used in diagnosis.

Longitudinal studies have shed light on the brain correlates of ADHD over the lifespan.

The effects of stimulant intake on the brain correlates of ADHD remain unclear.
Cognitive activity in a sitting position is protectively associated with cognitive impairment among older adults
Authors: Kurita Satoshi , Doi Takehiko , Tsutsumimoto Kota , Hotta Ryo , Nakakubo Sho , Kim Minji , Shimada Hiroyuki 
Published: October 2018

AimPrevious studies have obtained inconsistent results regarding the association between sedentary behavior and cognitive impairment. The present study aimed to examine the association between cognitive activity in a sitting position (CAS) and cognitive impairment among older adults.MethodsCommunity‐dwelling older adults, from Obu or Nagoya in Japan, participated in a survey in 2013. A total of 5300 participants (mean age 75.0 ± 5.1 years; women 52.9%) met the criteria for the present study. We assessed the frequency and variety of CAS composed of six activities, including reading books or newspapers, writing a diary or letters, solving crossword puzzles, playing board games, using a computer and maintaining housekeeping records. The frequency of engagement in CAS was one or more time(s)/week. The variety of CAS was assessed by the number of engagements in CAS. Cognitive impairment was defined by two or more tests at least 1.5 standard deviations below the reference threshold in four neuropsychological tests. Logistic regression analysis was carried out to examine the associations between the frequency and variety of CAS and cognitive impairment, adjusted for covariates.ResultsThe proportion of participants engaging in each CAS varied from 12.3% (playing board games) to 93.6% (reading books or newspaper). After adjustment, five CAS were significantly associated with cognitive impairment (OR 0.33–0.65, all P < 0.001). The variety of CAS was significantly associated with the reduced OR of cognitive impairment (OR 0.61, 95% confidence interval 0.55–0.68).ConclusionsAlmost every CAS and a greater variety of CAS are associated with cognitive impairment among older people. Geriatr Gerontol Int 2019; 19: 98–102.
IDIOSYNCRATIC RISK, AGGREGATE RISK, AND THE WELFARE EFFECTS OF SOCIAL SECURITY
Authors: Harenberg Daniel , Ludwig Alexander 
Published: October 2018

AbstractWe ask whether a pay‐as‐you‐go financed social security system is welfare improving in an economy with idiosyncratic and aggregate risk. We show that the whole welfare benefit from insurance against both risks is greater than the sum of benefits from insurance against the isolated risks. One reason is the convexity of the welfare gain. The other reason is a direct risk interaction amplifying the utility losses from risk. Our quantitative evaluation shows that introducing a minimum pension leads to sizeable welfare gains, despite substantial crowding out. About 60% of these gains would be missing from summing up the isolated benefits.
Predictors of biochemical recurrence after Retzius‐sparing robot‐assisted radical prostatectomy: Analysis of 359 cases with a median follow‐up period of 26 months
Authors: Abdel Raheem Ali , Chang Ki Don , Alenzi Mohammed Jayed , Ham Won Sik , Han Woong Kyu , Choi Young Deuk , Rha Koon Ho 
Published: October 2018

ObjectivesOur aim was to evaluate the predictors of biochemical recurrence after Retzius‐sparing robot‐assisted radical prostatectomy.MethodsThe study cohort consisted of 359 consecutive non‐metastatic prostate cancer patients who underwent Retzius‐sparing robot‐assisted radical prostatectomy between November 2012 and January 2016. According to the National Comprehensive Cancer Network prostate cancer risk classification, 164 patients (45.7%) had high‐ or very high‐risk prostate cancer. No patient received adjuvant therapy until documented biochemical recurrence. Biochemical recurrence‐free survival was estimated using the Kaplan–Meier method. Univariable and multivariable Cox proportional hazards regression models were used to determine variables predictive of biochemical recurrence.ResultsThe median follow‐up period was 26 months (interquartile range 19–38 months). The overall biochemical recurrence rate was 14.8%, and the median time to biochemical recurrence was 11 months (interquartile range 6–22 months). The 3‐year biochemical recurrence‐free survival probability was 71.2%, 72.1%, 88.7%, 82.3% and 95.7% in very high‐, high‐, intermediate‐, low‐ and very low‐risk prostate cancer, respectively (log–rank, P < 0.001). On multivariable analysis, preoperative prostate‐specific antigen (hazard ratio 1.03, 95% confidence interval 1.02–1.04; P < 0.0001), percentage of maximum core involvement on biopsy (hazard ratio 1.02, 95% confidence interval 1.01–1.03; P = 0.029) and clinical stage ≥T3a (hazard ratio 2.12, 95% confidence interval 1.02–4.39; P = 0.043) were predictors of biochemical recurrence, whereas pathological Gleason score ≥8 (hazard ratio 5.63, 95% confidence interval 1.62–19.61; P = 0.007) and pathological tumor volume (hazard ratio 1.08, 95% confidence interval 1.04–1.20; P < 0.001) were the main pathological predictors of biochemical recurrence.ConclusionsRetzius‐sparing robot‐assisted radical prostatectomy confers effective biochemical recurrence control at the mid‐term follow‐up period. Preoperative prostate‐specific antigen, advanced clinical stage and higher Gleason score were important predictors of biochemical recurrence after Retzius‐sparing robot‐assisted radical prostatectomy. Long‐term oncological safety still needs to be established.
L‐carnitine prevents ammonia‐induced cytotoxicity and disturbances in intracellular amino acid levels in human astrocytes
Authors: Wang Ting , Suzuki Kazuyuki , Kakisaka Keisuke , Onodera Mio , Sawara Kei , Takikawa Yasuhiro 
Published: October 2018

AbstractBackground and AimL‐carnitine (L‐CA) has been used therapeutically to treat hepatic encephalopathy with hyperammonemia, but the mechanism by which L‐CA contributes to ammonia detoxification in the brain is still unclear. Thus, the cytotoxicity and changes in intracellular amino acids (AAs) in astrocytes with hyperammonemia following L‐CA administration were studied.MethodsHuman astrocytes were treated with ammonium chloride (NH4Cl), L‐CA or a mixture of NH4Cl, and L‐CA under defined conditions. Total intracellular reactive oxygen species and lactate dehydrogenase leakage were measured following different treatment periods. The intracellular levels of AAs in astrocytes were determined using metabolomic analysis.ResultsIntracellular total reactive oxygen species and lactate dehydrogenase leakage were significantly increased after treatment with NH4Cl. In contrast, co‐treatment with L‐CA significantly inhibited the cytotoxic effects of NH4Cl. The intracellular levels of almost all AAs involving glutamine and branched‐chain AAs (BCAAs) were significantly increased in the NH4Cl‐treated cells compared with in the control cells; these changes in BCAA levels were reduced with L‐CA co‐treatment. Additionally, the level of 3‐methyl‐2‐oxovaleric acid, which is a metabolite from isoleucine and plays a critical role in neurological damage, was significantly increased in the NH4Cl‐treated cells, but this metabolite was significantly decreased with L‐CA co‐treatment.ConclusionL‐CA protects human astrocytes from ammonia‐induced acute cytotoxic effects and the increased intracellular levels of glutamine and BCAAs.
Favorable outcomes of prepackaged low‐residue diet on bowel preparation for colonoscopy: Endoscopist‐blinded randomized controlled trial
Authors: Lee Jung Won , Choi Joon Young , Yoon Hyuk , Shin Cheol Min , Park Young Soo , Kim Nayoung , Lee Dong Ho 
Published: October 2018

AbstractBackground and Aim2 L polyethylene glycol plus an ascorbic acid (PEGA) is known to be as effective. However, 2 L polyethylene glycol‐based regimens are often still difficult for patients to tolerate. Therefore, we conducted this study to evaluate the potential of 1 L PEGA with prepackaged low‐residue diet (PLD) as an alternative to 2 L PEGA before colonoscopy.MethodsThe subjects were randomly assigned to either of the two groups. The 2 L PEGA group received 2 L PEGA split regimen. The 1 L PEGA with PLD group received PLD on the day preceding colonoscopy and 1 L PEGA. All endoscopic procedures were performed by one physician who did not know patients allocation. Bowel preparation status were graded using Boston Bowel Preparation Score (BBPS). A questionnaire regarding tolerability and safety was administered. This trial is registered at ClinicalTrials.gov (NCT03329339).ResultsA total of 173 patients completed the study (86 in the 2 L PEGA group and 87 in the 1 L PEGA with PLD group). Bowel preparation was adequate in 88.4% (76/86) of patients in the 2 L PEGA group and 93.1% of patients in the 1 L PEGA with PLD group (81/87, P = 0.28). The patients in the 1 L PEGA with PLD group had higher whole Boston Bowel Preparation Scale score (P = 0.02) and expressed more satisfaction and willingness to repeat the procedure (P < 0.01). There was no significant difference with respect to compliance or safety.Conclusion1 L PEGA with PLD showed equivalent efficacy, greater satisfaction, and more willingness to repeat compared with 2 L PEGA for bowel preparation.
The Case for Mobility Assessment in Hospitalized Older Adults: American Geriatrics Society White Paper Executive Summary
Authors: Wald Heidi L. , Ramaswamy Ravishankar , Perskin Michael H. , Roberts Lloyd , Bogaisky Michael , Suen Winnie , Mikhailovich Anna ,   for the Quality and Performance Measurement Committee of the American Geriatrics Society
Published: October 2018

ABSTRACTMobility can be defined as the ability to move or be moved freely and easily. In older adults, mobility impairments are common and associated with risk for additional loss of function. Mobility loss is particularly common in these individuals during acute illness and hospitalization, and it is associated with poor outcomes, including loss of muscle mass and strength, long hospital stays, falls, declines in activities of daily living, decline in community mobility and social participation, and nursing home placement. Thus, mobility loss can have a large effect on an older adult's health, independence, and quality of life. Nevertheless, despite its importance, loss of mobility is not a widely recognized outcome of hospital care, and few hospitals routinely assess mobility and intervene to improve mobility during hospital stays. The Quality and Performance Measurement Committee of the American Geriatrics Society has developed a white paper supporting greater focus on mobility as an outcome for hospitalized older adults. The executive summary presented here focuses on assessing and preventing mobility loss in older adults in the hospital and summarizes the recommendations from that white paper. The full version of the white paper is available as Text S1. J Am Geriatr Soc 67:11–16, 2019.
Interenterprise Credit and Adjustment during Financial Crises: The Role of Firm Size
Authors: CORICELLI FABRIZIO , FRIGERIO MARCO 
Published: October 2018

AbstractSmall and medium‐sized enterprises (SMEs) suffered a sharp contraction in their borrowing from banks during the Great Recession. Analyzing a large firm‐level database for European countries, the paper shows that trade credit amplified the liquidity squeeze on SMEs, with adverse effects on their real activity. SMEs sharply increased their net trade credit and thus transferred financial resources to larger firms. Given the large weight of SMEs in the economy of European countries, the liquidity squeeze of SMEs likely contributed to the depth of the output fall and the slow recovery in Europe during the Great Recession.