bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutant Nmnat1 leads to a retina-specific decrease of NAD+ accompanied by increased poly(ADP-ribose) in a mouse model of NMNAT1-associated retinal degeneration
Authors: Greenwald Scott H , Brown Emily E , Scandura Michael J , Hennessey Erin , Farmer Raymond , Du Jianhai , Wang Yekai , Pierce Eric A 
Published: March 2021

Abstract
Nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1) is required for nuclear nicotinamide adenine mononucleotide (NAD+) biosynthesis in all nucleated cells, and despite its functional ubiquity, mutations in this gene lead to an isolated retinal degeneration. The mechanisms underlying how mutant NMNAT1 causes disease are not well understood, nor is the reason why the pathology is confined to the retina. Using a mouse model of NMNAT1-associated retinal degeneration that harbors the p.Val9Met mutation, we tested the hypothesis that decreased function of mutant NMNAT1 has a greater effect on the levels of NAD+ in the retina than elsewhere in the body. Measurements by liquid chromatography with tandem mass spectrometry showed an early and sustained decrease of NAD+ in mutant retinas that was not observed in other tissues. To understand how consumers of nuclear NAD+ are affected by the reduced availability of NAD+ in mutant retinas, poly(ADP-ribose) polymerase (PARP) and nuclear sirtuin activity were evaluated. PARP activity was elevated during disease progression, as evidenced by overproduction of poly(ADP-ribose) (PAR) in photoreceptors, whereas histone deacetylation activity of nuclear sirtuins was not altered. We hypothesized that PARP could be activated because of elevated levels of oxidative stress; however, we did not observe oxidative DNA damage, lipid peroxidation, or a low glutathione to oxidized glutathione ratio. Terminal deoxynucleotidyl transferase dUTP nick end labeling staining revealed that photoreceptors appear to ultimately die by apoptosis, although the low NAD+ levels and overproduction of PAR suggest that cell death may include aspects of the parthanatos cell death pathway.
Disruption of Long-Term Depression Potentiates Latent Inhibition: Key Role for Central Nucleus of the Amygdala
Authors: Ashby Donovan M , Dias Carine , Aleksandrova Lily R , Lapish Christopher C , Wang Yu Tian , Phillips Anthony G 
Published: March 2021

Abstract

Background
Latent inhibition (LI) reflects an adaptive form of learning impaired in certain forms of mental illness. Glutamate receptor activity is linked to LI, but the potential role of synaptic plasticity remains unspecified.

Methods
Accordingly, the present study examined the possible role of long-term depression (LTD) in LI induced by prior exposure of rats to an auditory stimulus used subsequently as a conditional stimulus to signal a pending footshock. We employed 2 mechanistically distinct LTD inhibitors, the Tat-GluA23Y peptide that blocks endocytosis of the GluA2-containing glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, or the selective glutamate n-methyl-d-aspartate receptor 2B antagonist, Ro25-6981, administered prior to the acquisition of 2-way conditioned avoidance with or without tone pre-exposure.

Results
Systemic LTD blockade with the Tat-GluA23Y peptide strengthened the LI effect by further impairing acquisition of conditioned avoidance in conditional stimulus-preexposed rats compared with normal conditioning in non-preexposed controls. Systemic Ro25-6981 had no significant effects. Brain region–specific microinjections of the Tat-GluA23Y peptide into the nucleus accumbens, medial prefrontal cortex, or central or basolateral amygdala demonstrated that disruption of glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor endocytosis in the central amygdala also potentiated the LI effect.

Conclusions
These data revealed a previously unknown role for central amygdala LTD in LI as a key mediator of cognitive flexibility required to respond to previously irrelevant stimuli that acquire significance through reinforcement. The findings may have relevance both for our mechanistic understanding of LI and its alteration in disease states such as schizophrenia, while further elucidating the role of LTD in learning and memory.
Monetary Incentives in Large-Scale Face-to-Face Surveys: Evidence from a Series of Experiments
Authors: Blohm Michael , Koch Achim 
Published: March 2021

Abstract
Monetary respondent incentives are a means to counteract the trend toward declining response rates. This article summarizes the results of a series of experiments conducted in the past decade in the German General Social Survey. We found that prepaid monetary incentives led to a higher increase in response than promised incentives. There was no evidence that either promised or prepaid incentives had a systematic effect on sample composition. The incentives helped to reduce fieldwork efforts. Thus, the costs of incentives can—at least partially—be offset by a reduction in the number of contact attempts required to achieve a certain number of completed interviews. Our findings are highly credible due to the replicative design of the experiments.
Partial Regularity of Harmonic Maps From Alexandrov Spaces
Authors: Ge Huabin , Jiang Wenshuai , Zhang Hui-Chun 
Published: March 2021

AbstractIn this paper, we prove the Lipschitz regularity of continuous harmonic maps from a finite-dimensional Alexandrov space to a compact smooth Riemannian manifold. This solves a conjecture of F. H. Lin in [38]. The proof extends the argument of Huang-Wang [28].
Use of machine learning to predict clinical decision support compliance, reduce alert burden, and evaluate duplicate laboratory test ordering alerts
Authors: Baron Jason M , Huang Richard , McEvoy Dustin , Dighe Anand S 
Published: March 2021

Abstract

Objectives
While well-designed clinical decision support (CDS) alerts can improve patient care, utilization management, and population health, excessive alerting may be counterproductive, leading to clinician burden and alert fatigue. We sought to develop machine learning models to predict whether a clinician will accept the advice provided by a CDS alert. Such models could reduce alert burden by targeting CDS alerts to specific cases where they are most likely to be effective.

Materials and Methods
We focused on a set of laboratory test ordering alerts, deployed at 8 hospitals within the Partners Healthcare System. The alerts notified clinicians of duplicate laboratory test orders and advised discontinuation. We captured key attributes surrounding 60 399 alert firings, including clinician and patient variables, and whether the clinician complied with the alert. Using these data, we developed logistic regression models to predict alert compliance.

Results
We identified key factors that predicted alert compliance; for example, clinicians were less likely to comply with duplicate test alerts triggered in patients with a prior abnormal result for the test or in the context of a nonvisit-based encounter (eg, phone call). Likewise, differences in practice patterns between clinicians appeared to impact alert compliance. Our best-performing predictive model achieved an area under the receiver operating characteristic curve (AUC) of 0.82. Incorporating this model into the alerting logic could have averted more than 1900 alerts at a cost of fewer than 200 additional duplicate tests.

Conclusions
Deploying predictive models to target CDS alerts may substantially reduce clinician alert burden while maintaining most or all the CDS benefit.
Assessment of Semiochemical Repellents for Protecting Walnut Trees From Walnut Twig Beetle (Coleoptera: Curculionidae) Attack in a Commercial Orchard Setting in California
Authors: Audley Jackson P , Bostock Richard M , Seybold Steven J 
Published: March 2021

Abstract
The walnut twig beetle, Pityophthorus juglandis Blackman, the vector of thousand cankers disease (TCD), poses a significant threat to North American walnut (Juglandaceae Juglans) trees. Despite discovery of TCD-related tree mortality over a decade ago, management options are lacking. This study represents the culmination of several years of investigating the chemical ecology of P. juglandis in hopes of developing a semiochemical repellent to disrupt the beetle’s host colonization and aggregation behaviors. Numbers of P. juglandis landing on semiochemical-treated Juglans regia L. trees in a commercial walnut orchard were compared based on captures on sticky traps. Two repellent combinations were tested: R-(+)-limonene and trans-conophthorin (LimeCon), and R-(+)-limonene, trans-conophthorin, and R-(+)-verbenone (LCV). Both repellents reduced P. juglandis aggregation (captures) equally; thus, we proceeded with the LimeCon combination to reduce potential treatment cost. Subsequent trials included a 2× dose (Dual) of LimeCon. Both LimeCon and Dual significantly reduced the number of P. juglandis caught compared with the baited control, however, only for the lower of two trap positions. Beetle landings were modeled by trap distance from repellent placement on each tree. Beetle responses to the pheromone lure were surprisingly localized and did not bring the whole tree under attack. LimeCon, LCV, and Dual treatments averaged fewer than a single beetle caught for all trap distances; however, performance of the repellents beyond 150 cm is not clear due to the localized landing response of P. juglandis to pheromone lures. Further testing is required to fully analyze the zone of inhibition of the LimeCon repellent.
Risk factors of post-operative pneumonia in elderly patients with gastric cancer: a retrospective cohort study
Authors: Cho Haruhiko , Tsuchida Kazuhito , Iwasaki Kenichi , Maezawa Yukio 
Published: March 2021

Abstract

Background
Post-operative pneumonia is a major complication after general elective surgery in elderly patients and is often caused by aspiration associated with oesophageal reflux. The aim of this study was to identify the risk factors of post-operative pneumonia after gastrectomy in elderly patients with gastric cancer with two potential risk factors of ageing and oesophageal reflux.

Methods
We retrospectively examined the data of 251 patients ≥75 years old who underwent gastrectomy between January 2014 and December 2018 in our institution. The reconstruction methods were Billroth-I or Roux-Y after distal gastrectomy, jejunal interposition or double tract after proximal gastrectomy and Roux-Y after total gastrectomy. The severity of pneumonia was evaluated by the Clavien–Dindo classification.

Results
Post-operative pneumonia was identified in 15 patients (5.9%) and was significantly associated with an age ≥80 years old, poor performance status, history of smoking and cardia-non-preserving gastrectomy (total gastrectomy and proximal gastrectomy) in univariate analyses. Multivariate analyses showed that a poor performance status and cardia-non-preserving gastrectomy were independent risk factors for post-operative pneumonia. The patients who suffered post-operative pneumonia required a longer hospital stay than those without post-operative pneumonia (P = 0.002).

Conclusion
We identified a poor performance status and cardia-non-preserving gastrectomy, which are likely to lead to oesophageal reflux, as risk factors for post-operative pneumonia in elderly patients with gastric cancer. These results warrant further prospective studies to evaluate their utility for reducing the rate of post-operative pneumonia in elderly patients through cardia-preserving gastrectomy or anti-reflux reconstruction.
Evolution of State Aid Rules
Authors: Kreuschitz Viktor , Nehl Hanns Peter 
Published: March 2021

Abstract
This chapter looks at the evolution of the legal framework for State aid during the past six decades of economic integration and addresses State aid rules in the context of balancing national policy objectives with the necessity to review aids at a supranational level. A dual trend emerges from the evolution of State aid rules over the last sixty years. On the one hand, the Court of Justice has played a key role in establishing new principles and designing rules governing State aid. In parallel, the Commission also acts as a rule-maker, by introducing relevant soft law and regulatory texts. In this context, the adoption of the Procedural Regulation in 1999 can be regarded as a turning point in the codification and development of State aid rules. The development of State aid is, however, not completed, as reflected in the last reforms of the State Aid Action Plan and the State Aid Modernization initiative.
The Legal Framework to Subsidies and State Aid Review
Authors: Kreuschitz Viktor , Nehl Hanns Peter 
Published: March 2021

Abstract
This chapter assesses the legal framework of the multi-level system of State aid and subsidies control not only on the level of the EU but also on the international level—the World Trade Organization (WTO)—and the national level by EU Member States. The control of subsidies and State aids as a multi-level phenomenon has been a laboratory of design solutions for procedural law provisions, enforcement techniques, and the development of general principles of law. It is one of the fields of law which has been most influential for the development of modern public law as a multi-level legal system with several constitutionalized levels. Not only by the sheer force of numbers and issues raised, State aid and subsidies cases have had a great influence on the development of procedural rights such as defence rights. It also added to the clarification of notions of discretion, the protection of legitimate interests, and principles of equality.
De Jure Compatible Aid under Article 107(2) TFEU
Authors: Kreuschitz Viktor , Nehl Hanns Peter 
Published: March 2021

Abstract
This chapter assesses the de jure compatible aid under Article 107(2) TFEU. As is well known, Article 107(1) TFEU introduces a general prohibition on granting State aid in the EU legal order. Nevertheless, this prohibition is not absolute because the same article permits derogations provided for in the TFEU. Article 107(2) provides for these de jure derogations, that is to say State aid which is compatible with the Treaty. According to this provision, three categories of State aid accord with the internal market, namely: (a) aid of a social character granted to individual consumers, provided that such aid is granted without discrimination related to the origin of the product concerned; (b) aid to make good the damage caused by natural disasters or exceptional occurrences; and (c) aid granted to certain areas of Germany affected by the division of that country.
Transport Aid
Authors: Kreuschitz Viktor , Nehl Hanns Peter 
Published: March 2021

Abstract
This chapter focuses on transport aid. Transport has, in many regards, always had a special place in EU law. In this diverse sector, the Union's powers are constrained and wide-ranging at the same time. On the one hand, the freedom to provide services only applies to transport if the Union legislators have adopted secondary legislation on market opening. On the other hand, the Court has emphasized on several occasions that the Treaty chapter on transport, Title VI, confers wide-ranging competences on the Union, enabling it to develop a common transport policy. Within this, the Union's powers with regards to State aid have steadily been growing in significance. The transport sector is not only ‘special’ when it comes to its place within EU law and State aid law in general, but also with regards to its place in services of general economic interest.
The Different Stages in the State Aid Procedure
Authors: Kreuschitz Viktor , Nehl Hanns Peter 
Published: March 2021

Abstract
This chapter discusses the different stages in the State aid procedure. Regulation 2015/1589 distinguishes mainly between two categories of aid: those that have been duly notified and those that are considered as ‘unlawful State aid’ because they have not been notified to the Commission prior to implementation. The Procedural Regulation 2015/1589 is firmly based on two related concepts: (i) loyal cooperation between the Member States and the Commission; and (ii) the conduct of the administrative procedures as a form of privileged dialogue between these two parties. In so far as the Member State cooperates loyally, by notifying a planned measure together with all the relevant information such as to allow the Commission to reach a preliminary decision on the measure, the Regulation provides at least for the Member State concerned a clear framework for the investigation in its first phase.
Vertical Agreements in EU Competition Law
Authors: Tuytschaever Filip , Wijckmans Frank 
Published: March 2021

Abstract
The book discusses the EU competition law regime and practice in respect of vertical agreements. The concept of vertical agreements is not limited to distribution arrangements, but covers also supply and subcontracting scenarios. Particular attention is paid to e-commerce and the sector-specific rules applicable to the automotive industry (Regulation 461/2010). The book covers systematically the various aspects of Regulation 330/2010, which is the European block exemption regulation generally applicable to vertical agreements, as well as the Vertical Guidelines related thereto. In addition to a systematic presentation of the relevant legal concepts, the book provides practical guidance and concrete cases. Such cases include European precedents and decisions adopted in national competition law proceedings. The authors have inserted concrete examples stemming from their private practice in the field. The book offers concrete guidance for vertical agreements falling outside of the scope of Regulation 330/2010 where the parties may need to conduct a so-called self-assessment. It describes the economic theories underpinning such assessment and presents the relevant economic concepts in a digestible manner. The book is intended as an easy reference tool for private practitioners and legal scholars. The second edition of the book has been labelled by many practitioners as their ‘bible’ on vertical agreements.
Motor Vehicle Distribution
Authors: Wijckmans Frank , Tuytschaever Filip 
Published: March 2021

Abstract
This chapter addresses the specific block exemption regime that applies to the automotive industry. The relevant regime is contained in Regulation 461/2010. Different from past practice, Regulation 461/2010 closely resembles the general block exemption (Regulation 330/2010) and limits itself to adding certain hardcore restrictions applicable in the secondary markets. The chapter provides an overview of the impact of the block exemption from the perspective of the various stakeholders active in the sector. It then goes on to describe separately the block exemption principles governing the distribution of motor vehicles, the provision of after-sales services, and the distribution of spare parts.
France
Authors: Chagny Muriel 
Published: March 2021

Abstract
This chapter examines how the Antitrust Damages Directive has been transposed in France. It begins with an overview of the transposition procedure, focusing on the French private enforcement context from the Ordinance of 1 December 1986—the ‘Magna Carta’ of French competition law—to Law no. 2008-776 of 4 August 2008 and the Consumer Law Act of 17 March 2014 (Hamon Law). It then discusses the scope of the transposition measure, noting that the French government went beyond the Directive and instituted a single regime for damages actions, before analysing specific issues that arose during the transposition, including those relating to the concept of an undertaking, the binding effect of competition authorities' decisions, the presumption of harm, the passing-on of overcharges, types of harm and assessment of damages, joint and several liability and the recovery of contributions from co-infringers, consensual dispute resolution, time-barring deadlines, access to evidence, and class actions.
Italy
Authors: Lopopolo Susanna 
Published: March 2021

Abstract
This chapter focuses on the transposition of the Antitrust Damages Directive in Italy. It first considers the transposition procedure, with emphasis on the Italian competition law system and more specifically public enforcement of antitrust law under the Autorità Garante per la concorrenza ed il mercato (AGCM), before discussing the issue of the ‘topographic’ location of the implementing regulation within the current legal system. It then examines the substantive and temporal scope of Italy’s transposition measure, known as Legge Delega, as well as specific issues that arose during the transposition, including those relating to disclosure of evidence, penalties, the binding force of National Competition Authority (NCA) decisions and judicial review, time limitation rules, joint and several liability, parent company liability, the passing-on of overcharges, the use of AGCM expertise in quantifying damages, consensual resolution of disputes, collective redress, and the concentration of jurisdiction.
Luxembourg
Authors: Cauffman Caroline 
Published: March 2021

Abstract
This chapter discusses the transposition of the Antitrust Damages Directive in Luxembourg. It first provides a general overview of the transposition procedure, focusing on the Transposition Act that was adopted by first vote in the plenary session of the Chambre des députés of 15 November 2016 and entered into force on 11 December 2016. It then considers the substantive and temporal scope of Luxembourg’s Transposition Act before concluding with an analysis of specific issues that arose during the transposition, including those relating to certain articles of the Directive that have not been specifically transposed, the protection of confidential information, principles of joint and several liability, the probative value of decisions of National Competition Authorities of other Member States, the presumption and quantification of harm by cartels, time-barring deadlines, sanctions, actions for damages by claimants from different levels in the supply chain, consensual dispute resolution, and parent company liability.
Transposition Context, Processes, Measures, and Scope
Authors: Rodger Barry , Ferro Miguel Sousa , Marcos Francisco 
Published: March 2021

Abstract
This chapter discusses the context, processes, measures, and scope of transposition of the Antitrust Damages Directive across 16 Member States. It first provides a general overview of the competition litigation context in MS, including Cyprus, France, Greece, Hungary, Italy, Spain, and the Netherlands, before considering the timescale for the Directive’s implementation. It then examines other particular aspects of the national processes involved in the adoption of the Directive transposition measures, including the authorities responsible for overseeing the implementation, as well as the form, level, and extent of consultation undertaken with interested parties and stakeholders. The chapter also analyses the nature of the transposition measures adopted across the Member States, key aspects of the debates and issues surrounding the substantive and temporal scope of the Directive’s application, and the difficulties that might arise in the interpretation of transposition measures by the national courts.