bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis of indoles: recent advances
Authors: Bugaenko Dmitry I. , Karchava Alexander V. , Yurovskaya Marina A. 
Published: August 2018

Published data of the last 10 years concerning the development of new and upgrading of known approaches to indole synthesis are integrated and analyzed. Modern versions of the classical syntheses such as the Fischer synthesis, Nenitzescu synthesis, Ullmann reaction, Leimgruber – Batcho synthesis, Reissert synthesis, Bartoli reaction, Madelung synthesis and Cadogan – Sundberg reaction are considered. The presented new approaches include transformations of heterocycles, synthesis from o-alkynylanilines, reductive cyclization of nitrobenzene derivatives, synthesis with the use of arynes and catalysis by N-heterocyclic carbenes. The final Section summarizes original methods for the synthesis of indoles other than those listed above; they are classified in terms of the nature of the forming bond (C–C, C–N). Rarely used methods based on benzene ring construction in pyrrole derivatives are discussed separately.
The bibliography includes 246 references
The use of environmental DNA as an early warning tool in the detection of new freshwater invasive non-native species.
Authors: Blackman R. C. , Hänfling B. , Lawson-Handley L. 
Published: August 2018

Abstract
Successful removal and eradication of invasive non-native species (INNS) relies on early detection, ideally with pathway screening, to prevent any spread or outbreak in to a new region. The collection of DNA from environmental samples, known as environmental DNA or eDNA, is a revolutionary technique allowing the screening of target species without their prior collection or observation. This technique has been referred to as a 'game changer' for biodiversity monitoring, and the potential for INNS detection is particularly appealing. Current freshwater monitoring methods are heavily dependent on specimens being in sufficient number to be collected, thus making early detection at the beginning of an invasion, when numbers are likely to be low, challenging. However, the DNA of new INNS may still be prevalent in the environment, even at low densities, making detection possible. Here we review the recent developments in the application of eDNA for the detection of INNS, and assess the promise and pitfalls for its more widespread application.
Morning Home Blood Pressure and Cardiovascular Events in a Japanese General Practice Population Over 80 Years Old: The J-HOP Study
Authors: Kawauchi Dai , Hoshide Satoshi , Kario Kazuomi 
Published: August 2018

Abstract

BACKGROUND
Home blood pressure (BP) measurement has been well accepted for use in the diagnosis and treatment of hypertension. However, data regarding the association between home BP levels and cardiovascular events in a general practice population aged ≥80 years are sparse.

METHODS
We analyzed the cases of 349 patients ≥80 years old from the Japan Morning Surge-Home Blood Pressure (J-HOP) Study, a nationwide practice-based study of 4,310 Japanese with a history of and/or risk factors for cardiovascular disease. Home BP measurements were performed twice daily (morning and evening) over 14 consecutive days at baseline.

RESULTS
During a median follow-up of 3.0 years, 32 composite cardiovascular events (13 strokes and 19 nonstroke events) occurred. Higher morning systolic BP (SBP) was a significant risk factor for composite cardiovascular events (hazard ratio (HR) per 10mm Hg, 1.23; 95% confidence interval (CI): 1.01–1.50) and stroke events (HR per 10mm Hg, 1.47; 95% CI: 1.08–2.00) after adjustment by the 4-year cardiovascular risk scores and clinic SBP. In the adjusted model, morning diastolic BP also tended to be a significant risk factor of stroke events (HR per 5 mm Hg, 1.43; 95% CI: 1.00–2.05). However, these associations were not found for evening BP or clinic BP.

CONCLUSIONS
Morning home BP showed a positive linear association with cardiovascular events, especially with stroke. This association was not observed for clinic BP or evening home BP. Based on these results, in very elderly Asian populations, measuring morning home BP might be important in clinical practice regardless of the individual’s office BP level.
Deconvoluting essential gene signatures for cancer growth from genomic expression in compound-treated cells
Authors: Jung Jinmyung , Kang Yeeok , Paik Hyojung , Kwon Mijin , Yu Hasun , Lee Doheon 
Published: August 2018

Abstract

Motivation
Essential gene signatures for cancer growth have been typically identified via RNAi or CRISPR–Cas9. Here, we propose an alternative method that reveals the essential gene signatures by analysing genomic expression profiles in compound-treated cells. With a large amount of the existing compound-induced data, essential gene signatures at genomic scale are efficiently characterized without technical challenges in the previous techniques.

Results
An essential gene is characterized as a gene presenting positive correlation between its down-regulation and cell growth inhibition induced by diverse compounds, which were collected from LINCS and CGP. Among 12 741 genes, 1092, 1 228 827 962, 1 664 580 and 829 essential genes are characterized for each of A375, A549, BT20, LNCAP, MCF7, MDAMB231 and PC3 cell lines (P-value ≤ 1.0E–05). Comparisons to the previously identified essential genes yield significant overlaps in A375 and A549 (P-value ≤ 5.0E–05) and the 103 common essential genes are enriched in crucial processes for cancer growth. In most comparisons in A375, MCF7, BT20 and A549, the characterized essential genes yield more essential characteristics than those of the previous techniques, i.e. high gene expression, high degrees of protein–protein interactions, many homologs and few paralogs. Remarkably, the essential genes commonly characterized by both the previous and proposed techniques show more significant essential characteristics than those solely relied on the previous techniques. We expect that this work provides new aspects in essential gene signatures.

Availability and implementation
The Python implementations are available at https://github.com/jmjung83/deconvolution_of_essential_gene_signitures.

Supplementary information
Supplementary data are available at Bioinformatics online.
Specialization Models of Network Growth
Authors: Bunimovich L A , Smith D C , Webb B Z 
Published: August 2018

AbstractOne of the most important features observed in real networks is that, as a network’s topology evolves so does the network’s ability to perform various complex tasks. To explain this, it has also been observed that as a network grows certain subnetworks begin to specialize the function(s) they perform. Herein, we introduce a class of models of network growth based on this notion of specialization and show that as a network is specialized using this method its topology becomes increasingly sparse, modular and hierarchical, each of which are important properties observed in real networks. This procedure is also highly flexible in that a network can be specialized over any subset of its elements. This flexibility allows those studying specific networks the ability to search for mechanisms that describe their growth. For example, we find that by randomly selecting these elements a network’s topology acquires some of the most well-known properties of real networks including the small-world property, disassortativity and a right-skewed degree distribution. Beyond this, we show how this model can be used to generate networks with real-world like clustering coefficients and power-law degree distributions, respectively. As far as the authors know, this is the first such class of models that can create an increasingly modular and hierarchical network topology with these properties.
Multimorbidity Patterns, Frailty, and Survival in Community-Dwelling Older Adults
Authors: Nguyen Quoc Dinh , Wu Chenkai , Odden Michelle C , Kim Dae Hyun 
Published: August 2018

Abstract

Background
Frailty and multimorbidity are independent prognostic factors for mortality, but their interaction has not been fully explored. We investigated the importance of multimorbidity patterns in older adults with the same level of frailty phenotype.

Methods
In a cohort of 7,197 community-dwelling adults aged 65 years and older, physical frailty status (robust, pre-frail, frail) was defined using shrinking, exhaustion, inactivity, slowness, and weakness. Latent class analysis was used to identify individuals with multimorbidity patterns based on 10 self-reported chronic conditions. We estimated hazard ratios (HR) and incidence rate differences (IRDs) for mortality comparing multimorbidity patterns within each frailty state.

Results
Five multimorbidity classes were identified: minimal disease (24.7%), cardiovascular disease (29.0%), osteoarticular disease (27.3%), neuropsychiatric disease (8.9%), and high multisystem morbidity (10.0%). Within each frailty state, the mortality rate per 1,000 person-years over 4 years was greatest in the neuropsychiatric class and lowest in the minimal disease class: robust (56.3 vs 15.7; HR, 2.11 [95% CI: 1.05, 4.21]; IRD, 24.1 [95% CI: −11.2, 59.3]), pre-frail (85.3 vs 40.4; HR, 1.74 [95% CI: 1.28, 2.37]; IRD, 27.1 [95% CI: 7.6, 46.7]), and frail (218.1 vs 96.4; HR, 2.05 [95% CI: 1.36, 3.10]; IRD, 108.4 [95% CI: 65.0, 151.9]). Although HRs did not vary widely by frailty, the excess number of deaths, as reflected by IRDs, increased with greater frailty level.

Conclusions
Considering both multimorbidity patterns and frailty is important for identifying older adults at greater risk of mortality. Of the five patterns identified, the neuropsychiatric class was associated with lower survival across all frailty levels.
Low-value clinical practices and harm caused by non-adherence to ‘do not do’ recommendations in primary care in Spain: a Delphi study
Authors: Mira José Joaquín , Caro Mendivelso Johanna , Carrillo Irene , González de Dios Javier , Olivera Guadalupe , Pérez-Pérez Pastora , Nebot Cristina , Silvestre Carmen , Agra Yolanda , Fernandez Ana , Valencia-Martín José L , Ariztegui Ana , Aranaz Jesús ,   SOBRINA Research Team
Published: August 2018

Abstract

Objective
To determine the non-adherence to the primary care ‘do not do’ recommendations (DNDs) and their likelihood to cause harm.

Design
Delphi study.

Setting
Spanish National Health System.

Participants
A total of 128 professionals were recruited (50 general practitioners [GPs], 28 pediatricians [PEDs], 31 nurses who care for adult patients [RNs] and 19 pediatric nurses [PNs]).

Interventions
A selection of 27 DNDs directed at GPs, 8 at PEDs, 9 at RNs and 4 at PNs were included in the Delphi technique. A 10-point scale was used to assess whether a given practice was still present and the likelihood of it causing of an adverse event.

Main outcome measure
Impact calculated by multiplying an event’s frequency and likelihood to cause harm.

Results
A total of 100 professionals responded to wave 1 (78% response rate) and 97 of them to wave 2 (97% response rate). In all, 22% (6/27) of the practices for GPs, 12% (1/8) for PEDs, 33% (3/9) for RNs and none for PNs were cataloged as frequent. A total of 37% (10/27) of these practices for GPs, 25% (2/8) for PEDs, 33% (3/9) for RNs and 25% (1/4) for PNs were considered as potential causes of harm. Only 26% (7/27) of the DNDs for GPs showed scores equal to or higher than 36 points. The impact measure was higher for ordering benzodiazepines to treat insomnia, agitation or delirium in elderly patients (mean = 57.8, SD = 25.3).

Conclusions
Low-value and potentially dangerous practices were identified; avoiding these could improve care quality.
The ceroplastic collection of the Royal Veterinary School in Madrid: a history waiting to be recovered
Authors: Sánchez de Lollano Prieto Joaquín , Sánchez Ortiz Alicia 
Published: August 2018

Abstract
The principal aim of this article is to raise awareness of a collection whose singular nature endows it with enormous heritage value. It presents a historiographical and artistic analysis of the collection of wax models formed at the Royal Veterinary College in Madrid in the period from 1793 to 1863 and currently preserved in the Complutense Veterinary Museum. The data extracted from primary documentary sources, such as the records from the old school which have been preserved, have been verified using secondary bibliography, complemented by scientific observations on the sculptures in question. The results obtained have enabled us to reconstruct the history of the creation and functioning of the ‘Waxworks Laboratory’, to identify the manufacturers and the technical choices they made, to date each model, and to determine the reasons behind the loss of a significant number of them.
Cancer Risk in Myotonic Dystrophy Type I: Evidence of a Role for Disease Severity
Authors: Alsaggaf Rotana , St. George Diane Marie M , Zhan Min , Pfeiffer Ruth M , Wang Youjin , Wagner Kathryn R , Greene Mark H , Amr Sania , Gadalla Shahinaz M 
Published: August 2018

Abstract

Background
Myotonic dystrophy type 1 (DM1) is an inherited trinucleotide repeat disorder in which specific cancers have been implicated as part of the disease phenotype. This study aimed to assess whether cancer risk in DM1 patients is modified by disease severity.

Methods
Using the United Kingdom Clinical Practice Research Datalink (primary care electronic medical records), we identified a cohort of 927 DM1 and a matched cohort of 13 085 DM1-free individuals between January 1, 1988 and February 29, 2016. We used Cox regression models to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of organ-specific cancer risks. Analyses were stratified by age at DM1 diagnosis as a surrogate for disease severity. Statistical tests were two-sided.

Results
Patients with classic DM1 (age at diagnosis: 11–40 years) were at elevated risk of cancer overall (HR = 1.81; 95% CI = 1.12 to 2.93); cancers of the thyroid (HR = 15.93; 95% CI = 2.45 to 103.64), uterus (HR = 26.76; 95% CI = 2.32 to 309.26), and cutaneous melanoma (HR = 5.98; 95% CI = 1.24 to 28.79) accounted for the excess. In late-onset DM1 patients (age at diagnosis >40 years), a reduced overall cancer risk was observed (HR = 0.53; 95% CI = 0.32 to 0.85), possibly driven by the deficit in hematological malignancies (DM1 = 0 cases, DM1-free = 54 cases; P = .02). The difference between the observed HR for classic and late-onset DM1 was statistically significant (P < .001).

Conclusions
The observed difference in relative cancer risk between classic and late-onset DM1 patients compared with their DM1-free counterparts provides the first evidence that disease severity modifies DM1-related cancer susceptibility. This novel finding may guide clinical management and scientific investigations for the underlying molecular mechanisms in DM-related carcinogenesis.
The obligations of Member States under the EU competition rules
Authors: Whish Richard , Bailey David 
Published: August 2018

Abstract
This chapter examines the obligations of Member States in relation to EU competition law. Specifically, it considers the obligations that Article 4(3) TEU and Articles 37 and 106 TFEU place upon Member States. Article 4(3) requires all Member States to take all appropriate measures to ensure fulfilment of the obligations arising out of the Treaties, and to avoid any measure which could jeopardise the attainment of the EU’s objectives. Article 106 particularly obligates Member States to refrain from enacting or maintaining measures contrary to the rules provided in Article 18 and Articles 101 to 109 of the TFEU. Article 37 is concerned with the procurement of goods.
Articles 101 and 102: private enforcement in the courts of Member States
Authors: Whish Richard , Bailey David 
Published: August 2018

Abstract
This chapter describes the private enforcement of Articles 101 and/or 102 as a matter of EU law, with particular emphasis on the Damages Directive. It also deals with the extensive experience of private actions in the UK courts. The chapter considers the use of competition law as a defence, for example to an action for breach of contract or infringement of an intellectual property right. The chapter concludes with a brief discussion of issues that can arise where competition law disputes are referred to arbitration rather than to a court for resolution.
Enterprise Act 2002: market studies and market investigations
Authors: Whish Richard , Bailey David 
Published: August 2018

Abstract
This chapter describes the UK system of market studies and market investigation references. It begins by describing the CMA’s ‘general function’ of gathering information about markets, followed by an explanation of what is meant by a ‘super-complaint’. It examines the purpose, procedure and outcomes of market studies, including possible outcomes. Market studies sometimes lead to market investigation references, although there are several other possible outcomes of a market study. The chapter describes the making and determination of analyses and the market investigation provisions under Part 4 of the Enterprise Act 2002. Having briefly considered public interest cases, enforcement and other supplementary matters, the chapter discusses how the market investigation provisions have been working in practice. The final section of the chapter briefly refers to the enforcement and review of undertakings and orders still in force under the monopoly provisions in the former Fair Trading Act 1973.
The international dimension of competition law
Authors: Whish Richard , Bailey David 
Published: August 2018

Abstract
This chapter explores the international dimension of competition law. Along with the introduction of the theory of extraterritoriality, sections 2 to 6 are concerned with two questions. The first issue is whether an offended country could apply its competition rules extraterritorially against an undertaking or undertakings in another country behaving anti-competitively. The second issue is whether there should be laws or so-called ‘blocking statutes’ to prevent the ‘excessive’ assertion of extraterritorial jurisdiction. However, the international dimension of competition law has undoubtedly evolved beyond these somewhat parochial concerns: the final section describes the work of international organisations, such as the International Competition Network (‘the ICN’), which encourages cooperation between competition authorities, and more importantly fosters convergence between competition policies, procedures and substantive analysis.
Horizontal agreements (1): cartels
Authors: Whish Richard , Bailey David 
Published: August 2018

Abstract
This chapter is concerned with the prohibition of cartels, also referred to as ‘hard-core’ horizontal agreements. The chapter begins with a discussion of the widespread consensus among competition authorities worldwide that cartels should be condemned, and gives examples of recent enforcement that has led to the imposition of significant fines and sentences of imprisonment. It also looks at the European Commission’s enforcement activity in relation to cartels. The chapter then considers the application of Article 101 to particular types of cartels: price fixing, market sharing, production quotas and other hard-core cartel practices. The final section of the chapter looks at anti-cartel enforcement and judicial practice in the UK.
The relationship between intellectual property rights and competition law
Authors: Whish Richard , Bailey David 
Published: August 2018

Abstract
This chapter considers the relationship between intellectual property rights and competition law. After a brief introduction, it deals in general terms with the application of Article 101 to licences of intellectual property rights. The chapter proceeds to discuss the provisions of Regulation 316/2014, the block exemption for technology transfer agreements. It also considers the application of Article 101 to various other agreements concerning intellectual property rights such as technology pools and settlements of litigation. This is followed by a section on the application of Article 102 to the way in which dominant undertakings exercise their intellectual property rights, including an examination of the controversial subject of refusals to license intellectual property rights which are sometimes found to be abusive. The chapter concludes with a look at the position in UK competition law.
Particular sectors
Authors: Whish Richard , Bailey David 
Published: August 2018

Abstract
This chapter deals with three issues. First it examines those sectors of the economy that are wholly or partly excluded from EU competition law, namely nuclear energy, military equipment and agriculture; the special regime for coal and steel products under the former European Coal and Steel Community (‘the ECSC’) Treaty is briefly referred to. Secondly, it describes how the EU competition rules apply to the transport sector. Finally, the chapter considers the specific circumstances of so-called ‘regulated industries’ such as electronic communications, post and energy and the way in which EU and UK competition law apply to them. Constraints of space mean that these matters can be described only in outline; references to specialised literature on the application of competition law to particular sectors will be provided where appropriate.
Implementation of an Alternative Pathway for Patients Seeking Care for Low Back Pain: A Prospective Observational Cohort Study
Authors: Magel John , Hansen Pamela , Meier Whitney , Cohee Kim , Thackeray Anne , Hiush Matthew , Fritz Julie M 
Published: August 2018

Abstract

Background
In the United States, low back pain (LBP) is among the most common symptoms prompting a health care visit. Patients can receive escalated care, such as advanced imaging or invasive procedures, before guideline-recommended options offered by physical therapists. A guideline-concordant alternative care pathway (RapidAccess) that emphasized early physical therapy for patients with LBP before they consulted a physiatrist was implemented. Evaluating the implementation of care pathways, such as RapidAccess using the RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) framework, provides a broader understanding of the barriers to implementation.

Objective
The purpose of this study was to evaluate the implementation of a guideline-concordant care pathway for patients with LBP using a RE-AIM framework.

Design
This study used a prospective observational cohort design.

Methods
Patients with a chief complaint of LBP who were scheduling a new appointment with physiatry were eligible. Eligible patients chose whether or not to participate in RapidAccess before a consultation with a physiatrist. Implementation outcomes were evaluated using the RE-AIM framework.

Results
During the study period, 1556 patients with LBP called to schedule a new visit with a physiatrist. Of these, 400 (25.7%) were eligible for RapidAccess, and 124 (31% of those eligible) participated in the program (reach). Of the 400 eligible patients, 225 (56.3%) were offered RapidAccess (adoption). Compared with patients who were managed in physical therapy following a consultation with a physiatrist, RapidAccess participants demonstrated improvement in physical function with physical therapist management (effectiveness); 58.9% cancelled their physiatrist visit (implementation), and rates of imaging and injections were lower (effectiveness). Reach and adoption (maintenance) trended downward beyond the first 6 months of the project.

Limitations
The results are from a single health system and might not be broadly generalizable.

Conclusions
The RE-AIM framework was useful in evaluating the implementation of RapidAccess. Factors influencing reach and adoption must be further examined.