bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic implications of left ventricular myocardial work indices in cardiac amyloidosis
Authors: Clemmensen Tor Skibsted , Eiskjær Hans , Ladefoged Bertil , Mikkelsen Fabian , Sørensen Jens , Granstam Sven-Olof , Rosengren Sara , Flachskampf Frank A , Poulsen Steen Hvitfeldt 
Published: May 2020

Abstract

Aims
Left ventricular (LV) myocardial work index (LVMWI) derived from pressure–strain analysis resembles a novel non-invasive method for LV function evaluation. LV global longitudinal strain (LVGLS) has proven beneficial for risk stratification in cardiac amyloidosis (CA) patients. This study aimed to evaluate the potential additive value of LVMWI for outcome prediction in CA patients.

Methods and results
We enrolled 100 CA patients in the period 2014–19 from Aarhus University Hospital, Denmark and Uppsala University Hospital, Sweden. All patients underwent comprehensive echocardiographic evaluation and were prospectively followed until censuring date on 31 March 2019 or death. During follow-up, we registered major adverse cardiac events (MACE) comprising heart failure requiring hospitalization and all-cause mortality. The median follow-up was 490 (228–895) days. During follow-up, a total of 42% of patients experienced MACE and 29% died. Patients with LVMWI &lt;1043 mmHg% had higher MACE risk than patients with LVMWI &gt;1043 mmHg% [hazard ratio (HR) 2.3, 95% confidence interval (CI) 1.2–4.3; P = 0.01]. Furthermore, patients with LVMWI &lt;1039 mmHg% also had higher all-cause mortality risk than patients with LVMWI &gt;1039 mmHg% (HR 2.6, 95% CI 1.2–5.5; P &lt; 0.05). Moreover, the apical-to-basal segmental work ratio was a significant MACE and all-cause mortality predictor. By combining LVMWI and apical-to-basal segmental work ratio, we obtained an independent model for all-cause mortality prediction (high vs. low risk: HR 6.4, 95% CI 2.4–17.1; P &lt; 0.0001). In contrast, LVGLS did not predict all-cause mortality.

Conclusion
LV myocardial work may be of prognostic value in CA patients by predicting both MACE and all-cause mortality.
The interplay between cardiology and diabetology: a renewed collaboration to optimize cardiovascular prevention and heart failure management
Authors: Sabouret Pierre , Galati Giuseppe , Angoulvant Denis , Germanova Olga , Castelletti Silvia , Pathak Atul , Metra Marco , Margonato Alberto 
Published: May 2020

Abstract
Type 2 diabetes mellitus (T2DM) portends high risk of atherosclerotic cardiovascular (CV) events and of CV mortality; moreover, this group of patients has a very high probability of developing heart failure (HF). In this review, we discuss new advances in pharmacological treatment both in CV prevention and in HF management with a special focus on T2DM patients. A large number of randomized clinical trials and meta-analyses provided strong evidence about therapeutic strategies acting on glucose metabolism, such as GLP-1 RA and SGLT2i and about lipid-lowering treatment, such as PCSK9i and icosapent ethyl. Moreover, SGLT2i demonstrated strong evidence of benefit particularly in HF management both in diabetic and non-diabetic patients. The pathophysiological bases of multiple mechanisms of benefit of this class of drug explain the unexpected and remarkable results demonstrated both by prevention trials and by trials dedicated only to HF (like DAPA-HF). These, new drugs in the CV therapeutic armamentarium are establishing a new comprehensive approach from prevention to therapy of HF, giving more emphasis on HF classification in four stages (A→D). New therapies, which are on the horizon, promise to further reduce CV mortality and morbidity in HF patients irrespective of diabetic status.
Grazing effect of flagellates on bacteria in response to phosphate addition in the oligotrophic Cretan Sea, NE Mediterranean
Authors: Oikonomou Andreas , Livanou Eleni , Mandalakis Manolis , Lagaria Anna , Psarra Stella 
Published: May 2020

ABSTRACT
The planktonic food web in the oligotrophic Mediterranean Sea is dominated by small-sized (&lt;20 μm) microbes, with nanoflagellates being the major bacterial grazers and the main participants in nutrient cycling. Phosphate is a key nutrient in the P-limited Cretan Sea (NE Mediterranean) and P-availability can affect its trophic dynamics. Here, we examined the grazing potential of heterotrophic (HF) and pigmented (PF) nanoflagellates as a response mechanism to phosphate amendment. Flagellate grazing effect on bacteria was quantified in P-amended nutrient-depleted water from the Cretan Sea over the course of 4 days using microcosm experiments. P-addition positively affected HF abundance, while PF abundance remained unchanged. At the community level, P-addition had a negative effect on PF bacterial removal rates. In the control, PF-grazing rate was significantly higher than that of HF throughout the experiment. Pigment analysis showed no changes in phytoplankton community composition as a result of P-addition, indicating that PF grazing rate declined as a physiological response of the cells. The present study emphasizes the dominant grazing role of PF under P-depleted conditions and reveals that during the late stratified season PF respond to P-addition by lowering their grazing rates, enhancing the relative importance of bacterial removal by HF.
Upregulated insulin receptor tyrosine kinase substrate promotes the proliferation of colorectal cancer cells via the bFGF/AKT signaling pathway
Authors: Wang Song , Liu Zheng , Ma Yi-Ming , Guan Xu , Jiang Zheng , Sun Peng , Liu En-Rui , Zhang Yu-Kun , Wang Hong-Ying , Wang Xi-Shan 
Published: May 2020

Abstract

Background
Some recent studies on insulin receptor tyrosine kinase substrate (IRTKS) have focused more on its functions in diseases. However, there is a lack of research on the role of IRTKS in carcinomas and its mechanism remains ambiguous. In this study, we aimed to clarify the role and mechanism of IRTKS in the carcinogenesis of colorectal cancer (CRC).

Methods
We analysed the expression of IRTKS in CRC tissues and normal tissues by researching public databases. Cancer tissues and adjacent tissues of 67 CRC patients who had undergone radical resection were collected from our center. Quantitative real-time polymerase chain reaction and immunohistochemistry were performed in 52 and 15 pairs of samples, respectively. In vitro and in vivo experiments were conducted to observe the effect of IRTKS on CRC cells. Gene Set Enrichment Analysis and Metascape platforms were used for functional annotation and enrichment analysis. We detected the protein kinase B (AKT) phosphorylation and cell viability of SW480 transfected with small interfering RNAs (siRNAs) with or without basic fibroblast growth factor (bFGF) through immunoblotting and proliferation assays.

Results
The expression of IRTKS in CRC tissues was higher than that in adjacent tissues and normal tissues (all P &lt; 0.05). Disease-free survival of patients with high expression was shorter. Overexpression of IRTKS significantly increased the proliferation rate of CRC cells in vitro and the number of tumor xenografts in vivo. The phosphorylation level of AKT in CRC cells transfected with pLVX-IRTKS was higher than that in the control group. Furthermore, siRNA-IRTKS significantly decreased the proliferation rate of tumor cells and the phosphorylation level of AKT induced by bFGF.

Conclusion
IRTKS mediated the bFGF-induced cell proliferation through the phosphorylation of AKT in CRC cells, which may contribute to tumorigenicity in vivo.
Measuring Self-Perceptions of Aging: Differences Between Measures When Predicting Health Outcomes
Authors: Boeder Jordan , Tse Dwight C K 
Published: May 2020

Abstract

Objectives
The majority of self-perceptions of aging (SPA) research uses either a combination of the Aging-related Cognitions (AgeCog) scales of Ongoing Development and Physical Loss, or the Attitudes Towards Own Aging (ATOA) subscale to assess views on aging. Although these scales are used interchangeably, the valence (positive/negative) and the specificity of the view on aging (domain-based/general) being assessed are not consistent. This study investigates how different measures of SPA relate to one another and whether they differentially predict various types of health outcomes (psychological/physiological; well-being/ill-being).

Method
Data from the 2008 and 2014 waves of the German Aging Survey (DEAS; N = 3,745), a population-based representative survey of adults aged 40–95, was used to examine the relationship between the AgeCog scales and the ATOA subscale, as well as the differences in the types of health outcomes each predicts.

Results
The correlations between the AgeCog scales and the ATOA were higher than the correlation between the AgeCog scales (p &lt; .001). The AgeCog scale of Ongoing Development significantly predicted psychological health outcomes across a 6-year period, while the AgeCog scale of Physical Loss and the ATOA subscale predicted both physiological and psychological health outcomes.

Discussion
Evidence supports using the AgeCog scale of Ongoing Development to predict domain-relevant, psychological health outcomes. However, the multidimensionality of SPA is best measured by the ATOA subscale or a combination of the two AgeCog scales. Both forms of measurement were found to maximize the amount of explained variance for psychological and physiological indicators of well-being and ill-being.
Evaluation of the in vitro activity of new polymyxin B analogue SPR206 against clinical MDR, colistin-resistant and tigecycline-resistant Gram-negative bacilli
Authors: Zhang Yawei , Zhao Chunjiang , Wang Qi , Wang Xiaojuan , Chen Hongbin , Li Henan , Zhang Feifei , Wang Hui 
Published: May 2020

AbstractBackgroundSPR206 is a novel polymyxin analogue. Activity against clinical isolates is little documented.MethodsA collection of 200 MDR, carbapenem-resistant, tigecycline-resistant, colistin-resistant and non-MDR clinical isolates of Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Enterobacter cloacae and Stenotrophomonas maltophilia was obtained from 50 centres across China (2016–17). All isolates were derived from respiratory tract, urine and blood samples. Strains were purposely selected on the basis of phenotypes, genotypes and specimen origins. MICs of SPR206 and other antimicrobials were determined.ResultsSPR206 was active against all bacteria tested except colistin-resistant isolates. The MIC50/90 values of SPR206 for colistin-resistant strains were comparable to known polymyxins (16/128 versus 8/128 mg/L). SPR206 exhibited potent activity against colistin-susceptible OXA-producing A. baumannii (MIC50/90 = 0.064/0.125 mg/L), NDM-producing Enterobacteriaceae (MIC50/90 = 0.125/0.25 mg/L) and KPC-2-producing Enterobacteriaceae (MIC50/90 = 0.125/0.5 mg/L). In fact, SPR206 was the most potent agent tested, with 2- to 4-fold lower MICs than colistin and polymyxin B for A. baumannii, P. aeruginosa and Enterobacteriaceae. Additionally, MIC values of SPR206 (MIC50/90 = 0.064/0.125 mg/L) were 16- to 32-fold lower than those of tigecycline (MIC50/90 = 2/2 mg/L) for tigecycline-susceptible carbapenem-resistant A. baumannii.ConclusionsSPR206 showed good in vitro activity against MDR, tigecycline-resistant and non-MDR clinical isolates of Gram-negative pathogens. SPR206 also exhibited superior potency to colistin and polymyxin B, with 2- to 4-fold lower MIC50/90 values.
Modeling consent in the time of COVID-19
Authors: Knoppers Bartha Maria , Beauvais Michael J S , Joly Yann , Zawati Ma'n H , Rousseau Simon , Chassé Michaël , Mooser Vincent 
Published: May 2020

Abstract
Effective responses to the COVID-19 pandemic require novel solutions for research and responsible data sharing. Biobanking presents itself as a key priority in furthering our understanding of COVID-19. In this article, we propose a tripartite approach to consent to create resources for research relating to COVID-19. The approach aims to link three levels of participation: COVID-19 patients, respiratory/infectious disease patients, and longitudinal study participants. We explore the potential approaches that can be taken to consent processes with these three participant groups. We furthermore describe an access model for both single-site and multi-site data and sample storage. Through dealing with these topics at a high level, the model may be adapted to local legal and ethical requirements while still pursuing its ultimate goal: the creation of a research infrastructure that supports transparent, strong, and open science.
Underperformed and Underreported Testing for Persistent Oropharyngeal Poliovirus Infections in Primary Immune Deficient Patients—Risk for Reemergence of Polioviruses
Authors: Shulman Lester M , Weil Merav , Somech Raz , Stauber Tali , Indenbaum Victoria , Rahav Galia , Mendelson Ella , Sofer Danit 
Published: May 2020

Abstract

Background
Individuals with primary immune deficiencies (PIDs) may excrete poliovirus for extended periods and remain a major reservoir for polio after eradication. Poliovirus can spread by fecal–oral or oral–oral transmission. In middle- and high-income countries, oral–oral transmission may be more prevalent than fecal–oral transmission of polioviruses where PIDs patients survive longer. Our aim was to determine the prevalence of prolonged or persistent oropharyngeal poliovirus infections in PIDs.

Methods
We performed a literature search for reports of prolonged (excreting poliovirus for ≥6 months and ≤5 years) or persistent (excreting poliovirus for &gt;5 years) poliovirus infections in PIDs.

Results
There were 140 PID cases with prolonged or persistent poliovirus infections. All had poliovirus-positive stools. Testing of oropharyngeal mucosa was only reported for 6 cases, 4 of which were positive. Molecular analyses demonstrated independent evolution of poliovirus in the gut and oropharyngeal mucosa in 2 cases. Seven PIDs had multiple lineages of the same poliovirus serotype in stools without information about polioviruses in oropharyngeal mucosa.

Conclusions
Testing for persistence of poliovirus in oropharyngeal mucosa of PID patients is rare, with virus recovered in 4 of 5 cases in whom stools were positive. Multiple lineages or serotypes in 7 additional PID cases may indicate separate foci of infection, some of which might be in oropharyngeal mucosa. We recommend screening throat swabs in addition to stools for poliovirus in PID patients. Containment protocols for reducing both oral–oral and fecal–oral transmission from PID patients must be formulated for hospitals and community settings.
Similar yet critically different: the distribution, dynamics and function of histone variants
Authors: Probst Aline V , Desvoyes Bénédicte , Gutierrez Crisanto 
Published: May 2020

AbstractOrganization of the genetic information into chromatin plays an important role in the regulation of all DNA template-based reactions. The incorporation of different variant versions of the core histones H3, H2A, and H2B, or the linker histone H1 results in nucleosomes with unique properties. Histone variants can differ by only a few amino acids or larger protein domains and their incorporation may directly affect nucleosome stability and higher order chromatin organization or indirectly influence chromatin function through histone variant-specific binding partners. Histone variants employ dedicated histone deposition machinery for their timely and locus-specific incorporation into chromatin. Plants have evolved specific histone variants with unique expression patterns and features. In this review, we discuss our current knowledge on histone variants in Arabidopsis, their mode of deposition, variant-specific post-translational modifications, and genome-wide distribution, as well as their role in defining different chromatin states.
Insurance
Authors: Benatar Martin , Hussain Munib 
Published: May 2020

Abstract
This chapter discusses the importance of project insurance. Financiers take an onerous approach to insurance in project finance transactions, requiring a comparably more robust insurance programme than would be adopted in a project that is financed on balance sheet alone. This reflects the fact that until the project company has established a reliable revenue stream, it will have a low level of capitalization and be highly leveraged. The primary function of insurance is to act as a risk transfer mechanism. In return for a known cost (the premium) the uncertainty associated with both the frequency and severity of loss is transferred to the insurer. The discussions cover insurance programme design, project company control, the breadth and scope of the insurance programme, legal and commercial influences on procurement, and insurance risk itself and lenders’ clauses.
The IPO Process, IPO Disclosure, and the Prospectus Regulation
Authors: Teerink Han 
Published: May 2020

Abstract
This chapter offers insight into a typical initial public offering (IPO) process, highlighting key practical and legal considerations around disclosure, through the IPO prospectus and otherwise. The prospectus plays a key role in the preparations for, and execution of, an IPO. As an IPO prospectus typically constitutes a company's first public dissemination of financial and business information, the company and other parties involved in the IPO process must carefully consider the right balance between, on the one hand, drafting the IPO prospectus as a marketing document introducing the company and its business to potential investors, whilst, on the other hand, being able to use the prospectus as a disclosure document that protects the company against liability arising from claims from investors or others after the IPO. Here, the chapter summarizes the different phases in an IPO process and the most important documents and parties involved, focusing on the central role of the IPO prospectus. In addition, a number of changes resulting from the enactment of the Prospectus Regulation are likely to be of particular relevance to IPO processes. The expected impact of these changes is therefore also discussed.
Stabilization and Underpricing in IPOs
Authors: Lombardo Stefano 
Published: May 2020

Abstract
This chapter zooms in on stabilization and underpricing in IPOs. The Market Abuse Regulation (MAR) provides an exemption from the prohibitions of insider dealing and of market manipulation for the stabilisation of securities. This is usually realised in the case of an initial public offering (IPO) and is regulated in detail by Commission Delegated Regulation 2016/1052. The chapter thus introduces the economic theory of IPOs, analysing in particular the underpricing phenomenon (and its opposite, the overpricing). After a comparative and useful description of the US system of IPO stabilization activity, the chapter focuses on a detailed analysis of the European regime under MAR and Regulation 2016/1052.
The Obligation to Publish a Prospectus and Exemptions
Authors: Lieverse Kitty 
Published: May 2020

Abstract
This chapter offers a comprehensive treatment of the obligation to publish a prospectus, including the available exemptions. The Prospectus Regulation provides for an update of the prospectus obligation and the exemptions thereto. However, the provisions that determine the requirement to publish an approved prospectus have remained unaltered. In addition, the exemptions to have a prospectus available compliant with the Prospectus Regulation have largely remained the same. The chapter shows, however, that there have been some changes when it comes to exemptions. Notably, the regime for small size offerings has changed. The chapter concludes that the goal of the European legislator to enhance harmonisation between the member states by including the prospectus regime in a regulation, has not been achieved for these small-size offerings. In addition, some exemptions for the prospectus requirement in the event of a listing have either been extended or restricted. Finally, the chapter notes that the disclosure regime as such, as is provided by a prospectus under the Prospectus Regulation, has not been truly reconsidered, in the context also of concurrence with other disclosure regimes.
‘Light’ Disclosure Regimes
Authors: Perrone Andrea 
Published: May 2020

Abstract
This chapter zooms in on the ‘light’ disclosure regime for small and medium-sized enterprises (SMEs). It shows that SME financing through capital markets is no easy task. On the supply side, adverse selection and lack of liquid secondary markets hamper the access of both retail and professional investors. On the demand side, lack of financial literacy, costs of compliance, and the possibility for the owners to lose control of the firm discourage SMEs from turning to capital markets for funds. For both reasons, it is therefore understandable why SMEs are typically financed through banking and banks maintain a ‘monopolistic’ power over SMEs. In this context, the chapter argues that the light disclosure regime introduced by the Prospectus Regulation is mostly toothless. Still shaped by the ‘myth of the informed layman’ and of little use to institutional investors, the EU Growth prospectus does reduce compliance costs for issuers but suffers the lack of a EU-based ‘eco-system’ fully supporting SMEs seeking finance.
‘Light’ Disclosure Regimes
Authors: Horsten Pim 
Published: May 2020

Abstract
This chapter analyses and discusses the ‘light’ disclosure regime available for secondary issuances. Here, it remains to be seen whether this new simplified regime will be used much in practice. The proportionate disclosure regime for statutory rights issues introduced by the 2010 amendment of the Prospectus Directive was little used. Moreover, at a conceptual level the chapter submits that not many would disagree that for investors at some stage more disclosure makes a prospectus difficult to understand, as it may be difficult to discern important facts in a mass of less important detail. The chapter asserts that the ideal disclosure document is short, clear, and comprehensive in including all information an investor needs to make an informed investment decision. The tension, however, is between short and comprehensive, in the sense of including all necessary information. The chapter concludes that time will tell whether in case of secondary issuances one will see simplified prospectuses with reduced disclosure only.
Luxembourg
Authors: Hoffeld Veronique 
Published: May 2020

Abstract
This chapter focuses on the Luxembourg civil liability regime which applies to information given in a prospectus. Luxembourg has implemented certain specific provisions on prospectus liability; however, these do not constitute an entirely autonomous civil liability regime on prospectus liability as such. Most aspects with regards to a person's liability must be determined in accordance with the general Luxembourg provisions on civil liability from the Luxembourg Civil Code. No questions have yet arisen before the Luxembourg courts on the liability regime which applies to those persons responsible for the information given in a prospectus. There is therefore no established Luxembourg case law complementing the provisions currently in place. This chapter thus concerns those situations where a prospectus contains misleading information or omits to include material information infringing the requirements of the Luxembourg legal provisions on prospectuses.