bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuronal SETD2 activity links microtubule methylation to an anxiety-like phenotype in mice
Authors: Koenning Matthias , Wang Xianlong , Karki Menuka , Jangid Rahul Kumar , Kearns Sarah , Tripathi Durga Nand , Cianfrocco Michael , Verhey Kristen J , Jung Sung Yun , Coarfa Cristian , Ward Christopher Scott , Kalish Brian Thomas , Grimm Sandra L , Rathmell W Kimryn , Mostany Ricardo , Dere Ruhee , Rasband Matthew Neil , Walker Cheryl Lyn , Park In Young 
Published: May 2021

AbstractGene discovery efforts in autism spectrum disorder have identified heterozygous defects in chromatin remodeller genes, the ‘readers, writers and erasers’ of methyl marks on chromatin, as major contributors to this disease. Despite this advance, a convergent aetiology between these defects and aberrant chromatin architecture or gene expression has remained elusive. Recently, data have begun to emerge that chromatin remodellers also function directly on the cytoskeleton. Strongly associated with autism spectrum disorder, the SETD2 histone methyltransferase for example, has now been shown to directly methylate microtubules of the mitotic spindle. However, whether microtubule methylation occurs in post-mitotic cells, for example on the neuronal cytoskeleton, is not known. We found the SETD2 α-tubulin lysine 40 trimethyl mark occurs on microtubules in the brain and in primary neurons in culture, and that the SETD2 C-terminal SRI domain is required for binding and methylation of α-tubulin. A CRISPR knock-in of a pathogenic SRI domain mutation (Setd2SRI) that disables microtubule methylation revealed at least one wild-type allele was required in mice for survival, and while viable, heterozygous Setd2SRI/wtmice exhibited an anxiety-like phenotype. Finally, whereas RNA-sequencing (RNA-seq) and chromatin immunoprecipitation-sequencing (ChIP-seq) showed no concomitant changes in chromatin methylation or gene expression in Setd2SRI/wtmice, primary neurons exhibited structural deficits in axon length and dendritic arborization. These data provide the first demonstration that microtubules of neurons are methylated, and reveals a heterozygous chromatin remodeller defect that specifically disables microtubule methylation is sufficient to drive an autism-associated phenotype.
The Emergence of Objective Guidelines for Granting Immunity to International Non-Governmental Organizations
Authors: Pavot David , Laperle-Forget Lolita 
Published: May 2021

Abstract
Out of thousands of international non-governmental organizations (INGOs), only five benefit from immunities from jurisdiction and execution: the International Committee of the Red Cross (ICRC), the International Union for Conservation of Nature (IUCN), the Global Fund to Fight AIDS, Tuberculosis, and Malaria; Gavi, the Vaccine Alliance (Gavi), and the World Anti-Doping Agency (WADA). Based on empirical research, this article argues that there is an emerging State practice in granting immunity only to INGOs that meet two cumulative criteria: a hybridity character and a mission of international interest, formally recognized in a source of international law. This article proposes a new approach based on both Functionalism and Institutionalism that addresses the specificities of INGOs and thus shows that international law provides guidance on the granting of immunities.
Patient Adherence to Fecal Calprotectin Testing Is Low Compared to Other Commonly Ordered Tests in Patients With Inflammatory Bowel Disease
Authors: Khakoo Nidah S , Lewis Ayanna , Roldan Giovanni A , Al Khoury Alex , Quintero Maria A , Deshpande Amar R , Kerman David H , Damas Oriana M , Abreu Maria T 
Published: May 2021

Abstract

Background
Limited data exist on adherence to fecal calprotectin (FCP) testing in patients with inflammatory bowel disease.

Methods
Completion rates for patients who had at least one FCP test ordered (n = 3082) and a subgroup with C-reactive protein, complete blood count, and Clostridium difficile tests also ordered (n = 1563) were analyzed.

Results
More patients completed blood than stool tests, with FCP having the poorest adherence of all tests analyzed. Older patients had higher FCP completion rates. No differences were noted in completion rates across age, gender, or ethnicity for blood tests.

Conclusions
Further studies are needed to develop strategies that improve the uptake of FCP.
Epidemiology of dementia onset captured in Canadian primary care electronic medical records
Authors: Pham Anh N Q , Voaklander Don , Wagg Adrian , Drummond Neil 
Published: May 2021

Abstract

Background
Dementia is an increasing concern in many countries, especially in those experiencing rapid growth in the proportion of older adults in their population.

Objective
This study aims to describe trends and demographic characteristics of incident dementia cases in community-dwelling older adults managed by primary care physicians.

Methods
We used electronic medical records from the Canadian Primary Care Sentinel Surveillance Network database to conduct a retrospective analysis to determine the number of, and trends for, incident diagnoses of dementia. Age-standardized annual incidence rates were calculated. Participants in our cohort are Canadian community dwelling seniors aged 65+ years who were not diagnosed with dementia before baseline with at least six years of record at their primary care clinics.

Results
The cohort consisted of 39 067 patients of whom 57% were females; the mean (SD) follow-up was 8.4 (1.5) years. During follow-up, 4935 patients were diagnosed with dementia. The risk for dementia diagnosis increased with increasing age but decreased in the last four years among people aged 80 and older at baseline (P &lt; 0.001). People with dementia were more likely to be females (P = 0.001) and urban residents (P &lt; 0.001), they are less likely to be classified into the least deprived group (P = 0.012).

Conclusions
The incidence of dementia diagnosis increased with age except in the oldest old in both sexes. This may be attributed to the effect of mortality competing risk. Future research on the association between risk factors and dementia should consider studying dementia among the oldest old separately to minimize bias.
Exemption for the poor or the rich? An assessment of socioeconomic inequalities in Ghana’s national health insurance exemption policies
Authors: Novignon Jacob , Atakorah Yaw Boateng , Chijere Chirwa Gowokani 
Published: May 2021

Abstract
Out-of-pocket payments for health are considered a major limitation to universal health coverage (UHC). Policymakers across the globe are committed to achieving UHC through the removal of financial barriers to health care. In Ghana, a national health insurance scheme was established for this purpose. A unique feature of the scheme is its premium exemption policies for vulnerable groups. In this article, we access the nature of socioeconomic inequality in these exemption policies. We used data from the Ghana Living Standards Survey rounds six and seven. Socioeconomic inequality was assessed using concentration curves and indices. Real household annual total consumption expenditure adjusted by adult equivalence scale was used as a wealth indicator. Four categories of exemption were used as outcome variables. These were exemptions for indigents, individuals &lt;18 years, the aged and free maternal service. The analysis was also disaggregated by rural and urban locations of individuals. We found that while overall national health insurance scheme (NHIS) coverage was concentrated among the wealthy, all categories of premium exemption were concentrated among the poor. There was also evidence of a general decline in the magnitude of inequality over the survey years. With the specific exemptions, inequalities in exemption for indigents and maternal services were most relevant in rural locations, while inequalities in exemption for individuals &lt;18 years and the aged were significant in urban areas. The findings suggest that the exemption policies under the NHIS are generally progressive and achieve the objective of inclusion for the underprivileged. However, it also provides lessons for better targeting and effective implementation. There may be a need for separate efforts to better target individuals in rural and urban locations to improve enrolment.
Rethinking sustainability in childhood obesity prevention interventions: learning from South Australia’s Obesity Prevention and Lifestyle (OPAL) Programme
Authors: Jones Michelle G , Verity Fiona 
Published: May 2021

Summary
Increases in childhood obesity have occurred across a relatively short time-period, yet childhood obesity prevention is a longer-term game. Programmes have only identified population-level changes after 12 years of on-the-ground activity [Romon et al.]. Community stakeholders can impact the success of public health interventions [Ganter et al.; Lee et al.] and they have been identified as a critical success factor for programme sustainability [Schell et al.]. Qualitative research with stakeholders (n = 59) provides their insights and understandings of the sustainability of OPAL, a South Australian childhood obesity prevention programme. Stakeholders identified activities that they thought contributed to improved sustainability of action such as embedding obesity prevention into organizational policy and plans; and installation of infrastructure within communities to modify physical environments. In contrast, there was little appetite for sustaining OPAL or other formulations of a childhood obesity prevention programme. This research has implications for planning and implementation of community-based childhood obesity prevention initiatives when considering the balance of the portfolio of activities for implementation.
The effects of smoking on pregnancy risks in women with polycystic ovary syndrome: a population-based study
Authors: Feferkorn I , Badeghiesh A , Mills G , Baghlaf H , Dahan M 
Published: May 2021

Abstract

STUDY QUESTION
Is there is an association between smoking and pregnancy complications in pregnant women with polycystic ovarian syndrome (PCOS)?

SUMMARY ANSWER
There is an increased risk of developing gestational diabetes mellitus (GDM) among women with PCOS who smoke.

WHAT IS KNOWN ALREADY
Smokers are at increased risk of developing Type 2 Diabetes Mellitus (DM). Given the common pathophysiology and shared risk factors between type 2 DM and GDM, we sought to assess whether an association between smoking and the development of GDM exists.

STUDY DESIGN, SIZE, DURATION
This is a retrospective population-based study utilizing data from the HCUP-NIS over 11 years from 2004 to 2014. Pregnant women with PCOS who did smoke were compared to pregnant women with PCOS who did not smoke. A second comparison was made between pregnant smokers with and without PCOS. Of the 443 590 women who smoked during pregnancy and the 14 882 women with PCOS, 631 women were both smokers and diagnosed with PCOS.

PARTICIPANTS/MATERIALS, SETTING, METHODS
The Healthcare Cost and Utilization Project—Nationwide Inpatient Sample (HCUP-NIS) is the largest inpatient sample database in the USA and is composed of hospital inpatient stays submitted by hospitals throughout the entire country. Each year, the database provides information relating to 7 million inpatient stays, including patient characteristics, diagnosis and procedures. The data are representative of ∼20% of admissions to US hospitals across 48 states and the District of Columbia.

MAIN RESULTS AND THE ROLE OF CHANCE
There were no differences in the risks of preterm delivery (aOR1.2; CI 0.8–1.9), placental abruption (aOR1.1; CI 0.4–3.2), pregnancy induced hypertension (aOR1.0; CI 0.7–1.5), rate of operative vaginal delivery (aOR1.5; CI 0.9–2.5) and rates of cesarean section (C/S) (aOR1.0; CI 0.7–1.3) between smoking and non-smoking women with PCOS. A significant association between smoking and GDM was observed in women with PCOS (aOR1.5; CI1.01–2.1).

LIMITATIONS, REASONS FOR CAUTION
The limitations of our study are its retrospective nature and the fact that it relies on an administrative database. Data regarding smoking and PCOS diagnosis could be skewed due to patients’ underreporting, lack of documentation and documentation differences.

WIDER IMPLICATIONS OF THE FINDINGS
The public health implications of confirming smoking as a risk for GDM among women with PCOS are many. This can lead to earlier screening in pregnancy of smokers for GDM. Earlier initiation of interventions could decrease fetal complications and possibly have an impact on the life and long-term health of the offspring. Future studies are needed in order to assess whether smoking cessation during pregnancy decreases the risk of GDM in that gestation.

STUDY FUNDING/COMPETING INTEREST(S)
No external funding was used. The authors report no competing interests.

TRIAL REGISTRATION NUMBER
N/A.
Applying health-six-sigma principles helps reducing the variability of length of stay in the emergency department
Authors: KOBO-GREENHUT Ayala , HOLZMAN Keren , RAVIV Osnat , ARAD Jakov , BEN SHLOMO Izhar 
Published: May 2021

Abstract

Background
Reducing length of stay (LOS) is one of the urgent problems in healthcare systems worldwide. Popular methods that are used to reduce LOS are the Lean and the 6 Sigma, which in practice result in limited improvements. In this paper, we introduce and test a tailored method for implementing the 6 Sigma principles in healthcare (we call H-6S).

Objective
To reduce the variability in the time between admission and discharge of patients in the emergency department.

Methods
The study took place within the emergency department (ED) of Josephtal Medical Center in Eilat, Israel. Our analysis focused on the processes of examining and treating patients from admission to ED until discharge home. The analysis was done during the second quarter of 2018. The implementation of the recommendations took place during Q3 2018. The reported results are from Q3 2018 to Q2 2019, compared to the corresponding period in 2017 (experienced team).

Results
In Q2 2017, LOS was 2.42 ± 2.07 h (experienced team, n = 9928). In Q2 2018, the LOS was 2.62 ± 7.04 h (before the H-6S, inexperienced team, n = 9484). In Q2 2019 following the intervention, it reached 2.3 ± 1.74 h (n = 7647). The differences between the standard deviations of the three periods are significant.

Conclusion
Implementing H-6S dropped the variance of LOS within 3 months and remained low for the whole year. Each new team of physicians who enter the ED should be thoroughly instructed as to the routines and expectations of the system from them, which should narrow the differences of previous education between them.
Epigenetic approaches to crop breeding: current status and perspectives
Authors: Dalakouras Athanasios , Vlachostergios Dimitrios 
Published: May 2021

Abstract
In order to tackle the cumulative adverse effects of global climate change, reduced farmland, and heightened needs of an ever-increasing world population, modern agriculture is in urgent search of solutions that can ensure world food security and sustainable development. Classical crop breeding is still a powerful method to obtain crops with valued agronomical traits, but its potential is gradually being compromised by the menacing decline of genetic variation. Resorting to the epigenome as a source of variation could serve as a promising alternative. Here, we discuss current status of epigenetics-mediated crop breeding (epibreeding), highlight its advances and limitations, outline currently available methodologies, and propose novel RNA-based strategies to modify the epigenome in a gene-specific and transgene-free manner.
UK Listing, Prospectus, and Disclosure Regime
Authors: Pearce Will 
Published: May 2021

Abstract
This chapter talks about the current UK listing regime that stems from the EU legislation that was enacted as part of the European Commission's action plan for the Capital Markets Union (CMU) and Financial Services Action Plan (FSAP). It describes the aims of the CMU and the FSAP in order to achieve a single financial services market with no obstacles to cross—border activity and a sound supervisory structure. It also highlights the key EU legislation that governs the UK listing regime, which includes the prospectus regulation that regulates the prospectus to be published when a company's securities are to be offered to the public or admitted to trading on a regulated market in the European Economic Area (EEA). This chapter discusses the Market Abuse Regulation (MAR), which covers the disclosure and control of inside information and the offences of market manipulation and insider dealing. It also mentions the Transparency Directive that harmonizes transparency requirements for issuers whose securities are admitted to trading on a regulated market.
Credit Rating Agencies
Authors: Eborall Charlotte 
Published: May 2021

Abstract
This chapter concentrates on credit rating agencies (CRAs), which play a key role in financial markets. It explains how CRAs help reduce information asymmetry between investors and issuers by providing an independent assessment of the relative creditworthiness of countries or companies. It also describes how CRA's role has expanded significantly in recent decades with financial globalization, such as the introduction of references to credit ratings in regulations and the embedding by market participants of ratings in their operating procedures, investment decisions, and contracts. This chapter identifies the heavy reliance on CRAs as one of the main contributors to the global financial crisis in 2008. It also talks about the efficacy of CRAs' credit ratings after 2008, in which regulators in the United States (US) and Europe introduced new regulations intended to address the reliability of CRAs' predictions of probability of default.
OHADA
Authors: Monsenepwo Justin 
Published: May 2021

Abstract
This chapter describes the relationship between the Organisation pour l’Harmonisation en Afrique du Droit des Affaires (OHADA; the Organization for the Harmonization of Business Law in Africa) and the Hague Principles. OHADA is an African supranational organization which was created on October 17, 1993. As per the Preamble and Article 1 of the OHADA Treaty, OHADA aims at creating simple, modern, and harmonized business law rules in Africa. To achieve this goal, OHADA has five institutions: (i) the Conference of Heads of State and Government; (ii) the Council of Ministers; (iii) the Common Court of Justice and Arbitration; (iv) the Regional Training Centre for Legal Officers; and (v) the Permanent Secretariat. Uniform Acts are the main instrument of OHADA. To understand the rules governing choice of law in commercial international contracts under OHADA law, it is important to examine the relation between the acts of OHADA (Uniform Acts and regulations) and the domestic law of the Member States. Meanwhile, there is no uniform codification of private international law under OHADA law. The chapter then explains that the Working Group on the Preliminary Draft Uniform Act on the Law of Obligations in the OHADA Region in 2015 did not use the Hague Principles, and why this omission should be reversed.
Common Law Africa
Authors: Oppong Richard Frimpong 
Published: May 2021

Abstract
This chapter studies the common law African countries Gambia, Ghana, Kenya, Malawi, Nigeria, Sierra Leone, Tanzania, Uganda, and Zambia. Their main source of private international law rules is judicial decisions or case law. Because of the relatively underdeveloped nature of their private international law regimes, foreign case law often serves as an important source of persuasive authority. In this regard, the jurisprudence of the English courts is particularly persuasive and is often referred to by the courts. In general, an international convention or treaty does not have the force of law in the legal systems of the countries under study, unless it is expressly incorporated into national law. In essence, they are dualist countries. However, courts in some of the countries under study have demonstrated a willingness to seek guidance from international treaties that are not yet domestically in force, if the circumstances are appropriate. Thus, it is possible, that courts in the countries under study may be receptive to the Hague Principles, especially if argued by counsel.
Tunisia
Authors: Elbalti Béligh 
Published: May 2021

Abstract
This chapter focuses on Tunisian perspectives on the Hague Principles. The main source of private international law in Tunisia is the 1998 Code of private international law (CPIL). Tunisia has not signed any convention on choice of law in international contractual matters. However, it is worth mentioning that, in the field of international arbitration, some conventions to which Tunisia is party include an express reference to party autonomy. As a matter of principle, Tunisian courts are bound only by Tunisian law and other international instruments duly ratified by Tunisia. Nevertheless, it is not uncommon that Tunisian courts refer to foreign laws, international conventions not ratified by Tunisia, model laws, foreign case law, or even foreign legal literature when such reference is deemed persuasive. Therefore, it can be safely said that nothing prevents Tunisian courts from referring to the persuasive authority of the Hague Principles. This would be the case if the parties invoked the Principles in support of their arguments in the case where a clear solution is lacking under Tunisian law.
Japan
Authors: Nishitani Yuko 
Published: May 2021

Abstract
This chapter discusses Japanese perspectives on the Hague Principles. Japan belongs to the civil law system, although some legal institutions grounded in common law also exist. At the end of the nineteenth century, Japan transplanted Western legal systems. Along with the codification of the Civil Code and other statutes, the Private International Law Act, Hôrei, was adopted in 1898, which was modernized and substituted by the Japanese Act on General Rules for Application of Laws (AGRAL) in 2006. The AGRAL designates, out of several conflicting laws, the law which has the closest connection with the legal relationship concerned. This value-neutral, multilateral method consists in localizing the legal relationship in a certain jurisdiction, grounded on the equality and interchangeability of domestic law and foreign law. While the judge does not have the authority to directly apply the Hague Principles instead of the AGRAL in litigation, the judge can certainly refer to the Hague Principles in seeking guidance for interpretation or filling gaps of the AGRAL, same as for other international, regional, or domestic conflicts rules, including the relevant Hague Conventions.
Macau
Authors: Tu Guangjian 
Published: May 2021

Abstract
This chapter focuses on Macau perspectives on the Hague Principles. It clarifies a few points before examining the contractual choice of law rules in Macau in detail. First, the Macau Civil Code that is the most important source for conflict of laws rules was derived from the 1966 Portuguese Civil Code. Second, due to the fact that Macau is a jurisdiction belonging to the civil law family, court decisions in Macau, theoretically, are not a source of law and do not formally have binding legal effects. Third, while legal doctrine developed by scholars in Macau is not a formal source of law, it may have influence on legislation and provide guidance for court decisions. Fourth, although some revision has been made for the Macau Civil Code since its entry into force in 1999, so far there has not been any initiative to revise its conflicts system, let alone its contractual conflicts rules. Unfortunately, the Hague Principles as a whole or any part therein cannot be incorporated into Macau’s legislation in the near future. Nevertheless, theoretically speaking, broadly accepted international customs and usages could be resorted to as ‘persuasive authority’ by Macau judges in judicial practice. The chapter then provides a comparison between the Hague Principles and Macau law.