bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic structural variations link multiple genes to bone mineral density in a multi-ethnic cohort study: Louisiana osteoporosis study
Authors: Su Kuan-Jui , Qiu Chuan , Greenbaum Jonathan , Zhang Xiao , Liu Anqi , Liu Yong , Luo Zhe , Mungasavalli Gnanesh Shashank Sajjan , Tian Qing , Zhao Lan-Juan , Shen Hui , Deng Hong-Wen 
Published: August 2024

Abstract
Osteoporosis, characterized by low BMD, is a highly heritable metabolic bone disorder. Although single nucleotide variations (SNVs) have been extensively studied, they explain only a fraction of BMD heritability. Although genomic structural variations (SVs) are large-scale genomic alterations that contribute to genetic diversity in shaping phenotypic variations, the role of SVs in osteoporosis susceptibility remains poorly understood. This study aims to identify and prioritize genes that harbor BMD-related SVs. We performed whole genome sequencing on 4982 subjects from the Louisiana Osteoporosis Study. To obtain high-confidence SVs, the detection of SVs was performed using an ensemble approach. The SVs were tested for association with BMD variation at the hip (HIP), femoral neck (FNK), and lumbar spine (SPN), respectively. Additionally, we conducted co-occurrence analysis using multi-omics approaches to prioritize the identified genes based on their functional importance. Stratification was employed to explore the sex- and ethnicity-specific effects. We identified significant SV-BMD associations: 125 for FNK-BMD, 99 for SPN-BMD, and 83 for HIP-BMD. We observed SVs that were commonly associated with both FNK and HIP BMDs in our combined and stratified analyses. These SVs explain 13.3% to 19.1% of BMD variation. Novel bone-related genes emerged, including LINC02370, ZNF family genes, and ZDHHC family genes. Additionally, FMN2, carrying BMD-related deletions, showed associations with FNK or HIP BMDs, with sex-specific effects. The co-occurrence analysis prioritized an RNA gene LINC00494 and ZNF family genes positively associated with BMDs at different skeletal sites. Two potential causal genes, IBSP and SPP1, for osteoporosis were also identified. Our study uncovers new insights into genetic factors influencing BMD through SV analysis. We highlight BMD-related SVs, revealing a mix of shared and specific genetic influences across skeletal sites and gender or ethnicity. These findings suggest potential roles in osteoporosis pathophysiology, opening avenues for further research and therapeutic targets.
Causal inference in health and disease: a review of the principles and applications of Mendelian randomization
Authors: Lovegrove Catherine E , Howles Sarah A , Furniss Dominic , Holmes Michael V 
Published: August 2024

Abstract
Mendelian randomization (MR) is a genetic epidemiological technique that uses genetic variation to infer causal relationships between modifiable exposures and outcome variables. Conventional observational epidemiological studies are subject to bias from a range of sources; MR analyses can offer an advantage in that they are less prone to bias as they use genetic variants inherited at conception as “instrumental variables”, which are proxies of an exposure. However, as with all research tools, MR studies must be carefully designed to yield valuable insights into causal relationships between exposures and outcomes, and to avoid biased or misleading results that undermine the validity of the causal inferences drawn from the study. In this review, we outline Mendel’s laws of inheritance, the assumptions and principles that underlie MR, MR study designs and methods, and how MR analyses can be applied and reported. Using the example of serum phosphate concentrations on liability to kidney stone disease we illustrate how MR estimates may be visualized and, finally, we contextualize MR in bone and mineral research including exemplifying how this technique could be employed to inform clinical studies and future guidelines concerning BMD and fracture risk. This review provides a framework to enhance understanding of how MR may be used to triangulate evidence and progress research in bone and mineral metabolism as we strive to infer causal effects in health and disease.
Osteoclast indices in osteogenesis imperfecta: systematic review and meta-analysis
Authors: Aksornthong Sirion , Patel Priyesh , Komarova Svetlana V 
Published: August 2024

Abstract
Osteogenesis imperfecta (OI) is a rare bone fragility disorder caused by mutations in genes encoding collagen type I or that affect its processing. Alterations in osteoclasts were suggested to contribute to OI pathophysiology. We aimed to systematically identify studies reporting measures of osteoclast formation and function in patients and mouse models of OI, to quantify OI-induced changes. The systematic search of Medline, Ovid, and Web of Science identified 798 unique studies. After screening, we included 23 studies for meta-analysis, reporting osteoclast parameters in 310 patients with OI of 9 different types and 16 studies reporting osteoclast parameters in 406 animals of 11 different OI mouse models. The standardized mean difference with 95% confidence interval (CI) was used as the effect size, and random-effects meta-analysis was performed. In patients with OI, collagen degradation markers were significantly higher compared with age-matched controls, with an effect size of 1.23 (CI: 0.36, 2.10]. Collagen degradation markers were the most elevated in the 3- to 7-year-old age group and in patients with more severe forms of OI. Bone histomorphometry demonstrated the trends for higher osteoclast numbers (1.16; CI: −0.22, 2.55) and osteoclast surface (0.43; CI: −0.63, 1.49), and significantly higher eroded surface (3.24; CI: 0.51, 5.96) compared with age-matched controls. In OI mice, meta-analysis demonstrated significant increases in collagen degradation markers (1.59; CI: 1.07, 2.11), in osteoclast numbers (0.94; CI: 0.50, 1.39), osteoclast surface (0.73; CI: 0.22, 1.23), and eroded surface (1.31; CI: 0.54, 2.08). The largest differences were in OI mice with the mutations in Col1a1 and Col1a2 genes. There were no differences between males and females in clinical or animal studies. Quantitative estimates of changes in osteoclast indices and their variance for patients with OI are important for planning future studies. We confirmed that similar changes are observed in mice with OI, supporting their translational utility.
Improving electronic health record documentation and use to promote evidence-based pediatric care
Authors: Till Lance , Leis Julie , McCombs-Thornton Kimberly , Lee Helen , Reinhart Shauna , Valado Trenna , Briggs Rahil , Bushar Jessica , Fritz Laila 
Published: August 2024

Abstract

Objective
Electronic health records (EHRs) often lack the necessary functionalities to support the full implementation of national clinical guidelines for pediatric care outlined in the American Academy of Pediatrics Bright Futures Guidelines. Using HealthySteps (HS), an evidence-based pediatric primary care program, as an exemplar, this study aimed to enhance pediatric EHRs, identify facilitators and barriers to EHR enhancements, and improve data quality for delivering clinical care as part of HS implementation and evidence building.

Methods
Three HS sites—each differing in location, setting, number of children served, and mix of child insurance coverage—participated in the study. Sites received technical assistance to support data collection and EHR updates. A comprehensive evaluation, including a process evaluation and outcomes monitoring, was conducted to gauge progress toward implementing study data requirements over time. Data sources included administrative records, surveys, and interviews.

Results
All sites enhanced their EHRs yet relied on supplemental data systems to track care coordination. Sites improved documentation of required data, demonstrating reductions in missing data and increases in extractable data between baseline and follow-up assessments. For example, the percentage of missing social-emotional screening results ranged from 0% to 8.0% at study conclusion. Facilitators and barriers to EHR enhancements included organizational supports, leadership, and capacity building.

Conclusions
With significant investment of time and resources, practices modified their EHRs to better capture services aligned with HS and Bright Futures. However, more scalable digital solutions are necessary to support EHR updates to help drive improvements in clinical care and outcomes for children and families.
Hepatitis B Virus Treatment in Children: Common Challenges and Management Options in a Case-Based Format
Authors: Ravanbakhsh Naseem , Rivera Campana Andres , Chapin Catherine , Jhaveri Ravi 
Published: August 2024

Abstract
The management of hepatitis B virus (HBV) in pediatrics presents many challenges, given the potential sequelae of untreated infection including hepatic fibrosis, cirrhosis, and malignancy, and a lack of clear guidance on the timing of treatment initiation. The goal of this review is to feature common clinical scenarios that occur in the evaluation and treatment of HBV infection in children. Each vignette presents an opportunity to discuss guidelines and evidence-based practices as well as review landmark studies and evolving practices.
Cognitive effects of altitude exposure
Authors: Burtscher Johannes , Gassmann Max , Ehrenreich Hannelore , Hüfner Katharina , Kopp Martin , Burtscher Martin 
Published: August 2024

It is a common misconception that cognitive function is impaired in a linear fashion by declining oxygen availability (e.g. at altitude). While this may apply for prolonged exposures to high altitudes (&gt;2500 m), moderate altitude (1500–2500 m) or short intermittent hypoxic episodes can even be beneficial for the brain.
A market correction mechanism regulation as a consequence of the 2021–2023 energy crisis
Authors: Priem Randy 
Published: August 2024

Abstract
This article discusses the impact of the energy crisis, as a consequence of the Russian–Ukrainian conflict, on commodity derivatives trading regulation in Europe. More specifically, as a consequence of elevated and highly volatile gas futures prices, European legislators introduced a market correction mechanism (MCM) regulation on 22 December 2022, which came into effect on 15 February 2023. This article provides a detailed discussion of the MCM regulation and puts forward possible adverse scenarios in case of government intervention. This article also discusses the daily LNG price assessments and benchmark that the Agency for the Cooperation of Energy Regulators needs to publish for the MCM to function properly.
Introduction to IP and Anti-Monopoly Legislation and Practice in China
Authors: Kokkoris Ioannis , Maniatis Spyros , Gao Yajie 
Published: August 2024

Abstract
This introductory chapter discusses how there has been a transformation within China's Intellectual Property (IP) law enforcement as well as numerous other IP-related regulations. In addition, other more general laws have been amended or are under reform with important implications for global IP enforcement. The civil procedure law was also recently amended, with potentially important repercussions for IP rights holders, particularly in terms of provisional measures for trade secrets. Furthermore, since law enforcement responsibilities of trademark and patent shall also be borne by the comprehensive legal enforcement team of the State Administration for Market Regulation, the chapter argues that it would be more efficient for IP-related and competition-related legislation and enforcement to go hand in hand in the future.
The Economics of Competition Law: Relevant Market and Market Power
Authors: Lianos Ioannis , Korah Valentine , Siciliani Paolo 
Published: August 2024

Abstract
This chapter discusses the economics of competition law, with particular emphasis on the role of market and market power. It begins with an analysis of competition from an economic perspective, taking into account the meaning of competition, the importance of the concept of market power, and competition in relation to the nature of strategic interaction. It then considers the conceptual foundations of welfare economics, the factors of production and commodification, the distinction between firms and consumers, monopoly vs. perfect competition, and the social costs of market power. It also reviews the history and many dimensions of market definition, the concept and function of market definition in EU and UK competition law, substitutability and the Hypothetical Monopolist Test, the ‘Cellophane Fallacy’ and ‘Reverse-Cellophane Fallacy’, aftermarkets, and brands and product differentiation. Finally, the chapter provides an overview of barriers to entry and/or expansion and the future of market definition.
National Security and FDI Screening in the EU
Authors: Kokkoris Ioannis 
Published: August 2024

Abstract
The chapter looks at national security considerations in European merger control. It begins by illustrating the way in which the EUMR gives room to public-interest considerations. The chapter describes the tools available to Member States to obstruct cross-border transactions, then moves on to examine the EU Commission’s decisional practice in the area. The analysis encompasses a diverse range of cases in which EU Member States have taken measures to safeguard interests including energy security, national sovereignty, and technological autonomy. The tensions are palpable as governments grapple with the task of balancing their strategic interests with the principles of open markets and cross-border business. This balancing act is further complicated by the fact that public interest considerations, though pivotal, may diverge between nations. Finally, the chapter presents the Commission’s two legislative initiatives for the screening of FDI and for the regulation of foreign subsidies.
Civil Jurisdiction and Judgments in Europe
Authors: Hartley Trevor C 
Published: August 2024

Abstract
This book contains a study of three legal instruments on civil jurisdiction and judgments: the Brussels I Regulation (2012 version), the Lugano Convention (2007 version), and the Hague Choice of Court Convention. A feature all three instruments have in common is that, as far as the Member States of the European Union are concerned CJEU, the final word on their interpretation lies with the Court of Justice of the European Union (CJEU). They thus have a certain unity— a unity of function (the international regulation of civil litigation) and a unity of interpretation. This leads to common features, features which make it appropriate to treat them together as constituting different aspects of a single subject. The book identifies the legal principles that lie behind the individual provisions of the instruments and provides a clear and systematic explanation of their operation, based on what the instruments are trying to achieve and the legal concepts through which it is intended that these objectives will be attained. Every branch of the law tries to balance different objectives and uses different principles and concepts to do so. This is as true in the area of international litigation as in other areas. An important feature of the book, therefore, is to show how these different policies and principles interact to form a coherent system.
Cooperation through Central Authorities in the Area of Parental Responsibility and General Provisions
Authors: Wilderspin Michael 
Published: August 2024

Abstract
This chapter tackles the rules on cooperation concerning parental responsibility and general provisions. It notes Article 76’s designation of central authorities to assist with the Brussels IIb Regulation and specification of the geographical or functional jurisdiction of the aforementioned authorities. The rules primarily aim to improve the operation of the Regulation by developing communication between the courts and authorities in the Member States. Central authorities are mandated to communicate information surrounding national laws and cooperate with competent authorities while considering the usage of the European Judicial Network. Moreover, central authorities must meet regularly in an effort to facilitate the application of the Regulation.
Governing Law Risks in International Business Transactions
Authors: Wood Philip R 
Published: August 2024

Abstract
This book is about the advantages and the risks involved in the choice of law governing an international contract or other transaction, plus the accompanying choice of courts, in the fields of wholesale (non-consumer) financial, corporate, commercial, and insolvency law—broadly business law—on a comparative basis. The book discusses how to reduce legal risk by choice of law and courts. It proposes about seventy key indicators to rank the four main jurisdictions of England, New York, France, and Germany, together with their families of law numbering about 320 jurisdictions in the world, on thirteen risk tests. These include contract predictability, business orientation, freedom of contract, insolvency regimes, corporate law, regulatory law, courts, litigation, and other factors.
Corporate Law Indicators and Risks
Authors: Wood Philip R 
Published: August 2024

Abstract
This chapter discusses the role of choice of governing law and the main corporate transactions, and compares shares to bonds. It discusses risk mitigation techniques, summarises the key indicators of corporate law around the world, and examines the comparative law of the key indicators of financial assistance to buy own shares and director personal liability. It discusses other key indicators of corporate law, including the veil of incorporation, bankruptcy consolidation, subordination of shareholder loans, maintenance of capital, shareholder equality, minority protections, corporate governance, takeovers, and corporate guarantees. It lists the main corporate transactions and explains why the free choice of governing law has less of a role to play in the main corporate transactions. It explains that the risks are mitigated mainly by the formation of subsidiaries as opposed to a choice of governing law.
Interest in International Arbitration
Authors: Secomb Matthew 
Published: August 2024

Abstract
Interest plays a vital and increasing role in international arbitration proceedings, with almost every case having an element of interest involved. However, until now, the topic has received very little attention, meaning that arbitrators have had very little concrete foundation on which to judge decisions on interest awards. This book is the first authoritative guidance to address this, providing a uniform approach to the awarding of interest in international arbitration. The book aligns arbitrators' decisions with standard commercial practice, offering a practical and logical approach to how interest should be awarded. It sets out traditional approaches that arbitrators have followed in the past, such as using conflict of law to apply a statutory rate from a given law, or awarding instead a subjectively ‘reasonable’ rate, and examines how these inconsistent approaches have resulted in a variety of awards and decisions. The book uses this analysis as a basis for a uniform approach to the issue: granting compound interest at appropriate rates unless constrained by truly mandatory law. It sets out the calculation method, explores the benefits and limitations, and presents a thorough argument for the movement toward a uniform approach to interest awards.
European Union Law of State Aid
Authors: Bacon QC Kelyn 
Published: August 2024

Abstract
This book aims to provide a comprehensive description of the EU law of State aid, which covers all of the relevant legislation, case-law, and important decisional practice of the Commission in this field, as well as exploring the policy themes that have shaped the approach of the various EU institutions to State aid control. The book is divided into three sections: general rules, which include discussion of the definition of State aid and the compatibility assessment under the Treaties; specific types of aid, including the application of the General Block Exemption Regulation and sector-specific treatment of State aid rules; and a final section on enforcement of State aid rules and remedies for breach of State aid law. This third edition is published in the context of rapid changes to the legislation and case-law, after a process of State Aid Modernisation involving the review of most of the legislation and guidelines in the field of State aid. The new texts include a new GBER and De Minimis Regulation, the Commission’s Notice on the Notion of State aid, a new Procedural Regulation, various new horizontal aid guidelines (Rescue & Restructuring Guidelines, R&D&I Framework, Risk Finance Guidelines and Environmental and Energy Aid Guidelines), and new sectoral guidelines for aviation, cinemas, agriculture, and fisheries. The book is aimed primarily at practitioners, and its content is therefore presented in a concise and accessible style. Two new chapters have also been added, dealing with disaster aid and culture, heritage, sport, and local infrastructure respectively.
Non-Shareholder Voice in Bank Governance
Authors: Davies Paul , Hopt Klaus J 
Published: August 2024

Abstract
This chapter assesses the arguments for and against reforms which aim to make bank boards more sensitive to the risks of negative externalities in the bank’s operating model. It looks at mechanisms for increasing the influence on the board of two groups likely to suffer from the negative externalities of board failure, namely, society at large and creditors. Prudential supervisors are one obvious representative of the interests of society as a whole and a potential source of risk-averse influence on boards, since the prudential supervisor’s principal goal is the safety and soundness of the banking system. Possible additional or alternative sources of caution in relation to bank board decision-making are the holders of bank debt. The chapter then argues that it is important to consider to change the composition of the boards of the banks by giving interested non-shareholders a say or even a seat in the board.
Corporate Culture in the Governance of Financial Institutions
Authors: Zhu Shanshan , Ferrarini Guido 
Published: August 2024

Abstract
This chapter looks at the role of ethics and culture in the financial services industry as determinants of either good or bad behaviour. Because banks are run by human beings, one should know first how to fix people’s behaviour if one wants to understand how to fix banks. Therefore, governance models should be rather analysed with a focus on the organizational and cultural aspects of institutions. A proactive inclusion of cultural and ethical issues in banking supervision has been accomplished by the De Nederlandsche Bank (DNB), which was in 2010 the first banking supervisor globally to treat culture and behaviour as risk factors in supervision. At EU level, the European Banking Authority (EBA) Guidelines on common procedures and methodologies for the supervisory review and evaluation process (SREP) make reference to culture and ethics in banks.
Conflicts of Interest
Authors: Helleringer Geneviève , Skinner Christina 
Published: August 2024

Abstract
This chapter focuses on conflicts of interest in the retail space. Because of the structure of incentives, conflicts of interest situations regularly arise in the context of retail investment advice. As such, conflicts of interest have been the focal point of regulators' efforts to improve conduct in the retail investment space. In the United States, both the Securities and Exchange Commission (SEC) and the Department of Labor (DOL) have embarked on rulemaking projects to heighten and refine the fiduciary duties that investment advisors owe to retail clients — and, in particular, the duty of loyalty that dictates the identification and management of conflicts of interest. Similarly, as a result of the Financial Conduct Authority’s ‘Retail Distribution Review’, U.K. regulators have issued new guidance on how the investment adviser can best comply with his or her fiduciary duties.