bluuebunny/crossref_metadata_2025_split huggingface dataset:
ETMM-01. CANCER STEM CELL ENRICHMENT AND METABOLIC SUBSTRATE ADAPTABILITY ARE DRIVEN BY HYDROGEN SULFIDE SUPPRESSION IN GLIOBLASTOMA
Authors: Silver Daniel J , Roversi Gustavo A , Bithi Nazmin , Neumann Chase K A , Troike Katie M , Ahuja Grace K , Reizes Ofer , Brown J Mark , Hine Christopher , Lathia Justin D 
Published: March 2021

Abstract
Glioblastoma (GBM) remains among the deadliest of human malignancies. The emergence of the cancer stem cell (CSC) phenotype represents a major challenge to disease management and durable treatment response. The extrinsic, environmental, and lifestyle factors that result in CSC enrichment are not well understood. The CSC state endows cells with a fluid metabolic profile, enabling the utilization of multiple nutrient sources. Therefore, to test the impact of diet on CSC enrichment, we evaluated disease progression in tumor-bearing mice fed an obesity-inducing high-fat diet (HFD) versus an energy-balanced, low-fat control diet. HFD consumption resulted in hyper-aggressive disease that was accompanied by CSC enrichment and shortened survival. HFD consumption also drove intracerebral accumulation of saturated fats, which in turn inhibited the production and signaling of the gasotransmitter hydrogen sulfide (H2S). H2S is an endogenously produced bio-active metabolite derived from sulfur amino acid catabolism. It functions principally through protein S-sulfhydration and regulates a variety of programs including mitochondrial bioenergetics and cellular metabolism. Inhibition of H2S synthesis resulted in increased proliferation and chemotherapy resistance, whereas treatment with H2S donors led to cytotoxicity and death of cultured GBM cells. Compared to non-cancerous controls, patient GBM specimens were reduced in overall protein S-sulfhydration, which was primarily lost from proteins regulating cellular metabolism. These findings support the hypothesis that diet-regulated H2S signaling serves to suppress GBM by restricting metabolic adaptability, while its loss triggers CSC enrichment and disease acceleration. Interventions augmenting H2S bioavailability concurrent with GBM standard of care may improve outcomes for GBM patients.
FSMP-17. GLOBAL METABOLOMIC PROFILING OF GLIOBLASTOMA MULTIFORME REVEALS METABOLIC VULNERABILITIES IN RESPONSE TO RADIATION THERAPY
Authors: Durairaj Aarooran , McReynolds Melanie , Wang Congcong , He Joy , Rabinowitz Joshua , Andreasson Katrin , Minhas Paras 
Published: March 2021

Abstract
Glioblastoma multiforme (GBM), the most aggressive primary brain tumor, originates in astrocytes and oligodendrocytes and yields a median survival time of less than 2 years and a 5-year survival of 2.5%. There has been little in the way of treatments and novel approaches are needed to combat the poor prognosis of GBM. Recent studies have established that GBM cells exhibit metabolic reprogramming to adapt to diverse metabolic gradients within heterogenous tumor microenvironments. Using an unbiased metabolomics approach, we investigated metabolic changes both pre- and post-ionizing radiation across several patient-derived GBM cell lines. Surprisingly, acute high dosage of ionizing radiation resulted in significant changes in the synthesis of aminolevulinic acid (ALA), a non-proteinogenic amino acid. Fractionation of radiation therapy resulted in dose-dependent changes in the heme synthesis pathway within these cells. Using an orthotopic xenograft mouse model of GBM, we identify several enzymatic vulnerabilities in vivo and discuss a novel combinatorial therapeutic approach of radiation and targeted pharmacological intervention. Our findings reveal the fundamental biosynthetic changes that GBMs adopt when exposed to ionizing irradiation as well as the benefits of a combinatorial approach.
TBMT-02. APOLLO: RAMAN-BASED PATHOLOGY OF MALIGNANT GLIOMA
Authors: Lita Adrian , Sjöberg Joel , Filipescu Stefan , Celiku Orieta , Petre Luigia , Gilbert Mark , Noushmehr Houtan , Petre Ion , Larion Mioara 
Published: March 2021

Abstract

BACKGROUND
DNA methylation is an essential component for integrative diagnosis of gliomas. Methylation subtype prediction of gliomas is currently done via sample extraction of high-quality DNA (~1ug), methylome profiling, followed by probe identification, curation and subsequent analysis via different random forest classifiers. However, the DNA methylation classification is not always available for all the samples. Examples include when the existing material is not suitable for methylation profiling or the sample is very limiting. Therefore, we hypothesized that Raman spectroscopy might be suitable to predict the glioma methylome, based upon its ability to create a molecular fingerprint of the tumor and would provide biological insights unknown before.

METHODS
Coherent Raman Spectroscopy was used for molecular fingerprinting of the regions of interest using 1mm2 FFPE tissue spots from 39 patient samples with LGm1 to LGm6 methylation subtypes. Spectral information was then used to train a convolutional neural network (CNN) and develop a prediction algorithm, capable of detecting the glioma methylation subtypes. 70 % of the dataset was used for model training while the remaining 30% for validation. Oversampling was used to obtain a subtype-balanced data distribution. In addition, supervised wrapper methods and random forests were used to identify the top 50 most discriminatory Raman frequencies out of 1738.

RESULTS
We demonstrate that Raman spectroscopy can accurately and rapidly classify gliomas according to their methylation subtype from achieved FFPE samples, which are routinely present in pathological laboratories as a complementary mean to obtain this important classification when other analyses are not available. The most discriminatory frequencies show differential spectral intensities depending upon the glioma subtypes across the larger areas of the tissue.

CONCLUSIONS
The non-destructive nature of this method and the ability to be applied on FFPE samples directly, allows the histopathologist to reuse of the same slide for subsequent staining and downstream analyses.
Age profile of NHS workers in occupational physician clinics
Authors: Telling W A 
Published: March 2021

Abstract

Background
The population in the UK is predicted to increase in size and age. The National Health Service (NHS) is the largest employer in the UK and demographic changes in the working population would be expected to be reflected in the NHS workforce. Such changes may present different challenges to an NHS occupational physician (OP).

Aims
To evaluate how the age profile of an NHS workforce is reflected in referral patterns, diagnoses and occupational outcomes for workers assessed by OPs.

Methods
NHS workers employed by a large acute Trust who were referred to an OP for assessment during 2011–12 were identified. Occupational health data relating to their assessment were analysed to investigate relationships with age.

Results
Seven hundred and two workers were identified; they were from all staff and age groups employed by the NHS Trust. The highest referral rate to an OP was in staff aged between 41 and 60 years. There was no evidence that workers with long-term conditions assessed by an OP were likely to be older. The occupational outcome of ill-health retirement was linked to age.

Conclusions
This study suggested that older workers, aged between 41 and 60 years, may be more likely to be referred for assessment by an OP than younger workers. The only occupational outcome linked to age was ill-health retirement, which was more likely for workers over 50 years of age.
Techniques of Onyx Embolization of Arteriovenous Malformation: 2-Dimensional Operative Video
Authors: Wagner Kathryn M , Srinivasan Visish M , Kan Peter 
Published: March 2021

Abstract
Advances in endovascular techniques and tools have allowed for treatment of complex arteriovenous malformations (AVMs), which historically may have posed unacceptable risk for open surgical resection. Endovascular treatment may be employed as an adjunct to surgical resection or as definitive therapy. Improvements in embolization materials have made endovascular AVM treatment safer for patients and useful across a variety of lesions. While many techniques are employed for transarterial AVM embolization, the essential tenets apply to all procedures: (1) great care should be taken to cannulate only vessels directly supplying the lesion, and not en passage vessels, prior to injecting embolisate; (2) embolisate should travel into the nidus, but not into the draining veins; (3) embolistate reflux proximal to the microcatheter should be avoided. There are several techniques that accomplish these goals, including the plug and push method, or using a balloon to prevent embolisate reflux. We use controlled injection of liquid Onyx (Medtronic), with increasing pressure over multiple injections pushing the embolisate forward into the AVM. This is repeated in multiple feeding vessels to decrease or eliminate supply to the AVM. Here, we present a 36-yr-old female with a right parietal AVM discovered on workup of headaches. After informed consent was obtained, she underwent preoperative embolization using this technique prior to uncomplicated surgical resection. The video shows the endovascular Onyx embolization of multiple feeding vessels over staged treatment.
Judicial Review
Authors: Schillig Michael 
Published: March 2021

Abstract
The exercise of extensive powers by authorities during the recovery and resolution process may interfere with constitutionally protected fundamental rights of stakeholder in a multitude of ways. Particularly relevant are the right to conduct a business and the right to property under the EU Charter of fundamental rights, as well as the takings clause under the US constitution. A balance needs to be struck between the aims and objectives of bank resolution and the rights of investors and the requirements of due process. This is normally achieved through expedited and limited judicial review. This chapter assesses whether and to what extent the respective procedures are in line with constitutional and fundamental rights requirements.
Resolution Funding
Authors: Schillig Michael 
Published: March 2021

Abstract
The chapter traces the hierarchy of resolution funding from the most readily available sources to the ultima ratio of government bailouts and the possibility of a supranational bailout as a last resort. Resolution-funding arrangements and deposit guarantee schemes interact in a multitude of ways. The discussion of this interaction is followed by an analysis of deposit guarantee schemes and resolution financing arrangements in the EU and the US, including the Single Bank Resolution Fund and the Orderly Liquidation Fund. The chapter further considers the available government financial stabilization tools in the form of direct recapitalization of an institution and temporary public ownership. It also provides a brief assessment of direct bank recapitalization through the European Stability Mechanism (ESM).
Resolution and Corporate Insolvency Law
Authors: Schillig Michael 
Published: March 2021

Abstract
The chapter seeks to delineate the interaction of corporate insolvency law and resolution proceedings. In Europe, the legal framework provided by the Bank Recovery and Resolution Directive and even the Single Resolution Mechanisms remain incomplete, with national corporate insolvency law filling the gaps. This is perhaps most relevant for the ranking of creditors under national law. The chapter provides an overview of the corporate insolvency procedures that are available in the jurisdictions under consideration. These may function as either a self-standing resolution mechanism or as supplementary devices within the framework of resolution. Given the relevance for all insolvency procedures under consideration as well as for resolution, not least through the ‘no-creditor-worse-off’ principle, the chapter discusses the ranking of different classes of creditors as determined by the Directive and national law, as well as the privileged treatment of certain financial creditors.
Winding-Up and Liquidation
Authors: Schillig Michael 
Published: March 2021

Abstract
Liquidation procedures may be relevant for unprofitable or defunct subsidiaries, even though other parts of a financial group may be successfully restructured. For certain types of financial companies, liquidation may be the only available process. The chapter provides an overview of the liquidation proceedings available for financial institutions in England, Germany and the US. It focuses on the English compulsory winding-up procedure and bank insolvency, the German general insolvency procedure with an enhanced role for BaFin as the competent authority, and the liquidation of broker-dealers in the US through a Chapter 7 stockbroker liquidation and under the Securities Investor Protection Act of 1970 (SIPA liquidation).
RCDs
Authors: Stone David 
Published: March 2021

Abstract
Article 12 of the Regulation provides for the registration of RCDs. Upon registration by the Office, a design which meets the requirements under Section 1 of Title II of the Regulation is protected as an RCD for a period of five years as from the date of the filing of the application. The RCD may be renewed in periods of five years each, up to a total term of 25 years from the date of filing.
Safe Harbours
Authors: Riordan Jaani 
Published: March 2021

Abstract
European law recognises various limits on the primary and secondary liability which may be imposed upon internet intermediaries for the acts of third parties. These limits fall into four categories: first, ‘safe harbours’ which insulate passive and neutral information society service providers from monetary liability for transmitting, caching, and storing third parties’ information; second, protection from general duties to monitor third parties’ information and activity; third, limits necessary to protect the fundamental rights of intermediaries and their users; and fourth, miscellaneous general limits on injunctive relief.
Website Blocking in Europe
Authors: Riordan Jaani 
Published: March 2021

Abstract
This chapter considers website blocking practices in European nations besides the United Kingdom. Most member states have enacted legislation to permit courts or administrative authorities to issue website blocking injunctions in some form. The majority of these statutory remedies are restricted to the enforcement of copyright and related rights, but some target other rights or pursue public policies such as the regulation of online gaming or the prohibition of images depicting child abuse. In some jurisdictions, blocking orders are available without any specific legislative basis, pursuant to ordinary rules governing injunctive relief.
Data Retention and Interception
Authors: Riordan Jaani 
Published: March 2021

Abstract
This chapter considers statutory duties that are owed by internet intermediaries to retain communications metadata for periods beyond their ordinary lifespan, and to disclose those data (and in narrower circumstances, the contents of the communications) for use in criminal investigations. These duties serve a range of public purposes—principally the preservation of national security, law enforcement, and public order. Their justification is said to be a rise in the criminal exploitation of internet and communications technologies, in particular to perpetrate cybercrime and to plan and carry out terrorist activities.
The Interaction with Other Areas of the Law
Authors: Mühlendahl Alexander , Botis Dimitris , Maniatis Spyros , Wiseman Imogen 
Published: March 2021

Abstract
Competition law and the free movement of goods principles have guided the development of trade mark law in Europe. This chapter will examine other relationships. The first part considers the use of trade marks in comparative advertisements. We have seen in Chapter 7 how comparative advertising has delineated the limits of trade mark law. Here the other side of the relationship is examined. Chapter 5 considered whether a geographical name can function and be protected as a trade mark and the limits of such protection. The second part of this chapter gives a flavour of the system of protecting product designations as geographical indications of origin. The third part looks at the clash between trade marks and domain names and the catalysing role of the concept of bad faith. The fourth part is a good example of how one dispute between distinguishing signs can become the common theme of distinct plots performed before different European audiences;
Conclusion
Authors: Mühlendahl Alexander , Botis Dimitris , Maniatis Spyros , Wiseman Imogen 
Published: March 2021

Abstract
The Court of Justice has considered within a relatively short period of time a large number of trade mark cases from two perspectives: as an interpretive court for the purposes of both the Directive and the Regulation and as a supreme court of appeal under the Regulation and its implementing rules. In both contexts it has interpreted and applied provisions that were essentially identical. However, under the Regulation the Court also had to be supportive of the new Union-wide trade mark right and the bodies administering it. For example, by strengthening the role of the Boards of Appeal and streamlining their decision-making trends, the Court could achieve a number of things: make the registration process more efficient, raise the level of dependency on the decision-making instances of OHIM, make the appeal route to the courts in Luxembourg more difficult, and lessen the burden imposed on the General Court (previously the Court of First Instance) and the Court of Justice.
Void or Voidable?
Authors: Ashdown Michael 
Published: March 2021

Abstract
For almost as long as the existence of the Re Hastings-Bass rule has been acknowledged, there has been uncertainty as to the consequences of the rule being successfully invoked in respect of the exercise of a power or discretion. Three principal possibilities have been put forward: first, that the trustee or fiduciary exercising the power may incur personal liability, but the exercise is nevertheless valid and effective; secondly, that the exercise of the power is voidable, and so is effective until set aside; and thirdly, that the purported exercise is wholly void and ineffective. The first of these has attracted no judicial support, and in any case Pitt v Holt puts beyond doubt that the validity of trustees’ decision can be called into question by the Re Hastings-Bass rule, with Lord Walker in the Supreme Court giving a clear endorsement of Lloyd LJ’s judgment to this effect in the Court of Appeal. As between the second and third options, though, the question of ‘void’ versus ‘voidable’ has been hard-fought.
Argentina
Authors: Araya Tomás M 
Published: March 2021

Abstract
The author would like to express his gratitude to M & M Bomchil associate Pedro de Elizalde for his valuable help in reviewing the cases mentioned in this chapter. The material contained herein is intended as a general guide only and is not intended to be a memorandum of law study, nor to provide legal advice, and should not be treated as a substitute for legal advice concerning particular situations. Legal advice should always be sought before taking any action based on the information provided. The publishers, editors, and author bear no responsibility for any errors or omissions contained therein.
Canada
Authors: Weinczok Mike , Le Kathy 
Published: March 2021

Abstract
We thank Lisa S Corne, a Partner in the Bankruptcy and Insolvency Group of Dickinson Wright LLP for her revisions to and comments on the chapter. The material contained herein is intended as a general guide only and is not intended to be a memorandum of law study, nor to provide legal advice, and should not be treated as a substitute for legal advice concerning particular situations. Legal advice should always be sought before taking any action based on the information provided. The publishers, editors, and authors bear no responsibility for any errors or omissions contained therein.
Czech Republic
Authors: Hájek Daniel 
Published: March 2021

Abstract
The material contained herein is intended as a general guide only and is not intended to be a memorandum of law study, nor to provide legal advice, and should not be treated as a substitute for legal advice concerning particular situations. Legal advice should always be sought before taking any action based on the information provided. The publishers, editors, and author bear no responsibility for any errors or omissions contained therein.
Greece
Authors: Klissouras Constantinos 
Published: March 2021

Abstract
The material contained herein is intended as a general guide only and is not intended to be a memorandum of law study, nor to provide legal advice, and should not be treated as a substitute for legal advice concerning particular situations. Legal advice should always be sought before taking any action based on the information provided. The publishers, editors, and author bear no responsibility for any errors or omissions contained therein.
Thailand
Authors: Pereira Santhapat , Duncan David 
Published: March 2021

Abstract
The material contained herein is intended as a general guide only and is not intended to be a memorandum of law study, nor to provide legal advice, and should not be treated as a substitute for legal advice concerning particular situations. Legal advice should always be sought before taking any action based on the information provided. The publishers, editors, and authors bear no responsibility for any errors or omissions contained therein.
Corporate Group Restructuring Finance Global Law Reform
Authors: Baer Gregor 
Published: March 2021

Abstract
The material contained herein is intended as a general guide only and is not intended to be a memorandum of law study, nor to provide legal advice, and should not be treated as a substitute for legal advice concerning particular situations. Legal advice should always be sought before taking any action based on the information provided. The publishers, editors, and author bear no responsibility for any errors or omissions contained therein. Provisions of UNCITRAL and World Bank texts quoted or summarized in this chapter are provided courtesy of the United Nations Commission on International Trade Law and the World Bank, the respective copyright owners.
Members’ Unfair Prejudice Claims and Winding-Up Petitions
Authors: Adam Al-Attar 
Published: March 2021

Abstract
The 2006 Act, Part 30, ss 994–9 contains the provisions protecting members from unfair prejudice arising from the conduct of the affairs of the company. These provisions came into force on 1 October 2007 and replaced provisions in the 1985 Act, ss 459–61 without change, except for the introduction of the 2006 Act, s 999, which contains new supplementary provisions where the company’s constitution is altered. With effect from 6 April 2008 a new s 994(1A) was inserted which provides that the removal from office of the company’s auditor should in certain circumstances be treated as unfairly prejudicial to the interests of some part of the members.
Directors’ liabilities in Insolvency Proceedings
Authors: Cooke Charlotte 
Published: March 2021

Abstract
This chapter discusses the liabilities of directors in consequence of a company entering insolvency proceedings. Sections B and C(1) concern claims which were available to the company when it entered insolvency proceedings and can be brought in its own name or by a liquidator using the summary procedure in the Insolvency Act, s 212. Sections C(2) and (3) and D consider a director’s personal liability under the Insolvency Act for wrongful trading, fraudulent trading, or contravention of the restriction on reuse of a company name, which may result from the company entering insolvency proceedings. Section E discusses the impact on directors of the provisions in the Insolvency Act for adjusting prior transactions.