bluuebunny/crossref_metadata_2025 huggingface dataset:
Humanitarian Assistance
Authors: Lattanzi Flavia
Published: August 2024

This chapter begins by presenting the notion of humanitarian assistance and its international legal history. The analysis of the relevant provisions of the Geneva Conventions and the Additional Protocols is then conducted with respect to the following subjects: beneficiaries and actors of relief activities, consent requirement, free passage obligation, other specific relief obligations of the parties to an international armed conflict. These provisions are interpreted in light of customary international rules such as the prohibition of starvation that, in the author’s view, limits the effect of the consent requirement. The same approach is followed with respect to the relief rules applicable to situations of non-international armed conflict. The legal consequences of violations of relief rules conclude the chapter. In this context, particular relevance is given to international rules and practice on individual criminal responsibility.
Judicial Guarantees under Common Article 3
Authors: Doswald-Beck Louise
Published: August 2024

This chapter discusses provisions for judicial guarantees in the Geneva Conventions applicable in non-international armed conflicts. It focuses on the meaning and application of the Common Article 3 paragraph 1(1)(d), covering the nature of the court required to pronounce judgment, guarantees recognized as ‘indispensable’, other important judicial guarantees, and pre-trial judicial guarantees for detainees. The most important new developments since 1949 include the adoption of Article 6 of Additional Protocol II which provides further detail to Common Article 3, the recognition of such standards as customary, and the interpretation of identical norms by human rights treaty bodies. The legal consequences of a violation include both state responsibility and international crimes. The chapter highlights the particular difficulties of providing the same rights and duties on fair trial to rebel groups. It considers different scenarios and discusses possible alternatives.
Applicability of the Conventions by Means of Ad Hoc Agreements
Authors: Vierucci Luisa
Published: August 2024

According to Common Article 3 paragraph 3, the parties to a non-international armed conflict (NIAC), ‘should […] endeavour to bring into force, by means of special agreements, all or part of the other provisions of the […] Convention[s]’. The interest in concluding such agreements lies in the fact that, beyond the rules that are applicable between the parties via custom or treaty, they also become bound by ad hoc rules for the specific conflict the agreement covers. This chapter discusses the practice and content of the ad hoc agreements, legal status of the ad hoc agreements, and the legal consequences in case of a violation of the ad hoc agreements.
The Obligations to Respect, Protect, Collect, and Care for the Wounded, Sick, and Shipwrecked
Authors: Giacca Gilles
Published: August 2024

This chapter analyses the provisions under the Geneva Conventions to understand the obligations owed to wounded, sick, and shipwrecked combatants and civilians. The main legal issues discussed are: whether wounded, sick, and shipwrecked civilians are entitled to the same protection as combatants in international armed conflict (IAC); whether the required treatment of the shipwrecked differs from that afforded to the wounded and sick; whether the civilian population has any rights and obligations towards combatant or civilian wounded, sick, and shipwrecked; whether Common Article 3 provides comparable standards of protection to those detailed in IAC; whether civilians and relief societies in non-international armed conflicts (NIACs) are protected against penalties for offering assistance, similar to the way in which they are protected in IAC; and whether/how these obligations to respect, protect, collect, and care for apply to armed groups in NIAC.
The Status, Rights, and Obligations of Medical and Religious Personnel
Authors: Casey-Maslen Stuart
Published: August 2024

This chapter discusses the protection afforded to medical and religious personnel under the 1949 Convention for the Amelioration of the Condition of the Wounded and Sick in Armed Forces in the Field. The duty to respect and protect both military and civilian medical and religious personnel in all circumstances is applicable in international armed conflict (IAC) and non-international armed conflict (NIAC). The protection applies ‘at all times and in all places, both on the battlefield and behind the lines’, and whether such personnel are retained ‘only temporarily by the enemy or for a lengthy period’. Deliberate killing or wounding of military and civilian medical and religious personnel entitled to protection under IHL (i.e., not committing acts harmful to the enemy) would amount to a war crime.
Who is a Protected Civilian?
Authors: Salmón Elizabeth
Published: August 2024

This chapter discusses the protection of civilians during international armed conflicts (IACs) in Geneva Convention (GC) IV. GC IV contains two parallel regimes of protection. On the one hand, there are general rules for the protection of the civilian population set forth in Part II GC IV, such as respect for protected zones and hospitals, the protection of children under the age of 15, the provision of humanitarian assistance for certain beneficiaries, and facilitating family reunifications. On the other hand, in Part III, the Convention establishes a much more detailed and protective regime in favour of certain human groups, called ‘protected persons’.
Special Rules on Women
Authors: Quénivet Noëlle
Published: August 2024

This chapter discusses the protection afforded to women under the Geneva Conventions. It covers provisions for the protection of women, protection of specific categories of women, and protection of women detainees. Overall, the Conventions provide special protection for pregnant women, maternity cases, and mothers of children under the age of 7, and address the vulnerability of women to sexual violence in armed conflict. However, these provisions have been criticized for perpetuating stereotypical ideas of women as weak individuals whose ‘honour’ is defined by reference to male views on women, associating women with children, and failing to consider gender rather than sex as the distinguishing factor.
Special Rules on Children
Authors: Heintze Hans-Joachim , Lülf Charlotte
Published: August 2024

This chapter discusses rules governing the protection of children in the Geneva Conventions. It covers the legal definition of a child which is different in international humanitarian law and human rights law and therefore needs to be addressed in order to define the respective rights’ holders. Children constitute a vulnerable group and are entitled to special protection in international armed conflicts. Issues of the recruitment of child soldiers are discussed as well as the problems of direct and indirect participation of children in hostilities. The legal status of children detained and the treatment of children as POW is furthermore of relevance and is addressed separately. The chapter analyses also the established legal framework on the protection of children in non-international armed conflicts in comparison to the rules on international armed conflicts. The legal consequences of violations of the Geneva Conventions’ rules on child protection as well as the entitlement of international criminal law to deal with cases of child recruitment end this chapter on special rules on children.
The Geneva Conventions and the End of Occupation
Authors: Grignon Julia
Published: August 2024

This chapter examines provisions for the end of occupation in Geneva Convention (GC) IV. These include Article 6 paragraph 3, which states that the rules of GC IV cease to apply one year after the general close of military operations, but which also provides for a longer application of certain specific provisions in cases of occupation lasting more than one year; Article 47, which limits the effects of any agreement that might be concluded, e.g., in order to end an occupation, as illustrated by the Iraqi example of 2004; and Article 2 paragraph 2, which deals with the specific situation of occupation arising without any armed resistance from the opposing side. An analysis of Article 3 of Additional Protocol I is also provided, regarding its potential customary nature. The chapter finally considers a specific situation: the Gaza Strip after the ‘unilateral disengagement’ of the Israeli Army completed in September 2005.
Ship Management and Finance
Authors: Vella Ivan
Published: August 2024

This chapter analyses ship management and the finances of shipping activities. Ship management involves the care of one or more ships and their operations, usually in a commercial context. Accordingly, this means taking responsibility for these operations and various related matters including maintenance, equipment, manning, provisioning and supplies, insurance, the actual employment of the ships, and, where applicable, fulfilment of flag State and port State requirements. Traditionally, ship management functions were exercised by the owner (or operator) of a ship but nowadays almost every operator outsources specialist third parties. The chapter then examines ship finance, which is requested for the purchase of tonnage, for assistance towards capital projects relating to a ship, towards major repair work, and for any other specific purposes. Ship finance is usually provided by institutional lenders and other sources such as joint venture capital and initial public offerings (IPOs).
Law of Salvage
Authors: Bishop Archie
Published: August 2024

This chapter provides an introduction to international salvage law. It draws the definition of salvage from the former Queen’s Counsel Geoffrey Brice in his Maritime Law of Salvage, where he incorporated the four essential ingredients of salvage. Brice defined the right to salvage arising when a person, acting as a volunteer, preserves or contributes to preserving at sea any vessel, cargo, freight, or other recognized subject of salvage in danger. The chapter analyses each essential characteristic which are: to be a volunteer; to be successful; for the property salved to be a subject of salvage; and for there to be an element of danger. It also looks into some of the Articles of the Salvage Convention 1989 which expanded on the principle that a salvor is only rewarded if the salvage operation successfully rescues the ship or its cargo.
The International Convention for the Prevention of Pollution from Ships (MARPOL)
Authors: Fitzmaurice Malgosia
Published: August 2024

This chapter details the history and development of the International Convention on the Prevention of Pollution from Ships (MARPOL), and how it regulates ship-based marine pollution. Shipping contributes to a limited extent to marine pollution from human activities, in particular when compared to pollution from land-based sources (or even dumping). MARPOL’s regulatory regime is the reason why ship source pollution incidents since 1970 have been in decline, especially the so-called operational pollution vis-à-vis accidents. Credit should also be given to the International Maritime Organisation (IMO) for its dynamism in responding to the many challenges of the maritime industry, especially for forging consensus on many difficult issues confronting member States due to the diverging interest of the maritime industry’s stakeholders. The apparent success of MARPOL has been crucial in achieving IMO’s goal for safe, secure, and efficient shipping on clean oceans.
Regulation of Land-Based Marine Pollution
Authors: Tanaka Yoshifumi
Published: August 2024

This chapter explores the regulation of land-based pollution, which presents the most serious threat to marine ecology. Pollutants resulting from land-based activities include sewage, industrial discharges, and agricultural run-off. Major contaminants include plastic litter, nutrients, heavy metals, sediments, oil, and radioactive wastes. Some of the contaminants produce eutrophication and oxygen depletion, resulting in loss of marine life and biological diversity. Other substances are directly toxic to humans. In spite of these hazards the regulation of land-based marine pollution at the global level remains a weak one-in the sense that attempts to address land-based marine pollution have been made solely in the form of non-binding documents.
Regional Seas Programme
Authors: Maruma Mrema Elizabeth
Published: August 2024

This chapter reviews and assesses the role the United Nations Environment Programme (UNEP) has and continues to play in the development, administration, and management of a specific branch of international environmental law, namely, regional seas conventions and action plans forming part of the UNEP Regional Seas Programme and particularly, the ones administered by UNEP and/or where UNEP provides Secretariat functions. Development of the regional seas programme through the regional seas action plans, conventions, and protocols has been a priority programme of UNEP since it was established in 1974, as demonstrated through various UNEP governing council decisions taken over the years.
The Preamble of the Rio Declaration
Authors: Francioni Francesco
Published: August 2024

This chapter analyses the different preambular clauses of the Rio Declaration comparing them with the more ambitious ones formulated in the Stockholm Declaration and highlighting their mainly anthropocentric underpinnings.
Principle 1
Authors: Francioni Francesco
Published: August 2024

This chapter analyses the rationale, travaux préparatoires, conceptual scope, and normative and jurisprudential influence of Principle 1 of the Rio Declaration. It highlights the limited room given to human rights in the formulation of this principle and how the connection between human rights and environmental protection has subsequently evolved.
Principle 8
Authors: Voigt Christina
Published: August 2024

This chapter analyses the rationale, travaux préparatoires, conceptual scope, and normative influence of Principle 8 of the Rio Declaration. It pays particular attention to the efforts towards 'decoupling' economic growth and environmental degradation, and to how such efforts have been reflected in a number of international instruments.
Principle 11
Authors: Kunz Martina
Published: August 2024

This chapter analyses the rationale, travaux préparatoires, conceptual scope, and normative and jurisprudential influence of Principle 11 of the Rio Declaration. It then discusses different approaches to the coordination of domestic environmental legislation and regulations.
Principle 20
Authors: Mahon Claire
Published: August 2024

This chapter analyses the rationale, travaux préparatoires, conceptual scope, and normative relevance of Principle 20 of the Rio Declaration. It pays particular attention to how the specific situation of women has been increasingly reflected in sustainable development instruments.
Principle 21
Authors: Langer Magnus Jesko
Published: August 2024

This chapter analyses the rationale, travaux préparatoires, conceptual scope, and normative and jurisprudential relevance of Principle 21 of the Rio Declaration. It addresses an important yet underexplored area of international environmental law, namely the initiatives to foster environmental education and awareness as well as to enhance the participatory channels offered to young people.
Principle 27
Authors: Sand Peter H
Published: August 2024

This chapter analyses the rationale, travaux préparatoires, conceptual scope, and normative and jurisprudential relevance of Principle 27 of the Rio Declaration. It pays particular attention to the instruments through which cooperation among States but also peoples on global issues can find legal expression.
A New Theory of Jurisdiction in International Law
Authors: Ryngaert Cedric
Published: August 2024

This chapter first shows how the exercise of unilateral jurisdiction by States has become nearly inevitable in an era of globalization of business transactions as well as value conceptions. It then sets out the tenets of “substantivism”. It argues that multilateral solutions to transnational regulatory problems are unlikely to materialize across the board, and that internationally harmonized laws are, in terms of fairness, not necessarily preferable over the unilateral exercise of jurisdiction. Next, the chapter presents this study’s de lege ferenda approach to solving jurisdictional conflict. A “positive sovereignty” principle is proposed, pursuant to which States are allowed to apply their laws to a foreign situation, to the extent that the State that has the stronger nexus to the situation fails to adequately deal with, in a manner that is, on aggregate, harmful to the regulatory interests of the international community. By emphasizing global economic and value interests, this principle of subsidiary jurisdiction departs from the classical, negative understanding of the law of jurisdiction as a law that protects the interests of sovereign States.
Life
Authors: Antkowiak Thomas M , Gonza Alejandra
Published: August 2024

The American Convention, in its Article 4, is the only human rights treaty that expressly determines the point from which the right to life must be protected: “in general, from the moment of conception.” The Court has found arbitrary deprivations of life in numerous contexts, such as cases involving the death penalty, disproportionate police or military force, and internal armed conflicts. The Inter-American System has been a pioneer in the conceptual development of the crime of forced disappearance. Inter-American human rights law demands that States adopt numerous positive measures to safeguard life, including legislative action, prevention of violence, and the investigation and punishment of crime—all according to the due diligence standard. At times, the Court’s judgments blur positive and negative State duties in this area. The Tribunal has recognized rights to health, education, culture, food, and clean water as components of the right to life.
Personal Liberty
Authors: Antkowiak Thomas M , Gonza Alejandra
Published: August 2024

The Convention’s Article 7 establishes the general right of all persons to not be deprived illegally or arbitrarily of their liberty; in addition, it contains specific protections for individuals who have been deprived of their freedom. To activate the protections of Article 7, the Court does not require a minimum duration or specific location for the detention. Consequently, the Tribunal has found violations to Article 7 in a wide range of detention scenarios. We consider the Court’s current method of interpreting legality and arbitrariness to be flawed in certain respects. For example, unlike other international human rights tribunals, the Court often considers only the relevant domestic law, and not international law, in its assessment of a detention’s legality. When the Court narrows its legality inquiry to the letter of national law, international human rights may be limited or distorted, and the State’s discretion to restrict liberty may be increased.
Expropriation
Authors: Dolzer Rudolf , Schreuer Rudolf
Published: August 2024

This chapter discusses the concept of expropriation. Topics covered include the right to expropriate, the three branches of the law, the legality of expropriation, direct and indirect expropriation, and expropriation of contractual rights.
The Modern System of Investor-State Arbitration
Authors: Dugan Christopher F , Wallace Jr , Rubins Noah , Sabahi Borzu
Published: August 2024

This chapter discusses the emergence of the modern system of investor-state arbitration. Topics covered include the origins of investor-state arbitration, the creation of the International Centre for the Settlement of Investment Disputes (ICSID) and its role in the new system of investor-state arbitration, bilateral investment treaties, multilateral investment treaties, and national investment legislation.
Consolidation under Relevant Arbitration Rules or Treaties
Authors: Dugan Christopher F , Wallace Jr , Rubins Noah , Sabahi Borzu
Published: August 2024

Consolidation in the context of investment treaty arbitration is a challenging task. Apart from the complexity of legal and factual issues involved, which makes it difficult to assess whether separate arbitrations are similar enough to allow a tribunal to consolidate them, the institutional and ad hoc rules governing investment treaty arbitrations usually do not have any rules governing this matter. This chapter examines the consolidation of claims under the ICSID, UNCITRAL, NAFTA, and International Chamber of Commerce (ICC) rules, as well as the potential ramifications for enforcement of awards under the New York Convention.
The Nationality of the Investor
Authors: Dugan Christopher F , Wallace Jr , Rubins Noah , Sabahi Borzu
Published: August 2024

This chapter examines a range of legal issues which relate to the qualification of a natural or legal person as an investor under customary international law, investment protection treaties and legislation, and the Washington Convention. These include the status of minority, noncontrolling, and indirect shareholders; and issues arising out of change of nationality of investors and their implications for jurisdiction of arbitral tribunals under investment treaties and the Washington Convention.
Discrimination
Authors: Dugan Christopher F , Wallace Jr , Rubins Noah , Sabahi Borzu
Published: August 2024

The principle of non-discrimination is one of the basic protections for foreign investors and investments in host nations. Investment treaties provide guarantees against discrimination in three different ways. First, national treatment ensures that foreign investors will be treated no less favorably than similarly situated domestic investors. Second, most-favored-nation (MFN) treatment ensures that foreign investors will not be treated less favorably than investors from any third country. Finally, some treaties contain a provision that prohibits arbitrary and discriminatory impairment of investments by the host state. This chapter analyzes the basic elements of these protections and the difficulties faced by tribunals adjudicating discrimination claims
Expropriation
Authors: Dugan Christopher F , Wallace Jr , Rubins Noah , Sabahi Borzu
Published: August 2024

Expropriation is the taking by a government of privately owned property, also known in the common law as eminent domain. Such a taking is universally recognized as within the inherent power of a state over property located in its territory, and where the state expropriates only its own citizens' property, international law is not implicated. This chapter begins by presenting a historical overview of expropriation. It then discusses investments and property protected against expropriation, the role of investment treaties and investment insurance regimes, the problem of indirect or regulatory expropriation, and the current US approach to indirect or regulatory expropriation.
Damages, Compensation, and Non-Pecuniary Remedies
Authors: Dugan Christopher F , Wallace Jr , Rubins Noah , Sabahi Borzu
Published: August 2024

This chapter focuses on compensation, which is the most common remedy awarded by international tribunals. The chapter proceeds as follows. Section B examines the function of reparation by analyzing the dictum of the Permanent Court of International Justice in the Chorzów Factory case. Section C covers non-pecuniary remedies, including restitution and specific performance. Section D examines standards of compensation for expropriation and other treaty breaches. Section E explains a variety of valuation methods that have been used by international tribunals. Section F discusses the specific problem of valuing projects that have not become profitable. Section G examines compensation for breach of contract. Section H examines factors limiting the amount of compensation, such as absence of causation, contributory fault, and the obligation to mitigate damages. Section I examines the role of equity in awarding damages. Finally, sections J and K provide an overview of interest, costs, and attorneys' fees.
The Relationship between Patent and Antitrust Law
Authors: Devlin Alan
Published: August 2024

This chapter explores the issue of how competition policy governs intellectual property rights (IPRs). It addresses whether antitrust performs a limiting function, applying only to anticompetitive effects falling outside the scope of a patent. Showing that the answer is no, it examines how competition and patent law actually intersect. It considers how recent US and EU decisions shed light on their relationship, and articulates a theory governing doctrine in this space. It argues that a better way to understand the antitrust–patent intersection is to treat each of the two systems as sovereign—that is, mutually exclusive in application—but to discern discrete roles for each. The patent-scope approach, which relies on claim construction to identify lawful anticompetitive restraints, has one thing right: it tries to carve out non-overlapping roles for the competition and IP laws.
Manipulation of the Standard-Setting Process
Authors: Devlin Alan
Published: August 2024

This chapter focuses on issues unique to the use of patents in the standard-setting process. In particular, some patentees have convinced standard setting organizations (SSOs) to adopt their proprietary technologies through false promises to license on fair, reasonable, and nondiscriminatory (FRAND) terms or by concealing their patent holdings. Competition issues may arise if owners of standard-essential patents (SEPs) either renege on their FRAND-licensing promises or assert their undisclosed patents against those implementing the standards. The chapter is organized as follows. Section II explores the smartphone wars that have brought many SEP-antitrust issues to the fore. Section III addresses three questions. First, can a patentee violate antitrust law by concealing a SEP and later seeking non-FRAND licensing terms? Second, may the owner of a FRAND-encumbered SEP demand an injunction? Third, how do courts define FRAND royalty terms? Section IV discusses antitrust limits on SEP assertion in the EU.
Exclusionary Agreements in the Biopharmaceutical Industry
Authors: Devlin Alan
Published: August 2024

This chapter discusses antitrust issues in the biopharmaceutical industry, focusing on pay-for-delay agreements. Paying for delay raises fascinating policy issues, dividing commentators and courts alike. Post-Actavis, for instance, both US and EU law would condemn a patentee that settles infringement litigation by paying the accused infringer to stay out of the market. If the same patentee later successfully sued another entrant, proving infringement and successfully opposing an invalidity challenge, its earlier reverse-payment settlement would thus have imposed anticompetitive effects subsumed within the claims of a valid patent. Yet, an antitrust violation would endure. Given the complexity of pay-for-delay agreements, the chapter begins with an economic assessment of this conduct. Having explained that, in most cases, reverse exclusionary payments benefit the contracting parties at disproportionate cost to society, it discusses the current state of US and EU law, which remains in flux at the time of writing.
Distinct relapse pattern across molecular ependymoma types
Authors: Obrecht-Sturm Denise , Schoof Melanie , Eckhardt Alicia , Mynarek Martin , Gilbert Mark R , Aldape Kenneth , Armstrong Terri S , Ramaswamy Vijay , Bockmayr Michael , von Hoff Katja , Fleischhack Gudrun , Adolph Jonas E , Tippelt Stephan , Pfister Stefan M , Pajtler Kristian , Sturm Dominik , Drexler Richard , Ricklefs Franz L , Stepien Natalia , Gojo Johannes , Pietsch Torsten , Warmuth-Metz Monika , Kortmann Rolf , Timmermann Beate , Haberler Christine , Rutkowski Stefan , Schüller Ulrich
Published: August 2024

Background

Ependymoma (EPN) is not a uniform disease but represents different disease types with biological and clinical heterogeneity. However, the pattern of when and where different types of EPN relapse is not yet comprehensively described.

Methods

We assembled 269 relapsed intracranial EPN from pediatric (n = 233) and adult (n = 36) patients from European and Northern American cohorts and correlated DNA methylation patterns and copy-number alterations with clinical information.

Results

The cohort comprised the following molecular EPN types: PF-EPN-A (n = 177), ST-EPN-ZFTA (n = 45), PF-EPN-B (n = 31), PF-EPN-SE (n = 12), and ST-EPN-YAP (n = 4). First relapses of PF-EPN-B (PF: posterior-fossa) and PF-EPN-SE (SE: subependymoma) occurred later than of PF-EPN-A, ST-EPN-YAP (ST: supratentorial), or ST-EPN-ZFTA (median time to relapse: 4.3 and 6.0 years vs. 1.9/1.0/2.4 years; P < .01). Metastatic or combined recurrences in PF-EPN-B and -A more often involved the spinal cord than in ST-EPN-ZFTA (72.7% and 40.0 vs. 12.5%; P < .01). No distant relapses were observed in ST-EPN-YAP (n = 4) or PF-EPN-SE (n = 12). Post-relapse survival (PRS) was poor for PF-EPN-A and ST-EPN-ZFTA (5-year PRS: 44.5% ± 4.4%/47.8% ± 9.1%), whereas PF-EPN-B and PF-EPN-SE displayed a 5-year PRS of 89.5% ± 7.1%/90.0% ± 9.5% (P = .03). However, 10-year PRS for PF-EPN-B dropped to 45.8% ± 17.3%. Neither between the radiation field and relapse pattern nor between the radiation field and spinal involvement at relapse an impact was identified. Notably, all patients with relapsed ST-EPN-YAP did not receive upfront radiotherapy but were successfully salvaged using irradiation at relapse.

Conclusions

Relapse patterns of specific EPN types are different. Future clinical trials, treatment adaptions, duration of surveillance, and diagnostics should be planned to incorporate entity-specific relapse information.
Falsifying falsification
Authors: Young Jae Choi
Published: August 2024

Almost a decade after the UKSC’s decision of AIB v Redler, there remains significant academic criticism and judicial scepticism towards the employment of causal inquiries in equity’s remedial response to trustees’ misapplications of trust property. This article seeks to defend AIB, and the causal principles enunciated therein, from those criticisms. It does so by arguing that the interpretative arguments and normative justifications propounded in the literature in favour of falsification orders rest on shaky foundations. Consequently, it takes the view that the remedial principles espoused in AIB should be broadly accepted as representing equity’s general remedial approach to custodial breaches of trust.
The anti‐tumor effects of cosmosiin through regulating AhR/CYP1A1‐PPARγ in breast cancer
Authors: Wang Dan , Zhang Jing , Yin Houqing , Yan Ribai , Wang Zequn , Deng Jinhai , Li Gang , Pan Yan
Published: August 2024

Breast cancer is one of the threatening malignant tumors with the highest mortality and incidence rate over the world. There are a lot of breast cancer patients dying every year due to the lack of effective and safe therapeutic drugs. Therefore, it is highly necessary to develop more effective drugs to overcome breast cancer. As a glycoside derivative of apigenin, cosmosiin is characterized by low toxicity, high water solubility, and wide distribution in nature. Additionally, cosmosiin has been shown to perform anti‐tumor effects in cervical cancer, hepatocellular carcinoma and melanoma. However, its pharmacological effects on breast cancer and its mechanisms are still unknown. In our study, the anti‐breast cancer effect and mechanism of cosmosiin were investigated by using breast cancer models in vivo and in vitro. The results showed that cosmosiin inhibited the proliferation, migration, and adhesion of breast cancer cells in vitro and suppressed the growth of tumor in vivo through binding with AhR and inhibiting it, thus regulating the downstream CYP1A1/AMPK/mTOR and PPARγ/Wnt/β‐catenin signaling pathways. Collectively, our findings have made contribution to the development of novel drugs against breast cancer by targeting AhR and provided a new direction for the research in the field of anti‐breast cancer therapy.
Serotonin syndrome
Authors: Mungul Daniel , Bila Nick , Petr Grace , Satterberg Katie , Knueven Alyssa
Published: August 2024

Serotonin syndrome is a rare, life-threatening toxidrome caused by serotonergic agents. This syndrome classically presents with a combination of mental status changes, autonomic hyperactivity, and neuromuscular abnormalities. However, diagnosing the condition is difficult because of its variable symptoms at presentation. As a result, serotonin syndrome often is underreported, making it harder to understand, recognize, and treat. Patients with this condition may present to primary or urgent care or an ED, and may become acutely symptomatic during an inpatient admission. Clinicians must be able to identify at-risk patients and intervene to prevent potentially lethal complications.
Mentorship effect for PAs at an academic medical center and its healthcare system
Authors: Herndon Justine S. , Louwagie Victoria S. , Strelow Brittany A. , Schenzel Holly A. , Cumberland Elizabeth A. , Oxentenko Amy S.
Published: August 2024

Purpose:

Mentorship has many notable benefits. Research about mentorship for physician associates/assistants (PAs) is limited. This study sought to uncover more detailed information on mentorship and its effect on PAs.

Methods:

A survey was sent via email to all PAs and advanced practice registered nurses at our institution. Subgroup analysis was performed on PA respondents, including satisfaction and independent predictors associated with mentorship.

Results:

Of the 295 PAs, 63 (21.4%) identified having a mentor. Those with a mentor were statistically more likely to function as a mentor (OR 2.7 [95% CI 1.5-4.9], P = .001), have an academic rank of assistant professor or higher (OR 2.7 [95% CI 1.3-5.5], P = .007), be under age 45 years (OR 6.1 [95% CI 2.1-17.4], P = .008), be less than 10 years into their career (OR 3.1 [95% CI 1.7-5.7], P = .002), and be satisfied with mentorship (88.9% versus 23.9%, P < .001).

Conclusions:

Mentorship for PAs is crucial and can boost academic promotion and career satisfaction.
Efficacy of Hypothermic Compression Bandages in Cardiac Device Surgical Wounds: A Randomized Controlled Trial
Authors: Cano Valls Alba , Niebla Mireia , Diago Clara , Domingo Rebeca , Tolosana Jose Maria , Pérez Sílvia
Published: August 2024

BACKGROUND

Pocket hematoma is the most prevalent complication with cardiac implantable electronic devices (CIEDs), especially in patients who are undergoing oral anticoagulation and/or antiplatelet therapy.

OBJECTIVE

To evaluate the efficacy of hypothermic compression bandaging versus conventional compression bandaging for the prevention of surgical wound hematoma of CIEDs in patients who are undergoing chronic anticoagulant drug use and/or antiplatelet therapy.

METHODS

This was a single-center randomized prospective study. The intervention group received a hypothermic compression bandage, and the control group received a conventional compression bandage. The primary endpoint was the appearance of hematoma 10 days after the intervention.

RESULTS

A total of 310 patients participated in the study. The mean age of the participants was 73.77 ± 10.68 years, and 74.8% were men. In the intervention group, 5.88% (n = 18) of patients developed ecchymosis, and 1.3% (n = 4) developed mild hematoma. In the control group, 5.88% (n = 18) of patients developed ecchymosis, and 2.9% (n = 9) developed mild hematoma. No patient in either group had a severe hematoma. No significant differences were observed between the two types of dressing in any of the three degrees of hematoma.

CONCLUSIONS

This study demonstrated that compression bandaging with or without hypothermic therapy effectively prevents pocket hematoma of CIEDs in patients at high risk of bleeding.
Screening of a kinase inhibitor library identified novel targetable kinase pathways in triple-negative breast cancer
Authors: Rinderle Caroline H. , Baker Christopher V. , Lagarde Courtney B. , Nguyen Khoa , Al-Ghadban Sara , Matossian Margarite D. , Hoang Van T. , Martin Elizabeth C. , Collins-Burow Bridgette M. , Ali Simak , Drewry David H. , Burow Matthew E. , Bunnell Bruce A.
Published: August 2024

Triple-negative breast cancer (TNBC) is a highly invasive breast cancer subtype that is challenging to treat due to inherent heterogeneity and absence of estrogen, progesterone, and human epidermal growth factor 2 receptors. Kinase signaling networks drive cancer growth and development, and kinase inhibitors are promising anti-cancer strategies in diverse cancer subtypes. Kinase inhibitor screens are an efficient, valuable means of identifying compounds that suppress cancer cell growth in vitro, facilitating the identification of kinase vulnerabilities to target therapeutically. The Kinase Chemogenomic Set is a well-annotated library of 187 kinase inhibitor compounds that indexes 215 kinases of the 518 in the known human kinome representing various kinase networks and signaling pathways, several of which are understudied. Our screen revealed 14 kinase inhibitor compounds effectively inhibited TNBC cell growth and proliferation. Upon further testing, three compounds, THZ531, THZ1, and PFE-PKIS 29, had the most significant and consistent effects across a range of TNBC cell lines. These cyclin-dependent kinase (CDK)12/CDK13, CDK7, and phosphoinositide 3-kinase inhibitors, respectively, decreased metabolic activity in TNBC cell lines and promote a gene expression profile consistent with the reversal of the epithelial-to-mesenchymal transition, indicating these kinase networks potentially mediate metastatic behavior. These data identified novel kinase targets and kinase signaling pathways that drive metastasis in TNBC.
Association Between Persistent Hypothermia After Cardiopulmonary Bypass in Neonates and Odds of Serious Complications
Authors: Helman Stephanie M. , Sereika Susan , Hravnak Marilyn , Henker Richard , Gaynor J. William , Herrup Elizabeth , Olsen Robert , Kochanek Patrick M. , Ghassemzadeh Rod , Baust Tracy , Riek Nathan T. , Domnina Yuliya , Lisanti Amy Jo , Al-Zaiti Salah
Published: August 2024

IMPORTANCE:

Persistent hypothermia after cardiopulmonary bypass (CPB) in neonates with congenital heart defects (CHD) has been historically considered benign despite lack of evidence on its prognostic significance.

OBJECTIVES:

Examine associations between the magnitude and pattern of unintentional postoperative hypothermia and odds of complications in neonates with CHD undergoing CPB.

DESIGN:

Retrospective cohort study.

SETTING:

Single northeastern U.S., urban pediatric quaternary care center with an established cardiac surgery program.

PARTICIPANTS:

Population-based sample of neonates greater than or equal to 34 weeks gestation undergoing their first CPB between 2015 and 2019.

INTERVENTIONS:

None.

MAIN OUTCOMES AND MEASUREMENTS:

Hourly temperature measurements for the first 48 postoperative hours were extracted from inpatient medical records, and clinical characteristics and outcomes were accessed through the local patient registry. Group-based trajectory modeling (GBTM) identified latent temporal temperature trajectories. Associations of trajectories with outcomes were assessed using multivariable binary logistic regression. Outcomes (postoperative complications) were manually adjudicated by experts or were predefined by the patient registry.

RESULTS:

Four hundred fifty neonates met inclusion criteria. Their mean (sd) gestational age was 38 weeks (1.3), mean (sd) birth weight was 3.19 kilograms (0.55), median (interquartile range) surgical age was 4.7 days (3.3–7.0), 284 of 450 (63%) were male, and 272 of 450 (60%) were White. GBTM identified three distinct curvilinear temperature trajectories: persistent hypothermia (n = 38, 9%), resolving hypothermia (n = 233, 52%), and normothermia (n = 179, 40%). Compared with the normothermic group, those with persistent hypothermia had significantly higher odds of cardiac arrest, actionable arrhythmia, delayed first successful extubation, prolonged cardiac ICU length of stay, very poor weight gain, and 30-day hospital mortality. The persistent hypothermia group was characterized by greater odds of having a lower gestational age, more prevalent neurologic abnormalities, more unplanned reoperations, and a low surgical mortality risk assessment.

CONCLUSIONS:

Persistent postoperative hypothermia in neonates after CPB is independently associated with having greater odds of complications. Recovery patterns from postoperative hypothermia may be a clinically useful marker to identify patient instability in neonates. Additional research is needed for causal modeling and prospective validation before clinical adoption.
Social Dynamics and Discourse Moves: A Closer Look Into a Twitter-Facilitated Professional Learning Space
Authors: Zheng Binbin , Beck Dallaghan Gary , Wang Zilu
Published: August 2024

Introduction:

Professionals use Twitter because of its potential to support easy and rapid communication among like-minded people. It is also used widely by educators to support the establishment of professional learning spaces. This study investigates social interactions and knowledge construction in synchronous online discussions using the Twitter hashtag #MedEdChat.

Methods:

Three synchronous Twitter discussions on #MedEdChat during the early part of the COVID-19 pandemic were analyzed. Social network analysis was conducted to capture the social interactions among their participants and network dynamics. Content analysis was used to examine the nature of tweets posted on #MedEdChat, including social-related, cognitive-related, and moderation-related tweets.

Results:

In all three discussions, a small number of individuals dominated the interactions, while also serving as hubs for connections with others in more peripheral positions. Very few participants were isolated nodes who never interacted with others during the online discussions. Our content analysis suggested that parties to these discussions posted social-related posts the most, followed by cognitive-related ones. Social posts focused on others' messages, continuing threads, issuing compliments and greetings, and expressing emotions. Cognitive-related posts, on the other hand, mostly focused on information exchange/sharing or asking content-related questions to promote discussion (ie, triggering event).

Discussion:

By examining social dynamics and discourse moves in Twitter-supported online synchronous discussions using the #MedEdChat hashtag, this study found that Twitter has the potential to facilitate professional learning spaces in which a few highly active individuals serve as portals for connections and interactions among all discussants. In addition, in such communities, social-related and cognitive-related tweets could promote social interactions and knowledge construction.
The Effect of Breathing Exercises Using a Breathing Exercise Device and Virtual Reality Applications During Pregnancy and Labor on Labor
Authors: Karacan Emine , Akkoz Cevik Semra
Published: August 2024

The study aimed to determine the effects of breathing exercises using a breathing exercise device and virtual reality applications during pregnancy and labor on labor pain, duration, and birth satisfaction. This study was planned as a single-blind randomized controlled experimental study. The study was conducted with a total of 114 pregnant women who were randomized between September 2022 and May 2023 at a maternity hospital in Southeastern Anatolia, Turkey. The participants were divided into three groups: the breathing exercise group (39), the virtual reality group (37), and the control group (38). The data were collected by using the descriptive information form, labor observation form, visual analog scale, and Birth Satisfaction Scale. The incidence of average pain scores and labor duration were lower in the intervention groups when compared with the control group (P < .05). The average birth satisfaction scores of pregnant women in both experimental groups were determined to be higher than those in the control group (P < .05). The research results show that breathing exercises using a breathing exercise device during pregnancy and labor and virtual reality applications shorten the duration of labor, reduce labor pain, and increase birth satisfaction.
Utility of the Repetitive Nerve Stimulation Test and Needle EMG in the Trapezius Muscle for the Early Diagnosis of ALS
Authors: Takahashi Kazusa , Hamada Yuichi , Kobayashi Masahito , Kobayashi Shunsuke , Kanbayashi Takamichi , Hatanaka Yuki , Nakayama Takahiro , Imafuku Ichiro , Matsuno Hiromasa , Iguchi Yasuyuki , Katada Fumiaki , Fukutake Toshio , Ando Tetsuo , Mikata Takashi , Usui Toru , Uchino Katsuyuki , Nishiyama Kazutoshi , Sonoo Masahiro
Published: August 2024

Objectives:

To document the utility of decremental responses in the repetitive nerve stimulation test (RNS) and spontaneous activities in needle electromyography (EMG) in the trapezius muscle for the diagnosis of amyotrophic lateral sclerosis.

Methods:

Subjects were retrospectively identified from our EMG database. Cervical spondylosis was represented as a disease control group. We investigated the sensitivity and specificity of RNS and EMG in the trapezius muscle and those of diagnostic criteria including the Gold Coast criteria (GCC).

Results:

We reviewed 120 patients with amyotrophic lateral sclerosis and 17 patients with cervical spondylosis. “RNS or EMG” achieved the highest sensitivity (85%). The specificity was the highest for RNS (94%). Addition of RNS of the deltoid muscle achieved 98% sensitivity in the upper-limb onset amyotrophic lateral sclerosis. The sensitivity of the GCC was very high (88%).

Conclusions:

Neurophysiological parameters investigated in this study having close to 100% specificities or sensitivities are useful as complements to the GCC.
What is in the Myopathy Literature?
Authors: Isfort Michael , Lacomis David
Published: August 2024

This update begins with a section on inflammatory myopathies covering inclusion body myositis in younger patients, the possibility of a pathogenic role for anti-cN1A antibodies, and a negative trial of arimoclomol in inclusion body myositis. The potential study of Janus kinase inhibitors in dermatomyositis is discussed as well as the possible role of targeted therapy for immune checkpoint inhibitor neuromuscular complications. Next, studies of disease-modifying or potential disease-modifying therapies for inherited myopathies are addressed including the encouraging follow-up study of gene replacement therapy for Duchenne muscular dystrophy (DMD), a negative trial of tamoxifen in DMD, and the complex topic of gene therapy for X-linked myotubular myopathy. A newly identified condition of muscular dystrophy from 3-hydroxy-3-methylglutaryl-CoA reductase mutations is addressed along with possible therapy. Other papers regarding GNE myopathy and long-term outcome of enzyme replacement therapy in infantile onset Pompe disease round out that section. Updates on the expanding spectra of anoctamin-5 myopathies, caveolinopathies, and congenital and mylagic myopathies from CACNA1S mutations follow as well as extensive discussion of Valosin containing protein proteinopathies, comprehensive management of Becker muscular dystrophy, and gastrointestinal complications in adult DMD.