bluuebunny/crossref_metadata_2025_split huggingface dataset:
Upregulation of Phosphodiesterase 7A Contributes to Concurrent Pain and Depression via Inhibition of cAMP-PKA-CREB-BDNF Signaling and Neuroinflammation in the Hippocampus of Mice
Authors: Chen Shi-cai , Chen Yan-han , Song Yan , Zong Shu-hua , Wu Ming-xia , Wang Wei , Wang Hao , Zhang Feng , Zhou Yan-meng , Yu Hai-yang , Zhang Han-ting , Zhang Fang-fang 
Published: September 2024

Abstract

Background
Phosphodiesterases (PDEs) are enzymes that catalyze the hydrolysis of cyclic adenosine monophosphate AMP (cAMP) and/or cyclic guanosine monophosphate (cGMP). PDE inhibitors can mitigate chronic pain and depression when these disorders occur individually; however, there is limited understanding of their role in concurrent chronic pain and depression. We aimed to evaluate the mechanisms of action of PDE using 2 mouse models of concurrent chronic pain and depression.

Methods
C57BL/6J mice were subjected to partial sciatic nerve ligation (PSNL) to induce chronic neuropathic pain or injected with complete Freund’s adjuvant (CFA) to induce inflammatory pain, and both animals showed depression-like behavior. First, we determined the change in PDE expression in both animal models. Next, we determined the effect of PDE7 inhibitor BRL50481 or hippocampal PDE7A knockdown on PSNL- or CFA-induced chronic pain and depression-like behavior. We also investigated the role of cAMP-protein kinase A (PKA)-cAMP response element binding protein (CREB)-brain-derived neurotrophic factor (BDNF) signaling and neuroinflammation in the effect of PDE7A inhibition on PSNL- or CFA-induced chronic pain and depression-like behavior.

Results
This induction of chronic pain and depression in the 2 animal models upregulated hippocampal PDE7A. Oral administration of PDE7 inhibitor, BRL50481, or hippocampal PDE7A knockdown significantly reduced mechanical hypersensitivity and depression-like behavior. Hippocampal PDE7 inhibition reversed PSNL- or CFA-induced downregulation of cAMP and BDNF and the phosphorylation of PKA, CREB, and p65. cAMP agonist forskolin reversed these changes and caused milder behavioral symptoms of pain and depression. BRL50481 reversed neuroinflammation in the hippocampus in PSNL mice.

Conclusions
Hippocampal PDE7A mediated concurrent chronic pain and depression in both mouse models by inhibiting cAMP-PKA-CREB-BDNF signaling. Inhibiting PDE7A or activating cAMP-PKA-CREB-BDNF signaling are potential strategies to treat concurrent chronic pain and depression.
Antimicrobial resistance profiles of and associated risk factors for Pseudomonas aeruginosa nosocomial infection among patients at two tertiary healthcare facilities in Lusaka and Copperbelt Provinces, Zambia
Authors: Mukomena Patrice Ntanda , Simuunza Martin , Munsaka Sody , Kwenda Geoffrey , Bumbangi Flavien , Yamba Kaunda , Kabwe Josephine , Kayembe Jean-Marie , Muma John Bwalya 
Published: September 2024

Abstract

Background
Antimicrobial resistance (AMR) of pathogens such as Pseudomonas aeruginosa is among the top 10 threats to global health. However, clinical and molecular data are scarce in Zambia. We, therefore, evaluated the AMR profiles of P. aeruginosa nosocomial infections (NIs).

Methods
A year-long hospital-based cross-sectional study was conducted at two large tertiary-level hospitals in Zambia. Patients with current or previous hospital contact were screened for NIs. The current study focused on patients diagnosed with P. aeruginosa NIs. Clinical specimens were collected for bacteriological culture, and PCR amplification of 16S rRNA gene fragments was performed on pure isolates. Hospital or NIs were defined as infections that arise during hospitalization, occurring at least 48 h after admission. The Kirby–Bauer’s disk diffusion method was used to evaluate antibiotic resistance patterns. The association between AMR and risk factors was analysed using the χ2 test.

Results
Eight hundred and forty-one patients were screened, and clinical specimens were collected and analysed. Of them, 116 (13.7%) were diagnosed with P. aeruginosa NIs. The participants’ ages ranged from 15 to 98 years, with a mean of 51 (SD ± 18). Catheter-associated urinary tract infections (57%) were the most common, followed by pressure sores (38.7%). P. aeruginosa isolates were primarily susceptible to amikacin, which had the highest resistance to FEP. We observed a high prevalence of multidrug resistance (73.6%). The AMR was associated with carbapenem-hydrolysing β-lactamase gene blaOXA-51 and surgical care.

Conclusions
This study has demonstrated that multidrug-resistant P. aeruginosa is prevalent in hospitals in Zambia’s Lusaka and Ndola districts and possibly countrywide.
Drafting History*
Authors: Khan Daniel-Erasmus 
Published: September 2024

Abstract
This chapter traces the drafting history of the UN Charter from the genesis of the United Nations at the time the collapse of the League of Nations became evident and the war triggered by the aggression of Nazi Germany widened into a world war thus raising the inevitable question of a new legal world order for the post-war era. The chapter then identifies four phases in which the constitutive instrument of the UN was conceived, negotiated, drafted, signed, and ratified. It looks at the stages in the creation of the new world organization, considering the Dumbarton Oaks Conference, the Yalta compromise, and the Founding Conference. The chapter also discusses the selection of the site of the UN headquarters as well as the transition from the League of Nations to the United Nations.
Reform
Authors: Rensmann Thilo 
Published: September 2024

Abstract
This chapter begins by looking at the concept of reform, a process in which political and legal elements are inextricably intertwined. What measures will improve the UN’s effectiveness and efficiency and hence constitute a ‘change for the better’ is largely a matter of political judgement. Indeed, the process of reforming the UN has a distinct political dimension insofar as it responds to changes in political reality, requires political judgement and initiative, and is dependent on mustering the requisite political support amongst the member States. At the same time, however, it remains firmly embedded in the ‘constitutional’ framework of the Charter. The role of the Charter within this process encompasses three dimensions: the Charter is a programme for reform; it imposes limits on reform; and it may itself be the object of reform. The chapter then identifies different phases of reform, considering the Cold War and collective security; decolonization; administrative and budgetary reform; the 2005 World Summit; and the Sustainable Development Goals.
Article 1
Authors: Kleinlein Thomas 
Published: September 2024

Abstract
This chapter evaluates Art 1 of the UN Charter. Article 1 defines four ‘purposes’ of the United Nations: to maintain international peace and security; to develop friendly relations among nations based on respect for the principle of equal rights and self-determination of peoples; to achieve international cooperation in solving international problems of an economic, social, cultural, or humanitarian character; and to be a centre for harmonizing the actions of nations in the attainment of these common ends. These four purposes are obviously vague and thus contribute to the nature of the UN as a political organization. However, the purposes of the Organization are legally binding both for its member States as State parties to the Charter and for its organs and agencies. From the case law, it is not clear whether the enumeration of purposes attributes powers to the UN and is per se sufficient authorization for its organs to act.
Article 2 (2)
Authors: Kolb Robert 
Published: September 2024

Abstract
This chapter assesses Art 2 (2) of the UN Charter. Article 2 (2) lays down the obligation for all members of the UN to fulfil their obligations ‘in accordance with the present Charter’. Technically, two interpretations of this sentence are possible. First, that the members are called upon to fulfil all—but only—the obligations under international law that can be reconciled with the law of the Charter. Conversely, obligations contrary to the Charter should not so be fulfilled. Second, that the members shall apply all their obligations under international law against the backdrop of the Charter by using the latter as a touchstone of interpretation. Both interpretations can be squared with the text of Art 2 (2). The chapter then looks at the specific content of the obligation of good faith in the framework of the Charter, as well as its application in UN practice.
Article 2 (3)
Authors: Tomuschat Christian 
Published: September 2024

AbstractThis chapter addresses Art 2 (3) of the UN Charter. The core element of Art 2 (3) is constituted by the concept of dispute and the means suited to bring about a peaceful settlement to any such disturbance in international relations. No distinction is made in Art 2 (3) between ‘political’ and ‘legal’ disputes in departure from a traditional line of doctrinal thinking. Obviously, however, any dispute brought before the International Court of Justice must be related to some legal norm and cannot be derived solely from political claims. All disputes between and among States contain political elements that do not impede their assessment according to legal standards. The chapter then looks at the elaboration of the principle of the peaceful settlement of disputes in the practice of the United Nations.
Article 2 (7)*
Authors: Nolte Georg 
Published: September 2024

Abstract
This chapter discusses Art 2 (7) of the UN Charter. According to its text, Art 2 (7) protects member States only against acts of the UN and not against acts of other member States. It was originally intended to strengthen the protection of States against incursions by the new collective security organization into their domestic affairs. In practice, however, Art 2 (7) has been increasingly eroded and emptied of substance. This not so much because the term ‘intervention’ has been narrowly interpreted but rather because more and more matters are no longer recognized as belonging to the domestic jurisdiction of States. This development raises the question of whether Art 2 (7) has become largely obsolete or whether a new interpretation is necessary.
Self-Determination
Authors: Oeter Stefan 
Published: September 2024

Abstract
This chapter discusses the right of self-determination as a concept of the UN Charter. The right of self-determination is mentioned in the UN Charter in Art 1 (2). With this reference, guaranteeing self-determination of all nations became a central political purpose of the United Nations, inextricably linked with the purpose of achieving friendly relations among nations. Such friendly relations should be based—according to the Charter—on respect for the principle of equal rights and self-determination of peoples. Such wording already indicates that the drafters considered self-determination to be a fundamental principle of international law. Although Art 1 (2), due to its programmatic character, cannot define in detail the content and scope of a right to self-determination, it sets beyond dispute that it forms part of the law of the Charter and is binding upon all members of the UN. Self-determination is also explicitly mentioned in Art 55 of the Charter.
Article 4
Authors: Riznik Donald , Fastenrath Ulrich 
Published: September 2024

Abstract
This chapter evaluates Art 4 of the UN Charter, which governs subsequent membership in the United Nations. It sets out the material requirements for subsequent UN membership and the associated procedure involving the two main organs of the UN, the Security Council and the General Assembly. From the beginning, it had been undisputed that the UN, as an organization to preserve world peace and security, should have as broad a membership as possible. Nevertheless, the San Francisco Conference did not opt for the idea of automatic membership for all States, which would have guaranteed the UN’s absolute universality. Instead, it was thought that the objectives of the UN would be better and more effectively realized under a concept of conditional universality. In the course of decolonization, however, the concept of conditional universality seems to have been largely replaced by a concept of automatic admission. With the admission of (mostly decolonized) developing States, the UN assumed responsibility for providing multilateral support to States characterized by weak statehood.
Article 14
Authors: Thielbörger Pierre 
Published: September 2024

Abstract
This chapter examines Art 14 of the UN Charter. At its core, Art 14 gives the General Assembly the competence to recommend the adjustment of any situation—including, arguably, treaties—if otherwise the general welfare or international relations between States were likely to be impaired. The background to this provision is the idea that at times a given situation can become incompatible with the changed political, economic, or cultural reality so that international tensions could arise. The question then is should and can the situation be brought ‘up to date’, and by which mechanism and on whose initiative? Article 14 is sometimes said to have become more or less irrelevant today. Indeed, a large part of the GA’s work today lies in making recommendations for peaceful change.
Article 15
Authors: Tichy Helmut , Bittner Philip 
Published: September 2024

Abstract
This chapter evaluates Art 15 of the UN Charter, which is one of the provisions of the Charter that define the central position of the General Assembly within the structure of the Organization. The GA is the only principal organ that receives and considers reports from all other principal organs and, therefore, exercises the ‘function of overall review of the work of the Organization’. All other principal organs are accountable to the GA, although to varying degrees. The GA exercises its review function primarily through the consideration of the annual reports of the other principal organs. Each of these annual reports is structured differently, according to the specific needs of the respective organ, but they all give an account of the activities of the organ during the reporting period. These reports are essential for deliberations in the GA and for taking action in the form of resolutions and decisions.
Article 17
Authors: Mangelsdorf Hans-Christian 
Published: September 2024

Abstract
This chapter focuses on Art 17 of the UN Charter. The first two paragraphs of Art 17 circumscribe the fiscal powers of the General Assembly to approve the budget and to apportion the expenses of the Organization. Together with the requirement of a two-thirds majority present and voting on budgetary questions prescribed by Art 18 (2), and the loss of voting rights according to Art 19 of a member whose contributions are in arrears for the two preceding years, they represent the foundation pillars of the fiscal constitution of the Organization. Both the financial management and general management of the Organization have evolved significantly over the last decades. The Organization has developed or incorporated various governance practices leading to a rich set of rules, regulations, and policies. The chapter then considers the third paragraph of Art 17, which defines the authority of the GA in administrative, financial, and budgetary matters with regard to specialized agencies.
Article 22
Authors: Khan Daniel-Erasmus , Kirchmair Lando 
Published: September 2024

Abstract
This chapter studies Art 22 of the UN Charter, which provides an important legal basis for the complex organizational structure of the UN. Under Art 22, ‘the General Assembly may establish such subsidiary organs as it deems necessary for the performance of its functions’. Today, diversity is still the dominant feature of the GA’s organizational sub-structure. Indeed, due to an enormously wide range of organizational forms; of the fields and scope of activities; of duration and methods of appointment and termination; of the legal, institutional, and factual ties with the GA itself; and the lack of any kind of uniformity in the terminology used for denomination purposes, attempts to put the subsidiary organs established under Art 22 into the straitjacket of doctrinal ‘typology’ have hitherto failed to produce satisfying results. Even the UN itself has not succeeded in producing any kind of classification.
Article 23
Authors: von Arnauld Andreas 
Published: September 2024

Abstract
This chapter discusses Art 23 of the UN Charter. Following the Dumbarton Oaks Proposals, the original version of Art 23 (1) provided that the Security Council should consist of eleven members, five permanent and six non-permanent. The significant rise in UN membership in the course of decolonization pressed for an amendment to the Charter which was effected in 1965. Thus, the number of non-permanent members was raised to ten. To keep the SC small and capable of acting, according to Art 23 (3), each SC member has only one representative. As State representatives, these ‘are bound to act in conformity with the instructions given to them by the competent organs of their states’. Ultimately, the SC’s composition of two groups of members, permanent and non-permanent, influences the distribution of power within the SC.
Article 28
Authors: Bühler Konrad 
Published: September 2024

Abstract
This chapter focuses on Art 28 of the UN Charter. Learning the lessons from the failures of the League of Nations, the main idea behind Art 28 was to create a more effective executive organ of the new Organization that would be able to act promptly in order to discharge its primary responsibility for the maintenance of international peace and security. Article 28 is composed of three separate paragraphs: Art 28 (1) stipulates the ‘continuous functioning’ of the Security Council, for which purpose the members of the SC shall be ‘represented at all times’ at the seat of the UN. Article 8 (2) deals with SC meetings at which the SC members are, as a rule, represented by ‘a member of the government or by some other specially designated representative’. Article 28 (3), which covers both ordinary and extraordinary meetings, deals with the places where the meetings may be held.
Article 29
Authors: Lippold Matthias , Paulus Andreas 
Published: September 2024

Abstract
This chapter assesses Art 29 of the UN Charter. In line with the general authority contained in Art 7 (2) of the Charter, Art 29 empowers the Security Council to establish subsidiary organs to perform its functions effectively. Due to the limited size of its membership, the SC has greater leeway for effective action than the General Assembly. The SC depends on the support of more flexible subsidiary organs in carrying out its duties of investigating, negotiating, administering, and offering services. In addition, subsidiary organs such as the international criminal tribunals for the former Yugoslavia and Rwanda, the International Residual Mechanism for Criminal Tribunals (IRMCT), or the UN Compensation Commission can perform tasks which the SC cannot perform itself, namely the adjudication of claims and the prosecution of alleged offenders of international criminal law. While Art 29 focuses on the procedural aspect of subsidiary organs and their establishment, it does not set out their substantive limits.
Article 30
Authors: Rodiles Alejandro 
Published: September 2024

Abstract
This chapter addresses Art 30 of the UN Charter, the normative content of which is brief. The first section provides that the Security Council, and no other UN body, has the competence to adopt its rules of procedure. The second section makes clear that the rules concerning the President of the SC form part of the rules of procedure which come under the first section and are thus also to be decided by the SC. In this way, the Charter implicitly provides that the SC shall have a president. As a corollary to these provisions, it is often said that the SC is ‘master of its procedure’ and, in any event, it is not subordinate to any other UN body.
Article 37*
Authors: Giegerich Thomas 
Published: September 2024

Abstract
This chapter discusses Art 37 of the UN Charter, which supplements cases in which the parties to a dispute with the potential of endangering the maintenance of international peace and security have been unable to settle the dispute on their own. It points out that the use of force is no longer an acceptable means of settling disputes in the UN era. It also describes the League Covenant that placed greater emphasis on the actual settlement of disputes, while the UN Charter is primarily concerned with preventing breaches of the peace to which they may give rise. The chapter explores how serious disputes that remain unsettled can lead to tensions that may ultimately lead to armed conflict. It explains that the UN Charter was conceived to ensure that armed force will not be used.
Peacekeeping
Authors: Bothe Michael 
Published: September 2024

Abstract
This chapter discusses the term ‘peacekeeping’, which describes a type of military action used as a tool in the United Nations system of collective security. It explains that peace was designed as an alternative to enforcement action or enforcement measures that imply the use of military force. It also details how the League of Nations and the UN Charter established a system of collective security where coercion exercised by the international community against a State threatening or breaking the peace has been an essential element. The chapter recounts the case of the attacks by North Korea and China on South Korea in 1950, where the Security Council recommended that member States assist the victim and allowed the coalition to use the flag of the United Nations. It describes the concept of the use of military components based on consent and cooperation.
Introduction to Chapter VII: The General Framework
Authors: de Wet Erika 
Published: September 2024

Abstract
This chapter highlights Chapter VII of the UN Charter, wherein the Security Council enjoys greater powers than any other international organ in the history of international organizations. It details how the SC may take enforcement action and resort to military measures in order to deal effectively with threats to the peace and how the UN Charter poses few express limitations to such action. It also discusses the decision to grant the SC broad powers, which was mainly a reaction to the unsatisfactory experience with the system of sanctions in the framework of the League of Nations. The chapter describes the League Covenant that had enforced international responsibilities by the community of nations. It emphasizes that member States were obligated to take independent measures against a law-breaker.
Article 39
Authors: de Wet Erika 
Published: September 2024

Abstract
This chapter covers Art 39 of the UN Charter, which opens the way for the adoption of enforcement measures in cases of threats to the peace and breaches of the peace or acts of aggression. It considers Art 39 as the single most important provision of the Charter. It also discusses the travaux préparatoires for Art 39 which allow the Security Council to take enforcement action in a broad range of cases and not to subject it to severe restrictions in its decision of when to act. The chapter describes various States that have sought to ensure consistent and predictable enforcement action by defining its prerequisites. It emphasizes how the SC enjoys considerable discretion in determining whether a threat to the peace, a breach of the peace, or an act of aggression exists.