bluuebunny/crossref_metadata_2025 huggingface dataset:
Cruel, Inhuman or Degrading Treatment or Punishment
Authors: Zach Gerrit , Birk Moritz
Published: June 2024

This chapter discusses Article 16 of the Convention against Torture, covering the chronology of draft texts, analysis of Working Group discussions, and issues of interpretation. Article 16 mirrors Article 2 and provides a broad obligation of States to prevent cruel, inhuman or degrading treatment, or punishment. Issues of interpretation that have been thoroughly debated are the scope of Article 16 and which State obligations, as outlined by the Convention, are not only applicable to torture, but also to cruel, inhuman or degrading treatment or punishment. Developments over time in terms of how to interpret these State obligations can especially be witnessed vis-à-vis the legal qualification of corporal and capital punishment.
State Reporting Procedure
Authors: Monina Giuliana
Published: June 2024

This chapter discusses Article 19 of the Convention against Torture, covering the chronology of draft texts, analysis of Working Group discussions, and issues of interpretation. The State reporting process monitors the implementation of human rights treaties at the national level and creates a basis for constructive dialogue between States and treaty bodies. It is the only mandatory monitoring mechanism included in all nine core human rights treaties and under two Optional Protocols to the Convention of the Right of the Child. Article 19 requires States parties to submit to the Committee, through the Secretary-General of the United Nations, reports on the measures they have taken to give effect to their undertakings under this Convention, within one year after the entry into force of the Convention for the State Party concerned.
Amendment
Authors: Monina Giuliana
Published: June 2024

This chapter discusses Article 29 of the Convention against Torture, covering the chronology of draft texts, analysis of Working Group discussions, and issues of interpretation. Article 29 allows any State Party to this Convention to propose an amendment and file it with the Secretary-General of the United Nations. Article 29 is based on the fairly complicated and impractical amendment procedure of Article 51 of the International Covenant on Civil and Political Rights. While Article 51(2) of the International Covenant on Civil and Political Rights requires approval by the General Assembly and a two-thirds majority of the States parties, Article 29 of the Convention against Torture excludes any role of the General Assembly. Instead of four stages, Article 29 only requires three stages: (1) approval of a special conference by one-third of the States parties; (2) adoption of the text of the amendment by simple majority of the States parties present at such a conference; and (3) the subsequent acceptance by two-thirds of the States parties in accordance with their respective constitutional processes.
Settlement of Disputes
Authors: Monina Giuliana
Published: June 2024

This chapter discusses Article 30 of the Convention against Torture, covering the chronology of draft texts, analysis of Working Group discussions, and issues of interpretation. The article states that any dispute between two or more States Parties concerning the interpretation or application of this Convention which cannot be settled through negotiation shall be submitted to arbitration. If within six months from the date of the request for arbitration the Parties are unable to agree on the organization of the arbitration, any of those Parties may refer the dispute to the International Court of Justice. Thus far, neither the optional inter-State communication procedure nor the dispute settlement procedure have proven more successful. Out of 162 States parties, only 24 States parties are currently making use of their opting-out power under Article 30(2) — until now Article 30 was applied only once in the case Belgium v Senegal before the International Court of Justice.
Denunciation
Authors: Monina Giuliana
Published: June 2024

This chapter discusses Article 31 of the Convention against Torture, covering the chronology of draft texts, analysis of Working Group discussions, and issues of interpretation. The article states that State a Party may denounce this Convention by written notification to the Secretary-General of the United Nations. Such a denunciation shall not have the effect of releasing the State Party from its obligations under this Convention in regard to any act or omission which occurs prior to the date at which the denunciation becomes effective, nor shall denunciation prejudice in any way the continued consideration of any matter which is already under consideration by the Committee prior to the date at which the denunciation becomes effective.
Authentic Texts
Authors: Monina Giuliana
Published: June 2024

This chapter discusses Article 33 of the Convention against Torture, covering the chronology of draft texts, analysis of Working Group discussions, and issues of interpretation. Article 33 of the Convention against Torture represents the customary final clause of treaties concluded under the auspices of the United Nations. In conformity with the procedure common for UN treaties, it states that the text is equally authentic in all UN languages officially recognized at the date the treaty was adopted. This means that the six designated languages, which are also today recognized as the official UN languages, are equally controlling for the interpretation of the text, whereby it can be assumed that the terms in the Convention have the same meaning in each authentic text. Should a comparison of the authentic texts discover a difference in meaning, the true meaning is to be ascertained by applying the rules of interpretation set down in Articles 31, 32 and 33(4) of the Vienna Convention on the Law of Treaties.
Obligations of the Subcommittee Concerning Country Missions
Authors: Buchinger Kerstin
Published: June 2024

This chapter discusses Article 13 of the Optional Protocol to the Convention against Torture and other Cruel, Inhuman or Degrading Treatment or Punishment, covering the chronology of draft texts, analysis of Working Group discussions, and issues of interpretation. Article 13 of the Optional Protocol contains corresponding Subcommittee on Prevention of Torture (SPT) obligations regarding the conduct of missions and visits. Taking into account the main objective of the Protocol, namely to establish a system of regular and preventive visits to places of detention, and the guiding principles of impartiality, non-selectivity, universality, and objectivity, the SPT shall establish a programme of regular missions, at first by lot. It shall notify the States parties of this programme in order to enable the governments concerned to make the necessary practical and logistical arrangements for the country missions.
Establishment of National Preventive Mechanisms
Authors: Krisper Stephanie
Published: June 2024

This chapter discusses Article 17 of the Optional Protocol to the Convention against Torture and other Cruel, Inhuman or Degrading Treatment or Punishment, covering the chronology of draft texts, analysis of Working Group discussions, and issues of interpretation. Article 17 of the Optional Protocol repeats the obligation of States parties under Article 3 of the Optional Protocol to maintain, designate, or establish one or several independent national mechanisms for the prevention of torture at the domestic level. The two-pillar system corresponds to a general rule that States have the primary responsibility under international law to respect, protect, and ensure the human rights of all people subject to their jurisdiction, whereas monitoring by international bodies of States' compliance with their international human rights obligations is only of a complementary nature.
Relation to the International Committee of the Red Cross
Authors: Krisper Stephanie
Published: June 2024

This chapter discusses Article 32 of the Optional Protocol to the Convention against Torture and other Cruel, Inhuman or Degrading Treatment or Punishment, covering the chronology of draft texts, analysis of Working Group discussions, and issues of interpretation. In times of international armed conflict, the International Committee of the Red Cross (ICRC) is authorized by the Geneva Conventions to visit all places of detention where prisoners of war, detained civilians, and other protected persons are or may be. The original Costa Rica Draft and Article 17(3) of the European Committee for the Prevention of Torture are based on the principle that a visit by the ICRC should be given preference to visits by a human rights-monitoring body which, therefore, shall refrain from visiting place of detention that are visited by the ICRC. Article 32 of the Optional Protocol is, however, based on the opposite principle, namely that both types of visits are complementary and demand cooperation between the Subcommittee and the ICRC.
Amendments
Authors: Krisper Stephanie
Published: June 2024

This chapter discusses Article 34 of the Optional Protocol to the Convention against Torture and other Cruel, Inhuman or Degrading Treatment or Punishment, covering the chronology of draft texts, analysis of Working Group discussions, and issues of interpretation. The article allows any State Party to the present Protocol to propose an amendment and file it with the Secretary-General of the United Nations. The Secretary-General shall thereupon communicate the proposed amendment to the States Parties to the present Protocol with a request that they notify him whether they favour a conference of States Parties for the purpose of considering and voting upon the proposal.
The Environmental Sustainability Principles
Authors: Sourgens Frédéric G , Sempertegui Leonardo
Published: June 2024

This chapter considers principles concerned with the transboundary environmental sustainability of energy systems in transition outside of the climate context. It mentions how environmental sustainability adds further consideration to energy transition governance. Moreover, transboundary environmental sustainability in the climate context is closely related to climate principles. The transboundary environmental sustainability issues faced by energy transition outside of the immediate climate context range between resource extraction, building a circular energy economy, and climate engineering. Meanwhile, the core principles significant in the international environmental setting beyond the climate regime are the right to participation in environmental decision-making, the obligation to protect biodiversity, and the obligation to protect the oceans.
Community and Indigenous Rights Principles
Authors: Sourgens Frédéric G , Sempertegui Leonardo
Published: June 2024

This chapter explores community and indigenous rights principles. While energy transition is a global policy problem, the work needed for the energy transition is always local somewhere. The protection of local communities directly affected by energy transition activities is a critical component of energy transition governance. As energy transition requires a radical shift in energy value chains, energy transition imposes a significant strain on affected communities and then communities will have to navigate the benefits and drawbacks of having large energy value chain projects located in their backyard. The chapter clarifies the general applicability of the aforementioned eight principles as they do not strictly apply to energy transition issues.
Definition of Natural Heritage
Authors: Catherine Redgwell
Published: June 2024

This chapter covers the definition of natural heritage as per indicated in the 1972 Convention's Article 2. The innovation of the Convention aims to embrace the natural environment within a wider category of world heritage and to express the intergenerational obligation of conservation and transmission. The chapter explains that the Convention's natural heritage category was largely inspired by the US' proposal for a World Heritage Trust in the mid-1960s. It highlights the importance of outstanding universal value when it comes to protecting, conserving and transmitting natural heritage. Recent trends found in the evolution of the article's application include the number of serial property and transboundary nominations.
National and International Protection of the Cultural and Natural Heritage
Authors: Guido Carducci
Published: June 2024

This chapter details Chapter II of the 1972 Convention. Private and public international law offers various mechanisms of legal protection for cultural property and heritage. They offer a higher or lower protection threshold depending on the applicable law or international law rule. Chapter II primarily focuses on the national protection and international protection of cultural and natural heritage. Moreover, Chapter II operates autonomously by requiring States Parties to identify and protect both categories of heritage regardless of Chapter III. The chapter explains that the Convention's Chapter II holds importance from a legal and policy-making perspective. It also tackles the articles and their importance under Chapter II.
List of World Heritage in Danger and Deletion of a Property from the World Heritage List
Authors: Gionata P Buzzini , Luigi Condorelli
Published: June 2024

This chapter discusses Article 11 of the 1972 Convention, which governs the inscription of a property on the List of World Heritage in Danger. It explains that clarification is needed of the condition laid down by the article. The request for assistance under the Convention should not be confused with a State Party request concerned for the inscription of a property on the List of World Heritage in Danger. The chapter looks into the process of the deletion of a property from the World Heritage List. It explains how the World Heritage Committee is responsible for examining whether or not the property in question should be removed from the World Heritage List.
International Assistance
Authors: Federico Lenzerini
Published: June 2024

This chapter looks into 1972 Convention provisions on international assistance. Due to its correlation with the World Heritage Fund, the scheme of international assistance represents the operational core of the World Heritage Convention. The chapter explains that Articles 19-26 of the Convention must be read in conjunction with the commentary of Article 13. It also details the modalities, conditions, priorities, and benefits of international assistance. Since its inception in 1972, the Convention and its World Heritage Fund have provided different forms of international assistance, such as emergency assistance, preparatory assistance, and conservation and management assistance. The chapter explains that the forms of assistance may be granted by the World Heritage Fund.
Educational Programmes
Authors: Federico Lenzerini
Published: June 2024

This chapter expounds on Article 27 of the World Heritage Convention. The provision's paragraph 2 highlights the need to raise awareness of the threats to World Heritage and inform the public about safeguarding activities undertaken. The chapter explains the application of the provision through either raising awareness or education. It discusses the Higher Education and Forum UNESCO—University and Heritage (FUUH) Network under the responsibility of the World Heritage Centre. Moreover, the implementation of Article 28 correlates closely with Article 27 since it concerns raising awareness about the benefits of varying international assistance that States Parties receive from the World Heritage Fund.
Federal or Non-Unitary Constitutional Systems
Authors: Ben Boer
Published: June 2024

This chapter considers the responsibilities indicated in the World Heritage Convention's Article 34. It explains that the provision addressed the responsibilities for the implementation of the Convention of States Parties that are federally organized or have a non-unitary constitutional system. Article 34 can potentially raise some thorny issues in situations where sub-national levels of government do not wish to cooperate with federally-organized or non-unitary national governments. The chapter elaborates on the judicial scrutiny surrounding Article 34, which concerns federal-state conflicts over the distribution of environmental powers. It also looks into the differences between unitary systems, non-unitary systems, and federal systems.
The World Heritage Convention and Other Conventions Relating to the Protection of the Natural Heritage
Authors: Catherine Redgwell
Published: June 2024

This chapter looks into the World Heritage Convention and other conventions relating to the protection of natural heritage. It starts with how the Convention does not necessarily explicitly address its relationship with other treaty instruments. However, the proliferation of environmental treaty-making in 1972 resulted in the need for formal and informal modes of cooperation between the Convention and other instruments with similar objectives for the protection of the natural heritage. Thus, the Operational Guidelines provide for the strengthening of synergies with other agreements. The chapter explains the general international law principles that led to the resolution of any dispute as to the priority of the World Heritage Convention.
World Heritage and Human Rights
Authors: Ana Filipa Vrdoljak
Published: June 2024

This chapter covers the correlation between world heritage and international human rights law. It cites that the promotion of human rights and fundamental freedoms is foundational to the interpretation, implementation and operation of the World Heritage Convention. However, the Convention nor its final text does not make specific reference to human rights, so the absence is unusual when the Convention was drafted during the adoption of key human rights instruments. The chapter elaborates on the centrality of human rights to UNESCO’s raison d’être. It then overviews the international legal responsibility of various actors in respect of gross, systematic violations of human rights related to World Heritage properties.
The World Heritage Convention and the Law of the Sea
Authors: Patrizia Vigni
Published: June 2024

This chapter considers the World Heritage Convention's reach towards the law of the sea. It mentions that the 1972 UNESCO Convention does not have any norms concerning the seas. However, the World Cultural Heritage is broad enough to encompass marine sites. Moreover, some maritime areas have already been inscribed on the World Heritage List. The chapter mentions the high chance of overlap between the norms of the World Heritage Convention and other international treaties when concerned with marine sites. It explains that the 1972 World Heritage Convention and international norms on the law of the sea are based on the jurisdictional criteria of State sovereignty principles.
The World Heritage Convention and International Investment Law
Authors: Valentina Vadi
Published: June 2024

This chapter expounds on the correlation between the World Heritage Convention and international investment law. World heritage holds incommensurable value for both present and future generations, so it receives strengthened protection at the international level. Moreover, the universal ratification of the Convention suggests that adjudicators must consider cultural concerns when handling world heritage-related disputes. The chapter examines principal legal tools to enable a better balance between economic and cultural interests in international investment law and arbitration. It also tackles the adoption of legality requirements, cultural clauses, and/or provisions reaffirming a state’s cultural sovereignty and the obligations to protect world heritage.
The Actors of International Economic Law
Authors: Herdegen Matthias
Published: June 2024

This chapter focuses on the actors of international economic law. It starts with the subjects of international law, which is primarily the States, and the actors in international economic relations. The scope of actors in international economic relations reaches well beyond international legal subjects as they shape today’s international economic acne and influence the formulation of rules and standards. The chapter mentions the significance of the development of human rights standards and the possibility of investors bringing claims against a State before the International Centre for Settlement of Investment Disputes (ICSID). It then discusses the interplay between private enterprises and standards for transnational corporations.
The General Agreement on Trade in Services (GATS)
Authors: Herdegen Matthias
Published: June 2024

This chapter highlights the importance of The General Agreement on Trade in Services (GATS). It defines GATS' scope of application, which also coincides with its concurrent application with the General Agreement on Tariffs and Trade (GATT) 1994. The GATS extends to all measures which affect trade in services and covers all services in any sector except for those supplied in the exercise of governmental authority. However, some commitments under the GATS generally prohibit restrictive measures, even if these are applied in a non-discriminatory manner. The chapter also cites that the GATS establishes specific rules for the financial sector which have great potential for cross-border services but also create opportunities for tax evasion.
Letters of Credit
Authors: Herdegen Matthias
Published: June 2024

This chapter highlights the importance of letters of credit in international sales as an instrument for payment in international documentary sales. Letters of credit primarily establish an undertaking of a bank acting on behalf of the buyer or the seller. The chapter then discusses the key concepts of documentary credit and a standby letter of credit. On the other hand, a revocable letter of credit can be altered or cancelled by the applicant or the issuing bank without prior notice or consultation with the beneficiary. However, a revocable letter of credit offers little protection to the beneficiary so it is hardly used.
International Accounting Standards
Authors: Herdegen Matthias
Published: June 2024

This chapter notes how International accounting standards play a vital role for any internationally operating public company. It elaborates on the broad recognition of the standards of the International Accounting Standards Board (IASB) on a global level. Additionally, the standards are the basis for international annual accounts and other financial statements. In the United States, on the other hand, annual accounts must conform to the United States Generally Accepted Accounting Principles (US-GAAP). The chapter then cites that the IASB and the Financial Accounting Standards Board (FASB) are constantly updating their standards while establishing an agreement on a roadmap for convergence.
Insulting Speech
Authors: Webb Philippa , Milo Dario , Garciandia Rosana
Published: June 2024

This chapter assesses the current state of international and domestic laws on insulting speech, and how these laws are used to attack journalists and other speakers. International and regional bodies generally agree that imprisonment is not an appropriate penalty in defamation laws or similar laws used to target insults to public officials, such as sedition or lèse-majesté. However, more than 160 countries still have criminal defamation laws on their books, and many of these—instead of providing extra protection for political speech—include aggravated punishment for speech that criticizes public officials, heads of state or the state itself. These laws are used to devastating effect on citizens and the media across the world. The chapter proposes recommendations based on international standards to address gaps or inconsistencies in international human rights law, including the decriminalization of insulting speech.
Speech Related to National Security: Terrorism Laws
Authors: Gardoll Alice
Published: June 2024

Regulation of terrorist-related speech walks a legal tightrope. Terrorist attacks can lead to huge loss of life, and limiting their occurrence is a key priority of governments and social media companies the world over. But fundamental disagreements exist about the definition of terrorism, the type of speech that may cause or contribute to it, and where the line should be drawn between protecting speech versus protecting communities against potential violence. Counterterrorism and public order laws have also been used across the world to chill speech by journalists or state critics. This chapter assesses international and state practice regarding the application of terrorism, extremism and public order laws. It discusses the international standards applicable to this speech and areas of divergence between international and regional bodies in applying these standards. For example, this chapter explores the challenges that arise when considering whether offences such as ‘glorification’, ‘promotion’ and ‘justification’ of terrorism fulfil minimum intent and causation requirements under international law. The chapter provides recommendations to both states and technology and social media companies, drawing on international standards and best practices, to ensure that their approach to terrorist-related speech does not violate freedom of expression.
Dynamical structures of misaligned circumbinary planets under hierarchical three-body systems
Authors: Lei Hanlun , Gong Yan-Xiang
Published: June 2024

All circumbinary planets (CBPs) currently detected are located in almost co-planar configurations with respect to the binary orbit, due to the fact that CBPs with higher misalignment are more difficult to detect. However, observations of polar circumbinary gas and debris discs in recent years and long-term orbital stability of inclined planets indicate that it is possible to form misaligned CBPs around eccentricity binaries (even polar CBPs). In this work, we focus on the dynamical structures of CBPs in a wide range of parameters in order to provide a guidance for the space where the binary can host planets for a long enough time. To this end, the dynamical model is approximated as a hierarchical three-body problem, and the secular approximation is formulated up to the hexadecapolar order in semimajor axis ratio. Dynamical maps show that there are complex structures in the parameter space. A web of secular resonances is produced in the entire parameter space and it can well explain those numerical structures arising in dynamical maps. Based on perturbative treatments, an adiabatic invariant is introduced and thus dynamical structures can be explored by analysing phase portraits. It is found that (a) the quadrupole-order resonance (nodal resonance) is responsible for the distribution of V-shape region, and high-order and secondary resonances dominate those structures inside or outside V-shape region, and (b) the secondary 1:1 resonance is the culprit causing symmetry breaking of dynamical structures inside polar region.
High-density resolution of the Kaposi's sarcoma associated herpesvirus transcriptome identifies novel transcript isoforms generated by long-range transcription and alternative splicing
Authors: Shekhar Ritu , O'Grady Tina , Keil Netanya , Feswick April , Amador David A Moraga , Tibbetts Scott A , Flemington Erik K , Renne Rolf
Published: June 2024

Kaposi's sarcoma-associated herpesvirus is the etiologic agent of Kaposi's sarcoma and two B-cell malignancies. Recent advancements in sequencing technologies have led to high resolution transcriptomes for several human herpesviruses that densely encode genes on both strands. However, for KSHV progress remained limited due to the overall low percentage of KSHV transcripts, even during lytic replication. To address this challenge, we have developed a target enrichment method to increase the KSHV-specific reads for both short- and long-read sequencing platforms. Furthermore, we combined this approach with the Transcriptome Resolution through Integration of Multi-platform Data (TRIMD) pipeline developed previously to annotate transcript structures. TRIMD first builds a scaffold based on long-read sequencing and validates each transcript feature with supporting evidence from Illumina RNA-Seq and deepCAGE sequencing data. Our stringent innovative approach identified 994 unique KSHV transcripts, thus providing the first high-density KSHV lytic transcriptome. We describe a plethora of novel coding and non-coding KSHV transcript isoforms with alternative untranslated regions, splice junctions and open-reading frames, thus providing deeper insights on gene expression regulation of KSHV. Interestingly, as described for Epstein-Barr virus, we identified transcription start sites that augment long-range transcription and may increase the number of latency-associated genes potentially expressed in KS tumors.
Applying an equity lens to social prescribing
Authors: Khan Koser , Tierney Stephanie , Owen Gwilym
Published: June 2024

Background

Social prescribing is often described as an intervention that can help reduce health inequalities yet there is little evidence exploring this. This study aimed to assess the feasibility of accessing and analysing social prescribing (SP) service user data to demonstrate the impact of SP on health inequalities.

Methods

The sample size consisted of records for 276 individuals in Site 1 and 1644 in Site 2. Descriptive analyses were performed to assess the characteristics of people accessing SP, the consistency of data collected and the missingness across both sites.

Results

Both sites collected basic demographic data (age gender, ethnicity and deprivation). However, data collection was inconsistent; issues included poor recording of ethnicity in Site 2, and for both sites, referral source data and health and well-being outcome measures were missing. There was limited data on the wider determinants of health. These data gaps mean that impacts on health inequalities could not be fully explored.

Conclusions

It is essential that SP data collection includes information on user demographics and the wider determinants of health in line with PROGRESS Plus factors. Considering equity around who is accessing SP, how they access it and the outcomes is essential to evidencing how SP affects health inequalities and ensuring equitable service delivery.
XIThe Eighteenth Century
Authors: Turner Joseph , Saggini Francesca , Carver Dylan , Bender Ashley
Published: June 2024

This chapter has four sections: 1. General and Prose; 2. The Novel; 3. Poetry; 4. Drama. Section 1 is by Joseph Turner; section 2 is by Francesca Saggini; section 3 is by Dylan Carver; section 4 is by Ashley Bender.
XVIIIBibliography, Textual Criticism, Reference Works, and Miscellaneous
Authors: Baker William
Published: June 2024

This chapter, in common with Chapter XVII, has broadly six sections, although there is crossing over between them: 1. Periodicals; 2. Edited Collections; 3. Editions and Associated Books; 4. Bibliography; 5. Miscellaneous; 6. Late Arrivals, which includes some items not covered in earlier chapters . In order to avoid confusion, YWES readers are strongly advised to consult the excellent ‘YWES Index of Authors and Subjects’ found at the end of the present volume. Thanks are due to Professor James May for input on the 2022 volume of The Eighteenth-Century Intelligencer, and to Professor Patrick Scott for his input on the Burns Chronicle and Studies in Scottish Literature. The compiler is also grateful to those who facilitated ease of access to their journals such as Professor Shef Rogers and Script & Print, the Bulletin of the Bibliographical Society of Australia & New Zealand, Emma Brown and James Fleming in the instance of The Book Collector, and Dr Sarah Werner for access to PBSA—The Papers of the Bibliographical Society of America. Last but by no means least Juan Christian Pellicer, of the University of Oslo, a former YWES contributor, for generously making available to me his fascinating study Preposterous Virgil: Reading through Stoppard, Auden, Wordsworth, Heaney. If anyone or organization has been omitted, my apologies.
Hypoxia exosome derived CEACAM5 promotes tumor‐associated macrophages M2 polarization to accelerate pancreatic neuroendocrine tumors metastasis via MMP9
Authors: Ye Mujie , Lu Feiyu , Gu Danyang , Xue Bingyan , Xu Lin , Hu Chuanhua , Chen Jinhao , Yu Ping , Zheng Hongxia , Gao Yue , Wang Jianhua , Tang Qiyun
Published: June 2024

Exosomes play significant roles in the communications between tumor cells and tumor microenvironment. However, the specific mechanisms by which exosomes modulate tumor development under hypoxia in pancreatic neuroendocrine tumors (pNETs) are not well understood. This study aims to investigate these mechanisms and made several important discoveries. We found that hypoxic exosomes derived from pNETs cells can activate tumor‐associated macrophages (TAM) to the M2 phenotype, in turn, the M2‐polarized TAM, facilitate the migration and invasion of pNETs cells. Further investigation revealed that CEACAM5, a protein highly expressed in hypoxic pNETs cells, is enriched in hypoxic pNETs cell‐derived exosomes. Hypoxic exosomal CEACAM5 was observed to induce M2 polarization of TAM through activation of the MAPK signaling pathway. Coculturing pNETs cells with TAM or treated with hypoxic exosomes enhanced the metastatic capacity of pNETs cells. In conclusion, these findings suggest that pNETs cells generate CEACAM5‐rich exosomes in a hypoxic microenvironment, which in turn polarize TAM promote malignant invasion of pNETs cells. Targeting exosomal CEACAM5 could potentially serve as a diagnostic and therapeutic strategy for pNETs.
The Pharmacological Management of Ketamine Use Disorder: A Systematic Review
Authors: Roberts Emmert , Sanderson Elizabeth , Guerrini Irene
Published: June 2024

Objectives

There has been limited evidence synthesis examining treatment of ketamine use disorder. We aimed to conduct a systematic review to assess the efficacy and tolerability of pharmacological interventions in the management of ketamine use disorder.

Methods

We searched MEDLINE, EMBASE, PsychINFO, and CENTRAL (Cochrane Central Register of Controlled Trials) from database inception to November 14, 2023, for studies of any design that reported on any pharmacological intervention in the management of ketamine use disorder. We extracted any reported measure of efficacy or tolerability and assessed outcome quality using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework. We planned to combine outcomes using random-effects meta-analysis, where this was not possible results were reported narratively.

Results

Twelve studies met the inclusion criteria reporting on 368 participants. These comprised 1 controlled trial, 2 retrospective case series, and 9 case reports. Two studies reported on ketamine intoxication, 6 on withdrawal, and 4 on craving/relapse prevention. All studies reported only descriptive outcomes, and all evidence was of very low quality. Benzodiazepine regimens and haloperidol were reported to have potential utility in intoxication and withdrawal, whereas naltrexone, lamotrigine, and a combination of paliperidone palmitate and bupropion were reported to have potential utility in craving/relapse prevention.

Conclusions

There is a paucity of research into pharmacological management of ketamine use disorder. The limited very low-quality evidence suggests benzodiazepine regimens may be most salient for future exploration in management of ketamine intoxication and withdrawal, whereas case reports suggest naltrexone, lamotrigine, and paliperidone palmitate plus bupropion may potentially merit further investigation with regard to craving/relapse prevention.
Zalunfiban: A Review of Current Knowledge and Future Applications of an Innovative Antiplatelet Agent
Authors: Veasaw Kassidy , Sharma Pritika , Frishman William H. , Aronow Wilbert S.
Published: June 2024

Zalunfiban is a novel glycoprotein IIb/IIIa inhibitor currently being tested for its use in the prehospital setting for antiplatelet effect in patients with ST-elevation myocardial infarction. It has shown to be safe and effective in both phase 1 and phase 2 trials and is under investigation in phase 3 trials. In this review, we discuss zalunfiban in detail, including its mechanism of action, adverse effects, current recommendations for use, and ongoing trials.
The Potential Impact of Renin–Angiotensin System Inhibitors on Cancer Survival and Recurrence: A Systemic Review and Meta-Analysis
Authors: Fatima Kaneez , Ellahi Aayat , Adil Mariam , Kashif Haider , Uzair Muhammad , Ashraf Naela , Barolia Mehak , Hyder Mujtaba , Nakhuda Areeba , Ayub Michelle , Butt Sofia Jamil , Rashid Ahmed Mustafa
Published: June 2024

Renin–angiotensin system inhibitors (RASis), specifically angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs), are widely used antihypertensives. Their impact on the prognostic outcomes among patients with cancer has been subject to scrutiny and debate. The aim of this study was to evaluate the effect of RASis on survival in patients with cancer.

We systematically searched PubMed, Web of Science, Embase, and Cochrane Library for relevant studies published until April 1, 2022. All the studies, interventional or observational, which examined effects of ARBs and ACEis on cancer prognosis compared with a control group and reported the survival outcomes and hazard ratios were included in the analysis. From each study, pooled hazard ratios (HRs) with corresponding 95% confidence intervals (95% CIs) were identified and collected. Subgroup analysis was conducted to investigate heterogeneity.

61 studies were included in this meta-analysis. Data of 343,283 participants were used in the study. It was found that RASis improved overall survival (HR = 0.88; 95% CI, 0.82–0.93; P < 0.0001), progression-free survival (HR = 0.72; 95% CI, 0.65–0.79; P < 0.00001), disease-specific survival (HR = 0.86; 95% CI, 0.71–1.04; P = 0.03), and recurrence-free survival (HR = 0.74; 95% CI, 0.58–0.93; P = 0.01) in patients with cancer. The effect of RASis on overall survival varied depending on the type of cancer or type of RASis (ACEis or ARBs), according to subgroup analysis.

The usage of renin–angiotensin system inhibitors has a positive impact on survival outcomes and recurrence among patients with cancer.
Alcohol-associated liver disease: Emerging therapeutic strategies
Authors: Mullish Benjamin H. , Thursz Mark R.
Published: June 2024

The large and growing burden of alcohol-associated liver disease—and the considerable burden of morbidity and mortality associated with it—has been a drive toward ongoing research into novel strategies for its treatment, with a particular focus upon alcohol-associated hepatitis (AH). Management of alcohol-use disorder forms the central pillar of alcohol-associated liver disease care, with evidence-based psychological and pharmacological approaches being well established, and certain models demonstrating improved clinical outcomes when hepatology and addiction services are co-located. Corticosteroids have previously been used somewhat indiscriminately in patients with severe AH, but effective tools now exist to assess early response (and limit futile ongoing exposure). Techniques to predict risk of corticosteroid-related infection are also available, although current clinical strategies to mitigate this risk are limited. A variety of novel therapeutic approaches to AH are at different phases of trials and evidence gathering, with some of the most promising signals related to cytokine manipulation, epigenetic modulation, and targeting of the gut microbiota (ie, by means of fecal microbiota transplant). While remaining an ongoing source of debate, early liver transplant in severe AH has grown in interest and acceptability over the past decade as evidence supporting its efficacy builds, in the process challenging paradigms about mandatory pretransplant sobriety periods. However, uncertainty remains regarding the optimal selection criteria, and whether liver transplant has a role for only a highly limited proportion of patients with AH or more widespread application. This review aims to provide an overview of this fast-moving field.
Negative predictive value of fecal immunochemical testing in significant bowel disease screening: a systematic review and meta-analysis
Authors: Junhai Zhen , Fei Liao , Jixiang Zhang , Huabing Xie , Cheng Tan , Weiguo Dong
Published: June 2024

Objectives:

General practitioners (GPs) must assess significant bowel disease (SBD) in patients with lower bowel symptoms during primary care. Studies have evaluated the efficacy of fecal immunochemical testing (FIT) for SBD screening. However, the effectiveness of FIT remains controversial. This study aimed to investigate the value of FIT in SBD screening.

Methods:

PubMed, the Cochrane Database, and EMBASE were systematically searched. Studies that estimated FIT values in screening for SBD among patients with lower bowel symptoms were included. Sensitivity, specificity, negative likelihood ratio (NLR), positive likelihood ratio (PLR), diagnostic odds ratio (DOR), and negative predictive value (NPV) were calculated. Additionally, the pooled area under the summary receiver operating characteristic (SROC) curve was analyzed.

Results:

A total of 8615 patients with lower bowel symptoms who underwent FIT and colonoscopy to screen for SBD were enrolled and assessed in this meta-analysis; of these, 1226 patients were ultimately diagnosed with SBD. The pooled sensitivity, specificity, PLR, NLR, DOR, and NPV of FIT in SBD screening were 0.65 (95% CI: 0.50–0.78), 0.85 (95% CI: 0.72–0.92), 4.2 (95% CI: 2.60–6.90), 0.41 (95% CI: 0.29–0.58), 10 (95% CI: 6–17), and 0.90 (95% CI: 0.87–0.94), respectively. Besides, the pooled SROC was 0.82 (95% CI: 0.78–0.85).

Conclusions:

This study indicates that the FIT provides a favorable NPV for SBD screening and could be a valuable technique for GPs to rule out SBD in primary care. At the same time, GPs need to remain vigilant and refer patients to gastroenterologists when necessary.
Influence of body fat tissue on outcomes in patients undergoing hepatectomy or liver transplantation: a systematic review and meta-analysis
Authors: Zhang Lilong , Xia Zhijia , Li Zhongyi , Zhang Jing , Wang Kunpeng , Wang Weixing
Published: June 2024

Objective:

The purpose of this study is to investigate potential associations between body fat composition and postoperative outcomes in patients with hepatectomy or liver transplantation.

Methods:

Three online databases, including Embase, PubMed, and the Cochrane Library, were thoroughly searched for literature describing the relationship between body fat composition and outcomes of patients with liver surgery from the start of each database to 29 October 2023. The Newcastle–Ottawa Scale was used to rate the quality of the studies.

Results:

This analysis included a total of 29 articles with a combined patient cohort of 6435 individuals. The results demonstrated that patients with high intramuscular fat content (IMFC) had significantly inferior overall survival (OS) [hazard ratio (HR): 2.07, 95% CI: 1.69–2.53, P<0.001] and recurrence-free survival (RFS) (HR: 1.61, 95% CI: 1.20–2.16, P=0.002) and a higher risk of major complications (HR: 2.20, 95% CI: 1.59–3.05, P<0.001). We also found that the presence of high visceral-to-subcutaneous fat tissue ratio (VSR) in patients with liver surgery was significantly related to poorer OS (HR: 1.70, 95% CI: 1.44–2.00, P<0.001) and progression-free survival (PFS) (HR: 1.29, 95% CI: 1.11–1.50, P=0.001) and a higher major complication rate (HR: 2.31, 95% CI: 1.17–4.56, P=0.016). Besides, the synthesized findings indicated there is no significant correlation between visceral fat tissue and survival outcomes or postoperative complications.

Conclusion:

In summary, preoperative IMFC and VSR have the potential to forecast poorer OS and RFS and a higher risk of complications for patients undergoing hepatectomy or liver transplantation.
Recurrence of breast cancer after reconstruction with macro-textured silicone breast implants: a retrospective cohort study
Authors: Spoor Jonathan , Dieleman Frederike , Bleiker Eveline M.A. , Koppert Linetta B. , Vrancken Peeters Marie-Jeanne T.F.D. , van Leeuwen Flora E. , Mureau Marc A.M.
Published: June 2024

Background:

Recently, old concerns linking silicone breast implants (SBIs) with breast cancer have resurfaced. These concerns apply specifically to the risk of breast cancer recurrence in patients who received breast reconstructions with macro-textured SBIs. In this study, the authors investigated the effect of breast reconstruction with macro-textured SBIs on long-term oncologic outcomes of breast cancer patients.

Materials and methods:

The authors conducted a retrospective cohort study in two large cancer centres in the Netherlands. Patients who had been treated for primary breast cancer between 1 January 2000 and 31 December 2015 were included. Data on treatment and oncologic outcomes were obtained from prospectively maintained institutional and nationwide registries. Patient files were reviewed manually to complement missing information. Missing data were accounted for by multiple imputations by chained equations (MICE). Reconstruction with a macro-textured SBI was analysed as a time-dependent variable. The main outcomes of interest were locoregional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS). Hazard ratios (HRs) were estimated using multivariable Cox proportional hazard models.

Results:

Of the 4695 women who were eligible for inclusion, 2393 had undergone mastectomy. Of these women, 1187 (25%) had received breast reconstruction with a macro-textured SBI. The mean follow-up time was 11.5 (SD, 5.0) years. Compared with women who had undergone a simple mastectomy or autologous breast reconstruction, women with an implant-based reconstruction did not differ significantly in LRRFS or DMFS after accounting for various confounding factors [HR 1.27 (95% CI 0.93–1.72) and HR 0.94 (95% CI 0.74–1.20), respectively]. Sensitivity analysis in complete cases of patients and various subgroup analyses yielded similar results.

Conclusion:

Reassuringly, in this multi-centre cohort study no difference was found in long-term oncologic outcomes between women who had received breast reconstruction with a macro-textured SBI and women who had undergone a simple mastectomy or autologous breast reconstruction.
Nonsurgical pancreatic cancer: the role of radiotherapy in prolonging survival – a retrospective cohort study in the SEER database
Authors: Di Yupeng , Song Jiazhao , Sun Zhijia , Wang Yingjie , Meng Lingling
Published: June 2024

Background:

Limited research has compared external beam radiotherapy (RT) to non-RT in patients with nonsurgical locally advanced pancreatic cancer (LAPC). Therefore, this study investigates the impact of RT on overall survival (OS) in patients with nonsurgical LAPC in a real-world context.

Methods:

The authors conducted an analysis of patients with nonsurgical LAPC using data from the Surveillance, Epidemiology, and End Results (SEER) database. This analysis involved the utilization of Kaplan–Meier survival curves and multivariable Cox regression analyses.

Results:

A total of 5413 individuals with nonsurgical LAPC were included in this analysis. Among them, 2320 (42.9%) received RT, while 3093 (57.1%) underwent non-RT treatment. The median OS was 12.0 months for the RT group and 9.0 months for the non-RT group, with a statistically significant difference (P<0.001). Multivariate analysis revealed that RT had a statistically significant impact on OS (HR, 0.86; 95% CI: 0.81–0.91; P<0.001). Propensity score matching analysis confirmed a statistically significant association of RT with improved OS (HR, 0.84, 95% CI: 0.79–0.90; P<0.001). These results remained consistent after conducting sensitivity analyses, subgroup analyses, and propensity score matching.

Conclusion:

The study findings suggest that RT could be advantageous for patients with nonsurgical LAPC. Further investigations are warranted to explore the relationship between RT and OS.