bluuebunny/crossref_metadata_2025 huggingface dataset:
Regional Refugee Regimes
Authors: Muntarbhorn Vitit
Published: June 2021

This chapter focuses on the 10 States that form the Association of Southeast Asian Nations: Brunei Darussalam, Cambodia, Indonesia, Lao People’s Democratic Republic (Laos), Malaysia, Myanmar, Singapore, Thailand, the Philippines, and the Socialist Republic of Vietnam. There has been a tendency by Southeast Asian States to avoid using the term ‘refugees’ at the national level, even though they have to deal with the term in international fora. Most States in the region do not have specific laws on refugee protection; their legal structure tends to classify people who seek refuge as ‘illegal immigrants’ under national immigration law. Occasionally, policies allowing asylum seekers to reside temporarily in the country pending durable solutions help to exempt them from the strictures of such law. Ultimately, two salient features emerge in the chapter’s discussion. First, most Southeast Asian countries are still not parties to the international refugee instruments. Secondly, however, there is an extensive practice within the region of affording temporary refuge to most people seeking asylum, even if local integration or settlement remains the exception rather than the rule.
Protection at Sea and the Denial of Asylum
Authors: Moreno-Lax Violeta
Published: June 2021

This chapter grapples with the vexed issue of protection at sea, unpacking destination States’ practices of interdiction and their justification on purported humanitarian grounds. After introducing the rules governing interdiction powers and the obligation to render assistance to persons in distress, it problematizes the instrumentalization of maritime rescue, based on the supposed benevolent effect of ‘stopping the boats’ as a means to ‘save lives’. Two competing yet complementary dynamics are detected and critiqued. First, while destination States inflate their policing competence through reliance on rescue rhetoric and intervene beyond prerogatives explicitly recognized in the law of the sea, they tend to maintain minimalistic constructions of the associated concepts of ‘distress’ or ‘place of safety’ to reduce the scope of their legal responsibilities. Thus, secondly, they deflate their rescue duties and detach them from related international protection obligations, either by deflecting them to third countries or by negating them altogether. Drawing on examples from the US Caribbean interdiction programme, the Australian ‘Pacific Strategy’, and the mare clausum approach favoured in the Mediterranean, the chapter traces the shift from direct to indirect forms of interdiction, increasingly performed by third countries or private actors, culminating in practices of interdiction by omission, which not only tolerate but purposively embed the risk of death as part of the migration control toolbox of destination States. The final effect is one that paradoxically transforms rescue into an interdiction tool that denies access to asylum to ‘boat migrants’.
The Evolution of Safe Third Country Law and Practice
Authors: Freier Luisa Feline , Karageorgiou Eleni , Ogg Kate
Published: June 2021

This chapter details how States and regions use safe third country (STC) practices to deny protection to asylum seekers and refugees on the grounds that they have, or may have, protection in another country. The STC notion originated in Switzerland in 1979, spread throughout Europe in the 1980s, and was adopted by the European Union and countries such as Australia and Canada in the 1990s. Since then, developments in STC law and practice globally include new bilateral agreements, reforms to STC provisions in domestic and supranational legislation, and landmark decisions of superior courts. The chapter studies these changes in Europe, Australia, and North and South America, focusing in particular on the period from 2010 to 2020. It argues that there has been a dilution of STC protection standards in these four regions. The thresholds for effective protection have diminished and are lower than the minimum laid down in international treaties. Moreover, in the introduction and evolution of these STC practices, lawmakers and judges have disregarded the legal principle of international solidarity. While STC practices have long been critiqued as burden-shifting rather than -sharing, new STC law and jurisprudence exacerbates inequities between States with respect to responsibility for hosting refugees.
Asylum Procedure
Authors: Botero Álvaro , Vedsted-Hansen Jens
Published: June 2021

This chapter addresses the standards on asylum procedures that apply within various regulatory contexts. Its normative focus includes not only the standards for determination of refugee status under the Refugee Convention and Protocol, but also those concerning the examination of applications for complementary or subsidiary forms of protection. Nonetheless, the legal interaction between asylum procedures and Convention refugee status will be the starting point. As the Refugee Convention is scant on procedural standards, the chapter discusses the soft law standards that partly fill the normative gap. It also examines procedural standards concerning subsidiary or complementary protection that have been developed on the basis of human rights norms prohibiting refoulement beyond the scope of the Refugee Convention. Human rights treaties generally include the right to effective remedies at national level and are therefore relevant for the administrative or/and judicial procedures that apply when States parties to such treaties examine asylum applications. Although directly linked to the protection against refoulement under human rights treaties, the requirement of effective remedies has indirect effect also for procedures concerning the determination of Convention refugee status.
The International and Regional Refugee Definitions Compared
Authors: Wood Tamara
Published: June 2021

The universal refugee definition in Article 1A(2) of the Refugee Convention provides the cornerstone of the international refugee protection regime. However, it is far from the final word. At the regional level, states in Africa and Latin America have supplemented the universal refugee definition with their own, expanded criteria for refugee status. The regional refugee definitions – Article I(2) of the OAU Refugee Convention and paragraph III(3) of the Cartagena Declaration – extend refugee protection beyond those with a well-founded fear of being persecuted to people fleeing a range of other, more widespread situations and harms, including generalised violence, massive human rights violations and serious disturbances to public order. This chapter provides a closer look at the universal and regional refugee definitions, exploring the scope and application of their respective terms, and comparing and contrasting their criteria for refugee status.
UNRWA and Palestine Refugees
Authors: Akram Susan M.
Published: June 2021

This chapter studies the relationship between Palestinian refugees and the UN Relief and Works Agency for Palestine Refugees in the Near East (UNRWA). UNRWA’s role is to provide humanitarian ‘relief’ and to provide economic opportunities—‘works’—for refugees in the areas of major displacement: the West Bank, Gaza, Syria, Jordan, and Lebanon. Initially, the definition of Palestine refugee for UNRWA’s purposes was a sub-category of the United Nations Conciliation Commission on Palestine definition for purposes of relief provision, but it also included other categories of persons displaced from later conflicts. Following the passage of the Convention on the Reduction of Statelessness, the General Assembly authorized UNHCR to include stateless persons within its mandate. The Arab host States do not recognize Palestinians as falling under the international legal definitions of ‘refugees’ or ‘stateless persons’, however, and have refused to accept any UNHCR involvement vis-à-vis Palestinians in the UNRWA areas. The effect of these provisions is that Palestinians are excluded from UNHCR’s protection mandate in UNRWA areas, and since UNRWA has no durable solutions mandate, Palestinians have no access to durable solutions either as refugees or as stateless persons in UNRWA fields.
Women in Refugee Jurisprudence
Authors: Dauvergne Catherine
Published: June 2021

This chapter investigates the state of refugee law jurisprudence about women. It begins by surveying recent scholarship in this area, highlighting two points: first, that the production of scholarship about women as refugee claimants has slowed; and secondly, that the issues being researched and written about are generally the same as those on offer since the 1990s. Stagnated progress is not to say that decisions about women have not become central to refugee law jurisprudence. Women have indeed moved from the margins to the centre of refugee law. The chapter then analyses elements of the refugee definition in turn, considering how each applies to women. These elements include well-founded fear, being persecuted, reasons for being persecuted, nexus, and exclusion. This structure is a useful rubric for summarizing trends, and isideal for demonstrating that because every element of the refugee definition must be satisfied in order for a claim to be successful, there is a significant tendency for problems to slip from one definitional element to another as the jurisprudence advances. In other words, once it becomes settled law that women can fit in the category of membership in a particular social group, a series of contestations then emerge in another area such as nexus or State protection. This tendency for slippage has driven forward much jurisprudential growth.
Protecting Refugees with Disabilities
Authors: Crock Mary
Published: June 2021

This chapter evaluates the law and policy concerning persons with disabilities displaced as refugees, beginning with a broad survey of international legal and policy frameworks. It is accepted as axiomatic that events producing refugees are a major cause of death and disability in vulnerable human populations. Counterintuitively, however, statistical data collected by both national and United Nations agencies, including UNHCR, has traditionally identified only very small numbers of refugees as having disabilities. The supposition seems to have been that persons with disabilities are not able to travel and that these individuals are most likely to be left behind to perish or otherwise suffer the slings and arrows of fate and misfortune. Research in more recent times has revealed such assumptions about the mobility of refugees with disabilities to be patently false. The chapter then looks at the intersections between refugee law and human rights laws, examining how key elements of the definition of refugee should apply to persons with disabilities. It also addresses the procedural implications of requirements that ‘reasonable accommodations’ be made in status determinations and treatment of refugees with disabilities. Finally, the chapter comments on durable solutions for refugees with disabilities and the future impact of the UN Convention on the Rights of Persons with Disabilities on international refugee law and policy.
Conflict Refugees
Authors: Wouters Cornelis (Kees)
Published: June 2021

Armed conflicts have always been and still are major causes of refugee movements. They invariably cause human suffering, destroying State and societal structure and affecting the lives of civilian populations. While it is difficult to contest that people should not be returned to conflict, different thinking and practices are discernable in relation to the applicable legal framework for providing refugee protection to people displaced across borders by conflict. These discrepancies arise in part from the way in which conflicts are understood; the way in which the definition of a refugee in the Refugee Convention has been interpreted and applied; and in part from limitations in the definition itself. Recognizing ‘conflict refugees’ as refugees within the international legal framework requires an understanding of the dynamics of conflicts and a dynamic interpretation of the refugee definitions at global and regional levels.
National Constitutions and the Right to Asylum
Authors: Meili Stephen
Published: June 2021

This chapter studies the constitutional right to asylum, which until recently was a rather neglected backwater of international refugee law. This is due to a variety of factors, including the Refugee Convention’s domination of the refugee law regime, the weakness of the judiciary in many of the countries whose constitutions contain a right to asylum, and the non-humanitarian motivations for inclusion of that right in many constitutions. More recently, however, a combination of factors has breathed new life into the constitutional right to asylum in some countries. These factors include the limitations of the Refugee Convention, the rise in nationalism and anti-globalization, and the growing influence of refugee lawyers who are utilizing the constitutional right to asylum in domestic courts, particularly in Latin America. The chapter then traces the evolution of the constitutional right to asylum and considers how it has manifested itself in different countries and regions of the world over time. It also looks at recent strategic litigation in Latin America that has successfully utilized the constitutional right to asylum and may provide a blueprint for the effective use of such provisions in other countries.
The Right to Education
Authors: Dryden-Peterson Sarah , Mariën Hania
Published: June 2021

This chapter examines the right to education of refugees. International human rights instruments, including the International Covenant on Economic, Social and Cultural Rights (ICESCR) and the Refugee Convention, provide a framework for the right to education for refugees. As a social right, and as reflected in the ICESCR, the right to education is to be progressively realized and requires positive action and allocation of funding. Like all human rights, it is dependent on action by government, the availability of public resources, and enforcement mechanisms. The devolution of responsibility for the education of refugees to States through recent policy further entrenches the role of the State in respecting, protecting, and fulfilling refugees’ right to education. The chapter then explores the intersection of global and national frameworks for the right to education for refugees and its realization in the form of access to schools. Despite the widely embraced global articulation of the right to education for all refugee children, the realization of the right to education is highly variable, being largely dependent upon their State of asylum.
The Right to Family Reunification
Authors: Nicholson Frances
Published: June 2021

This chapter investigates the right to family reunification. Refugees fleeing persecution and armed conflict often become separated from their families or have to leave family members behind. Border guards, armed groups, smugglers, or simply force of circumstance may separate refugee families in the chaos of flight. For refugees and other beneficiaries of international protection, family reunification in the country of asylum is generally the only way to ensure respect for their right to family life and family unity. The chapter examines the extent of the rights to family life and family unity under human rights law both globally and regionally, with the right to family reunification itself also receiving widespread recognition. In practice, however, in order to realize these rights, refugee families must surmount numerous legal and practical obstacles that can render reunification a tortuous or even impossible undertaking. The chapter then takes a children’s rights perspective, focusing notably on the situation of adopted, fostered, and unaccompanied children.
Resettlement
Authors: Kneebone Susan , Macklin Audrey
Published: June 2021

This chapter describes and critiques refugee resettlement, ostensibly a ‘durable solution’ to displacement. Contemporary resettlement is practised mainly by high-income liberal democracies of the Global North, the same States that reluctantly receive asylum seekers coming mainly from the Global South. This tension between asylum and resettlement explains many of the features of contemporary resettlement practices, whereby asylum is governed through law and resettlement is usually framed as a matter of discretion. To reveal and explore this tension between asylum and resettlement, and examine resettlement’s shifting and problematic role in refugee protection, the chanoteppter surveys its historical development. It then looks at three key aspects of contemporary practice, namely its relationship with sovereignty, its decision-making processes, and how States treat resettled refugees.
Onward Migration
Authors: Long Katy
Published: June 2021

This chapter examines an important question about the relationship between displacement and migration: how does ‘onward migration’, or ‘onward movement’, fit into existing frameworks for refugee protection? The chapter first explores how approaches to refugees’ onward movement are often heavily politicized: many States tend to view refugee movements as a problem because they threaten to undermine national control of immigration. By contrast, advocates of refugee mobility point to the important role that migration can play in helping refugees to secure effective protection. Next, the chapter considers the rights of asylum seekers and refugees to engage in onward migration as part of a search for effective, durable protection. It also addresses the potential challenges—both legal and political—that may be faced by refugees trying to use migration as a ‘fourth durable solution’. The chapter concludes by suggesting that debates about refugee movement reflect much broader unresolved tensions in a world of unequal bordered States and restricted immigration.
The Responsibility of Armed Groups Concerning Displacement
Authors: Saul Ben
Published: June 2021

This chapter studies the responsibility of armed groups concerning displacement. Displacement frequently occurs in non-international armed conflicts (NIACs), whether as an incidental effect of actual or impending hostilities, a deliberate tactic of warfare, or as a preventive, protective measure to evacuate civilians at risk. In contrast to States parties to a NIAC, however, non-State armed groups (NSAGs) involved in conflict bear far fewer international obligations concerning protection from, during, and after displacement. The chapter charts how most of the relevant international law imposes obligations principally on States. Under the law of State responsibility, a State is only responsible for a NSAG’s conduct in a limited range of situations. Even where State responsibility formally exists, it will often be an ineffective means of accountability in practice, and NSAGs themselves may not separately bear direct responsibility for their conduct. A critical, second issue the chapter discusses, therefore, is the extent to which international law directly binds NSAGs and holds them responsible for their breaches. By disaggregating the applicable specialized branches of law, it shows that NSAGs are clearly bound by international humanitarian law as groups, while international criminal law imposes individual criminal liability on their members.
Border Crimes as Crimes against Humanity
Authors: Mann Itamar
Published: June 2021

This chapter examines border violence as ‘crimes against humanity’. It begins by explaining what it takes to interpret the phrase ‘crimes against humanity’, as it appears in article 7 of the Rome Statute, in light of rules of interpretation articulated in the Vienna Convention on the Law of Treaties. The chapter then looks at three theories of crimes against humanity. The first follows a basic tenet of Kantian ethics: the charge of crimes against humanity denounces the transformation of humans from ends in themselves to means of governing, or even of eliminating, the lives of others. A second option posits that the key aspect of claims concerning crimes against humanity directed at refugees is that they exert a kind of structural violence: certain kinds of border violence establish a system that extinguishes legal protections for humans, while making such results appear natural. Unlike other cases in which structural violence is rendered transparent to criminal law, contemporary border violence against asylum seekers and refugees can be effectively captured within a criminal law framework. A third interpretive theory suggests that border violence is deleterious towards people’s social lives, as it separates them into hermetic units and prevents interaction and mobility between groups. Proponents of this view may proceed to argue that sealing borders and eliminating the right to asylum is part of a larger plan for solidifying global racial and economic hierarchies: a ‘global apartheid’.
Regional Refugee Regimes
Authors: Fischel de Andrade José H.
Published: June 2021

This chapter shows how Latin America has played a rather innovative and creative role in the development of regional political asylum and refugee regimes. It reviews both the historical contribution of Latin America’s political asylee and refugee sub-regimes, and the region’s protection situation and key challenges. The chapter aims to answer the following questions: what is the concept of the prevailing asylum regime in Latin America and what are its sub-regimes? What is the current protection legal framework in the region? What is the institutional framework and its contribution to the protection of asylum seekers, political asylees, and refugees in Latin America? What are the major protection challenges currently faced by the region? In terms of its regional coverage, it considers that, of the 35 independent States of the Americas that are members of the Organization of American States, 20 of these may be regarded as Latin American States—that is, bearers of Spanish, Portuguese, or French cultural and linguistic heritage.
Numerical analysis of long-term variability of AGN jets through RMHD simulations
Authors: Acharya Sriyasriti , Borse Nikhil S , Vaidya Bhargav
Published: June 2021

Relativistic AGN (active galactic nucleus) jets exhibit multitime-scale variability and a broad-band non-thermal spectrum extending from radio to gamma-rays. These highly magnetized jets are prone to undergo several magnetohydrodynamic (MHD) instabilities during their propagation in space and could trigger jet radiation and particle acceleration. This work aims to study the implications of relativistic kink mode instability on the observed long-term variability in the context of the twisting in-homogeneous jet model. To achieve this, we investigate the physical configurations preferable for forming kink mode instability by performing high-resolution 3D relativistic MHD simulations of a portion of highly magnetized jets. In particular, we perform simulations of cylindrical plasma column with Lorentz factor ≥5 and study the effects of magnetization values and axial wavenumbers with decreasing pitch on the onset and growth of kink instability. We have confirmed the impact of axial wavenumber on the dynamics of the plasma column including the growth of the instability. In this work, we have further investigated the connection between the dynamics of the plasma column with its time-varying emission features. From our analysis, we find a correlated trend between the growth rate of kink mode instability and the flux variability obtained from the simulated light curve.
Patterns of primary beam non-redundancy in close-packed 21 cm array observations
Authors: Choudhuri Samir , Bull Philip , Garsden Hugh
Published: June 2021

Radio interferometer arrays such as HERA consist of many close-packed dishes arranged in a regular pattern, giving rise to a large number of ‘redundant’ baselines with the same length and orientation. Since identical baselines should see an identical sky signal, this provides a way of finding a relative gain/bandpass calibration without needing an explicit sky model. In reality, there are many reasons why baselines will not be exactly identical, giving rise to a host of effects that spoil the redundancy of the array and induce spurious structure in the calibration solutions if not accounted for. In this paper, we seek to build an understanding of how differences in the primary beam response between antennas affect redundantly calibrated interferometric visibilities and their resulting frequency (delay-space) power spectra. We use simulations to study several generic types of primary beam variation, including differences in the width of the main lobe, the angular and frequency structure of the sidelobes, and the beam ellipticity and orientation. For all of these types, we find that additional temporal structure is induced in the gain solutions, particularly when bright point sources pass through the beam. In comparison, only a low level of additional spectral structure is induced. The temporal structure modulates the cosmological 21 cm power spectrum, but only at the level of a few per cent in our simulations. We also investigate the possibility of signal loss due to decoherence effects when non-redundant visibilities are averaged together, finding that the decoherence is worst when bright point sources pass through the beam, and that its magnitude varies significantly between baseline groups and types of primary beam variation. Redundant calibration absorbs some of the decoherence effect however, reducing its impact compared to if the visibilities were perfectly calibrated.
The integrated three-point correlation function of cosmic shear
Authors: Halder Anik , Friedrich Oliver , Seitz Stella , Varga Tamas N
Published: June 2021

We present the integrated three-point shear correlation function iζ± – a higher order statistic of the cosmic shear field – which can be directly estimated in wide-area weak lensing surveys without measuring the full three-point shear correlation function, making this a practical and complementary tool to two-point statistics for weak lensing cosmology. We define it as the one-point aperture mass statistic Map measured at different locations on the shear field correlated with the corresponding local two-point shear correlation function ξ±. Building upon existing work on the integrated bispectrum of the weak lensing convergence field, we present a theoretical framework for computing the integrated three-point function in real space for any projected field within the flat-sky approximation and apply it to cosmic shear. Using analytical formulae for the non-linear matter power spectrum and bispectrum, we model iζ± and validate it on N-body simulations within the uncertainties expected from the sixth year cosmic shear data of the Dark Energy Survey. We also explore the Fisher information content of iζ± and perform a joint analysis with ξ± for two tomographic source redshift bins with realistic shape noise to analyse its power in constraining cosmological parameters. We find that the joint analysis of ξ± and iζ± has the potential to considerably improve parameter constraints from ξ± alone, and can be particularly useful in improving the figure of merit of the dynamical dark energy equation of state parameters from cosmic shear data.
Identification of a Novel Class of Photolyases as Possible Ancestors of Their Family
Authors: Xu Lei , Chen Simeng , Wen Bin , Shi Hao , Chi Changbiao , Liu Chenxi , Wang Kangyu , Tao Xianglin , Wang Ming , Lv Jun , Yan Liang , Ling Liefeng , Zhu Guoping
Published: June 2021

UV irradiation induces the formation of cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts in DNA. These two types of lesions can be directly photorepaired by CPD photolyases and 6-4 photolyases, respectively. Recently, a new class of 6-4 photolyases named iron–sulfur bacterial cryptochromes and photolyases (FeS-BCPs) were found, which were considered as the ancestors of all photolyases and their homologs—cryptochromes. However, a controversy exists regarding 6-4 photoproducts only constituting ∼10–30% of the total UV-induced lesions that primordial organisms would hardly survive without a CPD repair enzyme. By extensive phylogenetic analyses, we identified a novel class of proteins, all from eubacteria. They have relatively high similarity to class I/III CPD photolyases, especially in the putative substrate-binding and FAD-binding regions. However, these proteins are shorter, and they lack the “N-terminal α/β domain” of normal photolyases. Therefore, we named them short photolyase-like. Nevertheless, similar to FeS-BCPs, some of short photolyase-likes also contain four conserved cysteines, which may also coordinate an iron–sulfur cluster as FeS-BCPs. A member from Rhodococcus fascians was cloned and expressed. It was demonstrated that the protein contains a FAD cofactor and an iron–sulfur cluster, and has CPD repair activity. It was speculated that this novel class of photolyases may be the real ancestors of the cryptochrome/photolyase family.
Dissecting the Fitness Costs of Complex Mutations
Authors: Yubero Pablo , Poyatos Juan F
Published: June 2021

The fitness cost of complex pleiotropic mutations is generally difficult to assess. On the one hand, it is necessary to identify which molecular properties are directly altered by the mutation. On the other, this alteration modifies the activity of many genetic targets with uncertain consequences. Here, we examine the possibility of addressing these challenges by identifying unique predictors of these costs. To this aim, we consider mutations in the RNA polymerase (RNAP) in Escherichia coli as a model of complex mutations. Changes in RNAP modify the global program of transcriptional regulation, with many consequences. Among others is the difficulty to decouple the direct effect of the mutation from the response of the whole system to such mutation. A problem that we solve quantitatively with data of a set of constitutive genes, those on which the global program acts most directly. We provide a statistical framework that incorporates the direct effects and other molecular variables linked to this program as predictors, which leads to the identification that some genes are more suitable to determine costs than others. Therefore, we not only identified which molecular properties best anticipate fitness, but we also present the paradoxical result that, despite pleiotropy, specific genes serve as more solid predictors. These results have connotations for the understanding of the architecture of robustness in biological systems.
Translation mediated by the nuclear cap-binding complex is confined to the perinuclear region via a CTIF–DDX19B interaction
Authors: Park Yeonkyoung , Park Joori , Hwang Hyun Jung , Kim Leehyeon , Jeong Kwon , Song Hyun Kyu , Rufener Simone C , Mühlemann Oliver , Kim Yoon Ki
Published: June 2021

Newly synthesized mRNA is translated during its export through the nuclear pore complex, when its 5′-cap structure is still bound by the nuclear cap-binding complex (CBC), a heterodimer of cap-binding protein (CBP) 80 and CBP20. Despite its critical role in mRNA surveillance, the mechanism by which CBC-dependent translation (CT) is regulated remains unknown. Here, we demonstrate that the CT initiation factor (CTIF) is tethered in a translationally incompetent manner to the perinuclear region by the DEAD-box helicase 19B (DDX19B). DDX19B hands over CTIF to CBP80, which is associated with the 5′-cap of a newly exported mRNA. The resulting CBP80–CTIF complex then initiates CT in the perinuclear region. We also show that impeding the interaction between CTIF and DDX19B leads to uncontrolled CT throughout the cytosol, consequently dysregulating nonsense-mediated mRNA decay. Altogether, our data provide molecular evidence supporting the importance of tight control of local translation in the perinuclear region.
Deep learning-based automatic tumor burden assessment of pediatric high-grade gliomas, medulloblastomas, and other leptomeningeal seeding tumors
Authors: Peng Jian , Kim Daniel D , Patel Jay B , Zeng Xiaowei , Huang Jiaer , Chang Ken , Xun Xinping , Zhang Chen , Sollee John , Wu Jing , Dalal Deepa J , Feng Xue , Zhou Hao , Zhu Chengzhang , Zou Beiji , Jin Ke , Wen Patrick Y , Boxerman Jerrold L , Warren Katherine E , Poussaint Tina Y , States Lisa J , Kalpathy-Cramer Jayashree , Yang Li , Huang Raymond Y , Bai Harrison X
Published: June 2021

Background

Longitudinal measurement of tumor burden with magnetic resonance imaging (MRI) is an essential component of response assessment in pediatric brain tumors. We developed a fully automated pipeline for the segmentation of tumors in pediatric high-grade gliomas, medulloblastomas, and leptomeningeal seeding tumors. We further developed an algorithm for automatic 2D and volumetric size measurement of tumors.

Methods

The preoperative and postoperative cohorts were randomly split into training and testing sets in a 4:1 ratio. A 3D U-Net neural network was trained to automatically segment the tumor on T1 contrast-enhanced and T2/FLAIR images. The product of the maximum bidimensional diameters according to the RAPNO (Response Assessment in Pediatric Neuro-Oncology) criteria (AutoRAPNO) was determined. Performance was compared to that of 2 expert human raters who performed assessments independently. Volumetric measurements of predicted and expert segmentations were computationally derived and compared.

Results

A total of 794 preoperative MRIs from 794 patients and 1003 postoperative MRIs from 122 patients were included. There was excellent agreement of volumes between preoperative and postoperative predicted and manual segmentations, with intraclass correlation coefficients (ICCs) of 0.912 and 0.960 for the 2 preoperative and 0.947 and 0.896 for the 2 postoperative models. There was high agreement between AutoRAPNO scores on predicted segmentations and manually calculated scores based on manual segmentations (Rater 2 ICC = 0.909; Rater 3 ICC = 0.851). Lastly, the performance of AutoRAPNO was superior in repeatability to that of human raters for MRIs with multiple lesions.

Conclusions

Our automated deep learning pipeline demonstrates potential utility for response assessment in pediatric brain tumors. The tool should be further validated in prospective studies.
Regulation of carotenoid and chlorophyll pools in hesperidia, anatomically unique fruits found only in Citrus
Authors: Zhu Kaijie , Zheng Xiongjie , Ye Junli , Huang Yue , Chen Hongyan , Mei Xuehan , Xie Zongzhou , Cao Lixin , Zeng Yunliu , Larkin Robert M. , Xu Qiang , Perez-Roman Estela , Talón Manuel , Zumajo-Cardona Cecilia , Wurtzel Eleanore T. , Deng Xiuxin
Published: June 2021

Domesticated citrus varieties are woody perennials and interspecific hybrid crops of global economic and nutritional importance. The citrus fruit “hesperidium” is a unique morphological innovation not found in any other plant lineage. Efforts to improve the nutritional quality of the fruit are predicated on understanding the underlying regulatory mechanisms responsible for fruit development, including temporal control of chlorophyll degradation and carotenoid biosynthesis. Here, we investigated the molecular basis of the navel orange (Citrus sinensis) brown flavedo mutation, which conditions flavedo that is brown instead of orange. To overcome the limitations of using traditional genetic approaches in citrus and other woody perennials, we developed a strategy to elucidate the underlying genetic lesion. We used a multi-omics approach to collect data from several genetic sources and plant chimeras to successfully decipher this mutation. The multi-omics strategy applied here will be valuable in driving future gene discovery efforts in citrus as well as in other woody perennial plants. The comparison of transcriptomic and genomic data from multiple genotypes and plant sectors revealed an underlying lesion in the gene encoding STAY-GREEN (SGR) protein, which simultaneously regulates carotenoid biosynthesis and chlorophyll degradation. However, unlike SGR of other plant species, we found that the carotenoid and chlorophyll regulatory activities could be uncoupled in the case of certain SGR alleles in citrus and thus we propose a model for the molecular mechanism underlying the brown flavedo phenotype. The economic and nutritional value of citrus makes these findings of wide interest. The strategy implemented, and the results obtained, constitute an advance for agro-industry by driving opportunities for citrus crop improvement.
Migraine Monitoring in the Time of COVID-19: Triggers and Protectors During a Pandemic
Authors: Schiano di Cola Francesca , Caratozzolo Salvatore , Di Cesare Marco , Liberini Paolo , Rao Renata , Padovani Alessandro
Published: June 2021

Objective

Aim of the present observational study was to assess the impact of coronavirus disease 2019 (COVID-19) quarantine on migraine and evaluate potential influencing factors. Previous studies reported mixed results regarding clinical outcome during quarantine in patients with migraine. In particular, data from areas strongly affected by COVID-19 pandemic are missing.

Methods

One hundred and seventy patients, previously assessed at the Headache Centre—ASST Spedali Civili Brescia, underwent a telephonic interview regarding migraine features and clinical, occupational, and lifestyle variables.

Results

Compared to baseline, during quarantine, we found a significant overall reduction in migraine days (14.7 ± 0.6 vs 12.3 ± 0.7, P < .001), with 47.1% patients reporting a clinical improvement. Outdoor living spaces (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.7–3.07, P = .009), a positive attitude throughout quarantine (OR 4.12, 95% CI 2.3–7.1, P = 0.03), working full-time (OR 1.03, 95% CI 0.5–1.9, P < .001) and a baseline diagnosis of chronic migraine (OR 1.4, 95% CI 1.1–2.02, P = 0.002) were associated with an increased chance of migraine improvement. Being single (OR 1.5, 95% CI 1.1–2.01, P = .05) and physical inactivity (OR 1.3, 95% CI 1.1–1.6, P = .02) were associated with an increased risk of worsening.

Conclusions

Quarantine had an overall positive impact on migraine. Based on our results, we hypothesize the reduction of daily hassles and challenges might be the main reason for such improvement.
Psoriasis and coronary heart disease—not as severe as predicted
Authors: Hadi Y , Or T , Moady G , Atar S
Published: June 2021

Background

Psoriasis is a systemic disorder involved in several disease processes, including cancer, metabolic syndrome and cardiovascular disease (CVD). Previous studies showed that psoriasis is most likely an independent risk factor for CVD, yet the extent of its impact on CVD and the extent of coronary artery disease (CAD) remains unclear. We investigated the correlation of psoriasis to the severity of CAD in age and gender-matched patients with CAD with and without psoriasis.

Methods

This is a retrospective, case–control study of 59 patients with psoriasis who underwent coronary angiography were matched using a computer software to 59 patients without psoriasis according to age, gender, smoking status, hyperlipidemia, hypertension and diabetes. CAD severity was defined according to number of affected vessels (single vs. multiple) and location of lesions (proximal vs. distal).

Results

CAD severity was significantly higher in the control group compared to the psoriasis group (P = 0.038). Among patients with psoriasis, 20.3% were disease free or with low severity (42.4%), while only 37.3% had severe CAD. Among patients without psoriasis, the majority had severe CAD (57.6%), followed by low severity (30.5%) or disease free (11.9%). We did not find an association of prior treatment with anti-inflammatory medications and the severity of CAD.

Conclusions

Our results show that although psoriasis may be a risk factor for CAD, psoriatic patients have a less severe CAD compared to the general population. The use of anti-inflammatory medications does not explain this finding.
Integrating imaging and biomarker assessment to better define psoriatic arthritis and predict response to biologic therapy
Authors: Elliott Ashley , McGonagle Dennis , Rooney Madeleine
Published: June 2021

The treatment options for PsA have substantially expanded over the last decade. Approximately 40% of patients will not respond to first-line anti-TNF-α therapies. There is limited data to help clinicians select the most appropriate biologic therapy for PsA patients, including guidance for decisions on biologic therapy switching. In this review we will examine the current understanding of predictors of response to treatment. Imaging technology has evolved to allow us to better study psoriatic disease and define disease activity, including synovitis and enthesitis. Enthesitis is implicated in the pathogenesis, diagnosis and prognosis of PsA. It appears to be a common thread among all of the various PsA clinical presentations. Enthesitis mainly manifests as tenderness, which is difficult to distinguish from FM, chronic pain and mechanically associated enthesopathy, and it might be relevant for understanding the apparent 40% failure of existing therapy. Excess adipose tissue makes if more difficult to detect joint swelling clinically, as many PsA patients have very high BMIs. Integrating imaging and clinical assessment with biomarker analysis could help to deliver stratified medicine in PsA and allow better treatment decision making. This could include which patients require ongoing biologic therapy, which class of biologic therapy that should be, and who alternatively requires management of non-inflammatory disease.
Governing varieties of mission-oriented innovation policies: A new typology
Authors: Wittmann Florian , Hufnagl Miriam , Lindner Ralf , Roth Florian , Edler Jakob
Published: June 2021

Many governments in Europe and beyond have subscribed to mission-oriented innovation policies (MOIPs), aiming to steer innovation systems to directly address grand societal challenges. The emerging diversity of MOIPs, however, creates difficulties to define this approach and assess its effectiveness and efficiency. In this paper, we propose a new typology for MOIPs. It consists of four ideal types of missions and extends the established dichotomy of transformer and accelerator missions. The framework emphasizes the role of the state in MOIPs, drawing attention to the implementation process and governance requirements as key features of mission implementation. A first application across the diverse missions of the German Hightech Strategy 2025 demonstrates the analytical value of the framework and allows identifying type-specific challenges. In sum, the new typology and its operationalization improve the understanding of MOIPs and enhance the possibilities for systematic comparisons and impact assessments.
Case report of acute liver injury caused by the eszopiclone in a patient with chronic liver disease
Authors: Wu Tong , Yu Ge , Li Zhaoxia , Xin Guijie
Published: June 2021

Rationale:

Eszopiclone, sold under the brand name Lunesta, is a new type of non-benzodiazepine hypnotic. Eszopiclone is a zopiclone dextrorotation, which is classified as a cyclopyrrolone. It functions by binding gamma-aminobutyric acid (GABA) receptors. Compared with benzodiazepines hypnotics, eszopiclone has higher selectivity for certain subunits of the GABA(A) receptor. So far, there are no reports about the elevation of serum enzymes or severe liver injury caused by eszopiclone. Here, we present a case report of acute liver injury following eszopiclone treatment in a patient with chronic hepatitis B virus (HBV).

Patient concerns:

The patient was a 53-year-old female with a 36-year history of positive HBV markers. Due to poor sleep, the patient took trazodone hydrochloride orally for 1 year. After hospital admission for positive hepatitis B pathogenic markers, abdominal distension, fatigue, and aggravation, she was treated with eszopiclone under the guidance of the mental health department.

Diagnoses:

Her transaminase levels increased abnormally after eszopiclone treatment and rapidly decreased after drug withdrawal. This was determined to be an acute liver injury event. liver-protecting treatment was maintained. Considering the patient's anxiety and depression, the patient's family members refused a liver biopsy.

Outcomes:

Transaminase levels decreased rapidly within one week, and the patient continued to take trazodone hydrochloride after discharge. No adverse events occurred in the follow-up period.

Lessons:

Sleep disorders are more common in patients with chronic diseases, especially patients with chronic liver disease. Recently, it has become common for patients with hepatitis B and C to use antidepressants along with antiviral treatment. Patients with chronic hepatitis B or C may have a threefold risk of liver dysfunction after receiving antituberculosis treatment.
[1,2]
A proinflammatory environment induced by actively replicating the hepatitis virus may alter the detoxication process and increase drug toxicity.
[3]
At this time, the safety of other drugs should be reevaluated. Although hepatitis and liver injury are listed as rare adverse reactions of eszopiclone, this case is the first to report the eszopiclone-involved acute liver injury.
HIV viral exposure and mortality in a multicenter ambulatory HIV adult cohort, United States, 1995–2016
Authors: Palella Frank J. , Armon Carl , Cole Stephen R. , Hart Rachel , Tedaldi Ellen , Novak Richard , Battalora Linda , Purinton Stacey , Li Jun , Buchacz Kate
Published: June 2021

The aim of this study was to identify viral exposure (VE) measures and their relationship to mortality risk among persons with HIV.

Prospective multicenter observational study to compare VE formulae.

Eligible participants initiated first combination antiretroviral therapy (cART) between March 1, 1995 and June 30, 2015. We included 1645 participants followed for ≥6 months after starting first cART, with cART prescribed ≥75% of time, who underwent ≥2 plasma viral load (VL) and ≥1 CD4+ T-lymphocyte cell (CD4) measurement during observation. We evaluated all-cause mortality from 6 months after cART initiation until June 30, 2016. VE was quantified using 2 time-updated variables: viremia copy-years and percent of person-years (%PY) spent >200 or 50 copies/mL. Cox models were fit to estimate associations between VE and mortality.

Participants contributed 10,453 person years [py], with median 14 VLs per patient. Median %PY >200 or >50 were 10% (interquartile range: 1%–47%) and 26% (interquartile range: 6%–72%), respectively. There were 115 deaths, for an overall mortality rate of 1.19 per 100 person years. In univariate models, each measure of VE was significantly associated with mortality risk, as were older age, public insurance, injection drug use HIV risk history, and lower pre-cART CD4. Based on model fit, most recent viral load and %PY >200 copies/mL provided the best combination of VE factors to predict mortality, although all VE combinations evaluated performed well.

The combination of most recent VL and %PY >200 copies/mL best predicted mortality, although all evaluated VE measures performed well.