bluuebunny/crossref_metadata_2025 huggingface dataset:
The liberal script on refugee admission and the significance of national cultural repertoires
Authors: Drewski Daniel , Gerhards Jürgen
Published: August 2024

Admitting refugees fleeing war and persecution underpins the liberal script as the last resort for protecting the right to individual self-determination in a world of sovereign nation-states. This obligation is well justified in liberal political theory and inscribed in contemporary world culture, whose core principles became enshrined in international law after World War II. Against this background, Chapter 10 summarizes our empirical findings and shows that governments and opposition parties only rarely refer to liberal principles and international law when debating whether to admit refugees. Moreover, the least liberal countries in our analysis—Uganda and Turkey—seem to be the most “open” in terms of admitting refugees. This indicates that rather than the degree of adherence to (or rejection of) the liberal script explaining countries’ different responses to admitting refugees, it is the national context, country-specific cultural repertoires, and the way political actors frame the “we” and the “others.”
Theories of Recognition
Authors: Kilibarda Pavle
Published: August 2024

Since the early nineteenth century, legal scholarship has been trying to explain the role of recognition in international law. Two major schools of thought have emerged in this regard: the constitutive doctrine, which insists on the crucial role of recognition in creating statehood, and the declaratory view, which posits that statehood exists regardless of recognition. Neither school is uniform in its approach and constitutivist and declaratist views have been expressed with considerable variations. This chapter summarises and reflects on the views of the major proponents of both positions and examines the value of ‘mixed’ theories that cannot easily be attributed to either school.
When Recognition is Constitutive
Authors: Kilibarda Pavle
Published: August 2024

If there exists no rule of international law applicable to a given situation that would make an entity’s statehood opposable to other States, then opposability could only be based on recognition. International law does not require States to engage in recognition, but it will authorise recognition if the principles of effectivity and legality have been respected. Effectivity means that the recipient of recognition must meet the requirements of material statehood with a reasonable degree of stability so that recognition would not be premature, whereas legality necessitates that the creation of the new State did not entail violations of international law, especially jus cogens. If recognition is given while respecting both principles, then it may be regarded as lawful and will render its object opposable to the recognising State.
Statehood Beyond Recognition
Authors: Kilibarda Pavle
Published: August 2024

The fact that a State does not enjoy recognition by others, nor can its legal statehood be established by means other than recognition, does not mean that it exists in a legal vacuum. In claiming statehood, the newcomer is assuming the legal duties incumbent upon all States and essentially engaging in ‘self-recognition’. It will therefore be bound by the rules of general international law, especially jus cogens, in all its activities, including towards non-recognising States if their own statehood is opposable to it. This chapter considers the obligations of States even if they do not enjoy recognition from any other State, especially under international humanitarian law and international human rights law.
Voiceless Subalterns
Authors: Grint Keith
Published: August 2024

This short chapter considers those voices missing from the book, usually the subaltern voices of the weak. What we know about resistance derives, in the main, from the extant records of those subaltern groups that either succeeded or left accounts of their resistance. But by and large history is written by the victors and most definitely is not written by the huge mass of people who either lived or died at the hands of their oppressors, and sometimes those resisting them. It starts with a personal acknowledgement to those silenced by my own historical narrative and procedures to illustrate the wider point through a brief review of similar acts of silencing.
The Medieval Era
Authors: Shrock Dennis
Published: August 2024

Salve regina Venecie, mundi splendor / Michael, qui Stena domus / Italie, mundicie
Labour Law in Supply Chains
Authors: Hyde Alan
Published: August 2024

Supply chains are organizations, created by lead firms, that permit goods sold under the lead firm’s name to be manufactured by notionally independent, though functionally controlled, factories, typically in the developing world, typically with labour conditions well below those in facilities owned by the lead firm. Lead firms are rarely held legally responsible for labour conditions in the suppliers they control, even conditions that are dangerous or human rights violations. Legal devices for extending liability up the supply chain are evaluated. These include: treating the supply chain as a legal entity; doctrines like vicarious liability, nondelegable duties, joint employment, and enterprise liability; human rights due diligence statutes; statutes imposing labour responsibility on various entities that contract with others; and voluntary assumption of responsibility in contracts such as the International Accord for Health and Safety in the Textile and Garment Industry.
Working Time
Authors: Davies A.C.L.
Published: August 2024

This chapter considers three modern problems of working time. First, there are new versions of the familiar problem of long-hours working: the use of technology to drive an ‘always-on’ culture in which workers are expected to be available to employers at all times, and the blurring of boundaries between work and home generated by the shift to hybrid working. Second, there are ongoing challenges of maintaining a balance between work and family life, addressed in some legal systems by giving workers a right to request flexible working. Third, precarious workers face many issues: not having enough hours to make a living, being expected to spend time waiting for work without getting paid, and being called in to work at short notice. The chapter examines whether traditional legal strategies to limit working time are capable of meeting these new challenges, or whether new regulatory approaches are required.
Race and the Workplace
Authors: Green Llezlie L.
Published: August 2024

Race in the workplace is complex and nuanced. Racial subordination and exploitation manifest not only in the hiring and terms of employment regulated by traditional civil rights statutes, but also in the racialized application of workplace laws that do not explicitly contemplate race. The racial exploitation of low-wage workers is grounded in the racist historical and structural underpinnings of workplace regulations that continue to subordinate Black and brown workers. In the US, this enduring racial subordination is particularly acute in low-wage worker workplaces. The COVID-19 pandemic elevated ‘essential workers’, many of whom were Black and brown workers toiling in low-wage jobs. This shift in the narrative around low-wage work should have created an opportunity to improve workers’ legal protections and ameliorate their racial subordination, yet few long-term changes occurred. This chapter proffers racial capitalism as a theoretical lens to explain why countering racism in the low-wage workplace remains elusive.
Age Discrimination and Mandatory Retirement
Authors: Blackham Alysia
Published: August 2024

This chapter examines emerging issues in age discrimination law in the workplace and mandatory retirement. While age discrimination laws have been passed in many countries, there are still fundamental tensions regarding how such laws are framed and implemented. Our ambivalence towards age and age equality limits the drafting and implementation of age discrimination laws. There is a need for age discrimination law scholarship to continue to engage with questions of intersectionality and intergenerational solidarity in the world of work. To better address ageism at work, and meaningfully achieve age equality, requires moving beyond a reliance on individual enforcement of discrimination law, and demands us to reprioritize age and age equality in the workplace.
Trafficking, ‘Modern Slavery’, and Forced Labour
Authors: Kotiswaran Prabha
Published: August 2024

This chapter considers the overlap between the law of work and the criminal law in addressing the most exploitative forms of labour exploitation in the twenty-first century, also referred to as trafficking, modern slavery, and forced labour. The chapter tracks the development of anti-trafficking law and discourse since 2000 and whether and how its shifting focus over the past twenty years can reduce extreme forms of labour exploitation by addressing structural inequalities in global labour markets and supply chains. In the absence of systemic approaches to reducing workers’ vulnerability to trafficking, the chapter argues that the anti-‘modern slavery’ rhetoric does more to legitimize humanitarian efforts of global elites than support workers’ rights.
Freedom of Speech at and Away from Work
Authors: Fisk Catherine L.
Published: August 2024

Laws addressing work-related speech are both more ubiquitous than ever, and more hotly contested. Organizational hierarchy normalizes the idea that those at the top have the right to control any worker expression that might plausibly be attributed to or harm the organization, yet as whistleblower laws make clear, there are strong reasons to allow at least some speech that may be perceived as harmful. The challenge of regulation stems from the fact that there are libertarian and egalitarian arguments both for and against legal restraint on workplace speech of both workers and managers. The difficulty is compounded by the absence of trust, among people of widely different political orientations, in the institutions, including courts, corporations, and educational institutions, that are empowered to make judgements about which speech to allow and to prohibit.
Trade Agreements and Labour Law
Authors: Compa Lance
Published: August 2024

This chapter examines how labour provisions in trade agreements can drive reforms in countries’ domestic labour law systems. It first analyses reforms that occur during the negotiation stage and later under enforcement mechanisms. Case studies include US trade agreements beginning with NAFTA in 1994; post-NAFTA trade pacts that followed; trans-Pacific agreements; and EU agreements with Canada, Vietnam, Korea, and others. Special attention is paid to the North American USMCA trade agreement, which brought far-reaching labour law reforms in Mexico and whose unique ‘rapid response’ enforcement mechanism fosters independent union organizing. In conclusion, this chapter cautions that the question of causality is nuanced, and that trade negotiations can promote labour reforms only with pressure from other actors as well. These include national and global trade unions, political parties, ILO, and civil society advocates. Most important, trade-labour negotiations and enforcement must accompany efforts by workers to exercise rights that labour chapters in trade agreements seek to protect.
Artificial Intelligence, Big Data, Algorithmic Management, and Labour Law
Authors: Kim Pauline T.
Published: August 2024

This chapter explores the use of artificial intelligence (AI) and algorithmic management systems in the workplace. It examines how these automated systems affect fundamental worker interests and how existing law applies, focusing primarily on non-discrimination and privacy. Although current law provides some protections, it fails to fully apprehend the risks posed by algorithmic tools. Current legal doctrine prohibits discrimination by workplace algorithms but fits awkwardly with the nature of automated decision systems, leaving gaps and uncertainties. Traditional worker privacy protections are ill-equipped to address the volume and granularity of worker data collected today, and the ability of computational techniques to extract new insights and infer sensitive information from that data. The expansion of algorithmic management affects other fundamental worker interests by increasing employer power vis-à-vis labour. This chapter concludes by briefly considering the role that data protection laws might play in addressing the risks of algorithmic management.
The Need for Seed
Authors: Saul Hayley
Published: August 2024

The Hindu Kush Himalayas are home to an extraordinary diversity of plants and animals, including an array of traditional crop varieties and landraces. Whilst most scholarship has, to date, sought to preserve this biodiversity by documenting the breadth of species’ and genetic variation, this chapter investigates what we know about the wealth of underlying cultural practices that are generative of agrodiversity. Such practices include festivals in which cultural observances incorporate traditions of care and selection for certain plant qualities, religious sanctuaries that encode the manner of interaction with plants within the sacred boundary, and local cuisines in which knowledge-holders give rise to genetic diversity through selections of different tastes, textures, and aesthetics. Foregrounding biocultural heritage in this way refocuses away from questioning ‘what is diverse’, to ask more fluid questions about how that agrodiversity is brought about by human-plant-animal collaborations through time.
Racial Bias in Police Officer Deadly Force Decisions
Authors: Cesario Joseph , Carrillo Alejandro
Published: August 2024

This chapter provides a critical overview of experimental studies of racial bias in police shootings, with a focus on methodological and statistical quality. The most informative studies include police officers making decisions in shooting simulators; these are few in number but do not provide strong evidence of anti-Black bias. The least informative studies include undergraduates making decisions with computer tasks; these are plentiful and provide some evidence of anti-Black bias in response times. One consistent finding using shooting simulators is the importance of suspect behavior and situational information, features which are absent in computer tasks. Although process analyses have been attempted, progress has been inhibited by a narrow conceptualization of the decision to shoot. Strengths and weaknesses of all experimental approaches are discussed, with the overarching theme that researchers have missed opportunities to generate a strong and useful body of knowledge on this important topic.
Attitudes and Social Cognition
Authors: Granados Samayoa Javier A. , Fazio Russell H.
Published: August 2024

Social cognition and the study of attitudes have long enjoyed a synergistic relationship. This chapter provides an overview of different research programs that exemplify such synergies. The main theme that emerges from this tour through the literature is that adopting a social cognitive perspective helped attitudes researchers better understand central issues and resolve crises in the field. In turn, early theoretical and methodological advances in the attitudes field formed part of the zeitgeist that led to the rise of the social cognition movement. Moreover, these advances sometimes aligned the attitudes literature with those literatures that are traditionally considered to fall under the umbrella of social cognition (e.g. impression formation, stereotypes, the self). Last, the adoption of theoretical and methodological developments by attitudes researchers sometimes acted as catalysts for progress in traditional social cognition literatures.
The Development of Social Group Cognition in Infancy and Childhood
Authors: Charlesworth Tessa E. S. , Banaji Mahzarin R.
Published: August 2024

Although they are far from biological or social maturity, infants and children show surprising early-emerging capacities in social group cognition. This chapter reviews research on when and how infants and children categorize, evaluate, stereotype, and behave differently toward social groups defined by gender, race, age, and language. Research across these groups reveals three thematic conclusions. First, an early-emerging preference for the familiar (e.g., looking at faces most prevalent in infants’ environments), beyond similarity or in-group status. Second, generally similar trajectories across group targets (e.g., looking preferences at three to six months, evaluative associations formed around nine to twelve months) suggesting domain-general cognitive developments may scaffold infant social group cognition. Third, an additional internalization of culturally dominant beliefs and norms of fairness in early to middle childhood (e.g. the emergence of socially desirable, fair responding in middle childhood). Understanding social group cognition is advanced by understanding its origins in early in life.
Methods in Social Cognition
Authors: Klauer Karl Christoph
Published: August 2024

This chapter reviews methods and paradigms that have been influential in shaping social cognitive theories. The review is organized roughly along a processing stream beginning with paradigms probing into attentional-perceptual processes, followed by central processing and response-related processes. The reviewed methods and paradigms include the emotional Stroop task and attentional cuing paradigms, eye tracking and mouse tracking, indirect measures based on sequential priming paradigms, the Implicit Association Test and some of its variants, evaluative conditioning procedures, measures of concept activation and inference, and linguistic methods. For each method, procedural aspects, possible confounds, and, where appropriate, controllability, mechanisms, and psychometric criteria are considered. The chapter concludes with a selective review of mathematical models that have provided deeper analyses of some of these methods.
Social Cognition and Consumer Psychology
Authors: Ackerman Joshua M. , Merrell Wilson N. , Williams Lawrence E.
Published: August 2024

Research on consumer psychology has traditionally been organized from an information processing perspective—the principles and mechanisms associated with what consumers attend to and value and the ways this content shapes consumer choice. This chapter reviews key insights from the past decade of consumer literature through this lens. It then introduces a more holistic framework emphasizing multiple explanatory levels of analysis. A levels-of-analysis framework can encompass the information processing approach, expand the understanding of consumer psychology, and address recent calls for theoretical advancements intended to counter concerns about empirical reproducibility. To support this framework, this chapter discusses recent social cognitive and consumer behavior research relevant to different levels of analysis and ends with a set of actionable proposals intended to improve the study of consumers.
Social Cognition and Health
Authors: Hunger Jeffrey M. , Howell Jennifer L.
Published: August 2024

The social cognition approach has undoubtedly shaped how researchers understand the role of the social world in physical health. In the first edition of this handbook, Shelley Taylor contributed an overview of social cognition and health that centered on cognitive processes and neural and physiological mechanisms underlying health and well-being. The current chapter builds on this foundational work by highlighting three prominent areas of research where a social cognitive lens on health has flourished: the role of automaticity and automatic processes, interpersonal processes (e.g. social support, ostracism), and intergroup processes (e.g. stigma, discrimination). Both the interpersonal and the intergroup domains have proven particularly important for health, and both have addressed similar social cognitive processes, which highlights the need for future research that more comprehensively bridges these two literatures. Understanding the social cognitive factors that contribute to health is a critical step in developing effective interventions to promote it.
Social Cognition Today and Tomorrow
Authors: Hugenberg Kurt , Carlston Donal E. , Johnson Kerri L.
Published: August 2024

The present volume was prepared following a time of remarkable upheaval in social psychology and during a time of remarkable upheaval in society. This chapter documents both. First, it argues that social cognition (and social psychology more broadly) has been through a substantial process of methodological maturation in recent years, changing both techniques and values when it comes to doing social cognition. The field has adopted a large variety of methods, meaning that there is no longer a shared template for science, and trustworthy inferences are valued like never before. Second, the chapter argues that social cognition is ripe for a pivot toward real-world concerns, in the vein of Fiske and Taylor’s classic definition of social cognition. The chapter argues that this will make for a more impactful, influential, and just discipline, which befits what some see as a leading discipline in social psychology.
A Dynamic Perspective on Visual Perception in Social Cognition and Action
Authors: Balcetis Emily , Cole Shana
Published: August 2024

Although people believe they see the world as it really is, perceptual experience contradicts this conception. This chapter discusses the conditions of the visual system and psychological process by which visual representations fail to correspond to reality. It argues that perception is not simply a product of the qualities of the actual object present but also a result of characteristics of the perceiver. Because the visual input the sensory system receives is imprecise and because attentional resources are relatively limited, an ambiguity arises that is resolved by social context, past experience, and directed and selective visual attention. This chapter proposes the dynamic integration of multiple sources of information that collectively work to shape visual experience and comments on the distinction between visual experience and cognitive judgment. Finally, it discusses the social psychological implications of such a dynamic visual system for regulating action in a social world, including for legal decisions, intergroup relations, discrimination, health, relationships, and culture.
Social Categorization
Authors: Freeman Jonathan B. , Chwe John Andrew
Published: August 2024

Social categorization is central to the field of social cognition and has been an integral topic of study since the field’s conception. Social categorization has long been viewed as the starting point of various downstream cognitive, affective, motivational, and behavioral processes. This chapter discusses a modern understanding of social categorization that bridges social cognition and visual perception research to examine the visual and perceptual determinants of social categorization and how they can inform an understanding of these downstream social cognitive processes. As the social world changes, a revised perspective of social categorization is necessary to drive future research. The chapter focuses on three emerging topics in social categorization research, namely, (a) how perceivers handle intersectionality and the complexity of multiply categorizable targets; (b) how perceivers categorize along a seemingly infinite set of perceptually ambiguous category dimensions, such as sexual orientation or religious groups; and (c) how perceivers navigate the blurring of traditionally studied categories, as in perceiving multiracial and transgender individuals.
Perception and Action
Authors: Witt Jessica K. , van der Wel Robrecht
Published: August 2024

Cognition would be maladaptive, energy consuming, and wasteful if not for the processes of perception and action to sense the surrounding world and act within it. Yet, the importance of perception and action for understanding cognition is much debated. This chapter outlines a variety of ways that perception, action, and cognition are not independent processes merely feeding information from one to the other, but intertwined and functionally connected. The consequences of this functional connection are seen in a variety of phenomena. We start with the dependency of the visual system on action and then describe Gibson’s ecological approach to psychology, including the role of action in perceiving and the perception of affordances. We then cover how perception of others’ actions and its impact on one’s own cognition and movements. We finish with the action-specific approach to perception. Perception and action influence each other, and these influences have consequences for social cognition.
Extracellular Vesicle–Mediated Secretion of Chlorophyll Biosynthetic Intermediates in the Cyanobacterium Leptolyngbya boryana
Authors: Usui Kentaro , Yamamoto Haruki , Mori Hitoshi , Fujita Yuichi
Published: August 2024

Extracellular vesicles (EVs) are derived from outer membranes (OMs) in Gram-negative bacteria and have diverse physiological functions. EV-mediated secretion of monovinyl protochlorophyllide (MV-Pchlide), the chlorophyll a (Chl) biosynthetic intermediate, was previously reported in a mutant lacking dark-operative Pchlide reductase in the cyanobacterium Leptolyngbya boryana. This study showed a detailed characterization of EVs from wild-type (WT) strain of L. boryana grown under photoautotrophic and dark heterotrophic conditions, focusing on the accumulation of Chl intermediates. WT L. boryana cells produce two types of EVs, low-density EVs (L-EVs) and high-density EVs (H-EVs), both under light and dark conditions. L-EVs and H-EVs showed distinct morphological features and protein compositions. L-EVs from cells grown under both light and dark conditions commonly contained carotenoids, ketomyxol glycoside and zeaxanthin as major pigments. Based on the protein compositions of EVs and other cellular membrane fractions, L-EVs and H-EVs are probably derived from low-density OMs and high-density OMs interacting with cell walls, respectively. Fluorescence detection of pigments was applied to EVs, and the two Chl intermediates, protoporphyrin IX and protoporphyrin IX monomethyl ester, were commonly detected in both L-EVs from light- and dark-grown cells, whereas L-EVs from dark-grown cells contained additional MV-Pchlide, MV-protopheophorbide and pheophorbide. The pigment ratios of L-EVs to the total culture medium of the Chl intermediates were much higher than those of carotenoids, suggesting an active transport of the Chl intermediates from the thylakoid membrane to L-EVs. Cyanobacterial EVs may play a novel role in alleviating the accumulation of Chl intermediates in cells.
Abstract 3: Adapting to Evolving Demands: Diversifying Cord Blood Processing to Mitigate Supply Chain and Vendor Risks
Authors: Merayo-Rodriguez Juan , Hernandez Luis , Dominguez-Gutierrez Paul , Kinsell Kim
Published: August 2024

Introduction

The shifting landscape of cord blood utilization, with decreasing demand for clinical applications and a rapidly expanding need for cellular therapies, is driving changes in processing practices. However, the industry's continued reliance on single-vendor systems (SVS) for processing poses significant risks. Stringent FDA validation requirements, coupled with increasing vulnerability to supply chain disruptions and the potential for discontinued vendor support, can result in costly and irreplaceable losses of cord blood units (CBU). These losses not only have financial implications but can also delay or prevent life-saving treatments for patients in need. To optimize this valuable resource, a strategic balance between clinical and therapeutic needs is essential. This study investigates the hidden costs associated with SVS reliance and explores the potential benefits of maintaining secondary processing capabilities as a risk mitigation strategy, ensuring the availability of CBU for both current and future therapeutic applications.

Objectives

This study analyzes the experiences of a FACT accredited public cord blood bank in the USA to:

-Highlight the challenges associated with onboarding and validating a new SVS for CBU processing.

-Quantify the CBU losses resulting from validation, supply chain disruptions, and instrument downtime.

-Demonstrate the long-term cost-effectiveness of maintaining secondary processing capabilities to mitigate such losses.

Methods

A retrospective review of cord blood processing techniques and product disposition from February 2020 to February 2024 was conducted. Data analysis was performed using SAS JMP Pro 17.0.

Results

While SVS initially offer lower startup costs, the long-term risks outweigh these savings. CBU losses due to supply chain issues and the need to validate alternative kits can be financially significant. Implementing a secondary, manual processing and by leveraging existing resources increases the total cost by 2%.

Discussion

The traditional model of relying solely on SVS for CBU processing is unsustainable in the face of modern challenges. This study provides compelling evidence for the cost-effectiveness and risk mitigation potential of maintaining a diversified processing approach. By investing in secondary processing capabilities, cord blood banks can ensure the continued availability of this vital resource for patient transplantation and other cellular therapies, even in the face of supply chain disruptions and vendor changes.
Abstract 6: Value of a Multi-Regional Cord Blood Bank Program: Multiple Collection Centers to Select High-Quality Units for Transplantation
Authors: Farssac Elisenda , Azqueta Carmen , Castillo Nerea , Valdivia Elena , Martorell Lluis , Rubio Nuria , Garcia-Buendia Ana , Samarkanova Dinara , Montoiro Raquel , Martínez María José , Fernández Esperanza , Calvo Javier , Roldán José , Cemborain Arantxa , Arroyo José Luis , Pello Oscar , Pérez Cristina , Querol Sergi , Fernández-Sojo Jesús
Published: August 2024

Introduction

The Barcelona Cord Blood Bank (BCBB) was established 28 years ago and developed the Concordia CB donation program, with over 60 maternity units in six regions of Spain and Andorra. These units are connected to a single processing and storage facility. Initially, collections were based on a total nucleated cell (TNC) count > 900x10^6. This criterion evolved, and since 2015, a strict minimum TNC of 1500x10^6 has been applied.

Objectives

to analyze the characteristics of the stored Cord Blood Units (CBUs) over the years to classify the cryopreserved units according to different variables, allowing for an understanding of the bank's quality and future orientation towards new needs and applications

Methods

a retrospective analysis to determine the percentage of high-quality units available for transplantation. For this purpose, CBUs were classified into four categories based on initial cellular quality: category 1 (>1500x10^6 TNC), category 2 (1200-1500x10^6 TNC), category 3 (900-1200x10^6 TNC), and category 4 (<900x10^6 TNC). Additionally, the geographical origin of the donors was analyzed

Results

Among 124,988 donations collected, 24,661 were cryopreserved (20%), of which 2,171 were canceled due to freezing problems or not meeting quality criteria and nearly 2,100 were shipped for transplantation. Currently, there are 19,094 CBUs (15% of all collected) active in the bone marrow donor registry. According cell number, CBU inventory is divided into categories, and 6,922 (36%) belong to category 1. In contrast, majority of CBU shipped comes from this category (77%), Figure 1). Interestingly, all participating regions maintained equivalent shipping rates. In terms of geographical origins, of the 19,094 cryopreserved units, 54,00% belonged to the European Community (EC), 3,95% were Latin America, 2,08% Sub-Saharan 0,07% were Asian and 39,90% did not have the data to classify the samples (Fig 2)

Discussion

This analysis enhances the understanding of the characteristics and quality of units requested for transplantation and the geographical distribution of donors. The current operational inventory is smaller than expected, highlighting the need to continue collecting high-quality units from diverse ethnic backgrounds to meet patient needs. A multi-regional donation model and collaboration with health professionals and social awareness are crucial for sustaining cord blood banks
Abstract 14: Contribution of US Public Cord Blood Banking to Improved Engraftment and Survival after Allogeneic Cord Blood Transplantation (CBT)
Authors: Hof Wouter Van't , Troy Jesse , Kurtzberg Joanne
Published: August 2024

Introduction

US public cord blood banks (CBBs) produce either licensed or unlicensed HPC, Cord Blood as per FDA guidance. Accreditation and licensure status of cord blood banks using standardized banking procedures is a key parameter for selection of units for clinical transplant (I. Politikos et al., Biol Blood Marrow Transplant 26 (2020) 2190-2196).

Objectives

To evaluate the premise that US public cord blood banks have contributed to improvement of clinical engraftment and survival outcomes after allogeneic CBT, through delivery of high-quality cord blood units that fulfill critical CD34 and total cell dose requirements.

Methods

Retrospective analysis using deidentified CIBMTR outcome data-files, with investigators blinded to the identities of the donors, cord blood banks and recipients. Analysis of licensure, time in storage, cell dose, degree of HLA match, recipient age, and recipient diagnosis in three study groups, namely pre-licensure 1988-2011, (“IND pre-2012”), unlicensed and licensed units infused starting 2012 and after (“IND” and “licensed”, respectively). Statistical analyses are per Ballen et al., Biol Blood Marrow Transplant. 2020 April ; 26(4): 745–757).

Results

Initial analysis shows improved engraftment and overall survival for single cord CBT performed with IND and licensed units versus pre-2012 IND units. Higher TNC and CD34 doses per kg and fewer reports of contamination by TCs are seen for licensed units, which were used more frequently in single cord transplants in adults, mostly for treatment of AML with higher use of reduced intensity and non-ablative regimens. Licensed products had a higher representation of minority B/AA donors. After licensed single cord CBT, time to engraftment trended to be faster, with a 1 and 2-year overall survival benefit seen in adult recipients.

Discussion

8 US cord blood banks have received license approval, contributed >50,000 licensed units to the US registry, and shipped >1,800 licensed units for transplant (NMDP registry®). FDA licensure has improved overall quality of banked CBUs translating into improvement in clinical outcomes of CBT.
Abstract 15: Invasive Aspergillus Niger Infection Cured after V Hematopoietic Stem Cell Transplantation in a Pediatric Patient with Severe Congenital Neutropenia
Authors: Marinelli Giulia , Caddeo Giulia , Chinello Matteo , Bonetti Elisa , Pezzella Vincenza , Zaccaron Ada , Esposto Maria , Balter Rita , Cesaro Simone
Published: August 2024

Introduction

Severe congenital neutropenia (SCN) is a non-malignant haematological disorder characterized by a quantitative deficit of neutrophils (N<500/mmc), recurrent severe infections and need for prolonged granulocyte growth factor (G- CSF) therapy.

Objectives

This clinical case describes a life-saving unrelated cord blood transplant in a patient with previous multiple graft failures while ha had a severe active maxillary aspergillosis.

Methods

R.A. is a child suffering from SCN type I (mutation of the ELANE gene) who required the administration of granulocyte growth factor (G-CSF) from birth, at progressively increasing doses. The patient was a haploidentical allogeneic HSCT given the lack of HLA matched/minor mismatched donors from the international registries. The patients received sequentially 4 haplo HSCTs (2 from father with αβ+/CD19+ depletion of the graft, 2 from mother without in vitro graft manipulation and using post-transplant cyclophosphamide) without obtaining myeloid engraftment. and remaining aplastic. DSAs (patient-specific antibodies against the donor's HLA antigens) were found after the third transplant but the desensitization procedures did not prevent the rejection of the 4th transplant. Being aplastic for 4 months, he developed a progressively worsening Aspergillus niger infection of the oral cavity, maxillary bone and right maxillary sinus, with intermediate sensitivity to amphotericin B (Image 1). After identification of a DSA-negative unrelated cord blood unit (HLA match 6/8) a 5th HSCT was performed.

Results

The 5th transplant successfully engrafted for neutrophils and platelets and the aspergillosis infection gradually solved. Currently, three years after the transplant, the patient is in good conditions with a complete donor chimerism and without significant immunological consequences post-HSCT

Discussion

in this patient, the use of an unrelated cord blood allowed to bypass the lack of donors in the international registries and the graft failure/rejection of the haploidentical donors due to DSAs. Moreover, Aspergillosis refractory to antifungal medical therapy is not a contraindication to HSCT because myeloid recovery and immune reconstitution after HSCT are able to achieve a control of the infection together with antifungal therapy.
Abstract 18: A Case of Successful Poor Graft Function Treatment with Wharton Jelly Mesenchymal Stem Cells
Authors: Romiszewski Michał , Nasadiuk Khrystyna , Malinowska Iwona , Olearczyk Aleksandra , Snarski Emilian , Ołdak Tomasz , Łaguna Paweł
Published: August 2024

Introduction

Poor graft function (PGF) is a life-threatening complication that occurs after hematopoietic stem cell transplantation (HSCT). This is persistent neutropenia/thrombocytopenia, with complete donor chimerism, lack of severe GVHD or relapse, during the first 12 months after HSCT.

Objectives

To present a case study of PGF treatment with Wharton jelly (WJ) mesenchymal stem cells (MSC).

Methods

A 16-year-old boy was performed allogeneic bone marrow HSCT from a fully matched family donor due to secondary myelodysplastic syndrome, diagnosed 4 years after treatment of pineablastoma. Engraftment was documented on day +28 (95%) and 99% on day +42. The patient was discharged home in good general condition on day +37 post-transplant. From day +54, a deterioration of blood count parameters was observed. Partial secondary graft failure was diagnosed and no hematological response was achieved with 4 planned doses of Rituximab. Secondary causes of bone marrow failure and cytopenias were excluded. A bone marrow biopsy showed absence of the primary disease but significantly reduced bone marrow cellularity. Finally PGF was diagnosed and the patient was re-transplanted HSC from the same donor, without conditioning with prior administration of WJ MSCs (obtained from FamiCord Group) in the number of 120 x 106. No post-transplantation immunosuppression was used.

Results

As a result of the procedure, the blood count parameters increased and stabilized at a level that no longer required additional transfusions support. No adverse effects and no early and late post-tranplant complications were observed. Currently, the patient remains in good general condition. Due to hemochromatosis previously caused by numerous red blood cells transfusions, he requires chelation therapy. Administration of MSCs is a safe method and might by an effective therapy for patients with PGF.

Discussion

Our clinical case is consistent with several literary reports showing efficacy of third parties MSCs in the treatment of PGF. The mechanism of therapeutic effect of MSCs in PGF is poorly known, it may be hypothesized that MSCs modulate bone marrow microenvironment and exert pracrine regenerative effect.
Abstract 27: Physiologic Oxygen Expansion Enhances Lymphocyte and Neutrophil Recovery Following Transplantation
Authors: Gutch Sarah , Ropa Jim , Beasley Lindsay , Whitacre Grace , Hof Wouter Van't , Capitano Maegan
Published: August 2024

Introduction

Expeditious recovery of lymphocytes after hematopoietic cell transplantation is a major determinant of patient outcome. There are few efficient clinical therapies to enhance lymphocyte recovery, indicating a clear unmet need. Ex vivo expansion of cord blood (CB) units is an approved therapy to increase numbers of hematopoietic stem and progenitor cells, but impact on lymphocyte recovery remains uncertain. Moreover, culture in physioxic (physiological oxygen) conditions results in increased lymphoid-biased RNA levels.

Objectives

We hypothesize that ex vivo expansion in physioxic conditions will increase lymphoid-biased cells and increase lymphocyte counts post-transplantation (PT). The objective of this study is to increase lymphocyte numbers following transplantation without sacrificing reconstitution of potent hematopoietic cells.

Methods

Three independent transplants were conducted. 1) Murine lineage- bone marrow (BM) was expanded for 7 days then transplanted into lethally irradiated mice with/without additional common lymphoid progenitors (CLPs). 2) Murine lineage- BM was expanded in 1%, 3%, 5%, 14%, and 21% O2 for 7 days and transplanted into lethally irradiated mice. 3) Human CD34+ CB cells were expanded for 7 days in 1%, 3%, 5%, 14%, and 21% O2 and transplanted into NSG mice. Unexpanded BM or CB cells were used as controls.

Results

Additional CLPs did not contribute to lymphocyte recovery. Mice transplanted with expanded BM had increased lymphocyte counts compared to transplantations with unexpanded BM at weeks 2 and 5 PT via complete blood count (CBC) and increased B-cell reconstitution in the spleen, BM, and peripheral blood (PB) at weeks 2, 5, and 8 PT. LSK (Lin- SCA1+ cKIT+) and neutrophil frequencies were increased at 3% O2 in the BM and 5% O2 in the PB, respectively. Compared to 21% O2, CB cells expanded at 1%, 3%, 5%, 14% O2 had increased neutrophil and lymphocyte frequencies in the PB at weeks 2 and 10, respectively, and demonstrated greater recovery than unexpanded at week 2.

Discussion

Expansion increases lymphocyte counts via CBC and immunophenotyping. Physioxic expansion increases numbers of potent hematopoietic cell subpopulations and frequencies of specific lymphocyte compartments in multiple organs. Thus, expansion under physioxia is a viable strategy to enhance recovery of lymphocytes PT.
Abstract 28: Cord Blood Derived Macrophages Promote the Differentiation of Oligodendrocyte Precursor Cells
Authors: Xu Li , O'Neil Shane , Min Hyunjung , Ozamiz April , Kurtzberg Joanne , Filiano Anthony
Published: August 2024

Introduction

Krabbe Disease (KD) is a rare neurodegenerative disorder caused by a mutation in the gene encoding galactocerebrosidase (GALC). GALC deficiency leads to accumulation of the toxic metabolite psychosine in myelin-forming oligodendrocytes causing severe demyelination. Presymptomatic hematopoietic stem cell transplants can slow the progression of disease, but ultimately there is no cure. We previously demonstrated that DUOC-01, a first-generation macrophage cell-therapy manufactured from banked human umbilical cord blood cells, which when injected into the corpus callosum, enhanced remyelination in immunocompromised mice treated with the demyelinating agent, cuprizone. Further, DUOC-01 could promote the maturation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes via remyelinating factors (Remy-Macs).

Objectives

In this study, we set out to test if DUOC-01 and their secreted Remy-Macs could rescue oligodendrocyte deficits and improve survival in GALC deficient mice.

Methods

First, we generated primary OPC cultures from GALC deficient mice and measured OPC maturation by immunohistochemistry and qRT-PCR of myelin basic protein (MBP). To test if DUOC-01 impacted OPCs via secreted factors, we incorporated the use of transwell assays. To test if DUOC-01 or Remy-Macs could promote remyelination in vivo, we injected DUOC-01 or used Alzet osmotic pumps to deliver therapies into the cerebrospinal fluid (CSF).

Results

We first tested the effects of DUOC-01 and Remy-Macs on primary OPC cultures isolated from neonatal control of GALC deficient mice. We observed comparable oligosphere growth in cultures derived from GALC deficient mice and their wild-type litter mates, indicating a normal function for twitcher OPC proliferation. However, OPC differentiation was compromised in GALC deficient mice, demonstrated by decreased MBP expression. DUOC-01 and Remy-Macs increased the production of MBP at both mRNA and protein levels. Additionally, infusion of Remy-Macs into the CSF of GALC deficient mice improved survival.

Discussion

Our data demonstrated that DUOC-01 or Remy-Macs promoted the differentiation of OPCs isolated from GALC deficient mice. Further, infusing Remy-Macs into the CSF of GALC deficient mice extended life span. Our data suggest DUOC-01 or Remy-Macs have the potential to be further developed into a novel cell-therapy to treat Krabbe and other demyelinating diseases.
Abstract 33: Transcriptomic Identification of Functionally Potent Umbilical Cord Blood Units
Authors: Ropa James , Gutch Sarah , Beasley Lindsay , Hof Wouter Van't , Sun Jessica , Capitano Maegan , Kaplan Mark
Published: August 2024

Introduction

Umbilical cord blood (UCB) is an important donor source for standard of care cellular therapies as well as innovative new treatments. Universal potency criteria for cord blood unit (CBU) selection for different cellular therapy applications are still desired and efficient methods to elucidate these criteria remain elusive.

Objectives

Our goal is to find molecular markers that identify potent CBUs for use in cellular therapies. Here, we utilized transcriptomics to reveal genes associated with hematopoietic stem and progenitor cell (HSC/HPC) potency in hematopoietic cell transplantation.

Methods

We performed three separate transcriptomic analyses of human UCB used in mouse models of transplantation. This included bulk RNA-sequencing of HSCs/HPCs from CBUs with known engraftment capacities (n=9 CBUs), bulk RNA-sequencing of homed/early engrafted CD34+ cells (n=3 CBUs), and single cell RNA-sequencing of CD34+ cells expanded in varying oxygen tensions, which affects their transplantation potency (n=4 CBUs).

Results

HSCs/HPCs enriched for dehydrogenase and cell cycle associated genes yield better repopulating cell frequency. Early homed CD34+ cells have enriched expression of immune activation and cell cycle genes compared to input transplanted cells. Distinct clusters of UCB cells marked by genes such as PRSS2 and AVP are enriched in oxygenation conditions that drive increased potency. Dehydrogenase and stress response genes are enriched in populations predicted to be more functional regardless of HSC/HPC subpopulation. Integration of all three studies reveals genes that may define highly potent CBUs, including DDIT4, a stress response gene. Indeed, DDIT4 independently predicts engraftment outcomes in mouse models of transplantation. Future work will examine a qPCR based gene panel potency assay to predict outcomes in patient transplantations.

Discussion

We have identified genes associated with HSC/HPC potency using transcriptomic approaches. These findings have immediate translational implications for CBU selection for transplantation, but also provides a blueprint for finding CBUs best suited for use in developing off-the-shelf immune effector therapies or those that are best for treating non-hematologic central nervous system disorders such as cerebral palsy, among other applications. Importantly, this study highlights the importance for omics technology as a valuable tool to define potency criteria for UCB as a donor source for cellular therapies.