bluuebunny/crossref_metadata_2025 huggingface dataset:
Singapore
Authors: Lee Jack Tsen-Ta
Published: October 2024

Barring some radical change in policy or party, it seems likely that the executive and legislative branches of government will continue to strongly influence the development of Singaporean constitutional law, including the very structure of government, given the ease with which Parliament can amend the constitution and enact legislation. Where judicial review by the courts is concerned, the predominant trend appears to be one of deference to the government’s policy choices, while retaining a measure of judicial latitude for action in exceptional circumstances. Whether the courts will be prepared to scrutinize the acts of the political branches more strictly remains to be seen.
Vowel Harmony in Optimality Theory
Authors: Finley Sara
Published: October 2024

This chapter provides an overview of how research on vowel harmony (VH) in Optimality Theory (OT) has contributed to discussions related to the typology, representation, and learnability of VH systems. OT has made a tremendous impact on Generative Phonology, and VH is no exception. In OT, the grammar of every language is encoded in a (possibly universal) set of constraints, making OT particularly well suited for the study of both typology and learnability. The chapter includes a basic overview of OT and Harmonic Grammar, including summaries of several major approaches to VH in OT and Harmonic Grammar (e.g., Align, Agree, and Agreement by Correspondence constraints). In addition, theoretical issues particularly pertinent to VH in OT are discussed. Such questions include differentiating between the explanatory value of various harmony-inducing constraints, integrating constraints on the typology of VH into learning algorithms, and issues of gradience in VH.
Vowel Harmony In Emergent Phonology
Authors: Archangeli Diana , Pulleyblank Douglas
Published: October 2024

This chapter explores how a stripped-down theory of phonology can account for complex patterns of phonological distribution and alternation found in vowel harmony. The hypothesis is that the complex patterns found in phonological systems arise from general human cognition, learning language from the bottom up—Emergent Grammar. Without innate predispositions, lexical items are represented as sets of surface morphs, replacing the unique underlying representations posited in much of generative grammar. Harmony is characterized by well-formedness conditions which prohibit certain feature sequences, a formalization of asymmetries in directly observed distributions. Through examination of harmony in four languages, we demonstrate Emergent analyses of root-restricted harmony (Kɔɖa), root and word harmony (Dàgáárè), opacity and directionality (Fula), non-canonical harmony (Nata), and lexical disharmony (Kinande). The Emergent analyses relate transparently to surface forms, yet express generalizations about phonological and morpho-phonological patterns with analyses that very directly characterize the properties of the harmony systems themselves.
Vowel Harmony in Bantu Niger-Congo Languages
Authors: Boyd Virginia (Ginger)
Published: October 2024

Vowel harmony is a common, although not universal, feature of Bantu languages. It affects languages throughout the Bantu region, from the northwestern Zone A languages to the southeastern Zone S languages and virtually everywhere in between. However, how vowel harmony functions varies rather widely from zone to zone and language to language. The most common types of Bantu vowel harmony are height harmony and advanced tongue root (ATR) harmony. Retracted tongue root (RTR) harmony is also recognized as fairly common in Bantu C languages among others. While other types of vowel harmonies are found in Bantu languages, this chapter presents these more common types of vowel harmony in Bantu with an emphasis on some of the particularities found.
Vowel Harmony in Mongolic Languages
Authors: Svantesson Jan-Olof
Published: October 2024

The main section of this chapter describes vowel harmony (VH) in Khalkha Mongolian, which has both tongue-root harmony and rounding harmony. The vowels are divided into two classes, retracted tongue root (RTR), a, ɔ, ʊ, and advanced tongue root (ATR), e, o, u, while i is neutral. There is rich inflectional and derivational morphology based on suffixes, whose vowels alternate with the harmony class of the word. Rounding harmony applies only to the non-high vowels a, ɔ, e, o, high rounded ʊ and u being opaque and i transparent. There is interaction between tongue-root harmony and velar versus uvular consonants. The contrast between palatalized and plain consonants occurs only in the context of RTR vowels. The VH status of the other Mongolic languages is described briefly. Some have lost VH altogether, and others have retained it in different forms. Oirat (including Kalmyk) is the only Mongolic language with palatal harmony.
Vowel Harmony in Papuan Languages
Authors: Klamer Marian
Published: October 2024

This chapter reflects the current descriptive and typological asymmetry of vowel harmony (VH) in Papuan languages by presenting two cases of ‘unbounded’ VH: Amele and Umbu-Ungu, and four cases where harmony is more local: Mian, Ngkolmpu, Komnzo, and Kaera. Ngkolmpu and Umbu-Ungu show harmony of a particular phonetic feature, while the other languages show harmony with the entire vowel. In most cases, harmony is leftward, but it is rightward in Umbu-Ungu, while Amele has harmony in both directions. The vowel triggering the harmony is part of a lexical root in Ngkolmpu, Mian, Umbu-Ungu, and Kaera. In Komnzo and Amele, it is part of functional items, but in Amele harmony in the nominal domain is also triggered by noun stem vowels. Umbu-Ungu is the only language where harmony occurs beyond the morphological word to include phrasal enclitics. VH is related to unspecified vowels and epenthesis in Amele.
Laxing Vowel Harmony
Authors: Henriksen Nicholas , Kendro Kelly
Published: October 2024

This chapter sets out to review multiple cases of the phenomenon known as laxing harmony—that is, an assimilation process in which two nearby vowels are produced having an identical tense/lax quality. First, the chapter distinguishes between laxing harmony and advanced tongue root (ATR) harmony, limiting the scope of laxing harmony to language varieties for which the tense/lax distinction is otherwise not phonemic. It then moves on to discuss the current understanding of why and how laxing harmony occurs, summarizing research on three key examples: Eastern Andalusian Spanish, Laurentian French, and Cantabrian Spanish. Finally, it offers ideas for future empirical work regarding production and perception.
Kant on Method
Authors: Schafer Karl
Published: October 2024

This chapter offers an opinionated overview of the central elements of Kant’s philosophical methodology during the Critical period. It begins with a brief characterization of how Kant conceives of the aims of human inquiry—focusing on the idea that inquiry ideally aims at not just cognition (Erkenntnis), but also the more demanding cognitive achievements that Kant labels insight (Einsehen) and comprehension (Begreifen). It then explores the implications of this picture for philosophy, emphasizing Kant’s distinction between critical and doctrinal phases of philosophical inquiry, with the first of these playing both a negative and a positive role with respect to the second. It argues that this positive role is possible, according to Kant, only insofar as philosophy follows a ‘capacities-first’ methodology—that is, one that treats basic cognitive capacities (such as reason) and their self-conscious activities as fundamental (in both a cognitive sense and in an explanatory sense) for the sort of philosophy human beings are capable of. It is this methodology that allows Kant to introduce the first principles that philosophy in its doctrinal phase requires in a manner that is neither arbitrary nor (at least obviously) incompatible with Kant’s own Critical restrictions on cognition. The chapter concludes by discussing some of the implications of this methodological picture, including the methodological significance of self-consciousness and regressive or ‘transcendental’ arguments, Kant’s distinction between analytic and synthetic methods in philosophy, and Kant’s conception of reason as autonomous.
Kant on the Special Sciences
Authors: Williams Jessica J.
Published: October 2024

While Kant was arguably as deeply engaged with the emerging special sciences of his time as he was with Newtonian physics, there is a deep tension in his treatment of these disciplines. On the one hand, Kant endorses a reductionist approach in natural science. On the other hand, Kant is committed to a variety of anti-reductionist positions in empirical psychology, chemistry, and the emerging biological sciences. This chapter examines the precise form that Kant’s anti-reductionism takes in each of these domains and the corresponding set of questions about the extent to which each of these constitutes a genuine science for Kant.
Kant on the Moral Law
Authors: Herman Barbara
Published: October 2024

The task of this chapter is to answer three questions about the moral law. (1) How is the moral law a principle of practical cognition? (2) In what way does the moral law make a rational demand on the human will? (3) How is the moral law related to our duties? The answers begin with an account of the moral law as the principle of a rational will’s causality. Practical cognition then involves a representing of the will’s object, either as an object of subjective interest, or as what the moral law, represented as a causal principle, can make real. The moral law thus determines the will of the rational being to act for what is objectively good. E.g. the moral goodness of a promise kept is the result of a representation of the moral law as a practical cognition of the promisor that it is good to do. While the moral law is the source of the freedom or power of the human being to act for the objective good, it does not prevent our acting for the merely apparent good. Last, it is argued that our duties are the working principles of the moral law, necessary to secure the existence conditions of free, rational action where our natural tendencies in choice and action would undermine them. This puts duties of right, along with duties of virtue, at the centre of Kant’s moral project.
Kant on Humanity
Authors: Grenberg Jeanine , Vinton Matthew
Published: October 2024

Kant’s second formulation of the Categorical Imperative, the so-called Formula of Humanity, appeals to the humanity in our persons as an unconditional end-in-itself that may never be used merely as a means. Various interpretive challenges have led to scholarly disagreement concerning what Kant meant by the term ‘humanity’ in this formulation. Four views emerge from the literature: (1) humanity is an abstract idea, (2) humanity is the capacity for end-setting generally, (3) humanity is the capacity for morality, and (4) humanity is a good will. After surveying each of these views, this chapter argues for a teleological reading of ‘humanity’ in one’s person. A focus on Kant’s first Critique discussion of ideas and ideals reveals that the ‘idea of humanity’ and ‘ideal of humanity’ both determine which capacities define an actually existing human being and provide the regulative ideal or telos articulating the vocation of that human being’s existence. This ‘idea’ and ‘ideal’ of humanity reveal that the capacity for morality, broadly conceived as autonomous self-legislation of categorical moral demands extending both to the choice of maxims and the setting of obligatory ends, a capacity which undergirds and makes possible one’s non-moral capacities for end-setting and prudential choice, is definitional of humanity. This capacity simultaneously identifies human beings as the kind of being they are, and allows those beings to become worthy of that humanity through moral development.
Kant on Community
Authors: Lau Chong-Fuk , Lowe Chun-Yip
Published: October 2024

This chapter examines the concept of community through its different facets and far-reaching implications in Kant’s philosophy. It first addresses the concept of community as one of the twelves categories in the Critique of Pure Reason, showing its synthetizing role for the categories of substance and causality. It argues that Kant’s concept of the phenomenal world assumes a communalistic unity in reference to which individual objects acquire their identities. The main part of the chapter then focuses on Kant’s practical philosophy, in which the notion of community plays an even more significant role, even though Kant’s concept of autonomy and the theory of the categorical imperative may seem to be founded on an individualistic conception of morality. Not only does the formula of humanity presuppose the intersubjective endorsability of moral maxims in a community of rational agents, but more importantly the realization of the highest good in the unity of morality and happiness requires the idea of a kingdom of ends in which every autonomous agent can be considered a law-giving member. In the earthly world, the kingdom of ends has to be realized by the establishment of a political and an ethical community, to which the last two sections of the chapter are devoted. While a political community is concerned with the external freedom of rational agents to protect everyone as free and equal, an ethical community aims at cultivating the virtue of rational agents towards holiness.
Kant on Practical Reason
Authors: Kitcher Patricia
Published: October 2024

Kant’s declaration in the Critique of Practical Reason that the freedom established by the moral law ‘forms the keystone of the whole edifice of a system of reason’ (5:3) invites readers to view his theory of practical reason through the lens of his moral theory. But Marcus Willaschek (1992) argued that Kant scholars erred in narrowing their study of Kant’s theory of practical reason to just the faculties required for the possibility of a Categorical Imperative. He maintained that Kant drew on his predecessors’ concepts and theories to develop a more general account of practical reasoning, one that is not limited to moral reasoning. To explain practical reasoning, Kant appealed to the faculty psychology of his day and to his own views about the systematicity of empirical sciences. He began his study of the possibility of morality by regressing from the ordinary person’s judgments about morally good and bad actions—and about the necessary psychological conditions for moral action. The two desiderata for Kant’s theories of moral and practical reasoning—ordinary moral consciousness and a systematic faculty psychology—are not fated to conflict. This chapter shows, however, that there are real tensions between the two, and serious problems with his use of a psychological concept that he borrows from the tradition, ‘Willkür’. Its central claim is that it is not Kant’s goal of vindicating free will and morality that limits his theory to moral creatures, but his understanding of how practical reasoning can be cognized.
Kant on Peace and History
Authors: Maliks Reidar
Published: October 2024

The first part of this chapter is devoted to the concept of peace, the second part is devoted to the concept of history and historical progress towards peace. Peace is to Kant a condition in which the rights of individuals and states are protected by law and where disputes can be settled by a court; it is the highest good of the Doctrine of Right. Heads of states are under an obligation to exit the international state of nature and enter a league of nations governed by the right of nations (Völkerrecht). Despotic states are prone to war while republics are peaceful, a claim contemporary international relations theorists have used to generate the democratic peace theory. Kant is concerned not only to justify the moral duty to pursue peace, but also to motivate humans to strive for it by demonstrating that it is not unachievable. To this end he develops a teleological history that holds humanity inevitably to progress to the better, both through the perfectibility of moral agency and through the perfectibility of legal institutions. The chapter discusses various objections to this idea of providential history and suggests that Kant’s theory has an emancipatory purpose. It was to give confidence to agents that their moral strivings can be effective in subjecting power to law and realizing perpetual peace.
Kant on Beauty and Humility
Authors: Matherne Samantha
Published: October 2024

At the heart of Kant’s aesthetics is a universalist theory of beauty. On his view, when I judge something to be beautiful, I am not judging it to be beautiful just ‘for me’; I am judging it to be beautiful ‘for everyone’. However, some have worried that this universalist view of beauty promotes a kind of arrogance in aesthetic appreciators. Although one can see why these concerns have been raised, a closer look at Kant’s theory of beauty reveals that far from encouraging aesthetic arrogance, his theory promises to serve as a corrective for it. In this vein, this chapter examines how Kant’s account of the conditions that we must meet in order to make a judgment of the beautiful cuts against such arrogance. It, furthermore, explores how Kant’s view of beauty implicitly offers resources for developing an account of aesthetic humility as a virtue of aesthetic appreciation, which can serve as a corrective to the vices of aesthetic arrogance and servility. By attending to Kant’s account of these conditions and this Kantian model of aesthetic humility, this chapter aims to bring out a more promising version of Kant’s universalist account of beauty than he is often credited with.
Kant on the Empirical Self
Authors: Moran Kate
Published: October 2024

This chapter examines the empirical self insofar as it is involved in moral conflict, deliberation, and action. To begin, it outlines the faculties of feeling and desire that constitute a large part of what Kant characterizes as the empirical self, paying special attention to the precise ways in which feeling and desire might pose a threat to morality. Despite these dangers, Kant’s suggestion is not that we should extirpate sensibility altogether. Indeed, the faculty of feeling, in particular, is fundamentally bound up with our moral capacity and our moral experience. The chapter goes on to explore various ‘aesthetic preconditions’ related to feeling that must already be in place in order for an agent to be bound or obligated by morality. Crucially, however, this is not a claim that the moral law itself is somehow secretly grounded in feeling. The chapter concludes with some reflections on the proper place of the empirical self in Kant’s moral theory, including the attitudes that we ought to take toward the empirical self, and how this might ultimately inform our interpretation of moral action and moral choice.
Kant on Enlightenment
Authors: Proops Ian
Published: October 2024

Kant defines ‘enlightenment’ as ‘humankind’s emergence from its self-imposed immaturity’. This essay considers the meaning, role, and novelty of this definition, while also examining its relation to the Enlightenment slogans: ‘sapere aude’ (‘Dare to be wise!’) and ‘Think for yourself’. It is argued that there are two subtly different aspects to the ‘immaturity’ from which Kant, insofar as he endorses the transformative process of enlightenment, is urging us to ‘emerge’. These aspects correspond to his two images of immaturity: first, confinement within a kind of baby walker (Gängelwagen), and, second, attachment to ‘leading strings’ (Leitbande). It is argued that the first is a matter of thinking only ‘by courtesy’, the second a matter of thinking under the guidance of another—one’s guardian. It is asked whether Kant’s slogan ‘think for yourself’ might not be self-defeating, and whether his insistence that one think for oneself can be made consistent with his permitting belief formation on the basis of the testimony of another. Kant’s concept of enlightenment is situated with respect to his distinction between the public and private ‘uses of reason’, on the one hand, and his defence of ‘freedom of the pen’, on the other.
Kant on Mathematics
Authors: Dunlop Katherine
Published: October 2024

Kant discusses mathematical cognition as a species of a priori theoretical cognition which is distinguished mainly by the use it makes of pure intuition. Pure intuition is closely linked to mathematical concepts, in particular, which gives us a way to understand Kant’s view of mathematical knowledge in general. This chapter argues that the linkage between mathematical concepts and pure intuition (which Kant draws only in the Critical period) puts Kant in a better position to explain features of mathematical cognition that he singles out as distinctive from the pre-Critical period onward. One central such feature is that only mathematics has definitions, in Kant’s demanding sense of ‘definition’. Kant closely associates mathematical definitions with constructions, even claiming that they are identical. The chapter considers how this view yields justification for the use of particular figures in diagrammatic reasoning, and how to reconcile it with Kant’s contention that mathematical cognition is synthetic. Interpreters disagree as to whether Kant bases this contention on the view that intuition has a necessary role in mathematical inference, over and above its role in knowing mathematics’ first principles. The chapter discusses this debate not to settle it but to show how one prominent position affords a way of understanding the connection between mathematical concepts and pure intuition. Finally, it considers the role of empirical intuition in proving the objective reality of mathematical concepts and the role of schemata in justifying generalizations from particular instances.
The Emergence of Blockchain Constitutionalism
Authors: Mannan Morshed , de Filippi Primavera , Reijers Wessel
Published: October 2024

This chapter presents the first analysis of the concept of ‘blockchain constitutionalism’ using the framework of digital constitutionalism. Drawing on Suber’s Nomic game, we introduce the paradox of self-amendment found within legal orders. Although such a paradox can be domesticated by traditional legal orders, it cannot be readily accommodated within technological legal orders, such as the rule of code instantiated by blockchain technologies. Instead, building on the perspective of digital societal constitutionalism, the paradoxes and tensions generated by the rule of code are best resolved by the actors that are endogenous to blockchain networks. We provide an overview of the functional purposes of state constitutions, distinguish between formal and material constitutions, and explain the liberal and societal perspectives of digital constitutionalism. Section 3 applies insights from constitutional theory to demonstrate that blockchain-based systems are constitutional orders. We use the example of The DAO attack to highlight the tension between the formal and material constitutions of a blockchain-based system, and how even in such systems the material constitution always exercises pressure on the formal on-chain constitution. In order to ensure the legitimacy of blockchain constitutions, it is important to formalize and codify the off-chain constitution of blockchain-based systems, by means of formal constitutions.
Origin of division of labor is decoupled from polymorphism in colonial animals
Authors: Leventhal Sarah , Edie Stewart M , Morrison Rebecca , Simpson Carl
Published: October 2024

Division of labor, the specialization of sometimes phenotypically divergent cell types or group members, is often associated with ecological success in eukaryotic colonial organisms. Despite its many independent evolutionary origins, how division of labor emerges remains unclear. Conventional hypotheses tend toward an “economic” model, so that biological division of labor may reflect a partitioning of preexisting tasks and morphologies into specialized colony members. Here, we present an alternative model of the origin of division of labor, which can explain the evolution of new functions within a colony. We show that in colonies of the Cretaceous aged (103–96 Ma) fossil bryozoan of the genus Wilbertopora, the first cheilostome bryozoan to evolve polymorphism, preexisting morphologies were not simply partitioned among new members, but instead expanded into novel morphospace as they lost functions, specifically feeding. This expansion occurred primarily during two pulses of heightened morphological disparity, suggesting that the evolution of polymorphism corresponded to relaxed constraints on morphology and perhaps to the exploration of novel functions. Using a simple model of physiological connections, we show that regardless of the functionality of these new colony members, all nonfeeding members could have been supported by neighboring feeding members. This suggests that geometric constraints and physiological connectedness could be prerequisites for evolving both polymorphism and division of labor in modular organisms, and that a classic partitioning model of specialization cannot be broadly applied to biological systems.
Multifunctional role of the tumor-associated monocytes/macrophages in the metastatic potential of inflammatory breast cancer
Authors: Mohamed Mona Mostafa , Schneider Robert J
Published: October 2024

Inflammatory breast cancer (IBC) is the most aggressive and lethal phenotype form of breast cancer, which afflicts young women at high incidence in North Africa compared to other continents of the world. IBC is characterized by highly metastatic behavior and possesses specific pathobiological properties different from non-IBC. IBC disease displays unusual common properties at typical presentation, including positive metastatic lymph nodes, high infiltration of tumor-associated monocytes/macrophages (TAMs/Ms), rapid progression to distant metastasis and possibly the production of a unique repertoire of growth factors, cytokines and chemokines, as well as a striking association with different polarized macrophages compared to non-IBC. Indeed, TAMs/Ms play a crucial role in breast cancer development. Previously, we showed that cross-talk between IBC cells and patient-derived TAMs occurs via secretion of inflammatory mediators from TAMs that act on specific extracellular domain receptors activating down-stream signaling pathways that promote the epithelial-to-mesenchymal transition, cancer cell invasion, IBC stem cell properties, drug resistance, local and metastatic recurrence of residual tumor cells and other key markers of malignancy, including in vitro colony formation capacity. In this mini-review, we will discuss the role of TAMs in IBC cancer metastatic potential and molecules involved. The review also discusses the recent discoveries in the field of IBC research.
The Fossilized Birth–Death Model Is Identifiable
Authors: Truman Kate , Vaughan Timothy G , Gavryushkin Alex , Gavryushkina Alexandra “Sasha”
Published: October 2024

Time-dependent birth–death sampling models have been used in numerous studies to infer past evolutionary dynamics in different biological contexts, for example,  speciation and extinction rates in macroevolutionary studies, or effective reproductive number in epidemiological studies. These models are branching processes where lineages can bifurcate, die, or be sampled with time-dependent birth, death, and sampling rates, generating phylogenetic trees. It has been shown that in some subclasses of such models, different sets of rates can result in the same distributions of reconstructed phylogenetic trees, and therefore, the rates become unidentifiable from the trees regardless of their size. Here, we show that widely used time-dependent fossilized birth–death (FBD) models are identifiable. This subclass of models makes more realistic assumptions about the fossilization process and certain infectious disease transmission processes than the unidentifiable birth–death sampling models. Namely, FBD models assume that sampled lineages stay in the process rather than being immediately removed upon sampling. The identifiability of the time-dependent FBD model justifies using statistical methods that implement this model to infer the underlying temporal diversification or epidemiological dynamics from phylogenetic trees or directly from molecular or other comparative data. We further show that the time-dependent FBD model with an extra parameter, the removal after sampling probability, is unidentifiable. This implies that in scenarios where we do not know how sampling affects lineages, we are unable to infer this extra parameter together with birth, death, and sampling rates solely from trees.
Visualizing Tomato Spotted Wilt Virus Protein Localization: Cross-Kingdom Comparisons of Protein-Protein Interactions
Authors: Martin K. M. , Chen Y. , Mayfield M. A. , Montero-Astúa M. , Whitfield A. E.
Published: October 2024

Tomato spotted wilt virus (TSWV) is an orthotospovirus that infects both plants and insect vectors, and understanding its protein localization and interactions is crucial for unraveling the infection cycle and host-virus interactions. We investigated and compared the localization of TSWV proteins. The localization between plant and insect cells was overall consistent, indicating a similar mechanism is utilized by the virus in both types of cells. However, a change in localization over time was associated with the viral proteins that did not contain signal peptides and transmembrane domains such as N, NSs, and NSm, which only occurred in the plant cells and not in the insect cells. We also tested the localization of the proteins during an active plant infection using free red fluorescent protein (RFP) as a marker to highlight the nucleus and cytoplasm. Voids in the cytoplasm were shown only during infection, and N, NSs, NSm, and to a lesser extent GN and GC were surrounding these areas, suggesting it may be a site of replication or morphogenesis. Furthermore, we tested the interactions of viral proteins using both bimolecular fluorescence complementation (BiFC) and membrane-based yeast two-hybrid (MbY2H) assays. These revealed self-interactions of NSm, N, GN, GC, and NSs. We also identified interactions between different TSWV proteins, indicating their possible roles, such as between NSs and GC and N and GC, which may be necessary during the replication and assembly processes, respectively. This research expands our knowledge of TSWV infection and elaborates on the intricate relationships between viral proteins, cellular dynamics, and host responses.

[Formula: see text] Copyright © 2025 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
M proteins of group A Streptococcus bind hyaluronic acid via arginine–arginine/serine–arginine motifs
Authors: McEwan Tahnee B.‐D. , De Oliveira David M. P. , Stares Emily K. , Hartley‐Tassell Lauren E. , Day Christopher J. , Proctor Emma‐Jayne , Nizet Victor , Walker Mark J. , Jennings Michael P. , Sluyter Ronald , Sanderson‐Smith Martina L.
Published: October 2024

Tissue injury, including extracellular matrix (ECM) degradation, is a hallmark of group A Streptococcus (GAS) skin infection and is partially mediated by M proteins which possess lectin‐like properties. Hyaluronic acid is a glycosaminoglycan enriched in the cutaneous ECM, yet an interaction with M proteins has yet to be explored. This study revealed that hyaluronic acid binding was conserved across phylogenetically diverse M proteins, mediated by RR/SR motifs predominantly localized in the C repeat region. Keratinocyte wound healing was decreased through the recruitment of hyaluronic acid by M proteins in an M type‐specific manner. GAS strains 5448 (M1 serotype) and ALAB49 (M53 serotype) also bound hyaluronic acid via M proteins, but hyaluronic acid could increase bacterial adherence independently of M proteins. The identification of host–pathogen mechanisms that affect ECM composition and cell repair responses may facilitate the development of nonantibiotic therapeutics that arrest GAS disease progression in the skin.
The Impact of Pandemic-Induced Separation and Visitation Restrictions on the Maternal-Infant Dyad in Neonatal Units
Authors: Kain Victoria J. , Phumdoung Sasitorn , Vetcho Siriporn , Chaisri Piyada
Published: October 2024

Background:

The COVID-19 pandemic affected the maternal-infant dyad, especially due to visitation restrictions in neonatal units. These changes may impact the psychological, physical, and developmental health of mothers and newborns.

Purpose:

This systematic review evaluates the impact of enforced separation and restrictive visitation policies in neonatal units during the pandemic, focusing on the maternal-infant dyad.

Data Sources:

Data sources include CINAHL, MEDLINE, Web of Science, APA PsycINFO, Academic Search Ultimate, and Embase, covering studies published between 2020 and 2024.

Study Selection:

A detailed search was conducted using terms related to COVID-19, maternal and neonatal health, and visitation restrictions in neonatal units. Articles were included if they were peer-reviewed, written in English, and focused on the impact of visitation restrictions on maternal and neonatal health.

Data Extraction:

The data extraction process began with 789 references. After removing duplicates, we screened titles and abstracts. We then conducted a full-text assessment of the remaining studies, selecting 14 that met the inclusion criteria.

Results:

The analysis showed significant emotional, psychological, and developmental impacts on mothers and newborns due to pandemic-induced separation and inconsistent policies. It highlighted depressive symptoms, stress, bonding disruptions, and the effectiveness of virtual bonding.

Implications for Practice and Research:

The review emphasizes the need for family-centered care, coping strategies, and virtual bonding in neonatal units. It calls for culturally sensitive policies to support mothers and infants during crises. The review also highlights the importance of studying the long-term effects of pandemic-induced separations and improving support for future health emergencies.
Eyedealistic Vision
Authors: Wilborn Nikki , Lynch Robert , Allen Patricia , Toon Molly
Published: October 2024

Background:

Rates of severe retinopathy of prematurity (ROP) continue to rise globally despite advances in healthcare. Differences in practices related to optimizing oxygenation is among key factors that increase the risk of severe ROP. A recent increase in severe ROP rates at 2 local neonatal intensive care units (NICUs) prompted further investigation into potential preventative practices.

Purpose:

The project team’s goal was to reduce rates of severe ROP by 20% in the 2 participating units.

Methods:

A level IV and level III NICU were targeted, including 255 infants at risk for ROP. Interventions included staff education, implementation of new established oxygen guidelines, as well as use of order sets, and alarm limits. Compliance rates and severe ROP rates before and after new guideline implementation were assessed.

Results:

After implementing the new guidelines, average alarm limit compliance met project goals of 90% at both sites. Severe ROP rates declined from 10% to 7% in the level IV NICU site and from 6% to 0% in the level III NICU site during the 24-month study period from 2022 to 2023.

Implications for practice and research:

Education and increased understanding regarding risk factors for ROP patients are crucial to successfully implementing and sustaining standardized oxygenation guidelines. Including the entire healthcare team and patient families is key to successful QI initiatives and improving patient outcomes. Further research is needed for optimal standardized oxygen alarm limits for this patient population.

Video Abstract:

One of the leading causes of childhood blindness is retinopathy of prematurity (ROP).1 ROP is a disease of the retina that affects premature infants, with the highest risk to very low birthweight (VLBW) infants born with a gestational age of less than 30 to 32 weeks or infants weighing less than 1500 grams.2 There are 5 stages of ROP. Stages 1 and 2 are considered mild and resolve on their own. Stage 3 is considered moderate-severe and sometimes resolves independently, with many cases requiring treatment. Stages 4 and 5 ROP are deemed severe and require treatment.
The Role of Neonatal Nurse Practitioners in the Implementation of a Bedside Point-of-Care Ultrasound Program
Authors: Tong Jacklin H. , Manipon Christine , Vallandingham-Lee Shelby , Dasani Reedhi , Davis Alexis S. , Bhombal Shazia
Published: October 2024

Background:

Point-of-care ultrasound (POCUS) in the neonatal intensive care unit (NICU) is becoming increasingly utilized, with the focus of training aimed at physicians. However, the role of neonatal nurse practitioners (NNPs) in the development of POCUS programs is not well described.

Purpose:

To describe the NNP role in the implementation of a NICU POCUS program and exemplify the potential to expand the professional scope and educational advancement of NNPs.

Methods:

In 2018, a multidisciplinary team assembled to develop a POCUS program in the NICU at Lucile Packard Children’s Hospital (LPCH). Three NNPs received formal POCUS training in order to provide onsite training, perform and supervise POCUS imaging, and participate in quality assurance sessions. NNPs also assisted with the development of a REDCap database and imaging protocols.

Results:

The LPCH POCUS NNP providers contributed to the advancement of the profession by practicing to the full scope of their role, providing leadership in program development, research, and education. Incorporating NNPs into the programmatic structure of a POCUS program can be a model for others. With advancing skill set, NNPs can be positioned to be national leaders and educators.

Implications for practice and research:

NICUs developing POCUS programs can benefit from the integration of NNPs to serve as consistent content experts to expand the number of trained providers while assuring the quality of image capture. POCUS is becoming increasingly essential to the care of newborns. NNPs can play a central role in performing POCUS, participating in quality improvement and research, and educating other NICU providers.
Immediate Correction of Idiopathic Scoliosis With Nighttime Braces Created by a Fully Automated Generative Design Algorithm
Authors: Coulombe Maxence , Guy Aymeric , Joncas Julie , Manitiu Anton , Poirier Philippe , Barchi Soraya , Chémaly Olivier , Brassard Félix , Parent Stefan , Labelle Hubert , Aubin Carl-Éric
Published: October 2024

Study Design.

Single-center, double-blinded, prospective crossover randomized controlled trial.

Objective.

To clinically validate the efficacy of nighttime braces designed automatically by a generative design algorithm to treat idiopathic scoliosis (IS). The tested hypothesis was the clinical equivalence of immediate in-brace correction for the new automatically generated brace design versus a standard Providence-type brace.

Summary of Background Data.

Documented efficacy of brace treatment varies between centers, and depends on the empirical expertise of the treating orthotist. Our group previously developed a fully automated generative brace design algorithm that leverages a patient-specific finite-element model (FEM) to optimize brace geometry and correction before its fabrication.

Methods.

Fifty-eight skeletally immature patients diagnosed with IS, aged between 10 and 16 years were recruited. All patients received both a nighttime brace automatically generated by the algorithm (test) and a Providence-type brace designed by an expert orthotist (control). Radiographs were taken for each patient with both braces in a randomized crossover approach to evaluate immediate in-brace correction.

Results.

The targeted 55 patients (48 females, 7 males) completed the study. The immediate Cobb angle correction was 57%

19 (test) versus 58%

21 (control) for the main thoracic (MT) curve, whereas it was 89%

25 (test) versus 87%

28 (control) for the thoracolumbar/lumbar (TLL) spine. The immediate correction with the test brace was noninferior to that of the Control brace (P

0.001). The order in which the braces were tested did not have a residual effect on the immediate correction.

Conclusion.

The fully automated generative brace design algorithm proves to be clinically relevant, allowing for immediate in-brace correction equivalent to that of braces designed by expert orthotists. Patient 2 years follow-up will continue. This method’s integration could help design and rationalize the design of braces for the treatment of IS.

Level of Evidence.

Level 2
Progressing “Positive Epidemiology”: A Cross-national Analysis of Adolescents’ Positive Mental Health and Outcomes During the COVID-19 Pandemic
Authors: O’Connor Meredith , Olsson Craig A. , Lange Katherine , Downes Marnie , Moreno-Betancur Margarita , Mundy Lisa , Viner Russell M. , Goldfeld Sharon , Patton George , Sawyer Susan M. , Hope Steven
Published: October 2024

Purpose:

“Positive epidemiology” emphasizes strengths and assets that protect the health of populations. Positive mental health refers to a range of social and emotional capabilities that may support adaptation to challenging circumstances. We examine the role of positive mental health in promoting adolescent health during the crisis phase of the COVID-19 pandemic.

Methods:

We used four long-running Australian and UK longitudinal cohorts: Childhood to Adolescence Transition Study (CATS; analyzed N = 809; Australia); Longitudinal Study of Australian Children (LSAC) – Baby (analyzed N =1,534) and Kindergarten (analyzed N = 1,300) cohorts; Millennium Cohort Study (MCS; analyzed N = 2,490; United Kingdom). Measures included prepandemic exposure: positive mental health (parent reported, 13–15 years) including regulating emotions, interacting well with peers, and caring for others; and pandemic outcomes: psychological distress, life satisfaction, and sleep and alcohol use outside of recommendations (16–21 years; 2020). We used a two-stage meta-analysis to estimate associations between positive mental health and outcomes across cohorts, accounting for potential confounders.

Results:

Estimates suggest meaningful effects of positive mental health on psychosocial outcomes during the pandemic, including lower risk of psychological distress (risk ratio [RR] = 0.83, 95% confidence interval [CI] = 0.71, 0.97) and higher life satisfaction (RR = 1.1, 95% CI = 1.0, 1.2). The estimated effects for health behaviors were smaller in magnitude (sleep: RR = 0.95, 95% CI = 0.86, 1.1; alcohol use: RR = 0.97, 95% CI = 0.85, 1.1).

Conclusions:

Our results are consistent with the hypothesis that adolescents’ positive mental health supports better psychosocial outcomes during challenges such as the COVID-19 pandemic, but the relevance for health behaviors is less clear. These findings reinforce the value of extending evidence to include positive health states and assets.
The administration of a phentolamine infusion into the basolateral amygdala enhances long-term memory and diminishes anxiety-like behavior in stressed rats
Authors: Dehghani Ali , Meftahi Gholam Hossein , Sahraei Hedayat
Published: October 2024

The basolateral amygdala (BLA) contains adrenergic receptors, which are known to be involved in stress, anxiety, and memory. The objective of this study was to explore whether inhibition of α-adrenergic receptors (by phentolamine, an α-adrenergic receptor antagonist) in the BLA can reduce foot-shock stress–induced anxiety-like behavior, memory deficits, and long-term potentiation (LTP) deficits within the CA1 region of the rat hippocampus. Forty male Wistar rats were assigned to the intact, control, stress (Str), Phent (phentolamine), and Phent + Str groups. Animals were subjected to six shocks on 4 consecutive days, and phentolamine was injected into BLA 20 min before the animals were placed in the foot-shock stress apparatus. Results from the elevated plus maze test (EPM) revealed a reduction in anxiety-like behaviors (by an increased number of entries into the open arm, percentage of time spent in the open arm, and rearing and freezing) among stressed animals upon receiving injections of phentolamine into the BLA. The open-field test results (increased rearing, grooming, and freezing behaviors) were consistent with the EPM test results. Phentolamine infusion into the BLA enhanced spatial memory, reducing errors in finding the target hole and decreasing latency time in the Barnes maze test for stress and nonstress conditions. Injecting phentolamine into the BLA on both sides effectively prevented LTP impairment in hippocampal CA1 neurons after being subjected to foot-shock stress. It has been suggested that phentolamine in the BLA can effectively improve anxiety-like behaviors and memory deficits induced by foot-shock stress.
Deubiquitinase USP47 Ameliorates Cardiac Hypertrophy Through Reducing Protein O-GlcNAcylation
Authors: Jiang Yu , Cai Wenyao , Lei Guangtao , Cai Guorong , Wu Qinghua , Lu Peng
Published: October 2024

Cardiac hypertrophy is a crucial risk factor for heart failure when the heart is confronted with physiologic or pathologic stimuli. The ubiquitin–proteasome system plays a critical role in the pathogenesis of cardiac hypertrophy. However, as a key component of the ubiquitin–proteasome system, the role of deubiquitinating enzymes in cardiac hypertrophy is not well understood. In this study, we observed that the expression level of deubiquitinase USP47 was increased in hypertrophic hearts and angiotensin II (Ang II)-stimulated neonatal rat cardiomyocytes. Adenovirus-mediated gain- and loss-of-function approaches indicated that USP47 overexpression significantly attenuated Ang II-induced cardiac hypertrophy in vitro and in vivo, whereas endogenous USP47 deficiency promoted the prohypertrophic effect of Ang II. Further investigation demonstrated that USP47 inhibited O-GlcNAcylation in cardiomyocytes by controlling the expression of O-GlcNAcase. Mechanistically, USP47 bound, deubiquitinated, and stabilized protein arginine methyltransferase 5 (PRMT5), thus upregulating O-GlcNAcase expression. We found that the restoration of PRMT5 abolished the prohypertrophic effects of USP47 silence in vitro. Therefore, our results provide the first evidence of the involvement of USP47 in cardiac hypertrophy and identify USP47 as a potential target for hypertrophic therapy.