bluuebunny/crossref_metadata_2025 huggingface dataset:
Agents in International Tax Treaties
Authors: Jogarajan Sunita
Published: October 2023

This chapter discusses agents in international tax treaties. One of the most common ways through which an enterprise may undertake business in another jurisdiction is through the provision of services by an agent. The chapter examines one particular issue in relation to agents in international tax treaties: the treatment of commissionaire arrangements. The question here is whether the commissionaire constitutes a ‘dependent agent’. The issue has arisen due to different conceptions of agents under civil law and common law. The potential for differing tax treatment arising from the various concepts of agents was recognized during the drafting of the first model tax treaties in 1928 but the issue was left unresolved. However, the potential to avoid taxation or minimize taxes through the use of commissionaire arrangements has recently been addressed through the coordinated global effort to target base erosion and profit shifting (BEPS).
The Role of the ECJ in the Development of International Tax Law
Authors: Cloer Adrian
Published: October 2023

This chapter describes the role of the European Court of Justice (ECJ) in the development of international tax law. The ECJ is the authoritative institution for the interpretation and application of European tax law. The case law of the ECJ and the interpretation of legal provisions shaped by the court transcends the borders of the EU member states when the member states apply the law and thereby creating sensitivity for the interpretation of terms in relation to third countries. The mode of operation of Union law is of fundamental importance, as it constitutes binding law for the member states. In terms of the binding nature of international tax law, European tax law has a broader impact. The extent to which the role of the ECJ in European and international tax law has changed or will change from the interpretation of Union law to a restriction of the freedom of the national legislator to shape tax law must be clarified in conclusion.
The Chinese Perspective on International Tax Law
Authors: Mingxing Cao Bristar
Published: October 2023

This chapter looks at international tax reform in the digitalized economy from a Chinese perspective. As the second largest country of the digitalized economy but still a developing country, China is currently confronted with many issues concerning its stance on the complex goals of tax base security, fairness, and cooperation in the digital economy. Yet China needs a clear position because the competition and cooperation of market countries’ taxation rights relates not only to China’s national taxation interests but also to the world’s industrial structure, and it will greatly affect the reshaping of the global political and economic structure in future years. In the era of the digitalized economy, there is a need for the international taxation governance mechanisms to be reshaped. With the increasingly deepening recognition in the multi-dimensional framework of cross-border transactions in the digitalized economy, there is a need for Chinese thinking on and a Chinese plan for the global governance of international taxation in the digitalized economy. This is particular so with regard to multi-party competition; patterns of residence, source, and market; tax havens; as well as in the urgent need to deal with problems of tax base erosion and tax base mismatch,.
The German Perspective on International Tax Law
Authors: Kraft Gerhard
Published: October 2023

This chapter addresses the German perspective on international tax law. The current German international tax system encompassing all rules dealing with cross-border taxation is considered extremely complex. There is little doubt that this complexity is partly due to the incremental development of the complexity of economic systems all over the world now in place to deal with cross-border trade activity. In addition, Germany presides over an unprecedented system of anti-abuse rules with a particular focus on international taxation. For international as well as for domestic tax purposes, the notion of tax under German definitory standards refers to a mandatory financial charge or some other type of levy typically imposed upon an individual or other legal entity, the so-called taxpayer, by a governmental organization in order to fund various public expenditures. The chapter then looks at the history and constitutional foundations of German international taxation. It also considers Germany’s tax treaty policy and anti-abuse tax legislation concerning international tax matters, as well as the role of the courts in international tax matters in Germany.
International Tax Law and its Influence on National Tax Systems
Authors: Elliffe Craig
Published: October 2023

This chapter evaluates international tax law and its influence on national tax systems. International tax law has components drawn from different areas of law, some parts of which are peculiarly domestic or sovereign in the sense that they are the exclusive decision of a state to impose taxation. In contrast, other parts reside in public international law because they deal with the rules, norms, and standards generally accepted in relations between nations. This dual dynamic is central to why international tax law is influential on national tax systems. The chapter proposes that there is an emerging system based on common understandings, with the legal duties of cooperation and underpinning expectations of implementation which should be recognized as creating obligations upon states even though the system does not constitute customary international law. This can be described as ‘consensus international tax law’ (CITL). CITL is a phenomenon that recognizes both the sovereignty and politics of national tax laws, as well as the need for harmonization and reasonableness in international dealings with other states and their tax systems.
Digitalization and the Future of VAT in the European Union
Authors: Tumpel Michael
Published: October 2023

This chapter evaluates digitalization and the future of VAT in the EU. VAT is affected by digitalization in many ways. First, digital transformation of businesses forces changes in VAT law in order to ensure the revenue stream. Digitalization has led to the development of new business models parallel or overlapping with traditional business or complementing those business. These characteristics of the digital economy increase the already existing challenges of cross-border trade in goods and services for the VAT system. Over the last two decades, the EU has adjusted its VAT system to cope with those challenges. Secondly, digitalization allows governments to process more information on economic activities of taxpayers. Tax-enforcement technology will be improved through digitalization and can therefore contribute to efforts to lower tax evasion.
Bond in the Middle
Authors: Salfen Kevin
Published: October 2023

The James Bond franchise of the 1960s resonates with critical descriptors “masscult” and “midcult,” described influentially by Dwight MacDonald at the start of the same decade. A study of the first five Eon Productions Bond films, which featured Sean Connery as 007, reveals an aspirational trajectory, from their origins in spy and gumshoe television series to evocations of Golden Age Hollywood film to the limits of technological achievement and trial gestures in the direction of art film and cultural diplomacy. This chapter focuses on sound, and particularly on the music of John Barry, in these films—Dr. No, From Russia with Love, Goldfinger, Thunderball, and You Only Live Twice—as a revealing and underexplored index of aspiration and therefore as a feature that permits more nuanced consideration of midcult aspects of one of the world’s most popular film franchises.
A History of Borges’s Reception in Argentina
Authors: Pastormerlo Sergio
Published: October 2023

Before reaching the uppermost echelons of international and media canonization at the age of sixty, at which time the main body of his work was already complete, Borges long enjoyed the recognition of peers from his very first publications in the early 1920s through the 1950s. Literary journals, from Nosotros (1907–1943), to the crucial first two decades of Sur (1931–1970), to Punto de Vista (1978–2008) tell a better tale than any book can of how Borges became a writer, both loved and hated, in a literary and political history whose chronology was also punctuated significantly by adverse readings and silences.
The Twin Miracle
Authors: Tinsley Elizabeth Noelle
Published: October 2023

This chapter examines the Ryōzu Aizen icon, a combination of two Wisdom Kings, and its possible connections to possession and exorcism rituals at thirteenth-century Kōyasan, a major community of Shingon monks. This icon appears to be unique to Japanese tantric Buddhism and has been used by the Shingon school. An examination of a branch-exclusive oracular text produced by the Chūin-ryū reveals that at Kōyasan it seems to have been ritually employed in an attack in 1242 on a rival within the community, during a period of sectarian conflict. The possible meanings of Ryōzu Aizen, as expressed in the branch’s texts, are explored along with an explanation of origins, its demonic and demon-slaying associations, and its transmission to Kōyasan.
Frances Ellen Watkins Harper
Authors: Robinson Marcia C.
Published: October 2023

African American poet-activist Frances Ellen Watkins Harper addressed the meaning of democracy in America throughout her long social reform career. In “Our Greatest Want,” a short essay-speech from the high point of her abolitionist career, Harper maintains that democracy is fundamentally a type of free moral society, grounded in the idea of human kinship, and made out of religion. Harper inherits this idea from her uncle, Reverend William Watkins, Jr., and presents it in this piece as a means to counter two features of American democracy that Alexis de Tocqueville identified as religious—or pseudo-religious—namely, the pursuit of wealth and the dynamic of public opinion. Synthesizing and poeticizing her uncle’s and de Tocqueville’s ideas, she challenges her black audience’s disregard for the negative impact of these forces on their people. In the process, she critiques both de Tocqueville and his well-known supporter, Catharine Beecher, for their positions on race and gender.
Ida B. Wells
Authors: James Joy
Published: October 2023

This chapter explores anti-lynching journalist, organizer, and theorist Ida B. Wells-Barnett through the lens of the Captive Maternal, a self-identified female, male, trans, or ungendered person feminized and socialized into caretaking functions within the legacy and structure of anti-Black violence and dishonor within US democracy. Before she married Ferdinand Barnett, Wells emerged in 1892 as a fierce political analyst and journalist, an opponent to the lynching of Black people and theft of their lands and property by white civilians and officials of the state. Analyzing Wells’s political ethics reveals the relevance of theorists such as Bernard Lonergan, Seylah Benhabib, and the Chinese philosopher of war Sun Tzu in struggles against predatory violence within Western democracies.
Educational Challenges in Latin America
Authors: Whitehead Laurence
Published: October 2023

This broad survey chapter outlines the fitful and uneven progress of both formal and informal educational provision in Latin America since the European Conquest. It underscores heterogeneous and unstable features that may also be present in other large world regions, but that are especially visible in the subcontinent. These large-scale geographical and historical variations leave lasting legacies that affect educational attainments up to the present day. In addition, the chapter also highlights the complex aftermath of the region’s 1982 debt crisis, which caused a partial rollback of hitherto expansionary state provided education, and it notes the (probably major) setback represented by the current pandemic.
The OECD’s Boundary Work in Education in the United States and Brazil
Authors: Ydesen Christian , Ramsing Enemark Nanna
Published: October 2023

Global governance processes have created key reference points for education worldwide in the shape of data, indicators, values, problem solutions, and even ideologies. Nevertheless, national education systems and local education practices remain diverse and complex. Therefore, research into the workings of global education requires analytical sensitivity to the interactions and intermeshing relations among local, national, and global agents, instruments, knowledge, data, and policies populating and constituting spaces. Starting from this insight and drawing on archival sources from the Organization for Economic Cooperation and Development (OECD) archive in Paris, the United States National Archive in Washington, DC, and the Brazilian National Archive in Brasilia, this chapter investigates the interactions and intermeshing relations in education between the OECD and two federal states; the United States, a member state, and Brazil, a non-member state, in a historical and comparative perspective.
Reforming Higher Education in India in Pursuit of Excellence, Expansion, and Equity
Authors: Tilak Jandhyala B. G.
Published: October 2023

After decades of neglect, higher education in India began receiving public attention. Apart from continuing problems relating to quantitative expansion, quality, and inequalities, the system also faces serious challenges with shortage of teachers, public funds, governance, and a rapidly growing commercially motivated private sector. The unforeseen crisis caused by COVID-19 added further problems to higher education. Reforming higher education has been on the public agenda for quite some time: Some reforms have already been introduced, and some are at the stage of discussions and deliberations; the need for a search for new and innovative measures is also being realized. This chapter provides a critical review of on some of the recent reforms introduced and the reforms that are being proposed in the most recent years.
Subnational Variations in Education and Policy Innovation in Argentina
Authors: Behrend Jacqueline
Published: October 2023

In federal systems, education is often shaped to a considerable extent by subnational politics. This provides a comparative basis for evaluation and learning within a nation state and not just between states. This chapter focuses on Argentina to show how public policies that are developed by national governments, but implemented at the subnational level, can lead to important variations within countries. This variation is increasingly relevant in Latin American nations, which are often unequal and have territorially uneven patterns of development. The chapter analyses the implementation of the 2005 Education Financing Law in Argentina and shows how levels of implementation and compliance varied across subnational jurisdictions and how these subnational variations affected the transition to online education during the COVID-19 pandemic in 2020–2021. It also focuses on subnational initiatives of digital education to show how subnational jurisdictions can innovate or build on national policies to improve the quality of services.
Technocrats and Unions in the Politics of Reforming Teacher Careers in Colombia and Peru
Authors: Cuenca Ricardo , García Sandra , Schneider Ben Ross
Published: October 2023

Beginning in 2002, Colombia was one of the first countries in Latin America to devise a major, meritocratic reform to teacher careers. However, the reform applied only to new teachers, and their numbers grew slowly, reaching around half of teachers by 2020. The reform was slow, but it avoided major conflict with Fecode, the teachers’ union, that ended up negotiating a revised evaluation system in 2015. Reforms in Peru started slowly in 2001. After 2006, technocrats played a larger role in implementing reforms which met several strikes by Sutep, the teachers’ union. Critical to both reform successes was consistent policy implementation by a series of different technocratic ministers of education. In comparative terms, union opposition was muted.
Policy Advice and Policy Advisory Systems in Education
Authors: Galanti Maria Tullia
Published: October 2023

Creating and diffusing knowledge about policies represents a challenge for both academics and practitioners. At the same time, the demand for policy advice from policymakers is constantly increasing, while globalization contributes to differentiate the forms and the actors of expert knowledge on public policies. The literature has recently focused on this issue by proposing to view not the single advisor, but the policy advisory systems, intended as the systems of actors who deliver policy advice from within and from outside institutions in a given policy sector. These trends are also visible in the globalization of education policies, which creates pressures for policy diffusion, borrowing or leaning on local policymakers. This chapter presents the characteristics of policy advisory systems in education policies emerging in a comparative perspective, with a particular focus on the Organization for Economic Cooperation and Development and the European countries.
Reduction and Method
Authors: Kane Brian
Published: October 2023

This chapter examines the role of reduction in phenomenological method. Reduction plays a number of significant roles in phenomenological method and thus in the phenomenology of music. The first section examines the relationship between phenomenology and science, arguing that phenomenology’s commitment to reduction is not to be confused with scientific “reductionism.” After examining the difference between reductionism and reduction, the chapter discusses the two primary modes of reduction used in standard phenomenological method, the “phenomenological reduction” and the “eidetic reduction.” Both modes are explicated in relation to their use in the phenomenology of music. Finally, the three phases of Husserl’s career are used as a framework for considering different styles of musical phenomenology and their primary concerns. The article also makes an argument that a commitment to reduction as a method can be used as a criterion for identifying the authors and ideas that should be included within the “phenomenological movement.” At the same time, ongoing problems with reduction as a method also point to ongoing problems with the phenomenology of music.
The Ambivalent Aesthetics of Muhammad Hasan Askari
Authors: Mian Zain R.
Published: October 2023

This chapter reads Jazīre, a notable short-story collection by the canonical Urdu modernist Hasan Askari, against the grain to reveal the conflicting commitments of his oeuvre. Askari’s stories reveal a consistent engagement with the category of ordinary Indians, or the ‘avām, who inspire both progressive and modernist tendencies in his work. Where Askari initially deploys a self-reflexive progressivism to advocate for a more capacious representation of the ‘avām in literature, his later stories stress his inability to pursue just such a depiction in positive terms. The internal development of Jazīre, the chapter suggests, necessitates a rethinking of the assumed oppositions between progressivism and modernism in Urdu literature, especially as they inhibit our interpretation of authors such as Askari.
What Difference Do Museums Make?
Authors: Balcells Laia , Voytas Elsa
Published: October 2023

What role do museums play in societies recovering from violence? Transitional justice museums are often constructed to help legitimize inchoate legal and political systems and promote reconciliation. In some cases, however, these sites can be coopted by self-interested elites, and a museum’s mere existence and content could be sources of polarization. Despite the popularity of transitional justice museums, few have examined their impact. This chapter proposes a research agenda that endeavors to understand the role of museums in shifting public opinion, promoting peace, and preventing returns to violence. The authors develop a general theory of how and why museums affect visitors, suggesting that their nature and impacts are dependent on context: the form they take, and their effects vary, based on the type of conflict memorialized and whether they were established by the state or through grassroots efforts. The results of this research will be of value to both transitioning societies and the international community at large, which stands to benefit from tactics that break cycles of violence and establish stability.
Sugar Signals and R2R3-MYBs Participate in Potassium-Repressed Anthocyanin Accumulation in Radish
Authors: Niu Mengyang , Chen Xuan , Guo Youyou , Song Jinxue , Cui Jin , Wang Lu , Su Nana
Published: October 2023

Anthocyanin biosynthesis in plants is influenced by a wide range of environmental factors, such as light, temperature and nutrient availability. In this study, we revealed that the potassium-repressed anthocyanin accumulation in radish hypocotyls was associated with altered sugar distribution and sugar signaling pathways rather than changes in oxidative stress status. Sugar-feeding experiments suggested a hexokinase-independent glucose signal acted as a major contributor in regulating anthocyanin biosynthesis, transport and regulatory genes at the transcriptional level. Several R2R3-MYBs were identified as anthocyanin-related MYBs. Phylogenetic and protein sequence analyses suggested that RsMYB75 met the criteria of subgroup 6 MYB activator, while RsMYB39 and RsMYB82 seemed to be a non-canonical MYB anthocyanin activator and repressor, respectively. Through yeast-one-hybrid, dual-luciferase and transient expression assays, we confirmed that RsMYB39 strongly induced the promoter activity of anthocyanin transport–related gene RsGSTF12, while RsMYB82 significantly reduced anthocyanin biosynthesis gene RsANS1 expression. Molecular models are proposed in the discussion, allowing speculation on how these novel RsMYBs may regulate the expression levels of anthocyanin-related structural genes. Together, our data evidenced the strong impacts of potassium on sugar metabolism and signaling and its regulation of anthocyanin accumulation through different sugar signals and R2R3-MYBs in a hierarchical regulatory system.
Quality of ethnicity data within Scottish health records and implications of misclassification for ethnic inequalities in severe COVID-19: a national linked data study
Authors: Amele Sarah , McCabe Ronan , Kibuchi Eliud , Pearce Anna , Hainey Kirsten , Demou Evangelia , Irizar Patricia , Kapadia Dharmi , Taylor Harry , Nazroo James , Bécares Laia , Buchanan Duncan , Henery Paul , Jayacodi Sandra , Woolford Lana , Simpson Colin R , Sheikh Aziz , Jeffrey Karen , Shi Ting , Daines Luke , Tibble Holly , Almaghrabi Fatima , Fagbamigbe Adeniyi Francis , Kurdi Amanj , Robertson Chris , Pattaro Serena , Katikireddi Srinivasa Vittal
Published: October 2023

Background

We compared the quality of ethnicity coding within the Public Health Scotland Ethnicity Look-up (PHS-EL) dataset, and other National Health Service datasets, with the 2011 Scottish Census.

Methods

Measures of quality included the level of missingness and misclassification. We examined the impact of misclassification using Cox proportional hazards to compare the risk of severe coronavirus disease (COVID-19) (hospitalization & death) by ethnic group.

Results

Misclassification within PHS-EL was higher for all minority ethnic groups [12.5 to 69.1%] compared with the White Scottish majority [5.1%] and highest in the White Gypsy/Traveller group [69.1%]. Missingness in PHS-EL was highest among the White Other British group [39%] and lowest among the Pakistani group [17%]. PHS-EL data often underestimated severe COVID-19 risk compared with Census data. e.g. in the White Gypsy/Traveller group the Hazard Ratio (HR) was 1.68 [95% Confidence Intervals (CI): 1.03, 2.74] compared with the White Scottish majority using Census ethnicity data and 0.73 [95% CI: 0.10, 5.15] using PHS-EL data; and HR was 2.03 [95% CI: 1.20, 3.44] in the Census for the Bangladeshi group versus 1.45 [95% CI: 0.75, 2.78] in PHS-EL.

Conclusions

Poor quality ethnicity coding in health records can bias estimates, thereby threatening monitoring and understanding ethnic inequalities in health.
Prevalence and mortality associations of interstitial lung abnormalities in rheumatoid arthritis within a multicentre prospective cohort of smokers
Authors: McDermott Gregory C , Hayashi Keigo , Yoshida Kazuki , Moll Matthew , Cho Michael H , Doyle Tracy J , Kinney Gregory L , Dellaripa Paul F , Putman Rachel K , San Jose Estepar Raul , Hata Akinori , Hino Takuya , Hida Tomoyuki , Yanagawa Masahiro , Nishino Mizuki , Washko George , Regan Elizabeth A , Hatabu Hiroto , Hunninghake Gary M , Silverman Edwin K , Sparks Jeffrey A
Published: October 2023

Objective

To investigate the prevalence and mortality impact of interstitial lung abnormalities (ILAs) in RA and non-RA comparators.

Methods

We analysed associations between ILAs, RA, and mortality in COPDGene, a multicentre prospective cohort study of current and past smokers, excluding known interstitial lung disease (ILD) or bronchiectasis. All participants had research chest high-resolution CT (HRCT) reviewed by a sequential reading method to classify ILA as present, indeterminate or absent. RA cases were identified by self-report RA and DMARD use; non-RA comparators had neither an RA diagnosis nor used DMARDs. We examined the association and mortality risk of RA and ILA using multivariable logistic regression and Cox regression.

Results

We identified 83 RA cases and 8725 non-RA comparators with HRCT performed for research purposes. ILA prevalence was 16.9% in RA cases and 5.0% in non-RA comparators. After adjusting for potential confounders, including genetics, current/past smoking and other lifestyle factors, ILAs were more common among those with RA compared with non-RA [odds ratio 4.76 (95% CI 2.54, 8.92)]. RA with ILAs or indeterminate for ILAs was associated with higher all-cause mortality compared with non-RA without ILAs [hazard ratio (HR) 3.16 (95% CI 2.11, 4.74)] and RA cases without ILA [HR 3.02 (95% CI 1.36, 6.75)].

Conclusions

In this cohort of smokers, RA was associated with ILAs and this persisted after adjustment for current/past smoking and genetic/lifestyle risk factors. RA with ILAs in smokers had a 3-fold increased all-cause mortality, emphasizing the importance of further screening and treatment strategies for preclinical ILD in RA.
The prevalence and impact of polypharmacy in rheumatology
Authors: Lewis Justin , Östör Andrew J K
Published: October 2023

Polypharmacy is increasingly common in rheumatology due to the complex nature of managing chronic autoimmune diseases. To date there has been limited research into the impact of polypharmacy on rheumatology patients. In this article we reviewed the literature to characterize the prevalence of polypharmacy and its effect on patients. In addition, we have highlighted some key drug–drug interactions to consider involving DMARDs as well as complementary and alternative medicines. There is emerging evidence demonstrating that polypharmacy contributes to adverse outcomes and alters treatment response. This association is best described in RA and is less clear in other patient cohorts. It is also unclear whether polypharmacy is directly harmful or just a surrogate marker for other factors affecting outcomes. Rheumatologists should be aware of the risk of polypharmacy as well as specific drug–drug interactions that can occur in managing chronic autoimmune disease.
O013 Preliminary Results from a Phase 1 Study of ALKS 2680, an Orexin-2 receptor Agonist, in Healthy Participants and Patients with Narcolepsy or Idiopathic Hypersomnia
Authors: Yee B , Chapman J , Grunstein R , Argent C , D’Rozario A , Hopkinson C , Ramos J , Landry I , Yagoda S , Rege B
Published: October 2023

Introduction

ALKS 2680, a potent, brain-penetrant, highly selective orexin-2 receptor (OX2R) agonist, is being developed for treatment of narcolepsy and other hypersomnias. We report preliminary results from the ALKS 2680 first-in-human study.

Methods

This randomized, double-blind, phase 1 study of ALKS 2680 is being conducted at two Australia sites. Healthy participants received single- (n=48, 6 dosages) or multiple- (n=32, 4 dosages once-daily for 10 days) oral doses of ALKS 2680 or placebo. Patients with narcolepsy type 1 (NT1) or type 2 (NT2) or idiopathic hypersomnia (IH; up to 8 patients for each indication) will also be studied, receiving single doses ALKS 2680 or placebo in a 4-way crossover design with 3 active dose levels. Pharmacodynamic assessments will include the Maintenance of Wakefulness Test, Karolinska Sleepiness Scale, and tracking of sleep and cataplexy episodes.

Results

In healthy participants, ALKS 2680 was orally absorbed and showed biphasic distribution/elimination, with a terminal half-life suitable for maintaining daytime wakefulness with once-daily administration. There were no systematic changes in vital signs, safety laboratory tests, or ECG at any dose level, and no serious or severe adverse events (AEs). Most drug-related events were mild and resolved without medical intervention. There was a single discontinuation due to a nonserious AEs that resolved without treatment.

Conclusions

Preliminary results suggest that the OX2R agonist ALKS 2680 is generally well-tolerated with a pharmacokinetic profile potentially suitable for once-daily oral administration to promote daytime wakefulness. Effects of ALKS 2680 in patients with NT1, NT2, and IH are being evaluated.
Host Identity Determines the Bacterial and Fungal Community and Network Structures in the Phyllosphere of Plant Species in a Temperate Steppe
Authors: Guo Chunyan , Yang An , Zhang Wen-Hao
Published: October 2023

Elucidating the plant−microbiome network is of importance in understanding species coexistence in natural ecosystems. The phyllosphere, which is the aerial parts of terrestrial plants, is inhabited by diverse microbes. However, few studies have focused on the phyllosphere microbiome and plant-microbiome network in temperate grasslands. In this study, we explored the diversity, community structure, and network architecture of phyllosphere bacteria and fungi in 19 plant species native to the temperate grassland in Inner Mongolia, China. We obtained 3,313 and 758 phyllosphere bacterial and fungal operational taxonomic units, respectively, and found that the bacterial community was dominated by Proteobacteria, Actinobacteriota, and Firmicutes, whereas the fungal community was dominated by Ascomycota and Basidiomycota. Plant identity exerted significant impacts on α-diversities of both bacterial and fungal communities. The composition of bacterial and fungal communities differed among plant species. Plant identity had a greater effect on fungal than bacterial communities. Both bacterial and fungal network structures were characterized by specialized, modular, lowly connected, and no nested properties. The plant−fungal network had a high level of specification, modularity, antinestedness, and connectance compared with the plant−bacterial network. Our results suggest more intimate relationships between plants and phyllosphere fungi than between plants and phyllosphere bacteria and also that the phyllosphere fungal community in the temperate grassland ecosystem is more resistant to environmental disturbance than the phyllosphere bacterial community. These findings may contribute to our understanding of the mechanisms by which species coexist and communities stabilize in grassland ecosystems.
Femur Fractures in 5 Individuals With Pantothenate Kinase-associated Neurodegeneration: The Role of Dystonia and Suggested Management
Authors: Behrndt Laken , Gregory Allison , Wakeman Katrina , Freed Alison , Wilson Jenny L. , Spaull Robert , Kurian Manju A. , Mordekar Santosh , Fernandes James A. , Hayflick Susan J. , Hogarth Penelope , Yang Scott
Published: October 2023

Background:

Pantothenate kinase-associated neurodegeneration (PKAN) is a rare, neurodegenerative disorder that manifests with progressive loss of ambulation and refractory dystonia, especially in the early-onset classic form. This leads to osteopenia and stress on long bones, which pose an increased risk of atraumatic femur fractures. The purpose of this study is to describe the unique challenges in managing femur fractures in PKAN and the effect of disease manifestations on surgical outcomes.

Methods:

A retrospective case review was conducted on 5 patients (ages 10 to 20 y) with PKAN with a femur fracture requiring surgical intervention. Data regarding initial presentation, surgical treatment, complications, and outcomes were obtained.

Results:

All patients were non-ambulatory, with 4 of 5 patients sustaining an atraumatic femur fracture in the setting of dystonia episode. One patient had an additional contralateral acetabular fracture. Postoperatively, 4 of the 5 patients sustained orthopaedic complications requiring surgical revision, with 3 of these secondary to dystonia. Overall, 4 required prolonged hospitalization in the setting of refractory dystonia.

Conclusion:

Femur fractures in PKAN present distinct challenges for successful outcomes. A rigid intramedullary rod with proximal and distal interlocking screws is most protective against surgical complications associated with refractory dystonia occurring during the postoperative period. Multidisciplinary planning for postoperative care is essential and may include aggressive sedation and pain management to decrease the risk of subsequent injuries or complications.

Level of Evidence:

Level IV.
Laparoscopic continent cutaneous urinary diversion using a modified Yang–Monti technique in an adult: A case report including 5-year follow-up
Authors: Chen Silu , Wu Yuye , Zhang Peng , Li Zhihua , Li Xinfei , Li Zhenyu , Yang Kunlin , Li Xuesong
Published: October 2023

Continuous cutaneous urinary diversion is challenging when the appendix is physically unavailable. The Yang–Monti channel is an alternative to the tunneled appendix for urinary diversion. We present a case involving a 49-year-old man who underwent total urethrectomy and cystostomy 10 months previously. No tumor recurrence was observed; however, the patient experienced severe catheter-related bladder irritation after the procedure. The patient was readmitted to the authors’ hospital and underwent laparoscopic continent cutaneous urinary diversion using extracorporeal construction of a modified Yang–Monti channel. The operation lasted 232 minutes, with an estimated blood loss of 10 mL. The patient was discharged from hospital 6 days after surgery and removal of the cystostomy tube. After this, clean intermittent catheterization was performed every 3 hours for 4 weeks. Five years after the procedure, the modified Yang–Monti channel was still used for clean intermittent catheterization without any stomal stenosis being observed. The patient was satisfied with his postoperative quality of life.
Young Children's Development and Behavior: Associations with Timing of Household Food Insecurity in a Racially and Ethnically Diverse Early Head Start Sample
Authors: Treviño Monica S. , Cherry Kathryn E. , Njoroge Wanjikũ F. M. , Gerstein Emily D.
Published: October 2023

Objective:

The objective of this study was to assess the impact of household food insecurity (HFI) over time on behavioral and developmental health in early childhood while considering the impact of timing/persistence of HFI and potential differences among racially or ethnically minoritized children.

Methods:

Families from the Early Head Start Family and Child Experiences Study (N = 760) were followed longitudinally until age 3 years. Caregiver interview data were collected on HFI, problem behaviors (PBs), delays in development (DD), and sociodemographic information. Analysis of Covariances examined differences between persistent vs transient HFI. Multiple regressions examined the impact of HFI on PB and DD and whether this relation was stronger in racially or ethnically minoritized children.

Results:

The timing of HFI differentially affected PB, such that those with persistent HFI demonstrated greater PB than those with only early or only late HFI. A different pattern was identified for DD, in which those with late HFI had more DD than those with persistent HFI. Over and above other sociodemographics, including maternal risk factors and an income-to-needs ratio, HFI was associated with greater PB for children of all races and ethnicities. HFI was associated with more DD in non-Latino/a/e/x White families compared with non-Latino/a/e/x Black and Latino/a/e/x families.

Conclusion:

Meaningful differences were found in how the persistence/timing of HFI is differentially associated with PB and DD. In addition, while controlling for socioeconomic risk, a cumulative risk effect was not observed in how HFI affected racially or ethnically minoritized children.
Elucidating the Perspectives of Autistic Youth About Their Health Care Experiences: A Qualitative Study
Authors: O'Hagan Belinda , Foster Sarah , Ursitti Amy , Crable Erika L. , Friedman Alexander J. , Bartolotti Lauren , Krauss Shari
Published: October 2023

Objectives:

Autistic individuals have higher rates of co-occurring medical conditions and service use. However, autistic individuals and their families also reported lower satisfaction with health care service delivery. Previous studies described health care experiences of autistic adults, but less is known about those of autistic adolescents and young adults. This study aimed to qualitatively describe the health care experiences of autistic youth.

Methods:

Four longitudinal/serial focus groups were conducted with 8 autistic adolescents and young adults. Participants were members of an autistic patient advisory board, which is part of a broader initiative at a large, urban, safety-net hospital to improve the health care experiences of autistic patients. Focus groups were conducted virtually and were audio-recorded. Audio recordings were transcribed and verified for accuracy. Transcripts were consensus-coded with an inductive approach using tenets of grounded theory.

Results:

Findings included 4 recurring themes: accessibility and accommodations, barriers of health service use, patient involvement in health care decisions, and facilitators of patient-clinician relationship. Participants noted that visit preparation, sensory items, and repeated positive interactions with clinician were helpful to build a positive health care experience.

Conclusion:

Our findings support previous research that suggest the need to individualize care, ensure availability of accommodations, apply flexibility in practice whenever possible, and increase health care professional knowledge about this unique patient population.
Liposomal and Nonliposomal Bupivacaine for Mohs Surgery: A Systematic Review
Authors: Jeha George M. , Malinosky Hannah R. , Taylor Laura , Greenway Hubert T. , Kelley Benjamin
Published: October 2023

BACKGROUND

Lidocaine is the most commonly used local anesthetic for Mohs micrographic surgery (MMS), but given its limited half-life, postoperative pain remains a significant concern for patients. Bupivacaine is used in various surgical subspecialty procedures and has demonstrated improved pain control compared with lidocaine. However, its role in MMS is insufficiently explored.

OBJECTIVE

To systematically review the current literature for reports on use of bupivacaine, traditional nonliposomal and newer liposomal formulations, for MMS.

METHODS

A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. The MEDLINE, PubMed, and EMBASE databases were queried for articles presenting original data on the use of bupivacaine for MMS.

RESULTS

Of 483 potentially relevant articles, 3 studies met final inclusion criteria, capturing a total of 253 patients involved in primary investigations comparing bupivacaine to traditional local anesthesia for MMS. Bupivacaine was well-tolerated and associated with comparable or modestly reduced intraoperative and postoperative pain and opioid use.

CONCLUSION

Bupivacaine may have a role in prolonging intraoperative anesthesia, reducing acute postoperative pain, and reducing postoperative opioid use after MMS. However, large, prospective studies are needed to solidify the generalizability and clinical utility of these findings.
Impact of radiological response and pattern of progression in patients with HCC treated by atezolizumab-bevacizumab
Authors: Campani Claudia , Vallot Ariane , Ghannouchi Haroun , Allaire Manon , Evain Manon , Sultanik Philippe , Sidali Sabrina , Blaise Lorraine , Thabut Dominique , Nahon Pierre , Seror Olivier , Ganne-Carrié Nathalie , Nault Jean-Charles , Wagner Mathilde , Sutter Olivier
Published: October 2023

Background and Aims:

We aim to assess the role of radiological response to atezolizumab-bevacizumab in patients with HCC to predict overall survival.

Approach and Results:

We retrospectively included patients with HCC treated by atezolizumab-bevacizumab in 2 tertiary centers. A retrospective blinded analysis was performed by 2 radiologists to assess Response Evaluation Criteria in Solid Tumor (RECIST 1.1) and modified RECIST (mRECIST) criteria at 12 weeks. Imaging response and treatment decisions in the multidisciplinary tumor board at 12 weeks were registered. Among 125 patients, 9.6% and 20.8% had a response, 39.2% and 35.2% had stable disease, and 51.2% and 44% had progression, according to RECIST 1.1 and mRECIST, respectively, with a substantial interobserver agreement (k coefficient=0.79). Metastasis was independently associated with a higher risk of progression. Patients classified as responders did not reach median survival, which was 16.2 and 15.9 months for patients classified as stable and 9.1 and 9.0 months for patients classified as progressors, in RECIST 1.1 and mRECIST criteria, respectively. We observed a wide variability in the identification of progression in the multidisciplinary tumor board in clinical practice compared with the blind evaluation by radiologists mainly due to discrepancy in the evaluation of the increase in size of intrahepatic lesions. The appearance of new extrahepatic lesions or vascular invasion lesions was associated with a worse overall survival (p=0.032).

Conclusions:

RECIST 1.1 and mRECIST criteria predict overall survival with more responders identified by mRECIST and the appearance of new extrahepatic lesion or vascular invasion was associated with a poor prognosis. A noticeable discrepancy was observed between patients classified as progressors at reviewing and the decision reached during the multidisciplinary tumor board.
A genetic basis of mitochondrial DNAJA3 in nonalcoholic steatohepatitis-related hepatocellular carcinoma
Authors: Chang Ching-Wen , Chen Yu-Syuan , Huang Chen-Hua , Lin Chao-Hsiung , Ng Wailap Victor , Chu Lichieh Julie , Trépo Eric , Zucman-Rossi Jessica , Siao Kevin , Maher Jacquelyn J. , Chiew Men Yee , Chou Chih-Hung , Huang Hsien-Da , Teo Wan-Huai , Lee I-Shan , Lo Jeng-Fan , Wang Xin Wei
Published: October 2023

Background and Aims:

NAFLD is the most common form of liver disease worldwide, but only a subset of individuals with NAFLD may progress to NASH. While NASH is an important etiology of HCC, the underlying mechanisms responsible for the conversion of NAFLD to NASH and then to HCC are poorly understood. We aimed to identify genetic risk genes that drive NASH and NASH-related HCC.

Approach and Results:

We searched genetic alleles among the 24 most significant alleles associated with body fat distribution from a genome-wide association study of 344,369 individuals and validated the top allele in 3 independent cohorts of American and European patients (N=1380) with NAFLD/NASH/HCC. We identified an rs3747579-TT variant significantly associated with NASH-related HCC and demonstrated that rs3747579 is expression quantitative trait loci of a mitochondrial DnaJ Heat Shock Protein Family (Hsp40) Member A3 (DNAJA3). We also found that rs3747579-TT and a previously identified PNPLA3 as a functional variant of NAFLD to have significant additional interactions with NASH/HCC risk. Patients with HCC with rs3747579-TT had a reduced expression of DNAJA3 and had an unfavorable prognosis. Furthermore, mice with hepatocyte-specific Dnaja3 depletion developed NASH-dependent HCC either spontaneously under a normal diet or enhanced by diethylnitrosamine. Dnaja3-deficient mice developed NASH/HCC characterized by significant mitochondrial dysfunction, which was accompanied by excessive lipid accumulation and inflammatory responses. The molecular features of NASH/HCC in the Dnaja3-deficient mice were closely associated with human NASH/HCC.

Conclusions:

We uncovered a genetic basis of DNAJA3 as a key player of NASH-related HCC.
Wnt/β-catenin and NFκB signaling synergize to trigger growth factor-free regeneration of adult primary human hepatocytes
Authors: Oliva-Vilarnau Nuria , Beusch Christian M. , Sabatier Pierre , Sakaraki Eirini , Tjaden Amelie , Graetz Lukas , Büttner Florian A. , Dorotea Debra , Nguyen My , Bergqvist Filip , Sundström Yvonne , Müller Susanne , Zubarev Roman A. , Schulte Gunnar , Tredup Claudia , Gramignoli Roberto , Tietge Uwe J.F. , Lauschke Volker M.
Published: October 2023

Background and Aims:

The liver has a remarkable capacity to regenerate, which is sustained by the ability of hepatocytes to act as facultative stem cells that, while normally quiescent, re-enter the cell cycle after injury. Growth factor signaling is indispensable in rodents, whereas Wnt/β-catenin is not required for effective tissue repair. However, the molecular networks that control human liver regeneration remain unclear.

Methods:

Organotypic 3D spheroid cultures of primary human or murine hepatocytes were used to identify the signaling network underlying cell cycle re-entry. Furthermore, we performed chemogenomic screening of a library enriched for epigenetic regulators and modulators of immune function to determine the importance of epigenomic control for human hepatocyte regeneration.

Results:

Our results showed that, unlike in rodents, activation of Wnt/β-catenin signaling is the major mitogenic cue for adult primary human hepatocytes. Furthermore, we identified TGFβ inhibition and inflammatory signaling through NF-κB as essential steps for the quiescent-to-regenerative switch that allows Wnt/β-catenin-induced proliferation of human cells. In contrast, growth factors, but not Wnt/β-catenin signaling, triggered hyperplasia in murine hepatocytes. High-throughput screening in a human model confirmed the relevance of NFκB and revealed the critical roles of polycomb repressive complex 2, as well as of the bromodomain families I, II, and IV.

Conclusions:

This study revealed a network of NFκB, TGFβ, and Wnt/β-catenin that controls human hepatocyte regeneration in the absence of exogenous growth factors, identified novel regulators of hepatocyte proliferation, and highlighted the potential of organotypic culture systems for chemogenomic interrogation of complex physiological processes.