bluuebunny/crossref_metadata_2025 huggingface dataset:
Direct estimation and inference of higher-level correlations from lower-level measurements with applications in gene-pathway and proteomics studies
Authors: Wang Yue , Shi Haoran
Published: August 2024

This paper tackles the challenge of estimating correlations between higher-level biological variables (e.g. proteins and gene pathways) when only lower-level measurements are directly observed (e.g. peptides and individual genes). Existing methods typically aggregate lower-level data into higher-level variables and then estimate correlations based on the aggregated data. However, different data aggregation methods can yield varying correlation estimates as they target different higher-level quantities. Our solution is a latent factor model that directly estimates these higher-level correlations from lower-level data without the need for data aggregation. We further introduce a shrinkage estimator to ensure the positive definiteness and improve the accuracy of the estimated correlation matrix. Furthermore, we establish the asymptotic normality of our estimator, enabling efficient computation of P-values for the identification of significant correlations. The effectiveness of our approach is demonstrated through comprehensive simulations and the analysis of proteomics and gene expression datasets. We develop the R package highcor for implementing our method.
Sensing Toxic Injustice: Exploring the Polluting Touch of Colonialism
Authors: Lam Anita , Kohm Steven
Published: August 2024

The bodies of missing and murdered Indigenous women and girls are often discovered at polluted sites in Winnipeg, Canada, including the Red River. Left at toxic sites that authorities deem environmentally dangerous, these women became untouchable in death, mired in sociocultural representations of disposability and wasting practices. We link murdered and missing Indigenous women and girls to the polluting effects of white settler colonialism especially pertaining to the degradation of Winnipeg’s waterways. As a means for enacting slow, environmental violence, current waste allocation practices remain tied to colonial systems that continue to harm Indigenous peoples. To foreground overlapping devaluations of Indigenous lands and people, we argue for a sensory criminology that is sensitized to the ongoing damage of colonial violence.
Post-Disaster Social Connectedness in Parent–Child Dyads: A Qualitative Investigation of Changes in Coping and Social Capital of Rural Australian Families Following Bushfires
Authors: Stribley Lisa , Krishnamoorthy Govind , Dallinger Vicki , Ma Jennifer , Nielsen Thomas , Bryce India , Rees Bronwyn , Morse Alyssa , Rogers Marg , Burton Lorelle
Published: August 2024

The increasing frequency of natural disasters, such as bushfires, pose significant challenges for countries like Australia. This research investigates the changes in social connectedness following a bushfire disaster in 2019 in the rural community of Cudlee Creek, South Australia, Australia. Research has repeatedly highlighted the importance of social connectedness, social capital and secure attachment relationships in mitigating post-disaster mental health concerns. This study utilised semi-structured interviews with eight parent–child dyads twenty months post-disaster to understand changes in parent–child relationships, the quality of extended family ties and the role of the broader community in recovery and coping. Reflexive thematic analysis revealed three themes: (i) differences in children and parents in preferred forms of social support; (ii) a thinning of previously available support and (iii) altered patterns of communication in the parent–child relationships. The findings highlight the complex interactions of multi-systemic and intersectional disadvantages on social isolation and loss of social capital following disasters. The results also highlight the influence of stoic beliefs on patterns of miscommunication in parent–child dyads in rural contexts. Implications for the implementation of community-wide post-disaster supports, sociometric approaches to mental health screening and assessment, and targeted interventions for rural families.
Myxodiaspory inAdenostemma brasilianum(Asteraceae): morphological and histochemical strategies for diaspore dispersion
Authors: Dosil Hiriart Florencia D , Hernández Marcelo P , Segura Luciano N , Katinas Liliana
Published: August 2024

Myxodiaspory, the extrusion of sticky substances by the diaspores (seeds, fruits, anthocarps, and parts of infrutescences), has several selective advantages, one of which is aiding the adherence of diaspores between feathers/fur of animals that transport them over short or long distances. The diaspores of Asteraceae have three structures that can contain sticky substances: exocarp epidermal cells, exocarp trichomes, and viscid pappus. The South American species Adenostemma brasilianum (Asteraceae) has all three features. We examined the anatomy, secreted substances, and mode of adhesion of the diaspores of A. brasilianum to understand its strategies for dispersion. The fruit comprises an exocarp with glandular trichomes arranged spirally and scarce nonglandular trichomes, two layers of mesocarp separated by phytomelanin, and an endocarp. The pappus has a basal ring, a stalk, and a head with glandular trichomes. The mucilage, secreted by the glandular trichomes of fruit and pappus, reacted positively to tests for pectins, essential oils, lipophilic substances, and gums. The test for tannins gave a homogeneous positive reaction in the phytomelanin area, and as droplets, in the outer mesocarp layer and in the exocarp. The whole capitulum of A. brasilianum is adapted for successful transportation of its diaspores via diaspore release, secretion, and positioning. We discuss the idea that the dispersal adaptive traits found here evolved as phylogenetic parallelisms in the family.
Clinical genetic testing in Parkinson’s disease should become part of routine patient care
Authors: Gan-Or Ziv
Published: August 2024

This scientific commentary refers to ‘Relevance of genetic testing in the gene-targeted trial era: the Rostock Parkinson’s Disease Study’ by Westenberger et al. (https://doi.org/10.1093/brain/awae188) and ‘Parkinson’s disease variant detection and disclosure: PD GENEration, a North American study’ by Cook et al. (https://doi.org/10.1093/brain/awae142).
Machine learning based on biological context facilitates the identification of microvascular invasion in intrahepatic cholangiocarcinoma
Authors: Xu Shuaishuai , Wan Mingyu , Ye Chanqi , Chen Ruyin , Li Qiong , Zhang Xiaochen , Ruan Jian
Published: August 2024

Intrahepatic cholangiocarcinoma is a rare disease associated with a poor prognosis, primarily due to early recurrence and metastasis. An important feature of this condition is microvascular invasion (MVI). However, current predictive models based on imaging have limited efficacy in this regard. This study employed a random forest model to construct a predictive model for MVI identification and uncover its biological basis. Single-cell transcriptome sequencing, whole exome sequencing, and proteome sequencing were performed. The area under the curve of the prediction model in the validation set was 0.93. Further analysis indicated that MVI-associated tumor cells exhibited functional changes related to epithelial–mesenchymal transition and lipid metabolism due to alterations in the nuclear factor-kappa B and mitogen-activated protein kinase signaling pathways. Tumor cells were also differentially enriched for the interleukin-17 signaling pathway. There was less infiltration of SLC30A1+ CD8+ T cells expressing cytotoxic genes in MVI-associated intrahepatic cholangiocarcinoma, whereas there was more infiltration of myeloid cells with attenuated expression of the major histocompatibility complex II pathway. Additionally, MVI-associated intercellular communication was closely related to the SPP1–CD44 and ANXA1–FPR1 pathways. These findings resulted in a brilliant predictive model and fresh insights into MVI.
Case report: severe hypertrophic cardiomyopathy in a female neonate caused by de novo variant in NDUFB11
Authors: Tariq Javeria , Townsend Madeleine , Parikh Sumit , Bennett Jeffrey
Published: August 2024

Background

Hypertrophic cardiomyopathy in the neonate has a diverse genetic background, and non-sarcomeric variants may not be identified on commercial genetic testing panels. NDUFB11 is an X-linked mitochondrial Complex I protein and is known to cause histiocytoid cardiomyopathy but has not been described in female infants with hypertrophic cardiomyopathy. We present this first reported case of obstructive hypertrophic cardiomyopathy in a female neonate secondary to a pathogenic variant in NDUFB11.

Case summary

A term female neonate presented following a prenatal diagnosis of biventricular hypertrophy and growth restriction. She developed lactic acidosis after birth and whole-genome sequencing identified a de novo variant in the mitochondrial Complex I gene, NDUFB11 (c.391G>A, p.Glu131Lys). There was progression of left ventricular hypertrophy and obstruction, with rapid development of heart failure symptoms. She was unresponsive to beta-blocker medical therapy and was not suitable for advanced mechanical support. There was subsequent clinical deterioration resulting in death by 3 months of age.

Discussion

Hemizygous variants in NDUFB11 have been associated with hypertrophic cardiomyopathy in male infants previously, and skewed X-linked inactivation likely resulted in the presentation described here in a female infant. This variant was not identifiable by commercial cardiomyopathy panels. We highlight the importance of rapid whole-genome sequencing in cases of infantile hypertrophic cardiomyopathy and the importance of genetic diagnosis in guiding prognosis and care for these individuals.
Two-station Lg wave attenuation tomography in Eastern Asia
Authors: Chen Youlin , Xu Xiwei , Xie Jiakang , Ghalib Hafidh A A , Liang Shanshan
Published: August 2024

Utilizing over 31 000 Lg waveforms from 136 crustal earthquakes recorded at 346 regional stations, we conduct detailed tomographic mappings of the Lg Q structure across Eastern Asia in a frequency range from 0.5 to 4.0 Hz. By improving the standard two-station (TS) method, we effectively correct non-unity site response ratios using site responses estimated at individual stations. This innovative approach combines the flexible recording geometry of the TS method with the precision of reversed two-station (RTS) and reversed two-event (RTE) methods, producing a comprehensive data set devoid of source and site effects for Q tomography. To address unsolvable 3-D structural effects in the Lg spectral amplitude modelling, we justify these as modelling errors with a Gaussian distribution. This approach supports our SVD-based tomographic method, allowing for effective inversion of attenuation parameters and quantitative assessment of model resolution and errors. Our results reveal a complex relationship between Lg Q and the tectonic characteristics of Eastern Asia. In well-resolved regions, low Qo (1-Hz Q) values correspond to areas with high heat flow, partial melt, thick sediment and recent tectonic-thermal activities, in contrast to high Qo values in stable, ancient crusts lacking recent tectonic activity. Rift basins are characterized by low Lg Qo, whereas flexural basins generally have high Qo basements. We also note that post-formation factors, such as sedimentation and crustal flow intrusion, significantly impact Qo values. Furthermore, Lg Q shows a complex frequency relationship, though the power-law approximation with positive power η remains useful. The frequency dependence power η is inversely related to Qo: the regions with low Qo typically have high η and vice versa. This study provides reliable attenuation tomographic and relative site response models for Lg waves in Eastern Asia, pertinent for relative geophysical studies.
7. Welfare and Labour
Authors: Porte Caroline de la , Madama Ilaria
Published: August 2024

This chapter argues that welfare states and labour markets constitute a central issue in European political economy. It then discusses the main theoretical and empirical theories and concepts in regulating social policies and labour markets in the multi-tiered EU institutional setting. Under the Economic and Monetary Union (EMU), Member States aimed to enhance labour market participation, while modernizing their welfare states and maintaining a high level of social standards. The chapter presents three case studies on social investment. It also looks into the re-regulatory approach embodied in the European Pillar of Social Rights and the possibilities for selected social policies being fiscally supported through the Next Generation EU.
1. The Study of Global Political Economy
Authors: Ravenhill John , Hannah Erin
Published: August 2024

The multilateral economic order is facing several major challenges, including the persistent impact of COVID-19 on global output and growth, the shift towards decoupling and fragmentation in economic relations with China, the Russian invasion of Ukraine, the disruption of global value chains, and the rise of conservative populism. Together these challenge the principles of liberal internationalism and provide a clear illustration of the relationship between trade, finance, international institutions, and the difficulties governments face in coping with the problems generated by complex interdependence. This chapter explores past and emerging challenges in the Global Political Economy (GPE) through a range of theoretical lenses. It also pays attention to the significance of race, colonialism, gender, and the intersections of GPE with everyday life.
8. The Evolution of the International Monetary and Financial System
Authors: Helleiner Eric
Published: August 2024

The international monetary and financial system plays a central role in the global political economy (GPE). This work examines how the contemporary system is still shaped by many legacies of the Bretton Woods monetary and financial order established in 1944 and the political priorities of its architects. That order has also undergone several pivotal transformations. An important gradual change has been dramatic globalisation of financial markets since the 1960s. A more sudden one was the abandonment of the Bretton Woods gold exchange standard in 1971. The dollar standard that replaced it faces a number of challenges in the contemporary era. Also significant have been the breakdown of the adjustable peg exchange rate regime in the early 1970s as well as regionalization and decentralization trends.
15. The Global Political Economy of North–South Relations: A View from the South
Authors: Singh J. P.
Published: August 2024

Some major advances in the betterment of human life have been made in recent years but at the cost of accelerated climatic change and through uneven means of development. A reduction in child mortality, a rise in literacy and education, and by some measures the fewest people live in extreme poverty than they ever have before. Nevertheless, inequality on the multiple axes of health, income, environment, gender, education, technology, finance, shelter, food, water, and various other issues concerning access persist. This work examines efforts by various actors to deal with these problems with mixed and contested results. The analysis is centered around a key question: who benefits and why from globalised development? In so doing, it examines various development theories, traces the history of globalisation-led development post-WWII, and scrutinises contemporary challenges like the Great Recession and the Global Refugee Crisis, in order to understand the crisis prone tendencies of globalisation and its linkages to everyday practices in global political economy.
12. Poliheuristic Theory
Authors: Brummer Klaus , Oppermann Kai
Published: August 2024

This chapter looks into the Poliheuristic Theory of Decision-Making. This theory seeks to explain both the processes and the outcomes of foreign policy. The chapter then explains the theory's two-stage analytical framework and its subsequent shortcomings and empirical analysis. Poliheuristic Theory integrates insights from both cognitive and rationalist perspectives on foreign policy decision-making. A number of articles that have used Poliheuristic Theory in non-Western settings have deliberately used non-Western contexts to explore and expand the theory's context-sensitivity, applicability, and explanatory scope. The chapter cites that further research is needed concerning the applicability of Poliheuristic Theory to group decision-making, which correlates to the aggregation challenge cognizant to political dynamics in a group setting.
3. Liberalism and foreign policy
Authors: Doyle Michael W.
Published: August 2024

For more than two centuries, liberal countries have tended to maintain peaceful relations with each other. Liberal democracies are each other’s natural allies. They tend to respect and accommodate other democratic countries and negotiate rather than escalate their inter-liberal disputes. This provides a positive incentive to try to preserve and expand the liberal zone of peace. And that is the fundamental postulate of liberal foreign policy. But liberalism has also proved to be a dangerous guide to foreign policy, often exacerbating tensions with non-liberal states. Expanding liberalism can sometimes provoke danger and war. This chapter thus addresses a large and perplexing foreign policy question central to all democracies: Can the liberal peace be effectively preserved and expanded without provoking unnecessary danger and inflicting unnecessary harm? The chapter also addresses how scholars have analysed liberalism’s effects, distinguishing three key interpretations of liberal foreign policy: individualist, commercial, and republican.
5. Discourse analysis, post-structuralism, and foreign policy
Authors: Hansen Lene
Published: August 2024

This chapter provides an introduction to how discourse analysis can be used to study foreign policy. In the study of international relations, discourse analysis is associated with post-structuralism, a theoretical approach that shares realism’s concern with states and power, but differs from realism’s assumption that states are driven by self-interest. It also takes a wider view of power than realists normally do. Post-structuralists hold that states, and other political entities, strive to uphold particular visions of themselves and that they do so through policy discourses. Foreign policy discourse plays a crucial role in the construction of these visions as it draws a line between the state and what makes up its identity on the one hand, and that which is different from, and outside the scope of, the state on the other. Taking poststructuralist assumptions to the study of foreign policy implies a focus on the way that foreign policy decisions are legitimated or undermined within the wider public sphere. Epistemologically and methodologically, to understand foreign policy as discourse implies analysis of texts, and this chapter lays out the most important insights and challenges that come with this form of analysis.
7. Postcolonialism and foreign policy
Authors: Chacko Priya , Thakur Vineet
Published: August 2024

This chapter is an introduction to applying a postcolonial lens to foreign policy analysis. It provides helpful definitions of key terms and concepts related to postcolonialism and follows it with a brief overview of the history of postcolonial studies. Thereafter, it lays out the key assumptions associated with postcolonial approaches in International Relations in general, and foreign policy analysis in particular. Through detailed examples, this chapter illustrates how a postcolonial lens helps us critically think through structures, policies and performances that shape foreign policy and examine the ways in which colonial and racial histories continue to inform our present.
10. The national security state
Authors: Patman Robert G.
Published: August 2024

This chapter traces the development of the national security state as a US foreign policy actor to the early stages of the Cold War. However, the US national security state persisted in the post-Cold War era and after 9/11 experienced a massive expansion in what was called the global war on terrorism. The central argument that emerges from the chapter is that the model of the national security state is not only a potential threat to US democracy, but also constitutes an impediment to a US recognition in the 21st century that key security problems increasingly require multilateral solutions.
13. Aid diplomacy
Authors: Williams David
Published: August 2024

This chapter examines the role and significance of foreign aid in the foreign policies of both aid donors and aid recipients. The chapter starts by discussing what is meant by ‘aid’, and it goes on to look at the varied motivations for the provision of foreign aid before exploring some of the dilemmas and issues that arise within aid diplomacy, for both aid donors and aid recipients.
20. The Arab/Persian Gulf as a subregional security complex
Authors: Hassaniyan Allan , Stansfield Gareth
Published: August 2024

The Arab/Persian Gulf, a strategic subcomplex of the Middle East and North Africa, is a dynamic region experiencing a wide range of changes. Using the concept of the subregional security complex, this chapter focuses on security, inter-state rivalry and relationships within the Gulf, and how they affect regional security. It explains the regional security complex in the Arab/Persian Gulf through reflection on past and present foreign policy choices and behaviours of states in the region. The regional security complex theory is used to analyse the complex dynamics caused by inter-state alignment and cooperation, rivalry and competition, and foreign penetration. The chapter then examines regional activities, inter-state rivalry and competition, and how these interrelated factors have affected security and stability in the Gulf subregion.
21. The European Union
Authors: Aggestam Lisbeth
Published: August 2024

Membership of the European Union (EU) commits member states to cooperate on foreign policy and speak with a common European voice on international issues. Since the end of the Cold War, the European Union has developed a wide range of economic, diplomatic and military capabilities in foreign policy. The EU has gradually expanded its competencies, power, and actorness beyond what is normally associated with an international intergovernmental organization. This has spurred a lively academic debate about how to conceptualize the EU as an international actor and to what extent the EU represents a deeper process of foreign policy change and transformation. This chapter examines EU enlargement as one of the EU’s most important foreign policy instruments to achieve peace and stability in Europe. EU enlargement is an interesting case for examining the complexity of the EU as a foreign policy actor as it combines both supranational and intergovernmental methods of policy-making. The Eastern enlargement of 2004/2007 moved the EU’s border further east and into the regions that Russia considers its geopolitical spheres of interest.
1. Introduction
Authors: Costello Rory
Published: August 2024

This chapter begins by introducing the subject of comparative European politics. It describes the scope and main themes of the book and explains the rationale for the countries selected for inclusion. It discusses the prevalence of democracy in Europe and introduces some of the key features and terms associated with European democracies. A number of recent developments that have challenged the political status quo across the continent are highlighted. The chapter also introduces the main goals and methods of comparative politics research and explains the features of the book that are designed to help students to carry out their own research. It concludes with an outline of the book and a brief summary of its three main sections.
12. National Governments in the EU Political System
Authors: Piattoni Simona
Published: August 2024

The chapter describes the institutional configuration of the European Union (EU), focusing in particular on how national governments work together through the EU institutions. The EU is a political system in which many institutional and non-institutional, individual, and collective actors interact, but cannot yet be considered a state given that it lacks policy competence in some defining state areas such as defence, law and order, culture and education, and taxation. Many scholars have therefore converged on a description of the EU as a multilevel system of governance, in which multiple governmental levels and non-governmental actors interact differently in different policy areas, giving rise to flexible governance arrangements that do not crystallize into a single permanent and uniform constitutional configuration. Still, its institutional setup can be usefully analysed by reference to conventional state types and by investigating individual policy regimes.
5. Structural Realism
Authors: Mearsheimer John J.
Published: August 2024

This chapter examines why states pursue power from the perspective of structural realism. It considers a body of realist theories that argue that states have deep concern for the balance of power and compete among themselves either to gain power at the expense of others or at least to make sure they do not lose power. This competition for power makes for a dangerous world where states sometimes fight each other. There are, however, important differences among structural realists. The chapter first explains why states want power and how much power they want before discussing the causes of war. These theoretical issues are illuminated with a case study that assesses whether China can rise peacefully according to offensive realism vs defensive realism. Along the way, concepts such as the security dilemma, offence–defence balance, central war, buck-passing, unipolarity, bipolarity, multipolarity, and deterrence are analysed.
15. Normative International Relations Theory
Authors: Erskine Toni
Published: August 2024

This chapter deals with normative international relations theory, a field of study that relies on a variety of approaches and theories to explore moral expectations, decisions, and dilemmas in world politics. Normative IR theory has adopted—and adapted—conceptual categories such as communitarianism and cosmopolitanism from political theory. It also borrows from moral philosophy to designate different types of ethical reasoning, such as deontology and consequentialism. The chapter begins with an overview of the history, influences, and some of the categories that normative IR theory brings to the study of international relations. It then examines the ways in which normative IR theory engages with the hidden ethical assumptions of a range of IR approaches. The case study considers the ethics of war in two scenarios: the war in Iraq, and the Demilitarized Zone (DMZ) at the border between North and South Korea.
16. International Relations, the Environment, and Green Theory
Authors: Eckersley Robyn , Corry Olaf
Published: August 2024

This chapter examines how environmental concerns have influenced International Relations theory. It first provides a brief overview of the ecological crisis and the emergence of green theorizing in the social sciences and humanities in general, along with the status and impact of environmental issues and green thinking in IR theory. It then investigates green theory’s transnational turn and how it has become more global, while critical IR theory has become increasingly green. It also considers the different ways in which environmental issues have influenced the evolution of traditional IR theory. In the case study, climate change is explored to highlight the diversity of theoretical approaches, including the distinctiveness of different green approaches, in understanding how the international is relevant to global environmental crisis.
Jacobian Schemes Arising From Hypersurface Arrangements in ℙn
Authors: Migliore Juan , Nagel Uwe
Published: August 2024

Freeness is an important property of a hypersurface arrangement, although its presence is not well understood. A hypersurface arrangement in ${\mathbb{P}}^{n}$ is free if $S/J$ is Cohen–Macaulay (CM), where $S = K[x_{0},\ldots ,x_{n}]$ and $J$ is the Jacobian ideal. We study three related unmixed ideals: $J^{top}$, the intersection of height two primary components, $\sqrt{J^{top}}$, the radical of $J^{top}$, and when the $f_{i}$ are smooth we also study $\sqrt{J}$. Under mild hypotheses, we show that these ideals are CM. This establishes a full generalization of an earlier result with Schenck from hyperplane arrangements to hypersurface arrangements. If the hypotheses fail for an arrangement in projective $3$-space, the Hartshorne–Rao module measures the failure of CMness. We establish consequences for the even liaison classes of $J^{top}$ and $\sqrt{J}$.
Bridging the Gap Between Labour Law and Company Law: Wedderburn’s Legacy: An Appreciation
Authors: Villiers Charlotte
Published: August 2024

The paper surveys the extensive writings of the late Professor Lord Wedderburn and explores the interactions between company law and labour law. A set of case studies illustrates labour law’s relative weakness in the contemporary corporate law context. Whilst it does change over time, company law has largely remained consistent with its two fundamental principles of separate legal personality and limited liability and its complementary prioritisation of the shareholders’ interests. These stable features provide a foundation that grants powerful corporate actors considerable freedom to pursue their interests and to organise their corporations however they please with little regard for those providing labour. Labour law finds itself constantly having to adapt to changing economic (and connected political) realities, fraying further the already threadbare protections for workers, especially in the context of global trade. With modern globalisation and financialization, a variety of “shareholders” and increasingly byzantine corporate structural arrangements have emerged presenting few opportunities to mitigate the impacts of their harmful activities. Investors and managers extract value with exploitative and detrimental consequences for the workers and other stakeholders. Fundamental reforms to company law are required for more effective workers’ voice and protection. Key words Lord Wedderburn, company law, labour law, employment law.
Bacteroidia and Clostridia are equipped to degrade a cascade of polysaccharides along the hindgut of the herbivorous fish Kyphosus sydneyanus
Authors: Facimoto Cesar T , Clements Kendall D , White W Lindsey , Handley Kim M
Published: August 2024

The gut microbiota of the marine herbivorous fish Kyphosus sydneyanus are thought to play an important role in host nutrition by supplying short-chain fatty acids (SCFAs) through fermentation of dietary red and brown macroalgae. Here, using 645 metagenome-assembled genomes (MAGs) from wild fish, we determined the capacity of different bacterial taxa to degrade seaweed carbohydrates along the gut. Most bacteria (99%) were unclassified at the species level. Gut communities and CAZyme-related transcriptional activity were dominated by Bacteroidia and Clostridia. Both classes possess genes CAZymes acting on internal polysaccharide bonds, suggesting their role initiating glycan depolymerization, followed by rarer Gammaproteobacteria and Verrucomicrobiae. Results indicate that Bacteroidia utilize substrates in both brown and red algae, whereas other taxa, namely, Clostridia, Bacilli, and Verrucomicrobiae, utilize mainly brown algae. Bacteroidia had the highest CAZyme gene densities overall, and Alistipes were especially enriched in CAZyme gene clusters (n = 73 versus just 62 distributed across all other taxa), pointing to an enhanced capacity for macroalgal polysaccharide utilization (e.g., alginate, laminarin, and sulfated polysaccharides). Pairwise correlations of MAG relative abundances and encoded CAZyme compositions provide evidence of potential inter-species collaborations. Co-abundant MAGs exhibited complementary degradative capacities for specific substrates, and flexibility in their capacity to source carbon (e.g., glucose- or galactose-rich glycans), possibly facilitating coexistence via niche partitioning. Results indicate the potential for collaborative microbial carbohydrate metabolism in the K. sydneyanus gut, that a greater variety of taxa contribute to the breakdown of brown versus red dietary algae, and that Bacteroidia encompass specialized macroalgae degraders.
The Need for Dynamic Cybersecurity
Authors: Agyepong Enoch
Published: August 2024

Enoch Agyepong CITP, Cybersecurity Architect at Airbus, explains why cyber security frameworks (CSFs) alone are not a panacea for dealing with cyber attacks.
Internships: How to Get Your Foot in the Door
Authors: Iqbal Sobia , Daramola Kolawole
Published: August 2024

Sobia Iqbal and Kolawole Daramola from the BCS Early Careers Group discuss how to land your dream internship and begin your IT career in the best way.
Software Architecture Insights
Authors: Leigh Andrew
Published: August 2024

Dr Andrew Leigh MBCS CITP reflects on 25 years of professional experience as a software architect and offers his insights and a reading list of recommendations.
George Mallen and the Ecogame
Authors: Mason Catherine
Published: August 2024

CAS committee member Catherine Mason MBCS shares the history of the society and the contributions of the Specialist Group's co-founder and President Emeritus George Mallen upon the release of her new book Creative Simulations: George Mallen and the Early Computer Arts Society.
A pharmacometric multistate model for predicting long-term treatment outcomes of patients with pulmonary TB
Authors: Lin Yu-Jou , Zou Yuanxi , Karlsson Mats O , Svensson Elin M
Published: August 2024

Background

Studying long-term treatment outcomes of TB is time-consuming and impractical. Early and reliable biomarkers reflecting treatment response and capable of predicting long-term outcomes are urgently needed.

Objectives

To develop a pharmacometric multistate model to evaluate the link between potential predictors and long-term outcomes.

Methods

Data were obtained from two Phase II clinical trials (TMC207-C208 and TMC207-C209) with bedaquiline on top of a multidrug background regimen. Patients were typically followed throughout a 24 week investigational treatment period plus a 96 week follow-up period. A five-state multistate model (active TB, converted, recurrent TB, dropout, and death) was developed to describe observed transitions. Evaluated predictors included patient characteristics, baseline TB disease severity and on-treatment biomarkers.

Results

A fast bacterial clearance in the first 2 weeks and low TB bacterial burden at baseline increased probability to achieve conversion, whereas patients with XDR-TB were less likely to reach conversion. Higher estimated mycobacterial load at the end of 24 week treatment increased the probability of recurrence. At 120 weeks, the model predicted 55% (95% prediction interval, 50%–60%), 6.5% (4.2%–9.0%) and 7.5% (5.2%–10%) of patients in converted, recurrent TB and death states, respectively. Simulations predicted a substantial increase of recurrence after 24 weeks in patients with slow bacterial clearance regardless of baseline bacterial burden.

Conclusions

The developed multistate model successfully described TB treatment outcomes. The multistate modelling framework enables prediction of several outcomes simultaneously, and allows mechanistically sound investigation of novel promising predictors. This may help support future biomarker evaluation, clinical trial design and analysis.
Antimicrobial prescribing in referral hospitals in Timor-Leste: results of the first two national point prevalence surveys, 2020–21
Authors: Ximenes Guilherme , Saha Sajal K , Guterres Helio , Vieira Adriano , Harris Lisa , Mahony Michelle , Dos Santos Agata , Toto Lucia , Amaral Elfiana , Spargo Jessie C , Tay Sze Yen , Amaral Salvador , Champlin Karen , Draper Anthony D K , Francis Joshua R , Yan Jennifer , Lynar Sarah A
Published: August 2024

Objectives

To describe antimicrobial use (AMU) in patients admitted to hospitals in Timor-Leste.

Methods

In 2020 and 2021, we undertook antimicrobial prescribing point prevalence surveys across all six hospitals in Timor-Leste (one national and five municipal) to describe AMU and appropriateness in admitted patients.

Results

In 2020, 291/394 (73.9%) surveyed patients had been prescribed antimicrobials, compared with 260/403 (64.5%) in 2021 (P = 0.004). Most (309/551; 56.1%) were prescribed one antimicrobial, and 179/551 (32.5%) were prescribed two. The most commonly prescribed antibiotics were ceftriaxone (38.5% in 2020, 41.5% in 2021) and ampicillin (35.7% in 2020, 32.3% in 2021), followed by gentamicin, metronidazole and cloxacillin. Reserve antibiotics like meropenem and vancomycin were minimally used. Of all antimicrobial prescriptions, 70.8% were deemed appropriate in 2020 and 69.1% in 2021. Antimicrobial prescriptions for surgical and post-partum prophylaxis were frequently deemed inappropriate [37/50 (74.0%) and 39/44 (88.6%) prescriptions, respectively].

Conclusions

Most patients admitted to hospital in Timor-Leste are prescribed antimicrobials, and approximately one-third of these prescriptions are inappropriate. However, this was in the context of limited local guideline availability at the time of surveys and limited microbiological culture capacity outside of the capital, Dili. Improved microbiological guidance, iterative guideline revisions based on local antimicrobial resistance (AMR) surveillance data, and enhanced stewardship activities including further point prevalence studies, could improve antimicrobial use, optimize patient outcomes and reduce AMR in Timor-Leste.
Glycated Albumin to Predict Adverse Neonatal Outcomes among Women with Diabetes and Overweight or Obese Body Mass Index
Authors: Powers Carson Jennifer , Arora Jyoti , Carter Ebony
Published: August 2024

Background

Glycated albumin (GA) has shown promise in predicting risk of adverse neonatal outcomes (ANO) in pregnant women with type 2 diabetes (T2DM) and gestational diabetes (GDM). However, previous studies showing a negative correlation between GA and body mass index (BMI) suggest that lower predictive cutoffs may be needed in populations with elevated BMI.

Methods

We performed a case-control study of prospectively enrolled pregnant women with T2DM or GDM and BMI ≥25 kg/m2 matched to biobanked controls without diabetes. Serum collected during the second and/or third trimesters was used to measure the percentage of GA (% GA). Receiver operating characteristic (ROC) curves were used to examine % GA to predict an ANO composite, including macrosomia, hypoglycemia, respiratory distress syndrome, and/or hyperbilirubinemia for the second and third trimesters.

Results

The median BMIs for cases and controls were 34.0 and 31.0 kg/m2, respectively. The area under the ROC curve to predict the ANO composite was significant for second trimester values but ambiguous for third trimester due to its wide 95% CI. A cutoff of 12.3% GA during second trimester showed 100% sensitivity and 73% specificity. Transference of previously published reference ranges did not validate, suggesting lower ranges are needed for women with overweight/obesity.

Conclusions

In this pilot study, % GA shows promise to stratify pregnant patients with diabetes and obesity into risk categories for ANO with excellent predictive ability in the second trimester. If this holds in larger studies, using second trimester % GA could allow additional intervention to improve blood glucose control and minimize ANO.
Motivations behind complementary and alternative medicine use in patients with Crohn’s disease and ulcerative colitis
Authors: Klemm Natasha , Trasolini Roberto , Bressler Brian , Rosenfeld Gregory , Almasan Gina , Leung Yvette
Published: August 2024

Background

Complementary and alternative medicine (CAM) use is common in inflammatory bowel disease (IBD) patients and impacts compliance with conventional treatment. Gastroenterologists should understand the motivational factors of CAM use—factors that push patients away from standard therapy or pull towards CAM. Our study describes the motivations behind CAM use for IBD and evaluates differences between Crohn’s disease (CD) and ulcerative colitis (UC) patients.

Methods

Retrospective cohort survey of patients over 18 years old with IBD, evaluated by gastroenterologists at a tertiary care referral centre from January 1 to December 31, 2019. Only patients who reported CAM use were included. Chi-square and independent t-tests were performed and P-value <0.05 was significant.

Results

Of the 230 completed surveys, 193 reported CAM use (CD: 57.5% vs UC: 42.5%). Demographics, disease duration, and hospitalizations were similar, but CD patients had lower SIBDQ scores (CD: 48.1 vs UC: 53.5, P < 0.001). Both groups were largely influenced by their social network to use CAM (CD: 33% vs UC: 31.3%) and did not feel well informed about CAM (87.4%). CD and UC patients had similar push and pull factors. Push factors included lack of improvement (39%) and side effects (20%) with conventional treatment. Pull factors included the desire for a holistic approach (21%) and to improve mood (35%). UC patients wanted a natural approach to treat their IBD, which nearly reached significance (P = 0.049). Most patients hoped fatigue 62.7%, and diarrhoea 61.7% would improve with CAM, but more CD patients wanted to improve their appetite (P = 0.043).

Conclusion

Despite differences in QoL, push and pull motivations for CAM use did not differ between CD and UC patients. Most users do not feel well informed of CAM and ongoing dialogue is important for patient-centred care.
When criminality begets crime: the role of elected politicians in India
Authors: Prakash Nishith , Sahoo Soham , Saraswat Deepak , Sindhi Reetika
Published: August 2024

This article examines the effect of electing criminally accused politicians on crime in India, considering the severity of their alleged offenses. Employing an instrumental variable approach that exploits the quasi-random variation in outcomes of close elections between candidates with and without criminal accusations, we find that a standard deviation (SD) increase in the share of criminally accused leaders in institutionally weaker states leads to a 0.05 SD rise in yearly reported crimes. Leaders accused of serious crimes have a more pronounced effect on crime outcomes, including crimes against women. Crucially, leaders accused of serious crimes also exert a negative influence on female labor force participation, underlining their detrimental impact on socioeconomic welfare. Our findings highlight the significance of considering the nature and severity of criminal accusations when evaluating the impact of criminally accused politicians on crime and society.
Social vulnerability and survival in 112 000 adolescents and young adults with cancer: a population-based study
Authors: Tortolero Guillermo A , Betts Andrea C , Suragh Tiffany A , Pruitt Sandi L , Roth Michael E , Murphy Caitlin C
Published: August 2024

Evidence suggests neighborhood-level factors contribute to cancer outcomes, although most research focuses on pediatric and adult populations. Using population-based data from the Texas Cancer Registry, we examined neighborhood-level social vulnerability, a composite measure of 14 census tract-level social risk factors, and survival among 112 142 adolescents and young adults with cancer (AYAs, age 15-39 years). We estimated 1-, 5-, and 10-year overall survival by quintile of social vulnerability and used Cox proportional hazards models (2-sided significance testing) to estimate the association between social vulnerability and all-cause mortality. Survival decreased as social vulnerability increased; for example, 5-year survival was 86.5% (95% confidence interval [CI] = 85.1 to 87.0) in the least vulnerable quintile compared to 74.0% (95% CI = 73.4 to 74.5) in the most vulnerable quintile. Social vulnerability was associated with all-cause mortality in adjusted models (highest vs lowest quintile: adjusted hazard ratio [aHR] = 1.55, 95% CI = 1.48 to 1.63). Achieving equity in AYAs’ survival requires interventions to address neighborhood disparities.
The transcription factor EjNAC5 regulates loquat fruit chilling lignification
Authors: Huang Yiqing , Liang Zihao , Lu Jiao , Zhang Mengxue , Cao Xizhi , Hu Ruoqian , Li Dongdong , Grierson Donald , Chen Wenbo , Zhu Changqing , Wu Di , Shi Yanna , Chen Kunsong
Published: August 2024

Changes in both lignin biosynthesis and DNA methylation have been reported to be associated with chilling stress in plants. When stored at low temperatures, red-fleshed loquat is prone to lignification, with increased lignin content and fruit firmness, which has deleterious effects on taste and eating quality. Here, we found that 5 °C storage mitigated the increasing firmness and lignin content of red-fleshed ‘Dahongpao’ (‘DHP’) loquat fruit that occurred during 0 °C storage. EjNAC5 was identified by integrating RNA sequencing with whole-genome bisulfite sequencing analysis of ‘DHP’ loquat fruit. The transcript levels of EjNAC5 were positively correlated with changes in firmness and negatively correlated with changes in DNA methylation level of a differentially methylated region in the EjNAC5 promoter. In white-fleshed ‘Baisha’ (‘BS’) loquat fruit, which do not undergo chilling-induced lignification at 0 °C, the transcripts of EjNAC5 remained low and the methylation level of the differentially methylated region in the EjNAC5 promoter was higher, compared with ‘DHP’ loquat fruit. Transient overexpression of EjNAC5 in loquat fruit and stable overexpression in Arabidopsis and liverwort led to an increase in lignin content. Furthermore, EjNAC5 interacts with EjERF39 and EjHB1 and activates the transcription of Ej4CL1 and EjPRX12 genes involved in lignin biosynthesis. This regulatory network involves different transcription factors from those involved in the lignification pathway. Our study indicates that EjNAC5 promoter methylation modulates EjNAC5 transcript levels and identifies novel EjNAC5–EjERF39–Ej4CL1 and EjNAC5–EjHB1–EjPRX12 regulatory modules involved in chilling induced-lignification.
The evolution of ovarian somatic cells characterized by transcriptome and chromatin accessibility across rodents, monkeys, and humans
Authors: Zhang Qiancheng , Sun Fengyuan , Zhang Ruifeng , Zhao Donghong , Zhu Ran , Cheng Xin , Long Xin , Hou Xinling , Yan Rui , Cao Yu , Guo Fan , Yan Long , Hu Yuqiong
Published: August 2024

The ovary plays a crucial role in the reproductive system of female mammals by producing mature oocytes through folliculogenesis. Non-human model organisms are extensively utilized in research on human ovarian biology, thus necessitating the investigation of conservation and divergence in molecular mechanisms across species. In this study, we employed integrative single-cell analysis of transcriptome and chromatin accessibility to identify the evolutionary conservation and divergence patterns of ovaries among humans, monkeys, mice, rats, and rabbits. Our analyses revealed that theca cells exhibited the most significant changes during evolution based on scRNA-seq and scATAC-seq datasets. Furthermore, we discovered common cis-regulatory architectures in theca cells across species by conducting joint analyses of scRNA-seq and scATAC-seq datasets. These findings have potential applications in non-human biomedical and genetic research to validate molecular mechanisms found in human organisms. Additionally, our investigation into non-coding genomic regions identified intergenic highly transcribed regions (igHTRs) that may contribute to the evolution of species-specific phenotypic traits. Overall, our study provides valuable insights into understanding the molecular characteristics of adult ovaries while offering new perspectives for studying human ovarian physiology and diseases.