bluuebunny/crossref_metadata_2025 huggingface dataset:
Quieting the Storm: Hypoxia as a Strategy to Boost UC-MSC Therapies for Neonatal Hypoxic-Ischemic Encephalopathy
Authors: Serrenho Inês , Mendes Vera , Caramelo Inês , Cardoso Carla M. , Manadas Bruno , Baltazar Graça
Published: January 2025

Integrating stem cell therapies into clinical settings faces several challenges, particularly in achieving the high cell yields necessary for attaining therapeutic doses. Preconditioning with hypoxic conditions has shown promise in enhancing the UC-MSCs reparative capabilities of the central nervous system. Recent evidence suggests that oxygen concentration and exposure duration can shape MSCs’ phenotypes, supporting the need for further optimization of this strategy in a way to achieve maximal repair. In this study, we assessed the effects of both prolonged mild hypoxia (MH; 5% oxygen for 48 hours) and short severe hypoxia (SSH; 0.1% oxygen for 24 hours) on UC-MSCs’ ability to alleviate motor and cognitive deficits in a rodent model of neonatal HIE. Our results show that short, severe hypoxia led to more improvements in functional recovery than prolonged mild hypoxia, supporting that specific preconditioning parameters are crucial in maximizing UC-MSC therapeutic potential. To investigate the molecular effects of hypoxia-preconditioned MSCs in the neonatal brain post-HIE, we employed untargeted proteomics on ipsilesional brain samples from control, HIE, HIE treated with naïve UC-MSCs, and HIE treated with SSH-preconditioned UC-MSCs groups, 30 days after lesion induction. This approach identified protein signatures related to injury and therapeutic intervention. Pathway enrichment analysis further revealed that administration of UC-MSCs preconditioned with short severe hypoxia significantly impacted neural signaling, protein synthesis, and energy metabolism pathways, pointing to long-term mechanisms that may support neuronal repair. These findings enhance our understanding of hypoxia-preconditioning in MSCs therapy in driving a positive therapeutic response, supporting the development of more effective and feasible treatments for neonatal HIE.
Three-dimensional calculations of positron creation in supercritical collisions of heavy nuclei
Authors: Dulaev N. K. , Telnov D. A. , Shabaev V. M. , Kozhedub Y. S. , Ma X. , Maltsev I. A. , Popov R. V. , Tupitsyn I. I.
Published: January 2025

Energy-angle differential and total probabilities of positron creation in slow supercritical collisions of two identical heavy nuclei are calculated beyond the monopole approximation. The time-dependent Dirac equation (TDDE) for positrons is solved using the generalized pseudospectral method in modified prolate spheroidal coordinates, which are well suited for description of close collisions in two-center quantum systems. In the frame of reference where the quasimolecular axis is fixed, the rotational coupling term is added to the Hamiltonian. Unlike our previous calculations, we do not discard this term and retain it when solving the TDDE. Both three-dimensional angle-resolved and angle-integrated energy distributions of outgoing positrons are obtained. Three-dimensional angle-resolved distributions exhibit a high degree of isotropy. For the collision energies in the interval 6 to 8  MeV/u, the influence of the rotational coupling on the distributions and total positron creation probabilities is quite small.

Published by the American Physical Society
2025
Isospectral local Hermitian theory for the
PT
-symmetric
iϕ3
quantum field theory
Authors: Li Yi-Da , Wang Qing
Published: January 2025

We propose a new method to calculate perturbatively the isospectral Hermitian theory for the PT-symmetric iϕ3 quantum field theory in d dimensions, whose result is local. The result of the new method in 1 dimension reproduces our previous result in the ix3 quantum mechanics, and the new method can be seen as a generalization of our previous method to quantum field theory. We also find the isospectral local Hermitian theory has the same form in all dimensions and differs in coefficients only, and our previous results in quantum mechanics can be used directly to determine the form of the isospectral local Hermitian quantum field theory.

Published by the American Physical Society
2025
Nonmonotonic Constitutive Curves and Shear Banding in Dry and Wet Granular Flows
Authors: Ness Christopher , Fielding Suzanne M.
Published: January 2025

We use particle simulations to map comprehensively the shear rheology of dry and wet granular matter comprising particles of finite stiffness, in both fixed pressure and fixed volume protocols. At fixed pressure we find nonmonotonic constitutive curves that are shear thinning, whereas at fixed volume we find nonmonotonic constitutive curves that are shear thickening. We show that the presence of one nonmonotonicity does not imply the other. Instead, there exists a signature in the volume fraction measured under fixed pressure that, when present, ensures nonmonotonic constitutive curves at fixed volume. In the context of dry granular flow we show that gradient and vorticity bands arise under fixed pressure and volume, respectively, as implied by the constitutive curves. For wet systems our results are consistent with a recent experimental observation of shear thinning at fixed pressure. We furthermore predict discontinuous shear thickening in the absence of critical load friction.

Published by the American Physical Society
2025
Slow and stored light via electromagnetically induced transparency using a
Λ
-type superconducting artificial atom
Authors: Chu Kai-I , Lu Xiao-Cheng , Chiang Kuan-Hsun , Lin Yen-Hsiang , Chen Chii-Dong , Yu Ite A. , Liao Wen-Te , Chen Yung-Fu
Published: January 2025

Recent progresses in Josephson-junction-based superconducting circuits have propelled quantum information processing forward. However, the lack of a metastable state in most superconducting artificial atoms hinders the development of photonic quantum memory in this platform. Here we use a single superconducting qubit-resonator system to realize a desired Λ-type artificial atom, and to demonstrate slow light with a group velocity of 3.6 km/s and the microwave storage with a memory time extending to several hundred nanoseconds via electromagnetically induced transparency. Our results highlight the potential of achieving microwave quantum memory, promising substantial advancements in quantum information processing within superconducting circuits.

Published by the American Physical Society
2025
The periphery as a critical project: towards an architectural pedagogy for the Anthropocene
Authors: McEwan Cameron
Published: January 2025

Purpose

The aim of this paper is to advance a critical pedagogical framework, combining critical pedagogy, design research, architectural theory and experiential learning. It addresses global challenges at the intersection between urban peripheries and the Anthropocene – the centre of the climate crisis is a spatial crisis – preparing students as engaged architect citizens capable of reshaping collective life.

Design/methodology/approach

The framework is examined through a case study of the author’s final year architectural theory module, “The Periphery as a Critical Project”, elucidating its theoretical underpinning and presenting a visual analysis of student projects. Methods include reflective module design, fieldwork, close-reading of literature across disciplines, design research, experiential learning strategies and an inventive “theorypractice”.

Findings

The research demonstrates that theorypractice articulates a transformative and experiential learning experience, articulating architectural education as a site for critical engagement with urgent challenges. The approach equips students with critical thinking and making skills, cultivates a commitment to civic responsibility and encourages alternative visions for the Anthropocene. The paper concludes with concepts and practices to define an emerging architectural pedagogy for the Anthropocene.

Practical implications

The research provides guidance for educators in architecture, aligning with RIBA reforms emphasising “history, theories, methodologies” and experiential learning in allied fields such as urban studies, environmental planning and social policy, focused on climate and social resilience, spatial justice and critical literacy. More broadly it aims at preparing engaged architect citizens who can work on and with the world.

Originality/value

This paper contributes an original framework and novel methodology, bringing together theoretical and design research from architecture, urban studies, design, critical pedagogy and environmental humanities to expand experiential learning within architectural theory, an underexplored position. It addresses urgent issues related to urban peripheries, climate change, and how we educate future architects in times of crisis, offering a model for allied fields facing similar societal challenges.
Numerical investigation of wave dynamics in laminar falling films: influence of Kapitza number and inclination angle
Authors: Chen Yuanxiang , Zheng Jian , Liu Yue , Oliva Llena Asensio , Castro Gonzalez Jesus
Published: January 2025

Purpose

This study aims to optimize the design of falling film heat exchangers by providing a deeper understanding of wave characteristics and capillary flow in laminar inclined falling films at low Reynolds numbers. The focus is on the effects of different Kapitza numbers, influenced by fluid properties and inclination, on the interfacial wave behavior.

Design/methodology/approach

A numerical investigation was conducted using the volume of fluid method within OpenFOAM’s interFoam solver. This study examined the effects of Kapitza number, inclination angle and inlet disturbances on wave formation and flow dynamics, analyzing how these factors influence interfacial wave amplitude, wavelength and flow in the capillary region.

Findings

The results revealed that higher Kapitza numbers lead to the formation of stronger capillary waves. Flow separation was observed in the capillary wave region for materials with high Kapitza numbers. An improved Nosoko correlation model was developed, incorporating the inclination angle to more accurately predict the relationship between wave peaks and wavelengths in inclined cases.

Originality/value

This research investigates the impact of low Kapitza number on inclined falling film flow, and a correlation model was derived that provides a broader range for evaluating wave behavior in inclined conditions, offering extended references for the design of falling film heat exchangers.
Waste harvesting: lessons learned from the development of waste-to-energy power plants in Indonesia
Authors: Mudofir Mudofir , Astuti Septin Puji , Purnasari Nurwulan , Sabariyanto Sabariyanto , Yenneti Komali , Ogan Deinsam Dan
Published: January 2025

Purpose

The purpose of this research is to analyse the development and implementation of waste-to-energy (WtE) power plants as a strategy to manage municipal solid waste (MSW) in Indonesia. It aims to identify key determinants for the successful adoption of WtE technology in developing countries, focusing on the Benowo WtE power plant, Indonesia’s first large-scale WtE project.

Design/methodology/approach

This study reviews the development of the Benowo WtE power plant, examining political, regulatory and financial factors influencing its implementation. It analyses the roles of national and local government institutions, highlighting critical elements for the successful deployment of WtE projects in a developing country context.

Findings

The review shows that the success of WtE projects in Indonesia is significantly influenced by strong local government commitment, supported by political, financial and regulatory backing from the national government. The Benowo WtE power plant’s development demonstrates that with adequate support, WtE can be a viable solution for managing MSW and generating energy in developing countries. The study also identifies barriers to broader WtE adoption in similar contexts.

Research limitations/implications

The study is limited to 12 WtE projects in Indonesia, with in-depth analysis focused on a single case, potentially overlooking challenges and opportunities in other regions. Furthermore, the study does not include an economic analysis, such as a feasibility assessment. Future research could expand to multiple WtE projects and incorporate primary data collection to provide more comprehensive findings, including feasibility studies of each project.

Practical implications

The findings provide practical guidance for policymakers and stakeholders in developing countries, identifying critical areas for successful WtE deployment and offering a blueprint based on the Benowo WtE power plant.

Social implications

Implementing WtE projects can improve waste management, reduce pollution, enhance public health, create jobs and stimulate local economies. The study underscores the importance of government and community collaboration in addressing environmental challenges and fostering shared responsibility.

Originality/value

This research offers novel insights into WtE technology development in a developing country, specifically focusing on Indonesia’s first large-scale WtE power plant. By analysing the Benowo WtE power plant, the study provides valuable lessons and strategies for other developing nations aiming to adopt WtE solutions for MSW management, emphasising the critical role of government support.
From side effects to work attitudes influencing customer service quality: moderating impacts of work experience in banking industry
Authors: Kim Long , Yeo Sook Fern
Published: January 2025

Purpose

To help banks maintain competitive advantages, bank workers must develop superior financial products and services that meet customers’ needs and expectations, and developing customer service quality also merits closer attention. Research emphasizes that developing customer service quality has direct associations with not only individual career growth and development but also customer satisfaction, loyalty, retention. Thus, this research aims to explore how bank workers develop their customer service quality by investigating side effects (stress and satisfaction) on work attitudes (organizational commitment and employee performance) along with work experience acting as moderators (1) between organizational commitment and customer service quality and (2) between employee performance and customer service quality.

Design/methodology/approach

Researchers collected data from 650 Cambodian bank workers via a survey questionnaire. A path analysis technique was used to analyze the data.

Findings

Results revealed that bank commitment was significantly influenced by stress and satisfaction. Next, employee performance was significantly influenced by bank commitment, stress and satisfaction. Meanwhile, customer service quality was significantly influenced by bank commitment and employee performance. Finally, work experience moderated both relationships (1) between bank commitment and customer service quality and (2) between employee performance and customer service quality.

Originality/value

Although significant side effects of stress and satisfaction on worker behavior in various industries, not my researchers have investigated how side effects of stress and satisfaction influence work attitudes (commitment and performance) which develop customer service quality in banking industry, along with work experience as a moderator.
Psychometric stress risk assessments: proceed with caution
Authors: Hudson John , Weinberg Ashley
Published: January 2025

Purpose

Despite extensive psychometric research on psychosocial assessment tools, comparatively little explores the practical application and evaluation of these tools for prioritising workplace psychosocial risks. This paper addresses this gap by illustrating the use of one popular, freely available measure in an applied risk assessment context, alongside qualitative data, highlighting questions and challenges for organisations.

Design/methodology/approach

1,425 employees from a UK public-sector organisation completed the Management Standards Indicator Tool (MSIT), General Health Questionnaire, and open-text questions about stress-related and positive aspects of work. Three approaches to analysing MSIT data were adopted: descriptive statistics, multiple regression and risk calculation, complemented by analysis of open-text qualitative data.

Findings

Demands and change were ranked prominently by each method; however, there were major inconsistencies, for example, relationships ranked first using one method but sixth by another. Qualitative comments broadly reflected quantitative analyses, with demands mentioned most frequently, but highlighted issues and nuances not covered by the MSIT.

Research limitations/implications

Only a selection of potential approaches to analysis is considered here, future research to support employers with analysis and evaluation of quantitative risk assessment data would be valuable.

Practical implications

Risk-assessors’ choice of analysis could have major implications for where employers direct resources, supporting existing guidance to avoid sole reliance on quantitative surveys for risk assessment.

Originality/value

This paper builds on the necessary–but not sufficient–psychometric foundations of risk assessment tools, integrating qualitative data and illustrating questions and challenges in applying them for their stated purpose.
Rethinking the inherent jurisdiction of the high court in safeguarding adult reviews: beyond legal literacy
Authors: Mason Karl , Bedford Daniel , Leyman Alice , Bremner Philip
Published: January 2025

Purpose

The Inherent Jurisdiction of the High Court (the IJ) is used in safeguarding adults work to protect “vulnerable adults” whose autonomy is compromised but who have mental capacity as defined by the Mental Capacity Act 2005. Safeguarding Adult Reviews (SARs) frequently call on practitioners to develop legal literacy, including regarding the IJ. This study aims to explore and discuss how the IJ is presented in SARs and argues that there are systemic problems beyond legal literacy to consider in this area.

Design/methodology/approach

Relevant SARs (n = 29) were located through the National Network of Safeguarding Adult Board Chair’s library. These were thematically analysed to identify patterns regarding how the IJ is covered in these documents.

Findings

The reviews converged around specific experiential clusters (familial and domestic abuse, community-based exploitation and self-neglect). They entailed accounts of complex mental capacity issues and raised concerns about legal literacy. It was common to find situations where many other avenues for intervention had been exhausted and the IJ was proposed as a measure of last resort. The discussion of the IJ in SARs occasionally differs from prevailing legal accounts of its application, particularly regarding self-neglect and situations where a third party is not exerting coercion or control. The authors close the study with a discussion about legal literacy.

Originality/value

The IJ is an evolving area of law, and practitioners may therefore struggle to grasp its applicability. SARs are important resources for practitioners to learn lessons concerning this less commonly used legal mechanism. As a result, independent reviewers should be cautious about how they frame this legal remedy and consider whether this really is a case of “legal literacy”.
Proactive, trustworthy and adaptable? Linking ethical leadership and adaptive performance through sequential mediation of trust in leaders and job crafting
Authors: Zia Muhammad Qamar , Saraih Ummi Naiemah , Ramish Muhammad Sufyan , Faisal Asima , Naveed Muhammad
Published: January 2025

Purpose

The objective of this research is to investigate how ethical leadership (EL) directly or indirectly impacts adaptive performance (AP) within the hospitality industry, focusing on the mediation of trust in leaders (TiL) and job crafting (JC).

Design/methodology/approach

Data were gathered from 328 employees and 66 leaders across 28 hotels in central and northern areas of Pakistan using a time-lagged methodology. Structural equation modeling was applied for data analysis using SPSS and AMOS.

Findings

Findings present a strong connection between EL and AP, with both TiL and JC serving as independent and sequential mediators. The study also revealed that EL is directly linked to TiL and JC.

Practical implications

Findings suggest that hospitality firms should foster a culture of EL by focusing on hiring and employees’ development programs, enhancing their dynamic capabilities to adapt to the changes.

Originality/value

By examining the AP of frontline employees, this study identifies new outcomes of EL within the hospitality context. Furthermore, it also contributes to the literature by exploring the novel impact of EL on AP through TiL and JC.
Biophilia in servicescapes – review, reconciliation and reflections
Authors: Vinitha V. U. , Kumar Deepak S. , Krishnan Hemamala
Published: January 2025

Purpose

Increased urbanization has resulted in physical environments, including servicescapes, dominated by functional designs, with nature’s presence becoming scarcer. While “biophilia” designs have received attention in fields like environmental psychology and architecture, studies on biophilia in servicescapes remain scant, fragmented and often contextual. The purpose of this study is to do a semi-systematic review of studies on biophilia in physical servicescape designs (interior and exterior), identify prevailing critical gaps and develop a comprehensive framework for theory advancements in biophilic servicescapes.

Design/methodology/approach

Drawing from a critical review of 56 servicescape studies over 33 years and incorporating theoretical frameworks from environmental psychology, this paper introduces a typology of biophilia in physical servicescapes that includes direct, indirect and human–nature relationships. Furthermore, this study develops a conceptual framework using the Stimulus-Organism-Response model to systematically synthesize biophilia’s overall applicability in servicescapes for consumers and service employees, incorporating moderating factors related to service, servicescape and user types.

Findings

This review investigates the emergence and definition of biophilia in servicescapes, examines the benefits of biophilic design for consumers and service employees and highlights key design strategies. In the absence of robust frameworks to assess biophilia’s impact on consumer and employee responses, this paper presents a comprehensive framework and offers guidelines for future research in retail environments and servicescapes.

Originality/value

Drawing from the synthesis of research on biophilia in servicescapes, this study introduces a framework that demonstrates how antecedent variables, including both direct and indirect biophilic elements, foster human–nature relationships that lead to affective, cognitive and behavioral responses. These effects are moderated by situational factors (e.g. service and servicescape types) and individual differences (e.g. personality, values and nature-relatedness). Ultimately, these responses influence approach or avoidance behaviors in consumers and employees, with a taxonomy detailing responses aligned with biophilia.
Thermal affection on hydrogen diffusion in different structures of nickel alloy
Authors: Cavaliere Pasquale , Sadeghi Behzad , Chen Zhenghan , Stanislawska Alicja
Published: January 2025

Purpose

Based on previous research, we choose nickel alloy 718 as the research material and use finite element analysis (FEA) to simulate the hydrogen diffusion in lattice, grain, boundary grain and dislocation in different thermal loads, aiming to understand the intricate mechanisms underlying hydrogen diffusion in nickel-based alloys, which will contribute to driving progress in the field of hydrogen diffusion for understanding and management HE.

Design/methodology/approach

In this research, we focus on nickel alloy 718, creating a numerical model with traps to simulate the hydrogen diffusion in lattice, grain, boundary grain and dislocation with different thermal loads, by FEA.

Findings

The results demonstrated that traps improve the hydrogen saturation in materials, and because of thermal saturation and heat flux, higher temperatures decrease the hydrogen solubility and increase hydrogen diffusion velocity, which can decrease hydrogen saturation.

Originality/value

Based on our previous research and publications, we developed a finite element model to define the hydrogen trapping in different microstructural features of nickel-based superalloys. The model is very complex with a very large number of elements capable of obtaining very affordable results.
Greening or greenwashing? Corporate green bonds and stock pricing efficiency in China
Authors: Huang Xiulu , Tang Chuxiong , Liu Yichao , Ge Pengfei
Published: January 2025

Purpose

This paper aims to unveil the greenwashing intention of green bonds issuing in Chinese enterprises through the lens of stock pricing efficiency.

Design/methodology/approach

Drawing on data of Chinese listed companies during 2012–2021, this study uses a difference-in-differences method to study how and through what mechanisms issuing green bonds impacts stock pricing efficiency.

Findings

Issuing green bonds lowers stock pricing efficiency, verifying the greenwashing intention of green bonds in China. Potential mechanisms underlie the increased investor attention and sentiment resulting from the information disclosures about corporate green and low-carbon development. This greenwashing issue is more pronounced in firms facing lower financing constraints, having stronger relations with the government, and located in highly marketized regions. In the context of uncertainty surrounding economic policies, especially trade policies, issuing green bonds can signal a weakening of the greenwashing effect.

Practical implications

The quality of information disclosure should be emphasized to ensure a substantive commitment to environmental responsibility signaled by green bond issuance, thereby mitigating greenwashing concerns.

Social implications

Regulators and standard-setters should improve the issuance system for green bonds and promote the sustainable development of the green bond market through formulating unified certification criteria for green bonds and implementing a stringently periodic reporting system.

Originality/value

First, to the best of the authors’ knowledge, it is the first study to draw on the quality of information disclosure and the perspective of stock pricing efficiency to identify whether firms issuing green bonds engage in greenwashing. Second, the study uncovers the black-box underlying this greenwashing issue through investor attention and sentiment and examines further the moderating role of economic policy uncertainties.
Why, where and what to study? Exploring the university choices of Italian and Spanish graduates with disabilities
Authors: Biagiotti Gilda , Moriña Anabel
Published: January 2025

This article analyses the decisions and motivations that led 30 graduates with disabilities from Italy and Spain to pursue university studies, choose their degrees, and select their universities. Using a phenomenological approach, through semi‐structured interviews and inductive data analysis, several reasons for graduates' university access were identified, such as vocation, the search for job opportunities and the desire to pursue an academic education. The results showed that both personal factors (disability or personal interest) and external factors (family, partners, friends and teachers) played a role in their choice of studies. Regarding university selection, participants considered proximity to their homes, the services offered, and the possibility of having an experience outside of their hometown. This article highlights the relevance of previous educational experiences, collaboration between secondary education institutions and universities, and the importance of providing information about the support and services available for students with disabilities during their university careers.
The UK General Election in Scotland: The End of an Era, Age of Ultra‐Competition or Interregnum?
Authors: Hassan Gerry
Published: January 2025

The Scottish election results from the 2024 Westminster election were yet another contest defined by major change in constituencies, individuals and party performance. After a long period of dominance by Labour in Scotland, the aftermath of the 2014 independence referendum witnessed substantial change and volatility at each of the subsequent four UK elections. While Labour's re‐emergence as Scotland's dominant party at Westminster in 2024 and the political geographies underpinning it echo patterns pre‐2014, the dynamics of Scottish politics are still shaped for the foreseeable future by competition between Labour and the SNP, anti‐incumbency and the question of Scottish independence.
Evaluating the Cost‐Effectiveness of Antenatal Screening for Major Structural Anomalies During the First Trimester of Pregnancy: A Decision Model
Authors: Campbell Helen E. , Karim Jehan N. , Papageorghiou Aris T. , Wilson Edward C. F. , Rivero‐Arias Oliver ,   the ACCEPTS Study
Published: January 2025

Objective

To assess the cost‐effectiveness of modifying current antenatal screening by adding first trimester structural anomaly screening to standard of care second trimester anomaly screening.

Design

Health economic decision model.

Setting

National Health Service (NHS) in England and Wales.

Population

Pregnant women attending for first trimester antenatal screening.

Methods

The decision model estimated pregnancy outcomes (maternal and foetal) and 20‐year costs for current screening practice and for a policy adding a protocol screening for eight major structural anomalies to the current first trimester ultrasound scan. Event probabilities, costs, and outcomes for the model were informed by meta‐analyses, published literature, and expert opinion.

Main Outcomes Measures

Expected numbers of pregnancy outcomes, healthcare costs, and maternal quality‐adjusted life years (QALYs). Estimation of the incremental cost‐effectiveness ratio (ICER), likelihood of cost‐effectiveness, and a value of information (VoI) analysis assessing if further research is needed before making a decision about screening.

Results

First trimester anomaly screening increased mean per woman costs by £11 (95% CI £1–£29) and maternal QALYs by 0.002065 (95% CI 0.00056–0.00358). The ICER was £5270 per QALY and the probability of cost‐effectiveness at a willingness to pay value for a QALY of £20 000, exceeded 95%. VoI analysis showed further research would be unlikely to represent value for money. The protocol would likely lead to a reduction in infant healthcare costs and QALYs.

Conclusions

A protocol to screen for eight major structural anomalies during the first trimester appears to represent value for money for the NHS. The opposing implications for mothers and infants, however, raise complex, challenging, and sensitive issues.
Clinical Features and Risks of Congenital Melanocytic Naevi: A Retrospective Analysis of Patients at the Queensland Children's Hospital
Authors: Lobo Yolanka , Zhuang Jessica , Gribbin Hannah , Perez William Felipe Pinzon , Soyer H. Peter , Wheller Laura
Published: January 2025

Background/Objectives

Congenital melanocytic naevi (CMN) are a risk factor for melanoma. Melanoma risk is dependent on the congenital phenotype. Our primary aims were to assess the clinical characteristics of CMN that indicate a high risk of neurocutaneous melanosis (NCM) and melanoma in an Australian paediatric population group; to identify patient characteristics and clinical features of CMN that trigger further investigations; and to determine the rate of malignancy and other complications for CMN.

Methods

We retrospectively reviewed the electronic medical records of all patients under 18 years who were diagnosed with CMN at the Queensland Children's Hospital between 2014 and 2021.

Results

Eighty‐eight patients (38 males and 50 females) were included in the analysis. Eighteen patients (20%) had a biopsy to rule out malignancy. Central nervous system magnetic resonance imaging (MRI) was performed in 16 patients (18%). Five patients (5.7%) experienced complications, of which three had NCM and two had transient neurological symptoms with normal MRI. No cases of melanoma, non‐melanoma tumours or deaths were recorded.

Conclusions

CMN size, location over the posterior midline axis and multiple numbers of CMN were found to be significantly associated with the development of complications. CMN size, CMN site, presence of satellite naevi and location over the posterior midline axis were all significantly associated with the likelihood of an MRI or biopsy being performed. Large‐scale studies, such as a population‐based registry, are recommended to accurately assess the true lifetime risk of complications and associated risk factors.
Psychological Assessment and Motivations of Potential Donors Within the First Australian Uterine Transplant Trial
Authors: Gerstl Brigitte , Mallinder Hayley , Baker Tamika , Euler‐Vestey Pia , Kehag Eva , Stone Meredith , Lawrence Denise , Pippard Hayley , Arulpragasam Kaushalya , Walch Anna , Campion Finn , McGill Brittany , Deans Rebecca
Published: January 2025

Objective

This study aims to investigate the psychological characteristics, motivations and experiences of potential living donors assessed for the first uterus transplant (UTx) clinical trial in Australia.

Design

Mixed methods study.

Setting

Tertiary hospital.

Patient(s)

Seven female potential UTx donors.

Intervention(s)

A mixed‐methods design was used to evaluate seven self‐referred potential uterus donors for the UTx program. Potential donors underwent rigorous clinical and psychological screening, including self‐reported psychological assessments. Additionally, five potential donors participated in semi‐structured interviews conducted by the study social worker.

Main Outcome Measure(s)

Scores from measures of quality of life, depression, anxiety and stress, along with thematic analysis from semi‐structured interviews.

Result(s)

Thematic analysis identified six key themes: feelings about donating a uterus, health history, informed consent, impact of donation, relationships, and access to educational resources. Several sub‐themes were also identified, including awareness of surgical complications and dynamics of relationships and sexuality. Quantitative results indicated clinical levels of depression, anxiety, and stress in some donors. Overall, the quality‐of‐life scores of the donors were comparable to those of the general Australian female population.

Conclusion(s)

The study provides a deeper understanding of the psychological profiles and motivations of potential UTx donors in Australia. It reveals the complexity of donor motivations, which include altruistic desires to help others experience pregnancy, and practical considerations. The findings emphasise the need for rigorous psychological screening and continuous support to address potential mental health challenges. These insights are valuable for developing future UTx protocols and support systems to ensure donor wellbeing.
Paediatric breast disease and developmental breast cysts – reflection on 20 years of experience
Authors: Grant Katherine , Bochner Melissa
Published: January 2025

Introduction

Presentation with breast symptoms in the paediatric population is common but there is little existing literature on the workup and management of breast disease in this population.

Methods

Retrospective series of 140 cases of breast disease in the paediatric population managed by a single surgeon in Adelaide, South Australia between 2004 and 2024. Review of patient demographics, presentation, investigation, management and outcomes of various breast symptoms and pathologies using descriptive analysis.

Results

We reviewed 140 cases including 135 females and 5 males, aged 8–18 years (median = 15). The most common reason for presentation was breast lump (n = 86, 61%), followed by large breasts (n = 13, 9%), asymmetry (n = 11, 8%), abnormal development (n = 8, 6%). Most patients were investigated with ultrasound (n = 101, 71%) and FNA biopsy was performed in cases of non‐diagnostic ultrasound or to distinguish fibroadenoma from phyllodes tumour (n = 17, 12%). There was a single case of malignancy and the most common diagnoses were developmental breast cyst (n = 36, 26%) and fibroadenoma (n = 33, 24%). Gynaecomastia was the only diagnosis in males (n = 5, 4%). Majority of patients were managed non‐operatively (n = 101, 72%), indications for surgery included fibroadenoma (n = 18, 13%), breast hypertrophy (n = 8, 6%) or abnormal breast development (n = 4, 3%).

Conclusion

We reviewed 140 cases of breast disease in the paediatric population over a 20‐year period. Malignancy in this population is rare but requires exclusion with history, examination and ultrasound where appropriate. Developmental breast cysts are the most common pathology, require early identification to avoid unnecessary invasive investigation and should be managed expectantly where possible.
Efficacy of HA130 Hemoadsorption in Removing Advanced Glycation End Products in Maintenance Hemodialysis Patients
Authors: Ramírez‐Guerrero Gonzalo , Reis Thiago , Segovia‐Hernández Barbara , Aranda Francisca , Verdugo Constanza , Pedreros‐Rosales Cristian , Marcello Matteo , León Janina , Rojas Armando , Galli Francesco , Ronco Claudio
Published: January 2025

Background

Patients on maintenance hemodialysis (HD) face complications due to the accumulation of protein‐bound uremic toxins, such as advanced glycation end products (AGEs), which contribute to inflammation, oxidative stress, and cardiovascular disease. Conventional HD techniques inadequately remove AGEs. This study evaluates the efficacy of the HA130 hemoadsorption cartridge combined with high‐flux HD (HF‐HD) in enhancing AGE removal.

Methods

This prospective, single‐center study included 20 maintenance HD patients randomized into two groups: HF‐HD alone (n = 10) and HF‐HD plus hemoadsorption (n = 10). Blood samples were collected before and after a single session to measure carboxymethyllysine (CML), soluble RAGE (sRAGE), prolactin, and parathyroid hormone (PTH) levels. Reduction ratios (RR) were calculated, including corrected for hemoconcentration (RRc), to ensure accuracy. Statistical analyses included Mann–Whitney U and Chi‐square tests.

Results

The HF‐HD plus hemoadsorption group showed significantly enhanced removal of CML compared to HF‐HD alone, with RRc of 64.7% [52.6–74.9] versus 39.3% [33.8–49.4], respectively (p = 0.045). Similarly, uncorrected reduction ratios demonstrated a trend favoring hemoadsorption, with values of 57.5% [45.1–70.7] versus 30.3% [19.1–44.5] (p = 0.053). Importantly, sRAGE levels were preserved in both groups (RRc: 23.4% (15.1–30.4) vs. 21.8% (16.6–31.7), p = 0.791), highlighting the safety of hemoadsorption. Other biochemical parameters, including prolactin, PTH, albumin, and electrolytes, showed no significant differences between groups. All sessions were completed without adverse events.

Conclusion

Combining hemoadsorption with HF‐HD significantly enhances CML removal, as evidenced by corrected RR, without compromising protective sRAGE levels. This innovative approach offers a promising adjunctive therapy for reducing AGEs‐related complications in end‐stage renal disease patients. Further longitudinal studies are needed to confirm these findings and evaluate long‐term outcomes.
Pharmacokinetic characterization and exposure–response relationship of crovalimab in the COMMODORE 1, 2 and 3 and COMPOSER trials of patients with paroxysmal nocturnal haemoglobinuria
Authors: Cosson Valérie , Fu Rong , Kulasekararaj Austin , Nishimura Jun‐Ichi , Panse Jens , Röth Alexander , Scheinberg Phillip , Tong Hongyan , Yoon Sung‐Soo , Beveridge Leigh , Gotanda Keisuke , Jaminion Félix , Henrich Andrea , Lundberg Pontus , Shi Dayu , Sreckovic Sasha , Zhang Yuchen , Zhang Zilu , Benkali Khaled , Buatois Simon
Published: January 2025

Aims

Crovalimab is a novel C5 inhibitor administered first intravenously and then subcutaneously in patients with paroxysmal nocturnal haemoglobinuria (PNH) naive to complement inhibition or switching from eculizumab or ravulizumab. Crovalimab showed efficacy and safety comparable to eculizumab in the pivotal COMMODORE 2 and supporting studies.

Methods

We characterized crovalimab pharmacokinetics and the relationship between exposure pharmacokinetic parameters and pharmacodynamic biomarkers, efficacy and safety endpoints using pooled data (healthy volunteers [n = 9], naive [n = 210] and switched [n = 211] patients). Pharmacodynamic biomarkers included 50% complement activity and free C5; normalized lactate dehydrogenase was a marker of haemolysis. Adverse events (AEs) of special interest, related serious AEs, related Grade ≥3 AEs and infections were assessed.

Results

There was no clinically relevant difference in crovalimab concentrations between naive and switch patients. Bodyweight had a statistically significant impact on crovalimab clearances and volumes of distribution. Thus, the recommended dosing regimen used weight‐based, two‐tiered dosing (100 kg cutoff). Age did not have a clinically meaningful impact on crovalimab exposure. In COMMODORE 2, and the supporting COMMODORE 1 and 3 studies, complete terminal complement activity inhibition was achieved immediately at the end of the initial intravenous infusion and sustained throughout the treatment period in ≥97% of patients. Crovalimab concentrations above ≈100 μg/mL achieved complete inhibition of terminal complement activity, resulting in disease control with normalized lactate dehydrogenase ≤1.5 × upper limit of normal (ULN). There was no increased risk of AEs at higher exposure.

Conclusions

These data confirm an effective crovalimab‐dosing regimen that achieves complete terminal complement activity inhibition and disease control in patients with PNH.
Genetic deficiency or pharmacological inhibition of cGAS–STING signalling suppresses kidney inflammation and fibrosis
Authors: Jiao Baihai , An Changlong , Du Hao , Tran Melanie , Yang Duomeng , Zhao Yuqi , Wang Penghua , Hu Zhaoyong , Zhou Dong , Wang Yanlin
Published: January 2025

Background and Purpose

Chronic kidney disease (CKD) is characterised by inflammation, which can lead to tubular atrophy and fibrosis. The molecular mechanisms are not well understood. In this study, we investigated the functional role of the cyclic GMP–AMP synthase (cGAS)– stimulator of interferon genes (STING) signalling in renal inflammation and fibrosis.

Experimental Approach

Mice with global cGAS deficiency or global or myeloid cell‐specific STING deficiency or wild‐type mice treated with RU.521, a selective cGAS inhibitor, were used to examine the role of cGAS–STING signalling in renal inflammation and fibrosis in a preclinical model of obstructive nephropathy in vivo. Bone marrow‐derived macrophages were used to determine whether tubular epithelial cell‐derived DNA can activate cGAS–STING signalling in vitro.

Key Results

Following obstructive injury, cGAS–STING signalling was activated in the kidneys during the development of renal fibrosis. Mice with deficiency of cGAS or STING exhibited significantly less macrophage proinflammatory activation, myofibroblast formation, total collagen deposition, and extracellular matrix (ECM) protein production in the kidneys following obstructive injury. Pharmacological inhibition of cGAS with RU.521 reduced macrophage proinflammatory activation, suppressed myofibroblast formation, and attenuated kidney fibrosis following obstructive injury. Mechanistically, cGAS–STING signalling in macrophages is activated by double‐stranded DNA released from damaged tubular epithelial cells, which induces inflammatory responses.

Conclusions and Implications

Our study identifies the cGAS–STING signalling pathway as a critical regulator of macrophage proinflammatory activation during the development of renal fibrosis. Therefore, inhibition of cGAS–STING signalling may represent a novel therapeutic strategy for CKD.
Molecular Subtyping and Genomic Profiling Expand Precision Medicine in KRAS Wild‐Type Pancreatic Cancer
Authors: Su Dan , Ruan Yuli , Shi Yingfei , Cao Dandan , Wu Tong , Dang Tianjiao , Wang Hong , Xin Yaqun , Ma Ming , Meng Hongxue , Liu Chao , Zhang Yanqiao
Published: January 2025

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with poor prognosis and limited treatment options. While the majority of PDAC cases harbor KRAS mutations, approximately 8%–10% are KRAS wild‐type (KRAS‐WT). These KRAS‐WT tumors often contain actionable mutations and gene fusions, making them more suitable for precision therapies. Identifying these molecular alterations is crucial for improving outcomes in this subset of patients. This retrospective study involved 34 patients with KRAS‐WT PDAC. Genomic profiling was performed using next‐generation sequencing (NGS) and RNA sequencing to detect mutations and fusions. Comparative analysis was conducted with TCGA‐PAAD data, and immune infiltration was assessed using bioinformatic deconvolution methods. Targetable alterations were identified in multiple pathways. Key mutations included ATM (18%), PIK3CA (15%), and ROS1 (15%), while actionable gene fusions such as CCDC6‐RET and ETV6‐NTRK3 were present in 10.3% of patients. The gene mutations associated with homologous recombination deficiency (HRD) are predicted to increase sensitivity to platinum‐based chemotherapy (p = 0.047). Tumors with epigenetic regulatory genes mutations (e.g., ARID1A, KMT2C/D) exhibited enhanced immune cell infiltration, highlighting potential responsiveness to immune checkpoint inhibitors (ICIs). Kinase fusions (NTRK and RET) were linked to response to larotinib and RET‐specific inhibitors, respectively. KRAS‐WT PDAC contains actionable mutations and fusions, offering significant potential for targeted and immune‐based therapies. Further clinical studies are needed to validate these therapeutic approaches.
“I Really Want to Decide”: Norwegian and Estonian Primary and Secondary School Pupils' Participation in Decision‐Making in School‐Based Physical Activity
Authors: Pardali Eirini , Trangsrud Lise Katrine Jepsen , Bratland‐Sanda Solfrid , Koni Ingrid , Säre Egle , Lemberg Getter Marie , Mäestu Evelin , Kull Merike , Mandelid Mathias Brekke , Kjønniksen Lise
Published: January 2025

This study explores how Norwegian and Estonian primary and secondary school pupils experienced participation in decision‐making within the context of school‐based physical activity. A sample of thirty‐eight pupils, aged ten to fifteen years, participated in nine focus groups. Drawing on Hart's ladder of participation combined with Braun and Clarke's reflexive thematic analysis, the analysis presents five themes. Findings revealed a discrepancy between how pupils expressed their views in decision‐making in school‐based physical activity and how they perceived teachers' response to these expressions. It is suggested that future school‐based physical activity programmes should enable all pupils to co‐decide and participate fully.
Zombie firms, state subsidies and aggregate productivity
Authors: Gao Xijie
Published: January 2025

Using firm‐level data from the manufacturing sector in China, I document that zombie firms are larger and less productive, and receive higher subsidy rates on average. The difference in subsidy rates between zombies and non‐zombies reflects both the selection criteria of zombies and the underlying joint distribution of subsidy rate and productivity. I develop a model with heterogeneous firms to quantify the impact of zombies on aggregate productivity. Quantitative exercises show that while both policies—reducing subsidy dispersion and facilitating zombie exits—effectively reduce the zombie rate, the former yields greater productivity gains.