bluuebunny/crossref_metadata_2025 huggingface dataset:
Fractional heterogeneous telegraph processes: Interplay between heterogeneity, memory, and stochastic resetting
Authors: Sandev Trifce , Iomin Alexander
Published: August 2024

Fractional heterogeneous telegraph processes are considered in the framework of telegrapher's equations accompanied by memory effects. The integral decomposition method is developed for the rigorous treating of the problem. Exact solutions for the probability density functions and the mean squared displacements are obtained. A relation between the fractional heterogeneous telegrapher's equation and the corresponding Langevin equation has been established in the framework of the developed subordination approach. The telegraph process in the presence of stochastic resetting has been studied, as well. An exact expression for both the nonequilibrium stationary distributions/states and the mean squared displacements are obtained.

Published by the American Physical Society
2024
Does audit committee composition influence firm performance? Evidence from the top NSE-listed non-financial companies of India
Authors: Singhania Abhisheck Kumar , Panda Nagari Mohan
Published: August 2024

Purpose

This study aims to examine the influence of Audit Committee (AC) composition on Firm Performance (FP) by measuring AC composition (ACC) with a composite score based on the varying effect of each composition-characteristic.

Design/methodology/approach

Partial Least Squares- Structural Equation Modeling (PLS-SEM) technique is used to weigh ACC characteristics. Based on 133 companies and covering five years from 2016 to 2020, the study analyses data after controlling endogeneity through the Gaussian Copula approach.

Findings

We find a significant positive influence of ACC on Firm Performance. Among the ACC characteristics, the absence of executive directors has the highest positive weight on ACC to influence FP, followed by AC size and Gender diversity. AC independence and members' accounting and financial expertise have no significant weight on its composition.

Practical implications

Apart from the theoretical contribution, the study reveals that each ACC characteristic has a varying effect on AC effectiveness to influence the FP that needs to be considered by regulators while framing regulations on ACC and by BOD while constituting AC for a company.

Originality/value

The study claims originality by being pioneering to reveal that AC composition, with a synergy of its disparate characteristics, positively impacts FP. It highlights that the absence of executive directors and gender diversity in AC (characteristics overlooked by the extant literature) significantly and positively influence FP. Methodologically, it introduces the use of the PLS-SEM algorithm to weigh the characteristics in governance studies. Further, these findings remain relevant amid recent Indian legal reforms, offering contemporary insights for policy consideration.
Mapping the way to a dark green enterprise: fuzzy cognitive map based analysis of factors affecting environmental performance for sustainable development
Authors: Kocabey Ciftci Pinar
Published: August 2024

Purpose

It is crucial to transform current enterprises to greener versions of them to reach the sustainable development goals. The first step of this transformation can be understanding comprehensively environmental performances of enterprises. This study presents a practical analysis for evaluation of factors affecting environmental performance of enterprises to call them as a “dark green.”

Design/methodology/approach

For this purpose, a detailed factor search was primarily performed and then the weights of them on environmental performance of the enterprises to support sustainable development were analyzed using fuzzy cognitive map (FCM) that incorporates the casual relationships between factors and represents the dynamics of the complex systems. The FCM was also supported with extended great deluge algorithm (EGDA), which is an evolutionary algorithm with high performance to increase robustness of the study.

Findings

The findings indicated that the most influential factors on environmental performance of an activist enterprise are “loyalty to regulations,” “digitalization level,” “tendency to produce environmentally friendly products/services,” “productivity efforts” and “fossil fuel consumption,” respectively. While the first four of them affect the environmental performance positively, fossil fuel consumption affects it negatively.

Practical implications

The results of this study can help companies to prioritize the critical points for their environmental perspectives, observe at which factors they are good or lacking and find where to start improvement.

Originality/value

This study is one of the pioneering studies to investigate the importance of criteria for a dark green business, considering 21 factors from different sources to make a detailed representation of corporate environmental sustainability.
The influence of the board’s size, independence and sociodemography on the firm’s climate change orientation: evidence from the GALPLACC index
Authors: Lippi Andrea , Galavotti Ilaria
Published: August 2024

Purpose

This paper aims to explore the relationship between board composition and a firm’s commitment to combatting climate change. Specifically, this study investigates how various characteristics of the board, namely its size and presence of independent directors, and of the directors themselves, including gender diversity, age, educational background and national homogeneity, affect the corporate-level climate change orientation. From a theoretical standpoint, the authors take a cross-fertilizing perspective, bridging upper echelons theory with agency, resource dependence and critical mass theories.

Design/methodology/approach

The study uses ordered probit regression models on a hand-collected multi-country and multi-industry sample of 35 listed firms included in the Global Climate Change Liquid Equity Index (GALPLACC) provided by ECPI. This index is particularly relevant as it focuses on firms that have demonstrated a commitment to climate change, providing a robust dataset for the analysis.

Findings

The findings underscore the importance of disentangling various characteristics of corporate boards and directors. Specifically, the orientation toward climate change is negatively influenced by both board size and having a higher number of independent directors, while it is positively affected by reaching a critical mass of women on the board. Conversely, factors such as average age, educational background and the level of national homogeneity do not show significant effects.

Originality/value

This paper has an exploratory nature and contributes to the ongoing debate on the crucial, yet controversial role played by board-level and directors’ sociodemographic characteristics in shaping a firm’s environmental stance. Moreover, this study offers potential recommendations for policymakers regarding board composition to enhance firms’ climate change orientation.
Cautious or confident? Directors’ and officers’ liability insurance and enterprise strategic change: a model of mediating effect and joint moderating effects
Authors: Li Chao , Huo Mengjun , Liu Renhuai
Published: August 2024

Purpose

The purpose of this paper is to empirically analyze the impact of directors’ and officers’ (D&O) liability insurance on enterprise strategic change. It also explores the mediating role of litigation risk, the moderating roles of enterprise science and technology level and precipitation organizational slack between them. In addition, it examines the joint moderating roles of the top management team (TMT) external social network and enterprise science and technology level, and enterprise scale and precipitation organizational slack.

Design/methodology/approach

Using the unbalanced panel data of A-share listed companies in the Shanghai and Shenzhen stock exchanges of China from 2002 to 2020 as the research sample, this paper uses the ordinary least square method and fixed-effect model to study the relationship between D&O liability insurance and enterprise strategic change. The study also focuses on the mediating mechanism and moderating mechanisms between them.

Findings

The authors find that D&O liability insurance has an “incentive effect,” which can significantly promote enterprise strategic change. Litigation risk plays a partial mediating role between D&O liability insurance and enterprise strategic change. Enterprise science and technology level and precipitation organizational slack negatively moderate the relationship between D&O liability insurance and enterprise strategic change. TMT external social network and enterprise science and technology level, and enterprise-scale and precipitation organizational slack have joint moderating effects on the relationship between D&O liability insurance and enterprise strategic change.

Originality/value

This paper confirms the “incentive effect hypothesis” of the impact of D&O liability insurance on enterprise strategic change, which not only broadens the research perspective of enterprise strategic management but also further expands the research scope of D&O liability insurance. Besides, this paper thoroughly explores the influencing mechanisms between D&O liability insurance and enterprise strategic change, providing incremental contributions to the research literature in the field of enterprise risk management and corporate governance. The findings have practical guiding significance for expanding the coverage of D&O liability insurance, promoting the implementation of strategic changes and improving the level of corporate governance of Chinese enterprises.
Does ChatGPT generate fake results? Challenges in retrieving content through ChatGPT
Authors: Safdar Muhammad , Siddique Nadeem , Gulzar Ayesha , Yasin Haisim , Khan Muhammad Ajmal
Published: August 2024

Purpose

ChatGPT is a new development in this technological era. This artificial intelligence-based tool responds to individuals’ queries and produces the requested content within seconds. Therefore, it is becoming popular among academics, the research community and library professionals. This study aims to test (through personal interaction with the tool) the authenticity of the ChatGPT’s produced records. Another objective of the research is to check the relevance between the individuals’ queries and the tool’s results. The research also intends to identify the challenges in retrieving information through ChatGPT.

Design/methodology/approach

The five researchers from different countries and organizations experienced ChatGPT by asking questions on more than 70 subjects. The responses were recorded in Notepad and converted into MS Excel and MS Access to standardize and analyze the data. The investigators consulted 11 reputed databases/sources, including Web of Science and Scopus, to assess the authenticity of the data retrieved through ChatGPT.

Findings

The findings confirmed that over 90% of results produced by ChatGPT were fake (the information did not exist in the literature). Similarly, the study sheds light on the discrepancies, such as irrelevant and incomplete information in the data generated by ChatGPT.

Originality/value

This is a unique study that shares the findings based on the different regions’ researchers’ personal experiences with ChatGPT. The researchers covered different subject areas (above 70) while asking questions to ChatGPT. The paper shares implications for researchers, students, faculty members, academic/research organizations and policymakers.
The role of individual factors in perceived sustainable employability: an application in higher education
Authors: Álvarez-González Paula , López-Miguens María J. , Caballero Gloria
Published: August 2024

Purpose

Sustainable employability has emerged as a multifaceted construct that measures individuals' abilities to function in the labour market throughout their working lives. Therefore, it is no longer just about analysing how to achieve a successful transition from school/university to employment, but also about identifying the conditions that will allow people to continue to be capable and motivated in the long term. The aim of this work was to identify and rank the personal factors of an individual that contribute to his or her perceived sustainable employability.

Design/methodology/approach

The authors used a quantitative methodology to estimate the structural model proposed. A stratified random procedure was used to administer an online questionnaire to 202 university master’s degree students. Before testing the structural model, the validation of each scale was performed, both at the exploratory and confirmatory levels.

Findings

The results indicate that four groups were key to improve individual sustainable employability: (1) Health Status; (2) Career Competencies; (3) Core Self-Evaluations and (4) Overcoming Competencies.

Research limitations/implications

The results are of interest to any individual, employed or not, insofar as they can reflect on the relevance of each category and how to improve them at the individual level.

Originality/value

This study contributes to research on sustainable employability focus on the analysis of young people by providing empirical evidence on its relationship with other key variables, in an area where the literature remains mainly conceptual and centred in workers.
Gender and business creation: similarities and differences
Authors: Reynolds Paul D.
Published: August 2024

Purpose

This paper explores the scope and impact of gender in the process of starting new businesses, with a particular focus on understanding how participation, motivations and outcomes differ between men and women entrepreneurs.

Design/methodology/approach

This paper utilizes data from the Global Entrepreneurship Monitor (GEM) and the Panel Studies of Entrepreneurial Dynamics (PSED). The GEM data provide a global overview, drawing from representative national samples across over 100 countries to assess the extent of business creation activity and gender participation globally. The longitudinal PSED data set provides information on the business creation process and outcomes.

Findings

Over the last 20 years, the presence of women in the early stages of starting a business in the United States of America has seen a notable increase, doubling their representation among entrepreneurs and nearing parity with men, who also saw growth but at a slower rate. This shift marks a significant move towards greater gender balance in the entrepreneurial landscape.

Originality/value

The originality of this paper lies in its comprehensive analysis of the evolving landscape of gender dynamics within entrepreneurship over two decades, particularly highlighting the significant increase in women's participation in business creation.
Intent to stay of Chinese agency workers in the information technology outsourcing industry
Authors: Zhang Xiwei , Liang Xiaoyan , Xiao Qijie
Published: August 2024

Purpose

The literature on information technology outsourcing (ITO) prioritises monetary considerations and overlooks human aspects. This qualitative study adopts a contextualised approach to address a research gap in understanding agency workers’ intent to stay in the ITO sector.

Design/methodology/approach

In contrast to previous studies that focus on intra-organisational factors and use quantitative designs, this study takes a qualitative approach. It analyses data from 85 in-depth interviews with agency workers in the Chinese ITO supply chain and project managers of supplier and client firms.

Findings

The study constructs an integrated framework covering 15 factors at three levels and shows how they interact to influence Chinese agency workers’ intent to stay in the ITO supply chain. Variations in outsourcing management styles and practices among U.S., Japanese and Chinese client firms are presented to enrich the understanding of outsourcing dynamics in a global context.

Originality/value

This study contributes to the ITO literature by providing new insights into the retention of highly skilled agency workers and deepening the contextual understanding of this issue, throwing light on the human aspects often overshadowed by monetary considerations.
Metaverse, entrepreneurial learning and opportunity exploitation
Authors: Abaddi Samer
Published: August 2024

Purpose

In the cosmic expanse of the digital universe, a new celestial body emerges the Metaverse. This study embarks on an interstellar journey to scrutinize the dynamics of entrepreneurial learning (EL) and opportunity in the burgeoning realm of the metaverse. This study aims to understand how personal entrepreneurial characteristics (PEC) and Metaverse environment characteristics (MEC) influence these processes.

Design/methodology/approach

The study devotes a dual-lens approach, combining the power of interviews (Phase I) and the precision of a survey (Phase II). It harnesses the insights of the entrepreneurial event model (EEM) and the technology acceptance model (TAM), serving as twin beacons guiding our exploration of the constructs under PEC/MEC.

Findings

The study uncovers a fascinating tapestry of interwoven variables. Certain threads in the PEC/MEC weave significantly into the fabric of EL, which in turn embroiders the pattern of opportunity exploitation. However, some threads, namely, Metaverse scalability, entrepreneurial risk-taking and innovativeness, do not significantly contribute to the design of EL.

Practical implications

The findings serve as a compass for various stakeholders in the metaverse. They guide the design of entrepreneurial education programs, inform the development of user-friendly metaverse platforms, shape policies promoting entrepreneurship in the metaverse and provide strategic insights for entrepreneurs and investors.

Originality/value

This study is a trailblazer, being among the first to apply the EEM and TAM in the context of the Metaverse. It offers fresh perspectives on entrepreneurial processes in virtual environments, enriching the emerging narrative on metaverse entrepreneurship and charting unexplored territories for future research.
Islamic bonds (sukuk) a safe haven for investors? Truth or myth?
Authors: Qadri Hussain Mohi-Ud-Din , Mustafa Atta Ul , Ali Hassnian , Tahir Atta Ul Mustafa
Published: August 2024

Purpose

This study aims to find whether sukuk (Islamic bonds) possess a safe haven property for investors or not.

Design/methodology/approach

To analyze this statement, the study used data from MSCI World conventional and MSCI World Islamic indices from August 17, 2012 to June 8, 2022. The study used the generalized autoregressive conditional heteroskedasticity (GARCH) variance technique, the most common technique used in stock data analysis.

Findings

The results dictate the absence of sukuk as a safe haven for investors as both the conventional and Islamic markets show decoupling behavior. The study finds concrete evidence of a strong association between the debt-based bond market and the Islamic sukuk market. As these markets mostly like to move in a parallel direction, a recession in a conventional bond market likely means a recession in the Islamic sukuk market.

Originality/value

This study is unique in incorporating the MSCI World Islamic Index and other Islamic indices of several Muslim countries, which was absent in previous research. Second, this study is unique because it adds a separate regression for the COVID era to show whether the movement of indices changed during regression.
Organizational attachment in hybrids: identification, commitment and exit/voice/loyalty
Authors: Foreman Peter
Published: August 2024

Purpose

This study aims to examine member attachment in hybrid identity organizations (HIOs), assessing the distinct effects of identification with respect to two elements (normative and utilitarian) of a hybrid’s identity. Specifically, the author explored how such dual identifications influence commitment and exit/voice/loyalty.

Design/methodology/approach

To distinguish the effects of the two identities, the author used the mechanism of identity congruence – the gap between identity perceptions and expectations – as an analog of identification. The models of identity gap, commitment and exit/voice/loyalty were examined via a survey of agricultural cooperative members.

Findings

Both the social and economic forms of identity gap were significantly related to commitment and exit/voice/loyalty. In addition, commitment mediated the relationship between identity gap and exit/voice/loyalty.

Research limitations/implications

The results demonstrate the distinctive effects of the dual identities and reinforce the importance of delineating such differences when examining identification in hybrid organizations.

Practical implications

Managers should recognize the duality inherent in hybrid organizational identification and understand the potential for different outcomes stemming from the separate identities.

Originality/value

This study represents the first quantitative examination of an integrated model of dual identification and commitment in HIOs. It is also unique in exploring the exit/voice/loyalty framework as a consequent of identification.
The impact of social capital on the intention of Moroccan university students to engage in social entrepreneurship
Authors: Mgueraman Adil , EL Abboubi Manal
Published: August 2024

Purpose

This research seeks to analyse the process by which undergraduate students make decisions on social entrepreneurship intention (SEI) using the theory of planned behaviour (TPB) model, as well as to comprehend the influence of social capital (SC) on their SEI.

Design/methodology/approach

The sample was obtained from the Faculty of Legal, Economic and Social Sciences of Agdal in Rabat, consisting of third-year students enrolled in a bachelor’s or master’s degree programme. The study involved a total of 300 pupils. The authors used the multivariate analytic method known as partial least squares (PLS) to investigate the correlation between different components of our theoretical framework.

Findings

SC has demonstrated indirect influences on the development of intentions in the field of social entrepreneurship (SE). The perceived knowledge of the support network has a substantial impact on behavioural control and subjective norms, but it does not influence attitudes. In contrast, the perceived support from the friends and family network has a substantial impact on all three components of the model.

Research limitations/implications

Despite the study’s extensive coverage of several ideas and their consequences in both the theoretical and practical realms, it is important to acknowledge its inherent limitations. The cross-sectional design and use of a student sample may be perceived as restricting considerations.

Originality/value

This research provides valuable insights that support the investments in education, resources and human endeavours made by governmental entities, universities and the private sector. It also supports the initiatives undertaken by management and business schools, as well as trade associations. When individuals establish an intention to engage in SE, whether they act on it immediately or later on or whether they never act on it at all, there is a good signal that mentorship programmes and training in SE have an influence on the process of transitioning towards taking action.
Economic evaluation of alternative urban park designs that conserve irrigation water
Authors: Doll Claire A. , Pannell David J. , Burton Michael P.
Published: August 2024

Increasing the area of drought‐tolerant native vegetation in urban parks is a potential strategy to adapt to growing water scarcity under climate change. With a case study in Perth, Australia, we undertake benefit–cost analyses to understand the potential impacts of modifying urban park landscape designs away from conventions dominated by watered grass towards alternatives with more native vegetation. Considering the costs of establishing and maintaining alternative designs alone, we find that local governments can save money by reducing the extent of watered grass cover in parks. Incorporating nonmarket benefits into the analyses provides evidence of positive community net benefits from making changes to conventional park designs. We show that an alternative park design featuring a mix of 60% native vegetation and 40% watered grass delivers the highest net benefits for both new park development and retrofits to existing parks. These findings suggest it is time to rethink urban park design norms in Australia to better align landscaping choices with community preferences under a changing climate.
Unravelling the novel sex determination genotype with ‘ZY’ and a distinctive 2.15–2.95 Mb inversion among poplar species through haplotype‐resolved genome assembly and comparative genomics analysis
Authors: Li Juan , Chen Tingting , Gao Kai , Xue Yinxuan , Wu Ruqian , Guo Bin , Chen Zhong , Li Shanwen , Zhang Ren‐Gang , Jia Kai‐Hua , Mao Jian‐Feng , An Xinmin
Published: August 2024

Populus tomentosa, an indigenous tree species, is widely distributed and cultivated over 1,000,000 km2 in China, contributing significantly to forest production, ecological conservation and urban–rural greening. Although a reference genome is available for P. tomentosa, the intricate interspecific hybrid origins, chromosome structural variations (SVs) and sex determination mechanisms remain confusion and unclear due to its broad and even overlapping geographical distribution, extensive morphological variations and cross infiltration among white poplar species. We conducted a haplotype‐resolved de novo assembly of P. tomentosa elite individual GM107, which comprises subgenomes a and b with a total genome size of 714.9 Mb. We then analysed the formation of hybrid species and the phylogenetic evolution and sex differentiation across the entire genus. Phylogenomic analyses suggested that GM107 likely originated from a hybridisation event between P. alba (♀) and P. davidiana (♂) which diverged at approximately 3.8 Mya. A total of 1551 chromosome SVs were identified between the two subgenomes. More noteworthily, a distinctive inversion structure spanning 2.15–2.95 Mb was unveiled among Populus, Tacamahaca, Turaga, Aigeiros poplar species and Salix, highlighting a unique evolutionary feature. Intriguingly, a novel sex genotype of the ZY type, which represents a crossover between XY and ZW systems, was identified and confirmed through both natural and artificial hybrids populations. These novel insights offer significant theoretical value for the study of the species' evolutionary origins and serve as a valuable resource for ecological genetics and forest biotechnology.
METTL3/IGF2BP1 influences the development of non‐small‐cell lung cancer by mediating m6A methylation modification of TRPV1
Authors: Bai Wenjie , Xiao Gang , Xie Guijing , Chen Zhibo , Xu Xie , Zeng Jie , Xie Jianjiang
Published: August 2024

Background

Methyltransferase 3 (METTL3) accelerates N6‐methyladenosine (m6A) modifications and affects cancer progression, including non‐small‐cell lung cancer (NSCLC). In this study, we aimed to explore the regulatory mechanisms of METTL3 underling NSCLC.

Methods

Immunohistochemical assay, quantitative real‐time polymerase chain reaction (qRT‐PCR) assay, and western blot assay were conducted for gene expression. MTT assay and colony formation assay were performed to explore cell proliferation capacity. Cell apoptosis and THP‐1 cell polarization were estimated by flow cytometry analysis. Cell migration and invasion capacities were evaluated by transwell assay. Methylated RNA immunoprecipitation assay, dual‐luciferase reporter assay, actinomycin D treatment and RIP assay were performed to analyze the relationships of METTL3, insulin‐like growth factor 2 mRNA binding protein 1 (IGF2BP1), and transient receptor potential cation channel subfamily V member 1 (TRPV1). The functions of METTL3 and TRPV1 in vivo were investigated through establishing the murine xenograft model.

Results

TRPV1 expression was upregulated in NSCLC and related poor prognosis. TRPV1 silencing inhibited NSCLC cell growth and metastasis, induced NSCLC cell apoptosis, and repressed M2 macrophage polarization. The results showed that METTL3 and IGF2BP1 could regulate TRPV1 expression through m6A methylation modification. Moreover, METTL3 deficiency inhibited NSCLC cell growth, metastasis, and M2 macrophage polarization and facilitated NSCLC cell apoptosis, while TRPV1 overexpression restored the impacts. In addition, METTL3 knockdown restrained tumor growth in vivo via regulating TRPV1 expression.

Conclusion

METTL3 bound to IGF2BP1 and enhanced IGF2BP1's m6A recognition of TRPV1 mRNA, thereby promoting NSCLC cell growth and metastasis, and inhibiting M2 macrophage polarization.
Clinical significance of chronic pulmonary aspergillosis in lung cancer patients undergoing anticancer drug therapy
Authors: Morimoto Kenji , Hamashima Ryosuke , Yamada Tadaaki , Yokoyama Toshihide , Kobayashi Takehiko , Tsuyuguchi Kazunari , Kanematsu Takanori , Tamiya Nobuyo , Tsuji Taisuke , Nakamura Ryota , Katayama Yuki , Nishioka Naoya , Iwasaku Masahiro , Tokuda Shinsaku , Takayama Koichi
Published: August 2024

Background

Advances in anticancer drugs for lung cancer (LC) have improved the prognosis of LC. Chronic pulmonary aspergillosis (CPA) is a progressive and often exacerbating respiratory disease with a poor prognosis. To date, the prognosis of LC complicated by CPA has not been elucidated. This study investigated the clinical implications of concomitant CPA in patients with LC undergoing anticancer drug treatment.

Methods

Between January 2010 and May 2020, we consecutively enrolled patients with LC complicated with CPA at five different institutions in Japan. We analyzed patients with LC complicated by CPA who received anticancer drug treatment.

Results

A total of 10 patients with LC complicated by CPA received anticancer drug treatment. The median overall survival (OS) was 14.57 months (95% confidence interval [CI]: 5.37–21.67). The cause of death in all patients was LC. Six of the seven patients with LC did not show worsening pulmonary aspergillosis lesions during the anticancer drug treatment. Although two patients discontinued anticancer drug treatment due to pneumonitis, CPA complications did not interfere with the continuation of anticancer drug treatment. In univariate analyses, squamous histology (p = 0.01) and body mass index (<18.5 kg/m2) (p = 0.0008) were significantly associated with poorer OS.

Conclusions

This study demonstrated that the cause of death in LC patients with concomitant CPA who received anticancer drug treatments and effective antifungal treatment was LC progression. Further large‐scale studies are needed to identify the effect of CPA in patients with LC.
Retro‐age: A unique epigenetic biomarker of aging captured by DNA methylation states of retroelements
Authors: Ndhlovu Lishomwa C. , Bendall Matthew L. , Dwaraka Varun , Pang Alina P. S. , Dopkins Nicholas , Carreras Natalia , Smith Ryan , Nixon Douglas F. , Corley Michael J.
Published: August 2024

Reactivation of retroelements in the human genome has been linked to aging. However, whether the epigenetic state of specific retroelements can predict chronological age remains unknown. We provide evidence that locus‐specific retroelement DNA methylation can be used to create retroelement‐based epigenetic clocks that accurately measure chronological age in the immune system, across human tissues, and pan‐mammalian species. We also developed a highly accurate retroelement epigenetic clock compatible with EPICv.2.0 data that was constructed from CpGs that did not overlap with existing first‐ and second‐generation epigenetic clocks, suggesting a unique signal for epigenetic clocks not previously captured. We found retroelement‐based epigenetic clocks were reversed during transient epigenetic reprogramming, accelerated in people living with HIV‐1, and responsive to antiretroviral therapy. Our findings highlight the utility of retroelement‐based biomarkers of aging and support a renewed emphasis on the role of retroelements in geroscience.
Real‐world data confirm elexacftor/tezacaftor/ivacaftor modulators halves sweat chloride concentration in eligible people with cystic fibrosis
Authors: Bryrup Thomas , Faurholt‐Jepsen Daniel , Pressler Tacjana , Henriksen Esben Herborg , Leo‐Hansen Christian , Nielsen Bibi Uhre , Højte Christine , Mathiesen Inger Hee Mabuza , Katzenstein Terese L. , Jeppesen Majbritt , Jensen‐Fangel Søren , Olesen Hanne Vebert , Skov Marianne , Qvist Tavs , Olsen Mette Frahm ,   the TransformCF Study Group
Published: August 2024

Sweat chloride concentration, a diagnostic feature in cystic fibrosis (CF), reflects CF transmembrane conductance regulator (CFTR) activity. CFTR modulator therapies, especially elexacaftor/tezacaftor/ivacaftor (ETI), has improved CF outcomes. We report nationwide, real‐world data on sweat chloride concentration in people with CF (pwCF) with and without modulator therapies. All Danish pwCF with a minimum of one F508del allele were included. Sweat chloride measurements were stratified by genotype and modulator treatment. Differences were assessed using mixed‐effects models. We included 977 sweat chloride measurements from 430 pwCF, 71% of which were F508del homozygous. Heterozygous and homozygous ETI‐treated pwCF had an estimated mean sweat chloride concentration of 43 mmol/L (95% confidence interval: 39; 48) and 43 mmol/L (39; 47), respectively—48% and 59% lower than those without treatment. High variation in concentrations remained regardless of treatment status. Despite ETI treatment, 27% heterozygous and 23% homozygous pwCF had elevated concentrations (≥60 mmol/L). These real‐world data confirm a substantial decrease in sweat chloride concentration during modulator treatment, especially ETI, where mean concentrations halved. However, large variation remained, including persistently high concentrations. These findings emphasize the potential of sweat chloride concentration as a treatment response biomarker and the need to explore its heterogeneity and relationship with clinical outcomes.
Non‐selective beta‐blocker is associated with reduced mortality in critically ill patients with cirrhosis: A real‐world study
Authors: Kumar Rahul , Lin Su , Mehta Gautam , Mesquita Monica D. , Calvao Joana A. F. , Sheikh M. Faisal , Agarwal Banwari , Mookerjee R. P. , Jalan Rajiv
Published: August 2024

Background

Apart from direct portal pressure reduction, non‐selective beta‐blockers (NSBB) modulate inflammatory response, which could be beneficial in patients with acute decompensation (AD). We therefore aimed to evaluate the effect of NSBB on 28‐day mortality and markers of systemic inflammation in a propensity score‐matched (PSM) cohort of AD patients requiring intensive care unit (ICU) admission.

Methods

Patients were recruited from registry of AD patients requiring ICU admission. Out of total 445 patients, 108 patients on NSBB before admission (NSBB use group) were PSM for age, gender, pre‐admission Child–Turcotte–Pugh score and history of previous decompensation to 108 patients not on NSBB (non‐NSBB use group) which served as the control group. ICU parameters, markers of systemic inflammation and 28‐day mortality were compared by standard statistical tests.

Results

After PSM, no difference was observed in aetiology of cirrhosis, or precipitating event for AD between the groups. Pre‐admission creatinine, bilirubin, international normalised ratio and haemoglobin were similar between the groups, whereas pre‐admission white cell count (WCC) and neutrophil to lymphocyte ratio (NLR) was lower in NSBB‐group. On admission to ICU, NSBB group had lower heart rate (p = 0.006), platelets (p = 0.012), WCC (p = 0.006), NLR (p = 0.039) and C‐reactive protein (p = 0.007). Significantly more community acquired bacterial infections (p = 0.006), renal failure (p = 0.033) and higher grades of acute‐on‐chronic liver failure (ACLF; p = 0.012) were observed in non‐NSBB group. Significantly lower 28‐day (p = 0.001) and 90‐day (p = 0.002) mortality was seen in NSBB group. Univariate and multivariable analysis for 28‐day mortality showed that while ACLF at presentation and community acquired bacterial infection were independent negative predictors, prior NSBB use was positive predictors of survival.

Conclusions

Prior use of NSBB is associated with improved 28‐ and 90‐day mortality in critically ill cirrhosis patients with AD which is mediated probably by blunting of the inflammatory response.
The pregnancy rescue case versus typical abortion
Authors: Gillham Alex R
Published: August 2024

Hendricks' pregnancy rescue case (PRC) tries to show that abortion is typically morally wrong. I argue here that there are at least two morally relevant differences between the abortion in PRC and the typical abortion so that the latter isn't morally wrong even if the former is morally wrong. I develop five modifications to PRC to show that these two differences are morally important. First, in PRC we don't know whether the person gives informed consent to the abortion, nor does the medical professional who will perform the abortion, and so the abortion can't be performed because the patient gives informed consent to it. Second, not preventing the death of the fetus in PRC brings about the death of an additional fetus gestating in a separate pregnant person, whereas most abortions don't entail the termination of another's pregnancy.
The Visible and the Invisible: Reflections on Secrecy, Dehiscence and the Gaze of the Other in the Therapeutic Encounter
Authors: de Courcier Scarlett
Published: August 2024

Psychotherapy is broadly concerned with secrets. Often our clients bring us things which they have never told anyone, subjects they have felt unable to broach. What happens in the relationship when a secret is uncovered? In this article, I discuss how one's secrets finally being uncovered can invoke shame. However, the shame of being seen in a new way can also create an opening that allows for a deeper intersubjective experience to unfold. Using Sartre's concept of the gaze of the other alongside Merleau‐Ponty's ideas of dehiscence, visibility/invisibility and intertwining, I explore the meaning of secrecy, guilt and shame for both therapist and client within the therapeutic relationship.
Validation of Serbian version of the LittlEARS® Early Speech Production Questionnaire for the assessment of early language development in typically developing children
Authors: Nikolić Mina , Zeljković Sanja Ostojić , Ivanović Maja
Published: August 2024

Objective

The LittlEARS® Early Speech Production Questionnaire (LEESPQ) was developed to provide professionals with valuable information about children's earliest language development and has been successfully validated in several languages. This study aimed to validate the Serbian version of the LEESPQ in typically developing children and compare the results with validation studies in other languages.

Methods

The English version of the LEESPQ was back‐translated into Serbian. Parents completed the questionnaire in paper or electronic form either during the visit to the paediatric clinic or through personal contact. A total of 206 completed questionnaires were collected. Standardized expected values were calculated using a second‐order polynomial model for children up to 18 months of age to create a norm curve for the Serbian language. The results were then used to determine confidence intervals, with the lower limit being the critical limit for typical speech‐language development. Finally, the results were compared with German and Canadian English developmental norms.

Results

The Serbian LEESPQ version showed high homogeneity (r = .622) and internal consistency (α = .882), indicating that it almost exclusively measures speech production ability. No significant difference in total score was found between male and female infants (U = 4429.500, p = .090), so it can be considered a gender‐independent questionnaire. The results of the comparison between Serbian and German (U = 645.500, p = .673) and Serbian and English norm curves (U = 652.000, p = .725) show that the LEESPQ can be applied to different population groups, regardless of linguistic, cultural or sociological differences.

Conclusion

The LEESPQ is a valid, age‐dependent and gender‐independent questionnaire suitable for assessing early speech development in children aged from birth to 18 months.
Reliability and validity of a measure of service providers' perceptions of child and parent engagement in pediatric rehabilitation therapy sessions
Authors: King Gillian , Chiarello Lisa A. , McLarnon Matthew J. W. , Einarson Kathleen M. , Pinto Madhu
Published: August 2024

Background

There is growing interest in client engagement in pediatric rehabilitation. This article investigated the psychometric properties of a measure of service providers' perceptions of the affective, cognitive and behavioural engagement of both children with disabilities and their parents in pediatric rehabilitation therapy sessions.

Methods

Test–retest reliability of the Pediatric Rehabilitation Intervention Measure of Engagement—Service Provider version (PRIME‐SP) was examined using engagement ratings made by 60 service providers for 77 children and 73 parents. Construct validity was examined using the known‐group validity technique, utilizing service providers' ratings of the engagement of parents and their children attending the same session with the service provider. We hypothesized that there would be significantly different, yet moderately correlated engagement ratings for children and their parents.

Results

There was evidence of moderate test–retest reliability for the child ratings, indicative of dynamicity across occasions, but also a degree of consistency, as aligned with our expectations. Service providers' ratings of parent and child engagement were not significantly correlated and paired t‐tests indicated significantly higher engagement scores for parents than children.

Conclusions

The study provides preliminary evidence to support the reliability and validity of the PRIME‐SP as a tool for service providers to document, reflect on and monitor child and/or parent engagement.
Real‐world evidence to support regulatory submissions: A landscape review and assessment of use cases
Authors: Alipour‐Haris Golnoosh , Liu Xinyue , Acha Virginia , Winterstein Almut G. , Burcu Mehmet
Published: August 2024

Real‐world evidence (RWE) has an increasing role in preapproval settings to support the approval of new medicines and indications. The main objectives of this study were to identify and characterize regulatory use cases that utilized RWE and other related observational approaches through targeted review of publications and regulatory review documents. After screening and inclusion/exclusion, the review characterized 85 regulatory applications with RWE. A total of 31 were in oncology and 54 were in non‐oncology therapeutic areas. Most were for indications in adults only (N = 42, 49.4%), while 13 were in pediatrics only (15.3%), and 30 were in both (35.3%). In terms of regulatory context, 59 cases (69.4%) were for an original marketing application, 24 (28.2%) were for label expansion, and 2 (2.4%) were for label modification. Most also received special regulatory designations (e.g., orphan indication, breakthrough therapy, fast track, conditional, and accelerated approvals). There were 42 cases that utilized RWE to support single‐arm trials. External data to support single‐arm trials were utilized in various ways across use cases, including direct matching, benchmarking, natural history studies as well as literature or previous trials. A variety of data sources were utilized, including electronic health records, claims, registries, site‐based charts. Endpoints in oncology use cases commonly included overall survival, progression‐free survival. In 13 use cases, RWE was not considered supportive/definitive in regulatory decision‐making due to design issues (e.g., small sample size, selection bias, missing data). Overall, RWE is utilized in regulatory approval processes for new indications/label expansion across various therapeutic areas with wide range of approaches. Multifaceted cross‐sector efforts are needed to further improve the quality and utility of RWE in regulatory decision‐making.
Alcohol does not impact chronic hepatitis C treatment outcomes but increases risk for progressive liver disease: Findings from a prospective multicentre Australian study (OPERA‐C)
Authors: Clark Paul J. , Valery Patricia C. , Strasser Simone I. , Weltman Martin , Thompson Alex , Levy Miriam T. , Leggett Barbara , Zekry Amany , Rong Julian , Sinclair Marie , George Jacob , Sievert William , MacQuillan Gerry , Tse Edmund , Nicoll Amanda , Wade Amanda , Cheng Wendy , Roberts Stuart K.
Published: August 2024

Introduction

Alcohol use is common in patients with chronic hepatitis C virus (HCV) infection. We examined the impact of alcohol use on direct‐acting antiviral (DAA) therapy outcome and the clinical course of liver disease and 2‐year survival for patients receiving HCV DAA therapy.

Methods

Adults (n = 2624) recruited from 26 Australian hospital liver clinics during 2016–2021 were followed up for 2 years. Risky alcohol use was defined by a combination of self‐report (≥40 g/day of ethanol), physician‐reported history of problematic alcohol use, and anti‐craving medication prescription via population‐based database linkage. We examined factors associated with advanced liver fibrosis and survival using multivariable logistic and Cox regression.

Results

Among 1634 patients (62.3%) with risky alcohol use, 24.6% reported consuming ≥40 g/day of alcohol, 98.3% physician‐reported problematic alcohol use; only 4.1% were dispensed naltrexone/acamprosate. One hundred and forty‐three patients with cirrhosis reported ≥40 g/day of alcohol, 6 (4.3%) were prescribed naltrexone/acamprosate. Risky alcohol use was associated with advanced fibrosis (adjusted‐odds ratio 1.69, 95% confidence interval 1.32–2.17) and patients were over‐represented for cirrhosis (45.1% vs. 25.6% in no‐risky alcohol use [p < 0.001]) and hepatocellular carcinoma (5.7% vs. 2.5% [p < 0.001]). Sustained viral response (p = 0.319) and 2‐year survival (adjusted‐hazard ratio 1.98, 95% confidence interval 0.84–4.63) after DAA therapy were not associated with risky alcohol use.

Discussion and Conclusions

Risky alcohol use in HCV patients was prevalent, but did not reduce HCV cure. Treatment for alcohol dependence was low. Risky alcohol use may be under‐recognised in liver clinics. Better integration of addiction medicine into liver services and increased resourcing and addiction medicine training opportunities for hepatologists may help address this.
Immediate puncture of a dislocated partially covered self‐expandable metal stent in endoscopic ultrasound‐guided hepaticogastrostomy for prevention of bile leakage
Authors: Matsubara Saburo , Suda Kentaro , Nagoshi Sumiko
Published: August 2024

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