bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact pathways: unhooking supply chains from conflict zones—reconfiguration and fragmentation lessons from the Ukraine–Russia war
Authors: Srai Jagjit Singh , Graham Gary , Van Hoek Remko , Joglekar Nitin , Lorentz Harri
Published: August 2023

Purpose

The new geopolitical context being created by the Ukraine–Russia war highlights the need for structured approaches to planning and implementing unhooking strategies and developing associated supply chain reconfigurations.

Design/methodology/approach

The authors have interviewed six supply chain executives to begin the investigation of the key supply chain risks and disruptions caused by the Ukraine–Russia war.

Findings

Initial corporate responses to the Ukraine–Russia conflict were significant, perhaps unprecedented. However, as institutional, corporate and consumer sentiment influence reconfiguration responses, the authors have identified three supply chain pathways that underpin unhooking actions.

Research limitations/implications

The authors selected respondents from each different type of supply chain interaction with the conflict zone (inbound, outbound and within), covering both components/intermediate products and finished goods. Therefore the sample size was small and designed to fit in with the spirit of the pathway initiative.

Practical implications

The authors reinforce the key role of procurement and supply chain management in not just supply but also in downstream markets that can accelerate decoupling and mitigate the associated supply chain disruptions.

Social implications

The authors observe that supply chains are increasingly being weaponized, as external institutional and consumer influences necessitate companies to unhook from conflict zones, countries, or regimes. They are becoming increasingly intertwined with foreign policy.

Originality/value

The novelty of the contribution to the associated discourse is the perspective that after decades of increasing globalization and geographic dispersion of supply chains, the unhooking effort is not limited to a firm and its internal operations but involves multiple stakeholders. For instance, the full extent of the complex linkages of supply chains, networks and relationships that touch conflict zone geographies must be considered, particularly those that are incompatible with the firm's values and aims, including those of their stakeholders.
Sports fashion and sustainability: a perfect match?
Authors: Kopplin Cristopher Siegfried
Published: August 2023

Purpose

Sports fashion is marketed showing happiness, physical performance and self-care. Thus, sports fashion brands should see a good fit with sustainability: future orientation, self-care, care for others and going out for a physical experience, oftentimes in nature. On the other hand, sports fashion is regularly made of non-sustainable materials and produced under difficult work conditions. This paper aims to discuss the aforementioned issues.

Design/methodology/approach

The paper at hand seeks to investigate sports brands' approach to sustainability by examining their product portfolio and their annual report data, analyzing their status quo and sustainability strategy. A content analysis is conducted employing the brands' annual reports and their online shops as data sources to assess their status quo in terms of sustainability as well as future plans.

Findings

Results show that on the ecological side, brands unanimously focus on carbon reduction, organic cotton, recycled polyester, circularity-ready business model innovation and water and toxic waste management. The social aspect may be divided into the focal brand and the supply chain, including similar measures: equality and diversity, the promotion of ethnic and cultural minorities and increased safety and health for workers.

Originality/value

The paper derives development opportunities and pitfalls for sports fashion brands.
Women entrepreneurs in transport family business: a perspective article
Authors: Mogaji Emmanuel
Published: August 2023

Purpose

This paper underscores the importance of conducting studies that examine the experiences of women transport entrepreneurs within the context of the intersectionality of patriarchal culture, the challenges posed by insufficient infrastructure on business operations and the dominance of the male-dominated transport industry.

Design/methodology/approach

This paper is based on a concise literature review.

Findings

The intersectionality of these factors significantly influences women's prospects, opportunities and barriers as they navigate the entrepreneurial realm within the transportation sector. Understanding these complexities is essential to devise targeted strategies and policies that foster gender equality, promote inclusive economic growth and empower women entrepreneurs in this vital industry.

Originality/value

This paper synthesises existing research on family business, entrepreneurship and business operations in Africa.

Contribution to impact

This article has the potential to empower women in family-owned transportation businesses, promoting gender diversity and inclusivity. It achieves this by highlighting and encouraging women's leadership, leveraging their unique strengths, and fostering education and mentorship. As a result, the research is expected to drive industry growth, enhance customer satisfaction, and cultivate a more collaborative work culture. This emerging research is anticipated to transform these businesses, enabling women to become progressive leaders, thereby ensuring sustained success and fostering innovation in the transportation sector.
Distinguishing the determinants of low-cost and high-cost sustainable travel behaviors
Authors: Yin Jing
Published: August 2023

Purpose

Most research on sustainable tourism has been devoted to understanding the determinants of tourists' sustainable behavior on a unidimensional construct, overlooking the importance of behavioral costs in sustainable travel behavior. To shed light on this issue, this study aims to quantitatively differentiate sustainable travel behaviors based on behavioral costs and to examine the impact of psychological factors on both low-cost and high-cost sustainable travel behaviors.

Design/methodology/approach

A survey of 470 tourists used Rasch analysis to measure the behavioral costs associated with sustainable travel behavior and partial least squares structural equation modeling (PLS-SEM) to test hypotheses.

Findings

The results indicate that the value-identity-personal norm model explains more variance in low-cost sustainable travel behaviors than in high-cost sustainable travel behaviors. This supports the central tenet of the low-cost hypothesis and also suggests that values and self-identity factors have a stronger influence on low-cost sustainable travel behavior. However, personal norms have a stronger influence on high-cost behaviors.

Practical implications

This research highlights the importance for tourism and destination managers to distinguish between different categories of sustainable travel behavior and to analyze their determinants separately. This allows for the development of tailored messages for specific groups of tourists based on the psychological drivers of sustainable travel behavior.

Originality/value

This study provides insights into the determinants of sustainable travel behaviors with different behavioral costs and highlights the importance of analyzing different categories of behaviors separately.
Exploring the spread and scale of a web-based clinical decision support portal in Sydney, Australia, during COVID-19: a case study
Authors: McGlynn Anna , Ní Shé Éidín , Bennett Paul , Liaw Siaw-Teng , Jackson Tony , Harris-Roxas Ben
Published: August 2023

Purpose

HealthPathways is an online decision support portal, primarily aimed at General Practitioners (GPs), that provides easy to access and up to date clinical, referral and resource pathways. It is free to access, with the intent of providing the right care, at the right place, at the right time. This case study focuses on the experience and learnings of a HealthPathways program in metropolitan Sydney during the COVID-19 pandemic. It reviews the team's program management responses and looks at key factors that have facilitated the spread and scale of HealthPathways.

Design/methodology/approach

Available data and experiences of two HealthPathways program managers were used to recount events and aspects influencing spread and scale.

Findings

The key factors for successful spread and scale are a coordinated response, the maturity of the HealthPathways program, having a single source of truth, high level governance, leadership, collaboration, flexible funding and ability to make local changes where required.

Originality/value

There are limited published articles on HealthPathways. The focus of spread and scale of HealthPathways during COVID-19 is unique.
An empirical study of continuous knowledge contribution of doctors in online medical communities
Authors: Wen Dandan , Zhang Jianhua , Boamah Fredrick Ahenkora , Liu Yilin
Published: August 2023

Purpose

Continuous knowledge contribution behaviors (CKCB) are critical for the healthy development of online medical communities (OMCs). However, it is unclear that if and how contributors' prior actions and the responses they received from the community influence the nature of their future contributions. Drawing upon the Information Systems Continuance theory and Service Feedback theory, the purpose of the study is to examine the impact of knowledge contribution performance (KCP) on doctors' CKCB. Evaluation of social motivation, financial incentive and the moderating influence of expertise level (EL) provided further insight into the pathways that motivate various forms of CKCB.

Design/methodology/approach

In order to better understand the CKCB of physicians in OMCs, the authors divided it into two categories: A_CKCB (active CKCB) and P_CKCB (passive CKCB). Information Systems Continuance theory and Service Feedback theory are adapted and integrated with empirical findings from previous research on OMCs to develop a model of CKCB. This study used ordinary least squares (OLS) regression to test hypotheses in the preexisting research model based on data collected from a Chinese OMC platform.

Findings

The results show that KCP helps develop several facets of CKCB. According to the findings, doctors' CKCB improved dramatically after receiving feedback from A_CKCB and P_CKCB, but feedback from peers did not promote CKCB. This study found that financial rewards only have a significant positive effect on P_CKCB, and that the level of expertise has a negative effect on the effect. The findings also demonstrated that doctors' level of expertise moderates the relationship between fA_CKCB (a comprehensive evaluation of doctors' A_CKCB) and A_CKCB.

Research limitations/implications

Future studies should look at the role of self-efficacy as a mediator and attitudes as a moderator in the link between KCP and various forms of CKCB. This will help authors figure out how important KCP is for physicians' CKCB. And future research should use more than one way to gather data to prove the above roles.

Practical implications

This study makes a significant contribution to understanding the association between CKCB and KCP by highlighting the significance of distinguishing between the various forms of CKCB and their underlying causes.

Originality/value

This research has advanced both the theory and practice of OMCs' user management by illuminating the central role of KCP in this context.
Synergism between production and soil health through crop diversification, organic amendments and crop protection in wheat‐based systems
Authors: Walder Florian , Büchi Lucie , Wagg Cameron , Colombi Tino , Banerjee Samiran , Hirte Juliane , Mayer Jochen , Six Johan , Keller Thomas , Charles Raphaël , van der Heijden Marcel G. A.
Published: August 2023

One of the critical challenges in agriculture is enhancing yield without compromising its foundation, a healthy environment and, particularly, soils. Hence, there is an urgent need to identify management practices that simultaneously support soil health and production and help achieve environmentally sound production systems.

To investigate how management influences production and soil health under realistic agronomic conditions, we conducted an on‐farm study involving 60 wheat fields managed conventionally, under no‐till or organically. We assessed 68 variables defining management, production and soil health properties. We examined how management systems and individual practices describing crop diversification, fertiliser inputs, agrochemical use and soil disturbance influenced production—quantity and quality—and soil health focusing on aspects ranging from soil organic matter over soil structure to microbial abundance and diversity.

Our on‐farm comparison showed marked differences between soil health and production in the current system: organic management resulted in the best overall soil health (+47%) but the most significant yield gap (−34%) compared to conventional management. No‐till systems were generally intermediate, exhibiting a smaller yield gap (−17%) and only a marginally improved level of soil health (+5%) compared to conventional management. Yet, the overlap between management systems in production and soil health properties was considerably large.

Our results further highlight the importance of soil health for productivity by revealing positive associations between crop yield and soil health properties, particularly under conventional management, whereas factors such as weed pressure were more dominant in organic systems.

None of the three systems showed advantages in supporting production‐soil health‐based multifunctionality. In contrast, a cross‐system analysis suggests that multifunctional agroecosystems could be achieved through a combination of crop diversification and organic amendments with effective crop protection.

Synthesis and applications: Our on‐farm study implies that current trade‐offs in managing production and soil health could be overcome through more balanced systems incorporating conventional and alternative approaches. Such multifunctionality supporting systems could unlock synergies between vital ecosystem services and help achieve productive yet environmentally sound agriculture supported by healthy soils.
Interrogating the Political Economy of Age
Authors: Alexander‐Shaw Kate
Published: August 2023

This article considers the argument by Tim Vlandas, in this issue, that an ageing electorate may undermine democracies’ ability to make the right economic choices. Vlandas suggests that the emergence of gerontocratic politics may give rise to ‘gerontonomia’: an economy run for the old, at the expense of younger generations and of future prosperity. However, evidence from the UK suggests a more mixed picture. Age‐based voting patterns have been consequential around single issues, not least the 2016 Brexit referendum. However, voters’ interests in broad economic policy models are not easily reducible to age dynamics, and intergenerational politics are filtered through a set of normative and affective considerations beyond straightforward self‐interest. Moreover, since the rational interests of different age groups do not speak for themselves, cueing by political elites is potentially significant and may be contributing to older voters’ relative tolerance of a poor economic record.
From Gerontocracy to Gerontonomia: The Politics of Economic Stagnation in Ageing Democracies
Authors: Vlandas Tim
Published: August 2023

One in five people in the EU and nearly one in ten in the world are now aged 65 and over. This demographic transformation is one of the great successes of the twentieth century and has profoundly altered the composition of electorates in many democracies. This article explores whether and how this population ageing reshapes the relationship between democracy and capitalism. I argue that ageing changes the economic and policy priorities of a growing share of democracies’ electorates in ways that incentivise elected governments to prioritise certain social policies and economic outcomes, such as pensions and low inflation, at the expense of others, most notably greater social investments and pursuing economic growth. As a result, gerontocracies increasingly lead to what I call a ‘gerontonomia’ characterised by democratically sustained economic stagnation.
Demanding the Impossible: Public Procurement as Industrial Strategy
Authors: Coulter Steve , Meggitt‐Smith Benjamin
Published: August 2023

Governments have rediscovered industrial strategy as a central tool of economic policy in order to deal with a range of challenges, including ending the stagnation in productivity, transforming economies to meet net zero targets and coping with disruptive new technologies. An important emerging feature of this is a shift in emphasis from ‘supply‐side’ policies, focussing on tackling market failures, to ‘demand‐side’ policies, which aim to help entrepreneurs overcome uncertainty by providing a final market for their products. For UK policy makers, this shift represents opportunities to support nascent technology industries, but it also holds dangers of waste, overreach and political capture. The article assesses several possible approaches available to the UK and concludes that a viable strategy for the UK is not to try to compete with big spending schemes, like the USA's Inflation Reduction Act, but to work with entrepreneurs in de‐risking new product development.
Dealing with negative mentoring experiences: the roles of ‘can‐do’ and ‘reason‐to’ factors
Authors: Hu Zhonghui , Kwan Ho Kwong , Li Jinsong , Zhang Yingying
Published: August 2023

Academics and practitioners have long worked to reduce negative mentoring experiences. Drawing on social cognitive theory and expectancy–value theory, we examined the link between mentors' perceived organizational support and protégés' negative mentoring experiences, shedding light on the mediating effect of mentoring self‐efficacy and the moderating effect of mentors' self‐enhancement motives. Results based on data from 260 protégés and 214 mentors in Chinese organizations supported our proposed hypotheses. Mentoring self‐efficacy mediated the negative relationship between mentors' perceived organizational support and protégés' negative mentoring experiences. In addition, mentors' self‐enhancement motives intensified both the negative relationship between mentoring self‐efficacy and negative mentoring experiences and the indirect impact of mentors' perceived organizational support on protégés' negative mentoring experiences via mentoring self‐efficacy. A discussion of the theoretical and managerial implications of these findings is included.
A nephrologist dream of peritoneal dialysis catheter with zero migration: A multicenter prospective study
Authors: Al‐Hwiesh Abdullah K. , Abdul‐Rahman Ibrahiem Saeed , Divino‐Filho Jose Carolino , Nasreldin Mohamed A. , Al‐Hwiesh Amani A. , Al‐Audah Nadia , Althubaini Hatem H. , Abdulgalil Moaz , Salah Ghassan A. , Al‐Baggal Mohammad Z. , Abu‐Oun Bassam A. , Al‐Audah Nehad , Al‐Ramadan Habib S. , Alfalah Kaltham , Almarri Zahra , Al‐Awal Ayat A.
Published: August 2023

Introduction

PD catheter tip migration is a common complication and a significant cause of catheter malfunction. In this perspective, we present our experience with a new catheter and a new technique that involves the use of a new triple cuff PD catheter and a low entry site in an attempt to prevent PD catheter migration.

Methods

A total of 503 incident PD patients have been studied in more than one PD center over a period of 5 years.

Results

During the 5‐year follow up we recorded zero percent catheter migration. Other technical complications were poor drainage in 3.4%, omental wrap in 2.8%, early leakage in 3.4%, and catheter replacement in 2.4%. By the end of the study, the one‐year PD catheter survival was 97.6%.

Conclusion

Our new triple cuff PD catheter and our low‐entry approach seem to be effective in preventing PD catheter migration and minimizing other mechanical complications.
Effects of N‐acetyl‐L‐tryptophan on desorption of the protein‐bound uremic toxin indoxyl sulfate and effects on uremic sarcopenia
Authors: Ohashi Atsushi , Nakatani Masashi , Hori Hideo , Nakai Shigeru , Tsuchida Kunihiro , Hasegawa Midori , Tsuboi Naotake
Published: August 2023

Introduction

Indoxyl sulfate (IS) is a protein‐bound uremic toxin that causes uremic sarcopenia. IS has poor dialysis clearance; however, the addition of a binding competitor improves its removal efficiency.

Methods

Dialysis experiments were performed using N‐acetyl‐l‐tryptophan (L‐NAT) instead of l‐tryptophan (Trp) using pooled sera obtained from dialysis patients. The molecular structures of L‐NAT and Trp were similar to that of IS. Therefore, we examined whether Trp and L‐NAT were involved in muscle atrophy in the same manner as IS by performing culture experiments using a human myotube cell line.

Results

The removal efficiency of L‐NAT was the same as that of Trp. However, L‐NAT concentrations in the pooled sera increased at the end of the experiment. Trp (1 mM) decreased the area of human myocytes, similar to IS, whereas L‐NAT did not.

Conclusion

L‐NAT is a binding competitor with the ability to remove protein‐bound IS while preventing sarcopenia.
IRF5 promotes glycolysis in the progression of hepatocellular carcinoma and is regulated by TRIM35
Authors: Fang Ying , Lu Zhi Hui , Liu Bang Zhong , Li Nan , Yang Ming Zhen , Wang Ping
Published: August 2023

Objectives

The interferon regulatory factor (IRF) family of proteins are involved in tumor progression. However, the role of IRF5 in tumorigenesis remains unknown. In this study we aimed to elucidate the functions of IRF5 in the progression of hepatocellular carcinoma (HCC).

Methods

IRF5 expression in HCC was analyzed through quantitative polymerase chain reaction (qPCR), western blot, and immunohistochemistry (IHC), etc. The Cell Counting Kit 8 (CCK8) assay, anchorage‐independent assay, and EdU assay were used to evaluate the role of IRF5. The molecular mechanisms were studied by analyzing the metabolites with mass spectrum and immunoprecipitation.

Results

IRF5 was upregulated in HCC. Interfering with IRF5 inhibited the proliferation and tumorigenic potential of HCC cells. When studying the molecular mechanism, IRF5 was found to upregulate the expression of lactate dehydrogenase A (LDHA) and promoted glycolysis. Additionally, tripartite motif containing 35 (TRIM35) interacted with IRF5, promoting its ubiquitination and degradation. In the clinically obtained HCC samples, TRIM35 was negatively correlated with the expression of IRF5.

Conclusion

These findings reveal the oncogenic function of IRF5 in the progression of HCC by enhancing glycolysis, further supporting the potential of IRF5 as a viable target for HCC therapy.
Increased expression of autophagy‐related gene 5 indicates poor prognosis in patients with hepatocellular carcinoma
Authors: Guo Hong Ying , Yu Xiang Nan , Zhang Guang Cong , Yin Jie , Dong Ling , Liu Tao Tao , Qian Zhi Ping , Zhu Ji Min , Shen Xi Zhong
Published: August 2023

Objectives

As a critical component of the autophagic machinery, autophagy‐related gene 5 (ATG5) is essential for autophagosome formation. Autophagy participates in the transformation and progression of various malignant tumors, but the role of ATG5 in hepatocellular carcinoma (HCC) remains to be illustrated. In this study we aimed to investigate the prognostic significance of ATG5 in HCC.

Methods

ATG5 expression was evaluated in 89 pairs of HCC tissues and adjacent non‐tumor tissues. The relationship between ATG5 expression and patients' clinicopathological characteristics and prognosis were evaluated. Moreover, subgroup analyses were performed regarding patients’ age and number of tumors. Nomograms estimating overall survival (OS) and disease‐free survival (DFS) were conducted.

Results

ATG5 expression was increased in HCC specimens rather than adjacent non‐tumor tissues. The upregulated ATG5 expression was positively associated with serum α‐fetoprotein (AFP) level. Moreover, cases with a strong ATG5 expression had a poorer disease‐free survival (DFS) and overall survival (OS) than those with a weak ATG5 expression. Multivariate analysis showed that a strong expression of ATG5 was related to a poor OS and DFS in patients with HCC. Further analysis indicated that cases with a higher ATG5 expression had a poorer OS and DFS in the young patients (≤55 years) and those with solitary tumor. The nomogram suggested that there was a coherence between nomogram prediction and the actual situation of patient survival related to ATG5.

Conclusion

ATG5 promotes tumor progression in HCC, making it a potential biomarker in the diagnosis and a therapeutic target of HCC.
Angioembolisation for arterial haemorrhage related to pelvic ring injury
Authors: Kozak Thomas , Burrows Sally , Song Swithin , Soares Julian , Blakeney William
Published: August 2023

Introduction

Haemorrhage related to pelvic fractures has been associated with mortality rates of up to 50%. Angioembolisation for the management of pelvic haemorrhage was performed as early as 1972; however, there remains uncertainty over its exact use, timing and priority as a component of modern pelvic management protocols.

Methods

We retrospectively analysed cases of angioembolisation for arterial haemorrhage related to pelvic ring fractures at a level 1 trauma centre. Patient demographics were assessed as well as the time taken to reach the interventional radiology (IR) suite from the time of trauma and also arriving at the emergency room (ER). Other factors analysed included the volume of blood products consumed and fracture pattern.

Results

Fifty‐four patients received pelvic angiography for pelvic ring injuries between 2006 and 2021. The average age was 45.1 (20.5) years, with the male to female ratio 2.4:1. Forty (74.1%) of these patients had embolisation to actively bleeding pelvic arterial vessels. Median time to the IR was 4.4 [IQR 3.1–8.1] hours from time of trauma and 2.5 [IQR 2.1–4.2] hours from arrival to ER. The overall mortality rate was 18.5% and the median amount of blood transfused was 4584 mL [IQR 1643.5–8026.5]. In the subset of embolised patients (n = 40), mortality rate was 10% and there was an inverse association between time from ER to IR and volume of blood product consumption (P = 0.024).

Conclusion

Angioembolisation is a life‐saving intervention in very severely injured patients and is growing in popularity as a component of modern pelvic trauma management protocols.
A new genomic resource to enable standardized surveys of SNPs across the native range of brook trout (Salvelinus fontinalis)
Authors: Mamoozadeh Nadya R. , Whiteley Andrew R. , Letcher Benjamin H. , Kazyak David C. , Tarsa Charlene , Meek Mariah H.
Published: August 2023

Understanding how genetic diversity is distributed across spatiotemporal scales in species of conservation or management concern is critical for identifying large‐scale mechanisms affecting local conservation status and implementing large‐scale biodiversity monitoring programmes. However, cross‐scale surveys of genetic diversity are often impractical within single studies, and combining datasets to increase spatiotemporal coverage is frequently impeded by using different sets of molecular markers. Recently developed molecular tools make surveys based on standardized single‐nucleotide polymorphism (SNP) panels more feasible than ever, but require existing genomic information. Here, we conduct the first survey of genome‐wide SNPs across the native range of brook trout (Salvelinus fontinalis), a cold‐adapted species that has been the focus of considerable conservation and management effort across eastern North America. Our dataset can be leveraged to easily design SNP panels that allow datasets to be combined for large‐scale analyses. We performed restriction site‐associated DNA sequencing for wild brook trout from 82 locations spanning much of the native range and domestic brook trout from 24 hatchery strains used in stocking efforts. We identified over 24,000 SNPs distributed throughout the brook trout genome. We explored the ability of these SNPs to resolve relationships across spatial scales, including population structure and hatchery admixture. Our dataset captures a wide spectrum of genetic diversity in native brook trout, offering a valuable resource for developing SNP panels. We highlight potential applications of this resource with the goal of increasing the integration of genomic information into decision‐making for brook trout and other species of conservation or management concern.
Mitochondrial displacement loop region single nucleotide polymorphisms and mitochondrial DNA copy number associated with risk of ankylosing spondylitis
Authors: Zhang Jingjing , Peng Chenxing , Xu Shuo , Zhao Yufei , Zhang Xiaoyun , Zhang Shasha , Guo Zhanjun
Published: August 2023

Aim

The pathogenesis of ankylosing spondylitis (AS) seems to be associated with genetics, the environment, heredity, and oxidative stress. Single nucleotide polymorphisms (SNPs) in the displacement loop (D‐loop) region of mitochondrial DNA (mtDNA) and mtDNA copy number were investigated for their correlation with AS patients.

Methods

This study included 83 AS patients and 100 healthy controls from the Second Hospital of Hebei Medical University. DNAs were extracted from blood samples for polymerase chain reaction analysis and quantitative real‐time polymerase chain reaction analysis. Plasma reactive oxygen species (ROS) levels were measured by fluorescent probe technology.

Results

The distribution frequencies of the minor alleles of nucleotides 16304C (p = .037), 16311C (p = .027), and 152C (p = .034) were remarkably higher in AS patients than in healthy controls, which indicated that the16304C, 16311C, and 152C alleles were correlated with an increased risk of AS. Simultaneously, mtDNA copy number was statistically higher in patients with AS compared with controls (1.450 ± 0.876 versus 0.835 ± 0.626, p < .001). We also observed an increased ROS generation in AS patients compared with controls (27 066.169 ± 18 364.819 versus 14 758.330 ± 5854.946, p < .001) subsequently. In addition, the AS susceptible SNP 16311C is associated with high ROS levels (35 065.177 ± 26 999.934 vs. 25 005.818 ± 14 999.495, p = .043).

Conclusion

Our study demonstrated that SNPs in the mtDNA D‐loop could be AS risk biomarkers with the potential to promote oxidative stress levels; mtDNA copy number‐induced mitochondrial dysfunction may also be involved in AS pathogenesis.
Preliminary investigation of elevated collagen and blood‐clotting markers as potential noninvasive biomarkers for small cell lung cancer
Authors: Thorlacius‐Ussing Jeppe , Kristensen Søren Risom , Karsdal Morten Asser , Willumsen Nicholas , Pedersen Shona
Published: August 2023

Background

Small cell lung cancer (SCLC) is highly aggressive with limited therapeutic options and a poor prognosis. Moreover, noninvasive biomarker tools for detecting disease and monitoring treatment response are lacking. To address this, we evaluated serum biomarkers of extracellular matrix proteins not previously explored in SCLC.

Methods

We measured biomarkers in the serum of 16 patients with SCLC before and after chemotherapy as well as in the serum of 11 healthy individuals.

Results

Our findings demonstrated that SCLC serum had higher levels of collagen type I degradation, collagen type III formation, and collagen type XI formation than healthy controls. In addition, we observed higher levels of type XIX and XXII collagens, fibrinogen, and von Willebrand factor A formation in SCLC serum. The formation of type I collagen did not exhibit any discernible variation. However, we observed a decrease in the degradation of type I collagen following chemotherapy.

Conclusion

Overall, our findings revealed elevated levels of collagen and blood‐clotting markers in the serum of SCLC patients, indicating the potential of ECM proteins as noninvasive biomarkers for SCLC.
Earnings guidance stoppage and the value of financial analysts' research
Authors: Palmon Dan , Peng Xuan , Yezegel Ari
Published: August 2023

We examine the relation between voluntary disclosure and the value of analysts' research by studying the change in the informativeness of analysts' research after managers stop providing quarterly guidance to investors. We find that the market reaction to analysts' recommendation revisions increases significantly after guidance stoppage, controlling for confounding factors as well as for firm and time fixed effects. The increase in market reaction is greater for firms with more opaque information environments and for firms that previously provided disaggregated guidance. Further, the effect of guidance stoppage on the informativeness of analysts' research reverses after managers resume guidance. Finally, textual analyses of analysts' reports before and after guidance stoppage reveal that analysts issue longer, more frequent, and more detailed reports that convey more forward‐looking information after stoppages. These findings collectively shed light on the relation between the supply of voluntary disclosure and the value that sell‐side analysts add to price discovery in capital markets.
Stock market liberalization and earnings management: Evidence from a quasi‐natural experiment in China
Authors: Gao Kaijuan , Pittman Jeffrey , Wang Xiongyuan , Wang Zi‐Tian
Published: August 2023

Exploiting a quasi‐natural experiment in China in which some firms become investible to foreign investors across different times (i.e., pilot firms), we explore the role that stock market liberalization plays in shaping firms' earnings management activities. In one direction, the national‐level liberalization reform may elicit public attention from various stakeholders, piling pressure on managers to refrain from distorting their firms' earnings. In the other direction, the various restrictions that the government imposes on foreign investors cast doubt on whether China's capital control reform will materially affect pilot firms' incentives and scope to manipulate their earnings. To gauge which force is more dominant, we rely on a staggered difference‐in‐differences research design and find that pilot firms significantly reduce the magnitude of their discretionary accruals and the incidence of financial reporting irregularities from the pre‐ to the post‐liberalization period, compared to non‐pilot firms during the same time frame. Additional analysis implies that externalities in the form of stricter external monitoring from the media, institutional investors, and auditors is the major mechanism that helps market liberalization curb firms' earnings management. Our research provides insight on the importance of financial global integration to firms' earnings management practices.
Peripheral inflammatory biomarkers are associated with cognitive function and dementia: Framingham Heart Study Offspring cohort
Authors: Chen Jiachen , Doyle Margaret F. , Fang Yuan , Mez Jesse , Crane Paul K. , Scollard Phoebe ,   ADSP Data Harmonization Consortium Cognitive Harmonization Core, Satizabal Claudia L. , Alosco Michael L. , Qiu Wei Qiao , Murabito Joanne M. , Lunetta Kathryn L.
Published: August 2023

Inflammatory protein biomarkers induced by immune responses have been associated with cognitive decline and the pathogenesis of Alzheimer's disease (AD). Here, we investigate associations between a panel of inflammatory biomarkers and cognitive function and incident dementia outcomes in the well‐characterized Framingham Heart Study Offspring cohort. Participants aged ≥40 years and dementia‐free at Exam 7 who had a stored plasma sample were selected for profiling using the OLINK proteomics inflammation panel. Cross‐sectional associations of the biomarkers with cognitive domain scores (N = 708, 53% female, 22% apolipoprotein E (APOE) ε4 carriers, 15% APOE ε2 carriers, mean age 61) and incident all‐cause and AD dementia during up to 20 years of follow‐up were tested. APOE genotype‐stratified analyses were performed to explore effect modification. Higher levels of 12 and 3 proteins were associated with worse executive function and language domain factor scores, respectively. Several proteins were associated with more than one cognitive domain, including IL10, LIF‐R, TWEAK, CCL19, IL‐17C, MCP‐4, and TGF‐alpha. Stratified analyses suggested differential effects between APOE ε2 and ε4 carriers: most ε4 carrier associations were with executive function and memory domains, whereas most ε2 associations were with the visuospatial domain. Higher levels of TNFB and CDCP1 were associated with higher risks of incident all‐cause and AD dementia. Our study found that TWEAK concentration was associated both with cognitive function and risks for AD dementia. The association of these inflammatory biomarkers with cognitive function and incident dementia may contribute to the discovery of therapeutic interventions for the prevention and treatment of cognitive decline.
AAV‐Mediated nuclear localized PGC1α4 delivery in muscle ameliorates sarcopenia and aging‐associated metabolic dysfunctions
Authors: Guo Mingwei , Zhang Jun , Ma Ying , Zhu Zhenzhong , Zuo Hui , Yao Jing , Wu Xia , Wang Dongmei , Yu Jian , Meng Meiyao , Liu Caizhi , Zhang Yi , Chen Jiangrong , Lu Jian , Ding Shuzhe , Hu Cheng , Ma Xinran , Xu Lingyan
Published: August 2023

Sarcopenia is characterized of muscle mass loss and functional decline in elder individuals which severely affects human physical activity, metabolic homeostasis, and life quality. Physical exercise is considered effective in combating muscle atrophy and sarcopenia, yet it is not feasible to elders with limited mobility. PGC‐1α4, a short isoform of PGC‐1α, is strongly induced in muscle under resistance training, and promotes muscle hypertrophy. In the present study, we showed that the transcriptional levels and nuclear localization of PGC1α4 was reduced during aging, accompanied with muscle dystrophic morphology, and gene programs. We thus designed NLS‐PGC1α4 and ectopically express it in myotubes to enhance PGC1α4 levels and maintain its location in nucleus. Indeed, NLS‐PGC1α4 overexpression increased muscle sizes in myotubes. In addition, by utilizing AAV‐NLS‐PGC1α4 delivery into gastrocnemius muscle, we found that it could improve sarcopenia with grip strength, muscle weights, fiber size and molecular phenotypes, and alleviate age‐associated adiposity, insulin resistance and hepatic steatosis, accompanied with altered gene signatures. Mechanistically, we demonstrated that NLS‐PGC‐1α4 improved insulin signaling and enhanced glucose uptake in skeletal muscle. Besides, via RNA‐seq analysis, we identified myokines IGF1 and METRNL as potential targets of NLS‐PGC‐1α4 that possibly mediate the improvement of muscle and adipose tissue functionality and systemic energy metabolism in aged mice. Moreover, we found a negative correlation between PGC1α4 and age in human skeletal muscle. Together, our results revealed that NLS‐PGC1α4 overexpression improves muscle physiology and systematic energy homeostasis during aging and suggested it as a potent therapeutic strategy against sarcopenia and aging‐associated metabolic diseases.
Chronic administration of a norepinephrine antagonist prevents and partially reverses escalation of cocaine self‐administration
Authors: Beldjoud Hassiba , Avelar Alicia , de Guglielmo Giordano , Kallupi Marsida , Sedighim Sharona , Velarde Nathan , Boomhower Brent , Rizo Nathan , Carrette Lieselot L. G. , George Olivier
Published: August 2023

Anxiety is a critical component of the development and maintenance of drug addiction; however, anti‐anxiety medications such as benzodiazepines and beta‐blockers (β‐adrenergic receptor antagonists) are not used for the treatment of substance use disorder, except for the management of acute withdrawal syndrome. Preclinical studies have shown that beta‐blockers may reduce stress‐induced relapse; however, the effect of beta blockers on the escalation and maintenance of drug intake has not been tested. To address this issue, we chronically administered the β‐adrenergic receptor antagonist propranolol during the escalation or maintenance of cocaine intake in a model of extended access (6 h) to cocaine self‐administration (0.5 mg/kg). The behavioural specificity of propranolol was tested using a non‐drug reward (saccharin). Daily administration of propranolol (15 mg/kg) prevented the development of escalation of cocaine self‐administration and partially reversed self‐administration after the establishment of escalation of intake. Moreover, propranolol dose‐dependently decreased the motivation for cocaine tested under a progressive ratio schedule of reinforcement during the development of escalation and after maintenance. Finally, propranolol administration had no effect on the escalation and maintenance of saccharin self‐administration. These results demonstrate that chronic treatment with propranolol provides therapeutic efficacy in reducing cocaine self‐administration during the development and after the establishment of escalation of cocaine self‐administration in an animal model relevant to cocaine use disorder. These results suggest that beta blockers should be further investigated as a target for medication development for the treatment of cocaine use disorder.
Self‐control fluctuates from day to day and is linked to subjective well‐being within and between persons
Authors: Schmid Johanna , Moschko Tomasz , Riccio Matthew , Snyder Kenzie Aryn , Gawrilow Caterina , Stadler Gertraud
Published: August 2023

The psychological trait of self‐control has been linked to interindividual differences in subjective well‐being: Individuals with higher self‐control report less negative affect, more positive affect, and higher life satisfaction. However, less is known about how much self‐control fluctuates from day to day and how these fluctuations are related to subjective well‐being. This intensive longitudinal study describes day‐to‐day fluctuations in self‐control and investigates whether and how they are related to subjective well‐being. A sample of 64 undergraduate students at the entry phase of university (M = 22.55 years, SD = 6.51, range = 18–53, 97% female) provided 1459 reports of their self‐control and subjective well‐being, collected every evening across three 9‐day measurement bursts over 6 months. Participants' self‐control fluctuated substantially from day to day with less than 40% of the variability in daily self‐control being attributable to interindividual differences in self‐control. On days with higher self‐control, participants reported less negative affect, more serenity, and higher life satisfaction. We found no relationship between self‐control and vigor. The findings suggest that researchers need to go beyond current assessment practices and theories treating self‐control as a stable trait to help develop tailored well‐being interventions for everyday life.
A first‐in‐human study of the novel immunology antibody–drug conjugate, ABBV‐3373, in healthy participants
Authors: D'Cunha Ronilda , Kupper Hartmut , Arikan Dilek , Zhao Weihan , Carter David , Blaes Jonas , Ruzek Melanie , Pang Yinuo
Published: August 2023

Aims

ABBV‐3373, an immunology antibody–drug conjugate composed of adalimumab conjugated to a proprietary glucocorticoid receptor modulator (the small‐molecule payload), has the potential to treat immune‐mediated inflammatory diseases. This first‐in‐human study investigated the pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD) using a safety PD marker, and safety/tolerability of ABBV‐3373 in healthy adults.

Methods

Fifty‐five participants were randomly assigned to single‐dose subcutaneous (SC; 30, 100 or 300 mg) or intravenous (IV; 30, 300 or 900 mg) ABBV‐3373 or placebo. Eight additional participants received a single dose of 10 mg oral prednisone for evaluation of systemic glucocorticoid effects. Blood samples were collected for up to 85 days postdose for PK, anti‐drug antibody and serum cortisol (safety PD marker) assessments.

Results

ABBV‐3373 and total antibody displayed antibody‐like SC/IV PK profiles and the unconjugated/free payload in circulation exhibited formation rate‐limited kinetics with exposure several fold lower than ABBV‐3373 or total antibody. Treatment‐emergent anti‐drug antibody incidence was 69%, with loss of exposure in 6% (SC) and 5% (IV) of participants, but without any impact on safety. ABBV‐3373 up to 300 mg SC/IV had no apparent impact on serum cortisol, and only caused a transient decrease at 900 mg IV. Treatment‐emergent adverse events were primarily mild in severity, and no pattern emerged with respect to dose or route of administration.

Conclusions

ABBV‐3373 had favourable PK profiles, manageable immunogenicity, and was generally well‐tolerated. Except for a transient effect at 900 mg IV, there was no apparent impact on serum cortisol. Study results supported further clinical development of ABBV‐3373.
Association of haemolysis markers, blood viscosity and microcirculation function with organ damage in sickle cell disease in sub‐Saharan Africa (the BIOCADRE study)
Authors: Ranque Brigitte , Diaw Mor , Dembele Abdoul Karim , Lapoumeroulie Claudine , Offredo Lucile , Tessougue Oumar , Gueye Serigne Mourtalla , Diallo Dapa , Diop Saliou , Colin‐Aronovicz Yves , Jouven Xavier , Blanc‐Brude Olivier , Tharaux Pierre‐Louis , Le Jeune Sylvain , Connes Philippe , Romana Marc , Le Van Kim Caroline
Published: August 2023

Sickle cell anaemia (SCA) is a monogenic disease with a highly variable clinical course. We aimed to investigate associations between microvascular function, haemolysis markers, blood viscosity and various types of SCA‐related organ damage in a multicentric sub‐Saharan African cohort of patients with SCA. In a cross‐sectional study, we selected seven groups of adult patients with SS phenotype in Dakar and Bamako based on the following complications: leg ulcer, priapism, osteonecrosis, retinopathy, high tricuspid regurgitant jet velocity (TRV), macro‐albuminuria or none. Clinical assessment, echocardiography, peripheral arterial tonometry, laboratory tests and blood viscosity measurement were performed. We explored statistical associations between the biological parameters and the six studied complications. Among 235 patients, 58 had high TRV, 46 osteonecrosis, 43 priapism, 33 leg ulcers, 31 retinopathy and 22 macroalbuminuria, whereas 36 had none of these complications. Multiple correspondence analysis revealed no cluster of complications. Lactate dehydrogenase levels were associated with high TRV, and blood viscosity was associated with retinopathy and the absence of macroalbuminuria. Despite extensive phenotyping of patients, no specific pattern of SCA‐related complications was identified. New biomarkers are needed to predict SCA clinical expression to adapt patient management, especially in Africa, where healthcare resources are scarce.
A new case of platelet‐type von Willebrand disease supports the recent findings of gain‐of‐function GP1BA variants outside the C‐terminal disulphide loop enhances affinity for von Willebrand factor
Authors: Monteiro Catarina , Gonçalves Ana , Pereira Mónica , Lau Catarina , Morais Sara , Santos Rosário
Published: August 2023

Platelet‐type von Willebrand disease (PT‐VWD) is a rare autosomal dominant bleeding disorder characterized by an increased ristocetin‐induced platelet aggregation (RIPA) and enhanced affinity of platelet glycoprotein Ibα (GPIbα) to von Willebrand factor (VWF). To date, only seven variants have been described with this gain‐of‐function effect, most of them located in the C‐terminal disulphide loop of the VWF‐binding domain of GPIbα. We herein describe a patient with moderate bleeding symptoms, mild thrombocytopenia and increased RIPA. By direct sequencing of GP1BA, a novel leucine‐rich repeat heterozygous variant was identified (c.580C>T; predictably p.Leu194Phe), strongly suggestive as being the underlying cause for the PT‐VWD phenotype of our patient.