bluuebunny/crossref_metadata_2025 huggingface dataset:
How does audit digitalization stimulate corporate green innovation? The mediating role of R&D investment
Authors: Zhang Zenglian , Shi Wen
Published: October 2024

Purpose

This paper aims to investigate how digitalization empowers government auditing with technical power to serve national governance better.

Design/methodology/approach

This study measures the audit digitalization (AD) index by textual analysis method and matches the provincial AD index with the Chinese listed firm’s data from 2011 to 2019. The two-way fixed effect regression is used to explore the nexus of audit digitalization and corporate green innovation.

Findings

The empirical results demonstrate that government audit digitalization stimulates corporate green innovation, especially for substantive green innovation. Research and development expenditures on personnel and capital are influential mediators and are increased by audit digitalization. The heterogeneity analysis indicates the anti-driving effect for fewer audit informatization expenditures or lower environmental audit coverage, and the incentive effect for state-owned enterprises or firms with corporate social responsibility reports.

Originality/value

The incremental contribution lies in recognizing the progress of government audit digitalization and its role from digital to environmental governance, which extends digital capabilities and digital expertise into the government audit view. Based on textual analysis, a reliable dictionary of audit digitalization is built by machine-learning methods. Then, the authors confirm the effectiveness of audit digitalization, especially when other forms of digitalization fail to promote substantive green innovation. This study also attests to the anti-driving and incentive effect from the external governance perspective. The authors’ findings have implications for digital ecological civilization.
Clinician perspectives on endings and discharges in community mental health work
Authors: Moore Isobel , Archard Philip John , Simmonds Sarah
Published: October 2024

Purpose

The process of ending mental health support is often not well-attended to in practice or research, and clinicians in UK mental health services lack focused clinical guidance in this area. This paper aims to report on a service evaluation that sought to understand from clinicians working in a single adult community mental health team (CMHT) their experiences of discharge and issues arising in the process, factors considered in decision-making and what constitutes “good” endings and what support could be helpful to them in navigating this with clients.

Design/methodology/approach

Semi-structured interviews were completed with six members of the multi-disciplinary team and analysed thematically.

Findings

Clinicians described a range of criteria considered in discharge decision-making. Collaboration, planning and preparation were represented as key ingredients for “good” endings. Factors viewed as complicating discharge included complexity and changes in presentation, psychosocial contexts and re-referrals. Perceptions of clients’ feelings (resistance and dependence, fear and anger, relief and gratitude) and varying feelings evoked for clinicians (from little or no reported impact, to pride and confidence, sadness and worry) at the ending of the working relationship were reported. Suggested organisational supports for clinicians with endings and discharges involved opportunities to consult with colleagues, psychological formulation and advice and reflective supervision.

Originality/value

There has been limited empirical attention to practitioner experiences of discharge in the work of CMHTs in a UK context; this practitioner-led evaluation explored clinician perspectives.
Numerical characterizations of the thermomechanical response of power modules with ceramic substrates and lead-free bonds
Authors: Gharaibeh Mohammad A. , Wilde Jürgen
Published: October 2024

Purpose

The present paper aims to study the influence of the substrate system on the thermomechanical response of various lead-free die attach materials used in power electronics using nonlinear finite element simulations.

Design/methodology/approach

Particularly, three ceramic substrate systems, including direct copper bonded (DCB) and aluminum nitride (AlN) – as well as silicon nitride (Si3N4) –based insulated metal substrate (IMS) configurations are examined in this study. Additionally, three die attach systems, namely, silver-tin transient liquid phase (TLP), sintered silver (Ag) and sintered copper (Cu) are included in the analysis. ANSYS software is employed to build the finite element models of the power modules and to conduct the nonlinear thermomechanical investigations.

Findings

The simulation results revealed that the IMS, Si3N4 and DCB-based power modules end up with significantly lower interconnect inelastic strains and inelastic strain energies suggesting better fatigue life performance. Additionally, the bonding layer stresses and expected failure mechanism are not influenced by the substrate configuration rather than the bond material. For instance, the silver-tin TLP joints develop high stresses and hence brittle failures are expected. Nonetheless, the sintered Ag and sintered Cu have significantly lower stresses which could lead to fatigue-induced failures.

Originality/value

Power electronics use various ceramic-based substrate systems because of their improved thermal conductivity, electrical insulation and heat resistance properties. The proper selection of the substrate structure could highly enhance the thermal fatigue of the power modules. Markedly, the findings of this research are useful for designing highly reliable and effective power modules continuously subjected to thermomechanical loadings.
Teacher perspectives of ChatGPT as a pedagogical tool in the K-12 setting: a case study
Authors: Bateman Tiffani
Published: October 2024

Purpose

The purpose of this exploratory qualitative case study is to gain a deeper understanding of teacher experiences and perspectives of ChatGPT as a pedagogical tool.

Design/methodology/approach

This qualitative exploratory case study examined the benefits and concerns of using ChatGPT for curriculum and instruction. Approximately 3,000 graduate education students completed a survey and an invitation to participate in focus groups. Purposive sampling criteria included graduate education students holding a current teaching certificate and actively teaching in a K-12 setting. The sample resulted in 225 survey respondents, with 12 teachers from this group also participating in three focus group sessions. Data analysis involved descriptive statistics for the survey data and inductive thematic analysis was used to identify themes from the focus group transcripts.

Findings

Results suggest ChatGPT saves teachers time, expedites access to resources, helps create lessons and is a resource for student learning while concerns arose regarding artificial intelligence (AI) and student cheating. As teachers’ comfort level with ChatGPT increased, their perception of AI as a useful pedagogical tool increased and their perception of ChatGPT as an academic hindrance decreased.

Research limitations/implications

Results from this study are not generalizable; however, the description provided allows for transferability to similar populations.

Practical implications

This study provides guidelines for a balanced approach for policies regarding AI in the K-12 setting and using ChatGPT an instructional tool while providing clear communication regarding unethical practices.

Originality/value

This study provides guidelines for framing teacher training in the technology acceptance model and providing a balanced approach for implementing AI policies while promoting using ChatGPT and other AI technologies for curriculum and instruction in the K-12 classroom.
Prediction model of surrounding rock deformation in double-continuous-arch tunnel based on the ABC-WNN
Authors: Zhang Yahui
Published: October 2024

Purpose

The wavelet neural network (WNN) has the drawbacks of slow convergence speed and easy falling into local optima in data prediction. Although the artificial bee colony (ABC) algorithm has strong global optimization ability and fast convergence speed, it also has the drawbacks of slow speed while finding the optimal solution and weak optimization ability in the later stage.

Design/methodology/approach

This article uses an ABC algorithm to optimize the WNN and establishes an ABC-WNN analysis model. Based on the example of the Jinan Yuhan underground tunnel project, the deformation of the surrounding rock of the double-arch tunnel crossing the fault fracture zone is predicted and analyzed, and the analysis results are compared with the actual detection amount.

Findings

The comparison results show that the predicted values of the ABC-WNN model have a high degree of fitting with the actual engineering data, with a maximum relative error of only 4.73%. On this basis, the results show that the statistical features of ABC-WNN are the lowest, with the errors at 0.566 and 0.573, compared with the single back propagation (BP) neural network model and WNN model. Therefore, it can be derived that the ABC-WNN model has higher prediction accuracy, better computational stability and faster convergence speed for deformation.

Originality/value

This article uses firstly the ABC-WNN for the deformation analysis of double-arch tunnels. This attempt laid the foundation for artificial intelligence prediction in deformation analysis of multi-arch tunnels and small clearance tunnels. It can provide a new and effective way for deformation prediction in similar projects.
Enhancing M-Government service adoption in Saudi Arabia: the role of mobile edge computing in moderating technology acceptance
Authors: Nusir Muneer
Published: October 2024

Purpose

Mobile edge computing (MEC) services have long been used by private enterprises in Saudi Arabia with considerable success; however, there has been a stark lack of insight into how these services can be used to improve mobile government (M-Government) services for KSA citizens. This study aims to bridge this gap by integrating MEC with an enhanced version of the technology acceptance model (TAM) and examining its effects on user behavior and acceptance.

Design/methodology/approach

A closed-ended survey was administered to 1,500 people, and the responses were analyzed using sophisticated advanced statistical techniques to test an expanded TAM, using a quantitative method that uses structural equation modeling to validate the proposed model and hypotheses.

Findings

This study reveals that MEC significantly influences users’ intentions about using M-Government services and their tolerance for new technology adoption. Specifically, service cost and social influence are positively linked with end users’ intention to adopt M-Government services.

Originality/value

The novelty and contribution of this paper to existing literature are in highlighting the pivotal role of MEC in transforming public sector service delivery through technology. This study not only supports the adoption of M-Government services to enhance social welfare but also demonstrates and concludes some practical and theoretical ramifications of MEC service adoption.
Rearing impacts on dispersal and biocontrol performance: A case study on Phytoseiulus persimilis
Authors: Willden Samantha A. , Nyrop Jan , Sanderson John , Wentworth Karen , Stockton Dara G. , Loeb Gregory M.
Published: October 2024

Ecological theory on predator–prey interactions and an understanding of how environmental factors affect predator dispersal and host finding is foundational to biological control of herbivorous pests in agricultural systems. However, our knowledge about the potential interaction between (A) the individual experience or conditioning of the arthropod predator based on its rearing environment and (B) the environmental conditions at the ultimate release site to control a particular pest is quite limited.

We hypothesized that simplified rearing conditions present in commercial insectaries may produce predators that are less adept to navigate complex and challenging crop systems compared to those reared on target crops. We chose Phytoseiulus persimilis (Phytoseiidae) as a case study because it is an important commercialized predator of the twospotted spider mite on diverse crops worldwide. We established colonies of P. persimilis on bean (commercial rearing host plant) and strawberry (target crop plant) for over five generations and compared patterns of ambulatory dispersal when released on bean or strawberry and feeding efficiency on strawberry.

Dispersal of P. persimilis was largely predicted by the presence of prey (higher dispersal when prey was absent), followed by the host on which predators were released (higher dispersal on bean compared to strawberry), and lastly by source colony (few examples of a significant difference). We found little evidence of an interaction between the two latter main effects. Rather, they were likely independent and additive. Prey consumption by P. persimilis on strawberry was higher for P. persimilis reared on strawberry compared to bean, but this did not translate into higher rates of oviposition.

Synthesis and applications. This study provides insight into sources of variation in dispersal and host finding behaviour of biocontrol agents that may help to predict biocontrol success. To compensate for prey availability and host plant effects on predator dispersal and biocontrol efficacy, we suggest that release rates and strategies should be tailored to host plants given their physical characteristics and prey quality.
Genome‐wide differentiation corresponds to climatic niches in two species of lichen‐forming fungi
Authors: Wong Edgar L. Y. , Valim Henrique F. , Schmitt Imke
Published: October 2024

Lichens can withstand fluctuating environmental conditions such as hydration‐desiccation cycles. Many species distribute across climate zones, suggesting population‐level adaptations to conditions such as freezing and drought. Here, we aim to understand how climate affects population genomic patterns in lichenized fungi. We analysed population structure along elevational gradients in closely related Umbilicaria phaea (North American; two gradients) and Umbilicaria pustulata (European; three gradients). All gradients showed clear genomic breaks splitting populations into low‐elevation (Mediterranean zone) and high‐elevation (cold temperate zone). A total of 3301 SNPs in U. phaea and 138 SNPs in U. pustulata were driven to fixation between the two ends of the gradients. The difference between the species is likely due to differences in recombination rate: the sexually reproducing U. phaea has a higher recombination rate than the primarily asexually reproducing U. pustulata. Cline analysis revealed allele frequency transitions along all gradients at approximately 0°C, coinciding with the transition between the Mediterranean and cold temperate zones, suggesting freezing is a strong driver of population differentiation. Genomic scans further confirmed temperature‐related selection targets. Both species showed similar differentiation patterns overall, but different selected alleles indicate convergent adaptation to freezing. Our results enrich our knowledge of fungal genomic functions related to temperature and climate, fungal population genomics, and species responses to environmental heterogeneity.
From food inflation to cash transfers and food subsidies: Assessing impacts on households' consumption and welfare in Togo
Authors: Bayale Nimonka , Lanie Tomgouani , Ngaba Eric Allara , Nagou Madow , Abah Kokou
Published: October 2024

This paper assesses the impacts of food price increase on households' consumption and welfare in Togo and the efficiency of policy measures, such as cash transfers and food subsidies, implemented by the Togolese government to dampen the adverse impacts. A computable general equilibrium (CGE) model is used given its appropriateness in handling economy‐wide and the welfare effect of specific policies. Simulation results show that an increase in food prices has adversely affected the consumption and welfare of all categories of households. The most affected households are self‐employed in the agriculture and other sectors, seasonal workers, trainees, and housekeepers. However, the study reveals that these adverse effects are mitigated by the government's policy responses, notably through cash transfers and food subsidies. Furthermore, the cash transfer policy seems to have a slightly greater positive effect on household consumption and welfare in response to rising food prices in Togo compared to food subsidies. This indicates that cash transfers mitigated the negative impact of food price increases on the population more effectively than food subsidies policies. These findings offer valuable insights for policymakers in optimizing public interventions and striking a balance between various policy options to address hunger and malnutrition within targeted households in Togo.
The Multilevel Implications of a Sinn Féin Government in Ireland
Authors: Kelly Conor J.
Published: October 2024

The electoral growth of Sinn Féin on both sides of the Irish border has generated much political and academic attention in recent years. The party could form part of the government in Dublin for the first time at the next Irish general election, though that outcome is far from certain. If it were to gain power, Sinn Féin is likely to pursue policies which address the core socioeconomic issues its new supporters south of the border are concerned with, namely housing and healthcare. It will also be expected to push for an Irish unification referendum in the coming decade. While Sinn Féin entering government would clearly constitute a seismic event in the politics of the Irish state, there would also be knock‐on effects for politics in Northern Ireland, as well as British‐Irish and EU‐Irish relations. This article examines the impact Sinn Féin gaining power in Dublin could have on these various political dynamics, arguing the party exerts a unique influence on Irish, UK and European politics.
Coffee substitutes: A review of the technology, characteristics, application, and future perspective
Authors: Tahmouzi Sima , Nasab Sara Sanaei , Alizadeh‐Salmani Behnam , Zare Leila , Mollakhalili‐Meybodi Neda , Nematollahi Amene
Published: October 2024

Despite being one of the most frequently consumed beverages worldwide, there are concerns that excessive consumption of coffee can have adverse effects, especially concerning the addictive and stimulating effects of the alkaloid caffeine, which contributes to coffee's popularity. It is known to increase the risk of hypertension and heart rate among predisposed individuals, adversely affecting the nervous system. Even though they differ in nature from those found in coffee, coffee substitutes can be considered economically and health‐wise as a favorable alternative to natural coffee brews. This review summarizes the state‐of‐the‐art varieties of plants used as coffee substitutes and discusses their production technology, chemical composition, nutritional properties, health benefits, economic challenges, and rationale for choosing the plant as a substitute for coffee. Various instant products and coffee substitute blends are also available on the market especially based on different kinds of plants and herbs like ginger, rye, date pits, quinoa, lupine, chicory, barley, rye, oak, and so on. These coffee substitutes have several advantages especially having no caffeine and containing different beneficial phytochemicals, although the results of the difference between the levels of harmful compounds in coffee and coffee substitutes were contradictory. Therefore, it is no wonder that the development of coffee substitutes, which are beverages that are able to mimic the taste and aroma of coffee, is on the rise at present.
Future perspectives: Current trends and controversies of meat alternatives classified as ultra‐processed foods
Authors: Lee Seung Yun , Lee Da Young , Hur Sun Jin
Published: October 2024

This study reviewed the current state of meat alternatives including plant‐based or cell‐based ingredients and discussed the contentious factor surrounding the classification of meat alternatives as ultra‐processed foods (UPFs). The term UPFs refers to foods undergoing extensive industrial processing and containing additives such as flavors, colors, emulsifiers, and preservatives. There is growing concern regarding the potential adverse effects of UPF consumption on health, nutrition, and sociodemographic factors. Additionally, this study examined the market potential, drivers, and barriers associated with different types of meat alternatives. In light of barriers focused on UPFs, meat alternatives can be disputed in that they undergo extensive processing and are highly processed, including numerous ingredients, while meat alternatives offer potential solutions to the environmental, ethical, and health issues associated with animal meat consumption. Consequently, it is important to distinguish them from other UPFs, which are known to have detrimental effects on health. Therefore, this paper proposed a reassessment of the UPF classification system, the establishment of uniform nutritional profiles for meat alternatives, and the dissemination of their beneficial impacts. These measures are necessary to validate the exclusion of meat alternatives from the UPF category and to promote their development and adoption.
Understanding the impact of the gut microbiome on opioid use disorder: Pathways, mechanisms, and treatment insights
Authors: Kazemian Negin , Pakpour Sepideh
Published: October 2024

The widespread use of opioids for chronic pain management not only poses a significant public health issue but also contributes to the risk of tolerance, dependence, and addiction, leading to opioid use disorder (OUD), which affects millions globally each year. Recent research has highlighted a potential bidirectional relationship between the gut microbiome and OUD. This emerging perspective is critical, especially as the opioid epidemic intensifies, emphasizing the need to investigate how OUD may alter gut microbiome dynamics and vice versa. Understanding these interactions could reveal new insights into the mechanisms of addiction and tolerance, as well as provide novel approaches for managing and potentially mitigating OUD impacts. This comprehensive review explores the intricate bidirectional link through the gut–brain axis, focusing on how opiates influence microbial composition, functional changes, and gut mucosal integrity. By synthesizing current findings, the review aims to inspire new strategies to combat the opioid crisis and leverage microbiome‐centred interventions for preventing and treating OUD.
The effects of Pseudomonas strains isolated from Achnatherum inebrians on plant growth: A genomic perspective
Authors: Liang Jinjin , Liu Bowen , Christensen Michael J. , Li Chunjie , Zhang Xingxu , Nan Zhibiao
Published: October 2024

Achnatherum inebrians is a perennial grass widely distributed in northwest China. Nearly all wild A. inebrians plants are infected by Epichloë endophytes. In this study, bacteria from the phyllosphere were isolated from leaves of both endophyte‐free and endophyte‐infected A. inebrians and sequenced for identification. Pseudomonas, comprising 48.12% of the culturable bacterial communities, was the most dominant bacterial genus. Thirty‐four strains from 12 Pseudomonas species were used to inoculate A. inebrians seeds and plants. Results indicated that Epichloë significantly increased the diversity and richness index of the phyllosphere. Pseudomonas Sp1, Sp3, Sp5 and Sp7 had a significantly positive effect on plant growth and photosynthesis, whereas Sp10, Sp11 and Sp12 had a significantly negative effect. Whole‐genome and pan‐genome analysis suggested that the variability in the effects of Pseudomonas on A. inebrians was related to differences in genome composition and genomic islands.
SOX17 expression in tumor‐penetrating vessels in relation to CD8+ T‐cell infiltration in cancer stroma niches
Authors: Yamamoto Hirotaka , Hanamatsu Yuki , Saigo Chiemi , Takeuchi Tamotsu , Iwata Hisashi
Published: October 2024

Introduction

Sex‐determining region Y‐related high‐mobility group box 17 protein (SOX17), a proangiogenic transcription factor, is specifically expressed in tumor endothelial cells (TECs) of implanted Lewis lung carcinoma. However, the expression profile of SOX17 is largely unknown in human lung cancer. We aimed to elucidate SOX17 expression in cancer cells and the tumor microenvironment of lung adenocarcinoma.

Methods

In the present study, we examined SOX17 expression in whole‐tissue specimens of 83 lung adenocarcinomas by immunohistochemistry.

Results

SOX17 immunoreactivity was minimal in lung adenocarcinoma cells, except in five non‐mucinous adenocarcinomas in situ. SOX17 was also expressed in cultured A549 lung adenocarcinoma cells, which is widely used as a model of malignant alveolar type II epithelial cells. Notably, SOX17 immunoreactivity was found in endothelial cells of tumor‐penetrating vessels in 19 of 83 lung adenocarcinoma tissue specimens, with statistical significance to stromal infiltration of CD8+ T cells (p < 0.01) but was not associated with the number of tertiary lymph nodes. Although not statistically significant, SOX17 immunoreactivity was related to favorable patient outcomes.

Conclusion

Our findings indicate that SOX17 might play a pleiotropic role in lung adenocarcinoma in cancer cells and stromal niches. SOX17‐mediated CD8+ T‐cell‐rich tumor microenvironment might attract interest in improving the effect of cancer immunotherapy.
The use of cash flows metrics in CEO compensation and the design of loan contracts
Authors: Gong Guojin , Jiang Xin Daniel , Xie Biqin
Published: October 2024

This study examines whether using cash‐flow‐based performance metrics (CFM) in CEO compensation contracts affects the design of loan contracts. Cash‐flow‐based performance evaluation explicitly motivates the CEO to improve the firm's cash flows, which may enhance debt repayment ability and reduce credit risk. We thus hypothesize that lenders, anticipating this incentive effect, offer lower loan spreads and reduce cash‐flow‐based performance covenants when firms use CFM in CEO compensation contracts. Consistent with our expectation, the use of CFM is associated with lower loan spreads and less use of cash‐flow‐based performance covenants. These findings remain robust after we account for endogeneity. Furthermore, these results are more pronounced in firms with higher credit risk or risk of cash flow shortfalls, suggesting that lenders consider internally generated cash flows more valuable when borrowers face higher external financing costs or have greater liquidity concerns. Additionally, we find that using CFM is associated with improved cash flow performance and enhanced creditworthiness, which supports the notion that CFM is an effective incentive mechanism. Overall, our evidence suggests that lenders consider the incentive effect of cash‐flow‐based performance evaluation in the debt contracting process.
‘A life in the shadows’: Australian women and family business succession, 1910–2018
Authors: Wright Claire E. F.
Published: October 2024

This article examines gendered succession of Australia's large family companies between 1910 and 2018. It finds that female family members were not prepared to succeed, and their role in family companies was restricted by expectations of gender and class, and ideals of male lineage. As such, women were expected to perform social, domestic and philanthropic labour in service of the company, but were consistently overlooked for succession. This highlights the way family companies conferred both wealth and inequality to women, as well as the intersection between gendered succession decisions and the structures of Australian society.
Trends in racial/ethnic and geographic disparities in substance use disorders mortality in the United States, 2000–2019
Authors: Bhagavathula Akshaya S. , Daglis Theodoros , Nishimura Yoshito
Published: October 2024

Background and Objectives

Substance use disorders (SUD) are a major public health concern in the United States. This study examined racial/ethnic and state‐level disparities in SUD mortality in the United States from 2000 to 2019.

Methods

Age‐standardized mortality rates for SUD were obtained for 5 racial/ethnic groups (White respondents, Black respondents, Latino, Asian‐Pacific Islander [API], American Indian/Alaska Native [AIAN]) by state and sex from 2000 to 2019. Joinpoint regression analysis was used to model temporal trends overall and by demographic factors.

Results

From 2000 to 2019, the overall mortality rate increased from 8.0 to 28.8 deaths per 100,000 population across all groups. AIANs had the highest mortality in 2019 (57.8 per 100,000), followed by Black respondents, White respondents, Latinos, and APIs. Significant increases occurred across all racial/ethnic groups, with the greatest average annual percentage change (AAPC2000–2019) among White respondents (6.7%; 95% confidence interval [CI]: 6.2%–7.3%), APIs (6.0%, 95% CI: 5.6%–6.2%), and AIANs (5.9%, 95% CI: 5.6%–6.2%). Mortality rates increased more rapidly for females than males among White respondents, AIANs, Black respondents, and Latinos. Substantial state‐level variation emerged, with the highest mortality rates in 2019 seen in West Virginia, the District of Columbia, Delaware, Ohio, and Pennsylvania.

Discussion and Conclusions

Racial/ethnic and geographic disparities in SUD mortality have widened significantly from 2000 to 2019, highlighting priority areas for prevention efforts.

Scientific Significance

This study provides detailed insights into long‐term trends in racial, ethnic, and geographic disparities in SUD mortality across the United States, informing targeted prevention and intervention strategies.
Single‐arm study of testosterone gel replacement therapy and ambulatory blood pressure outcomes in men with hypogonadism
Authors: Weber Michael A. , Aslam Shamaila , Efros Mitchell D. , Chan Anna , Khan Nader , Li Xue , Dubcenco Elena , Miller Michael G.
Published: October 2024

Background and Objective

Studies examining ambulatory blood pressure (BP) response to testosterone replacement therapy are needed owing to inconsistent prior findings across formulations. This study assessed testosterone gel 1.62% and 24‐h ambulatory BP.

Materials and Methods

Single‐arm non‐inferiority trial (NCT04274894) conducted at 36 US sites enrolled 246 men with hypogonadism (mean age, 57.6 years; mean office systolic/diastolic BP [SBP/DBP], 129.8/79.5 mm Hg) who were treated for 16 weeks with once‐daily testosterone gel treatment (starting dose, 40.5 mg/day; min, max dose, 20.25, 81.0 mg/day) to achieve testosterone concentration of 350–750 ng/dL. Main outcome measures included mean change in 24‐h average SBP (primary endpoint) and DBP from baseline to week 16. The non‐inferiority threshold was a two‐sided 95% confidence interval (CI) upper limit <3.0 mm Hg for 24‐h average SBP.

Results

Increase in mean ± SD serum testosterone concentration to a physiologic level (baseline, 244.4 ± 93.9 ng/dL; week 16, 502.5 ± 394.4 ng/dL) was associated with a 1.9‐mm Hg mean change in 24‐h average SBP observed in the primary analysis (baseline, 123.5 mm Hg; week 16, 125.4 mm Hg; 95% CI, 0.63–3.13 mm Hg; n = 169). As the upper CI limit modestly exceeded the non‐inferiority margin (3 mm Hg), study drug effect on SBP could not be ruled out. Non‐inferiority was observed in subgroups without hypertension or diabetes (95% CI, upper limit <3.0 mm Hg) and was not observed in those with hypertension or diabetes. Daytime SBP and DBP changes were larger compared with nighttime. No clear cardiovascular adverse events or new safety signals were identified.

Discussion and Conclusions

While the effect of testosterone gel 1.62% on 24‐h average SBP could not be ruled out based on the study's non‐inferiority margin, the clinical relevance of the small‐magnitude mean increase of 1.9 mm Hg is anticipated to be minimal considering the results of the TRAVERSE study of testosterone gel 1.62% and major adverse cardiac events.

Clinical Trial Information

ClinicalTrials.gov identifier: NCT04274894 (registered February 17, 2020)
Ruxolitinib‐based regimen in children with autoimmune disease or autoinflammatory disease‐related haemophagocytic lymphohistiocytosis
Authors: Fang Zishi , Wang Dong , Ge Jian , Zhao Yunze , Lian Hongyun , Ma Honghao , Yao Jiafeng , Zhang Qing , Zhou Chenxin , Wang Wenqian , Wang Tianyou , Li Zhigang , Zhang Rui
Published: October 2024

For autoimmune disease (AD) and autoinflammatory disease (AID)‐related haemophagocytic lymphohistiocytosis (HLH) (AD/AID‐HLH), there is still a lack of standardized treatment. Glucocorticoids (GCs) are the main treatment currently; however, 37.9% to 61% of patients fail to achieve effective control of HLH, making it urgent to find novel treatment strategies. We conducted a retrospective, single‐centre study examining ruxolitinib (RUX)‐based regimen in children with AD/AID‐HLH. Patients were first treated with RUX monotherapy, and additional treatments including methylprednisolone and etoposide were added sequentially when the disease could not be controlled. The study included 26 patients with a median follow‐up of 23.9 months, of whom 15 had prior treatments. The overall response rate at week 8 with the RUX‐based regimen was 96.2%, with 92.3% attaining complete response (CR) and 3.9% attaining partial response. The 2‐year overall survival rate was 96.2% (95% CI, 80.4% to 99.9%). During RUX monotherapy, 46.1% of patients achieved CR as the best response, with a median first response time to RUX of 2 days. Additionally, 53.8% of patients required additional GCs and 23.1% required etoposide chemotherapy. All observed adverse events were manageable and acceptable. Overall, our study supports the efficacy and safety of the RUX‐based regimen in children with AD/AID‐HLH.
Multi‐mode gravity tectonics during northern North Sea rifting: the Snorre fault block case
Authors: Fossen Haakon
Published: October 2024

Continental rifts are characterized by up to 30 km wide rotated fault blocks with stratigraphic dip away from the central rift axis. Although gravity‐induced mass movements are well known features of collapsed fault block crests, I here demonstrate the occurrence of polymodal gravity‐driven mass transport down the back slope of a first‐order rift fault block. I identify (1) early sliding related to syntectonic crestal collapse of second‐order rift faults, (2) large‐scale bed‐parallel sliding of the L‐M Jurassic sedimentary package, and (3) the accumulation of two 7 km long, 1–2 km wide and up to 750 m thick volumes of complexly slumped material in the hanging walls of two ramp‐forming faults. Early sliding is documented by 100 m of repeated Brent Group stratigraphy in a cored well in the study area (well 34/4‐15A). These smaller slides have intact internal stratigraphy but show elevated deformation band densities. The seismic data also show evidence for ca. 2 km of massive translational sliding of the ca. 400 m thick and ca. 300 km2 large Jurassic section above a lowermost Jurassic bedding‐parallel detachment. This translational slide did not deform much internally, except for ductile folding where it slid over underlying active rift faults. Chaotic seismic facies in fault hanging walls are interpreted as contorted Jurassic beds, formed by multiple slumping and sliding events that stacked mobilized sediments into a 750 m thick column. These complex slump volumes occur where fault displacement is highest along two relayed faults. A model is favoured where the large translational slide ruptured with an opening of space against the fault that was progressively filled with slumped material from the footwall. While the large‐scale translational sliding only caused moderate internal subseismic deformation, early sliding and, particularly, the complex slumping caused significant internal deformation. This study shows the importance of carefully searching for and distinguishing between different types of mass movement in rift systems.
Prevalence and outcomes of germline pathogenic variants of homologous recombination repair genes in ovarian cancer
Authors: Miwa Maiko , Kitagawa Masakazu , Asami Yuka , Kobayashi‐Kato Mayumi , Watanabe Takafumi , Ogasawara Aiko , Hiranuma Kengo , Kato Hisamori , Saito Motonobu , Miyagi Yohei , Kato Tomoyasu , Yoshida Hiroshi , Momozawa Yukihide , Kohno Takashi , Shiraishi Kouya , Hasegawa Kosei
Published: October 2024

Germline pathogenic variants (PVs) are pivotal in gynecological oncology. We focused on the prevalence, clinicopathological features, and survival impact of homologous recombination repair (HRR) PVs in patients with epithelial ovarian cancer (EOC). This was a multicenter retrospective cohort study, and 1248 patients with EOC were registered. Eligible patients (n = 1112) underwent germline DNA analysis for 26 cancer predisposition genes, including nine HRR‐related genes, such as BRCA1/2, BRIP1, PALB2, RAD51C/D, and ATM. The associations between clinicopathological factors and HRR‐related PVs were examined. Kaplan–Meier and Cox regression analyses were conducted. Among 1091 analyzed patients, 153 (14.0%) carried PVs and 140 (12.8%) were HRR‐related. HRR‐PV‐positive status significantly correlated with serous carcinoma (22.9% vs. 4.8%, P < 0.0001) and advanced disease (18.5% vs. 5.9%, P < 0.0001). The HRR‐PV‐positive group exhibited higher prevalence of personal breast (12.9%) and familial breast/ovarian (29.2%) cancer history. HRR status independently improved overall survival in stage III/IV disease (P = 0.04) but not progression‐free survival. HRR‐related germline PVs exhibit distinct clinicopathological features with survival implications. Variants were significantly associated with serous carcinoma and advanced disease, underscoring the importance of genetic testing to develop individualized EOC treatment strategies. Considering the study period (2000–2019), the limited use of bevacizumab and poly (ADP‐ribose) polymerase inhibitors as maintenance therapy should be recognized.
Development of auditory cognition in 5‐ to 10‐year‐old children: Focus on speech‐in‐babble‐noise perception
Authors: Ginzburg Jérémie , Fornoni Lesly , Aguera P. E. , Pierre Caroline , Caclin Anne , Moulin Annie
Published: October 2024

Speech‐in‐noise perception is consistently reported to be impaired in learning disorders, which stresses the importance of documenting its developmental course in young children. In this cross‐sectional study, ninety children (41 females, 5.5–11.6 years old) and nineteen normal‐hearing adults (15 females, 20–30 years old) were tested with a newly developed closed‐set speech perception in babble‐noise test, combining two levels of phonological difficulty and two noise levels. Results showed that speech‐in‐babble‐noise perception takes a definite maturation step around 7 years of age (d = 1.17, grade effect) and is not mature at 10 years of age when compared to young adults (d = 0.94, group effect). Developmental trajectories of both accuracy and response times were evaluated, with influences of psycholinguistic factors, to foster the development of adequate screening tests.
Prenatal and Pregnancy Management of Congenital Adrenal Hyperplasia
Authors: Nowotny Hanna Franziska , Tschaidse Lea , Auer Matthias K. , Reisch Nicole
Published: October 2024

Management of patients with congenital adrenal hyperplasia (CAH) poses challenges during pregnancy and prenatal stages, impacting fertility differently in men and women. Women with CAH experience menstrual irregularities due to androgen and glucocorticoid precursor interference with endometrial development and ovulation. Genital surgeries for virilization and urogenital anomalies further impact fertility and sexual function, leading to reduced heterosexual relationships among affected women. Fertility rates vary, with a lower prevalence of motherhood, primarily among those with classic CAH, necessitating optimized hormonal therapy for conception. Monitoring optimal disease control during pregnancy poses challenges due to hormonal fluctuations. Men with CAH often experience hypogonadotrophic hypogonadism and complications like testicular adrenal rest tissue, impacting fertility. Regular monitoring and intensified glucocorticoid therapy may restore spermatogenesis. Genetic counselling is vital to comprehend transmission risks and prenatal implications. Prenatal dexamethasone treatment in affected female fetuses prevents virilization but raises ethical and safety concerns, necessitating careful consideration and further research. The international “PREDICT” study aims to establish safer and more effective prenatal therapy in CAH, evaluating dosage, safety, and long‐term effects.
Comparative analysis of medical treatments for long‐term control of normal tension glaucoma: A systematic review and model‐based network meta‐analysis
Authors: Yang Ting‐Kai , Kuo Hou‐Ting , Ju Yuh‐Jen , Chen Chun‐Yi , Chen Wen‐Hsien , Wu Albert Y. , Lin Chun‐Ju , Lee Chien‐Chang , Ho Jennifer Hui‐Chun
Published: October 2024

Background

To evaluate and compare the long‐term efficacy of medical treatments for normal tension glaucoma (NTG) in controlling intraocular pressure (IOP), and establish a hierarchical ranking based on their effectiveness. ‘Long‐term’ is defined as a treatment duration of over 12 weeks in randomised controlled trials (RCTs).

Methods

This systematic review and model‐based network meta‐analysis (MBNMA) collected data of 795 patients with 997 eyes from RCTs. Patients with NTG were selected based on strict inclusion/exclusion criteria, with randomsation procedures and masking as reported in the individual trials. Eight different medications were compared, including prostaglandin analogues, beta‐blockers, brimonidine, unoprostone isopropyl, brovincamine, and palmitoylethanolamide (PEA). Notably, PEA is an oral medication, while other drugs are topical agents.

Results

Primary outcome is the long‐term efficacy of IOP control across medications with different follow‐up durations. Among the eight medications, PEA demonstrates the highest efficacy (Surface under the cumulative ranking, SUCRA = 7.46%), followed by two prostaglandin analogues: travoprost (SUCRA = 6.86%) and latanoprost (SUCRA = 6.76%), then two beta‐blockers: nipradilol (SUCRA = 4.90%) and timolol (SUCRA = 4.89%). Both brimonidine and unoprostone isopropyl have SUCRA scores below 4.0%, indicating modest but limited efficacy. Brovincamine has the lowest SUCRA score (1.32%), reflecting minimal effectiveness.

Conclusions

This study revealed PEA as a promising agent for long‐term IOP control in NTG patients, suggesting potential use as primary or adjunctive therapy. The outcomes call for PEA's consideration in clinical practice and highlight the need for further research into its long‐term efficacy and safety for NTG.
Osseointegration of Anodized vs. Sandblasted Implant Surfaces in a Guided Bone Regeneration Acute Dehiscence‐Type Defect: An In Vivo Experimental Mandibular Minipig Model
Authors: Shahdad Shakeel , Rawlinson Simon , Razaghi Nahal , Patankar Anuya , Patel Mital , Roccuzzo Mario , Gill Thomas
Published: October 2024

Objectives

This controlled preclinical study analyzed the effect of implant surface characteristics on osseointegration and crestal bone formation in a grafted dehiscence defect minipig model.

Material and Methods

A standardized 3 mm × 3 mm acute‐type buccal dehiscence minipig model grafted with deproteinized bovine bone mineral and covered with a porcine collagen membrane after 2 and 8 weeks of healing was utilized. Crestal bone formation was analyzed histologically and histomorphometrically to compare three implant groups: (1) a novel, commercially available, gradient anodized (NGA) implant, to two custom‐made geometric replicas of implant “1,” (2) a superhydrophilic micro‐rough large‐grit sandblasted and acid‐etched surface, and (3) a relatively hydrophobic micro‐rough large‐grit sandblasted and acid‐etched surface.

Results

At 2 and 8 weeks, there was no difference between the amount and height of newly formed bone (NBH, new bone height; BATA, bone area to total area) for any of the groups (p > 0.05). First bone‐to‐implant contact (fBIC) and vertical bone creep (VBC) at 2 and 8 weeks were significantly increased for Groups 2 and 3 compared to Group 1 (p < 0.05). At 8 weeks, osseointegration in the dehiscence (dehiscence bone‐implant‐contact; dBIC) was significantly higher for Groups 2 and 3 compared to Group 1 (p < 0.05).

Conclusions

The amount of newly formed bone (BATA) and NBH was not influenced by surface type. However, moderately rough surfaces demonstrated significantly superior levels of osseointegration (dBIC) and coronal bone apposition (fBIC) in the dehiscence defect compared to the NGA surface at 2 and 8 weeks.

Trial Registration

For this type of study, clinical trial registration is not required. This study was conducted at the Biomedical Department of Lund University (Lund, Sweden) and approved by the local Ethics Committee of the University (M‐192‐14)
Aetiology of Pleural Effusions in a Large Multicentre Cohort: Variation Between Outpatients and Inpatients
Authors: Yousuf Asfandyar , Holland Sophie , Zhang Junyi , Hardy Cheryl , Charles‐Rudwick Madeline , Vivian Fredrik , Denniston Poppy , Thoppuram Nithin , Kisseljov Andrei , Panchal Rakesh K. , Mishra Eleanor K.
Published: October 2024

Introduction

This multi‐centre retrospective cohort study aimed to determine whether the cause of an undiagnosed pleural effusion differed depending on if a patient presented as an outpatient or inpatient.

Methods

A total of 1080 adult patients (556 inpatients and 524 outpatients) presenting primarily with an undiagnosed pleural effusion from 1 January 2021 to 31 December 2022 from four UK hospitals were included.

Results

We found malignant effusions were more common in outpatients compared to inpatients (48.3% vs. 36.0% p < 0.0001). Infection was common in inpatients but uncommon in outpatients (36.2% vs. 5.0% p < 0.0001). Other causes in all patients included heart and/or renal failure (13.1%) and non‐specific pleuritis (5.6%). No diagnosis was possible in 11.8% of patients referred.

Conclusion

Investigative pathways should vary depending on whether patients present as an inpatient or outpatient.
Solitary Renal Metastases From Stage IA Primary Lung Adenocarcinoma With Co‐Alteration of EGFR, RB1, and MAP3K1: A Case Report
Authors: Qin Zhu , Xin Chen , Zhenzhen He , Liang Xie , Wei Yi , Shuben Li
Published: October 2024

We report a case of 59‐year‐old female with solitary bilateral renal metastases after surgery of stage IA primary lung adenocarcinoma who underwent next‐generation sequencing (NGS) of both lesions. The patient received right upper lobectomy and lymph node dissection, which revealed primary invasive lung adenocarcinoma (pT1cN0M0, stage IA3). Two years following this, positron emission tomography–computed tomography (PET/CT) revealed multiple masses in both kidneys without other distant metastases, and ultrasonography‐guided puncture biopsy indicated the presence of metastatic lung adenocarcinoma. The NGS of both the primary and metastatic lesions revealed the co‐alteration of epidermal growth factor receptor (EGFR), RB transcriptional corepressor 1 (RB1), and mitogen‐activated protein kinase kinase 1 (MAP3K1), which is potentially associated with the risk of renal metastasis in early postoperative non‐small cell lung cancer.