bluuebunny/crossref_metadata_2025 huggingface dataset:
Do institutional investors affect corporate governance through proxy voting and shareholder activism? Evidence from India
Authors: Ganie Irfan Rashid , Haldar Arunima , Wani Tahir Ahmad , Manuj Hemant
Published: December 2023

Purpose

This study aims to examine the role of institutional investors (using proxy voting and voice) in influencing the decisions and governance landscape of their investee firms.

Design/methodology/approach

The authors use exploratory research design due to the underdevelopment of the problem phenomena, especially in the context of emerging economies. Using asset management companies (AMC) as a proxy for institutional investors, the authors use a multiple case study design. This design was relevant in the setting as it assured triangulation by studying the same phenomenon across firms with distinct characteristics. The authors sourced the data for the multiple cases from primary sources (such as semi-structured interviews) and secondary sources (such as official Webpages and social media pages of AMC and examination of archival documents). Finally, the authors used qualitative content analysis to analyse the data.

Findings

The findings suggest that shareholder activism by institutional investors has grown in India over the period, particularly in matters related to corporate governance, related party transactions, remuneration and compensation. These AMC in India use proxy voting services for advising on voting resolutions in their investee companies. However, voting by AMC does not generally affect resolution results. This is particularly true in the presence of a high concentration of promoter holdings in investee companies.

Originality/value

The study is a novel attempt in an emerging market context to explore the role of institutional investors in influencing firm decisions and improving the governance landscape of the company using proxy voting and voice. This is especially important as the institutional framework in emerging markets is not as strong as in developed markets.
Engaging elementary students in data science practices
Authors: Adisa Ibrahim Oluwajoba , Herro Danielle , Abimbade Oluwadara , Arastoopour Irgens Golnaz
Published: December 2023

Purpose

This study is part of a participatory design research project and aims to develop and study pedagogical frameworks and tools for integrating computational thinking (CT) concepts and data science practices into elementary school classrooms.

Design/methodology/approach

This paper describes a pedagogical approach that uses a data science framework the research team developed to assist teachers in providing data science instruction to elementary-aged students. Using phenomenological case study methodology, the authors use classroom observations, student focus groups, video recordings and artifacts to detail ways learners engage in data science practices and understand how they perceive their engagement during activities and learning.

Findings

Findings suggest student engagement in data science is enhanced when data problems are contextualized and connected to students’ lived experiences; data analysis and data-based decision-making is practiced in multiple ways; and students are given choices to communicate patterns, interpret graphs and tell data stories. The authors note challenges students experienced with data practices including conflict between inconsistencies in data patterns and lived experiences and focusing on data visualization appearances versus relationships between variables.

Originality/value

Data science instruction in elementary schools is an understudied, emerging and important area of data science education. Most elementary schools offer limited data science instruction; few elementary schools offer data science curriculum with embedded CT practices integrated across disciplines. This research assists elementary educators in fostering children's data science engagement and agency while developing their ability to reason, visualize and make decisions with data.
Level of students' academic integration in the physical environment of the classroom
Authors: Al-Tkhayneh Khawlah M.
Published: December 2023

Purpose

This study aimed to identify the level of students' academic integration in the physical environment of the classroom.

Design/methodology/approach

This study used an experimental approach. The study sample consisted of 60 students, who were divided into an experimental group (n = 30) and a control group (n = 30) in two classrooms (classes 9 and 13). To verify the equivalence of the two groups, an ANOVA test was performed to determine the level of academic integration, and identify any statistically significant differences between the two groups before separating them and controlling all the other variables, except for the classroom environment variable.

Findings

The results revealed no statistically significant differences in the mean of pre-application academic integration. Ten days later, the lecturer explained the topic within the academic course and redistributed the scale of academic integration. The results of the second application revealed differences in the average mean of academic integration in favour of the experimental group (class 13). To identify statistically significant differences, a t-test was used for independent samples. The results showed statistically significant differences in the level of academic integration of the experimental group attributed to the variable of physical environment in favour of class 13.

Originality/value

This study recommend to proposing future physical learning environments in classrooms by improving physical aspects. These new learning environments can enhance the cooperation between teachers and students, allow for easier conveyance of ideas and promote students' ability to solve problems more effectively. The use of Metaverse technology in education may create an appropriate virtual physical environment that solves the problem of the physical environment and raises the level of academic integration of students.
Entrepreneurial mindset and family business performance: the United Arab Emirates perspectives
Authors: Ramadani Veland , Alkaabi Khaula Abdulla , Zeqiri Jusuf
Published: December 2023

Purpose

This study aims to investigate the impact of entrepreneurial mindsets on the performance of family businesses in the United Arab Emirates (UAE). This study focused on the following entrepreneurial mindset factors: alertness to opportunity, ambiguity tolerance, dispositional optimism and risk-taking propensity.

Design/methodology/approach

A partial least squares structural equation modeling was used to evaluate the proposed research model. The gathered data consisted of 321 family businesses that operate in the UAE.

Findings

Findings showed that only two of the entrepreneurial mindset factors had a significant and positive impact on the firm’s performance, namely, alertness to opportunity and dispositional optimism.

Originality/value

This paper covers a research gap by reflecting the effect of the entrepreneurial mindset in an unstudied context, such as the UAE. To the best of the authors’ knowledge, this is the only study that measures the effect of the dimensions of the entrepreneurial mindset on the performance of family businesses in the UAE, and as such, it represents an additional value to the literature in this field.
Adopting sustainability business models for value creation and delivery: an empirical investigation of manufacturing firms
Authors: Jagani Sandeep , Deng Xiyue , Hong Paul C. , Mashhadi Nejad Narges
Published: December 2023

Purpose

This paper examines the role of a sustainability business model in clarifying a firm's sustainability value articulation (SVA) to achieve sustainability outcomes and examining the moderating role of supplier involvement practices SIP and technology systems integration (TSI) in attaining sustainability outcomes.

Design/methodology/approach

Drawing upon the foundational principles of business model innovation, specifically articulation and implementation, the authors formulated a theoretical construct and empirically validate it through analysis of data collected from 692 manufacturing firms dispersed across 23 countries.

Findings

The research shows that focusing on SVA significantly improves how a company implements sustainability efforts internally (ISI) and externally (ESI), leading to better social and environmental outcomes. It also highlights that SIP improve the relationship between SVA, ESI and ISI. Similarly, TSI boosts the effect of internal and external sustainability efforts on both social (SOP) and environmental performance (EnP).

Research limitations/implications

While acknowledging the inherent constraints of survey-based research methodologies, this study offers a theoretical and verified approach for manufacturers to achieve comprehensive sustainability. It emphasizes the need for clear, actionable sustainability goals that can be met through both internal operations and external partnerships.

Practical implications

This study clarifies how manufacturers can implement sustainable business models, emphasizing the importance of clear sustainability goals and initiatives both within and outside the company. It highlights the dual aspects of supplier engagement through operational tactics (ESI) and strategic collaborations (SIP).

Social implications

This study reveals a thrilling truth: when companies champion clear sustainability goals, they unlock powerful strategies that revolutionize practices within their walls and in their external dealings. It is not just about going green; it is about weaving financial prosperity, social responsibility and environmental stewardship into the very fabric of their business models. But there is more – by cleverly engaging suppliers and harnessing cutting-edge technology, companies are not just participants in the green revolution; they are leading it, crafting a world where business thrives alongside the planet and its people.

Originality/value

This research stands out for its empirical analysis of how manufacturing firms implement sustainability innovations at the plant level, an area previously underexplored despite extensive theoretical work on sustainability-centric business models.
Exploring power strategies for transformation in a service-ecosystem
Authors: Hogg Johannes
Published: December 2023

Purpose

The paper covers the topic of power strategies between actors and the interplay between the service ecosystem and the actor(s), and vice versa. The paper addresses the lack of conceptual development concerning power considerations beyond dyadic, rigid and role-based models found in general marketing literature. Further, the paper opens the area of power relationships, using the service ecosystem as conceptual framework.

Design/methodology/approach

The paper has a systemic and sociological view on service-ecosystems using mainly Giddens' structuration theory. Service-dominant logic literature from 2004 to 2021 is systematically reviewed for power issues and qualitatively analyzed. Mayring's step model of, firstly, inductive and, secondly, deductive category development is applied. Subcategories were identified, subsumed and finally grouped into five categories to increase the level of abstraction.

Findings

The article investigates power considerations and enables marketers to create power through (1) imbalance, to find strategies and counterstrategies for (2) actor's behavior, to understand the (3) actor's embeddedness within a service ecosystem and its dynamic nature, to learn about (4) institutions and actor's institutional work. A set of seven propositions is presented for the conceptualization of power strategies in a service ecosystem.

Research limitations/implications

The consideration of power on different levels supports both the zooming-in and zooming-out to observe and understand the power phenomena in a service ecosystem. Seven propositions about episodic as well as systemic power relations are presented. Power is conceptualized in service ecosystem as transformative capability of an actor to intervene on institutions and in some way alter them, recognizing that power relations are co-created, dynamic and context-dependent.

Practical implications

The article recognizes different levels (micro-meso-macro) of power considerations and helps practitioners and marketers to create power through (1) imbalance, find strategies and counterstrategies for (2) actor's behavior, understand the (3) actor's embeddedness within a service ecosystem and its dynamic nature, learn about (4) institutions and actor's institutional work. This enables managers to find an appropriate choice of action in their specific context to transform the service ecosystem(s) they are embedded in.

Social implications

As all social systems are power systems, a service ecosystem can only be fully understood by integrating the elementary concept of power. As such, power considerations within actor strategies and the service ecosystem are relevant to improve the understanding of transformation of the service ecosystem. Power, in the sense of the transformative capability of actors, changes the social and material world.

Originality/value

Power issues are important to understand the “hows” of resource integration in service ecosystems and its transformation or stability.
Beyond the storefront: empirical insights into consumers' responses to omnichannel apparel retailers
Authors: Chen Yini , Chi Ting
Published: December 2023

Purpose

This research investigates apparel consumers' psychological and behavioral responses to omnichannel (OC) integration. Specifically, the study applies the cognitive–affective–conative (CAC) model to reveal consumers' decision-making process under the impact of channel integration quality (CIQ), perceived fluency (PF) and cognitive and affective trust (AT).

Design/methodology/approach

Primary data were collected through an online survey. In total, 657 eligible responses were received. This study applied partial least square structural equation modeling for data analysis.

Findings

The findings demonstrate that the extrinsic cognitive factor, CIQ, substantially affects consumers' intrinsic cognition (cognitive trust [CT] and PF), which consequently fosters consumers' AT and shopping intentions. Specifically, integrated promotion and transaction information positively affects CT, while integrated product and price and information access negatively impact CT. All the dimensions of CIQ, except integrated promotion (IP), significantly affect PF. CT and AT exhibit mediation effects in the CAC model.

Practical implications

Apparel brands and retailers may apply the findings to effectively design their retail channels and implement channel integration to boost consumers' shopping intentions and trust.

Originality/value

This study is one of the pioneering studies applying the CAC model to empirically examine OC consumers' decision-making process. It is also among the first to determine that cognitive and AT have theoretical distinctions in the OC retailing setting.
Current surgical management for melanoma
Authors: Koizumi Shigeru , Inozume Takashi , Nakamura Yasuhiro
Published: December 2023

Melanoma is a major malignant cutaneous neoplasm with a high mortality rate. In recent years, the treatment of melanoma has developed dramatically with the invention of new therapeutic agents, including immune checkpoint inhibitors and molecular‐targeted agents. These agents are available as adjuvant therapies for postoperative patients with stage IIB, IIC, and III melanomas. Furthermore, neoadjuvant therapy has been studied in several global clinical trials and has demonstrated promising and favorable clinical efficacy, mainly in patients with palpable regional lymph nodes. A recent large phase III clinical trial investigating early lymph node dissection for sentinel lymph node metastases demonstrated no survival benefits. Based on these data, surgery should be reconsidered as an appropriate treatment modality for melanoma. The need for invasive surgical procedures will be reduced with the invention of effective adjuvant and neoadjuvant therapies and novel clinical trial data on regional lymph node dissection. However, surgery still plays an important role in treating early‐stage melanoma, accurately determining the disease stage, and effective palliative treatment for advanced melanoma. In this article, we focus on surgery for primary tumors, regional lymph nodes, and metastatic sites in an era of remarkably revolutionary drug treatments for melanoma.
Species‐specific foraging behavior and diets of stream salmonids: An implication for negative impacts on native charr by nonnative trout in Japanese mountain streams
Authors: Peterson Miles I. , Kitano Satoshi , Yamamoto Shoichiro , Kando Tomohiro , Tsuda Yoshiaki
Published: December 2023

Salmonids have been introduced globally as a food source and recreational fishing target. In Japan, brown trout (Salmo trutta) and brook trout (Salvelinus fontinalis) were introduced in the 19th century and have since spread. In many headwater streams, native white‐spotted charr (Salvelinus leucomaenis) are thought to be experiencing negative impacts from these species. The current study examined foraging behavior, microhabitat use, and diet overlap of these three species in Kamikochi, Nagano Prefecture: one of Japan's premier mountain areas. In Kamikochi, many spring‐fed headwater streams are currently dominated by these invasive salmonids and white‐spotted charr have declined drastically over the last half century. Underwater video analysis revealed that while total foraging rates and foraging modes were similar between the three species, brook trout and white‐spotted charr foraged benthically more frequently than brown trout. Microhabitat water depth and flow velocity were similar between species, and fish size had a positive effect on water depth and flow velocity in all three species. Diet analysis indicated that brook trout and white‐spotted charr diets were nearly identical, comprised primary of aquatic invertebrates, while brown trout preyed on a mix of terrestrial and aquatic invertebrates, as well as amphibians and fish. These results indicate that in Kamikochi, the decline of white‐spotted charr is likely most influenced by direct competition with brook trout for prey resources. However, brown trout likely also predate on juvenile white‐spotted charr, while also possibly causing a foraging niche shift of white‐spotted charr, and have ecosystem‐level impacts due to predation on terrestrial prey.
Body mass index and weight gain in pregnancy and cardiovascular health in middle age: A cohort study
Authors: Waagaard Lovisa , Herraiz‐Adillo Ángel , Ahlqvist Viktor H. , Higueras‐Fresnillo Sara , Berglind Daniel , Wennberg Patrik , Daka Bledar , Lenander Cecilia , Sundström Johan , Östgren Carl Johan , Rådholm Karin , Henriksson Pontus
Published: December 2023

Objective

To examine associations between body mass index (BMI) in early pregnancy and gestational weight gain (GWG) with cardiovascular health in middle age using the ‘Life's Essential 8’ (LE8) concept of the American Heart Association (AHA).

Design

Population‐based cohort study.

Setting

Swedish CardioPulmonary bioImage Study (SCAPIS).

Population

A total of 8871 women from SCAPIS were included.

Methods

Information on cardiovascular health in middle age was collected from SCAPIS and linked to pregnancy weight data obtained from the Swedish Medical Birth Register, with an average follow‐up time of 24.5 years. An LE8 score between 0 and 100 was determined, where a score under 60 points was defined as poor cardiovascular health. Binary logistic regression and restricted cubic splines were used.

Main outcome measures

Cardiovascular health according to LE8 in middle age.

Results

The odds of having poor cardiovascular health in middle age were significantly higher in women who had overweight (adjusted odds ratio, aOR 3.30, 95% CI 2.82–3.88) or obesity (aOR 7.63, 95% CI 5.86–9.94), compared with women classified as being of normal weight in pregnancy. Higher odds were also found for excessive GWG (aOR 1.31, 95% CI 1.09–1.57), compared with women who gained weight within the recommendations.

Conclusions

A high BMI in early pregnancy and excessive GWG were associated with greater odds of poor cardiovascular health in middle age. Although further studies are needed, our results highlight pregnancy as an important period to support long‐term cardiovascular health.
Primary pulmonary adenoid cystic carcinoma: A clinicopathological study of 64 patients
Authors: Tan Xiang , Xu Tao , Shen Wang , Ai Cheng , Zhang Weilin , Tang Xiaojun , Luo Feng , Zhou Qinghua
Published: December 2023

Background

This study aimed to investigate the clinicopathological features and prognostic indicators of primary pulmonary adenoid cystic carcinoma (PACC).

Methods

Clinical data were collected from 64 primary PACC patients and analyzed retrospectively at the Tianjin Medical University General Hospital, the West China Hospital of Sichuan University, the First Affiliated Hospital of Guangxi Medical University, and the Bishan Hospital of Chongqing Medical University from January 2003 to August 2023. The 64 patients (28 males and 36 females) were aged from 20 to 73 years, with a median age of 49 years and an average age of 49.3 years.

Results

Immunohistochemical staining showed that the tumors expressed CK7, S‐100 protein, CK5/6, CD117, and p63. Seven patients underwent fluorescence in situ hybridization (FISH) testing and three were found to have myeloblastosis (MYB) gene translocation. In total, 53 patients underwent surgery, among whom 31 received only surgery and 22 received both surgery and postoperative chemoradiotherapy. In addition, 10 patients received chemoradiotherapy only, while one patient underwent treatment with traditional Chinese medicine. The overall survival rates in the first, third, and fifth years were 98.4%, 95.3%, and 87.5%, respectively.

Conclusion

Prognostic analysis revealed that age, tumor size, lymph node metastasis status, margin status, and choice of treatment modality significantly influenced the patients' prognosis.
An experimental laboratory‐based minority stress paradigm for alcohol research among sexual minority women: A pilot study
Authors: Fahey Kalina M. L. , Cservenka Anita , Peltier Mackenzie R. , Mereish Ethan H. , Dermody Sarah S.
Published: December 2023

Background

Sexual minority women (SMW) use alcohol at higher rates and experience greater alcohol‐related harms than their heterosexual counterparts. Evidence from observational studies suggests that minority stress (i.e., stress experienced due to marginalization in society) is an important risk factor among SMW, yet there is a lack of experimental evidence to establish a direct causal role of minority stress on alcohol use in this population. We adapted the preexisting personalized guided stress induction paradigm to conduct a pilot study of how minority stress is related to stress response (assessed via subjective measures and salivary cortisol) and mechanisms of alcohol use (craving, demand, and risky decision making) in SMW.

Methods

Using a within‐subjects design (N = 8) cisgender SMW who endorsed high‐risk drinking (≥1 heavy drinking episode in the past 30 days) completed three study visits: a script development session and two in‐person imagery induction appointments (minority stress and neutral). Analyses examined feasibility and acceptability, stress response, and mechanisms of alcohol use.

Results

The paradigm significantly increased subjective stress response (g = 1.32). Data supported the feasibility, acceptability, and appropriateness of the paradigm for use with SMW. While the paradigm did not significantly change scores on minority stress and alcohol outcomes measures, effect sizes for craving and minority stress outcomes were in the small‐to‐medium range (gs = 0.24–0.54).

Conclusions

The adapted minority stress paradigm appears to be feasible and appropriate for use with SMW to induce stress in laboratory settings. Future research can use this paradigm to understand the causal effects of minority stress on alcohol use and related outcomes.
Prevalence and risk factors of chemotherapy‐induced oral mucositis among adult cancer patients at the cancer unit of Mbarara Regional Referral Hospital
Authors: Atwiine Fredrick , Kyomya Julius , Atukunda Esther C. , Isiiko John , Yadesa Tadele Mekuriya
Published: December 2023

Background

Chemotherapy is a common treatment for cancer, but it is associated with adverse drug reactions like oral mucositis. This condition destroys basal cells in the oral mucosal layer, causing inflammation and ulceration. This can impact the patient's physical, emotional, and psychological well‐being, affecting treatment outcomes and quality of life. This study aims to determine the prevalence, severity, and risk factors of chemotherapy‐induced oral mucositis among adult cancer patients.

Methods

The study was a cross‐sectional study conducted among adult cancer patients receiving chemotherapy at the cancer unit of Mbarara Regional Referral Hospital in southwestern Uganda. Data was collected through patient interviews, oral examinations, and patient chart reviews.

Results

Out of 268 patients, 115 (42.9%) experienced oral mucositis. Grade 2 oral mucositis was the most common (44.3%) followed by grade 1 (35.7%) and grade 3 (20.0%). Independent risk factors of chemotherapy‐induced oral mucositis were female gender (Adjusted Odds Ratio (AOR) = 2.19, 95% confidence interval [CI]: 1.27–3.78; p‐value = 0.005), poor oral hygiene (AOR = 3.70, 95% CI: 1.51–9.10; p‐value = 0.04), and receiving chemotherapy containing an alkylating agent (AOR = 3.17, 95% CI: 1.63–6.19; p‐value < 0.001).

Conclusion

The study found that two out of five chemotherapy patients developed oral mucositis, with nearly half being grade 2. The risk factors identified in our study were comparable to those reported in previous studies. Therefore, identification and assessment of cancer patients at high risk for chemotherapy‐induced oral mucositis should be routinely done for proper and timely management.
Alien merchant chambers and enterprise innovation: Evidence from China
Authors: Zhou Ran , Zhao Yali
Published: December 2023

Based on social capital theory, this paper aims to investigate the impact of member enterprises of alien merchant chambers on enterprise innovation, within A‐share listed companies on the Shanghai and Shenzhen Stock Exchanges of China from 2010 to 2020. Additionally, the study seeks to explore the role played by social capital resulting from participation in these alien merchant chambers. Furthermore, we delve into the moderating effects of the number of alien merchant chambers and the degree of marketization in the enterprise's location. Moreover, we analyze the influence of heterogeneity in firm ownership and firm type. Our findings reveal that member enterprises of alien merchant chambers can increase their social capital and consequently promoting innovation; both the quantity of alien merchant chambers and the level of marketization in an enterprise's location positively influence this enhancement. Furthermore, the impact of state‐owned enterprises and non‐high‐tech enterprises on enterprise innovation, following their engagement with alien merchant chambers, surpasses that of non‐state‐owned enterprises and high‐tech enterprises. This research bridges the gap in understanding the corporate governance implications of alien merchant chambers, provides empirical evidence concerning Chinese alien merchant chambers, and addresses inquiries regarding the influence of merchant chambers' social capital. Additionally, it proposes a novel approach for listed companies to overcome resource constraints and to collaboratively pursue development, especially in light of the challenges posed by the COVID‐19 pandemic.
Detection of sessile serrated adenoma using artificial intelligence‐enhanced endoscopy: an Asian perspective
Authors: Soo Joycelyn Mun‐Peng , Koh Frederick Hong‐Xiang
Published: December 2023

Background

As the serrated pathway has gained prominence as an alternative colorectal carcinogenesis pathway, sessile serrated adenomas or polyps (SSA/P) have been highlighted as lesions to rule out during colonoscopy. These lesions are however morphologically difficult to detect on endoscopy and can be mistaken for hyperplastic polyps due to similar endoscopic features. With the underlying nature of rapid progression and malignant transformation, interval cancer is a likely consequence of undetected or overlooked SSA/P. Real‐time artificial intelligence (AI)‐assisted colonoscopy via the computer‐assisted detection system (CADe) is an increasingly useful tool in improving adenoma detection rate by providing a second eye during the procedure. In this article, we describe a guide through a video to illustrate the detection of SSA/P during AI‐assisted colonoscopy.

Methods

Consultant‐grade endoscopists utilized real‐time AI‐assisted colonoscopy device, as part of a larger prospective study, to detect suspicious lesions which were later histopathologically confirmed to be SSA/P.

Results

All lesions were picked up by the CADe where a real‐time green box highlighted suspicious polyps to the clinician. Three SSA/P of varying morphology are described with reference to classical SSA/P features and with comparison to the features of the hyperplastic polyp found in our study. All three SSA/P observed are in keeping with the JNET Classification (Type 1).

Conclusion

In conclusion, CADe is a most useful aid to clinicians during endoscopy in the detection of SSA/P but must be complemented with factors such as good endoscopy skill and bowel prep for effective detection, and biopsy coupled with subsequent accurate histological diagnosis.
Mind the gap‐missing device on the shelf? Retrospective experience with 5/7 Occlutech duct Occluder
Authors: Steiner Kristoffer , Sjöberg Gunnar , Karsenty Clément , Bianco Lisa , Bautista‐Rodriguez Carles , Fraisse Alain
Published: December 2023

Aim

To describe our initial experience with the indications and results of the 5/7 Occlutech® duct Occluder (ODO, Occlutech International AB, Helsingborg, Sweden). A small incremental increase in occluder sizes is of utmost importance for successful outcomes, especially in smaller patients in whom protrusion of the distal disk towards the aorta should be minimised.

Methods

Retrospective study of all patients undergoing PDA closure with the 5/7 ODO in three institutions since 2018.

Results

The 5/7 ODO was used in 18 patients with median age and weight at the time of the procedure of 17.5 months (interquartile range 25th to 75th percentile 8 months– 4.4 years) and 13.6 kg (interquartile range 25th to 75th percentile 6.4–22.5 kg) respectively. All cases were successful. There were no cases of device embolisation, haemolysis, or flow disturbance of the LPA or the aorta.

Conclusions

This small retrospective study demonstrated an excellent outcome of transcatheter PDA closure with the 5/7 ODO. The device is a beneficial complement to the existing sizes of PDA devices, filling the gap between the 4/6 and 6/8 ODO and avoiding protrusion of a larger disk in the aortic isthmus.
Population pharmacokinetics of rotigotine extended‐release microspheres for intramuscular injection in patients with early‐stage Parkinson's disease
Authors: Sun Hong , Dong Chong , Wu Mengyi , Li Xiao , Song Hongtao , Zhang Yan , Liu Chunli , Liu Pinglan , Liu Wanhui , Chan Piu
Published: December 2023

Aims

Rotigotine extended‐release microspheres is a weekly intramuscular injection formulation to treat Parkinson's disease. This study aimed to develop a population pharmacokinetics (PK) model for rotigotine extended‐release microspheres to investigate its PK ethnic differences.

Methods

Data for the study were obtained from three studies in China, Japan and the US. The population PK model was developed using the Phoenix NLME 8.3.5 software. Two parallel absorption models were created to include both zero‐ and first‐order absorptions. The elimination phase was evaluated for one‐ and two‐compartment linear models. Moreover, covariates including sex, body weight, body mass index, albumin, creatinine clearance and race were input into the model using a stepwise covariate method.

Results

We constructed a one‐compartment linear model with the first parallel absorption model identified as the best‐fitting model. Simulation results in patients with lighter body weight (45 kg) exhibited a 27% increase in Cmax,ss and a 31% increase in AUCtau,ss compared to those with median body weight (65 kg). Patients with heavier body weight (103 kg) showed a 27% decrease in Cmax,ss and a 29% decrease in AUCtau,ss compared to the median body weight group. Asian patients displayed only a 21% increase in Cmax,ss and a 6% increase in AUCtau,ss compared to non‐Asian. While we could not fully conclude that race does not affect rotigotine exposure, dosage adjustments based on race were not deemed necessary.

Conclusions

Exposure differences were mainly attributed to body weight, while dose adjustments were not needed for patients of different racial identities.
How to improve treatment‐free remission eligibility in chronic myeloid leukaemia?
Authors: Costa Alessandro , Breccia Massimo
Published: December 2023

The achievement of treatment‐free remission (TFR) has become a significant clinical end‐point in the management of patients with chronic myeloid leukaemia (CML), providing an opportunity to discontinue therapy with tyrosine kinase inhibitors (TKIs) while maintaining deep molecular response (DMR). Early studies, such as the French STIM trial, have demonstrated that a portion of patients can maintain DMR after treatment cessation, with rates ranging from 40% to 50%, and most relapses occurring within the first 6 months. Key prognostic factors for successful TFR, including treatment duration, duration of DMR, risk scores, and transcript type, have been identified. Optimal patient selection for TFR remains a challenge, but recent research provides insights into potential strategies to increase TFR eligibility. Evidence suggests that early intervention switching to achieve optimal response, treatment combinations, proactive switch in the case of absence of DMR, dose‐optimization and induction‐maintenance approach can improve molecular responses and, consequently, enhance TFR eligibility. In this review, we report and discuss all the potential therapeutic strategies that may enhance eligibility for a first attempt at TFR, with a particular emphasis on potential future approaches.
Biased agonists of GPR84 and insights into biological control
Authors: Luscombe Vincent B. , Wang Pinqi , Russell Angela J. , Greaves David R.
Published: December 2023

GPR84 was first identified as an open reading frame encoding an orphan Class A G protein coupled receptor in 2001. Gpr84 mRNA is expressed in a limited number of cell types with the highest levels of expression being in innate immune cells, M1 polarised macrophages and neutrophils. The first reported ligands for this receptor were medium chain fatty acids with chain lengths between 9 and 12 carbons. Subsequently, a series of synthetic agonists that signal via the GPR84 receptor were identified. Radioligand binding assays and molecular modelling with site‐directed mutagenesis suggest the presence of three ligand binding sites on the receptor, but the physiological agonist(s) of the receptor remain unidentified. Here, we review the effects of GPR84 agonists on innate immune cells following a series of chemical discoveries since 2001. The development of highly biased agonists has helped to probe receptor function in vitro, and the remaining challenge is to follow the effects of biased signalling to the physiological functions of innate immune cell types.

LINKED ARTICLES

This article is part of a themed issue GPR84 Pharmacology. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.10/issuetoc
A bi‐allelic REC114 loss‐of‐function variant causes meiotic arrest and nonobstructive azoospermia
Authors: Xu Shuai , Zhao Jingpeng , Gao Feng , Zhang Yuxiang , Luo Jiaqiang , Zhang Chenwang , Tian Ruhui , Zhi Erlei , Zhang Jianxiong , Bai Furong , Sun Hongfang , Zhao Fujun , Huang Yuhua , Li Peng , Jiang Liren , Li Zheng , Yao Chencheng , Zhou Zhi
Published: December 2023

Nonobstructive azoospermia (NOA), the most severe manifestation of male infertility, lacks a comprehensive understanding of its genetic etiology. Here, a bi‐allelic loss‐of‐function variant in REC114 (c.568C > T: p.Gln190*) were identified through whole exome sequencing (WES) in a Chinese NOA patient. Testicular histopathological analysis and meiotic chromosomal spread analysis were conducted to assess the stage of spermatogenesis arrested. Co‐immunoprecipitation (Co‐IP) and Western blot (WB) were used to investigate the influence of variant in vitro. In addition, our results revealed that the variant resulted in truncated REC114 protein and impaired interaction with MEI4, which was essential for meiotic DNA double‐strand break (DSB) formation. As far as we know, this study presents the first report that identifies REC114 as the causative gene for male infertility. Furthermore, our study demonstrated indispensability of the REC114‐MEI4 complex in maintaining DSB homoeostasis, and highlighted that the disruption of the complex due to the REC114 variant may underline the mechanism of NOA.
Application of virtual reality and haptics system Simodont in Chinese dental education: A scoping review
Authors: Huang Yudong , Huang Shuheng , Liu Yangjingwen , Lin Zhengmei , Hong Yun , Li Xiaolan
Published: December 2023

Introduction

Virtual reality (VR) and haptic simulation technology have been increasingly implemented in dental training. Since the first haptic VR dental simulator (Simodont) was introduced 10 years ago, it has been applied in more than 40 universities in mainland China. This scoping review aimed to review literature, showcasing the teaching reform of dental virtual simulation in mainland China to global dental education peers.

Methods

This scoping review was conducted using the PRISMA extension for scoping review guidelines. Seven electronic databases were searched, and two reviewers independently performed the selection and characterization of the studies.

Results

The final scoping review included 12 studies. Four studies focused on the G. V. Black class II cavity, three on manual dexterity skills training, two on full metal crown preparation, one on pulpal access and coronal cavity preparation, one on flipped classroom teaching, and one on ‘doctor–patient communication’ skills.

Discussion

The most critical scenarios, self‐assessment, working posture, curriculum setting, training and cost are analysed and discussed.

Conclusion

Haptic simulation technology is a valuable complementary tool to the phantom head in dental education. The combined utilization of these two training devices has been superior to either in isolation. However, there is a lack of research on the sequencing of the two systems, as well as the appropriate distribution of curriculum between them. It is necessary for educators to organize or engage in experience sharing, collaboration and knowledge dissemination. These actions are essential for promoting effective teaching within dental educational institutions.
CD74–ROS1 L2026M mutant enhances autophagy through the MEK/ERK pathway to promote invasion, metastasis and crizotinib resistance in non‐small cell lung cancer cells
Authors: Xu Xiaobo , Li Ye , Xu Rui , Meng Yuting , Li Zengqiang , Zuo Daiying , Wu Yingliang
Published: December 2023

The treatment of non‐small cell lung cancer (NSCLC) patients harboring a proto‐oncogene tyrosine‐protein kinase c‐ros oncogene 1 (ROS1) fusion gene has greatly benefited from the use of crizotinib. However, drug resistance inevitably occurs after 1 year of treatment. Clinical studies have shown that patients with an L2026M mutation in the ROS1 kinase domain account for about 6% of the total number of crizotinib‐resistant cases, which is an important group that cannot be ignored. To explore the mechanism involved, we constructed the HLA class II histocompatibility antigen gamma chain (CD74)–ROS1 L2026M mutant gene by fusion polymerase chain reaction (PCR) and transfected it into H460 and A549 cells. We found that the invasion and metastasis abilities of drug‐resistant cells were increased. The results of monodansylcadaverine (MDC) staining, Acridine orange (AO) staining, and western blot indicated that the autophagy level of CD74–ROS1 L2026M mutant NSCLC cells was increased compared with the CD74–ROS1 group, and the inhibition of autophagy could reverse the increased invasion and metastasis abilities caused by the L2026M mutation. In addition, the L2026M mutation led to excessive activation of the MEK/ERK pathway, and MEK inhibitors could reduce the autophagy level, invasion, and metastasis abilities of cells; additionally, this process could be blocked by rapamycin, an activator of autophagy. Furthermore, crizotinib treatment activated expression of Src homology region 2 domain‐containing phosphatase‐2 (SHP2; also known as PTPN11) to upregulate the MEK/ERK pathway, and the combination of MEK inhibitors and crizotinib increased apoptosis compared with crizotinib alone. In conclusion, our results indicate that the MEK/ERK pathway mediates the induction of invasion, metastasis, and crizotinib resistance through autophagy caused by CD74–ROS1 L2026M mutation in NSCLC cells, and targeting MEK could reverse these processes.
Evaluation of a diagnostic platelet aggregation test strategy for platelet rich plasma samples with low platelet counts
Authors: Altahan Rahaf Mahmoud , Mathews Natalie , Bourguignon Alex , Tasneem Subia , Arnold Donald M. , Lim Wendy , Hayward Catherine P. M.
Published: December 2023

Introduction

Light transmission aggregometry (LTA) is important for diagnosing platelet function disorders (PFD) and von Willebrand disease (VWD) affecting ristocetin‐induced platelet aggregation (RIPA). Nonetheless, data is lacking on the utility of LTA for investigating thrombocytopenic patients and platelet rich plasma samples with low platelet counts (L‐PRP). Previously, we developed a strategy for diagnostic LTA assessment of L‐PRP that included: (1) acceptance of referrals/samples, regardless of thrombocytopenia severity, (2) tailored agonist selection, based on which are informative for L‐PRP with mildly or severely low platelet counts, and (3) interpretation of maximal aggregation (MA) using regression‐derived 95% confidence intervals, determined for diluted control L‐PRP (C‐L‐PRP).

Methods

To further evaluate the L‐PRP LTA strategy, we evaluated findings for a subsequent patient cohort.

Results

Between 2008 and 2021, the L‐PRP strategy was applied to 211 samples (11.7% of all LTA samples) from 192 unique patients, whose platelet counts (median [range] × 109/L) for blood and L‐PRP were: 105 [13–282; 89% with thrombocytopenia] and 164 [17–249], respectively. Patient‐L‐PRP had more abnormal MA findings than simultaneously tested C‐L‐PRP (p‐values <0.001). Among patients with accessible electronic medical records (n = 181), L‐PRP LTA uncovered significant aggregation abnormalities in 45 (24.9%), including 18/30 (60%) with <80 × 109 platelets/L L‐PRP, and ruled out PFD, and VWD affecting RIPA, in others. The L‐PRP LTA strategy helped diagnose VWD affecting RIPA, Bernard Soulier syndrome, familial platelet disorder with myeloid malignancy, suspected ITGA2B/ITGB3‐related thrombocytopenia, and acquired PFD.

Conclusion

Diagnostic LTA with L‐PRP, using a strategy that considers thrombocytopenia severity, is feasible and informative.
GnRH antagonist monotherapy versus a GnRH agonist plus bicalutamide for advanced hormone‐sensitive prostate cancer; KYUCOG‐1401
Authors: Yokomizo Akira , Shiota Masaki , Morokuma Futoshi , Eto Masatoshi , Matsuyama Hideyasu , Matsumoto Hiroaki , Kamoto Toshiyuki , Terada Naoki , Kawahara Kazuya , Enokida Hideki , Tatarano Shuichi , Fujimoto Naohiro , Higasijima Katsuyoshi , Sakai Hideki , Hakariya Tomoaki , Igawa Tsukasa , Suekane Shigetaka , Kamba Tomomi , Sugiyama Yutaka , Kishimoto Junji , Naito Seiji
Published: December 2023

Objectives

To compare the effectiveness and safety of gonadotropin‐releasing hormone (GnRH) antagonist monotherapy to combined androgen blockade (CAB) with a GnRH agonist and bicalutamide in patients with advanced hormone‐sensitive prostate cancer (HSPC).

Methods

The study was conducted as KYUCOG‐1401 trial (UMIN000014243) and enrolled 200 patients who were randomly assigned to either group A (GnRH antagonist monotherapy followed by the addition of bicalutamide) or group B (CAB by a GnRH agonist and bicalutamide). The primary endpoint was PSA progression‐free survival. The secondary endpoints were the time to CAB treatment failure, radiographic progression‐free survival, overall survival, changes in serum parameters, including PSA, hormones, and bone and lipid metabolic markers, and adverse events.

Results

PSA progression‐free survival was significantly longer in group B (hazard ratio [HR], 95% confidence interval [CI]; 1.40, 1.01–1.95, p = 0.041). The time to CAB treatment failure was slightly longer in group A (HR, 95% CI; 0.80, 0.59–1.08, p = 0.146). No significant differences were observed in radiographic progression‐free survival or overall survival. The percentage of patients with serum testosterone that did not reach the castration level was higher at 60 weeks (p = 0.046) in group A. No significant differences were noted in the serum levels of bone metabolic or lipid markers between the two groups. An injection site reaction was more frequent in group A.

Conclusions

The present results support the potential of CAB using a GnRH agonist and bicalutamide as a more effective treatment for advanced HSPC than GnRH antagonist monotherapy.
Investigation of phenotypic, genetic and genomic background of Milk spectra in Sarda dairy sheep
Authors: Congiu Michele , Falchi Laura , Carta Silvia , Cesarani Alberto , Dimauro Corrado , Correddu Fabio , Macciotta Nicolò Pietro Paolo
Published: December 2023

Aim of this study was to analyse the genetic background of milk Fourier transform infrared (FTIR) spectra in dairy sheep. Individual milk FTIR spectra, with 1060 wavenumbers each, were available for 793 adult Sarda breed ewes genotyped at 45,813 SNP. The absorbance values of each wavenumber was analysed using a linear mixed model that included dim class, parity and lambing month as fixed effects and flock‐test date and animal as random effects. The model was applied to estimate variance components and heritability and to perform a genome‐wide association study for each wavenumber. Average h2 of wavenumbers absorbance was 0.13 ± 0.08, with the largest values observed in the regions associated with the characteristic bonds of carbonylic and methylenic groups of milk fat (h2 = 0.57 at 1724–1728 cm−1; and h2 = 0.34 at 2811–2834 cm−1, respectively). The absorbance values of wavenumbers were moderately correlated with the estimated heritabilities. After the Bonferroni correction, a total of nine markers were found to be significantly associated with 32 different wavenumbers. Of particular interest was the SNP s63269.1, mapped on chromosome 2, that was found to be associated with 27 wavenumbers. Genes previously found to be related to traits of interest (e.g. disease resistance, milk yield and quality, cheese firmness) are located close to the significant SNP. As expected, the heritability estimated for the absorbance of each wavenumbers seems to be associated with the related milk components.