bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementing Data Workflows and Data Model Extensions with RDF-star
Authors: Rupp Florian , Schnabel Benjamin , Eckert Kai
Published: March 2024

Purpose

The purpose of this work is to explore the new possibilities enabled by the recent introduction of RDF-star, an extension that allows for statements about statements within the Resource Description Framework (RDF). Alongside Named Graphs, this approach offers opportunities to leverage a meta-level for data modeling and data applications.

Design/methodology/approach

In this extended paper, the authors build onto three modeling use cases published in a previous paper: (1) provide provenance information, (2) maintain backwards compatibility for existing models, and (3) reduce the complexity of a data model. The authors present two scenarios where they implement the use of the meta-level to extend a data model with meta-information.

Findings

The authors present three abstract patterns for actively using the meta-level in data modeling. The authors showcase the implementation of the meta-level through two scenarios from our research project: (1) the authors introduce a workflow for triple annotation that uses the meta-level to enable users to comment on individual statements, such as for reporting errors or adding supplementary information. (2) The authors demonstrate how adding meta-information to a data model can accommodate highly specialized data while maintaining the simplicity of the underlying model.

Practical implications

Through the formulation of data modeling patterns with RDF-star and the demonstration of their application in two scenarios, the authors advocate for data modelers to embrace the meta-level.

Originality/value

With RDF-star being a very new extension to RDF, to the best of the authors’ knowledge, they are among the first to relate it to other meta-level approaches and demonstrate its application in real-world scenarios.
ESG performance and disclosure quality: does a well-balanced board of directors matter when impression management occurs?
Authors: Hamza Sourour , Jarboui Anis
Published: March 2024

Purpose

This paper explores how the disclosure quality, measured by the abnormal tone of environmental and social report, may determine the environmental, social and corporate governance (ESG) performance of the firm. This study also investigates the impact of the moderator “board of directors” to explore the extent to which a well-balanced board of directors may affect this association within an impression management strategy.

Design/methodology/approach

This work uses a sample of 616 firm-year observations using a sample of French firms indexed on SBF120 index from 2010 to 2017. To test the developed hypotheses, the GLS regression is applied and to control for endogeneity issue and sample selection bias, the authors used, respectively, the two stage least square (2SLS) procedure and the Heckman model.

Findings

Findings suggest that a well-balanced board of directors moderates the relationship between the ESG performance and the disclosure quality. The positive effect of abnormal tone management on ESG is weakened by the presence of a good structure of the board, attenuating impression management initiatives.

Research limitations/implications

The research provides evidence of the impact of corporate social responsibility (CSR) reporting quality, in particular disclosure tone management, on the level of ESG performance in the French context. As the board of directors may have a major impact on weakening impression management strategies in particular tone management practices, in order to improve CSR report quality, the authors recommend French companies to ensure a well-balanced board of directors.

Originality/value

This study helps investors to comprehensively evaluate the information disclosed on CSR reports. It unveils that a strong board composition induces better quality of CSR report and brings better ESG performance. Thus, the study results point to the importance of a well-balanced board of directors and the regulation of the narrative disclosure of CSR information.
Can gamified e-service quality improve customer value co-creation and relationship quality in e-retailing?
Authors: Tabaeeian Reihaneh Alsadat , Mohammad Shafiee Majid , Ansari Azarnoush
Published: March 2024

Purpose

This paper aims to investigate the effect of gamified e-service quality (GE-SQ) on customer value co-creation, relationship quality and purchase intention in e-retailing.

Design/methodology/approach

A questionnaire was used to collect data from a sample of 549 e-retailing customers who participated in a gamified online service process. A structural equation modeling approach was adopted to analyze the model.

Findings

The empirical evidence confirmed that GE-SQ encouraged customer value co-creation behavior and relationship quality. Customer value co-creation and relationship quality led to higher purchase intention. Also, value co-creation and relationship quality partially mediated the relationship between GE-SQ and purchase intention.

Originality/value

The findings increase our knowledge of GE-SQ and its behavioral consequences. Moreover, the study proposes and validates a theoretical framework based on GE-SQ, value co-creation and customer relationship quality. This study provides insight into using gamification as a practical tool in the e-retailing industry.
A single-step firm-level identification of classification shifting
Authors: Mamatzakis Emmanuel , Tsionas Mike
Published: March 2024

Purpose

This study proposes a new model to measure unexpected core earnings, using Bayesian dynamic latent method.

Design/methodology/approach

The Bayesian dynamic latent modeling approach identifies the effects that stem from complex, multidimensional variables related to culture and legal framework, on unexpected core earnings. It also allows testing whether there is persistence over time in unexpected core earnings. We use sequential Bayesian Monte Carlo methods, also known as particle filtering, that simplify estimations.

Findings

In an international empirical application, we find evidence of persistence in unexpected core earnings as well as classification shifting. The impact of the legal framework on classification shifting shows variability across samples. Religion reduces classification shifting, whereas the cultural variables of power distance, masculinity and uncertainty avoidance enhances it. Interestingly, the persistence in unexpected core earnings is strong and moderates the ability of legal framework and religion in abating classification shifting.

Research limitations/implications

In terms of policy implications, we show that strengthening legal framework would improve financial reporting and reduce the scope for manipulation. This could involve stricter enforcement mechanisms, increased penalties for non-compliance and regular audits to detect and deter classification shifting practices. Given that religion plays a role in moderating classification shifting, policymakers may explore partnerships or collaborations with religious institutions to promote ethical financial practices. Engaging religious leaders and organizations can help emphasize the importance of integrity and ethical behavior in financial reporting, potentially influencing the behavior of individuals and organizations.

Originality/value

To the best of our knowledge this is the first study that opts for Bayesian dynamic latent model for an international sample.
Student engagement in a differentiated higher education system in Ethiopia: a multilevel analysis
Authors: Moges Bekalu Tadesse , Gebremeskel Melaku Mengistu , Tilwani Shouket Ahmad , Assefa Yalalem
Published: March 2024

Purpose

The purpose of this study is to examine effects of classroom-level and student-level factors on student engagement in the context of a higher education system vertically differentiated into research, applied and comprehensive university types.

Design/methodology/approach

The study used a cross-sectional multilevel design to explain student engagement based on class and student variables. Specifically, the study collects data from 656 students and 61 randomly selected teachers at both levels and uses multilevel modeling to explain relationship patterns.

Findings

The results show that institutions vary significantly in student engagement scores. In addition, while a significant variation is found at the student and classroom level, the effects of academic achievement, instructional quality, teaching experience and teacher qualifications on student engagement vary across classrooms in institutions. However, the interaction effect of classroom and student-level variables on student engagement remains non-significant.

Originality/value

The main contribution of this lies in the explanation of student engagement using classroom and student level factors in a vertically differentiated higher education system using multilevel modeling. Student engagement varied in classrooms research universities applied and comprehensive universities.
Positioning UAE archaeological sites in tourism supply chains
Authors: De Man Adriaan
Published: March 2024

Purpose

The purpose of this study is to address the relevance of archaeological heritage in the context of supply chains for the tourism industry. It does so by providing converging ideas on the usefulness of individual sites, not in their strict scientific or latent value but as an enhancer for optimizing cultural production in a wider scenario of aggregate demand.

Design/methodology/approach

While examples from the United Arab Emirates (UAE) illustrate this reasoning, the underlying principles have a widespread application and point to a need for defragmenting and realigning tangible heritage as a key production factor. Methods used consist of an inductive approach, based on secondary sources and semi-structured interviews.

Findings

Results indicate that, while archaeological resources remain central to the promotion of cultural tourism in the UAE, suppliers face challenges when incorporating particular sites into consumer-friendly packages.

Practical implications

The study contributes to the identification of common risks and opportunities for archaeological resource management in the development of UAE tourism products.

Originality/value

This represents an original angle, given the focus on the specific regional, cooperative added value of archaeological resources and the need for optimizing them in a functional supply chain.
The promotion of Spanish travel agencies from the 20th century to the present
Authors: Araque-Hontangas Natividad
Published: March 2024

Purpose

The purpose of this paper is to investigate the unexplored part of the historical evolution of travel agencies in Spain, from the end of the 20th century to the 21st century. When examining promotion strategies, the study focuses on the change in marketing and public relations strategies based on the incorporation of information and communication technologies and, in particular, the use of the internet.

Design/methodology/approach

This study draws on a qualitative analysis of the different strategies used by traditional agencies and online agencies in Spain from the mid-19th century to the present. This analysis shows how traditional communication strategies survived at the beginning of the 21st century, together with other more innovative ones, while some disappeared, being eliminated by the new online travel agencies, which created a particular conception of marketing and communication. This paper is divided into the following parts: the introduction; the beginnings of travel agency promotion in the 20th century; the evolution of promotion in travel agencies since the late 20th century; communication innovation at the beginning of the 21st century; online travel agencies; and conclusions.

Findings

This study shows that although online agencies did not manage to position themselves with a large turnover, they generated advantages and sharpened their imagination to create a new, more economical advertising model, eliminating the costs of public relations and advertising campaigns. In addition, they allowed clients to have greater independence when making their reservations, while enabling them to monitor the tastes of potential and real clients and add blogs so that consumers could express their degree of satisfaction with the product or services provided by the agency.

Originality/value

The focus of attention is the travel agency sector in Spain and, more specifically, communication. Studies on travel agencies and their marketing have been very scarce and partial, impeding professionals in the tourism sector from having a broad vision to direct their promotional and public relations actions. The originality of this article lies in its making a comparison between two different visions of tourism marketing and, specifically, of travel agencies, that is, the traditional vision and the innovative one. It thus helps all professionals in the sector to value and improve their marketing and communication strategies.
Measuring performance of metasearch engines to access information: an exploratory study based on precision metrics
Authors: Bhardwaj Raj Kumar , Kumar Ritesh , Nazim Mohammad
Published: March 2024

Purpose

This paper evaluates the precision of four metasearch engines (MSEs) – DuckDuckGo, Dogpile, Metacrawler and Startpage, to determine which metasearch engine exhibits the highest level of precision and to identify the metasearch engine that is most likely to return the most relevant search results.

Design/methodology/approach

The research is divided into two parts: the first phase involves four queries categorized into two segments (4-Q-2-S), while the second phase includes six queries divided into three segments (6-Q-3-S). These queries vary in complexity, falling into three types: simple, phrase and complex. The precision, average precision and the presence of duplicates across all the evaluated metasearch engines are determined.

Findings

The study clearly demonstrated that Startpage returned the most relevant results and achieved the highest precision (0.98) among the four MSEs. Conversely, DuckDuckGo exhibited consistent performance across both phases of the study.

Research limitations/implications

The study only evaluated four metasearch engines, which may not be representative of all available metasearch engines. Additionally, a limited number of queries were used, which may not be sufficient to generalize the findings to all types of queries.

Practical implications

The findings of this study can be valuable for accreditation agencies in managing duplicates, improving their search capabilities and obtaining more relevant and precise results. These findings can also assist users in selecting the best metasearch engine based on precision rather than interface.

Originality/value

The study is the first of its kind which evaluates the four metasearch engines. No similar study has been conducted in the past to measure the performance of metasearch engines.
Low pH condition impairs BP‐IgG binding to the basement membrane zone
Authors: Im Dongjun , Ueda Keisuke , Niwa Hirofumi , Tanaka Kayoko , Iwata Hiroaki
Published: March 2024

Bullous pemphigoid (BP), an autoimmune subepidermal blistering disease, shows tense blisters associated with urticarial erythema. Tissue‐bound Immunoglobulin G (IgG) at the basement membrane zone (BMZ) detected by direct immunofluorescence (DIF) is strong evidence for a diagnosis of BP. The sensitivity of DIF is higher in complement component 3 (C3) than in IgG, but the reason for this different sensitivity is not fully understood. In this study, we performed several ex vivo studies to investigate the possible mechanism of IgG negativity and C3 positivity at the BMZ by DIF in some BP cases. First, sera from BP patients showing IgG negativity by DIF were found to clearly react to the BMZ in their own DIF skin samples. Next, indirect immunofluorescence (IIF) was performed using sera diluted with different pH phosphate‐buffered saline (PBS), pH 7.4, 6.0, and 3.0. Patients' sera diluted with pH 7.4 PBS showed linear staining at the BMZ, but sera diluted with pH 6.0 PBS and pH 3.0 PBS showed lower fluorescence intensities. Finally, sections of skin from BP patients were pre‐incubated with different pH PBS (pH 3.0, 6.0, and 7.4), followed by staining with anti‐human IgG and C3. The fluorescence intensities were notably lower for IgG and C3 that had been pre‐incubated with pH 3.0 PBS and pH 6.0 PBS than for IgG and C3 that had been pre‐incubated with pH 7.4 PBS. These results suggest that a low pH condition hinders the binding of autoantibodies to the BMZ, that is, the drop in tissue pH induced by inflammation inhibits autoantibodies from depositing at the BMZ. Furthermore, the drop in tissue pH causes tissue‐bound autoantibodies to detach from the BMZ. Complement fragments are activated not only on IgG but also on the cell surface of cells close to IgG during complement activation. IgG may detach from the BMZ under low pH condition induced by inflammation, but some complement fragments remain at the BMZ. These phenomena may help to explain why C3 is more sensitive than IgG when DIF is used to diagnose BP.
Scalable semantic 3D mapping of coral reefs with deep learning
Authors: Sauder Jonathan , Banc‐Prandi Guilhem , Meibom Anders , Tuia Devis
Published: March 2024

Coral reefs are among the most diverse ecosystems on our planet, and essential to the livelihood of hundreds of millions of people who depend on them for food security, income from tourism and coastal protection. Unfortunately, most coral reefs are existentially threatened by global climate change and local anthropogenic pressures. To better understand the dynamics underlying deterioration of reefs, monitoring at high spatial and temporal resolution is key. However, conventional monitoring methods for quantifying coral cover and species abundance are limited in scale due to the extensive manual labor required. Although computer vision tools have been employed to aid in this process, in particular structure‐from‐motion (SfM) photogrammetry for 3D mapping and deep neural networks for image segmentation, analysis of the data products creates a bottleneck, effectively limiting their scalability.

This paper presents a new paradigm for mapping underwater environments from ego‐motion video, unifying 3D mapping systems that use machine learning to adapt to challenging conditions under water, combined with a modern approach for semantic segmentation of images.

The method is exemplified on coral reefs in the northern Gulf of Aqaba, Red Sea, demonstrating high‐precision 3D semantic mapping at unprecedented scale with significantly reduced required labor costs: given a trained model, a 100 m video transect acquired within 5 min of diving with a cheap consumer‐grade camera can be fully automatically transformed into a semantic point cloud within 5 min. We demonstrate the spatial accuracy of our method and the semantic segmentation performance (of at least 80% total accuracy), and publish a large dataset of ego‐motion videos from the northern Gulf of Aqaba, along with a dataset of video frames annotated for dense semantic segmentation of benthic classes.

Our approach significantly scales up coral reef monitoring by taking a leap towards fully automatic analysis of video transects. The method advances coral reef transects by reducing the labor, equipment, logistics, and computing cost. This can help to inform conservation policies more efficiently. The underlying computational method of learning‐based Structure‐from‐Motion has broad implications for fast low‐cost mapping of underwater environments other than coral reefs.
Flock health planning: How to move from a plan to a reflective planning process in Northern Irish sheep flocks?
Authors: Crawford Paul E. , Hamer Kim , Lovatt Fiona , Behnke Malgorzata C. , Robinson Philip A.
Published: March 2024

Flock health planning has been advocated as part of a wider drive within livestock production for veterinarians and farmers to adopt a prevention‐focused approach to veterinary medicine. This approach has, at its core, a cyclical process of assessment, evaluation, action and re‐assessment, and is documented, at least in summary, in a health plan (HP). The HP has become a defining pillar of farm quality assurance schemes (QASs), introduced to address calls for greater transparency and accountability in food production. There is limited current information on the attitudes and behaviours surrounding flock HPs in the sheep sector and the barriers to greater involvement in an active process of continual improvement through reflective flock health planning. This study aims to address these issues with reference to the national flock in Northern Ireland. A mixed‐methods approach was used to explore farmers' and veterinarians' opinions and behaviours related to QASs and HP, with data obtained through an online scoping questionnaire, semi‐structured interviews with 27 farmers and 15 veterinarians, and discussion groups with farmers and veterinarians. No evidence of a positive association between a farm having a HP and implementation of 12 industry‐recommended flock health activities was identified using the Fisher's exact test. Farmers reported a reluctance to pay for veterinary advice while some veterinarians reported a lack of time to develop HPs for farmers, and sheep‐related work generally. Farmers predominantly saw the HP as a static, physical document, which had limited impact on their management practices, rather than a proactive, reflective and collaborative planning process. Veterinarians tasked with completing HPs felt restricted by limited knowledge of on‐farm practices, flock production data and a lack of confidence in the accuracy of on‐farm medicine records. This led some to believe that the HPs may fail to address critical issues. A new approach to engage farmers and veterinarians together in active flock health planning needs to be developed. This will need a sustainable delivery plan. Then the focus can be shifted towards ongoing reflective health planning to drive change for the betterment of sheep health and welfare.
The aged microenvironment impairs BCL6 and CD40L induction in CD4+ T follicular helper cell differentiation
Authors: Fisher Jacob S. , Adán‐Barrientos Irene , Kumar Naveen R. , Lancaster Jessica N.
Published: March 2024

Weakened germinal center responses by the aged immune system result in diminished immunity against pathogens and reduced efficacy of vaccines. Prolonged contacts between activated B cells and CD4+ T cells are crucial to germinal center formation and T follicular helper cell (Tfh) differentiation, but it is unclear how aging impacts the quality of this interaction. Peptide immunization confirmed that aged mice have decreased expansion of antigen‐specific germinal center B cells and reduced antibody titers. Furthermore, aging was associated with accumulated Tfh cells, even in naïve mice. Despite increased numbers, aged Tfh had reduced expression of master transcription factor BCL6 and increased expression of the ectonucleotidase CD39. In vitro activation revealed that proliferative capacity was maintained in aged CD4+ T cells, but not the costimulatory molecule CD40L. When activated in vitro by aged antigen‐presenting cells, young CD4+ naïve T cells generated reduced numbers of activated cells with upregulated CD40L. To determine the contribution of cell‐extrinsic influences on antigen‐specific Tfh induction, young, antigen‐specific B and CD4+ T cells were adoptively transferred into aged hosts prior to peptide immunization. Transferred cells had reduced expansion and differentiation into germinal center B cell and Tfh and reduced antigen‐specific antibody titers when compared to young hosts. Young CD4+ T cells transferred aged hosts differentiated into Tfh cells with reduced PD‐1 and BCL6 expression, and increased CD39 expression, though they maintained their mitochondrial capacity. These results highlight the role of the lymphoid microenvironment in modulating CD4+ T cell differentiation, which contributes to impaired establishment and maintenance of germinal centers.
Effects of chronic mild stress induced from peripuberty on sexual behavior in male rats, with or without escitalopram treatment
Authors: Fischer Leonardo Wensing , Nunes Marina , Mendes Talita Biude , Simas Joana Noguères , Bernardi Maria Martha , de Oliva Samara Urban , Miraglia Sandra Maria
Published: March 2024

Background

After the Coronavirus Disease pandemic, depression became more present, including in adolescents. Escitalopram, a selective serotonin reuptake inhibitor, was approved in 2009 for treatment of the major depressive disorder, both in children and adolescents. The undesirable effects of antidepressants on sexual dysfunction are usually underestimated.

Aims

To investigate the effects of chronic mild stress, induced from peripuberty up to adulthood, on male sexual behavior parameters, with or without the escitalopram treatment, using rats as experimental model in a translational study.

Materials and methods

Forty‐four peripubertal male rats were distributed into four groups: Sham control, escitalopram, stress, and stress + escitalopram. The chronic mild stress consisted of nine different stressors randomly applied one per day, for 8 weeks (from 41 to 97 days postpartum). Escitalopram therapy by gavage (10 mg/kg) started at 70 days postpartum and lasted for 4 weeks. The male sexual behavior parameters were evaluated at 114 days postpartum. After that, euthanasia was performed for blood and testis collection. Histopathology of the testes and plasmatic testosterone level were carried out.

Results

There was a reduction in sexual activity and motivation in rats exposed to the stress protocol, which were treated or not with escitalopram, as well as an increase in the total number of mounts in animals exposed to the stress and treated with escitalopram. The testosterone levels were lower in animals exposed to the stress, which were or not treated with escitalopram (stress and stress + escitalopram). The frequency of histologically normal seminiferous tubule sections was lower in animals that were exposed to the stress and/or received escitalopram (escitalopram, stress, and stress + escitalopram).

Conclusion

Chronic mild stress induced from peripuberty, associated or not to escitalopram treatment, altered the testosterone levels and testicular histoarchitecture and seems to be related to the reduction in male sexual motivation.
Effects of edaravone on testicular torsion–detorsion injury in rats
Authors: Şahin Yaşar , Üstüner Evren , Tutun Hidayet , Yildirim Ebru , Eroğlu Oğuz , Kurtdede Efe , Ozkabadayi Yasin , Güncüm Enes , Kutluca Kürşat , Bilge Ahmet Bilgehan
Published: March 2024

Background and objective

This study aimed to assess the protective ability of edaravone on testicular torsion–detorsion injury in rats.

Methods

Eighteen adult male Sprague–Dawley rats were randomly divided into three groups: Sham group (control, n = 6); testicular torsion/detorsion (T/D group, n = 6) and T/D+edaravone (T/D+E group, n = 6). The spermatic cords of rats of the T/D group and the T/D+E group were rotated 720° in a clockwise direction and maintained for 120 min in this torsion position. Around 90 min after the torsion, edaravone at a dose of 10 mg/kg dissolved in saline was administered IP to the T/D+E group. The testicle was counter‐rotated to its normal position to allow reperfusion for 4 h. Left testes of each animal were excised 240 min after beginning of reperfusion. Oxidative stress markers (TAS, TOS, SOD, and MDA) and apoptotic pathways (Caspase 3, Caspase 8, Caspase 9, Bcl‐2, and Bax,) were assessed by ELISA methods. Also, testicles were subjected to the histopathologic and ultrasound examinations.

Results

Ultrasound imaging showed that edaravone reduced the surface area and increased vascularization in testicles with T/D (p < 0.0001, p < 0.05, respectively). Edaravone pretreatment markedly decreased the levels of MDA, TOS, Bcl‐2, Bax, Caspase 3, Caspase 8, and Caspase 9 (p < 0.0001). Also, it increased significantly TAS levels (p < 0.0001) and reduced insignificantly SOD activity. Histopathologic examinations demonstrated that edaravone significantly attenuated the histological damage caused by T/D in testicles.

Conclusion

Taken together, the findings indicate that pretreatment of edaravone has protective effect against testicular T/D injury.
Researchers propose ice 3D printing as a method to create internal channels in artificial organs
Authors: Han Jason J.
Published: March 2024

By freezing water droplets into smooth, even columns, researchers from Carnegie Mellon University created complex internal channels that may eventually render viable complex artificial tissue.
A review on the new age methodologies for early detection of Alzheimer's and Parkinson's disease
Authors: Ghosh Nabanita , Sinha Krishnendu , Sil Parames C.
Published: March 2024

Backgrounds

Neurodegenerative diseases (NDDs) such as Alzheimer's (AD) and Parkinson's (PD) are often diagnosed late, impeding effective treatment; therefore, early detection is imperative. Modern methodologies can serve a pivotal role in fulfilling the crucial need for timely detection and intervention in this context.

Objectives

Evaluate early detection's significance and summarize key technologies (biomarkers, neuroimaging, AI/ML, genetics, digital health) for enhanced diagnostic strategies in AD and PD.

Methods

This study employs a focused descriptive review approach, encompassing analysis of peer‐reviewed articles and clinical trials from existing literature, to provide a nuanced exploration of the subject matter.

Findings

This review underscores the efficacy of non‐invasive biomarkers, biosensors and emerging promising technologies for advancing early diagnosis of AD and PD.

Conclusion

The landscape of early NDD detection has been reshaped by technology, yet challenges persist, encompassing the domains of validation and ethics. A collaborative effort between medical professionals, researchers and technologists is imperative to effectively address and combat NDDs.
I help, therefore, I am? – A registered report on longitudinal inter‐relations of the three‐dimensional moral self‐concept and prosocial behaviours in preschool children
Authors: Söldner Lena , Paulus Markus
Published: March 2024

Children's moral self‐concept (MSC) has been proposed to relate to prosocial behaviour. However, systematic assessments of their inter‐relations are scarce. Therefore, this longitudinal study investigated the development, structure and inter‐relation of prosocial behaviours and the MSC in childhood, using three measurement points at ages 4, 5 and 6 years. We assessed children's MSC and helping, sharing and comforting behaviours in a laboratory setting. Confirmatory factor analyses revealed a three‐dimensional MSC structure at 5 and 6 years, but not at 4 years. There was inconsistent stability across time points regarding prosocial behaviour and MSC. For the comforting domain, but not the other domains, cross‐lagged relations between self‐concept and behaviour were present. Moreover, helping behaviour and self‐concept were inter‐related at 6 years. Results provide support for reciprocal associations between MSC and prosocial behaviour, albeit only in the comforting domain. They highlight the importance of distinguishing between types of prosocial behaviour and corresponding dimensions of the self‐concept, as different developmental trajectories and associations emerge.
Alix‐normalized exosomal programmed death‐ligand 1 analysis in urine enables precision monitoring of urothelial cancer
Authors: Woo Hyun‐Kyung , Park Juhee , Kim Kyung Hwan , Ku Ja Yoon , Ha Hong Koo , Cho Yoon‐Kyoung
Published: March 2024

Anti‐programmed death‐ligand 1 (PD‐L1) Ab‐based therapies have demonstrated potential for treating metastatic urothelial cancer with high PD‐L1 expression. Urinary exosomes are promising biomarkers for liquid biopsy, but urine's high variability requires normalization for accurate analysis. This study proposes using the PD‐L1/Alix ratio to normalize exosomal PD‐L1 signal intensity with Alix, an internal exosomal protein less susceptible to heterogeneity concerns than surface protein markers. Extracellular vesicles were isolated using ExoDisc and characterized using various methods, including ExoView to analyze tetraspanins, PD‐L1, and Alix on individual exosomes. On‐disc ELISA was used to evaluate PD‐L1 and Alix‐normalized PD‐L1 in 15 urothelial cancer patients during the initial treatment cycle with Tecentriq. Results showed that Alix signal range was relatively uniform, whereas tetraspanin marker intensity varied for individual exosome particles. On‐disc ELISA was more reliable for detecting exosomal PD‐L1 expression than standard plate ELISA‐based measurement. Using exosomal Alix expression for normalization is a more reliable approach than conventional methods for monitoring patient status. Overall, the study provides a practical and reliable method for detecting exosomal PD‐L1 in urine samples from patients with urothelial cancer.
Upregulation of HLA‐II related to LAG‐3+CD4+ T cell infiltration is associated with patient outcome in human glioblastoma
Authors: Guo Wenli , Peng Daijun , Liao Yuee , Lou Lei , Guo Moran , Li Chen , Yu Wangyang , Tian Xiaoxi , Wang Guohui , Lv Ping , Zuo Jing , Shen Haitao , Li Yuehong
Published: March 2024

Glioblastoma (GBM) is the most common malignant diffuse glioma of the brain. Although immunotherapy with immune checkpoint inhibitors (ICIs), such as programmed cell death protein (PD)‐1/PD ligand‐1 inhibitors, has revolutionized the treatment of several cancers, the clinical benefit in GBM patients has been limited. Lymphocyte‐activation gene 3 (LAG‐3) binding to human leukocyte antigen‐II (HLA‐II) plays an essential role in triggering CD4+ T cell exhaustion and could interfere with the efficiency of anti‐PD‐1 treatment; however, the value of LAG‐3–HLA‐II interactions in ICI immunotherapy for GBM patients has not yet been analyzed. Therefore, we aimed to investigate the expression and regulation of HLA‐II in human GBM samples and the correlation with LAG‐3+CD4+ T cell infiltration. Human leukocyte antigen‐II was highly expressed in GBM and correlated with increased LAG‐3+CD4+ T cell infiltration in the stroma. Additionally, HLA‐IIHighLAG‐3High was associated with worse patient survival. Increased interleukin‐10 (IL‐10) expression was observed in GBM, which was correlated with high levels of HLA‐II and LAG‐3+ T cell infiltration in stroma. HLA‐IIHighIL‐10High GBM associated with LAG‐3+ T cells infiltration synergistically showed shorter overall survival in patients. Combined anti‐LAG‐3 and anti‐IL‐10 treatment inhibited tumor growth in a mouse brain GL261 tumor model. In vitro, CD68+ macrophages upregulated HLA‐II expression in GBM cells through tumor necrosis factor‐α (TNF‐α). Blocking TNF‐α‐dependent inflammation inhibited tumor growth in a mouse GBM model. In summary, T cell–tumor cell interactions, such as LAG‐3–HLA‐II, could confer an immunosuppressive environment in human GBM, leading to poor prognosis in patients. Therefore, targeting the LAG‐3–HLA‐II interaction could be beneficial in ICI immunotherapy to improve the clinical outcome of GBM patients.
FAXC interacts with ANXA2 and SRC in mitochondria and promotes tumorigenesis in cholangiocarcinoma
Authors: Fujimori Haruna , Shima‐Nakamura Mao , Kanno Shin‐Ichiro , Shibuya‐Takahashi Rie , Mochizuki Mai , Mizuma Masamichi , Unno Michiaki , Wakui Yuta , Abue Makoto , Iwai Wataru , Fukushi Daisuke , Satoh Kennich , Yamaguchi Kazunori , Shindo Norihisa , Yasuda Jun , Tamai Keiichi
Published: March 2024

Cholangiocarcinoma (CCA) is one of the most difficult malignancies to treat as the therapeutic options are limited. Although several driver genes have been identified, most remain unknown. In this study, we identified a failed axon connection homolog (FAXC), whose function is unknown in mammals, by analyzing serially passaged CCA xenograft models. Knockdown of FAXC reduced subcutaneous tumorigenicity in mice. FAXC was bound to annexin A2 (ANXA2) and c‐SRC, which are tumor‐promoting genes. The FAXC/ANXA2/c‐SRC complex forms in the mitochondria. FAXC enhances SRC‐dependent ANXA2 phosphorylation at tyrosine‐24, and the C‐terminal amino acid residues (351–375) of FAXC are required for ANXA2 phosphorylation. Transcriptome data from a xenografted CCA cell line revealed that FAXC correlated with epithelial–mesenchymal transition, hypoxia, and KRAS signaling genes. Collectively, these findings advance our understanding of CCA tumorigenesis and provide candidate therapeutic targets.
Quality of life of families and siblings of children and adolescents with meningomyelocele
Authors: Dias Bruno Leonardo Scofano , de Rodrigues Maura Calixto Cecherelli , Duarte José Luiz Muniz Bandeira
Published: March 2024

Background

Children with meningomyelocele may require continuous care. Consequently, there is a risk for caregiver burden and impact on family quality of life (QoL), including siblings' QoL. Some studies analysed caregivers' burden and family QoL separately. However, none of these studies evaluated siblings' QoL and the associations between these three dimensions. This study investigated the associations between caregivers' burden, family QoL and siblings' QoL in Brazilian families of children with meningomyelocele and its correlations with sociodemographic, functional and clinical variables. Siblings' QoL was specifically assessed using as a parameter the QoL of typically developed Brazilian children.

Methods

One hundred and fifty families, 150 caregivers and 68 siblings completed the Family Quality of Life Scale, Burden Interview, KIDSCREEN‐27 Child and Adolescent Version and Parents Version questionnaires.

Results

Most families and caregivers reported a high family QoL and a low caregiver burden. Family QoL was significantly lower as caregivers' burden increased. Caregiver's burden was significantly lower with increasing family QoL levels. Self‐reported siblings' QoL was significantly worse than that of typically developed peers. There were no significant differences between self and parent‐reported siblings' QoL. Self‐reported siblings' QoL was significantly worse as their age increased and better with increasing family QoL levels. Parent‐reported siblings' QoL was significantly worse with increasing levels of caregiver's burden and significantly better as family QoL increased. There were no significant associations with functional and clinical variables.

Conclusions

Despite the cross‐sectional nature of the available data precludes any statements of causality, our results reinforce the relevance of knowing the factors that influence the QoL of families and siblings of children and adolescents with meningomyelocele and the relevance of actions aimed at reducing caregivers' burden, improving family QoL and meeting siblings' individual needs. Future multicenter studies may validate the generalizability of our findings.
Colon cancer: feeling the imbalance?
Authors: Ballal Devesh S. , Saklani Avanish P.
Published: March 2024

While neoadjuvant chemotherapy has become the standard of care for rectal cancers in most centres, there is much interest in neoadjuvant chemotherapy in colon cancer after the recent publication of the FOxTROT trial. The management of colon cancers seems to be heading down the same path as rectal cancer, where the radicality of surgery is replaced by chemotherapy intensification. The role of demanding procedures such as complete mesocolic excision with central venous ligation in this new paradigm of upfront chemotherapy remains uncertain and uninvestigated.
Hydrochlorothiazide and increased risk of atypical fibroxanthoma and pleomorphic dermal sarcoma
Authors: Kuntz Thomas , Grimm Alexander , Hofmann Silke C. , Michalowitz Alena‐Lioba , Schaller Jörg , Hellmich Martin , Assaf Chalid , Oellig Frank , Kreuter Alexander
Published: March 2024

Background and Objectives

Previous work has demonstrated that hydrochlorothiazide (HCTZ) is a risk factor for squamous cell carcinomas (SCC) and basal cell carcinomas (BCC) due to pro‐photocarcinogenic effects. Atypical fibroxanthoma (AFX) and pleomorphic sarcoma (PDS), both ultraviolet‐induced cancers, display a rare but rising cutaneous tumor entity. This study aimed to evaluate if the use of HCTZ is higher in patients with AFX/PDS than in patients with SCC/BCC and subsequently may be a risk factor for AFX/PDS‐development.

Patients and Methods

In a retrospective study of four German skin cancer centers, AFX/PDS cases and SCC/BCC controls were sex and age matched (1:3) over a time‐period of 7 years (2013–2019) to evaluate the use of HCTZ, immunosuppressive medication, second malignancies, and presence of diabetes mellitus.

Results

Overall, 146 AFX/PDS and 438 controls (SCC/BCC) were included in the study. The use of HCTZ was significantly higher in patients with AFX/PDS (44.5%) compared to patients with SCC/BCC (25.3%). Additionally, the presence of diabetes mellitus was significantly higher in AFX/PDS patients.

Conclusions

This study demonstrates a significantly higher use of HCTZ in patients with AFX/PDS compared to SCC/BCC. This result suggests that HCTZ may be a risk factor for AFX/PDS. Additionally, diabetes mellitus or its comorbidities may be associated with an increased risk for AFX/PDS.
Angiotensin II involvement in the development and persistence of amphetamine‐induced sensitization: Striatal dopamine reuptake implications
Authors: Basmadjian Osvaldo M. , Occhieppo Victoria B. , Montemerlo Antonella E. , Rivas Gustavo A. , Rubianes María D. , Baiardi Gustavo , Bregonzio Claudia
Published: March 2024

Amphetamine (AMPH) exposure induces behavioural and neurochemical sensitization observed in rodents as hyperlocomotion and increased dopamine release in response to a subsequent dose. Brain Angiotensin II modulates dopaminergic neurotransmission through its AT1 receptors (AT1‐R), positively regulating striatal dopamine synthesis and release. This work aims to evaluate the AT1‐R role in the development and maintenance of AMPH‐induced sensitization. Also, the AT1‐R involvement in striatal dopamine reuptake was analysed. The sensitization protocol consisted of daily AMPH administration for 5 days and tested 21 days after withdrawal. An AT1‐R antagonist, candesartan, was administered before or after AMPH exposure to evaluate the participation of AT1‐R in the development and maintenance of sensitization, respectively. Sensitization was evaluated by locomotor activity and c‐Fos immunostaining. Changes in dopamine reuptake kinetics were evaluated 1 day after AT1‐R blockade withdrawal treatment, with or without the addition of AMPH in vitro. The social interaction test was performed as another behavioural output. Repeated AMPH exposure induced behavioural and neurochemical sensitization, which was prevented and reversed by candesartan. The AT1‐R blockade increased the dopamine reuptake kinetics. Neither the AMPH administration nor the AT1‐R blockade altered the performance of social interaction. Our results highlight the AT1‐R's crucial role in AMPH sensitization. The enhancement of dopamine reuptake kinetics induced by the AT1‐R blockade might attenuate the neuroadaptive changes that lead to AMPH sensitization and its self‐perpetuation. Therefore, AT1‐R is a prominent candidate as a target for pharmacological treatment of pathologies related to dopamine imbalance, including drug addiction and schizophrenia.
A rights‐based approach to the choice of forum in climate displacement litigation: Lessons from the Americas
Authors: Gouritin Armelle
Published: March 2024

Few studies address climate litigation and climate forced mobility together, and the link between climate litigation and internal forced climate displacement remains poorly addressed. This article aims to participate in filling this void. We focus on climate displacement litigation argued before regional human rights courts (the Inter‐American Court) and national human rights protection bodies (the Mexican Commission) to determine the adequacy of each from the perspective of potential litigants. We address institutional, procedural and positive law within the context of water scarcity. We find that while institutional and procedural aspects reveal the potential of the Inter‐American Court in ruling on climate displacement cases, the application of the positive obligations doctrine by the Mexican National Human Rights Commission is more disaggregated and a priori suitable to ground the course of action of potential litigants.
Early developmental carry‐over effects on exploratory behaviour and DNA methylation in wild great tits (Parus major)
Authors: Sepers Bernice , Verhoeven Koen J. F. , van Oers Kees
Published: March 2024

Adverse, postnatal conditions experienced during development are known to induce lingering effects on morphology, behaviour, reproduction and survival. Despite the importance of early developmental stress for shaping the adult phenotype, it is largely unknown which molecular mechanisms allow for the induction and maintenance of such phenotypic effects once the early environmental conditions are released. Here we aimed to investigate whether lasting early developmental phenotypic changes are associated with post‐developmental DNA methylation changes. We used a cross‐foster and brood size experiment in great tit (Parus major) nestlings, which induced post‐fledging effects on biometric measures and exploratory behaviour, a validated personality trait. We investigated whether these post‐fledging effects are associated with DNA methylation levels of CpG sites in erythrocyte DNA. Individuals raised in enlarged broods caught up on their developmental delay after reaching independence and became more explorative as days since fledging passed, while the exploratory scores of individuals that were raised in reduced broods remained stable. Although we previously found that brood enlargement hardly affected the pre‐fledging methylation levels, we found 420 CpG sites that were differentially methylated between fledged individuals that were raised in small versus large sized broods. A considerable number of the affected CpG sites were located in or near genes involved in metabolism, growth, behaviour and cognition. Since the biological functions of these genes line up with the observed post‐fledging phenotypic effects of brood size, our results suggest that DNA methylation provides organisms the opportunity to modulate their condition once the environmental conditions allow it. In conclusion, this study shows that nutritional stress imposed by enlarged brood size during early development associates with variation in DNA methylation later in life. We propose that treatment‐associated DNA methylation differences may arise in relation to pre‐ or post‐fledging phenotypic changes, rather than that they are directly induced by the environment during early development.