Exploratory Studies Research Articles

Qualifying a novel clinical trial endpoint (iBOX) predictive of long-term kidney transplant outcomes

New immunosuppressive therapies that improve long-term graft survival are needed in kidney transplant. Critical Path Institute’s Transplant Therapeutics Consortium received a qualification opinion for the iBOX Scoring System as a novel secondary efficacy endpoint for kidney transplant clinical trials through European Medicines Agency’s qualification of novel methodologies for drug development. This is the first qualified endpoint for any transplant indication and is now available for use in kidney transplant clinical trials. Although the current efficacy failure endpoint has typically shown the noninferiority of therapeutic regimens, the iBOX Scoring System can be used to demonstrate the superiority of a new immunosuppressive therapy compared to the standard of care from 6 months to 24 months posttransplant in pivotal or exploratory drug therapeutic studies.

Augmented digital human vs. human agents in storytelling marketing: Exploratory electroencephalography and experimental studies

AbstractAs the fourth industrial revolution unfolds and the use of digital humans becomes more commonplace, understanding digital humans' potential to replace real human interaction or enhance it, particularly in storytelling marketing contexts, is becoming evermore important. To promote interaction and increase the entertainment value of technology‐enhanced storytelling marketing, brands have begun to explore the use of augmented digital humans as storytelling agents. In this article, we examine the effectiveness of leveraging advanced technologies and delivering messages via digital humans in storytelling advertisements. In Study 1, we investigate the effectiveness of narrative transportation on behavioral responses after exposure to an interactive augmented reality mobile advertisement with a digital human storyteller. In Study 2, we compare how consumers respond to augmented digital human versus real human storytelling advertisements after conducting an exploratory neurophysiological electroencephalography study. The findings show that both types of agents promote narrative transportation when the story fits the product well. Moreover, a digital human perceived as more human‐like elicits stronger positive consumer responses, suggesting an effective new approach to storytelling marketing.

Development of Antecedent Factors for Malaysian Women’s Entrepreneurial Resilience Framework: A Fuzzy Delphi Method

This study assesses the antecedent factors of entrepreneurial resilience and the underlying criteria to develop a Malaysian women’s entrepreneurial framework based on the expert linguistic consensus to identify potential strategies to empower women entrepreneurship sector in Malaysia. The Delphi Fuzzy (FDM) method is used to obtain expert consensus on the important factors that stimulate and encourage entrepreneurial resilience based on a review of previous literature. The judgment sampling technique was used to develop a survey and distributed it to 20 experts. The linguistic consensus of experts is analyzed using Fuzzy Set Theory and Triangular Fuzzy Numbers (TFN). This study confirms the strategic factors that can foster the development of resilient women entrepreneurs and identifies key resilience criteria that play a vital role in boosting the business longevity of women-owned SMEs. Importantly, religion and psychological capital are key to developing entrepreneurial resilience among women entrepreneurs. In addition, technology skills should be leveraged to deal with an increasingly complex market environment and create opportunities in a crisis. This study focuses on the context of Malaysian women entrepreneurs, who may not represent other countries. This study highlights the importance of entrepreneurial psychological traits (i.e., cognitive, and behavioural) for theoretical and managerial implications in fostering the ability of women entrepreneurs to adjust to new circumstances and thereby contribute to the long-term sustainability of their businesses. Upcoming studies are recommended to test the resilience factor of these entrepreneurs on a sample of the female entrepreneur population through exploratory studies using questionnaire instruments.

Using evidence-based research approach and exploratory studies before conducting a new acupuncture randomized controlled trial

Adequate preliminary research is a prerequisite for ensuring the quality of randomized controlled trials (RCTs) on acupuncture. This paper proposes that prior to conducting a new RCT of acupuncture, an evidence-based research (EBR) approach and exploratory studies should be adopted to ensure value and avoid waste of research. EBR, defined as using systematic reviews of relevant clinical studies and obtain the perspectives of end users in a systematic and transparent way to justify research questions and inform trial design, is recommended as the first step before embarking on an acupuncture RCT to ensure its value and rationality. The subsequent exploratory studies can aid researchers in pre-evaluating the effect of acupuncture treatment protocols, identifying key factors that influence the outcome, and test trial feasibility for protocol optimization. This article elucidates the significance and implementation of the EBR approach and exploratory studies, with the aim of providing practical methods to enhance the quality of acupuncture RCTs.

Calcium Channel Blocker Use and Associated Glaucoma and Related Traits Among UK Biobank Participants

Calcium channel blocker (CCB) use has been associated with an increased risk of glaucoma in exploratory studies. To examine the association of systemic CCB use with glaucoma and related traits among UK Biobank participants. This population-based cross-sectional study included UK Biobank participants with complete data (2006-2010) for analysis of glaucoma status, intraocular pressure (IOP), and optical coherence tomography (OCT)-derived inner retinal layer thicknesses. Data analysis was conducted in January 2023. Calcium channel blocker use was assessed in a baseline touchscreen questionnaire and confirmed during an interview led by a trained nurse. The primary outcome measures included glaucoma status, corneal-compensated IOP, and 2 OCT-derived inner retinal thickness parameters (macular retinal nerve fiber layer [mRNFL] and macular ganglion cell-inner plexiform layer [mGCIPL] thicknesses). We performed logistic regression and linear regression analyses to test for associations with glaucoma status and IOP and OCT-derived inner retinal thickness parameters, respectively. This study included 427 480 adults. Their median age was 58 (IQR, 50-63) years, and more than half (54.1%) were women. There were 33 175 CCB users (7.8%). Participants who had complete data for glaucoma status (n = 427 480), IOP (n = 97 100), and OCT-derived inner retinal layer thicknesses (n = 41 023) were eligible for respective analyses. After adjustment for key sociodemographic, medical, anthropometric, and lifestyle factors, use of CCBs (but not other antihypertensive agents) was associated with greater odds of glaucoma (odds ratio [OR], 1.39 [95% CI, 1.14 to 1.69]; P = .001). Calcium channel blocker use was also associated with thinner mGCIPL (-0.34 μm [95% CI, -0.54 to -0.15 μm]; P = .001) and mRNFL (-0.16 μm [95% CI, -0.30 to -0.02 μm]; P = .03) thicknesses but not IOP (-0.01 mm Hg [95% CI, -0.09 to 0.07 mm Hg]; P = .84). In this study, an adverse association between CCB use and glaucoma was observed, with CCB users having, on average, 39% higher odds of glaucoma. Calcium channel blocker use was also associated with thinner mGCIPL and mRNFL thicknesses, providing a structural basis that supports the association with glaucoma. The lack of association of CCB use with IOP suggests that an IOP-independent mechanism of glaucomatous neurodegeneration may be involved. Although a causal relationship has not been established, CCB replacement or withdrawal may be considered should glaucoma progress despite optimal care.

The “SMARTER” framework and real application cases of blockchain

Today, blockchain is a very critical technology for many industrial operations. In this study, we aim to study the applications of blockchain in the industry. We reveal the latest blockchain-supported solutions developed by companies, identify the key challenges and discuss the long-term benefits of blockchain adoption. To be specific, this study adopts a multi-methodological approach by systematically reviewing the literature, and conducting exploratory case studies and a semi-structured interview. Based on the findings, we establish a “SMARTER” framework to illustrate the “SMART” challenges that companies may face and discuss the “ER” long-term benefits that can be generated to the business enterprises. We further propose some important future research areas, such as the impacts of blockchain technology to support corporate social responsibility, the co-opetition effect when the companies form partnership in the blockchain development, the feasibility of integration between blockchain technology and other disruptive technologies, and the values of blockchain adoption in the industry.

A user study for evaluation of formal verification results and their explanation at Bosch

ContextEnsuring safety for any sophisticated system is getting more complex due to the rising number of features and functionalities. This calls for formal methods to entrust confidence in such systems. Nevertheless, using formal methods in industry is demanding because of their lack of usability and the difficulty of understanding verification results.ObjectiveWe evaluate the acceptance of formal methods by Bosch automotive engineers, particularly whether the difficulty of understanding verification results can be reduced.MethodWe perform two different exploratory studies. First, we conduct a user survey to explore challenges in identifying inconsistent specifications and using formal methods by Bosch automotive engineers. Second, we perform a one-group pretest-posttest experiment to collect impressions from Bosch engineers familiar with formal methods to evaluate whether understanding verification results is simplified by our counterexample explanation approach.ResultsThe results from the user survey indicate that identifying refinement inconsistencies, understanding formal notations, and interpreting verification results are challenging. Nevertheless, engineers are still interested in using formal methods in real-world development processes because it could reduce the manual effort for verification. Additionally, they also believe formal methods could make the system safer. Furthermore, the one-group pretest-posttest experiment results indicate that engineers are more comfortable understanding the counterexample explanation than the raw model checker output.LimitationsThe main limitation of this study is the generalizability beyond the target group of Bosch automotive engineers.

The sufficiency economy philosophy as an approach to social innovation: case studies of local governments in Thailand

The late Thai King Bhumibol Adulyadej formulated the Sufficiency Economy Philosophy (SEP). “Sufficiency” means balancing reasonable moderation in production against the need for protection from sudden internal and external shocks. SEP follows the middle path as a guiding principle for all classes of society and government. Knowledge, thoughtfulness, prudence, and ethical integrity are essential to achieve the middle path. This paper explores the use of SEP as a method of social innovation for enhancing delivery of public services and for localizing the process of sustainable development. Such innovative use of SEP is illustrated by three exploratory case studies of local administrative organisations (LAOs) in Thailand. All three LAOs' case studies have mayors with significant entrepreneurial talent useful in teaching entrepreneurial action to their residents, their staff, and other local leaders. Together, these cases show the potential of SEP as a method of bottom up social action and sustainable development. A brief discussion of the wider need for and use of innovation, including social innovations, and underpinning entrepreneurship, is included prior to the Thai case studies. There is also a short section examining similar types of activities to those observed in the cases in the European context by way of comparison.

Timing Estimation and Limits in TOF-PET Detectors Producing Prompt Photons.

The production of prompt photons providing high photon time densities is a promising avenue to reach ultrahigh coincidence time resolution (CTR) in time-of-flight PET. Detectors producing prompt photons are receiving high interest experimentally, ignited by past exploratory theoretical studies that have anchored some guiding principles. Here, we aim to consolidate and extend the foundations for the analytical modeling of prompt generating detectors. We extend the current models to a larger range of prompt emission kinetics where more stringent requirements on the prompt photon yield rapidly emerge as a limiting factor. Lower bound and estimator evaluations are investigated with different underlying models, notably by merging or keeping separate the prompt and scintillation photon populations. We further show the potential benefits of knowing the proportion of prompt photons within a detection set to improve the CTR by mitigating the detrimental effect of population (prompt vs scintillation) mixing. Taking into account the fluctuations on the average number of detected prompt photons in the model reveals a limited influence when prompt photons are accompanied by fast scintillation (e.g., LSO:Ce:Ca) but a more significant effect when accompanied by slower scintillation (e.g., BGO). Establishing performance characteristics and limitations of prompt generating detectors is paramount to gauging and targeting the best possible timing capabilities they can offer.

Nursing interventions for pediatric patients with cancer and their families: a scoping review protocol.

This scoping review will identify and map available nursing interventions provided by pediatric oncology hospital services to pediatric patients with cancer and/or their family members. The aim is to develop a comprehensive overview of the characteristics of nursing interventions and to identify potential knowledge gaps. Clinical nursing care is an essential part of pediatric oncology. In pediatric oncology nursing research, a shift from explanatory studies to intervention studies is recommended. The body of research on interventions for pediatric oncology patients and their families has grown in recent years. However, there are no reviews on nursing interventions currently available for pediatric oncology. Studies will be considered for inclusion if they refer to pediatric patients with cancer, and/or family members of a pediatric patient with cancer, who have received non-pharmacological and non-procedural nursing interventions provided by a pediatric oncology hospital service. Studies must also be peer-reviewed, published from the year 2000 onward, and written in English, Danish, Norwegian, or Swedish. The review will be conducted in accordance with the JBI guidelines for scoping reviews. A 3-step search strategy will be followed using the PCC mnemonic (Population, Content, Context). The databases to be searched will include Scopus, PubMed, CINAHL, PsyclNFO, and Embase. The identified studies will be screened based on title and abstract, as well as full text, by 2 independent reviewers. Data will be extracted and managed in Covidence. A summary of the results will be presented as a narrative description, supported by tables.

Updates to the Autism Intervention Research Network on Physical Health (AIR-P) Research Agenda.

Autistic individuals, now representing one in 36 individuals in the U.S., experience disproportionate physical health challenges relative to non-autistic individuals. The Health Resources and Services Administration's (HRSA) Autism Intervention Research Network on Physical Health (AIR-P) is an interdisciplinary, multi-center Research Network that aims to increase the health, well-being, and quality of life of autistic individuals. The current paper builds on the initial AIR-P Research Agenda (proposed in Year 1) and provides an updated vision for the Network. Updates to the Research Agenda were made via the administration of a Qualtrics survey, and disseminated widely to all AIR-P entities, including the Research Node Leaders, Steering Committee, Autistic Researcher Review Board, and collaborating academic and non-academic entities. Network members were tasked with evaluating the Year 1 Research Agenda and proposing additional priorities. Within each Research Node, all Year 1 priorities were endorsed as continued priorities for research on autism and physical health. Specific topics, including co-occurring conditions and self-determination, advocacy, and decision-making, were particularly endorsed. Opportunities for exploratory studies and intervention research were identified across Research Nodes. Qualitative responses providing feedback on additional research priorities were collected. The updated AIR-P Research Agenda represents an important step toward enacting large-scale health promotion efforts for autistic individuals across the lifespan. This updated agenda builds on efforts to catalyze autism research in historically underrepresented topic areas while adopting a neurodiversity-oriented approach to health promotion.

The State- and Trait-Level Effects and Candidate Mechanisms of Four Mindfulness-Based Cognitive Therapy (MBCT) Practices: Two Exploratory Studies

ObjectivesThe primary aim was to explore state- and trait-level effects and candidate mechanisms of four Mindfulness-Based Cognitive Therapy (MBCT) practices.MethodOne hundred sixty adults self-selected from the general population were randomized to one of four mindfulness practices: body scan, mindful movement, breath and body, and befriending. Study 1 explored state-level self-compassion, mindfulness, decentering (mechanisms), and pleasantness of thoughts, emotions, and body sensations at multiple time points using two single mindfulness sessions. Study 2 explored trait-level self-compassion, mindfulness, decentering, interoceptive awareness, attentional control (mechanisms), anxiety, depression, and psychological quality of life pre-post 2 weeks of daily practice.ResultsIn study 1, state-level effects were demonstrated in all candidate mechanisms and outcomes within the whole sample across time points (d = 0.27 to 0.86), except for state decentering. After controlling for pre-scores and additional covariates, no between-group effects were found (p = 0.050 to 0.973). In study 2, trait-level effects were demonstrated in psychological quality of life and most candidate mechanisms within the whole sample (d = 0.26 to 0.64) but no between-group effects were found (p = 0.080 to 0.805). Within the whole sample, after controlling for pre-scores, changes in mindfulness, self-compassion, decentering, and interoceptive awareness (i.e. body listening) were associated with improvements in psychological quality of life (r = 0.23 to 0.40) and self-led mindfulness practice (r = 0.18 to 0.23).ConclusionsFuture research should test the generated hypotheses using well-designed, adequately powered, and theory-driven studies that address universal and specific mechanisms in different populations and contexts.Pre-registrationThis study is not pre-registered.

Improving Outcomes for Military Families with Young Children: Effects of a Novel Dyadic Coaching-Based Parenting Intervention in Two Exploratory Case Studies

This article presents an intervention model for military families with young children reintegrating after deployment that aims to strengthen parent-child relationships and improve family outcomes. The Coaching and Parent Emotion Support (CaPES) program integrates emotion and behavioural regulation principles, within an intensive, dyadic, coaching-based delivery format. We outline the application and outcomes of CaPES in two case studies of Australian Defence Force (ADF) families. The results offer preliminary evidence of the efficacy of CaPES in improving parent-child relationship quality, parental mental health and wellbeing, and children’s behavioural and emotional outcomes in military families with young children.

Publications on the diagnostic accuracy of dermatopathology tests: A cross-sectional quality analysis.

Ancillary diagnostic tests are frequent in dermatopathology practice. Publications on their accuracy influence their utilization. The transparency and completeness of these publications are unknown. We performed a cross-sectional study on diagnostic accuracy studies in dermatopathology published between 2020 and 2022 for compliance with Standards for Reporting of Diagnostic Accuracy Studies (STARD) and the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). 14.67 ± 3.02 STARD items were reported in 62 publications (range, 9.5-23.5 out of the recommended total of 30). More items were reported in high-impact factor journals (16.01 vs. 13.32, p = 0.0002) and journals that endorsed STARD in their author instructions (17.22 vs. 14.11, p = 0.0039). Less than 10% of publications reported quantifiable hypotheses, sample size calculations, flow diagrams, or study registrations. The risk of bias by our analysis of QUADAS-2 criteria was high or uncertain for index test interpretation (36/62, 58%) and patient selection (44/62, 71%). Publications on dermatopathology tests are exploratory studies without prespecified hypotheses or study designs. They do not meet the criteria for transparent reporting. We suggest that medical journal leadership should consider updating their instructions with more explicit guidance on recommended manuscript elements.

ISO56005 in the Brazilian patent office: modeling

This study relates the chronology of INPI-BR services as an International Research Authority with the deadlines for delivering ISA forms to WIPO, proposing the complementation of ISO9001 through ISO56005 as an alternative to increase the quality of its services. Thus, exploratory case studies of revisions of ISA requests are carried out, considering the INPI-BR implementation phases and the response time that it met the quality needs imposed by WIPO, such as the maximum period of 3 months for the delivery of the international research report, as INPI-BR has not been able to meet 100% of this deadline for all PCT requests. In practice, this article is part of the project already started to increase the quality of INPI-BR's ISA/IPEA services using ISO9001, adding the tools of ISO56005, focusing on full compliance with the deadline. The analyzes carried out point to the ISA authority in Chile as a possible collaborator of INPI-BR activities as an ISA/IPEA office, due to its current partnership with Brazil and because it is already meeting the requirements of WIPO.

Stress response mechanisms in protein misfolding diseases: Profiling a cellular model of Huntington's disease

Stress response pathways like the integrated stress response (ISR), the mitochondrial unfolded protein response (UPRmt) and the heat shock response (HSR) have emerged as part of the pathophysiology of neurodegenerative diseases, including Huntington's disease (HD) – a currently incurable disease caused by the production of mutant huntingtin (mut-Htt). Previous data from HD patients suggest that ISR is activated while UPRmt and HSR are impaired in HD. The study of these stress response pathways as potential therapeutic targets in HD requires cellular models that mimic the activation status found in HD patients of such pathways. PC12 cells with inducible expression of the N-terminal fragment of mut-Htt are among the most used cell lines to model HD, however the activation of stress responses remains unclear in this model. The goal of this study is to characterize the activation of ISR, UPRmt and HSR in this HD cell model and evaluate if it mimics the activation status found in HD patients. We show that PC12 HD cell model presents reduced levels of Hsp90 and mitochondrial chaperones, suggesting an impaired activation or function of HSR and UPRmt. This HD model also presents increased levels of phosphorylated eIF2α, the master regulator of the ISR, but overall similar levels of ATF4 and decreased levels of CHOP - transcription factors downstream to eIF2α - in comparison to control, suggesting an initial activation of ISR. These results show that this model mimics the ISR activation and the impaired UPRmt and HSR found in HD patients. This work suggests that the PC12 N-terminal HD model is suitable for studying the role of stress response pathways in the pathophysiology of HD and for exploratory studies investigating the therapeutic potential of drugs targeting stress responses.

Reducing the false discovery rate of preclinical animal research with Bayesian statistical decision criteria.

The success of preclinical research hinges on exploratory and confirmatory animal studies. Traditional null hypothesis significance testing is a common approach to eliminate the chaff from a collection of drugs, so that only the most promising treatments are funneled through to clinical research phases. Balancing the number of false discoveries and false omissions is an important aspect to consider during this process. In this paper, we compare several preclinical research pipelines, either based on null hypothesis significance testing or based on Bayesian statistical decision criteria. We build on a recently published large-scale meta-analysis of reported effect sizes in preclinical animal research and elicit a non-informative prior distribution under which both approaches are compared. After correcting for publication bias and shrinkage of effect sizes in replication studies, simulations show that (i) a shift towards statistical approaches which explicitly incorporate the minimum clinically important difference reduces the false discovery rate of frequentist approaches and (ii) a shift towards Bayesian statistical decision criteria can improve the reliability of preclinical animal research by reducing the number of false-positive findings. It is shown that these benefits hold while keeping the number of experimental units low which are required for a confirmatory follow-up study. Results show that Bayesian statistical decision criteria can help in improving the reliability of preclinical animal research and should be considered more frequently in practice.

TikTok Use in Municipal Elections: From Candidate-Majors to Influencer-Politicians

TikTok is without any doubt the most successful social network among Gen Zers and, consequently, is increasingly becoming their preferred place to discuss, share opinions, rally around social issues, and express political alignments. Accordingly, both politicians and political parties around the world are joining the platform to connect with young voters: previous exploratory studies, however, have shown that most political actors struggle to adapt to the platform’s affordances, appearing cringy, out of touch, or simply using TikTok as an «old medium», without utilizing it to enhance interaction with citizens. This article contributes to the emerging stream of literature looking at the political uses of this platform in electoral campaigns by studying its application in a local election, focusing on how Ada Colau, candidate mayor for the 2023 Barcelona Municipal elections, has integrated TikTok in her communication strategy. Applying an affordance-based multimodal content analysis of all the tiktoks posted during the campaign, the paper discloses that, although not fully exploiting the platform’s affordances –in particular its participatory potential– the candidate optimally adapts to its vernaculars and cultural environment, constructing a highly recognizable personal style, which seems to borrow and implement the marketing techniques used by influencers and internet celebrities. Therefore, the study concludes that Ada Colau can be considered an example of a new category of celebrity politician, the «influencer-politician», suggesting that future research should dig deeper into this novel dynamic of hybridization and cross-pollination between politics and digital cultures.

Clinical features and prognostic outcomes of angioimmunoblastic T cell lymphoma in an Asian multicenter study

In our Asian multicenter retrospective study, we investigated the clinical prognostic factors affecting the outcomes of AITL patients and identified a novel prognostic index relevant in the Asian context. In our 174-patient cohort, the median PFS and OS was 1.8 years and 5.6 years respectively. Age > 60, bone marrow involvement, total white cell count >12 × 109/L and raised serum lactate dehydrogenase were associated with poorer PFS and OS in multivariate analyses. This allowed for a prognostic index (AITL-PI) differentiating patients into low (0-1 factors, n = 64), moderate (2 factors, n = 59) and high-risk (3-4 factors, n = 49) subgroups with 5-year OS of 84.0%, 44.0% and 28.0% respectively (p < 0.0001). POD24 proved to be strongly prognostic (5-year OS 24% vs 89%, p < 0.0001). Exploratory gene expression studies were performed and disparate immune cell profiles and cell signaling signatures were seen in the low risk group as compared to the intermediate and high risk groups.

Bibliometric analysis of RNA vaccines for cancer

ABSTRACT Cancer represents a challenging medical problem worldwide. Several exploratory studies have been conducted to overcome these limitations. RNA vaccines play an important role in cancer prevention and treatment. Recent studies have shown that RNA vaccines play an important role in cancer prevention. However, there are currently no relevant bibliometric studies. This study aimed to apply bibliometrics to summarize the knowledge structure and research hotspots regarding the role of RNA vaccines in cancer. Publications related to RNA vaccines in cancer were searched on the web of science core collection (WoSCC) database. VOSviewers, CiteSpace and R package “bibliometrix” were used to conduct this bibliometric analysis. A total of 1399 articles were included, comprising 803 original articles and 596 reviews. The number of studies on RNA vaccines against cancer has been increasing annually. China and the United States were the principal countries of origin of publications. Johannes Gutenberg University Mainz, NCI, and Duke University were the main organizations. Frontiers in Immunology is the leading journal in the field. Hot keywords included tumor antigens, lipid nanoparticles, emerging roles, and dendritic cells. This is the bibliometric study to summarize the research trends and development of RNA vaccines for cancer. This information will provide a reference for researchers studying RNA vaccines against cancer.