Mitochondrial neurogastrointestinal encephalomyopathy caused by thymidine phosphorylase enzyme deficiency: From pathogenesis to emerging therapeutic options

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a progressive metabolic disorder caused by thymidine phosphorylase (TP) enzyme deficiency. The lack of TP results in systemic accumulation of deoxyribonucleosides thymidine (dThd) and deoxyuridine (dUrd). In these patients, clinical features include mental regression, ophthalmoplegia, and fatal gastrointestinal complications. The accumulation of nucleosides also causes imbalances in mitochondrial DNA (mtDNA) deoxyribonucleoside triphosphates (dNTPs), which may play a direct or indirect role in the mtDNA depletion/deletion abnormalities, although the exact underlying mechanism remains unknown. The available therapeutic approaches include dialysis and enzyme replacement therapy, both can only transiently reverse the biochemical imbalance. Allogeneic hematopoietic stem cell transplantation is shown to be able to restore normal enzyme activity and improve clinical manifestations in MNGIE patients. However, transplant related complications and disease progression result in a high mortality rate. New therapeutic approaches, such as adeno-associated viral vector and hematopoietic stem cell gene therapy have been tested in Tymp−/− Upp1−/− mice, a murine model for MNGIE. This review provides background information on disease manifestations of MNGIE with a focus on current management and treatment options. It also outlines the pre-clinical approaches toward future treatment of the disease

Assessing Organizational Users’ Intentions and Behavior to AI Integrated CRM Systems: a Meta-UTAUT Approach

This paper tests the meta-analysis based unified theory of acceptance and use of technology (meta-UTAUT) model to predict the behavioral intentions of organizational users and their use behavior to artificial intelligence (AI) integrated customer relationship management (CRM) systems. Data was collected from 315 organizational users in India. The hypotheses draw on the theoretical underpinnings which have been statistically validated. Results show that CRM quality and satisfaction significantly influences an organization’s employees attitudes and intentions to use AI integrated CRM systems. The compatibility of CRM systems has, however, a limited impact on employees attitudes. The findings, which are aligned with the extended UTAUT model, provide useful insights into organizations and decision-makers for designing AI integrated CRM systems

Big Data in Food: Systematic Literature Review and Future Directions

The growing importance of Big Data in the food industry enables businesses to leverage information to gain a competitive advantage. This paper provides a systematic literature review (SLR) to provide an insight into the use of state-of-art of Big Data applications in the food industry. The SLR relies on available literature that provides the context, theoretical construct and identifies gaps. Based on the findings, we suggest recommendations, identify limitations and suggest policy implications and future directions. Using search databases were examined and 38 relevant studies were identified for retrospective analysis. The review shows that Big Data supports the food industry in ways that enable using Artificial Intelligence to manage restaurants and mobile based applications in supporting consumers with restaurant selection. This SLR open new avenues for future research in the importance of Big Data in the food industry, which will surely help researchers/practitioners in effective utilization of Big DataBig Data

Drivers of circular economy for small and medium enterprises: Case study on the Indian state of Tamil Nadu

The present paper highlights the growing relevance of the Circular Economy (CE), its adoption by Small- and Medium-sized Enterprises (SMEs), and the relationship between the drivers of CE. Using a case study of CE adoption by Tamil Nadu state in India, we analyse the interactions between the drivers and examine the challenges and benefits of CE adoption. Using Total Interpretive Structural Modelling (TISM) this paper identifies 10 main drivers relevant for SMEs in Tamil Nadu based on literature and discussions with 78 industrial-academic experts, comments on the driving, dependent and linking elements that impact the uptake and adoption of CE. The modelling results confirm that three drivers, namely urbanisation, funding availability and resource consumption, are relevant and support the successful adoption of CE. The paper is among the first that uses the TISM technique to establish a contextual linkage between CE drivers and relationship between the different drivers

Transplantation, gene therapy and intestinal pathology in MNGIE patients and mice

Background: Gastrointestinal complications are the main cause of death in patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). Available treatments often restore biochemical homeostasis, but fail to cure gastrointestinal symptoms. Methods: We evaluated the small intestine neuromuscular pathology of an untreated MNGIE patient and two recipients of hematopoietic stem cells, focusing on enteric neurons and glia. Additionally, we evaluated the intestinal neuromuscular pathology in a mouse model of MNGIE treated with hematopoietic stem cell gene therapy. Quantification of muscle wall thickness and ganglion cell density was performed blind to the genotype with ImageJ. Significance of differences between groups was determined by two-tailed Mann-Whitney U test (P < 0.05). Results: Our data confirm that MNGIE presents with muscle atrophy and loss of Cajal cells and CD117/c-kit immunoreactivity in the small intestine. We also show that hematopoietic stem cell transplantation does not benefit human intestinal pathology at least on short-term. Conclusions: We suggest that hematopoietic stem cell transplantation may be insufficient to restore intestinal neuropathology, especially at later stages of MNGIE. As interstitial Cajal cells and their networks play a key role in development of gastrointestinal dysmotility, alternative therapeutic approaches taking absence of these cells into account could be required

Exploring the darkverse: a multi-perspective analysis of the negative societal impacts of the metaverse

The Metaverse has the potential to form the next pervasive computing archetype that can transform many aspects of work and life at a societal level. Despite the many forecasted benefits from the metaverse, its negative outcomes have remained relatively unexplored with the majority of views grounded on logical thoughts derived from prior data points linked with similar technologies, somewhat lacking academic and expert perspective. This study responds to the dark side perspectives through informed and multifaceted narratives provided by invited leading academics and experts from diverse disciplinary backgrounds. The metaverse dark side perspectives covered include: technological and consumer vulnerability, privacy, and diminished reality, human–computer interface, identity theft, invasive advertising, misinformation, propaganda, phishing, financial crimes, terrorist activities, abuse, pornography, social inclusion, mental health, sexual harassment and metaverse-triggered unintended consequences. The paper concludes with a synthesis of common themes, formulating propositions, and presenting implications for practice and policy

Mapping geographical inequalities in childhood diarrhoeal morbidity and mortality in low-income and middle-income countries, 2000–17 : analysis for the Global Burden of Disease Study 2017

Background Across low-income and middle-income countries (LMICs), one in ten deaths in children younger than 5 years is attributable to diarrhoea. The substantial between-country variation in both diarrhoea incidence and mortality is attributable to interventions that protect children, prevent infection, and treat disease. Identifying subnational regions with the highest burden and mapping associated risk factors can aid in reducing preventable childhood diarrhoea. Methods We used Bayesian model-based geostatistics and a geolocated dataset comprising 15 072 746 children younger than 5 years from 466 surveys in 94 LMICs, in combination with findings of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, to estimate posterior distributions of diarrhoea prevalence, incidence, and mortality from 2000 to 2017. From these data, we estimated the burden of diarrhoea at varying subnational levels (termed units) by spatially aggregating draws, and we investigated the drivers of subnational patterns by creating aggregated risk factor estimates. Findings The greatest declines in diarrhoeal mortality were seen in south and southeast Asia and South America, where 54·0% (95% uncertainty interval [UI] 38·1–65·8), 17·4% (7·7–28·4), and 59·5% (34·2–86·9) of units, respectively, recorded decreases in deaths from diarrhoea greater than 10%. Although children in much of Africa remain at high risk of death due to diarrhoea, regions with the most deaths were outside Africa, with the highest mortality units located in Pakistan. Indonesia showed the greatest within-country geographical inequality; some regions had mortality rates nearly four times the average country rate. Reductions in mortality were correlated to improvements in water, sanitation, and hygiene (WASH) or reductions in child growth failure (CGF). Similarly, most high-risk areas had poor WASH, high CGF, or low oral rehydration therapy coverage. Interpretation By co-analysing geospatial trends in diarrhoeal burden and its key risk factors, we could assess candidate drivers of subnational death reduction. Further, by doing a counterfactual analysis of the remaining disease burden using key risk factors, we identified potential intervention strategies for vulnerable populations. In view of the demands for limited resources in LMICs, accurately quantifying the burden of diarrhoea and its drivers is important for precision public health

“So what if ChatGPT wrote it?” Multidisciplinary perspectives on opportunities, challenges and implications of generative conversational AI for research, practice and policy

Transformative artificially intelligent tools, such as ChatGPT, designed to generate sophisticated text indistinguishable from that produced by a human, are applicable across a wide range of contexts. The technology presents opportunities as well as, often ethical and legal, challenges, and has the potential for both positive and negative impacts for organisations, society, and individuals. Offering multi-disciplinary insight into some of these, this article brings together 43 contributions from experts in fields such as computer science, marketing, information systems, education, policy, hospitality and tourism, management, publishing, and nursing. The contributors acknowledge ChatGPT’s capabilities to enhance productivity and suggest that it is likely to offer significant gains in the banking, hospitality and tourism, and information technology industries, and enhance business activities, such as management and marketing. Nevertheless, they also consider its limitations, disruptions to practices, threats to privacy and security, and consequences of biases, misuse, and misinformation. However, opinion is split on whether ChatGPT’s use should be restricted or legislated. Drawing on these contributions, the article identifies questions requiring further research across three thematic areas: knowledge, transparency, and ethics; digital transformation of organisations and societies; and teaching, learning, and scholarly research. The avenues for further research include: identifying skills, resources, and capabilities needed to handle generative AI; examining biases of generative AI attributable to training datasets and processes; exploring business and societal contexts best suited for generative AI implementation; determining optimal combinations of human and generative AI for various tasks; identifying ways to assess accuracy of text produced by generative AI; and uncovering the ethical and legal issues in using generative AI across different contexts

Advancing sustainable development goals through interdisciplinarity in sustainable tourism research

The sustainable development goals (SDGs) address multifaceted problems that lie at the intersection between natural and socio-economic systems. While scholars agree that interdisciplinary research is needed to advance the SDGs, the concept of interdisciplinarity itself has been given limited attention. This article explores the interdisciplinarity of research published in the Journal of Sustainable Tourism using references cited by the journal’s articles. We use structural topic modeling to analyze research trends. The findings suggest that the research has become more interdisciplinary, however, knowledge is defined primarily by tourism studies and the business management discipline. To advance the SDGs, researchers should engage with disciplines such as anthropology and the humanities that can bring critical issues such as power relations and socio-cultural values to the forefront of sustainability discourses. Research should also conceptualize the SDGs as a network of targets to facilitate the integration of sustainable tourism outcomes with broader development goals

Factors impacting behavioural intentions to adopt the electronic marketplace: findings from small businesses in India

The pandemic has accelerated e-commerce adoption for both consumers and sellers. This study aims to identify factors critical to the adoption of electronic markets (EM) during the pandemic, from the perspective of small sellers in non-metro cities. The research design utilizes core dimensions of the UTAUT model and selected constructs from protection motivation theory; since business closure vulnerability also triggers electronic market adoption. A questionnaire survey method was used to collect data from 150 sellers from tier-II/III cities of India. Study results identified performance expectancy, effort expectancy, social influence and perceived vulnerability as significant determinants of behavioural intention towards adoption of EM. The findings also explain the moderating impact of sellers' awareness of information technology and merchants’ age on behavioural outcomes. Given the growing demands from such cities, the research offers insights for marketers to understand the bottlenecks and ways to motivate small sellers to get associated with EMs