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ATRX is a tumor suppressor that has been associated with protection from DNA replication stress, purportedly through resolution of difficult-to-replicate G-quadruplex (G4) DNA structures. While several studies demonstrate that loss of ATRX sensitizes cells to chemical stabilizers of G4 structures, the molecular function of ATRX at G4 regions during replication remains unknown. Here, we demonstrate that ATRX associates with a number of the MCM replication complex subunits and that loss of ATRX leads to G4 structure accumulation at newly synthesized DNA. We show that both the helicase domain of ATRX and its H3.3 chaperone function are required to protect cells from G4-induced replicative stress. Furthermore, these activities are upstream of heterochromatin formation mediated by the histone methyltransferase, ESET, which is the critical molecular event that protects cells from G4-mediated stress. In support, tumors carrying mutations in either ATRX or ESET show increased mutation burden at G4-enriched DNA sequences. Overall, our study provides new insights into mechanisms by which ATRX promotes genome stability with important implications for understanding impacts of its loss on human disease. ATRX is a chromatin remodeling protein, which loss has been associated to replication stress, DNA damage, and DNA repair failures that drive genome instability. Here the authors reveal that ATRX protects genomic integrity at G4-containing regions by maintaining these regions in a closed heterochromatic state.

Even though the combined use of ultrasound (US) and alpha-fetoprotein (AFP) is recommended for the surveillance of hepatocellular carcinoma (HCC), the utilization of AFP has its challenges, including accuracy dependent on its cut-off levels, degree of liver necroinflammation, and etiology of liver disease. Though various studies have demonstrated the utility of protein induced by vitamin K absence II (PIVKA-II) in surveillance, treatment monitoring, and predicting recurrence, it is still not recommended as a routine biomarker test. A panel of 17 experts from Asia-Pacific, gathered to discuss and reach a consensus on the clinical usefulness and value of PIVKA-II for the surveillance and treatment monitoring of HCC, based on six predetermined statements. The experts agreed that PIVKA-II was valuable in the detection of HCC in AFP-negative patients, and could potentially benefit detection of early HCC in combination with AFP. PIVKA-II is clinically useful for monitoring curative and intra-arterial locoregional treatments, outcomes, and recurrence, and could potentially predict microvascular invasion risk and facilitate patient selection for liver transplant. However, combining PIVKA-II with US and AFP for HCC surveillance, including small HCC, still requires more evidence, whilst its role in detecting AFP-negative HCC will potentially increase as more patients are treated for hepatitis-related HCC. PIVKA-II in combination with AFP and US has a clinical role in the Asia-Pacific region for surveillance. However, implementation of PIVKA-II in the region will have some challenges, such as requiring standardization of cut-off values, its cost-effectiveness and improving awareness among healthcare providers.

Large and unaccounted numbers of victims in disasters, events, or fires are often trapped in buildings or debris, and must be located and rescued as soon as possible. This study transforms smartphones into indoor locating tools without extra modification or complicated program installation, considering smartphones are likely to be carried when disasters strike. The study creates a system that converts smartphones into a lifesaving tool for trapped victims and rescuers. This study employs the Bluetooth beacon in smartphones to send signals using its low power consumption feature. The signal could continue transmitting for rescuers to locate trapped victims for longer. Rescuers could use the Bluetooth function on a regular notebook computer to search such signals without any hardware implementation or modification, allowing them to locate and determine the position of many trapped victims simultaneously. Implementing this system will decrease the search and rescue team’s need to enter unsafe areas and increase their rescue speed, a critical factor for the survival of trapped victims. Furthermore, when disasters strike, the smartphone calling function might not work, and the trapped victim might be too weak to call for help. Thus, autoreply messages from victims’ smartphones could help them be located within a 2-m error, even if covered by fallen debris such as wood piles or tiles. This effort will increase the chance of finding trapped victims within the golden rescue hours and reduce the exposure time of search and rescue teams in unsafe environments.

The support vector regression (SVR) has been employed to deal with stock price forecasting problems. However, the selection of appropriate kernel parameters is crucial to obtaining satisfactory forecasting performance. This paper proposes a novel approach for forecasting stock prices by combining the SVR with the firefly algorithm (FA). The proposed forecasting model has two stages. In the first stage, to enhance the global convergence speed, a modified version of the FA, which is termed the MFA, is developed in which the dynamic adjustment strategy and the opposition-based chaotic strategy are introduced. In the second stage, a hybrid SVR model is proposed and combined with the MFA for stock price forecasting, in which the MFA is used to optimize the SVR parameters. Finally, comparative experiments are conducted to show the applicability and superiority of the proposed methods. Experimental results show the following: (1) Compared with other algorithms, the proposed MFA algorithm possesses superior performance, and (2) The proposed MFA-SVR prediction procedure can be considered as a feasible and effective tool for forecasting stock prices.

Amidst the global digital transformation of educational institutions, digital technology has emerged as a significant area of interest among scholars. Such technologies have played an instrumental role in enhancing learner performance and improving the effectiveness of teaching and learning. These digital technologies also ensure the sustainability and stability of education during the epidemic. Despite this, a dearth of systematic reviews exists regarding the current state of digital technology application in education. To address this gap, this study utilized the Web of Science Core Collection as a data source (specifically selecting the high-quality SSCI and SCIE) and implemented a topic search by setting keywords, yielding 1849 initial publications. Furthermore, following the PRISMA guidelines, we refined the selection to 588 high-quality articles. Using software tools such as CiteSpace, VOSviewer, and Charticulator, we reviewed these 588 publications to identify core authors (such as Selwyn, Henderson, Edwards), highly productive countries/regions (England, Australia, USA), key institutions (Monash University, Australian Catholic University), and crucial journals in the field ( Education and Information Technologies , Computers & Education , British Journal of Educational Technology ). Evolutionary analysis reveals four developmental periods in the research field of digital technology education application: the embryonic period, the preliminary development period, the key exploration, and the acceleration period of change. The study highlights the dual influence of technological factors and historical context on the research topic. Technology is a key factor in enabling education to transform and upgrade, and the context of the times is an important driving force in promoting the adoption of new technologies in the education system and the transformation and upgrading of education. Additionally, the study identifies three frontier hotspots in the field: physical education, digital transformation, and professional development under the promotion of digital technology. This study presents a clear framework for digital technology application in education, which can serve as a valuable reference for researchers and educational practitioners concerned with digital technology education application in theory and practice.

Background Syphilis is a sexually transmitted disease caused by Treponema pallidum , and the infection source is syphilis patients. This study aimed to estimate the incidence, mortality rate, and disability-adjusted life years (DALYs) of syphilis to improve the understanding of the current global situation of syphilis. Methods This study collected data on syphilis incidence, mortality, and DALYs from the 2019 Global Burden of Disease database. Results The global number of incident cases and age-standardized incidence rate (ASIR) increased from 8,845,220 (95% UI: 6,562,510–11,588,860) in 1990 to 14,114,110 (95% UI: 10,648,490–18,415,970) in 2019 and 160.03/100,000 persons (95% UI: 120.66–208.1) to 178.48/100,000 persons (95% UI: 134.94–232.34), respectively. The estimated annual percentage change (EAPC) in the ASIR was 0.16 (95% CI: 0.07–0.26). The EAPC in the ASIR associated with high and high-middle sociodemographic indices increased. The ASIR increased among males but decreased among females, and the incidence peaked among males and females between the ages of 20 and 30 years. The EAPCs in the age-standardized death rate and age-standardized DALY rate decreased. Conclusions The incidence and ASIR of syphilis increased worldwide from 1990 to 2019. Only the regions with high and high-middle sociodemographic indices showed an increase in the ASIR. Moreover, the ASIR increased among males but decreased among females. The age-standardized death rate and DALY rate both declined worldwide. The increase in the global ASIR of syphilis is a challenge.

PurposeThe purpose of this paper is to investigate the effects of anthropomorphism and identify factors related to adopting voice shopping on smart speakers.Design/methodology/approachProgress in partial least squares structural equation modeling (PLS-SEM) approach is used to test the proposed research framework regarding anthropomorphism and user perceptions on voice shopping via smart speakers. Individuals' responses to questions about attitude and intention to use voice shopping via smart speakers were collected and analyzed.FindingsThe results showed that anthropomorphism had a positive influence on satisfaction, which, in turn, had a positive impact on intention to adopt voice shopping, and customers had positive opinions regarding smart speakers.Research limitations/implicationsThis study only reflects a younger perspective on smart speaker voice shopping. This study identified the characteristics of smart speakers that increase customers' intention to purchase, which can be used to formulate sales strategies and management guidelines.Practical implicationsThis research provided a new perspective to enable practitioners to promote smart speakers for voice shopping. Smart speaker manufacturers can utilize the findings of this research to improve the system design of smart speakers to further facilitate voice shopping.Originality/valueUnlike previous studies, which focused on product attributes of smart speakers or voice shopping experiences, this study provided a clear picture of how the anthropomorphic feature of smart speakers affects customers' intention to adopt voice shopping.

Purpose This study aims to examine how virtual influencers (VIs) affect purchase intentions in tourism and hospitality e-commerce live streaming (THCLS) by focusing on the roles of VIs’ source credibility, trust in products, trust in VIs, emotional engagement, parasocial relationships and influencer–product congruence. Design/methodology/approach Survey data from 416 active viewers of VIs in THCLS were analysed using partial least squares structural equation modelling. Findings This study highlights the importance of the VIs’ source credibility, which positively affects trust in the product, trust in VIs and emotional engagement. However, source credibility does not have a positive impact on parasocial relationships. Trust in products positively influences trust in VIs. Emotional engagement and trust in VIs significantly influence parasocial relationships, which, positively affects purchase intentions. Influencer–product congruence strengthens the link between parasocial relationships and purchase intentions but does not moderate the relationship between trust in VIs and purchase intentions. No significant gender differences were observed, although minor discrepancies were noted in the effect of trust in products on trust in VIs. The importance–performance map analysis revealed that parasocial relationships are the most important factor influencing purchase intentions, while influencer–product congruence has the highest performance, trust in products is the least important and VIs’ source credibility has the lowest performance. Practical implications This study provides actionable insights for marketers leveraging VIs in the THCLS sector, emphasizing strategies to enhance VI credibility, foster parasocial relationships, ensure influencer–product congruence and adopt gender-neutral marketing approaches to effectively influence purchase intentions. Originality/value This study offers theoretical and practical insights into the role of VIs in THCLS, illuminating their impact on consumer behaviour and purchase intentions.

Background This study examines global trends in acquired immune deficiency syndrome (AIDS) incidence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2019, focusing on regional disparities in AIDS incidence, mortality, and DALYs across various levels of socio-demographic index (SDI). It also investigates variations in AIDS incidence, mortality, and DALYs across different age groups, and projects specific trends for the next 25 years. Methods Comprehensive data on AIDS from 1990 to 2019 in 204 countries and territories was obtained from a GBD study. This included information on AIDS incidence, mortality, DALYs, and age-standardized rates (ASRs). Projections for AIDS incidence and mortality over the next 25 years were generated using the Bayesian age-period-cohort model. Results From 1990 to 2019, the global incidence of HIV cases increased from 1,989,282 to 2,057,710, while the age-standardized incidence rate (ASIR) decreased from 37.59 to 25.24 with an estimated annual percentage change (EAPC) of -2.38. The ASIR exhibited an upward trend in high SDI and high-middle SDI regions, a stable trend in middle SDI regions, and a downward trend in low-middle SDI and low SDI regions. In regions with higher SDI, the ASIR was higher in males than in females, while the opposite was observed in lower SDI regions. Throughout 1990 to 2019, the age-standardized death rate (ASDR) and age-standardized DALY rate remained stable, with EAPCs of 0.24 and 0.08 respectively. Countries with the highest HIV burden affecting women and children under five years of age are primarily situated in lower SDI regions, particularly in sub-Saharan Africa. Projections indicate a significant continued decline in the age-standardized incidence and mortality rates of AIDS over the next 25 years, for both overall and by gender. Conclusions The global ASIR decreased from 1990 to 2019. Higher incidence and death rates were observed in the lower SDI region, indicating a greater susceptibility to AIDS among women and < 15 years old. This underscores the urgent need for increased resources to combat AIDS in this region, with focused attention on protecting women and < 15 years old as priority groups. The AIDS epidemic remained severe in sub-Saharan Africa. Projections for the next 25 years indicate a substantial and ongoing decline in both age-standardized incidence and mortality rates.

Multidrug resistance (MDR) is a complicated ever-changing problem in cancer treatment, and P-glycoprotein (P-gp), a drug efflux pump, is regarded as the major cause. In the way of developing P-gp inhibitors, natural products such as phenolic acids have gotten a lot of attention recently. The aim of the present study was to investigate the modulating effects and mechanisms of caffeic acid on human P-gp, as well as the attenuating ability on cancer MDR. Calcein-AM, rhodamine123, and doxorubicin were used to analyze the interaction between caffeic acid and P-gp, and the ATPase activity of P-gp was evaluated as well. Resistance reversing effects were revealed by SRB and cell cycle assay. The results indicated that caffeic acid uncompetitively inhibited rhodamine123 efflux and competitively inhibited doxorubicin efflux. In terms of P-gp ATPase activity, caffeic acid exhibited stimulation in both basal and verapamil-stimulated activity. The combination of chemo drugs and caffeic acid resulted in decreased IC50 in ABCB1/Flp-InTM-293 and KB/VIN, indicating that the resistance was reversed. Results of molecular docking suggested that caffeic acid bound to P-gp through GLU74 and TRY117 residues. The present study demonstrated that caffeic acid is a promising candidate for P-gp inhibition and cancer MDR attenuation.