bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancing the effectiveness of infectious disease health education for children and adolescents in China: a national multicenter school-based trial
Authors: Wang Xinxin , Liu Jieyu , Wu Yu , Su Binbin , Chen Manman , Ma Qi , Ma Tao , Chen Li , Zhang Yi , Dong Yanhui , Song Yi , Ma Jun 
Published: June 2023

AbstractBackgroundInfectious diseases pose a significant risk to the health and well-being of children and adolescents, and can even be life-threatening. Thus, our study aimed to explore the effectiveness of health education based on the social-ecological model in improving the knowledge of infectious diseases among this vulnerable population.MethodsThis study was a school-based intervention conducted in seven Chinese provinces in 2013, involving a total of 26,591 children and adolescents in the intervention group and 24,327 in the control group. The intervention group received a comprehensive health intervention based on the social-ecological model (SEM) over six months, which included a supportive environment, health education on infectious diseases, guidance on self-monitoring infectious disease-related behaviors, and other measures. Data on infectious disease-related knowledge and other characteristics were collected through questionnaires. The main outcome measure will be the difference in the effectiveness of health education regarding infectious diseases in children and adolescents between baseline and post-intervention. A mixed-effects regression model was used to calculate the odds ratio (OR) and 95% confidence interval (95% CI) to assess the impact of infectious disease-related interventions on the participants.ResultsWe utilized a socioecological model as the foundation for a six-month health education program on infectious diseases targeting children and adolescents in the intervention group. At the individual and community levels, the correct rate of health behavior related to infectious diseases in the intervention group was higher than that in the control group (P < 0.05), the ORs (95% CI) were 0.94 (0.90–0.99) and 0.94 (0.89–0.99), respectively. But the intervention effect was not significant at the interpersonal level. The intervention effect at the organizational level was obvious, with an increase in opportunities for children and adolescents to acquire knowledge of infectious diseases from courses and lectures, teachers, and doctors, (all P < 0.05), with the ORs (95% CI) of 0.92 (0.87–0.97) and 0.86 (0.83–0.94), respectively. However, there was no significant difference between the intervention group and the control group in school infectious disease health education policy.ConclusionEnhancing health education regarding infectious diseases is crucial in promoting comprehensive prevention and control measures among children and adolescents. Nevertheless, it remains imperative to reinforce health education on infectious diseases at the interpersonal and policy levels. This holds significant reference value for mitigating childhood infectious diseases in the post-COVID-19 era.
Single-cell RNA-sequencing of stria vascularis cells in the adult Slc26a4-/- mouse
Authors: Koh Jin-Young , Affortit Corentin , Ranum Paul T. , West Cody , Walls William D. , Yoshimura Hidekane , Shao Jian Q. , Mostaert Brian , Smith Richard J.H. 
Published: June 2023

Abstract
Background
The primary pathological alterations of Pendred syndrome are endolymphatic pH acidification and luminal enlargement of the inner ear. However, the molecular contributions of specific cell types remain poorly characterized. Therefore, we aimed to identify pH regulators in pendrin-expressing cells that may contribute to the homeostasis of endolymph pH and define the cellular pathogenic mechanisms that contribute to the dysregulation of cochlear endolymph pH in Slc26a4−/− mice.

Methods
We used single-cell RNA sequencing to identify both Slc26a4-expressing cells and Kcnj10-expressing cells in wild-type (WT, Slc26a4+/+) and Slc26a4−/− mice. Bioinformatic analysis of expression data confirmed marker genes defining the different cell types of the stria vascularis. In addition, specific findings were confirmed at the protein level by immunofluorescence.

Results
We found that spindle cells, which express pendrin, contain extrinsic cellular components, a factor that enables cell-to-cell communication. In addition, the gene expression profile informed the pH of the spindle cells. Compared to WT, the transcriptional profiles in Slc26a4−/− mice showed downregulation of extracellular exosome-related genes in spindle cells. Immunofluorescence studies in spindle cells of Slc26a4−/− mice validated the increased expression of the exosome-related protein, annexin A1, and the clathrin-mediated endocytosis-related protein, adaptor protein 2.

Conclusion
Overall, cell isolation of stria vascularis from WT and Slc26a4−/− samples combined with cell type-specific transcriptomic analyses revealed pH-dependent alternations in spindle cells and intermediate cells, inspiring further studies into the dysfunctional role of stria vascularis cells in SLC26A4-related hearing loss.
Combination effects of amino acid transporter LAT1 inhibitor nanvuranlat and cytotoxic anticancer drug gemcitabine on pancreatic and biliary tract cancer cells
Authors: Nishikubo Kou , Ohgaki Ryuichi , Liu Xingming , Okanishi Hiroki , Xu Minhui , Endou Hitoshi , Kanai Yoshikatsu 
Published: June 2023

Abstract
Background
Cytotoxic anticancer drugs widely used in cancer chemotherapy have some limitations, such as the development of side effects and drug resistance. Furthermore, monotherapy is often less effective against heterogeneous cancer tissues. Combination therapies of cytotoxic anticancer drugs with molecularly targeted drugs have been pursued to solve such fundamental problems. Nanvuranlat (JPH203 or KYT-0353), an inhibitor for L-type amino acid transporter 1 (LAT1; SLC7A5), has novel mechanisms of action to suppress the cancer cell proliferation and tumor growth by inhibiting the transport of large neutral amino acids into cancer cells. This study investigated the potential of the combined use of nanvuranlat and cytotoxic anticancer drugs.

Methods
The combination effects of cytotoxic anticancer drugs and nanvuranlat on cell growth were examined by a water-soluble tetrazolium salt assay in two-dimensional cultures of pancreatic and biliary tract cancer cell lines. To elucidate the pharmacological mechanisms underlying the combination of gemcitabine and nanvuranlat, we investigated apoptotic cell death and cell cycle by flow cytometry. The phosphorylation levels of amino acid-related signaling pathways were analyzed by Western blot. Furthermore, growth inhibition was examined in cancer cell spheroids.

Results
All the tested seven types of cytotoxic anticancer drugs combined with nanvuranlat significantly inhibited the cell growth of pancreatic cancer MIA PaCa-2 cells compared to their single treatment. Among them, the combined effects of gemcitabine and nanvuranlat were relatively high and confirmed in multiple pancreatic and biliary tract cell lines in two-dimensional cultures. The growth inhibitory effects were suggested to be additive but not synergistic under the tested conditions. Gemcitabine generally induced cell cycle arrest at the S phase and apoptotic cell death, while nanvuranlat induced cell cycle arrest at the G0/G1 phase and affected amino acid-related mTORC1 and GAAC signaling pathways. In combination, each anticancer drug basically exerted its own pharmacological activities, although gemcitabine more strongly influenced the cell cycle than nanvuranlat. The combination effects of growth inhibition were also verified in cancer cell spheroids.

Conclusions
Our study demonstrates the potential of first-in-class LAT1 inhibitor nanvuranlat as a concomitant drug with cytotoxic anticancer drugs, especially gemcitabine, on pancreatic and biliary tract cancers.
Control of the injection velocity of embolic agents in embolization treatment
Authors: Ren Dongcheng , Zhou Bo , Li Jiasheng , Guo Shijie , Guo Baolei 
Published: June 2023

Abstract
Background
Embolization is a common treatment method for tumor-targeting, anti-organ hyper-function, and hemostasis. However, the injection of embolic agents largely depends on the experiences of doctors, and doctors need to work in an X-ray environment that hurts their health. Even for a well-trained doctor, complications such as ectopic embolism caused by excessive embolic agents are always inevitable.

Results
This paper established a flow control curve model for embolic injection based on local arterial pressure. The end-vessel network was simplified as a porous media. The hemodynamic changes at different injection velocities and embolization degrees were simulated and analyzed. Sponge, a typical porous medium, was used to simulate the blocking and accumulation of embolic agents by capillary networks in the in vitro experimental platform.

Conclusions
The simulation and experimental results show that the local arterial pressure is closely related to the critical injection velocity of the embolic agent reflux at a certain degree of embolization. The feasibility of this method for an automatic embolic injection system is discussed. It is concluded that the model of the flow control curve of embolic injection can effectively reduce the risk of ectopic embolism and shorten the time of embolic injection. The clinical application of this model is of great value in reducing radiation exposure and improving the success rate of interventional embolization.
Awareness and utilization of smoking cessation clinics in Saudi Arabia, findings from the 2019 Global Adult Tobacco Survey
Authors: Monshi Sarah S. , Alanazi Abdullah M. M. , Alzahrani Ali M. , Alzhrani Abdulrhman A. , Arbaein Turky J. , Alharbi Khulud K. , Z. Alqahtani Mansour , Alzahrani Ali H. , A. Elkhobby Ahmed , Almazrou Aljoharah M. , Al-Zalabani Abdulmohsen H. 
Published: June 2023

Abstract
Background
Tobacco use remains a leading cause of premature death. To combat tobacco use, the Ministry of Health (MOH) improved access to smoking cessation clinics (SCCs) by developing fixed SCCs and mobile SCCs, which move based on demand across locations. The goal of this study was to investigate awareness and utilization of SCCs among tobacco users in Saudi Arabia and the factors that influence their awareness and utilization.

Method
This cross-sectional study used the 2019 Global Adult Tobacco Survey. Three outcome variables were employed, including tobacco users’ awareness of fixed SCCs, mobile SCCs, and utilization of fixed SCCs. Several independent variables were examined, including sociodemographic characteristics and tobacco use. Multivariable logistic regression analyses were performed.

Results
One thousand six hundred sixty-seven tobacco users were included in this study. There were 60%, 26%, and 9% of tobacco users who were aware of fixed SCCs, aware of mobile SCCs, and visited fixed SCCs, respectively. The likelihood of being aware of SCCs increased among users residing in urban areas (fixed SCCs: OR = 1.88; 95% CI = 1.31–2.68; mobile SCCs: OR = 2.09; CI = 1.37–3.17) while it decreased among those reported self-employed (fixed SCCs: OR = 0.31; CI = 0.17–0.56; mobile SCCs: OR = 0.42; CI = 0.20–0.89). The likelihood of visiting fixed SCCs increased among educated tobacco users aged 25–34 (OR = 5.61; CI = 1.73–18.21) and 35–44 (OR = 4.22; CI = 1.07–16.64) while the odds of visiting SCCs decreased among those who were working in the private sector (OR = 0.26; CI = 0.09–0.73).

Conclusion
The decision to quit smoking must be supported by an effective healthcare system that provides accessible and affordable smoking cessation services. Knowing the factors that influence the awareness and utilization of SCCs would help policymakers dedicate efforts targeting those who desire to quit smoking yet face limitations in using SCCs.
A novel dammarane triterpenoid alleviates atherosclerosis by activating the LXRα pathway
Authors: Huang Yan , Ran Xiaodong , Liu Hongmei , Luo Mingming , Qin Yiyu , Yan Jinqiong , Li Xiaohui , Jia Yi 
Published: June 2023

Abstract
Background
We have previously demonstrated that ginsenoside compound K can attenuate the formation of atherosclerotic lesions. Therefore, ginsenoside compound K has potential for atherosclerosis therapy. How to improve the druggability and enhance the antiatherosclerotic activity of ginsenoside compound K are the core problems in the prevention and treatment of atherosclerosis. CKN is a ginsenoside compound K derivative that was previously reported to have excellent antiatherosclerotic activity in vitro, and we have applied for international patents for it.

Methods
Male C57BL/6 ApoE−/− mice were fed a high-fat and high-choline diet to induce atherosclerosis and were subjected to in vivo studies. In vitro, the CCK-8 method was applied to evaluate cytotoxicity in macrophages. Foam cells were utilized, and cellular lipid determination was performed for in vitro studies. The area of atherosclerotic plaque and fatty infiltration of the liver were measured by image analysis. Serum lipid and liver function were determined by a seralyzer. Immunofluorescence and western blot analysis were conducted to explore the alterations in the expression levels of lipid efflux-related proteins. Molecular docking, reporter gene experiments and cellular thermal shift assays were used to verify the interaction between CKN and LXRα.

Results
After confirming the therapeutic effects of CKN, molecular docking, reporter gene experiments and cellular thermal shift assays were used to predict and investigate the antiatherosclerotic mechanisms of CKN. CKN exhibited the greatest potency, with a 60.9% and 48.1% reduction in en face atherosclerotic lesions on the thoracic aorta and brachiocephalic trunk, reduced plasma lipid levels and decreased foam cell levels in the vascular plaque content in HHD-fed ApoE−/− mice. Moreover, CKN in the present study may exert its antiatherosclerotic effects through activated ABCA1 by promoting LXRα nuclear translocation and reducing the adverse effects of LXRα activation.

Conclusions
Our results revealed that CKN prevented the formation of atherosclerosis in ApoE−/− mice by activating the LXRα pathway.
Microwave therapy for the treatment of plantar warts
Authors: Hagon Wendy , Hagon Jonathan , Noble Greer , Brenton‐Rule Angela , Stewart Sarah , Bristow Ivan 
Published: June 2023

AbstractBackgroundPlantar warts, or verrucae plantaris, are common lesions causing considerable pain during weightbearing activity. Although current treatment modalities have low success rates, microwave therapy has been introduced as a promising intervention. This study aimed to determine the effectiveness of microwave therapy for the treatment of plantar warts and to determine the clinical factors associated with plantar wart resolution.MethodsA retrospective analysis of 150 plantar warts from 45 patients treated with microwave therapy was undertaken. Binomial regression was conducted to explore clinical characteristics (age, gender, immunosuppression, impaired healing, multiple vs single wart, location of lesion, lesion diameter) associated with lesion resolution.ResultsOf the total 150 plantar warts treated with microwave therapy, 125 (83.3%) warts resolved and 25 (17%) warts did not resolve. The mean (SD) total treatment sessions for resolved lesions was 2.8 (1.0). Decreasing age (P = 0.046) was the only clinical characteristic associated with resolution.ConclusionsThis retrospective study has shown that plantar warts may be resolved with two to three sessions of microwave therapy, which may be more successful in younger populations.
Critically buried avalanche victims can develop severe hypothermia in less than 60 min
Authors: Rauch Simon , Kompatscher Julia , Clara Andreas , Öttl Iris , Strapazzon Giacomo , Kaufmann Marc 
Published: June 2023

Abstract
Background
A major challenge in the management of avalanche victims in cardiac arrest is differentiating hypothermic from non-hypothermic cardiac arrest, as management and prognosis differ. Duration of burial with a cutoff of 60 min is currently recommended by the resuscitation guidelines as a parameter to aid in this differentiation However, the fastest cooling rate under the snow reported so far is 9.4 °C per hour, suggesting that it would take 45 min to cool below 30 °C, which is the temperature threshold below which a hypothermic cardiac arrest can occur.

Case presentation
We describe a case with a cooling rate of 14 °C per hour, assessed on site with an oesophageal temperature probe. This is by far the most rapid cooling rate after critical avalanche burial reported in the literature and further challenges the recommended 60 min threshold for triage decisions. The patient was transported under continuous mechanical CPR to an ECLS facility and rewarmed with VA-ECMO, although his HOPE score was 3% only. After three days he developed brain death and became an organ donor.

Conclusions
With this case we would like to underline three important aspects: first, whenever possible, core body temperature should be used instead of burial duration to make triage decisions. Second, the HOPE score, which is not well validated for avalanche victims, had a good discriminatory ability in our case. Third, although extracorporeal rewarming was futile for the patient, he donated his organs. Thus, even if the probability of survival of a hypothermic avalanche patient is low based on the HOPE score, ECLS should not be withheld by default and the possibility of organ donation should be considered.
Histone modification analysis reveals common regulators of gene expression in liver and blood stage merozoites of Plasmodium parasites
Authors: Reers Ashley B. , Bautista Rodriel , McLellan James , Morales Beatriz , Garza Rolando , Bol Sebastiaan , Hanson Kirsten K. , Bunnik Evelien M. 
Published: June 2023

AbstractGene expression in malaria parasites is subject to various layers of regulation, including histone post-translational modifications (PTMs). Gene regulatory mechanisms have been extensively studied during the main developmental stages ofPlasmodiumparasites inside erythrocytes, from the ring stage following invasion to the schizont stage leading up to egress. However, gene regulation in merozoites that mediate the transition from one host cell to the next is an understudied area of parasite biology. Here, we sought to characterize gene expression and the corresponding histone PTM landscape during this stage of the parasite lifecycle through RNA-seq and ChIP-seq onP. falciparumblood stage schizonts, merozoites, and rings, as well asP. bergheiliver stage merozoites. In both hepatic and erythrocytic merozoites, we identified a subset of genes with a unique histone PTM profile characterized by a region of H3K4me3 depletion in their promoter. These genes were upregulated in hepatic and erythrocytic merozoites and rings, had roles in protein export, translation, and host cell remodeling, and shared a DNA motif. These results indicate that similar regulatory mechanisms may underlie merozoite formation in the liver and blood stages. We also observed that H3K4me2 was deposited in gene bodies of gene families encoding variant surface antigens in erythrocytic merozoites, which may facilitate switching of gene expression between different members of these families. Finally, H3K18me and H2K27me were uncoupled from gene expression and were enriched around the centromeres in erythrocytic schizonts and merozoites, suggesting potential roles in the maintenance of chromosomal organization during schizogony. Together, our results demonstrate that extensive changes in gene expression and histone landscape occur during the schizont-to-ring transition to facilitate productive erythrocyte infection. The dynamic remodeling of the transcriptional program in hepatic and erythrocytic merozoites makes this stage attractive as a target for novel anti-malarial drugs that may have activity against both the liver and blood stages.
PARP-dependent and NAT10-independent acetylation of N4-cytidine in RNA appears in UV-damaged chromatin
Authors: Svobodová Kovaříková Alena , Stixová Lenka , Kovařík Aleš , Bártová Eva 
Published: June 2023

AbstractRNA modifications have been known for many years, but their function has not been fully elucidated yet. For instance, the regulatory role of acetylation on N4-cytidine (ac4C) in RNA can be explored not only in terms of RNA stability and mRNA translation but also in DNA repair. Here, we observe a high level of ac4C RNA at DNA lesions in interphase cells and irradiated cells in telophase. Ac4C RNA appears in the damaged genome from 2 to 45 min after microirradiation. However, RNA cytidine acetyltransferase NAT10 did not accumulate to damaged sites, and NAT10 depletion did not affect the pronounced recruitment of ac4C RNA to DNA lesions. This process was not dependent on the G1, S, and G2 cell cycle phases. In addition, we observed that the PARP inhibitor, olaparib, prevents the recruitment of ac4C RNA to damaged chromatin. Our data imply that the acetylation of N4-cytidine, especially in small RNAs, has an important role in mediating DNA damage repair. Ac4C RNA likely causes de-condensation of chromatin in the vicinity of DNA lesions, making it accessible for other DNA repair factors involved in the DNA damage response. Alternatively, RNA modifications, including ac4C, could be direct markers of damaged RNAs.
Identification of a methylation panel as an alternative triage to detect CIN3+ in hrHPV-positive self-samples from the population-based cervical cancer screening programme
Authors: de Waard J. , Bhattacharya A. , de Boer M. T. , van Hemel B. M. , Esajas M. D. , Vermeulen K. M. , de Bock G. H. , Schuuring E. , Wisman G. B. A. 
Published: June 2023

Abstract
Background
The Dutch population-based cervical cancer screening programme (PBS) consists of primary high-risk human papilloma virus (hrHPV) testing with cytology as triage test. In addition to cervical scraping by a general practitioner (GP), women are offered self-sampling to increase participation. Because cytological examination on self-sampled material is not feasible, collection of cervical samples from hrHPV-positive women by a GP is required. This study aims to design a methylation marker panel to detect CIN3 or worse (CIN3+) in hrHPV-positive self-samples from the Dutch PBS as an alternative triage test for cytology.

Methods
Fifteen individual host DNA methylation markers with high sensitivity and specificity for CIN3+ were selected from literature and analysed using quantitative methylation-specific PCR (QMSP) on DNA from hrHPV-positive self-samples from 208 women with CIN2 or less (< CIN2) and 96 women with CIN3+. Diagnostic performance was determined by area under the curve (AUC) of receiver operating characteristic (ROC) analysis. Self-samples were divided into a train and test set. Hierarchical clustering analysis to identify input methylation markers, followed by model-based recursive partitioning and robustness analysis to construct a predictive model, was applied to design the best marker panel.

Results
QMSP analysis of the 15 individual methylation markers showed discriminative DNA methylation levels between < CIN2 and CIN3+ for all markers (p < 0.05). The diagnostic performance analysis for CIN3+ showed an AUC of ≥ 0.7 (p < 0.001) for nine markers. Hierarchical clustering analysis resulted in seven clusters with methylation markers with similar methylation patterns (Spearman correlation> 0.5). Decision tree modeling revealed the best and most robust panel to contain ANKRD18CP, LHX8 and EPB41L3 with an AUC of 0.83 in the training set and 0.84 in the test set. Sensitivity to detect CIN3+ was 82% in the training set and 84% in the test set, with a specificity of 74% and 71%, respectively. Furthermore, all cancer cases (n = 5) were identified.

Conclusion
The combination of ANKRD18CP, LHX8 and EPB41L3 revealed good diagnostic performance in real-life self-sampled material. This panel shows clinical applicability to replace cytology in women using self-sampling in the Dutch PBS programme and avoids the extra GP visit after a hrHPV-positive self-sampling test.