bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integration of host gene regulation and oral microbiome reveals the influences of smoking during the development of oral squamous cell carcinoma
Authors: Liang Dan , Ma Xuemeng , Zhong Xiaoyi , Zhou Yinghua , Chen Wenxia , He Xuan 
Published: October 2024

ObjectiveThis study aims to investigate the regulation of host gene transcription and microbial changes during the development of oral squamous cell carcinoma (OSCC) associated with smoking.MethodsThe OSCC mouse model and smoking mouse model were established using 200 μg/mL 4-nitroquinoline-1-oxide (4NQO) in drinking water and exposure to cigarette smoke (four cigarettes per session, once a day, 5 days a week). Tongue tissues were harvested at 4 weeks and 16 weeks. Histopathological changes were evaluated using hematoxylin and eosin staining and Ki67 staining. RNA sequencing was performed on the mouse tongue tissues to identify differentially expressed genes (DEGs), and the results were validated by RT-PCR and immunohistochemistry. 16S rDNA sequencing was used to analyze changes in the oral microbiota during the early development of OSCC, identifying differentially abundant taxa associated with smoking. Finally, associations between the relative abundances of the oral microbiome and host gene expression were modeled using the Origin software.ResultsDEGs associated with smoking during the development of OSCC were identified. There were 12 upregulated genes, including NR4A3 and PPP1R3C, and 23 downregulated genes, including CD74 and ANKRD1. These genes were enriched in functions related to the signal transduction of cellular processes such as inflammation, differentiation, immunity, and PI3K/AKT, NF-κB signaling pathways. 4NQO and smoking treatment decreased oral microbial diversity and reduced the abundance of Bacteroidetes, Proteobacteria, and Lactobacillus but increased the abundance of Staphylococcus. Integrative analysis showed that the expression of CD74 was positively correlated with the relative abundance of Lactobacillus, while PPP1R3C was negatively correlated with Bacteroidota.ConclusionIn addition to characterizing host gene expression and the oral microbiome, our study explored the potential role of host–microbiome interactions in the development of OSCC. These findings enhance our understanding of smoking-related OSCC occurrence and development, providing new insights for its prevention.
Evaluating pain in non-verbal critical care patients: a narrative review of the critical care pain observation tool and Its clinical applications
Authors: Afenigus Abebe Dilie 
Published: October 2024

BackgroundAssessing pain in critically ill patients who cannot communicate verbally poses significant challenges. Traditional self-report measures are ineffective for these patients, making the need for reliable observational tools crucial.ObjectiveTo evaluate the effectiveness, reliability, and clinical applicability of the Critical Care Pain Observation Tool (CPOT) in various intensive care unit (ICU) settings and to explore potential innovations for improving its use and integration into clinical practice.MethodsA narrative review evaluated the Critical Care Pain Observation Tool (CPOT) for non-communicative ICU patients, comparing it to the Behavioral Pain Scale (BPS) and the FLACC scale. The review assessed CPOT's effectiveness across different ICU settings, identified limitations and challenges, and explored potential enhancements such as electronic scoring, additional physiological indicators, and improved training protocols.ResultsThe CPOT has been validated as an effective pain assessment tool for non-verbal ICU patients. It evaluates pain through facial expressions, body movements, muscle tension, and ventilator compliance. The CPOT shows superior sensitivity at 76.5% compared to 62.7% for the BPS and offers a more comprehensive assessment of pain indicators like muscle tension and ventilator compliance than the FLACC scale. Despite its strengths, the CPOT has limitations, including inter-rater variability and challenges in certain patient populations. Barriers to implementation include resource constraints and the need for extensive training.ConclusionThe Critical Care Pain Observation Tool (CPOT) is a highly effective instrument for assessing pain in non-verbal ICU patients, demonstrating superior accuracy and reliability compared to other tools like the Behavioral Pain Scale (BPS) and FLACC scale. Its detailed approach, covering facial expressions, body movements, muscle tension, and ventilator compliance, offers a detailed measure of pain. However, challenges such as inter-rater variability and limitations in specific patient populations highlight the need for ongoing refinement and research.
Willingness to pay and price elasticity of demand for long-acting injectable cabotegravir among men who have sex with men in Guangxi, China
Authors: Chen Shiwen , Ruan Yuhua , Liu Lu , Pei Hengyan , Jiang Yu , Huang Tengda , Wei Yuxia , Qin Litai , Dai Xuebin , Liu Yu , Liu Junhui , Xie Yihong 
Published: October 2024

ObjectivesThere is still no study focused on willingness to pay for long-acting injectable cabotegravir (CAB-LA) after it was available on the market in the United States in 2021. Here, we explored the willingness to pay for CAB-LA and associated factors and price elasticity of demand (PED) of CAB-LA among men who have sex with men (MSM) in Guangxi, China.MethodsA cross-sectional study was conducted. Univariate and multivariate ordinal logistic regression analyses were performed to explore the associated factors of willingness to pay for CAB-LA. PED was used to measure the change in the number of participants willing to pay to a change in price.ResultsA total of 1,006 MSM were recruited, among which 84.1% were aged between 18 and 39 years old. The median (interquartile) of the maximum amount of willing to pay for CAB-LA was 200 (100–500) Chinese yuan (CNY) per month. Most (84.2%) were willing to pay less than 600 CNY per month. The number of participants willing to pay for CAB-LA significantly increased with decrease in the price. When the price (CNY per month) decreased from 600 to 500, 500 to 400, 400 to 300, and 300 to 200, PED was 3.13, 1.64, 1.33, and 1.17, respectively. The maximum amount of willing to pay for CAB-LA was positively associated with younger age (vs. ≥40 years group, 18–24 years group, aOR: 1.94, 95% CI: 1.32–2.85; 25–39 year group, aOR: 1.70, 95% CI: 1.20–2.42), being high educated (vs. middle school or lower group, high school or college group, aOR: 1.61, 95% CI: 1.06–2.48; bachelor’s degree or above group, aOR: 2.21, 95% CI: 1.41–3.49), monthly income ≥6000 CNY (vs. &lt;3000 CNY, aOR: 1.46, 95% CI: 1.02–2.09), being bisexual/unsure sexual orientation (vs. gay, aOR: 1.73, 95% CI: 1.24–2.43), and heard of PrEP and used (vs. never heard of PrEP, aOR: 1.76, 95% CI: 1.11–2.77).ConclusionThe maximum amount of willing to pay for CAB-LA was low in Guangxi, China. PED of CAB-LA is relatively elastic. The waived patent protection should be considered for the wide promotion of CAB-LA, and the health education should be strengthened to improve the recognition of CAB-LA.
Rapid identification of chemical profiles in vitro and in vivo of Huan Shao Dan and potential anti-aging metabolites by high-resolution mass spectrometry, sequential metabolism, and deep learning model
Authors: Li Xueyan , Pan Fulu , Wang Lin , Zhang Jing , Wang Xinyu , Qi Dongying , Chai Xiaoyu , Wang Qianqian , Yi Zirong , Ma Yuming , Pan Yanli , Liu Yang , Wang Guopeng 
Published: October 2024

BackgroundAging is marked by the gradual deterioration of cells, tissues, and organs and is a major risk factor for many chronic diseases. Considering the complex mechanisms of aging, traditional Chinese medicine (TCM) could offer distinct advantages. However, due to the complexity and variability of metabolites in TCM, the comprehensive screening of metabolites associated with pharmacology remains a significant issue.MethodsA reliable and integrated identification method based on UPLC-Q Exactive-Orbitrap HRMS was established to identify the chemical profiles of Huan Shao Dan (HSD). Then, based on the theory of sequential metabolism, the metabolic sites of HSD in vivo were further investigated. Finally, a deep learning model and a bioactivity assessment assay were applied to screen potential anti-aging metabolites.ResultsThis study identified 366 metabolites in HSD. Based on the results of sequential metabolism, 135 metabolites were then absorbed into plasma. A total of 178 peaks were identified from the sample after incubation with artificial gastric juice. In addition, 102 and 91 peaks were identified from the fecal and urine samples, respectively. Finally, based on the results of the deep learning model and bioactivity assay, ginsenoside Rg1, Rg2, and Rc, pseudoginsenoside F11, and jionoside B1 were selected as potential anti-aging metabolites.ConclusionThis study provides a valuable reference for future research on the material basis of HSD by describing the chemical profiles both in vivo and in vitro. Moreover, the proposed screening approach may serve as a rapid tool for identifying potential anti-aging metabolites in TCM.
Computational identification of Vernonia cinerea-derived phytochemicals as potential inhibitors of nonstructural protein 1 (NSP1) in dengue virus serotype-2
Authors: Hossain Md. Shohel , Hasnat Soharth , Akter Shilpy , Mim Maria Mulla , Tahcin Anika , Hoque Majedul , Sutradhar Durjoy , Keya Mst. Alifa Akter , Sium Namin Rouf , Hossain Sophia , Masuma Runa , Rakib Sakhawat Hossen , Islam Md. Aminul , Islam Tofazzal , Bhattacharya Prosun , Hoque M. Nazmul 
Published: October 2024

BackgroundDengue virus (DENV) infection, spread by Aedes aegypti mosquitoes, is a significant public health concern in tropical and subtropical regions. Among the four distinct serotypes of DENV (DENV-1 to DENV-4), DENV-2 is associated with the highest number of fatalities worldwide. However, there is no specific treatment available for dengue patients caused by DENV-2.ObjectiveThis study aimed to identify inhibitory phytocompounds in silico in Vernonia cinerea (V. cinerea), a widely used traditional medicinal plant, for treating DENV-2 associated illnesses.MethodsThe chemical structures of 17 compounds from V. cinerea were sourced from the Indian Medicinal Plants, Phytochemistry, and Therapeutics (IMPPAT) database. These compounds underwent geometry optimization, were screened against nonstructural protein 1 (NSP1) of DENV-2, and further validated through molecular dynamics simulations (MDS). Baicalein, an established drug against DENV-2, was used for validation in molecular screening, MDS, and MM-GBSA analyses.ResultsAmong these compounds, Beta-amyrin, Beta-amyrin acetate, Chrysoeriol, Isoorientin, and Luteolin showed promising potential as inhibitors of the NSP1 of DENV-2, supported by the results of thermodynamic properties, molecular orbitals, electrostatic potentials, spectral data and molecular screening. Besides, these compounds adhered to the Lipinski’s “rule of 5”, showing no hepatotoxicity/cytotoxicity, with mixed mutagenicity, immunotoxicity, and carcinogenicity. Furthermore, final validation through MDS confirmed their potential, demonstrating stable tendencies with significant inhibitory activities against NSP1 of DENV-2 over the control drug Baicalein. Among the screened compounds, Chrysoeriol emerged as the most promising inhibitor of NSP1 of DENV-2, followed by Luteolin and Isoorientin.ConclusionTaken together, our results suggest that Chrysoeriol is the best inhibitor of NSP1 of DENV-2, which could be evaluated as a therapeutic agent or a lead compound to treat and manage DENV-2 infections.
The single-strand DNA-binding protein SSB1 is involved in the expression of salivary gland radiation injury repair
Authors: Wang Xian , Wang Yuetong , Zeng Xianglin , Lu Haoyu , Mo Dongqin , Li Yuetao , Liu Zhiqing , Huang Yude , Yu Kun , Wang Daiyou 
Published: October 2024

ObjectivesSingle-strand DNA-binding protein 1 (SSB1) plays a crucial role in the cellular response to DNA damage. This study aimed to explore the expression and regulation of SSB1 in normal rat salivary gland tissues and tissues following radiation, with a specific emphasis on its involvement in the repair of salivary gland injury.MethodsA total of 45 adult SD rats were randomly assigned to one control group or eight experimental groups. In the control group, five rats were euthanized without irradiation, and their parotid gland tissues were collected for analysis. The experimental groups received a dose of 6 Gy of radiation targeting the head and neck region; subsequently, five rats from each group were euthanized hly to collect parotid gland tissue samples, resulting in a total of eight experimental groups. The expression levels of SSB1, γ-H2AX, and PARP1 in the parotid gland tissues were assessed via immunohistochemistry, while changes in SSB1 gene expression were quantified via RT-qPCR.ResultsNo significant morphological differences were observed between the two groups following HE staining. In the immunohistochemistry (IHC) analysis, notable tissue-specific variation in SSB1 expression was identified, with higher levels detected in the ducts than in the acini and connective tissue. The expression of SSB1 gene initially increased post-radiation before subsequently decreasing, ultimately returning to baseline levels, as corroborated by the RT-qPCR results. In contrast, γ-H2AX and PARP1 exhibited minimal expression in the control group; however, their expression peaked at 1 h in the experimental group before gradually declining to levels comparable to those of the control group.ConclusionRadiation induces time-dependent upregulation of SSB1 expression in rat salivary glands, indicating that SSB1 may play a role in radiation-induced repair processes.
Exploring global perspectives on the use of computer-based simulation in pharmacy education: a survey of students and educators
Authors: Gharib Ahmed M. , Bindoff Ivan K. , Peterson Gregory M. , Salahudeen Mohammed S. 
Published: October 2024

Background: Increasing student numbers and logistical challenges in pharmacy education limit patient counselling and clinical placement opportunities. Computer-based simulation (CBS) offers scalable, interactive learning but faces integration barriers.Objective: To explore global perceptions of CBS implementation in pharmacy education among educators and students. Methods: An online cross-sectional survey was developed based on literature review and expert feedback. The survey was distributed globally through academic pharmacy organisations, social media, and the authors’ networks. It included 20 questions targeting pharmacy educators and students.Results: Responses from 152 educators across 38 countries and 392 students from 46 countries, spanning six WHO regions (AFRO, AMRO, EMRO, EURO, SEARO, and WPRO) were analysed using descriptive and inferential statistics. The majority of educators (90.1%, n = 137) and students (84.2%, n = 330) expressed comfort with using CBS and implementing it in their curriculum. Despite this, CBS was perceived as underutilised by 53.5% (n = 81) of educators and 63.7% (n = 250) of students. Students valued CBS for enhancing communication and problem-solving skills, while educators highlighted its relevance to community pharmacy practice. Both groups supported CBS use in assessments. All educators (100%) identified workload reduction as a key priority, hoped CBS could assist in this area. Educators also reported barriers such as financial constraints (56.6%, n = 86) and insufficient technical support (53.3%, n = 81). On the other hand, students were less optimistic about institutional support, with only a few (7.4%, n = 29) believed institutional leaders would actively support CBS adoption. Regional differences emerged, with SEARO (Southeast Asia) and AFRO (Africa) showing the lowest CBS usage rates. Educators in SEARO, AFRO, and EMRO (Eastern Mediterranean) raised concerns about technical support, while those in SEARO, AFRO, and WPRO (Western Pacific, including Australia, New Zealand, and Singapore) expressed financial concerns. Educators in AFRO and WPRO, however, reported being 100% comfortable with using CBS.Conclusion: Both students and educators recognised the potential of CBS in pharmacy education, with strong support for its integration. Addressing barriers such as educator workload, financial constraints, and technical support is crucial for broader adoption. Improved resource allocation and targeted training for educators are essential to effectively incorporate CBS into the pharmacy curriculum.
Mechanical power is associated with cardiac output and pulmonary blood flow in an experimental acute respiratory distress syndrome in pigs
Authors: Zhang Yingying , Wittenstein Jakob , Braune Anja , Theilen Raphael , Maiello Lorenzo , Benzi Giulia , Bluth Thomas , Kiss Thomas , Ran Xi , Koch Thea , Rocco Patricia R. M. , Schultz Marcus J. , Kotzerke Jörg , Gama De Abreu Marcelo , Huhle Robert , Scharffenberg Martin 
Published: October 2024

BackgroundDespite being essential in patients with acute respiratory distress syndrome (ARDS), mechanical ventilation (MV) may cause lung injury and hemodynamic instability. Mechanical power (MP) may describe the net injurious effects of MV, but whether it reflects the hemodynamic effects of MV is currently unclear. We hypothesized that MP is also associated with cardiac output (CO) and pulmonary blood flow (PBF).Methods24 anesthetized pigs with experimental acute lung injury were ventilated for 18 h according to one of three strategies: 1) Open lung approach (OLA), 2) ARDS Network high-PEEP/FIO2 strategy (HighPEEP), or 3) low-PEEP/FIO2 strategy (LowPEEP). Total MP was assessed as the sum of energy dissipated to overcome airway resistance and energy temporarily stored in the elastic lung tissue per minute. The distribution of pulmonary perfusion was determined by positron emission tomography. Regional PBF and MP, assessed in three iso-gravitational regions of interest (ROI) with equal lung mass (ventral, middle, and dorsal ROI), were compared between groups.ResultsMP was higher in the LowPEEP than in the OLA group, while CO did not differ between groups. After 18 h, regional PBF did not differ between groups. During LowPEEP, regional MP was higher in the ventral ROI compared to OLA and HighPEEP groups (2.5 ± 0.3 vs. 1.4 ± 0.4 and 1.6 ± 0.3 J/min, respectively, P &lt; 0.001 each), and higher in the middle ROI compared to the OLA group (2.5 ± 0.4 vs. 1.6 ± 0.5 J/min, P = 0.04). MP in the dorsal ROI did not differ between groups (1.4 ± 0.9 vs. 1.4 ± 0.5 vs. 1.3 ± 0.8 J/min, P = 0.916). Total MP was independently associated with CO [0.34 (0.09, 0.59), P = 0.020]. Regional MP was positively associated with PBF irrespective of the regions [0.52 (0.14, 0.76), P = 0.01; 0.49 (0.10, 0.74), P = 0.016; 0.64 (0.32, 0.83), P = 0.001 for ventral, middle, and dorsal ROI, respectively]. Subgroup analysis revealed a significant association of MP and CO only in the OLA group as well as a significant association between MP with regional PBF only in the HighPEEP group.ConclusionIn this model of acute lung injury in pigs ventilated with either open lung approach, high, or low PEEP tables recommended by the ARDS network, MP correlated positively with CO and regional PBF, whereby these clinically relevant lung-protective ventilation strategies influenced the associations.
Genome-wide association mapping identifies novel SNPs for root nodulation and agronomic traits in chickpea
Authors: Chandana B. S. , Mahto Rohit Kumar , Singh Rajesh Kumar , Bhandari Aditi , Tandon Gitanjali , Singh K. K. , Kushwah Sunita , Lavanya Gera Roopa , Iquebal Mir Asif , Jain Neelu , Kudapa Himabindu , Upadhyaya H. D. , Hamwieh Aladdin , Kumar Rajendra 
Published: October 2024

IntroductionThe chickpea (Cicer arietinum L.) is well-known for having climate resilience and atmospheric nitrogen fixation ability. Global demand for nitrogenous fertilizer is predicted to increase by 1.4% annually, and the loss of billions of dollars in farm profit has drawn attention to the need for alternative sources of nitrogen. The ability of chickpea to obtain sufficient nitrogen via its symbiotic relationship with Mesorhizobium ciceri is of critical importance in determining the growth and production of chickpea.MethodsTo support findings on nodule formation in chickpea and to map the genomic regions for nodulation, an association panel consisting of 271 genotypes, selected from the global chickpea germplasm including four checks at four locations, was evaluated, and data were recorded for nodulation and 12 yield-related traits. A genome-wide association study (GWAS) was conducted using phenotypic data and genotypic data was extracted from whole-genome resequencing data of chickpea by creating a hap map file consisting of 602,344 single-nucleotide polymorphisms (SNPs) in the working set with best-fit models of association mapping.Results and DiscussionThe GWAS panel was found to be structured with sufficient diversity among the genotypes. Linkage disequilibrium (LD) analysis showed an LD decay value of 37.3 MB, indicating that SNPs within this distance behave as inheritance blocks. A total of 450 and 632 stringent marker–trait associations (MTAs) were identified from the BLINK and FarmCPU models, respectively, for all the traits under study. The 75 novel MTAs identified for nodulation traits were found to be stable. SNP annotations of associated markers were found to be related to various genes including a few auxins encoding as well as nod factor transporter genes. The identified significant MTAs, candidate genes, and associated markers have the potential for use in marker-assisted selection for developing high-nodulation cultivars after validation in the breeding populations.
Relationships between altitude and depressive symptoms among middle-aged and older adults in China: a longitudinal study from the China health and retirement longitudinal study
Authors: Ma Qing , Jiang Wei , Zhao Qiuyan , Xia Xin , Fang Ronghua 
Published: October 2024

BackgroundPrevious studies have consistently documented positive associations between depressive symptoms and altitude; however, a longitudinal study of these relationships among middle-aged and older adult community populations in China has not been previously reported.MethodsWe screened 17,705 subjects who met the inclusion criteria from the China Health and Retirement Longitudinal Study database 2011. The altitude is the altitude at which the participants lived in our study area. We estimated the prospective associations between altitude and depressive symptoms among middle-aged and older adults. The 10-item Center for Epidemiological Studies Depression Scale short form was used to measure depressive symptoms. A total of 6,594 participants without depressive symptoms were recruited from the same cohort in 2011 and were followed up in 2018. Multivariate logistic regression was used to assess the associations between altitude and depressive symptoms among middle-aged and older adults.ResultsThe prevalence of depressive symptoms was 27.3% in our study. The prevalence of depressive symptoms increased with increasing altitude, and the prevalence of depressive symptoms in women was greater than that in men. Multivariate logistic regression adjusted for all other relevant variables showed that sex, altitude, education level, professional status and marital status were associated with depressive symptoms.ConclusionsThis finding provides evidence of the relationship between altitude and depressive symptoms among middle-aged and older adult community populations in China and shows that depressive symptoms are significantly positively correlated with altitude and other factors, including sex, education level, professional status, and marital status.