bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic variants of LRRC8C, OAS2, and CCL25 in the T cell exhaustion-related genes are associated with non-small cell lung cancer survival
Authors: Lu Guojun , Liu Hongliang , Wang Huilin , Tang Xiaozhun , Luo Sheng , Du Mulong , Christiani David C. , Wei Qingyi 
Published: October 2024

BackgroundT cell exhaustion is a state in which T cells become dysfunctional and is associated with a decreased efficacy of immune checkpoint inhibitors. Lung cancer has the highest mortality among all cancers. However, the roles of genetic variants of the T cell exhaustion-related genes in the prognosis of non-small cell lung cancer (NSCLC) patients has not been reported.MethodsWe conducted a two-stage multivariable Cox proportional hazards regression analysis with two previous genome-wide association study (GWAS) datasets to explore associations between genetic variants in the T cell exhaustion-related genes and survival of NSCLC patients. We also performed expression quantitative trait loci analysis for functional validation of the identified variants.ResultsOf all the 52,103 single nucleotide polymorphisms (SNPs) in 672 T cell exhaustion-related genes, 1,721 SNPs were found to be associated with overall survival (OS) of 1185 NSCLC patients of the discovery GWAS dataset from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, and 125 of these 1,721 SNPs remained significant after validation in an additional independent replication GWAS dataset of 984 patients from the Harvard Lung Cancer Susceptibility (HLCS) Study. In multivariable stepwise Cox model analysis, three independent SNPs (i.e., LRRC8C rs10493829 T&gt;C, OAS2 rs2239193 A&gt;G, and CCL25 rs3136651 T&gt;A) remained significantly associated with OS with hazards ratios (HRs) of 0.86 (95% confidence interval (CI) = 0.77-0.96, P = 0.008), 1.48 (95% CI = 1.18-1.85, P &lt; 0.0001) and 0.78 (95% CI = 0.66-0.91, P = 0.002), respectively. Further combined analysis for these three SNPs suggested that an unfavorable genotype score was associated with a poor OS and disease-specific survival. Expression quantitative trait loci analysis suggested that the LRRC8C rs10493829 C allele was associated with elevated LRRC8C mRNA expression levels in normal lymphoblastoid cells, lung tissue, and whole blood.ConclusionOur findings suggested that these functional SNPs in the T cell exhaustion-related genes may be prognostic predictors for survival of NSCLC patients, possibly via a mechanism of modulating corresponding gene expression.
Profiling hypoxia signaling reveals a lncRNA signature contributing to immunosuppression in high-grade glioma
Authors: Li Xinqiao , Xu Jingcheng , Li Xue , Shi Jianghua , Wei Chunmi , Liang Qingyu 
Published: October 2024

BackgroundHypoxic conditions in glioma are linked to tumor aggressiveness, poor prognosis, and treatment resistance. Long non-coding RNAs (lncRNAs) play key roles in the hypoxic and immune microenvironment of cancers, but their link to hypoxia-induced immunosuppression in high-grade glioma (HGG) is not well-studied.MethodsGene expression profiles from TCGA and CGGA, along with clinical and genomic data, were analyzed. Bioinformatics methods including Consensus Clustering, Pearson correlation, and Cox regression analyses were used. Cell proliferation was assessed using cell counting kit-8 and colony formation assays. Glioma-macrophage interactions were evaluated using a co-culture model.ResultsHypoxia subtype clustering showed hypoxic stress correlates with worse HGG prognosis. Eight hypoxia-related lncRNAs (AP000695.4, OSMR-AS1, AC078883.3, RP11-545E17.3, LINC01057, LINC01503, TP73-AS1, and LINC00672) with prognostic value were identified, forming a risk signature that separated patients into distinct prognostic groups. Multivariate Cox regression confirmed the signature as an independent prognostic factor. High-risk patients had greater hypoxia, leading to an immunosuppressive environment and immunotherapy resistance via tumor-associated macrophages (TAMs). TP73-AS1 significantly influenced hypoxia-induced TAM infiltration and M2 polarization.ConclusionsWe profiled hypoxic stress in HGG and developed an 8-lncRNA hypoxia-related signature predicting patient survival and immunotherapy response, emphasizing its role in hypoxia-induced immunosuppression.
Chebulinic acid isolated from aqueous extracts of Terminalia chebula Retz inhibits Helicobacter pylori infection by potential binding to Cag A protein and regulating adhesion
Authors: Ou Ling , Hao Yajie , Liu Hengrui , Zhu Zhixiang , Li Qingwei , Chen Qingchang , Wei Ruixia , Feng Zhong , Zhang Guimin , Yao Meicun 
Published: October 2024

BackgroundTerminalia chebula Retz, known as the King of Tibet, is considered a functional food in China, celebrated for its antioxidant, immune-modulating, antibacterial, and anti-inflammatory properties. Chebulinic acid, derived from aqueous extracts of Terminalia chebula Retz, is known for its anti-inflammatory properties. However, its potential as an anti-Helicobacter pylori (HP) agent has not been fully explored.MethodsHerein, we extracted the main compound from Terminalia chebula Retz using a semi-preparative liquid chromatography (LC) system and identified compound 5 as chebulinic acid through Ultra-high performance liquid chromatography-MS/MS (UPLC–MS/MS) and Nuclear Magnetic Resonance (NMR). To evaluate its role, we conducted minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays, scanning electron microscope (SEM) imaging, inhibiting kinetics curves, urea fast test, cell counting kit-8 (CCK-8) assay, western blot analysis, griess reagent system, and molecular docking.ResultsOur results showed that chebulinic acid effectively inhibited the growth of the HP strain ATCC 700392, damaged the HP structure, and exhibited selective antimicrobial activity without affecting normal epithelial cells GES-1. Importantly, it suppressed the expression of Cytotoxin-associated gene A (Cag A) protein, a crucial factor in HP infection. Molecular docking analysis predicted a strong affinity (−9.7 kcal/mol) between chebulinic acid and Cag A protein.ConclusionOverall, our findings suggest that chebulinic acid acts as an anti-adhesive agent, disrupting the adhesion of HP to host cells, which is a critical step in HP infection. It also suppresses the Cag A protein. These results highlight the potential of chebulinic acid against HP infections.
Circulating levels of micronutrients and risk of osteomyelitis: a Mendelian randomization study
Authors: Zhang Xu , Wang Jiaxing , Wu Zhimeng , Xin Binglong , He Shuixiang , He Zitong , Li Yarui 
Published: October 2024

BackgroundFew observational studies have investigated the effect of micronutrients on osteomyelitis, and these findings are limited by confounding and conflicting results. Therefore, we conducted Mendelian randomization (MR) analyses to evaluate the association between blood levels of eight micronutrients (copper, selenium, zinc, vitamin B12, vitamin C, and vitamin D, vitamin B6, vitamin E) and the risk of osteomyelitis.MethodsWe performed the two-sample and multivariable Mendelian randomization (MVMR) to investigate causation, where instrument variables for the predictor (micronutrients) were derived from the summary data of micronutrients from independent cohorts of European ancestry. The outcome instrumental variables were used from the summary data of European-ancestry individuals (n = 486,484). The threshold of statistical significance was set at p &lt; 0.00625.ResultsWe found a significant causal association that elevated zinc heightens the risk of developing osteomyelitis in European ancestry individuals OR = 1.23 [95% confidence interval (CI) [1.07, 1.43]; p = 4.26E-03]. Similarly, vitamin B6 showed a similar significant causal effect on osteomyelitis as a risk factor OR = 2.78 (95% CI [1.34, 5.76]; p = 6.04E-03; in the secondary analysis). Post-hoc analysis suggested this result (vitamin B6). However, the multivariable Mendelian randomization (MVMR) provides evidence against the causal association between zinc and osteomyelitis OR = 0.98(95% CI [−0.11, 0.07]; p = 7.20E-1). After searching in PhenoScanner, no SNP with confounding factors was found in the analysis of vitamin B6. There was no evidence of a reverse causal impact of osteomyelitis on zinc and vitamin B6.ConclusionThis study supported a strong causal association between vitamin B6 and osteomyelitis while reporting a dubious causal association between zinc and osteomyelitis.
Spatiotemporal delivery of multiple components of rhubarb-astragalus formula for the sysnergistic treatment of renal fibrosis
Authors: Zhang Qibin , Ye Xiaofeng , Zhu Lin , Xu Zhishi , Hou Yu , Ke Qiaoying , Feng Jiawei , Xie Xiaowei , Chen Danfei , Piao Ji-Gang , Wei Yinghui 
Published: October 2024

PurposeRhubarb (Rheum palmatum L.) and astragalus (Radix astragali) find widespread used in clinical formulations for treating chronic kidney disease (CKD). Notably, the key active components, total rhubarb anthraquinone (TRA) and total astragalus saponin (TAS), exhibit superiority over rhubarb and astragalus in terms of their clear composition, stability, quality control, small dosage, and efficacy for disease treatment. Additionally, astragalus polysaccharides (APS) significantly contribute to the treatment of renal fibrosis by modulating the gut microbiota. However, due to differences in the biopharmaceutical properties of these components, achieving synergistic effects remains challenging. This study aims to develop combined pellets (CPs) and evaluate the potential effect on unilateral ureteral obstruction (UUO)-induced renal fibrosis.MethodsThe CPs pellets were obtained by combining TRA/TAS-loaded SNEDDS pellets and APS-loaded pellets, prepared using the fluidized bed coating process. The prepared pellets underwent evaluation for morphology, bulk density, hardness, and flowing property. Moreover, the in vitro release of the payloads was evaluated with the CHP Type I method. Furthermore, the unilateral ureteral obstruction (UUO) model was utilized to investigate the potential effects of CPs pellets on renal fibrosis and their contribution to gut microbiota modulation.ResultsThe ex-vivo study demonstrated that the developed CPs pellets not only improved the dissolution of TRA and TAS but also delivered TRA/TAS and APS spatiotemporally to the appropriate site along the gastrointestinal tract. In an animal model of renal fibrosis (UUO rats), oral administration of the CPs ameliorated kidney histological pathology, reduced collagen deposition, and decreased the levels of inflammatory cytokines. The CPs also restored the disturbed gut microbiota induced by UUO surgery and protected the intestinal barrier.ConclusionThe developed CPs pellets represent a promising strategy for efficiently delivering active components in traditional Chinese medicine formulas, offering an effective approach for treating CKD.
Predicting implementation of response to intervention in math using elastic net logistic regression
Authors: Wang Qi , Hall Garret J. , Zhang Qian , Comella Sara 
Published: October 2024

IntroductionThe primary objective of this study was to identify variables that significantly influence the implementation of math Response to Intervention (RTI) at the school level, utilizing the ECLS-K: 2011 dataset.MethodsDue to missing values in the original dataset, a Random Forest algorithm was employed for data imputation, generating a total of 10 imputed datasets. Elastic net logistic regression, combined with nested cross-validation, was applied to each imputed dataset, potentially resulting in 10 models with different variables. Variables for the models derived from the imputed datasets were selected using four methods, leading to four candidate models for final selection. These models were assessed based on their performance of prediction accuracy, culminating in the selection of the final model that outperformed the others.Results and discussionMethod50 and Methodcoef emerged as the most effective, achieving a balanced accuracy of 0.852. The ultimate model selected relevant variables that effectively predicted RTI. The predictive accuracy of the final model was also demonstrated by the receiver operating characteristic (ROC) plot and the corresponding area under the curve (AUC) value, indicating its ability to accurately forecast math RTI implementation in schools for the following year.
Shaping infants’ social brains through vicarious social learning: the importance of positive mother–father interactions
Authors: Rousseau Sofie , Avital Nuphar , Tolpyhina Yuliya 
Published: October 2024

IntroductionThis study is the first to assess whether infants’ developing social brains may be susceptible to the vicarious social experience of interparental positivity. Specifically, we explored whether infants’ exposure to interparental positivity may vicariously shape their neural substrates of social development.MethodsIn a sample of 45 infants (MAgeMonths = 11.01; 48.9% girls), infant left-frontal resting alpha electroencephalogram (EEG) asymmetry was derived as a reliable indicator of neural substrates linked to adaptive social development. Moreover, positive characteristics of the mother–father couple relationship were assessed both by means of observation and self-report by mother and father. Importantly, various relevant covariates were considered, including interparental negativity (observed and self-reported), as well as infants’ direct caregiving experiences and duration of infant exposure to mother–father relationship-dynamics (parent-report).ResultsResults indicated that higher levels of observed interparental positivity were associated with greater infant left-frontal alpha EEG asymmetry, even after accounting for covariates (β’s &gt; 0.422).DiscussionThe current study’s results are first to suggest that positive vicarious social experiences in infants’ day-to-day lives play a significant role for early neural development.
Association between sleep disturbances and suicidal behavior in adolescents: a systematic review and meta-analysis
Authors: Baldini Valentina , Gnazzo Martina , Rapelli Giada , Marchi Mattia , Pingani Luca , Ferrari Silvia , De Ronchi Diana , Varallo Giorgia , Starace Fabrizio , Franceschini Christian , Musetti Alessandro , Poletti Michele , Ostuzzi Giovanni , Pizza Fabio , Galeazzi Gian Maria , Plazzi Giuseppe 
Published: October 2024

IntroductionAdolescents’ health and well-being are seriously threatened by suicidal behaviors, which have become a severe social issue worldwide. Suicide is one of the leading causes of mortality for adolescents in low and middle-income countries, with approximately 67,000 teenagers committing suicide yearly. Although an association between sleep disturbances (SDs) and suicidal behaviors has been suggested, data are still scattered and inconclusive. Therefore, to further investigate this association, we conducted a meta-analysis to verify if there is a link between SDs and suicidal behaviors in adolescents without diagnosed psychiatric disorders.MethodsPubMed, CENTRAL, EMBASE, and PsycINFO were searched from inception to August 30th, 2024. We included studies reporting the estimation of suicidal behaviors in adolescents from 12 to 21 years of age, with SDs and healthy controls. The meta-analysis was based on odds ratio (OR, with a 95% confidence interval ([CI]), estimates through inverse variance models with random-effects.ResultsThe final selection consisted of 19 eligible studies from 9 countries, corresponding to 628,525 adolescents with SDs and 567,746 controls. We found that adolescents with SDs are more likely to attempt suicide (OR: 3.10; [95% CI: 2.43; 3.95]) and experience suicidal ideation (OR: 2.28; [95% CI 1.76; 2.94]) than controls.ConclusionThis meta-analysis suggests that SDs are an important risk factor for suicidal ideation and suicide attempts in healthy adolescents. The findings highlight the importance of early identification of SDs to prevent suicidal behaviors in this population.Systematic review registrationPROSPERO, identifier CRD42023415526.
Developing a rapid predictive model for falls in older hospitalized patients
Authors: Hu Mengmeng , Lu Sujuan , Guan Jiangan , Deng Wenqian , Hu Yu , Huang Yao , Li Keying , He Mengdan , Wang Zhiyi , Chen Chan , Chen Xiufang 
Published: October 2024

BackgroundThis study was aimed to identify the independent risk factors for falls n hospitalized older patients and develop a corresponding predictive model.MethodsA retrospective observational study design was adopted, comprising 440 older patients with falls history and 510 older patients without falls history during hospitalization. Data collected included demographic information, vital signs, comorbidities, psychiatric disorder, function absent, current medication, other clinical indicators.ResultsMobility disability, high-risk medications use, frequency of hospitalizations, psychiatric disorder, visual impairment are independent risk factors for falls in older patients. The A-M2-HPV scoring system was developed. The AUC value of the nomogram was 0.884, indicating the model has excellent discriminative ability. The AUC value of the A-M2-HPV score was 0.788, demonstrating better discrimination and stratification capabilities.ConclusionThe A-M2-HPV scoring system provides a valuable tool to assess the risk of falls in hospitalized older patients and to aid in the implementation of preventive measures.
Women’s knowledge, attitude, and practice regarding cervical precancerous lesions: a cross-sectional study in Beijing, China
Authors: Wang Lingyan , Wang Qianping , Zhou Xia , Liu Huan 
Published: October 2024

BackgroundThis study aimed to examine the knowledge, attitude, and practice (KAP) of women in Beijing regarding cervical precancerous lesions.MethodsThis web-based, cross-sectional study included women at Dongzhimen Hospital of Beijing University of Chinese Medicine between March 13, 2024 and April 9, 2024. A self-administered questionnaire was developed to collect participants’ demographic information and KAP scores toward cervical precancerous lesions.ResultsThe study included 951 valid questionnaires, with a mean age of 40.0 years. The mean knowledge, attitude, and practice scores were 12.55 ± 6.23 (possible range: 0–26), 50.66 ± 7.48 (possible range: 13–65), and 26.13 ± 4.98 (possible range: 7–35), respectively. The knowledge score (OR = 1.071, 95%CI: 1.040–1.103, p &lt; 0.001), currently married (OR = 0.548, 95%CI: 0.304–0.985, p = 0.045), and with a history of HPV infection (OR = 2.302, 95%CI: 1.062–4.990, p = 0.035) were independently associated with the attitude score. The knowledge score (OR = 1.155, 95%CI: 1.119–1.192, p &lt; 0.001), monthly income &gt;20,000 (OR = 2.793, 95%CI: 1.249–6.248, p = 0.012), a history of HPV infection (OR = 0.380, 95%CI: 0.222–0.650, p &lt; 0.001), unknown HPV infection status (OR = 0.289, OR = 0.177–0.473, p &lt; 0.001), vaccinated against HPV (OR = 1.752, 95%CI: 1.221–2.514, p = 0.002), giving birth to one child (OR = 1.991, 95%CI: 1.186–3.341, p = 0.009), and giving birth to two or more children (OR = 2.160, 95%CI: 1.240–3.763, p = 0.007) were independently associated with the practice score. The structured equation model showed that knowledge directly influenced attitude (β = 0.237, p = 0.004) and practice (β = 0.490, p = 0.010). Attitude directly influenced practice (β = 0.193, p = 0.009).ConclusionThis study revealed inadequate knowledge, moderate attitude, and practice toward cervical precancerous lesions among women in Beijing. Educational interventions should be developed to enhance knowledge in this regard.
Ethylene oxide exposure, inflammatory indicators, and depressive symptoms: a cross-sectional study and mediation analysis based on a non-institutionalized American population
Authors: Du Dongru , Yuan Yanling , Guan Xuan , Xie Qinglian , Dong Zaiquan 
Published: October 2024

BackgroundEthylene oxide (EO) is a volatile compound positively correlated with respiratory and cardiovascular diseases. Currently, evidence suggests that environmental exposure may contribute to depressive symptoms. This study evaluated the correlation between EO exposure and depressive symptoms and investigated whether inflammatory indicators had a mediation effect on this correlation.MethodsPatients were enrolled from the National Health and Nutrition Examination Survey during 2013–2016, and 2,764 (49.67% male and 50.33% female) participants were ultimately included. EO exposure was determined by measuring hemoglobin-EO adduct (Hb-EO) concentration due to its long half-life, which was log2-transformed. Depressive symptoms were assessed using the Patient Health Questionnaire-9. Multivariable logistic regression analysis was performed to identify any correlations before and after covariate adjustment. Sensitivity analysis, subgroup analyses, and interaction tests were performed to further evaluate identified correlations. Mediation analysis was conducted to reveal whether specific inflammatory indicators mediated the correlation.ResultsA high prevalence of depressive symptoms was observed in quartiles with increased levels of EO exposure, and male individuals exhibiting higher Hb-EO levels than female individuals. A positive correlation was observed between EO exposure and depressive symptoms (odds ratio [OR]: 1.439, 95% confidence interval [CI]: 1.310, 1.581), which remained stable even after covariate adjustment (OR: 1.332, 95% CI: 1.148, 1.545). Interaction tests showed significant effects of sex (p &lt; 0.001) and thyroid diseases (p = 0.048) on this correlation. In the mediation analysis, white blood cell (p = 0.010) and neutrophil counts (p = 0.010) exerted a mediating effect, accounting for 13.6 and 11.9%, respectively.ConclusionIncreased exposure to EO is associated with an elevated risk of depressive symptoms, where white blood cell and neutrophil counts exert a significant mediating effect. Further prospective studies are required to investigate the potential link among EO, other environmental pollutants, and human mental health.