bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression and clinical significance of interleukin-6 pathway in cholangiocarcinoma
Authors: Gu Dongqing , Zhao Xin , Song Jing , Xiao Jianmei , Zhang Leida , Deng Guohong , Li Dajiang 
Published: May 2024

BackgroundCholangiocarcinoma (CCA) is a typical inflammation-induced malignancy, and elevated serum interleukin-6 (IL-6) levels have been reported to be linked to the onset and progression of CCA. We aim to investigate the potential prognostic value of the IL-6 pathway for CCA.MethodsWe detected the expressions of IL-6, IL-6R, glycoprotein (gp130), C-reactive protein (CRP), Janus kinase 2 (JAK2), and signal transducer and activator of transcription 3 (STAT3) in CCA tissue microarray using multiplex immunofluorescence. Furthermore, the clinical associations and prognostic values were assessed. Finally, single-cell transcriptome analysis was performed to evaluate the expression level of IL-6 pathway genes in CCA.ResultsThe results revealed that the expression of IL-6 was lower, while the expression of STAT3 was higher in tumor tissues compared to normal tissues. Especially in tumor microenvironment, the expression of IL-6 pathway genes was generally downregulated. Importantly, gp130 was strongly correlated with JAK2 in tumor tissues, while it was moderately correlated with JAK2 in normal tissue. Although none of the gene expressions were directly associated with overall survival and disease-free survival, our study found that IL-6, IL-6R, CRP, gp130, and JAK2 were inversely correlated with vascular invasion, which is a risk factor for poor prognosis in patients with CCA.ConclusionThe findings from this study suggest that the IL-6 signaling pathway may have a potential prognostic value for CCA. Further investigation is needed to understand the underlying molecular mechanisms of the IL-6 pathway in CCA.
Associations of inflammatory cytokines with palmoplantar pustulosis: a bidirectional Mendelian randomization study
Authors: Liu Chengling , Liu Xingchen , Xin Haiming , Li Xin 
Published: May 2024

BackgroundVariations in circulatory cytokine levels have been observed during the onset and course of palmoplantar pustulosis (PPP); however, whether these changes are due to etiological or secondary factors is unclear. To clarify the causal relationship, we conducted a summarized-level bidirectional Mendelian randomization (MR) analysis in this study.MethodsA FinnGen biobank genome-wide association study (GWAS) of 212,766 individuals (524 PPP patients and 212,242 controls) provided summary data for PPP, whereas genetic instrumental variables (IVs) linked to circulation cytokine levels were gathered from a GWAS of 14,824 European individuals. The inverse-variance weighted (IVW), weighted median (WME), simple mode, and MR-Egger methods were used to ascertain the changes in PPP pathogenic cytokine taxa. Sensitivity analysis, which included horizontal pleiotropy analysis, was then conducted. The reliability of the results was assessed using the leave-one-out approach and the MR Steiger test, which evaluated the strength of a causal relationship. To evaluate the reverse causality between PPP and circulating cytokine levels, a reverse MR analysis was carried out.ResultsOur study demonstrated positive associations between C-X-C motif chemokine 6 (CXCL6) and PPP (odds ratio, OR 1.257, 95%CI: 1.001–1.570, p = 0.043). C-C motif chemokine 19 (CCL19) and interleukin-6 (IL-6) were suggested to be protectively associated with the development of PPP (OR: 0.698,95% CI: 0.516–0.944, p = 0.020; OR: 0.656, 95%CI:0.437–0.985, p = 0.042). The results were steady after sensitivity and heterogeneity analyses.ConclusionAt the genetic prediction level, we identified causally connected inflammation-related variables that contributed to the onset and development of PPP. The therapeutic options for some refractory PPP have expanded due to tailored cytokine therapy, generating fresh concepts for PPP diagnostics and mechanism investigation.
The CroMyop study: myopia progression in Croatian children and adolescents—a 15-year retrospective analysis
Authors: Varošanec Ana Maria , Marković Leon , Sonicki Zdenko 
Published: May 2024

PurposeMyopia is a major global health issue, especially among children and adolescents. Understanding its traits and progression is vital for proper management and prevention. This study aimed to fill a gap in research by analyzing demographic and refractive data concerning myopia among children and adolescents in Croatia, with the goal of providing insights into myopia prevalence, progression rates, and associated risk factors within the Croatian population.DesignThis retrospective study utilized a comprehensive dataset from pediatric ophthalmology clinics at the University Eye Department, University Hospital “Sveti Duh,” Zagreb, Croatia. The dataset included electronic medical records spanning from January 2008 to July 2023, encompassing demographic and refractive data.MethodsData analysis focused on individuals aged 4 to 18 years who were diagnosed with primary myopia and/or compound myopic astigmatism. Ophthalmic examinations, including visual acuity tests, cycloplegic refraction, and assessments for eye comorbidities, were conducted by experienced pediatric ophthalmologists. Statistical analysis, including t-tests, survival analysis, and logistic regression, was performed to assess myopia prevalence, progression rates, and associated factors. These analyses were adjusted for covariates such as age, parental myopia, and gender.ResultsThe study included 895 individuals, 51 premyopes, 813 low myopes, and 31 high myopes. The average age of diagnosis was 11.37 ± 3.59 years for premyopes, 11.18 ± 3.53 years for low myopes, and 11.44 ± 4.35 years for high myopes. The fastest progression occurred in 2021 and 2022, −0.5 ± 0.12 D/y for premyopes and − 0.45 ± 0.1 D/y for low myopes. Premyopic progression to low myopia was associated with age 7–9 years (HR 2.42, 1.53 to 3.21) and both parents being myopic (HR 920.27. 850.16 to 950.53). Low myopic individuals with both myopic parents displayed the fastest 11–24 months after first visit progression rates, −0.69 (−0.52 to −0.87) D/y, while the 7–9 age group demonstrated −0.36 (−0.24 to −0.45) D/y. Low myopes aged 7–9 years with baseline SE between −6 D and −4 D were more strongly associated with ≤ − 0.5 D progression (OR = 2.0, 95% CI −1.00 to 2.39).ConclusionThis study highlights the importance of environmental factors, genetics, and age in addressing myopia progression among Croatian youth, urging further research for effective local intervention strategies.
The rs11684747 and rs55790676 SNPs of ADAM17 influence tuberculosis susceptibility and plasma levels of TNF, TNFR1, and TNFR2
Authors: Choreño-Parra José Alberto , Ramon-Luing Lucero A. , Castillejos Manuel , Ortega-Martínez Emmanuel , Tapia-García Alan Rodrigo , Matías-Martínez Melvin Barish , Cruz-Lagunas Alfredo , Ramírez-Martínez Gustavo , Gómez-García Itzel Alejandra , Ramírez-Noyola Jazmín Ariadna , Garcia-Padrón Beatriz , López-Salinas Karen Gabriel , Jiménez-Juárez Fabiola , Guadarrama-Ortiz Parménides , Salinas-Lara Citlaltepetl , Bozena-Piekarska Karolina , Muñóz-Torrico Marcela , Chávez-Galán Leslie , Zúñiga Joaquín 
Published: May 2024

IntroductionThe proteolytic activity of A Disintegrin and Metalloproteinase 17 (ADAM17) regulates the release of tumor necrosis factor (TNF) and TNF receptors (TNFRs) from cell surfaces. These molecules play important roles in tuberculosis (TB) shaping innate immune reactions and granuloma formation.MethodsHere, we investigated whether single nucleotide polymorphisms (SNPs) of ADAM17 influence TNF and TNFRs levels in 224 patients with active TB (ATB) and 118 healthy close contacts. Also, we looked for significant associations between SNPs of ADAM17 and ATB status. TNF, TNFR1, and TNFR2 levels were measured in plasma samples by ELISA. Four SNPs of ADAM17 (rs12692386, rs1524668, rs11684747, and rs55790676) were analyzed in DNA isolated from peripheral blood leucocytes. The association between ATB status, genotype, and cytokines was analyzed by multiple regression models.ResultsOur results showed a higher frequency of rs11684747 and rs55790676 in close contacts than ATB patients. Coincidentally, heterozygous to these SNPs of ADAM17 showed higher plasma levels of TNF compared to homozygous to their respective ancestral alleles. Strikingly, the levels of TNF and TNFRs distinguished participant groups, with ATB patients displaying lower TNF and higher TNFR1/TNFR2 levels compared to their close contacts.ConclusionThese findings suggest a role for SNPs of ADAM17 in genetic susceptibility to ATB.
Prediction of microbe–drug associations based on a modified graph attention variational autoencoder and random forest
Authors: Wang Bo , Ma Fangjian , Du Xiaoxin , Zhang Guangda , Li Jingyou 
Published: May 2024

IntroductionThe identification of microbe–drug associations can greatly facilitate drug research and development. Traditional methods for screening microbe-drug associations are time-consuming, manpower-intensive, and costly to conduct, so computational methods are a good alternative. However, most of them ignore the combination of abundant sequence, structural information, and microbe-drug network topology.MethodsIn this study, we developed a computational framework based on a modified graph attention variational autoencoder (MGAVAEMDA) to infer potential microbedrug associations by combining biological information with the variational autoencoder. In MGAVAEMDA, we first used multiple databases, which include microbial sequences, drug structures, and microbe-drug association databases, to establish two comprehensive feature matrices of microbes and drugs after multiple similarity computations, fusion, smoothing, and thresholding. Then, we employed a combination of variational autoencoder and graph attention to extract low-dimensional feature representations of microbes and drugs. Finally, the lowdimensional feature representation and graphical adjacency matrix were input into the random forest classifier to obtain the microbe–drug association score to identify the potential microbe-drug association. Moreover, in order to correct the model complexity and redundant calculation to improve efficiency, we introduced a modified graph convolutional neural network embedded into the variational autoencoder for computing low dimensional features.ResultsThe experiment results demonstrate that the prediction performance of MGAVAEMDA is better than the five state-of-the-art methods. For the major measurements (AUC =0.9357, AUPR =0.9378), the relative improvements of MGAVAEMDA compared to the suboptimal methods are 1.76 and 1.47%, respectively.DiscussionWe conducted case studies on two drugs and found that more than 85% of the predicted associations have been reported in PubMed. The comprehensive experimental results validated the reliability of our models in accurately inferring potential microbe-drug associations.
Efficacy and safety of robot-assisted deep brain stimulation for Parkinson’s disease: a meta-analysis
Authors: Huang Zhilong , Meng Lian , Bi Xiongjie , Xie Zhengde , Liang Weiming , Huang Jinyu 
Published: May 2024

ObjectiveThis meta-analysis aims to assess the effectiveness and safety of robot-assisted deep brain stimulation (DBS) surgery for Parkinson’s disease(PD).MethodsFour databases (Medline, Embase, Web of Science and CENTRAL) were searched from establishment of database to 23 March 2024, for articles studying robot-assisted DBS in patients diagnosed with PD. Meta-analyses of vector error, complication rate, levodopa-equivalent daily dose (LEDD), Unified Parkinson’s Disease Rating Scale (UPDRS), UPDRS II, UPDRS III, and UPDRS IV were performed.ResultsA total of 15 studies were included in this meta-analysis, comprising 732 patients with PD who received robot-assisted DBS. The pooled results revealed that the vector error was measured at 1.09 mm (95% CI: 0.87 to 1.30) in patients with Parkinson’s disease who received robot-assisted DBS. The complication rate was 0.12 (95% CI, 0.03 to 0.24). The reduction in LEDD was 422.31 mg (95% CI: 68.69 to 775.94). The improvement in UPDRS, UPDRS III, and UPDRS IV was 27.36 (95% CI: 8.57 to 46.15), 14.09 (95% CI: 4.67 to 23.52), and 3.54 (95% CI: −2.35 to 9.43), respectively.ConclusionRobot-assisted DBS is a reliable and safe approach for treating PD. Robot-assisted DBS provides enhanced accuracy in contrast to conventional frame-based stereotactic techniques. Nevertheless, further investigation is necessary to validate the advantages of robot-assisted DBS in terms of enhancing motor function and decreasing the need for antiparkinsonian medications, in comparison to traditional frame-based stereotactic techniques.Clinical trial registration: PROSPERO(CRD42024529976).
Systematic review and dosage analysis: hyperbaric oxygen therapy efficacy in the treatment of posttraumatic stress disorder
Authors: Andrews Susan R. , Harch Paul G. 
Published: May 2024

BackgroundStudies of hyperbaric oxygen therapy (HBOT) treatment of mild traumatic brain injury persistent postconcussion syndrome in military and civilian subjects have shown simultaneous improvement in posttraumatic stress disorder (PTSD) or PTSD symptoms, suggesting that HBOT may be an effective treatment for PTSD. This is a systematic review and dosage analysis of HBOT treatment of patients with PTSD symptoms.MethodsPubMed, CINAHL, and the Cochrane Systematic Review Database were searched from September 18 to November 23, 2023, for all adult clinical studies published in English on HBOT and PTSD. Randomized trials and studies with symptomatic outcomes were selected for final analysis and analyzed according to the dose of oxygen and barometric pressure on symptom outcomes. Outcome assessment was for statistically significant change and Reliable Change or Clinically Significant Change according to the National Center for PTSD Guidelines. Methodologic quality and bias were determined with the PEDro Scale.ResultsEight studies were included, all with &lt; 75 subjects/study, total 393 subjects: seven randomized trials and one imaging case-controlled study. Six studies were on military subjects, one on civilian and military subjects, and one on civilians. Subjects were 3-450 months post trauma. Statistically significant symptomatic improvements, as well as Reliable Change or Clinically Significant changes, were achieved for patients treated with 40-60 HBOTS over a wide range of pressures from 1.3 to 2.0 ATA. There was a linear dose-response relationship for increased symptomatic improvement with increasing cumulative oxygen dose from 1002 to 11,400 atmosphere-minutes of oxygen. The greater symptomatic response was accompanied by a greater and severe reversible exacerbation of emotional symptoms at the highest oxygen doses in 30-39% of subjects. Other side effects were transient and minor. In three studies the symptomatic improvements were associated with functional and anatomic brain imaging changes. All 7 randomized trials were found to be of good-highest quality by PEDro scale scoring.DiscussionIn multiple randomized and randomized controlled clinical trials HBOT demonstrated statistically significant symptomatic improvements, Reliable Changes, or Clinically Significant Changes in patients with PTSD symptoms or PTSD over a wide range of pressure and oxygen doses. The highest doses were associated with a severe reversible exacerbation of emotional symptoms in 30-39% of subjects. Symptomatic improvements were supported by correlative functional and microstructural imaging changes in PTSD-affected brain regions. The imaging findings and hyperbaric oxygen therapy effects indicate that PTSD can no longer be considered strictly a psychiatric disease.
The associations between dietary flavonoid intake and hyperlipidemia: data from the national health and nutrition examination survey 2007–2010 and 2017–2018
Authors: Wan Yingying , Ma Dan , Yu Linghua , Tian Wende , Wang Tongxin , Chen Xuanye , Shang Qinghua , Xu Hao 
Published: May 2024

BackgroundHyperlipidemia is a worldwide health problem and a significant risk factor for cardiovascular diseases; therefore, it imposes a heavy burden on society and healthcare. It has been reported that flavonoids can increase energy expenditure and fat oxidation, be anti-inflammatory, and reduce lipid factor levels, which may reduce the risk of hyperlipidemia. However, the relationship between the prevalence of hyperlipidemia and dietary flavonoid intake in the population remains unclear.MethodsThis study included 8,940 adults from the 2007–2010 and 2017–2018 National Health and Nutrition Examination Surveys (NHANES). The relationship between dietary flavonoid intake and the prevalence of hyperlipidemia was analyzed using weighted logistic regression and weighted restricted cubic spline.ResultsWe found an inverse relationship between subtotal catechins intake and hyperlipidemia prevalence in the third quartile [0.74 (0.56, 0.98), p = 0.04] compared with the first quartile. The prevalence of hyperlipidemia and total flavan-3-ol intake in the third quartile were inversely correlated [0.76 (0.59, 0.98), p = 0.03]. Total anthocyanin intake was inversely related to the prevalence of hyperlipidemia in the third quartile [0.77 (0.62, 0.95), p = 0.02] and the fourth quartile [0.77 (0.60, 0.98), p = 0.04]. The prevalence of hyperlipidemia was negatively correlated with total flavonols intake in the fourth quartile [0.75 (0.60, 0.94), p = 0.02]. Using restricted cubic splines analysis, we found that subtotal catechins intake and total flavan-3-ol intake had a nonlinear relationship with the prevalence of hyperlipidemia.ConclusionOur study may provide preliminary research evidence for personalizing improved dietary habits to reduce the prevalence of hyperlipidemia.
The global burden and trends analysis of early-onset colorectal cancer attributable to dietary risk factors in 204 countries and territories, 1990–2019: a secondary analysis for the global burden of disease study 2019
Authors: Su Jiao , Liang Yuanhao , He Xiaofeng 
Published: May 2024

BackgroundRising trends in early-onset colorectal cancer (CRC) burden have been observed, but the distribution and temporal patterns of early-onset CRC attributable to dietary risks remain unclear.ObjectivesThis study aimed to estimate the burden of early-onset CRC attributable to dietary risk factors globally, regionally, and nationally, by age and sex, from 1990 to 2019.MethodsThe absolute number and age-specific rates (ASR) of diet-related early-onset CRC burden, as well as summary exposure value (SEV) of attributable dietary risk factors, were extracted from the Global Burden of Disease (GBD) Study 2019. The temporal changes in the burden between 1990 and 2019 were analyzed by calculating the percentage change in the absolute number of burden and the estimated annual percentage change (EAPC) in ASR of burden. The annualized rates of change (ARC) were calculated to evaluate the variation trend of SEV.ResultsIn 2019, diet-related early-onset CRC caused 30,096 (95% UI: 23,148 to 36,091) death cases and 1,465,755 (95% UI: 1,126,489 to 1,761,661) DALYs worldwide, accounting for 34.8% deaths and 34.4% DALYs of overall early-onset CRC, respectively. Moreover, a diet low in milk (responsible for 16.5% [95% UI: 11.1 to 21.9%] of DALYs in 2019), low in whole grains (15.2% [95% UI: 5.9 to 19.9%]), low in calcium (14.3% [95% UI: 10.7 to 18.9%]), high in red meat (5.3% [95% UI: 1.7 to 9.5%]), high in processed meat (2.5% [95% UI: 0.9 to 4.0%]), and low in fiber (2.3% [95% UI: 0.9 to 4.2%]) were early-onset CRC attributable dietary risk factors. The age-specific DALYs rate of early-onset CRC attributable to each dietary risk factor generally showed an increasing trend globally between 1990 and 2019, except for low intake of fiber (EAPC = −0.57, 95% CI: −0.76 to −0.38). In addition, from 1990 to 2019, males have a higher burden than females and this gap may continue to widen due to the increasing difference between the sexes in most dietary risk factors. Furthermore, dietary risks-attributable early-onset CRC burden has shifted from regions with high socio-demographic index (SDI) to high-middle and middle SDI quintiles with uncontrolled dietary risks.ConclusionEarly-onset CRC remains a concerning issue globally, and effective prevention and modification of dietary risk factors holds great promise to reduce early-onset CRC-related burden. Prioritizing diet improvement for males is critical and urgent for CRC control efforts, particularly for those living in developing countries with ongoing dietary pattern transition.
Integrated pan-cancer analysis reveals the immunological and prognostic potential of RBFOX2 in human tumors
Authors: Huang Fengxian , Jin Long , Zhang Xinyue , Wang Min , Zhou Congya 
Published: May 2024

BackgroundThe role of RNA-binding fox one homolog 2 (RBFOX2) in the progression of multiple tumors is increasingly supported by evidence. However, the unclearness pertaining to the expression of RBFOX2, its prognostic potential, and its correlation with the tumor microenvironment (TME) in pan-cancer persists. This study aims to comprehensively investigate the immunological prognostic value of RBFOX2.MethodsThe Cancer Genome Atlas Gene Expression Omnibus Genotype-Tissue Expression (GTEx), TIMER2.0, Kaplan-Meier (K–M) Plotter, University of Alabama at Birmingham Cancer data analysis Portal (UALCAN), cbioportal, and Gene Expression Profiling Interactive Analysis 2 (GEPIA2) were utilized for a systematic analysis of RBFOX2. This analysis included studying its expression, prognostic value, DNA methylation, enrichment analysis, immune infiltration cells, and immune-related genes. Additionally, qRT-PCR, CCK-8, colony formation, transwell assays, and immunohistochemistry were employed to analyze the expression and biological function of RBFOX2 in liver cancer.ResultsVariations in RBFOX2 expression have been observed across diverse tumors and have been identified as indicators of unfavorable prognosis. It is closely linked to immune infiltration cells, immune checkpoints, chemokines, and chemokine receptors in the TME. Higher levels of RBFOX2 have been significantly associated with low response and poor prognosis in patients with non-small cell lung cancer (NSCLC) and melanoma who receive immunotherapy. Furthermore, the DNA methylation of RBFOX2 varies across different types of cancer and has shown better prognosis in patients with BLCA, BRCA, CESC, COAD, DLBC, HNSC, LAML, LGG, LUAD, PAAD, SKCM and THYM. Interestingly, RBFOX2 expression was found to be lower in hepatocellular carcinoma (HCC) patients’ tumor tissues compared to their paired adjacent tissues. In vitro studies have shown that knockdown of RBFOX2 significantly promotes the growth and metastasis of liver cancer cells.ConclusionThis study investigates the correlation between DNA methylation, prognostic value, and immune cell infiltration with the expression of RBFOX2 in pan-cancer and indicates its potential role to inhibit metastasis of liver cancer.