bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of Tryptophan and Its Main Metabolite Kynurenine and the Risk of Multiple Cancers Based on the Bidirectional Mendelian Randomization Analysis
Authors: Li Ran , Wang Xuanyang , Zhang Yuntao , Xu Xiaoqing , Wang Lulu , Wei Chunbo , Liu Lin , Wang Ziqi , Li Ying 
Published: April 2022

BackgroundTryptophan and its metabolites have been found related to various cancers, but the direction of this relationship is still unclear. The purpose of this study is to explore the causal associations of tryptophan and kynurenine with multiple cancers based on the bidirectional Mendelian randomization analysis.MethodsThe data of a genome-wide association study meta-analysis on 7,824 individuals was used to explore the genetic variants strongly associated with tryptophan and kynurenine. Genetic instruments of four specific cancers were obtained from available summary-level data of 323,590 European participants. Bidirectional Mendelian randomization analysis was conducted to examine possible causality. Sensitivity analysis was performed to test heterogeneity and horizontal pleiotropy. COX regression analysis was conducted to explore associations between dietary tryptophan and cancer mortality in NHANES 1988-1994.ResultsNo evidence of any causal association of tryptophan and kynurenine with the risk of four specific cancers was shown, except for weak correlations were suggested between lung or prostate cancer and kynurenine. Multiple sensitivity analyses generated similar results. Our findings from COX regression analysis were consistent with the above results.ConclusionsOur study did not find any causal relationship between tryptophan and kynurenine and multiple cancers. The associations still need further research.
Prognostic Value of Heterogeneity Index Derived from Baseline 18F-FDG PET/CT in Mantle Cell Lymphoma
Authors: Liu Fei , Gu Bingxin , Li Nan , Pan Herong , Chen Wen , Qiao Ying , Song Shaoli , Liu Xiaosheng 
Published: April 2022

ObjectivesMantle cell lymphoma (MCL) represents a group of highly heterogeneous tumors, leading to a poor prognosis. Early prognosis prediction may guide the choice of therapeutic regimen. Thus, the purpose of this study was to investigate the potential application value of heterogeneity index (HI) in predicting the prognosis of MCL.MethodsA total of 83 patients with histologically proven MCL who underwent baseline fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) were retrospectively enrolled. The clinicopathologic index and PET/CT metabolic parameters containing maximum and mean standard uptake value (SUVmax and SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and HI were evaluated. Receiver operating characteristic (ROC) curve analyses were performed to determine the optimal cutoff values of the parameters for progression-free survival (PFS) and overall survival (OS). Univariate and multivariate Cox regression were used to assess relationships between risk factors and recurrence. Kaplan–Meier plots were applied for survival analyses.ResultsIn univariate analyses, age [HR = 2.51, 95% CI = 1.20–5.24, p = 0.041 for body weight (BW)] and HI-BW (HR = 4.17, 95% CI = 1.00–17.38, p = 0.050) were significantly correlated with PFS. In multivariate analyses, age (HR = 2.61, 95% CI = 1.25–5.47, p = 0.011 for BW) and HI-BW (HR = 4.41, 95% CI = 1.06–18.41, p = 0.042) were independent predictors for PFS, but not for OS. B symptoms (HR = 5.00, 95% CI = 1.16–21.65, p = 0.031 for BW) were an independent prognostic factor for OS, but not for PFS. The other clinicopathologic index and PET/CT metabolic parameters were not related to outcome survival in MCL.ConclusionThe age and HI derived from baseline PET/CT parameters were significantly correlated with PFS in MCL patients.
TIM-3 Expression Level on AML Blasts Correlates With Presence of Core Binding Factor Translocations Rather Than Clinical Outcomes
Authors: Hong Jian , Xia Leiming , Huang Zhenqi , Yuan Xiaodong , Liang Xinglin , Dai Jifei , Wu Zhonghui , Liang Li , Ruan Min , Long Zhangbiao , Cheng Xin , Chen Xiaowen , Ni Jing , Ge Jian , Li Qingsheng , Zeng Qingshu , Xia Ruixiang , Wang Yi , Yang Mingzhen 
Published: April 2022

BackgroundT-cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) expresses on leukemic stem and progenitor populations of non-M3 acute myeloid leukemia (AML) as well as T lymphocytes. TIM-3 is thought to be involved in the self-renewal of leukemic stem cells and the immune escape of AML cells, however its correlation with AML prognosis is still controversial and worthy of further investigation.Methodswe simultaneously assessed TIM-3 expression levels of leukemic blasts and T lymphocytes in the bone marrow of de novo AML patients using flow cytometry. The correlations of TIM-3 expression between leukemic blasts and T lymphocytes and the correlations of TIM-3 expression with various patient parameters were analyzed. In addition, the Cancer Genome Atlas (TCGA) data of AML patients were acquired and analyzed to verify the results.ResultsTIM-3 expression of CD34+ leukemic blasts (R2 = 0.95, p&lt;0.0001) and CD34+CD38- leukemic stem cells (R2 = 0.75, p&lt;0.0001) were significantly and positively correlated with that of the whole population of leukemic blasts. In addition, TIM-3 expression level of leukemic blasts correlated significantly and positively with that of CD8+ (R2 = 0.44, p&lt;0.0001) and CD4+ (R2 = 0.16, p=0.0181) lymphocytes, and higher TIM-3 expression of leukemic blasts was significantly associated with a greater proportion of peripheral CD8+ T lymphocytes (R2 = 0.24, p=0.0092), indicating that TIM-3 on leukemic blasts might alter adaptive immunity of AML patients. Regarding clinical data, the presence of core binding factor (CBF) translocations was significantly correlated with higher TIM-3 expression of leukemic blasts (CBF versus non-CBF, median 22.78% versus 1.28%, p=0.0012), while TIM-3 expression levels of leukemic blasts were not significantly associated with the remission status after induction chemotherapy (p=0.9799), overall survival (p=0.4201) or event-free survival (p=0.9873). Similar to our results, TCGA data showed that patients with CBF translocations had significantly higher mRNA expression level of HAVCR2 (the gene encoding TIM-3) (median, 9.81 versus 8.69, p&lt;0.0001), and as all patients in the cohort were divided into two groups based on the median HAVCR2 expression level, 5-year overall survivals were not significantly different (low versus high, 24.95% versus 24.54%, p=0.6660).ConclusionTIM-3 expression level on AML blasts correlates with presence of CBF translocations rather than clinical outcomes.
Insights From the Analysis of Clinicopathological and Prognostic Factors in Patients With Gallbladder Cancer
Authors: Wu Di , Jin Wenjian , Zhang Yue , An Yong , Chen Xuemin , Chen Weibo 
Published: April 2022

AimsTo investigate the clinical efficacy and prognostic factors of primary gallbladder cancer (GBC) treated by radical surgery.MethodsThe clinical and pathological data of 168 patients with primary gallbladder cancer admitted and treated in the Third Affiliated Hospital of Soochow University from January 1st, 2010 to December 31st, 2018 were analyzed retrospectively. Kaplan Meier method was used to draw the survival curve and evaluate the survival rate. Chi-square test was used for univariate analysis and binary logistic regression was used for multivariate analysis.Results94 cases showed symptoms of abdominal pain and abdominal distension. 7 cases showed symptoms of fatigue and weight loss. Jaundice occurred in 10 patients. Fever occurred in 6 patients. 51 patients had no symptoms at all. The median survival time of 168 patients was 35.0 (1.0 ~ 142.0) months. The overall 1-, 2- and 3-year cumulative survival rates were 69.6%, 55.4% and 48.8% respectively. The univariate analysis indicated that preoperative bilirubin, tumor size, tumor location, pathological type, degree of differentiation, liver invasion, nerve invasion, vascular invasion, surgical margin, filtration depth and N staging were significant factors influencing prognosis of patients with primary GBC (P&lt;0.05). The results of multivariate analysis demonstrated that degree of differentiation, nerve invasion, filtration depth and N staging were independent risk factors for prognosis of patients with primary GBC (P&lt;0.05).ConclusionPatients with risk factors of gallbladder cancer should be more active in early cholecystectomy to avoid the malignant transformation of benign diseases. Degree of differentiation, nerve invasion, filtration depth and N staging were important factors for poor prognosis of patients with primary GBC. For T4 staging patients, preoperative evaluation should be more comprehensive, and patients and surgeons should be more prudent in adopting appropriate clinical treatment. The primary purpose should be prolonging the survival time and improving the quality of life.
Changes in the Epidemiology and Causative Pathogens of Meningitis in Children After the Outbreak of the Coronavirus Disease 2019: A Multicenter Database Study
Authors: Lee Jooyoung , Choi Arum , Kim Kyunghoon , Bin Joong Hyun , Eom Tae Hoon , Yoo Il Han , Yoon Da Hye , Kim Sukil , Kim Young Hoon 
Published: April 2022

BackgroundWith the outbreak of the COVID-19 pandemic, non-pharmaceutical interventions such as social distancing have been implemented worldwide, and a decrease in other infectious diseases has been reported as an unexpected benefit. However, to date, studies are lacking regarding the effects of the COVID-19 pandemic on neuroinfectious diseases; therefore, we aimed to determine the effects of the COVID-19 pandemic on the incidence of meningitis, which is the most common infectious disease in children.MethodsThis retrospective study used electronic medical record data from five university hospitals located in the metropolitan cities in Korea. This study included patients aged &lt;18 years who were diagnosed with meningitis between January 2017 and December 2020. We analyzed the clinical characteristics of patients with meningitis and changes in the incidence and causative pathogens of meningitis before and after the COVID-19 outbreak.ResultsThe study included 677 patients with meningitis. Following the outbreak of COVID-19 in Korea in January 2020, the incidence of childhood meningitis significantly decreased and seasonal changes noted yearly disappeared. There was a difference in the age distribution of patients with meningitis. The incidence of meningitis decreased significantly in children aged &gt;5 years, and the incidence in children &lt;5 years of age relatively increased (p &lt; 0.001). In addition, there was a notable decrease in the cases of suspected meningitis (p &lt; 0.001). The incidence of enteroviral meningitis, the most common cause of meningitis, significantly decreased.ConclusionAfter the COVID-19 outbreak, the incidence of childhood meningitis significantly decreased with the implementation of non-pharmaceutical interventions. Absence of enteroviral meningitis and decrease in the proportion of patients aged ≥5 years with meningitis having mild symptoms were noted. Consequently, it can be concluded that the non-pharmaceutical interventions (NPIs) instituted to prevent the spread of COVID-19 had some effect on reducing the incidence of meningitis.
Circulating FGF21 and GDF15 as Biomarkers for Screening, Diagnosis, and Severity Assessment of Primary Mitochondrial Disorders in Children
Authors: Li Yi , Li Shengrui , Qiu Yinfeng , Zhou Maobin , Chen Min , Hu Yue , Hong Siqi , Jiang Li , Guo Yi 
Published: April 2022

BackgroundPrimary mitochondrial disorders (PMDs) are a diagnostic challenge for paediatricians, and identification of reliable and easily measurable biomarkers has become a high priority. This study aimed to investigate the role of serum fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) in children with PMDs.MethodsWe analysed serum FGF21 and GDF15 concentrations by enzyme-linked immunosorbent assay (ELISA) in children with PMDs, patients with non-mitochondrial neuromuscular disorders (NMDs), and aged-matched healthy children, and compared them with serum lactate and ratio of lactate and pyruvate (L/P). We also evaluated correlations between these biomarkers and the phenotype, genotype, and severity of PMDs.ResultsThe median serum GDF15 and FGF21 concentrations were significantly elevated in fifty-one patients with PMDs (919.46 pg/ml and 281.3 pg/ml) compared with those of thirty patients with NMDs (294.86 pg/ml and 140.51 pg/ml, both P &lt; 0.05) and fifty healthy controls (221.21 pg/ml and 85.02 pg/ml, both P &lt; 0.05). The area under the curve of GDF15 for the diagnosis of PMDs was 0.891, which was higher than that of the other biomarkers, including FGF21 (0.814), lactate (0.863) and L/P ratio (0.671). Calculated by the maximum Youden index, the critical value of GDF15 was 606.369 pg/ml, and corresponding sensitivity and specificity were 74.5and 100%. In the PMD group, FGF21 was significantly correlated with International Paediatric Mitochondrial Disease Scale (IPMDS) score. The levels of GDF15 and FGF21 were positively correlated with age, critical illness condition, and multisystem involvement but were not correlated with syndromic/non-syndromic PMDs, different mitochondrial syndromes, nuclear DNA/mitochondrial DNA pathogenic variants, gene functions, or different organ/system involvement.ConclusionRegardless of clinical phenotype and genotype, circulating GDF15 and FGF21 are reliable biomarkers for children with PMDs. GDF15 can serve as a screening biomarker for diagnosis, and FGF21 can serve as a severity biomarker for monitoring.
What Have We Learnt About the Treatment of Juvenile-Onset Systemic Lupus Erythematous Since Development of the SHARE Recommendations 2012?
Authors: Gallagher Kathy L. , Patel Pallavi , Beresford Michael W. , Smith Eve Mary Dorothy 
Published: April 2022

IntroductionJuvenile-onset systemic lupus erythematous (JSLE) is a rare multisystem autoimmune disorder. In 2012, the Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) initiative developed recommendations for the diagnosis/management of JSLE, lupus nephritis (LN) and childhood-onset anti-phospholipid syndrome (APS). These recommendations were based upon available evidence informing international expert consensus meetings.ObjectiveTo review new evidence published since 2012 relating to the management of JSLE, LN and APS in children, since the original literature searches informing the SHARE recommendations were performed.MethodMEDLINE, EMBASE and CINAHL were systematically searched for relevant literature (2012-2021) using the following criteria: (1) English language studies; (2) original research studies regarding management of JSLE, LN, APS in children; (3) adult studies with 3 or more patients &lt;18-years old, or where the lower limit of age range ≤16-years and the mean/median age is ≤30-years; (4) randomized controlled trials (RCTs), cohort studies, case control studies, observational studies, case-series with &gt;3 patients. Three reviewers independently screened all titles/abstracts against predefined inclusion/exclusion criteria. All relevant manuscripts were reviewed independently by at least two reviewers. Data extraction, assessment of the level of evidence/methodological quality of the manuscripts was undertaken in-line with the original SHARE processes. Specific PUBMED literature searches were also performed to identify new evidence relating to each existing SHARE treatment recommendation.ResultsSix publications met the inclusion/exclusion criteria for JSLE: three RCTs, one feasibility trial, one case series. For LN, 16 publications met the inclusion/exclusion criteria: eight randomized trials, three open label prospective clinical trials, five observational/cohort studies. For APS, no publications met the inclusion criteria. The study with the highest evidence was an RCT comparing belimumab vs. placebo, including 93 JSLE patients. Whilst the primary-endpoint was not met, a significantly higher proportion of belimumab-treated patients met the PRINTO/ACR cSLE response to therapy criteria. New evidence specifically addressing each SHARE recommendation remains limited.ConclusionSince the original SHARE literature searches, undertaken &gt;10-years ago, the main advance in JSLE treatment evidence relates to belimumab. Additional studies are urgently needed to test new/existing agents, and assess their long-term safety profile in JSLE, to facilitate evidence-based practice.
Network Pharmacology and Molecular Docking to Elucidate the Potential Mechanism of Ligusticum Chuanxiong Against Osteoarthritis
Authors: Xiang Cheng , Liao Yilin , Chen Zhuoyuan , Xiao Bo , Zhao Ziyue , Li Aoyu , Xia Yu , Wang Pingxiao , Li Hui , Xiao Tao 
Published: April 2022

Background: Osteoarthritis (OA) is a degenerative disease which serious affects patients. Ligusticum chuanxiong (CX) has been shown to have a certain curative effect on osteoarthritis in traditional Chinese medicine therapy. This study is based on network pharmacology and molecular docking technology to explore the potential mechanism of CX.Methods: Components of CX to treat osteoarthritis were screened in the TCMSP database and targets were predicted by the PharmMapper database, the osteoarthritis targets were collected from the GeneCards database, and intersection genes were found to be the possible targets of CX anti-OA. The STRING database and Cytoscape software were utilized for protein-protein interaction analysis and further screening of core targets. The Metascape database was used for KEGG and GO enrichment analyses. Then, the top 10 pathways were selected to construct “drug-compound-target-pathway-disease” network analysis. Finally, molecular docking was used to analyze the binding affinity of seven compounds with core targets and TNF-α.Results: Seven compounds with 253 non-repetitive targets of CX were screened from the TCMSP database and 60 potential intersection targets of CX anti-OA were found. PPI network analysis showed that the core targets were ALB, AKT1, IGF1, CASP3, MAPK1, ANXA5, and MAPK14, while GO and KEGG pathway enrichment analyses showed that the relevant biological processes involved in the treatment of osteoarthritis by CX might include the MAPK cascade and reactive oxygen species metabolic process. The KEGG pathway analysis result was mainly associated with the MAPK signaling pathway and PI3K-AKT signaling pathway. We further docked seven ingredients with MAPK1 and MAPK14 enriched in the MAPK pathway, and TNF-α as the typical inflammatory cytokine. The results also showed good binding affinity, especially FA, which may be the most important component of CX anti-OA.Conclusion: Our research revealed the potential mechanism of CX in the treatment of OA, and our findings can also pave the way for subsequent basic experimental verification and a new research direction.
The Compassionate Engagement and Action Scales for Self and Others: Turkish Adaptation, Validity, and Reliability Study
Authors: Ari Ela , Cesur-Soysal Gizem , Basran Jaskaran , Gilbert Paul 
Published: April 2022

AimThis study aims to translate the Compassionate Engagement and Action Scales (CEAS) into Turkish and to test their subsequent validity, reliability, and psychometric properties. Turkey is one of the blended cultures with eastern and western elements under the influence of traditional religion. This cultural diversity brings about a rich context to study compassion and its relationship to mental health. The scales assess the ability to be sensitive to suffering and engage and then take helpful actions in compassion. The motivation for compassionate engagement and action is measured at three ‘flows’ as follows: (1) compassion for others; (2) compassion from others; and (3) compassion for self.MethodsThe sample consists of 525 college students aged 18 years or older. The participants completed the CEAS Turkish Form for Others, Self and from Others, Self-Compassion Scale Short Form, Compassionate Love Scale, and Self-Criticism Scale.ResultsThe confirmatory factor analyses were conducted using AMOS version 27 to examine the validity of the three scales with two different factor structures each. All the three models show good fits to the data. The Cronbach’s alpha coefficient for the CEAS for Others and for Self and from Others are good to excellent (between 0.70 and 0.95 for all subscales). Compassion for self, compassion for others, and compassion from others correlated modestly.ConclusionIt can be concluded that the Turkish version of the Compassionate Engagement and Action Scales for Others and Self and from Others has sufficient psychometric properties and can be used as a reliable and valid measure to assess compassionate engagement and action.
The Validity and Reliability of the Short Form of the Five Facet Mindfulness Questionnaire in Japan
Authors: Takahashi Toru , Saito Junichi , Fujino Masahiro , Sato Masashi , Kumano Hiroaki 
Published: April 2022

BackgroundA brief measure of dispositional mindfulness is important for applied research on mindfulness. Although short forms of the Five Facet Mindfulness Questionnaire (FFMQ), which measures the five aspects of mindfulness (i.e., observing, describing, acting with awareness, non-judging, and non-reactivity), have been developed worldwide, the validity and reliability of the Japanese version has not been examined. This study aims to examine the validity and reliability of the 24-item and 15-item versions of the FFMQ in Japan, which are the most widely used versions worldwide.MethodsOnline surveys were conducted for 889 adults in Japan through an online survey company using self-reported questionnaires including the FFMQ to confirm the factor structure and validity. To examine construct validity, we examined the relationship between the short form of FFMQ and mind wandering, interoceptive awareness, experiential avoidance, cognitive fusion, openness, neuroticism, self-compassion, depression, and anxiety, which have been theoretically or empirically shown to be related to mindfulness. In addition, 137 adults responded to the FFMQ again, after four weeks, for the test-retest reliability.ResultsThe correlated five-factor and four-factor (excluding observing) models and the higher-order factor hierarchical model did not show sufficient goodness of fit, while the 24-item version showed acceptable fit when uncorrelated method factors loaded on by the positive and negative (reverse-scored) items were added. However, the 15-item version did not show acceptable fits for any of the models. Regarding reliability, the 24-item version showed acceptable values. In terms of the relationship between the original and the shortened version of the FFMQ, the 24-item version shared approximately 80% of the variance with the original one. In addition, although the wording effects of positive and negative items seemed to affect the correlations between the FFMQ and the other scales, the associations with related concepts were as predicted generally, supporting the construct validity of the short form of the FFMQ.ConclusionIn Japan, the 24-item version of FFMQ showed acceptable validity and reliability similar to the original version, and we recommend that the 24-item version be used.