bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel insight into m6A regulator-mediated methylation modification patterns and immune characteristics in intracranial aneurysm
Authors: Li Shifu , Zhang Qian , Weng Ling , Han Ying , Li Jian 
Published: August 2022

BackgroundGrowing evidence demonstrated that m6A modification in cardiovascular diseases. However, how it is involved in the intracranial aneurysm (IA) is still unclear. This study aimed to identify the role of m6A modification in IA.MethodsThree datasets downloaded from the Gene Expression Omnibus (GEO) database were used, including GSE122897, GSE15629, and GSE3679. The landscapes of 24 m6A regulators were depicted using the STRING database, Pearson’s correlation analysis, and Wilcoxon test. The targets of differentially expressed m6A (DEm6A) were predicted in the m6A2Target database and the modification m6A sites of hub targets were identified in SRAMP online tool. A diagnostic model based on DEm6A was constructed and verified in training and test databases. A consensus clustering algorithm was performed to classify IA patients into distinct m6A-related clusters. Functional analyses including gene ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set variation analysis, and gene set enrichment analysis analyses were conducted to elucidate the underlying mechanisms. ssGSEA algorithm was performed to uncover the immune characteristics. A PCA method was adopted to quantify the m6A score.ResultsNine DEm6A (IGF2BP1, IGF2BP3, YTHDF2, ZNF217, RBM15, YTHDF3, YTHDC1, FTO, and LRPPRC) significantly differed between IA and controls. Biological annotations showed that immune-related pathways (such as complement activation, inflammatory response, and interleukin signaling) and apoptosis were more enriched in IAs than in controls. Immune analyses indicate that the abundance of immune cells, immune responses, and HLA gene expression were elevated in IA samples than in controls. PCA results showed that IA has a lower m6A score than controls. An immune/apoptosis-related network modified by DEm6A was constructed. The m6A sites of six hub targets (CDK1, ASPM, AURKB, BUB1B, MKI67, and TPX2) were predicted with very high confidence. A diagnostic model with four genes (LRPPRC, YTHDF3, IGF2BP1, and ZNF217) was constructed and verified. Two m6A modification subtypes were identified with unsupervised cluster analysis. Immune infiltration analysis revealed that cluster 1 had higher immune activation than cluster 2. Further study showed that cluster 1 had a larger proportion of ruptured IAs.ConclusionThe m6A modification may shape the IAs microenvironment and participates in the formation and rupture of IAs by regulating immune infiltration.
Guilt is effectively induced by a written auto-biographical essay but not reduced by experimental pain
Authors: Schär Selina , Vehlen Antonia , Ebneter Julia , Schicktanz Nathalie , de Quervain Dominique J. F. , Wittmann Lutz , Götzmann Lutz , grosse Holtforth Martin , Protic Sonja , Wettstein Alexander , Egloff Niklaus , Streitberger Konrad , Schwegler Kyrill I. M. 
Published: August 2022

IntroductionThe aim of the present study was (1) to validate the method of guilt-induction by means of a written auto-biographical essay and (2) to test whether experimental pain is apt to alleviate the mental burden of guilt, a concept receiving support from both empirical research and clinical observation.MethodsThree independent groups of healthy male participants were recruited. Group allocation was not randomized but within group pain/sham administration was counterbalanced over the two test-days. Groups were tested in the following consecutive order: Group A: guilt induction, heat-pain/sham, N = 59; Group B: guilt induction, cold-pressure-pain/sham,N= 43; Group C: emotionally neutral induction, heat-pain/sham,N= 39. Guilt was induced on both test-days in group A and B before pain/sham administration. Visual analog scale (VAS) guilt ratings immediately after pain/sham stimulation served as the primary outcome. In a control group C the identical heat-pain experiment was performed like in group A but a neutral emotional state was induced.ResultsA consistently strong overall effect of guilt-induction (heat-pain:p&lt; 0.001,effect size r= 0.71; CPT-painp&lt; 0.001,r= 0.67) was found when compared to the control-condition (p= 0.25,r= 0.08). As expected, heat- and cold-pressure-stimuli were highly painful in all groups (p&lt; 0.0001,r= 0.89). However, previous research supporting the hypothesis that pain is apt to reduce guilt was not replicated.ConclusionAlthough guilt-induction was highly effective on both test-days no impact of pain on behavioral guilt-ratings in healthy individuals could be identified. Guilt induction per se did not depend on the order of testing. The result questions previous experimental work on the impact of pain on moral emotions.
Expanding the clinicopathological-genetic spectrum of glycogen storage disease type IXd by a Chinese neuromuscular center
Authors: Huang Kun , Duan Hui-Qian , Li Qiu-Xiang , Luo Yue-Bei , Bi Fang-Fang , Yang Huan 
Published: August 2022

BackgroundGlycogen storage disease (GSDs) is characterized by abnormally inherited glycogen metabolism. GSD IXd, which is caused by mutations in the PHKA1 gene, is an X-linked rare disease with mild myopathic symptoms. To date, only 13 patients with GSD IXd have been reported. In this study, we aimed to expand the clinicopathological-genetic spectrum of GSD IXd at a neuromuscular center in China.MethodsData on patients diagnosed with GSD IXd at our neuromuscular center were collected retrospectively. Clinical features, electrophysiology, muscle pathology, and genetic information were analyzed.ResultsBetween 2015 and 2021, three patients were diagnosed with GSD IXd based on clinical manifestations, pathological findings, and genetic testing. One patient presented with mitochondrial myopathy. All patients exhibited muscle weakness and elevated levels of creatine kinase. Electromyography-detected myopathic changes were found in two patients, whereas one patient refused to undergo this examination. Pathological examinations in all patients revealed subsarcolemmal accumulation of glycogen under PAS staining. All patients had mutations in the PHKA1 gene and the patient with mitochondrial myopathy also had a mutation in the MT-TL1 gene.ConclusionOur study expands the clinicogenotype and phenotype of GSD IXd in a Chinese population. Our study also expands the known mutation spectrum for GSD IXd, contributing to a better characterization and understanding of this ultrarare neuromuscular disorder.
A radiomics nomogram for invasiveness prediction in lung adenocarcinoma manifesting as part-solid nodules with solid components smaller than 6 mm
Authors: Zhang Teng , Zhang Chengxiu , Zhong Yan , Sun Yingli , Wang Haijie , Li Hai , Yang Guang , Zhu Quan , Yuan Mei 
Published: August 2022

ObjectiveTo investigate whether radiomics can help radiologists and thoracic surgeons accurately predict invasive adenocarcinoma (IAC) manifesting as part-solid nodules (PSNs) with solid components &lt;6 mm and provide a basis for rational clinical decision-making.Materials and MethodsIn total, 1,210 patients (mean age ± standard deviation: 54.28 ± 11.38 years, 374 men and 836 women) from our hospital and another hospital with 1,248 PSNs pathologically diagnosed with adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), or IAC were enrolled in this study. Among them, 1,050 cases from our hospital were randomly divided into a derivation set (n = 735) and an internal validation set (n = 315), 198 cases from another hospital were used for external validation. Each labeled nodule was segmented, and 105 radiomics features were extracted. Least absolute shrinkage and selection operator (LASSO) was used to calculate Rad-score and build the radiomics model. Multivariable logistic regression was conducted to identify the clinicoradiological predictors and establish the clinical-radiographic model. The combined model and predictive nomogram were developed based on identified clinicoradiological independent predictors and Rad-score using multivariable logistic regression analysis. The predictive performances of the three models were compared via receiver operating characteristic (ROC) curve analysis. Decision curve analysis (DCA) was performed on both the internal and external validation sets to evaluate the clinical utility of the nomogram.ResultsThe radiomics model showed superior predictive performance than the clinical-radiographic model in both internal and external validation sets (Az values, 0.884 vs. 0.810, p = 0.001; 0.924 vs. 0.855, p &lt; 0.001, respectively). The combined model showed comparable predictive performance to the radiomics model (Az values, 0.887 vs. 0.884, p = 0.398; 0.917 vs. 0.924, p = 0.271, respectively). The clinical application value of the nomogram developed based on the Rad-score, maximum diameter, and lesion shape was confirmed, and DCA demonstrated that application of the Rad-score would be beneficial for radiologists predicting invasive lesions.ConclusionsRadiomics has the potential as an independent diagnostic tool to predict the invasiveness of PSNs with solid components &lt;6 mm.
Comprehensive analysis of ferroptosis-related gene signatures as a potential therapeutic target for acute myeloid leukemia: A bioinformatics analysis and experimental verification
Authors: Zheng Zhiyuan , Hong Xiaoying , Huang Xiaoxue , Jiang Xiandong , Jiang He , Huang Yingying , Wu Wei , Xue Yan , Lin Donghong 
Published: August 2022

BackgroundFerroptosis plays an important role in the development of acute myeloid leukemia (AML); however, the exact role of ferroptosis-related genes in the prognosis of AML patients is unclear.MethodsRNA sequencing data and the clinicopathological characteristics of AML patients were obtained from The Cancer Genome Atlas database, and ferroptosis-related genes were obtained from the FerrDb database. Cox regression analysis and least absolute shrinkage and selection operator analysis were performed to identify ferroptosis-related gene signatures. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and single-sample gene set enrichment analysis (ssGSEA) were performed to explore the biological functions of the ferroptosis-related genes. Finally, ferroptosis of AML cells was induced by erastin and sulfasalazine to detect the changes in the expression of relevant prognostic genes and explore the underlying mechanisms using quantitative real-time polymerase chain reaction (qRT-PCR).ResultsSeven ferroptosis-related gene signatures (SOCS1, ACSF2, MYB, EIF2AK4, AIFM2, SLC7A11, and GPX4) were identified in the training group. Kaplan-Meier and Cox regression analyses confirmed that risk score was an independent prognostic predictor of AML in the training and validation groups (P&lt;0.05). Further, functional enrichment analysis revealed that seven ferroptosis-related genes were associated with many immune-related biological processes. Most importantly, erastin and sulfasalazine can induce the ferroptosis of AML cells. Overall, SLC7A11 and the SLC7A11/xCT-GSH-GPX4 pathway may be the respective key gene and potential regulatory pathway in erastin- and sulfasalazine-induced ferroptosis of AML cells.ConclusionsA novel signature involving seven ferroptosis-related genes that could accurately predict AML prognosis was identified. Further, the Food and Drug Administration-approved drug, sulfasalazine, was demonstrated for the first time to induce the ferroptosis of AML cells. SLC7A11 and the SLC7A11/xCT-GSH-GPX4 pathway may be the respective key gene and underlying mechanism in this process, ultimately providing new insights into the strategies for the development of new AML therapies.
Crocin-I Protects Against High-Fat Diet-Induced Obesity via Modulation of Gut Microbiota and Intestinal Inflammation in Mice
Authors: Xie Xiaoxian , Zhang Mengya , Sun Lei , Wang Ting , Zhu Zhengyan , Shu Ruonan , Wu Fengchun , Li Zezhi 
Published: August 2022

Crocin-I can regulate physiological changes in the human body by altering inflammation and microbial composition. Gut microbiota are also involved in modulating the pathophysiology of obesity. However, crocin-I’s effect on obesity and the mechanism underlying its effects on gut microbiota and inflammation remain poorly understood. Here, high-fat diet (HFD) -induced obese mice were administrated crocin-I (20 mg/kg/day) for 10 weeks using an oral gavage (HFD-C20 group). HFD-C20, HFD, and Normal chow (NC) groups were compared. The fat content, colon tissue inflammatory cytokine levels, gut microbiota, and short-chain fatty acids (SCFAs) levels were measured. We show that crocin-I reduced body weight and liver weight and improved glucose resistance in HFD-induced mice, and reduced the lipid accumulation in the liver. Strikingly, crocin-I alleviated intestinal microbial disorders and decreased the F/B ratio and the abundance of Proteobacteria in HFD-induced obese mice. Crocin-I also rescued the decrease in the levels of SCFAs and repaired altered intestinal barrier functioning and intestinal inflammation in HFD-induced obese mice. These findings indicate that crocin-I may inhibit obesity by modulating the composition of gut microbiota and intestinal inflammation.
Real-world effectiveness of biological therapy in patients with rheumatoid arthritis: Systematic review and meta-analysis
Authors: Castro Caroline Tianeze de , Queiroz Mariana Jorge de , Albuquerque Flavia Caixeta , Brandão Celmário Castro , Gerlack Leticia Farias , Pereira Daniella Cristina Rodrigues , Barros Sandra Castro , Andrade Wenderson Walla , Bastos Ediane de Assis , Azevedo Jessé de Nobrega Batista , Carreiro Roberto , Barreto Mauricio Lima , Santos Djanilson Barbosa dos 
Published: August 2022

Background: The treatment of rheumatoid arthritis (RA), a chronic systemic inflammatory autoimmune disease, is based on disease-modifying anti-rheumatic drugs (DMARDs). Typically, it starts with conventional synthetic DMARDs (csDMARDs), and depending on the patient’s response to the treatment and the adverse events experienced, biological DMARDs (bDMARDs) are initiated. bDMARDs are more specific to inflammatory factors than csDMARDs and more efficient in inducing remission and low disease activity. Thus, this study aimed to assess the effectiveness of biological therapy in patients with rheumatoid arthritis in administrative health databases.Methods: PubMed, Embase, Lilacs, Ovid, Scopus, and Web of Science databases were searched from inception to 21 October 2021, to identify observational studies that evaluated the effectiveness of biological therapy in patients with rheumatoid arthritis using administrative databases and real-world data. The methodological quality was assessed by the methodological index for non-randomized studies (MINORS). A fixed or random-effects model estimated risk ratios with 95% confidence intervals. The analysis was divided into four groups: tumor necrosis factor inhibitors (TNFi) versus non-TNFi; TNFi versus TNFi (adalimumab, etanercept, and golimumab versus infliximab); bDMARDs versus Janus kinase inhibitors (JAKi); and bDMARDs monotherapy versus combination therapy (bDMARDs and MTX).Results: Twenty-one records were eligible for inclusion in this systematic review and meta-analysis; seven population-based cohorts, eight prospective, and six retrospective cohort studies. Overall, 182,098 rheumatoid arthritis patients were evaluated. In the meta-analysis, lower effectiveness was observed among TNFi users than in non-TNFi (RR: 0.88; 95% CI: 0.81–0.95; p &lt; 0.01; I2 = 94.0%) and bDMARDs than in JAKi (RR: 0.86; 95% CI: 0.79–0.94; p &lt; 0.01; I2 = 93.0%). Higher effectiveness among adalimumab, etanercept, and golimumab than in infliximab (RR: 1.19; 95% CI: 1.05–1.36; p &lt; 0.01; I2 = 96.0%) was found. No significant differences in the effectiveness of bDMARD monotherapy compared to combination therapy (RR: 0.83; 95% CI: 0.68–1.00; p &lt; 0.01; I2 = 81.0%) was observed. E-value analysis indicated that the estimates were not robust against unmeasured confounding.Conclusion: According to the available real-world data, our results suggest that biological therapy effectively treats patients with rheumatoid arthritis, indicating higher effectiveness with non-TNFi and JAKi than with TNFi.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID#CRD42020190838, identifier CRD42020190838.
Chaperone activity of niflumic acid on ClC-1 chloride channel mutants causing myotonia congenita
Authors: Altamura Concetta , Conte Elena , Campanale Carmen , Laghetti Paola , Saltarella Ilaria , Camerino Giulia Maria , Imbrici Paola , Desaphy Jean-François 
Published: August 2022

Myotonia congenita (MC) is an inherited rare disease characterized by impaired muscle relaxation after contraction, resulting in muscle stiffness. It is caused by loss-of-function mutations in the skeletal muscle chloride channel ClC-1, important for the stabilization of resting membrane potential and for the repolarization phase of action potentials. Thanks to in vitro functional studies, the molecular mechanisms by which ClC-1 mutations alter chloride ion influx into the cell have been in part clarified, classifying them in “gating-defective” or “expression-defective” mutations. To date, the treatment of MC is only palliative because no direct ClC-1 activator is available. An ideal drug should be one which is able to correct biophysical defects of ClC-1 in the case of gating-defective mutations or a drug capable to recover ClC-1 protein expression on the plasma membrane for trafficking-defective ones. In this study, we tested the ability of niflumic acid (NFA), a commercial nonsteroidal anti-inflammatory drug, to act as a pharmacological chaperone on trafficking-defective MC mutants (A531V, V947E). Wild-type (WT) or MC mutant ClC-1 channels were expressed in HEK293 cells and whole-cell chloride currents were recorded with the patch-clamp technique before and after NFA incubation. Membrane biotinylation assays and western blot were performed to support electrophysiological results. A531V and V947E mutations caused a decrease in chloride current density due to a reduction of ClC-1 total protein level and channel expression on the plasma membrane. The treatment of A531V and V947E-transfected cells with 50 µM NFA restored chloride currents, reaching levels similar to those of WT. Furthermore, no significant difference was observed in voltage dependence, suggesting that NFA increased protein membrane expression without altering the function of ClC-1. Indeed, biochemical experiments confirmed that V947E total protein expression and its plasma membrane distribution were recovered after NFA incubation, reaching protein levels similar to WT. Thus, the use of NFA as a pharmacological chaperone in trafficking defective ClC-1 channel mutations could represent a good strategy in the treatment of MC. Because of the favorable safety profile of this drug, our study may easily open the way for confirmatory human pilot studies aimed at verifying the antimyotonic activity of NFA in selected patients carrying specific ClC-1 channel mutations.
Histological, physiological, and transcriptomic responses of hepatopancreas to air exposure in asian freshwater clam Corbicula fluminea
Authors: Zhang Ting , Xu Dongpu , Lv Guohua , Wang Anqi , Wen Haibo 
Published: August 2022

Corbicula fluminea (C. fluminea) is an important freshwater economy shellfish in China, but it often suffers from air exposure during transportation. In this study, we investigated the histological, physiological (mainly including respiratory metabolism, antioxidant capacity, and immune function), and transcriptomic responses of hepatopancreas in C. fluminea to different times of air exposure. At histological level, air exposure caused vacuolation of digestive cells (24–96 h) and enlargement of digestive tubule lumen (6–96 h) in hepatopancreas. At physiological level, the activities of enzymes related to glycolysis (hexokinase and pyruvate kinase) and anaerobic respiration (lactate dehydrogenase) were increased first (6–24 h) of air exposure, then came back to normal level or even decreased. The activity of aerobic respiration-related enzyme (succinic dehydrogenase) began to reduce from 24 h of air exposure. The activities of antioxidant enzymes (superoxide dismutase and catalase) were enhanced during 6–48 h of air exposure and then returned to control level or even inhibited. The content of malondialdehyde (MDA) increased from 96 h of air exposure. The activities of immune-related enzymes (acid phosphatase and alkaline phosphatase) increased during 6–48 h, then returned to normal or began to decline. At transcriptome level, 44 differentially expressed genes (DEGs) in the hepatopancreas were identified after 96-h air exposure. Among these DEGs, 8 were associated with glycolysis, TCA cycle, immune, and antioxidant, and were downregulated after 96-h air exposure. Taken together, these findings illuminated the response of C. fluminea to air exposure at histological, physiological, and transcriptomic levels, which will be beneficial to the aquaculture and transportation of C. fluminea.
Psychometric properties of the German version of the Psychological Consequences of Screening Questionnaire (PCQ) for liver diseases
Authors: Fichtner Urs A. , Maun Andy , Farin-Glattacker Erik 
Published: August 2022

BackgroundThis study aimed to translate the negative and positive items of the Psychological Consequences Questionnaire (PCQ) into German, to adapt this version to the context of screening for cirrhosis and fibrosis of the liver, and to test its psychometric properties.Materials and methodsThe three subscales (physical, emotional, and social) were translated into German using a forward-backward translation method. Furthermore, we adapted the wording to the context of liver diseases. In sum, the PCQ comprises twelve negative items and ten positive items. We tested the acceptability, distribution properties, internal consistency, scale structure, and the convergent validity using an analysis sample of 443 patients who were screened for cirrhosis or fibrosis of the liver.ResultsWe found low non-response and non-unique answer rates on the PCQ items in general. However, positive items had higher non-response rates. All items showed strong floor effects. McDonald’s Omega was high for both the negative (ω = 0.95) and the positive PCQ scale (ω = 0.90), as well as for the total PCQ scale (ω = 0.86). Confirmatory factor analysis could reproduce the three dimensions that the PCQ intends to measure. However, it suggests not summing up a total PCQ score and instead treat the subscales separately considering a higher order overall construct. Convergent validity with the short form of the Spielberger State-Trait Anxiety Inventory (STAI-Y-6) was acceptable.ConclusionOverall, our study results report a successful adaptation of the German PCQ with good performance in terms of acceptability, internal consistency, scale structure, and convergent validity. Floor-effects limit the content validity of the PCQ, which needs to be addressed in future research. However, the German version of the PCQ is a useful measurement for both negative and positive screening consequences - even in a non-cancer setting.