bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chrysin Modulates Aberrant Epigenetic Variations and Hampers Migratory Behavior of Human Cervical (HeLa) Cells
Authors: Raina Ritu , Almutary Abdulmajeed G. , Bagabir Sali Abubaker , Afroze Nazia , Fagoonee Sharmila , Haque Shafiul , Hussain Arif 
Published: January 2022

Purpose: Plant-derived phytochemicals have shown epigenetic modulatory effect in different types of cancer by reversing the pattern of DNA methylation and chromatin modulation, thereby restoring the function of silenced tumor-suppressor genes. In the present study, attempts have been made to explore chrysin-mediated epigenetic alterations in HeLa cells.Methods: Colony formation and migration assays followed by methylation-specific PCR for examining the methylation status of CpG promoters of various tumor-suppressor genes (TSGs) and the expression of these TSGs at the transcript and protein levels were performed. Furthermore, global DNA methylation; biochemical activities of DNA methyltransferases (DNMTs), histone methyl transferases (HMTs), histone deacetylases (HDACs), and histone acetyl transferases (HATs) along with the expression analysis of chromatin-modifying enzymes; and H3 and H4 histone modification marks analyses were performed after chrysin treatment.Results: The experimental analyses revealed that chrysin treatment encourages cytostatic behavior as well as inhibits the migration capacity of HeLa cells in a time- and dose-dependent manner. Chrysin reduces the methylation of various tumor-suppressor genes, leading to their reactivation at mRNA and protein levels. The expression levels of various chromatin-modifying enzymes viz DNMTs, HMTs, HDACs, and HATS were found to be decreased, and H3 and H4 histone modification marks were modulated too. Also, reduced global DNA methylation was observed following the treatment of chrysin.Conclusion: This study concludes that chrysin can be used as a potential epigenetic modifier for cancer treatment and warrants for further experimental validation.
MiR-654-3p Constrains Proliferation, Invasion, and Migration of Sinonasal Squamous Cell Carcinoma via CREB1/PSEN1 Regulatory Axis
Authors: Cui Xiao , Yang Ying , Yan Aihui 
Published: January 2022

Background: MiR-654-3p can repress malignant progression of cancer cells, whereas no relative reports were about its modulatory mechanism in sinonasal squamous cell carcinoma (SNSCC). This research committed to approaching modulatory effect of miR-654-3p on SNSCC cells.Methods: Bioinformatics methods were utilized for analyzing interaction of miR-654-3p/cAMP-responsive element binding protein 1 (CREB1)/presenilin-1 (PSEN1). Expression levels of miR-654-3p, CREB1, and PSEN1 mRNA were assessed by quantitative real-time polymerase chain reaction. Western blot was completed for level assessment of CREB1, PSEN1, and epithelial–mesenchymal transition–related proteins. The targeted relationship between miR-654-3p and CREB1, or CREB1 and PSEN1 was authenticated via dual-luciferase assay and ChIP assay. A trail of experiments in vitro was used for detection of the effects of miR-654-3p/CREB1/PSEN1 axis on malignant progression of SNSCC cells.Results: CREB1 as the downstream target mRNA of miR-654-3p could activate transcription of its downstream target gene PSEN1. Besides, miR-654-3p could target CREB1 to repress PSEN1 expression, thus restraining proliferation, migration, invasion, epithelial–mesenchymal transition, and hastening apoptosis of SNSCC cells.Conclusion: MiR-654-3p as an antitumor gene targeted CREB1 to hamper malignant progression of SNSCC through miR-654-3p/CREB1/PSEN1 axis.
The Kynurenine/Tryptophan Ratio Is a Sensitive Biomarker for the Diagnosis of Pediatric Tuberculosis Among Indian Children
Authors: Tornheim Jeffrey A. , Paradkar Mandar , Zhao Henry , Kulkarni Vandana , Pradhan Neeta , Kinikar Aarti , Kagal Anju , Gupte Nikhil , Mave Vidya , Gupta Amita , Karakousis Petros C. 
Published: January 2022

ObjectivesPediatric tuberculosis (TB) remains difficult to diagnose. The plasma kynurenine to tryptophan ratio (K/T ratio) is a potential biomarker for TB diagnosis and treatment response but has not been assessed in children.MethodsWe performed a targeted diagnostic accuracy analysis of four biomarkers: kynurenine abundance, tryptophan abundance, the K/T ratio, and IDO-1 gene expression. Data were obtained from transcriptome and metabolome profiling of children with confirmed tuberculosis and age- and sex-matched uninfected household contacts of pulmonary tuberculosis patients. Each biomarker was assessed as a baseline diagnostic and in response to successful TB treatment.ResultsDespite non-significant between-group differences in unbiased analysis, the K/T ratio achieved an area under the receiver operator characteristic curve (AUC) of 0.667 and 81.5% sensitivity for TB diagnosis. Kynurenine, tryptophan, and IDO-1 demonstrated diagnostic AUCs of 0.667, 0.602, and 0.463, respectively. None of these biomarkers demonstrated high AUCs for treatment response. The AUC of the K/T ratio was lower than biomarkers identified in unbiased analysis, but improved sensitivity over existing commercial assays for pediatric TB diagnosis.ConclusionsPlasma kynurenine and the K/T ratio may be useful biomarkers for pediatric TB. Ongoing studies in geographically diverse populations will determine optimal use of these biomarkers worldwide.
Identification of Robust Biomarkers for Early Predicting Efficacy of Subcutaneous Immunotherapy in Children With House Dust Mite-Induced Allergic Rhinitis by Multiple Cytokine Profiling
Authors: Xie Shaobing , Fan Ruohao , Tang Qingping , Cai Xiao , Zhang Hua , Wang Fengjun , Xie Shumin , Gao Kelei , Zhang Junyi , Xie Zhihai , Jiang Weihong 
Published: January 2022

BackgroundSubcutaneous immunotherapy (SCIT) is an effective treatment for children with allergic rhinitis (AR), but its efficacy fluctuates among patients. There are no reliable candidate biomarkers for monitoring and predicting the response to SCIT. The present study aims to identify novel biomarkers for early predicting the efficacy of SCIT in pediatric AR patients based on multiple cytokine profiling.MethodsWe prospectively recruited 72 children with house dust mite (HDM)-induced AR who were assigned to receive SCIT. The serum samples were collected and multiple cytokine profiling was conducted by Luminex assay at baseline. All patients were followed-up for 1 year and then categorized into effective and ineffective group based on their efficacy, and levels of 48 selected cytokines were tested and compared between the two groups. The potential cytokines were further validated by enzyme-linked immunosorbent assay (ELISA) in a cohort with 54 responders and 26 non-responders.ResultsSixty-nine of 72 children completed one-year follow-up schedule with 46 included in effective group and 23 in ineffective group. The results of multiple cytokine profiling showed that 15 cytokines (eotaxin, G-CSF, GM-CSF, IFN-γ, IL-12(p40), IL-13, IL-15, IL-16, IL-4, MIF, MIP-1α, RANTES, SCF, SDF-1α and VEGF) were dysregulated between effective and ineffective group (all P &lt; 0.05). Unadjusted and adjusted multivariate analysis models highlighted that serum eotaxin, IFN-γ, IL-4 and MIF levels closely associated with the efficacy of SCIT in pediatric HDM-induced AR patients. In addition, receiver operating characteristic (ROC) curves revealed potential values of these four biomarkers in predicting the response to SCIT. Further ELISA validation results in the cohort of 80 pediatric patients demonstrated that serum eotaxin and IL-4 levels were elevated in responders while IFN-γ levels decreased in responders (all P &lt; 0.05). ROC curves demonstrated that serum IL-4 exhibited more reliable accuracy in predicting SCIT efficacy than eotaxin and IFN-γ.ConclusionOur discover–validation study suggested that cytokines including IL-4, eotaxin and IFN- γ may serve as robust biomarkers for early predicting response of SCIT in children with HDM-induced AR. These results strengthen the evidence that cytokines were associated with the response of SCIT and contributed to understand its underlying therapeutic mechanisms.
High-Temperature Tribological Behavior of Al0.3Cr0.5Fe1.5Mn0.5Ni High-Entropy Alloys With Addition of Titanium and Carbon
Authors: Peng Chun-Hao , Tsai Che-Wei , Kuo Chia-Ming , Chiu Sheng-Min 
Published: January 2022

In this study, the Al0.3Cr0.5Fe1.5Mn0.5Ni high-entropy alloys (HEAs) with addition of titanium and carbon was prepared. The as-cast alloys were composed of FCC solid solution and TiC particles, and were further aged and strengthened by precipitation of B2-NiAl phase at 700°C for 10 h to increase hardness from Hv 200 to Hv 400. Tribological properties of the HEAs and commercial tool steel (AISI M2) against Al2O3 under dry sliding condition at room-temperature and elevated temperatures are compared. After high-temperature wear testing, the HEAs demonstrated exceptional oxidation resistance and a lower friction coefficient than M2 steel since the dense glazed layer on the surface of the HEAs served as a lubricant to decrease the friction coefficient, and protected the substrate from oxidation.
Extrinsic Adenomyosis Is Associated With Postoperative Recurrence of Ovarian Endometrioma
Authors: Sun Man , Xu Ping , Zou Gen , Wang Jianzhang , Zhu Libo , Zhang Xinmei 
Published: January 2022

Objective: To determine whether endometrioma recurrence is closely related to the presence of extrinsic adenomyosis, which was demonstrated by magnetic resonance imaging (MRI).Design: Observational crosssectional study involving patients with the recurrence of ovarian endometrioma (OMA). Correlations of endometrioma recurrence and adenomyosis subtypes shown by MRI were analyzed.Method: Between January 2018 and December 2020, a total of 233 patients with recurrence of OMA after ovarian cystectomy were administered for surgery at our institution. All patients were divided into subtype II (Group A), subtype I+IV (Group B), and nonadenomyosis (Group C) groups at preoperative MRI imaging. The correlations of endometrioma recurrence with clinical features, imaging appearance, and surgical findings were retrospectively analyzed.Results: We found 112 (48.07%) patients of endometrioma recurrence combined with subtype II adenomyosis, 8 (3.43%) subtype I adenomyosis, 47 (20.17%) subtype IV adenomyosis, 66 (28.32%) nonadenomyosis. The mean time of OMA recurrence (44.28 ± 8.37, vs. 63.96 ± 10.28, vs. 69.36 ± 9.34 mon), rate of pain symptoms (85.71, vs. 69.10, vs. 18.18%), and primary infertility (31.25, vs. 14.55, vs. 10.77%) were higher in Group A. Uterine volume (257.37± 42.61, vs. 203.14 ± 33.52, vs. 100.85 ± 26.67 cm3), and mean OMA size (4.97 ± 2.25, vs. 4.36 ± 2.38, vs. 4.46 ± 2.70 cm) were significantly larger in Group A. The rate of DIE (83.93, vs. 45.45, vs. 40.91%), the number of DIE (3.6 ± 1.8 vs. 2.3 ± 1.5 vs. 2.2 ± 1.3), the mean total revised American Society for Reproductive Medicine score (rASRM, 103.14 ± 23.89 vs. 74.23 ± 16.72 vs. 36.51 ± 14.23) were significantly higher in Group A. After a multiple logistic regression analysis, extrinsic adenomyosis (OR 2.5, 95% CI 1.2–3.4), DIE lesions (OR 2.1, 95% CI 1.4–2.8), and primary infertility (OR 1.8, 95% CI 1.3–4.3) were significantly associated with early recurrence (in 3-year) of OMA.Conclusions: Extrinsic adenomyosis was associated with postoperative recurrence of OMA. In addition, a pathogenic link between extrinsic adenomyosis and pelvic endometriosis needs to be clarified.
Probiotic Properties of Bifidobacterium longum KABP042 and Pediococcus pentosaceus KABP041 Show Potential to Counteract Functional Gastrointestinal Disorders in an Observational Pilot Trial in Infants
Authors: Astó Erola , Huedo Pol , Altadill Tatiana , Aguiló García Meritxell , Sticco Maura , Perez Marta , Espadaler-Mazo Jordi 
Published: January 2022

Functional gastrointestinal disorders (FGIDs) are a common concern during the first year of life. Recognized as gut-brain axis disorders by Rome IV criteria, FGIDs etiology is linked to altered gut-brain interaction, intestinal physiology, and microbiota. In this regard, probiotics have emerged as a promising therapy for infant FGIDs. In this study, we have investigated the probiotic potential of the strains Bifidobacterium longum KABP042 and Pediococcus pentosaceus KABP041—isolated from healthy children’s feces—in the treatment of FGIDs. To this scope, genome sequences of both strains were obtained and subjected to in silico analyses. No virulence factors were detected for any strain and only the non-transferable erm(49) gene, which confers resistance to erythromycin and clindamycin, was identified in the genome of B. longum KABP042. Safety of both strains was confirmed by acute oral toxicity in rats. In vitro characterization revealed that the strains tolerate gastric and bile challenges and display a great adhesion capacity to human intestinal cells. The two strains mediate adhesion by different mechanisms and, when combined, synergically induce the expression of Caco-2 tight junction proteins. Moreover, growth inhibition experiments demonstrated the ability of the two strains alone and in combination to antagonize diverse Gram-negative and Gram-positive bacterial pathogens during sessile and planktonic growth. Pathogens’ inhibition was mostly mediated by the production of organic acids, but neutralization experiments strongly suggested the presence of additional antimicrobial compounds in probiotic culture supernatants such as the bacteriocin Lantibiotic B, whose gene was detected in the genome of B. longum KABP042. Finally, an exploratory, observational, pilot study involving 36 infants diagnosed with at least one FGID (infant colic and/or functional constipation) showed the probiotic formula was well tolerated and FGID severity was significantly reduced after 14 days of treatment with the 2 strains. Overall, this work provides evidence of the probiotic and synergic properties of strains B. longum KABP042 and P. pentosaceus KABP041, and of their potential to treat pediatric FGIDs.Clinical Trial Registration: [www.ClinicalTrials.gov], [identifier NCT04944628].
Neuropsychiatric Symptoms Mediated the Relationship Between Odor Identification and Cognition in Alzheimer's Disease Spectrum: A Structural Equation Model Analysis
Authors: Wang Qiang , Chen Ben , Zhong Xiaomei , Zhou Huarong , Zhang Min , Mai Naikeng , Wu Zhangying , Chen Xinru , Yang Mingfeng , Zhang Si , lin Gaohong , Hummel Thomas , Ning Yuping 
Published: January 2022

Background: Odor identification dysfunction is an early predictor of the development of Alzheimer's disease (AD), but neuropsychiatric symptoms (NPS), which are common in AD and mild cognitive impairment (MCI), are also associated with odor identification dysfunction. Whether NPS affect the specificity of using odor identification dysfunction to predict cognitive decline in AD and MCI remains unclear.Methods: Patients (233 with MCI and 45 with AD) and 45 healthy controls (HCs) underwent assessments of odor identification (Sniffin' Sticks), NPS (Neuropsychiatric Inventory-12), and cognitive function (global cognition, memory, language, executive function, visual-spatial skill, and attention). Structural equation modeling (SEM) with bootstrapping estimation was conducted to explore the relationships between odor identification, NPS, and cognition.Results: Patients with NPS showed significantly worse performance in odor identification and cognition than patients without NPS and HCs. The SEM showed odor identification to be positively associated with cognition, and cognition had special indirect effects on odor identification through affective and psychosis symptoms (two factors extracted from Neuropsychiatric Inventory-12). Additionally, affective and psychosis symptoms partially mediated the effect of cognition on odor identification.Conclusion: Neuropsychiatric symptoms are associated with odor identification dysfunction in patients with AD and MCI. Studies exploring the relationship between odor identification dysfunction and cognitive decline in patients with AD and MCI should include an assessment of affective and psychosis symptoms, and adjust their confounding effects.
Impaired Topographic Organization in Patients With Idiopathic Blepharospasm
Authors: Hou Yanbing , Zhang Lingyu , Wei Qianqian , Ou Ruwei , Yang Jing , Gong Qiyong , Shang Huifang 
Published: January 2022

Background: Idiopathic blepharospasm (BSP) is a common adult-onset focal dystonia. Neuroimaging technology can be used to visualize functional and microstructural changes of the whole brain.Method: We used resting-state functional MRI (rs-fMRI) and graph theoretical analysis to explore the functional connectome in patients with BSP. Altogether 20 patients with BSP and 20 age- and gender-matched healthy controls (HCs) were included in the study. Measures of network topology were calculated, such as small-world parameters (clustering coefficient [Cp], the shortest path length [Lp]), network efficiency parameters (global efficiency [Eglob], local efficiency [Eloc]), and the nodal parameter (nodal efficiency [Enod]). In addition, the least absolute shrinkage and selection operator (LASSO) regression was adopted to determine the most critical imaging features, and the classification model using critical imaging features was constructed.Results: Compared with HCs, the BSP group showed significantly decreased Eloc. Imaging features of nodal centrality (Enod) were entered into the LASSO method, and the classification model was constructed with nine imaging nodes. The area under the curve (AUC) was 0.995 (95% CI: 0.973–1.000), and the sensitivity and specificity were 95% and 100%, respectively. Specifically, four imaging nodes within the sensorimotor network (SMN), cerebellum, and default mode network (DMN) held the prominent information. Compared with HCs, the BSP group showed significantly increased Enod in the postcentral region within the SMN, decreased Enod in the precentral region within the SMN, increased Enod in the medial cerebellum, and increased Enod in the precuneus within the DMN.Conclusion: The network model in BSP showed reduced local connectivity. Baseline connectomic measures derived from rs-fMRI data may be capable of identifying patients with BSP, and regions from the SMN, cerebellum, and DMN may provide key insights into the underlying pathophysiology of BSP.
Similar Profile and Magnitude of Cognitive Impairments in Focal and Generalized Epilepsy: A Pilot Study
Authors: Gauffin Helena , Landtblom Anne-Marie , Vigren Patrick , Frick Andreas , Engström Maria , McAllister Anita , Karlsson Thomas 
Published: January 2022

Introduction: Cognitive impairments in epilepsy are not well-understood. In addition, long-term emotional, interpersonal, and social consequences of the underlying disturbances are important to evaluate.Purpose: To compare cognitive function including language in young adults with focal or generalized epilepsy. In addition, quality of life and self-esteem were investigated.Patients and Methods: Young adults with no primary intellectual disability, 17 with focal epilepsy and 11 with generalized epilepsy participated and were compared to 28 healthy controls. Groups were matched on age (mean = 26 years), sex, and education. Participants were administered a battery of neuropsychological tasks and carried out self-ratings of quality of life, self-esteem, and psychological problems.Results: Similar impairments regarding cognitive function were noted in focal and generalized epilepsy. The cognitive domains tested were episodic long-term memory, executive functions, attention, working memory, visuospatial functions, and language. Both epilepsy groups had lower results compared to controls (effect sizes 0.24–1.07). The total number of convulsive seizures was predictive of episodic long-term memory function. Participants with focal epilepsy reported lower quality of life than participants with generalized epilepsy. Lowered self-esteem values were seen in both epilepsy groups and particularly in those with focal epilepsy. Along with measures of cognitive speed and depression, the total number of seizures explained more than 50% of variation in quality of life.Conclusion: Interestingly, similarities rather than differences characterized the widespread cognitive deficits that were seen in focal and generalized epilepsy, ranging from mild to moderate. These similarities were modified by quality of life and self-esteem. This study confirms the notion that epilepsy is a network disorder.
Antegrade or Retrograde Approach for the Management of Tandem Occlusions in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis
Authors: Min Xiaoli , Du Jianhua , Bai Xuesong , Wei Tao , Dmytriw Adam A. , Patel Aman B. , Zhang Xiao , Xu Xin , Feng Yao , Wang Tao , Wang Xue , Yang Kun , Hu Weiwu , Yi Tingyu , Chen Wenhuo , Jiao Liqun 
Published: January 2022

Background: Acute ischemic stroke (AIS) caused by tandem intracranial and extracranial occlusions is not rare. However, optimal strategy between antegrade (extracranial first) or retrograde (intracranial first) approaches still remains elusive. This systematic review and meta-analysis aim to compare the two approaches to provide updated clinical evidence of strategy selection.Methods: PubMed, Ovid, Web of Science, and the Cochrane Library were searched for literature comparing antegrade and retrograde approaches for patients with AIS with concomitant tandem occlusions. Outcomes including successful reperfusion [Throbolysis in Cerebral Infarction (TICI) 2b−3] and 90-day favorable outcome [modified Rankin Scale (mRS) 0–2], any intracerebral hemorrhage, symptomatic intracerebral hemorrhage, procedural complications, and mortality were evaluated. The risk of bias was assessed using the Newcastle–Ottawa Scale and illustrated in the Funnel plot. Heterogeneity was assessed by I2 statistic. Subgroup and sensitivity analyses were also performed.Results: A total of 11 studies accounting 1,517 patients were included. 831 (55%) patients were treated with an antegrade approach and 686 (45%) patients were treated with the retrograde approach. A higher successful reperfusion rate was achieved in retrograde group than that of antegrade group [83.8 vs. 78.0%; odds ratio (OR): 0.63, 95% CI: 0.40–0.99, p = 0.04]. 90-day favorable outcome (mRS 0–2 at 90 days) also showed significantly higher in retrograde group compared with antegrade group (47.3 vs. 40.2%; OR: 0.72, 95% CI: 0.58–0.89, p = 0.002). The incidence of any intracranial hemorrhage (ICH), symptomatic intracranial hemorrhage, 90-day mortality, and other complications did not differ between two groups.Conclusion: In AIS with tandem occlusions, the retrograde approach might achieve a higher successful reperfusion rate and better functional outcome with a comparable safety profile when compared with an antegrade approach. Further prospective controlled studies with more meticulous design and a higher level of evidence are needed to confirm these results.Systematic Review Registration: “PROSPERO” database (CRD 42020199093), https://www.crd.york.ac.uk/PROSPERO/.