bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-inflammatory effects of thymol: an emphasis on the molecular interactions through in vivo approach and molecular dynamic simulations
Authors: Islam Muhammad Torequl , Bappi Mehedi Hasan , Bhuia Md Shimul , Ansari Siddique Akber , Ansari Irfan Aamer , Shill Manik Chanda , Albayouk Tala , Saleh Na’il , El-Shazly Mohamed , El-Nashar Heba A. S. 
Published: June 2024

Thymol (THY), as the natural monoterpene phenol, acts against oxidative stress and inflammatory processes. This study aimed to evaluate the anti-inflammatory effects and possible molecular mechanisms of THY via formalin-induced mouse and egg albumin-induced chick models alongside molecular docking and molecular dynamic (MD) simulations. THY (7.5, 15, and 30 mg/kg) was investigated, compared to celecoxib and ketoprofen (42 mg/kg), as anti-inflammatory standards. THY dose-dependently and significantly (p &lt; 0.05) decreased paw-licking and edema diameter parameters in formalin (phases I and II) and egg albumin-induced models. Moreover, THY (15 mg/kg) exerted better anti-inflammatory effects in combination with the standard drug ketoprofen than alone and with celecoxib. In silico studies demonstrated elevated binding affinities of THY with cyclooxygenase-2 (COX-2) than the COX-1 enzyme, and the ligand binds at a similar location where ketoprofen and celecoxib interact. The results of MD simulations confirmed the stability of the test ligand. THY exerted anti-inflammatory effects on Swiss mice and young chicks, possibly by interacting with COX-2. As a conclusion, THY might be a hopeful drug candidate for the management of inflammatory disorders.
Promoting L2 learners’ critical thinking skills: the role of social constructivism in reading class
Authors: Le Ha Van , Nguyen Long Quoc 
Published: June 2024

IntroductionIn the rapidly evolving digital landscape, the imperative for success has increasingly spotlighted the essential need for students to develop critical thinking and reading skills as key competencies for the 21st century. This study sought to explore the potential of constructivism to enhance learners’ critical thinking and reading abilities, alongside evaluating their receptiveness to this pedagogical approach.MethodsA mixed-methods research design was employed, combining a quasi-experimental framework with semi-structured interviews. The quasi-experimental component compared the effectiveness of constructivist and traditional teacher-centered methods in promoting critical thinking skills. Semi-structured interviews were conducted to gauge participants’ satisfaction with the constructivist approach and to gather qualitative data on their experiences.ResultsThe investigation yielded two principal findings. First, the constructivist approach significantly outperformed traditional teacher-centered methods in promoting critical thinking skills among students. Second, the majority of participants reported a high level of satisfaction with the constructivist method, attributing this to the approach’s facilitation of deeper knowledge acquisition and increased opportunities for interaction with peers and instructors.DiscussionTheoretical implications of this study underscore the value of constructivism in fostering an engaging and interactive learning environment conducive to the development of critical analytical skills. Practically, the findings advocate for educational practitioners and institutional leaders to consider the integration of constructivist strategies in reading sessions to bolster students’ critical thinking and reading competencies. Moreover, it emphasizes the necessity for educators to receive comprehensive training on the nuances of constructivist pedagogy to ensure its effective implementation. This study thus contributes to the pedagogical discourse by affirming the efficacy of constructivism in enhancing critical cognitive skills and by outlining a pathway for its successful adoption in educational settings.
Effectiveness and safety of once-weekly semaglutide: findings from the SEMACOL-REAL retrospective multicentric observational study in Colombia
Authors: Buenaventura-Collazos Daisy C. , García-Ramos Andrés F. , Balcázar-Valencia Carlos M. , Aguilar-Londoño Carolina , Coronel-Restrepo Nicolás , Monsalve-Arango Claudia Y. , Cuesta-Castro Diana P. , Ramírez-Rincón Alex 
Published: June 2024

IntroductionDiabetes stands as one of the leading causes of death worldwide. Glucagon-like peptide-1 receptor agonists rank among the most effective medications for lowering blood glucose and body weight, as well as reducing cardiovascular risk in individuals with diabetes. Observational studies complement experimental evidence in new settings, different populations, and real-world healthcare practices.MethodsA multicentric observational study of adults with type 2 diabetes treated with once-weekly subcutaneous semaglutide in four health centers in Colombia was conducted. The protocol for the present study was not pre-registered.ResultsData from 186 patients were included. Most patients were women (57%) with a mean age of 62.8 ± 12.1 years. One year of once-weekly semaglutide usage was associated with a mean reduction in HbA1C of −1.47% (95% CI −1.76, −1.17), weight loss of −4.23 kg (95% CI −5.34, −3.12), and albumin/creatinine ratio of −18.6 mg/g (95% CI −60.2, −5.9). Approximately half the treated patients achieved a level of HbA1c ≤7% by the end of follow-up. Adverse events were rare and consistent with clinical trial safety profiles.ConclusionIn Colombia, administering semaglutide subcutaneously once a week over a 1-year period led to an average weight loss of 4.2 kg and a decrease of 1.4% in HbA1c.
Association between thyroid function and nonalcoholic fatty liver disease: a dose-response meta-analysis
Authors: Xiang Liu-lan , Cao Yu-tian , Sun Jing , Li Rui-han , Qi Fang , Zhang Yu-juan , Zhang Wen-hui , Yan Lou , Zhou Xi-qiao 
Published: June 2024

BackgroundThyroid hormones (THs) have been found that it is closely associated with the onset and progression of non-alcoholic fatty liver disease (NAFLD). However, the current study could not verify the intrinsic relationship between thyroid hormones and NAFLD, which requires further research.MethodsThe searches of studies reported both TH level in serum and NAFLD were performed in PubMed, Web of Science, Cochrane Library, and Embase databases. We combined an overall meta-analysis with a dose-response meta-analysis to assess the correlation and dose-response relationship between thyroid function levels and the risk of NAFLD.ResultsOverall, 10 studies were included with a total of 38,425 individuals. We found that the non-linear dose-response model showed that for every 1 ng/dL increase in FT4, the risk of NAFLD was reduced by 10.56% (p=0.003). The odds ratios (ORs) for NAFLD with high free triiodothyronine (FT3) exposure compared to those with low FT3 were 1.580 (95% CI 1.370 to 1.830, I2 = 0.0%, p&lt;0.001) in the overall meta-analysis. The continuous variable meta-analysis indicated that individuals with high levels of TSH (SMD=1.32, 95% CI 0.660 to 1.970, p&lt;0.001) had significantly higher levels of liver fibrosis than those with low levels.ConclusionsOur findings only validate that there is a correlation between the occurrence of NAFLD and abnormal levels of THs, and it is expected that more observational studies will still be conducted in the future to further demonstrate the relationship between thyroid hormones and NAFLD.Trial registrationRegistered number in PROSPERO: CRD42023405052.
Pelvic ultrasound and pubertal attainment in girls with sexual precocity: the pivotal role of uterine volume in predicting the timing of menarche
Authors: Cattoni Alessandro , Russo Gianni , Capitoli Giulia , Rodari Giulia , Nicolosi Maria Laura , Molinari Silvia , Tondelli Daniele , Pelliccia Ciretta , Radaelli Silvia , Arosio Andrea Mario Luciano , Fontana Katia , Tattesi Giulia , Passoni Paolo , Boneschi Annalisa , Giavoli Claudia , Meroni Silvia Laura Carla , Stancampiano Marianna Rita , Garuti Elda , Biondi Andrea , Balduzzi Adriana , Bizzarri Carla 
Published: June 2024

IntroductionAmong girls assessed for pubertal precocity, pelvic ultrasound (pUS) may represent a pivotal tool to predict the time expected to elapse between sonographic assessment and the onset of menarche (TUS-M). Accordingly, the present analysis is meant to define the statistical relationship between sonographic parameters and TUS-M, in order to identify the most reliable predictor of the timing of menarche.MethodsRetrospective, multicenter analysis. Girls assessed for sexual precocity and showing sonographic and clinical findings consistent with pubertal onset upon referral were considered eligible. Patients treated with GnRH analogues were excluded and only those who had subsequently achieved complete and spontaneous pubertal attainment and for whom the exact date of menarche was available were included. Overall, we enrolled 184 girls from five tertiary care Italian Centers.ResultsThe time elapsed (months) between baseline endocrine assessment and spontaneous achievement of menarche showed a negative statistically significant correlation (p&lt;0.0001) with LH (r:-0.61), FSH (r:-0.59), estradiol (r:-0.52) and stimulated LH values (r:-0.58). Among pUS parameters, ovarian volume (r:-0.17 left, -0.30 right) and uterine body-to-cervix ratio (r:-0.18) poorly correlated with TUS-M, while uterine diameters (r:-0.61 longitudinal, -0.64 anteroposterior) and volume (r:-0.70) achieved a highly statistical significance (p&lt;0.0001). Uterine volume (UV) showed a negative logarithmic relationship with TUS-M and represented the most reliable predictor of the timing of menarche in uni- and multivariable analyses (p &lt;0.001). ROC analyses identified the UV thresholds that best predict the onset of menarche within 18, 12 and 6 months, respectively: 3.76, 6.02 and 8.80 ml.ConclusionThe logarithm of UV shows the best statistical performance in predicting the timing of menarche in girls assessed for pubertal precocity. Accordingly, we developed a user-friendly online application that provides clinicians with an estimation of the months expected to elapse before menarche, based on the UV recorded upon pUS.
Causal association between major depressive disorder and venous thromboembolism: a bidirectional mendelian randomization study
Authors: Li Hong-Yan , Wang Li-Hong , Wang Jing , Wang Yong-Bo , Wang Hai-Shan 
Published: June 2024

PurposeMajor depressive disorder (MDD) and venous thromboembolism (VTE) may be linked in observational studies. However, the causal association remains ambiguous. Therefore, this study investigates the causal associations between them.MethodsWe performed a two-sample univariable and multivariable bidirectional Mendelian randomization (MR) analysis to evaluate the associations between MDD and VTE. The summary genetic associations of MDD statistics were obtained from the Psychiatric Genomics Consortium and UK Biobank. Information on VTE, deep vein thrombosis (DVT), and pulmonary embolism (PE) were obtained from the FinnGen Biobank. Inverse-variance weighting was used as the main analysis method. Other methods include weighted median, MR-Egger, Simple mode, and Weighted mode.ResultsUnivariable MR analysis revealed no significant associations between MDD and VTE risk (odds ratio (OR): 0.936, 95% confidence interval (CI): 0.736–1.190, p = 0.590); however, after adjusting the potential relevant polymorphisms of body mass index and education, the multivariable MR analysis showed suggestive evidence of association between them (OR: 1.163, 95% CI: 1.004–1.346, p = 0.044). Univariable MR analysis also revealed significant associations between MDD and PE risk (OR: 1.310, 95% CI: 1.073–1.598, p = 0.008), but the association between them was no longer significant in MVMR analysis (p = 0.072). We found no significant causal effects between MDD and DVT risk in univariable or multivariable MR analyses. There was also no clear evidence showing the causal effects between VTE, PE, or DVT and MDD risk.ConclusionWe provide suggestive genetic evidence to support the causal association between MDD and VTE risk. No causal associations were observed between VTE, PE, or DVT and MDD risk. Further validation of these associations and investigations of potential mechanisms are required.
Deciphering the molecular landscape of rheumatoid arthritis offers new insights into the stratified treatment for the condition
Authors: Chang Min-Jing , Feng Qi-Fan , Hao Jia-Wei , Zhang Ya-Jing , Zhao Rong , Li Nan , Zhao Yu-Hui , Han Zi-Yi , He Pei-Feng , Wang Cai-Hong 
Published: June 2024

BackgroundFor Rheumatoid Arthritis (RA), a long-term chronic illness, it is essential to identify and describe patient subtypes with comparable goal status and molecular biomarkers. This study aims to develop and validate a new subtyping scheme that integrates genome-scale transcriptomic profiles of RA peripheral blood genes, providing a fresh perspective for stratified treatments.MethodsWe utilized independent microarray datasets of RA peripheral blood mononuclear cells (PBMCs). Up-regulated differentially expressed genes (DEGs) were subjected to functional enrichment analysis. Unsupervised cluster analysis was then employed to identify RA peripheral blood gene expression-driven subtypes. We defined three distinct clustering subtypes based on the identified 404 up-regulated DEGs.ResultsSubtype A, named NE-driving, was enriched in pathways related to neutrophil activation and responses to bacteria. Subtype B, termed interferon-driving (IFN-driving), exhibited abundant B cells and showed increased expression of transcripts involved in IFN signaling and defense responses to viruses. In Subtype C, an enrichment of CD8+ T-cells was found, ultimately defining it as CD8+ T-cells-driving. The RA subtyping scheme was validated using the XGBoost machine learning algorithm. We also evaluated the therapeutic outcomes of biological disease-modifying anti-rheumatic drugs. ConclusionsThe findings provide valuable insights for deep stratification, enabling the design of molecular diagnosis and serving as a reference for stratified therapy in RA patients in the future.
Multi-omic validation of the cuproptosis-sphingolipid metabolism network: modulating the immune landscape in osteosarcoma
Authors: Li Qingbiao , Fang Jiarui , Liu Kai , Luo Peng , Wang Xiuzhuo 
Published: June 2024

BackgroundThe current understanding of the mechanisms by which metal ion metabolism promotes the progression and drug resistance of osteosarcoma remains incomplete. This study aims to elucidate the key roles and mechanisms of genes involved in cuproptosis-related sphingolipid metabolism (cuproptosis-SPGs) in regulating the immune landscape, tumor metastasis, and drug resistance in osteosarcoma cells.MethodsThis study employed multi-omics approaches to assess the impact of cuproptosis-SPGs on the prognosis of osteosarcoma patients. Lasso regression analysis was utilized to construct a prognostic model, while multivariate regression analysis was applied to identify key core genes and generate risk coefficients for these genes, thereby calculating a risk score for each osteosarcoma patient. Patients were then stratified into high-risk and low-risk groups based on their risk scores. The ESTIMATE and CIBERSORT algorithms were used to analyze the level of immune cell infiltration within these risk groups to construct the immune landscape. Single-cell analysis was conducted to provide a more precise depiction of the expression patterns of cuproptosis-SPGs among immune cell subtypes. Finally, experiments on osteosarcoma cells were performed to validate the role of the cuproptosis-sphingolipid signaling network in regulating cell migration and apoptosis.ResultsIn this study, seven cuproptosis-SPGs were identified and used to construct a prognostic model for osteosarcoma patients. In addition to predicting survival, the model also demonstrated reliability in forecasting the response to chemotherapy drugs. The results showed that a high cuproptosis-sphingolipid metabolism score was closely associated with reduced CD8 T cell infiltration and indicated poor prognosis in osteosarcoma patients. Cellular functional assays revealed that cuproptosis-SPGs regulated the LC3B/ERK signaling pathway, thereby triggering cell death and impairing migration capabilities in osteosarcoma cells.ConclusionThe impact of cuproptosis-related sphingolipid metabolism on the survival and migration of osteosarcoma cells, as well as on CD8 T cell infiltration, highlights the potential of targeting copper ion metabolism as a promising strategy for osteosarcoma patients.
Cerebral cortex functional reorganization in preschool children with congenital sensorineural hearing loss: a resting-state fMRI study
Authors: Yin Yi , Lyu Xinyue , Zhou Jian , Yu Kunlin , Huang Mingming , Shen Guiquan , Hao Cheng , Wang Zhengfu , Yu Hui , Gao Bo 
Published: June 2024

PurposeHow cortical functional reorganization occurs after hearing loss in preschool children with congenital sensorineural hearing loss (CSNHL) is poorly understood. Therefore, we used resting-state functional MRI (rs-fMRI) to explore the characteristics of cortical reorganization in these patents.MethodsSixty-three preschool children with CSNHL and 32 healthy controls (HCs) were recruited, and the Categories of Auditory Performance (CAP) scores were determined at the 6-month follow-up after cochlear implantation (CI). First, rs-fMRI data were preprocessed, and amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) were calculated. Second, whole-brain functional connectivity (FC) analysis was performed using bilateral primary auditory cortex as seed points. Finally, Spearman correlation analysis was performed between the differential ALFF, ReHo and FC values and the CAP score.ResultsALFF analysis showed that preschool children with CSNHL had lower ALFF values in the bilateral prefrontal cortex and superior temporal gyrus than HCs, but higher ALFF values in the bilateral thalamus and calcarine gyrus. And correlation analysis showed that some abnormal brain regions were weak negatively correlated with CAP score (p &lt; 0.05). The ReHo values in the bilateral superior temporal gyrus, part of the prefrontal cortex and left insular gyrus were lower, whereas ReHo values in the bilateral thalamus, right caudate nucleus and right precentral gyrus were higher, in children with CSNHL than HCs. However, there was no correlation between ReHo values and the CAP scores (p &lt; 0.05). Using primary auditory cortex (PAC) as seed-based FC further analysis revealed enhanced FC in the visual cortex, proprioceptive cortex and motor cortex. And there were weak negative correlations between the FC values in the bilateral superior temporal gyrus, occipital lobe, left postcentral gyrus and right thalamus were weakly negatively correlated and the CAP score (p &lt; 0.05).ConclusionAfter auditory deprivation in preschool children with CSNHL, the local functions of auditory cortex, visual cortex, prefrontal cortex and somatic motor cortex are changed, and the prefrontal cortex plays a regulatory role in this process. There is functional reorganization or compensation between children’s hearing and these areas, which may not be conducive to auditory language recovery after CI in deaf children.
Ameliorative action of “daitongxiao” against hyperuricemia includes the “uric acid transporter group”
Authors: Zheng Lijie , Bai Yuanmei , Wan Yan , Liu Feifan , Xie Yuhuan , He Jinglin , Guo Peixin 
Published: June 2024

This study aimed to investigate the potential mechanisms involved in the therapeutic effects of daitongxiao (DTX) on hyperuricemia (HUA). DTX was administered to two animal models of HUA via gavage feeding: HUA quail model (a uricotelic animal with urate oxidase deficiency), treated continuously for 35 days post-HUA induction, and HUA rats (an animal with active urate oxidase), treated continuously for 28 days post-HUA induction. HUA was induced in quail by administering a solution of sterile dry yeast powder via gavage feeding, while in rats, it was induced by intragastric gavage feeding of a solution of adenine and ethambutol hydrochloride. DTX improved overall health; increased bodyweight; reduced renal index, serum urate levels, serum xanthine oxidase activity, blood urea nitrogen, and creatinine; and enhanced urinary and fecal uric acid (UA) excretion in these two animal models. The results of hematoxylin and eosin and hexamine silver staining of kidney sections revealed that DTX significantly mitigated HUA-induced renal structural damage and inflammatory response. The results of quantitative real-time polymerase chain reaction, Western blotting, and immunofluorescence analyses revealed that DTX downregulated the renal expression levels of glucose transporter 9 (GLUT9) and upregulated the renal expression levels of organic anion transporters (OAT1 and OAT3) in both HUA models. Thus, the findings of this study suggest that DTX suppresses the progression of HUA by modulating the expression of the UA transporter group members.
Influence of sodium/glucose cotransporter-2 inhibitors on the incidence of acute kidney injury: a meta-analysis
Authors: Wang Qian , Yu Jianmin , Deng Weizhu , Liu Chao , Yang Jian , Li Yaqing , Cai Guangyan , Chen Xiangmei , Dong Zheyi 
Published: June 2024

BackgroundSodium/glucose cotransporter-2 inhibitors (SGLT2i) are associated with cardiovascular benefits. The aim of this systematic review and meta-analysis is to summarize the influence of SGLT2i on the incidence of acute kidney injury (AKI), and to ascertain whether it is affected by confounding variables such as age, baseline renal function and concurrent use of renin-angiotensin-aldosterone system inhibitors (RAASi) or mineralocorticoid receptor antagonists (MRA).MethodsPubMed, Embase, and Cochrane Library databases were searched for randomized controlled trials comparing the influence of SGLT2i versus placebo/blank treatment on AKI in the adult population. A fixed-effect model was used if the heterogeneity was not significant; otherwise, a randomized-effect model was used.ResultsEighteen studies comprising 98,989 patients were included. Compared with placebo/blank treatment, treatment with SGLT2i significantly reduced the risk of AKI (risk ratio [RR]: 0.78, 95% confidence interval [CI]: 0.71 to 0.84, p &lt; 0.001; I2 = 0%). Subgroup analysis suggested consistent results in patients with diabetes, chronic kidney disease, and heart failure (for subgroup difference, p = 0.32). Finally, univariate meta-regression suggested that the influence of SGLT2i on the risk of AKI was not significantly modified by variables such as age (coefficient: 0.011, p = 0.39), baseline estimated glomerular filtration rate (coefficient: −0.0042, p = 0.13) or concomitant use of RAASi (coefficient: 0.0041, p = 0.49) or MRA (coefficient: −0.0020, p = 0.34).ConclusionSGLT2i may be effective in reducing the risk of AKI, and the effect might not be modified by age, baseline renal function and concurrent use of RAASi or MRA.