bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lëttëra web platform: A game-based learning approach with the use of technology for reading competence
Authors: Leal Uhlig Emilia Fernanda , Garza León Carolina , Cruz Vargas Xóchitl , Hernández Franco Sheila , Portuguez-Castro May 
Published: April 2023

IntroductionThis study explores the potential of technology, metacognition, and game-based learning to improve reading literacy in upper secondary school students. The focus is on the Lëttëra educational innovation, a web-based platform that uses game-based learning and technology to develop reading literacy.MethodsThis is a quantitative, exploratory, descriptive, and quasi-experimental study that reviewed 149 responses from high school students who took the standardized test Planea 2017. The study aimed to analyze whether using the Lëttëra platform brought a change in the students’ reading competence. The authors also examined students’ motivation toward technology, the platform interface, and the game. The data was analyzed both descriptively and inferentially.ResultsThe results showed that using the Lëttëra platform significantly improved students’ competencies in literary text, information construction, and argumentative text. It also increased their motivation toward the proposed activities.DiscussionThis study demonstrates that integrating technology and game-based learning into reading instruction can lead to improved reading competencies and increased motivation among students. These findings are useful for educators, curriculum developers, and policymakers who aim to enhance reading instruction by integrating technology into their teaching practices.ConclusionOverall, this study highlights the potential of technology and game-based learning to improve reading literacy in upper secondary school students. The Lëttëra platform provides a promising approach for enhancing reading instruction, and its integration into teaching practices can benefit students, educators, and policymakers alike.
Design of a low carbon economy model by carbon cycle optimization in supply chain
Authors: Ding Jingwen 
Published: April 2023

IntroductionConcerning economic globalization, enterprises must work with the cooperative partner to obtain more profits and overall planning of the supply chain has become a new focus for enterprise development. This paper studies the joint emission reduction of the supply chain in green low-carbon economy development and achieve joint emission and economic cost reduction through the optimization of carbon emission and economic dispatch.MethodsThe paper firstly uses the multi-agent model to complete the fullcycle modeling of carbon emission and economic cost; Secondly, the simulated annealing-adaptive chaos-particle swarm optimization (SAACPSO) method is used to optimize various parameters in the model to achieve emission and cost reductionResultsThe results show that after the optimization, the economic cost is reduced by 0.07 and the carbon emission is also reduced by 0.16; Finally, the practical test of the model is conducted with the collected data from the local company. The results show that the multi-objective optimization model of a joint enterprise supply chain is significantly better than single optimization in terms of emission reduction.DiscussionIt provides new ideas for a green economy and technical support for the global planning of supply chain integration.
The immunosuppressive effects and mechanisms of loureirin B on collagen-induced arthritis in rats
Authors: Zou Yan , Zhao Qianru , Zhang Xu , Yu Hui , Zhou Yongsheng , Li Ziyi , Xiao Min , Xiang Qiu , Zhang Lirong , Shi Wenyi , Tao Haobo , Chen Lvyi , Han Bing , Yin Shijin 
Published: April 2023

IntroductionRheumatoid arthritis (RA) is a common disease mainly affecting joints of the hands and wrists. The discovery of autoantibodies in the serum of patients revealed that RA belonged to the autoimmune diseases and laid a theoretical basis for its immunosuppressive therapy. The pathogenesis of autoimmune diseases mainly involves abnormal activation and proliferation of effector memory T cells, which is closely related to the elevated expression of Kv1.3, a voltage-gated potassium (Kv) channel on the effector memory T cell membrane. Drugs blocking the Kv1.3 channel showed a strong protective effect in RA model animals, suggesting that Kv1.3 is a target for the discovery of specific RA immunosuppressive drugs.MethodsIn the present study, we synthesized LrB and studied the effects of LrB on collagen- induced arthritis (CIA) in rats. The clinical score, paw volume and joint morphology of CIA model rats were compared. The percentage of CD3+, CD4+ and CD8+ T cells in rat peripheral blood mononuclear and spleen were analyzed with flow cytometry. The concentrations of inflammatory cytokines interleukin (IL)-1b, IL-2, IL-4, IL-6, IL-10 and IL-17 in the serum of CIA rats were analyzed with enzyme-linked immunosorbent assay. The IL-1b and IL-6 expression in joints and the Kv1.3 expression in peripheral blood mononuclear cells (PBMCs) were quantified by qPCR. To further study the mechanisms of immunosuppressive effects of LrB, western blot and immunofluorescence were utilized to study the expression of Kv1.3 and Nuclear Factor of Activated T Cells 1 (NFAT1) in two cell models - Jurkat T cell line and extracted PBMCs.ResultsLrB effectively reduced the clinical score and relieved joint swelling. LrB could also decrease the percentage of CD4+ T cells, while increase the percentage of CD8+ T cells in peripheral blood mononuclear and spleen of rats with CIA. The concentrations of inflammatory cytokines interleukin (IL)-1b, IL-2, IL-6, IL-10 and IL-17 in the serum of CIA rats were significantly reduced by LrB. The results of qPCR showed that Kv1.3 mRNA in the PBMCs of CIA rats was significantly higher than that of the control and significantly decreased in the LrB treatment groups. In addition, we confirmed in cell models that LrB significantly decreased Kv1.3 protein on the cell membrane and inhibited the activation of Nuclear Factor of Activated T Cells 1 (NFAT1) with immune stimulus.ConclusionIn summary, this study revealed that LrB could block NFAT1 activation and reduce Kv1.3 expression in activated T cells, thus inhibiting the proliferation of lymphocytes and the release of inflammatory cytokines, thereby effectively weakening the autoimmune responses in CIA rats. The effects of immunosuppression due to LrB revealed its potential medicinal value in the treatment of RA.
Development of an ultrasensitive microfluidic assay for the analysis of Glial fibrillary acidic protein (GFAP) in blood
Authors: Fazeli Badrieh , Huss André , Gómez de San José Nerea , Otto Markus , Tumani Hayrettin , Halbgebauer Steffen 
Published: April 2023

Introduction: A rapid and reliable detection of glial fibrillary acidic protein (GFAP) in biological samples could assist in the diagnostic evaluation of neurodegenerative disorders. Sensitive assays applicable in the routine setting are needed to validate the existing GFAP tests. This study aimed to develop a highly sensitive and clinically applicable microfluidic immunoassay for the measurement of GFAP in blood.Methods: A microfluidic GFAP assay was developed and validated regarding its performance. Subsequently, serum and cerebrospinal fluid (CSF) of Alzheimer’s disease (AD), Multiple Sclerosis (MS) and control patients were analyzed with the established assay, and levels were compared to the commercial GFAP Simoa discovery kit.Results: The developed GFAP assay showed a good performance with a recovery of 85% of spiked GFAP in serum and assay variations below 15%. The established assay was highly sensitive with a calculated lower limit of quantification and detection of 7.21 pg/mL and 2.37 pg/mL, respectively. GFAP levels were significantly increased in AD compared to control patients with advanced age (p = 0.002). However, GFAP levels revealed no significant increase in MS compared to control patients in the same age range (p = 0.140). Furthermore, serum GFAP levels evaluated with the novel microfluidic assay strongly correlated with Simoa concentrations (r = 0.88 (95% CI: 0.81–0.93), p &lt; 0.0001).Conclusion: We successfully developed a sensitive and easy-to-use microfluidic assay to measure GFAP in blood. Furthermore, we could confirm previous findings of elevated GFAP levels in AD by applying the assay in a cohort of clinically characterized patients.
Transcranial direct current stimulation impairs updating of avoidance-based associative learning
Authors: van ’t Wout-Frank Mascha , Garnaat Sarah L. , Faucher Christiana R. , Arulpragasam Amanda R. , Cole Julia E. , Philip Noah S. , Burwell Rebecca D. 
Published: April 2023

IntroductionExposure-based psychotherapies for the treatment of anxiety- and fear-based disorders rely on “corrective” associative learning. Namely the repeated confrontation with feared stimuli in the absence of negative outcomes allows the formation of new, corrected associations of safety, indicating that such stimuli no longer need to be avoided. Unfortunately, exposure-facilitated corrective learning tends to be bound by context and often poorly generalizes. One brain structure, the prefrontal cortex, is implicated in context-guided behavior and may be a relevant target for improving generalization of safety learning. Here, we tested whether inhibition of the left prefrontal cortex causally impaired updating of context-bound associations specifically or, alternatively, impaired updating of learned associations irrespective of contextual changes. Additionally, we tested whether prefrontal inhibition during corrective learning influenced subsequent generalization of associations to a novel context.MethodsIn two separate experiments, participants received either 10 min of 2 mA cathodal transcranial direct current stimulation (tDCS) over EEG coordinate F3 (Experiment 1 n = 9, Experiment 2 n = 22) or sham stimulation (Experiment 1 n = 10, Experiment 2 n = 22) while previously learned associations were reversed in the same or a different context from initial learning. Next, to assess generalization of learning, participants were asked to indicate which of the previously seen images they preferred in a novel, never seen before context.ResultsResults indicate that tDCS significantly impaired reversal irrespective of context in Experiment 2 only. When taking learning rate across trials into account, both experiments suggest that participants who received sham had the greatest learning rate when reversal occurred in a different context, as expected, whereas participants who received active tDCS in this condition had the lowest learning rate. However, active tDCS was associated with preferring the originally disadvantageous, but then neural stimulus after stimulus after reversal occurred in a different context in Experiment 1 only.DiscussionThese results support a causal role for the left prefrontal cortex in the updating of avoidance-based associations and encourage further inquiry investigating the use of non-invasive brain stimulation on flexible updating of learned associations.
Adjuvant chemotherapy is associated with an overall survival benefit regardless of age in ER+/HER2- breast cancer pts with 1-3 positive nodes and oncotype DX recurrence score 20 to 25: an NCDB analysis
Authors: Stabellini Nickolas , Cao Lifen , Towe Christopher W. , Luo Xun , Amin Amanda L. , Montero Alberto J. 
Published: April 2023

BackgroundThe RxPONDER trial found that among breast cancer patients with estrogen receptor positive (ER+) breast cancer, 1-3 positive axillary nodes, and a recurrence score of ≤25, only pre-menopausal women benefitted from adjuvant chemoendocrine therapy; postmenopausal women with similar characteristic did not benefit from adjuvant chemotherapy. We aimed to replicate the RxPonder trial using a larger patient cohort with real world data to determine whether a RS threshold existed where adjuvant chemotherapy was beneficial regardless of age.MethodsThe National Cancer Database (NCDB) was queried for women with ER+, human epidermal growth factor receptor 2 (HER2) negative breast cancer, 1-3 positive axillary nodes, and RS ≤25 who received endocrine (ET) only or chemo-endocrine therapy (CET). Cox regression interaction was explored between CET and age as a surrogate for menopausal status.ResultsThe final analytic cohort included 28,427 eligible women: 7,487 (26.3%) received adjuvant CET and 20,940 (73.7%) ET. In the entire cohort, RS had a normal distribution, with a median score of 14. After correcting for demographic and clinical variables, a threshold effect was observed with RS &gt;20 being associated with a significantly inferior overall survival (OS) (P value range: &lt; 0.001-0.019). In women with RS of 20-25, CET was associated with a significant improvement in OS compared to ET alone, regardless of age (age &lt;=50: HR = 0.334, P=0.002; age&gt;50: HR=0.521, P=0.019).ConclusionAmong women with ER+/HER2- breast cancer with 1–3 positive nodes, and a RS of 20-25—in contrast to the RxPONDER trial—we observed that CET was associated with an OS benefit in women regardless of age.
miRNome of Child A hepatocellular carcinoma in Egyptian patients
Authors: EL-shqnqery Hend E. , Mohamed Rania Hassan , Samir Omar , Ayoub Islam , El-Sayed Wael M. , Sayed Ahmed A. 
Published: April 2023

IntroductionHepatocellular carcinoma (HCC) has different etiologies that contribute to its heterogeneity. In regards to the number of HCC patients, Egypt ranks third in Africa and fifteenth worldwide. Despite significant advancements in HCC diagnosis and treatment, the precise biology of the tumor is still not fully understood, which has a negative impact on patient outcomes.MethodsAdvances in next-generation sequencing (NGS) have increased our knowledge of the molecular complexity of HCC.Results &amp; discussionIn this research, 16 HCC and 6 tumor adjacent tissues (control) of Child A Egyptian patients were successfully profiled for the expression profile of miRNAs by NGS. Forty-one differentially expressed miRNAs (DEMs) were found by differential expression analysis, with 31 being upregulated and 10 being downregulated. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was then conducted on these differentially expressed miRNAs revealing that Sensitivity and specificity analysis showed that hsa-miR-4488, hsa-miR-3178, and hsa-miR-3182 were unique miRNAs as they are expressed in HCC tissues only. These miRNAs were all highly involved in AMPK signaling pathways. However, hsa-miR-214-3p was expressed in control tissues about eight times higher than in cancer tissues and was most abundant in “pathways in cancer and PI3K-Akt signaling pathway” KEGG terms. As promising HCC diagnostic markers, we here suggest hsa-miR-4488, hsa-miR-3178, hsa-miR-3182, and hsa-miR-214-3p. We further urge future research to confirm these markers' diagnostic and prognostic potential as well as their roles in the pathophysiology of HCC.
A synthetic peptide from Sipunculus nudus promotes bone formation via Estrogen/MAPK signal pathway based on network pharmacology
Authors: Wang Peiran , Feng Zhenhui , Chen Siyu , Liang Yingye , Hou Haiyan , Ouyang Qianqian , Yu Hui , Ye Hua , Cai Lei , Qi Yi , Wu Kefeng , Luo Hui 
Published: April 2023

The tripeptide Leu-Pro-Lys (LPK), derived from the Sipunculus nudus protein, was synthesized and studied to investigate its potential protective effect on bone formation. The effect and mechanism of LPK were analyzed through network pharmacology, bioinformatics, and experimental pharmacology. The study found that LPK at concentrations of 25 μg/mL and 50 μg/mL significantly increased ALP activity and mineralization in C3H10 cells. LPK also increased the expression of COL1A1 and promoted bone formation in zebrafish larvae. Network pharmacology predicted 148 interaction targets between LPK and bone development, and analysis of the protein-protein interaction network identified 13 hub genes, including ESR1, MAPK8, and EGFR, involved in bone development. Through KEGG enrichment pathways analysis, it was determined that LPK promotes bone development by regulating endocrine resistance, the relaxin signaling pathway, and the estrogen signaling pathway. Molecular docking results showed direct interactions between LPK and ESR1, MAPK8, and MAPK14. Additional verification experiments using western blot assay revealed that LPK significantly upregulated the expression of genes related to bone formation, including COL1A1, OPG, RUNX2, ESR1, phosphorylated MAPK14, and phosphorylated MAPK8 in C3H10 cells. These results suggest that LPK promotes bone formation by activating the estrogen/MAPK signaling pathway.
Construct validity of the Danish version of the Work Rehabilitation Questionnaire (WORQ)—sensitivity and specificity of the objectively tested physical capacity items
Authors: Verpe Ida Skovborg , Thygesen Katrine Baltzer , Escorpizo Reuben , Mortensen Ole Steen , Korshøj Mette 
Published: April 2023

ObjectiveThe aim of this study was to examine the construct validity of the Danish version of the Work Rehabilitation Questionnaire (WORQ) and to compare the physical capacity items of WORQ to objective, standardized measures of physical capacity and selected SF-36 physical items.MethodsThe study took place at a job center in Holbæk municipality, and 40 clients of working age were enrolled. Participants completed the interviewer-administered version of WORQ, selected SF-36 items, and underwent objective, physical capacity testing, including a 30-s sit-to-stand-test, a hand-grip-strength test, and a 6-min walk test to estimate cardiorespiratory fitness. Correlations between variables were assessed using Spearman's correlation. Further, cross tabulations and chi-square tests were conducted, and sensitivity, specificity, positive predictive values (PPVs), and negative predictive values (NPVs) were calculated.ResultsWe found a moderate to strong correlation between WORQ and SF-36 items and a weak to moderate correlation between physical capacity items of WORQ and objectively tested physical capacity measures. On the basis of cross tabulations, calculations yielded overall higher NPVs than PPVs, whereas sensitivity and specificity varied more, with not one parameter being overall better than the other.ConclusionWe found evidence of construct validity of the WORQ-Danish. However, our study might also raise a question as to whether objective physical capacity tests are the gold standard for evaluating functioning. Our results are promising, and we suggest further investigations of the screening capabilities of WORQ, alongside other legacy measures or instruments, both self-reported and objective physical measures, to complement information—where specific answers to specific questions trigger work-related actions or interventions
Association of Work Schedules With Nurse Turnover: A Cross-Sectional National Study
Authors: Bae Sung-Heui 
Published: April 2023

Objective: To examine the relationship of work schedules with nurse turnover across various work settings.Methods: A cross-sectional study design was used with data collected from 17,046 nurses who participated in the 2018 National Sample Survey of Registered Nurses in the U.S. Multivariate logistic regression was used to examine the effects of work hours and overtime on nurse turnover.Results: Longer weekly work hours increased nurse turnover (OR = 1.104, 95% confidence interval [CI] = 1.006–1.023). A non-linear relationship was observed between overtime and turnover. Compared with nurses with no overtime, the turnover for nurses working 1–11 h overtime per week decreased (OR = 0.893, 95% CI = 0.798–0.999). When nurses worked ≥12 h, turnover increased (OR = 1.260, 95% CI = 1.028–1.545). Earning from the primary nursing position decreased turnover among nurses working in hospitals, other inpatient settings, and clinics. Job satisfaction decreased turnover.Conclusion: To prevent nurse turnover, it is important to monitor and regulate nurses’ working hours at institutional and government levels. Government support and policy implementations can help prevent turnover.
Prognostic role of pretreatment skeletal muscle index in gastric cancer patients: A meta-analysis
Authors: He Xiaohong , Zhou Sicheng , Li Hongjun , Gou Yue , Jia Dan 
Published: April 2023

Background: The association between pretreatment skeletal muscle index (SMI) and long-term survival of gastric cancer patients remains unclear up to now. The aim of this meta-analysis was to identify the prognostic value of pretreatment SMI in gastric cancer.Methods: The PubMed, EMBASE and Web of Science electronic databases were searched up to 5 June 2022 for relevant studies. The primary outcome was overall survival (OS) and the second outcomes were disease-free survival (DFS) and cancer-specific survival (CSS). The hazard ratios (HRs) and 95% confidence intervals (CIs) were combined to assess the relationship between pretreatment SMI and survival of gastric cancer patients. All statistical analyses were conducted by STATA 15.0 software.Results: A total of 31 retrospective studies involving 12,434 patients were enrolled in this meta-analysis. The pooled results demonstrated that lower pretreatment was significantly associated with poorer OS (HR = 1.53, p &lt; 0.001). Besides, lower pretreatment SMI was also related with worse DFS (HR = 1.39, p &lt; 0.001) and CSS (HR = 1.96, p &lt; 0.001).Conclusion: Pretreatment SMI was significantly associated with prognosis of gastric cancer patients and lower SMI predicted worse survival. However, more prospective high-quality studies are still needed to verify our findings.
Effects of Fermented Artemisia annua L. and Salicornia herbacea L. on Inhibition of Obesity In Vitro and In Mice
Authors: On Jeong-Yeon , Kim Su-Hyun , Kim Jeong-Mee , Park Sungkwon , Kim Ki-Hyun , Lee Choong-Hwan , Kim Soo-Ki 
Published: April 2023

Plant extracts including secondary metabolites have anti-inflammatory and anti-obesity activities. This study was conducted to investigate the anti-obesity properties of fermented Artemisia annua (AW) and Salicornia herbacea (GW) in vitro and in mice. The metabolite profiling of AW and GW extracts was performed using UHPLC−LTQ−Orbitrap–MS/MS, and gene expression was analyzed using real-time PCR for adipocyte difference factors. The anti-obesity effects in mice were measured using serum AST, ALT, glucose, TG, and cholesterol levels. Metabolites of the plant extracts after fermentation showed distinct differences with increasing anti-obesity active substances. The efficacy of inhibitory differentiation adipogenesis of 3T3-L1 adipocytes was better for GW than AW in a concentration-dependent manner. RT-PCR showed that the GW extract significantly reduced the expression of genes involved in adipocyte differentiation and fat accumulation (C/EBPα, PPARγ, and Fas). In C57BL/6 mice fed the HFD, the group supplemented with AW and GW showed reduced liver weight, NAS value, and fatty liver by suppressing liver fat accumulation. The GW group significantly reduced ALT, blood glucose, TG, total cholesterol, and LDL-cholesterol. This study displayed significant metabolite changes through biotransformation in vitro and the increasing anti-obesity effects of GW and AW in mice. GW may be applicable as functional additives for the prevention and treatment of obesity.