bluuebunny/crossref_metadata_2025_split huggingface dataset:
A longitudinal study on changes in weekend leisure time by age groups in Korea (1999–2019)
Authors: Cha Yu-Jin 
Published: February 2024

Abstract
Background
Data analysis was conducted on 20 years (1999–2019) of the Korean Time Use Survey (KTUS) to identify differences and characteristics among each types by extracting latent clusters of weekend leisure activities.

Methods
Using data from the KTUS, we classified weekend leisure time activities into 6 distinct categories. To identify the latent clusters for each year's KTUS data, we utilized latent profile analysis (LPA). Furthermore, independent samples t-tests and one-way ANOVA were conducted to investigate the characteristics of each latent cluster.

Results
As a result of leisure time analysis by survey period, media use accounted for the largest share in all three age groups. The results of the LPA, which included media, sports, culture, and tourism, revealed that the distribution of leisure time for these activities was lower throughout the entire study period.

Conclusion
Based on the results of this study, it is recommended to explore constructive leisure activities and to develop policy measures to promote the domestic leisure industry and leisure consumption.
HDL levels modulate the impact of type 2 diabetes susceptibility alleles in older adults
Authors: Sullivan Siobhán O.’ , Al Hageh Cynthia , Henschel Andreas , Chacar Stephanie , Abchee Antoine , Zalloua Pierre , Nader Moni 
Published: February 2024

Abstract
Background
Type 2 Diabetes (T2D) is influenced by genetic, environmental, and ageing factors. Ageing pathways exacerbate metabolic diseases. This study aimed to examine both clinical and genetic factors of T2D in older adults.

Methods
A total of 2,909 genotyped patients were enrolled in this study. Genome Wide Association Study was conducted, comparing T2D patients to non-diabetic older adults aged ≥ 60, ≥ 65, or ≥ 70 years, respectively. Binomial logistic regressions were applied to examine the association between T2D and various risk factors. Stepwise logistic regression was conducted to explore the impact of low HDL (HDL < 40 mg/dl) on the relationship between the genetic variants and T2D. A further validation step using data from the UK Biobank with 53,779 subjects was performed.

Results
The association of T2D with both low HDL and family history of T2D increased with the age of control groups. T2D susceptibility variants (rs7756992, rs4712523 and rs10946403) were associated with T2D, more significantly with increased age of the control group. These variants had stronger effects on T2D risk when combined with low HDL cholesterol levels, especially in older control groups.

Conclusions
The findings highlight a critical role of age, genetic predisposition, and HDL levels in T2D risk. The findings suggest that individuals over 70 years who have high HDL levels without the T2D susceptibility alleles may be at the lowest risk of developing T2D. These insights can inform tailored preventive strategies for older adults, enhancing personalized T2D risk assessments and interventions.
CD73 mitigates ZEB1 expression in papillary thyroid carcinoma
Authors: Vedovatto Samlai , Oliveira Fernanda Dittrich , Pereira Luiza Cherobini , Scheffel Thamiris Becker , Beckenkamp Liziane Raquel , Bertoni Ana Paula Santin , Wink Márcia Rosângela , Lenz Guido 
Published: February 2024

Abstract
Background
ZEB1, a core transcription factor involved in epithelial-mesenchymal transition (EMT), is associated with aggressive cancer cell behavior, treatment resistance, and poor prognosis across various tumor types. Similarly, the expression and activity of CD73, an ectonucleotidase implicated in adenosine generation, is an important marker of tumor malignancy. Growing evidence suggests that EMT and the adenosinergic pathway are intricately linked and play a pivotal role in cancer development. Therefore, this study focuses on exploring the correlations between CD73 and ZEB1, considering their impact on tumor progression.

Methods
We employed CRISPR/Cas9 technology to silence CD73 expression in cell lines derived from papillary thyroid carcinoma. These same cells underwent lentiviral transduction of a reporter of ZEB1 non-coding RNA regulation. We conducted studies on cell migration using scratch assays and analyses of cellular speed and polarity. Additionally, we examined ZEB1 reporter expression through flow cytometry and immunocytochemistry, complemented by Western blot analysis for protein quantification. For further insights, we applied gene signatures representing different EMT states in an RNA-seq expression analysis of papillary thyroid carcinoma samples from The Cancer Genome Atlas.

Results
Silencing CD73 expression led to a reduction in ZEB1 non-coding RNA regulation reporter expression in a papillary thyroid carcinoma-derived cell line. Additionally, it also mitigated ZEB1 protein expression. Moreover, the expression of CD73 and ZEB1 was correlated with alterations in cell morphology characteristics crucial for cell migration, promoting an increase in cell polarity index and cell migration speed. RNA-seq analysis revealed higher expression of NT5E (CD73) in samples with BRAF mutations, accompanied by a prevalence of partial-EMT/hybrid state signature expression.

Conclusions
Collectively, our findings suggest an association between CD73 expression and/or activity and the post-transcriptional regulation of ZEB1 by non-coding RNA, indicating a reduction in its absence. Further investigations are warranted to elucidate the relationship between CD73 and ZEB1, with the potential for targeting them as therapeutic alternatives for cancer treatment in the near future.
Clinicopathological analysis of rosette-forming glioneuronal tumors
Authors: Liu Jing , Lin Fan , Sun Yanhua , Liu Xia 
Published: February 2024

Abstract
Background
This study aimed to investigate the clinicopathological characteristics, diagnostic indicators, and critical factors for the differential diagnosis of rosette-forming glioneuronal tumor (RGNT).

Patients and methods
This retrospective study included six surgically treated RGNT cases. We analyzed and summarized their clinical manifestations, radiological features, histological morphology, immunophenotype, and molecular genetic changes, supplemented with a literature review.

Results
The patients comprised four males and two females with a mean age of 35 years. The tumors were located in the cerebellum (two cases); the fourth ventricle, quadrigeminal cistern, and third ventricle (one case each); and the fourth ventricle and brainstem (one case). Clinical manifestations included headaches in four cases, left eyelid ptosis in one case, and one asymptomatic case only identified during physical examination. Microscopically, the tumor cells were uniform in size and were marked by rosette-like or pseudorosette-like structures around the neuropil and blood vessels. Immunohistochemistry revealed biphasic patterns. The central neuropil components of the rosette-like structures around the neuropil and the pseudorosette structures of the perivascular regions expressed Syn, while the cells surrounding the rosettes expressed Olig2 and not GFAP. GFAP and S-100 were expressed in the glial components but not in the rosette or pseudorosette regions. The Ki-67 proliferation index was typically low. Molecular genetic analysis showed that the main molecular changes involved FGFR1 mutation accompanied by PIK3R1 mutation. None of the patients received chemoradiotherapy postoperatively. Follow-up durations varied between 4 and 23 months with no recorded recurrence or metastasis.

Conclusion
RGNT is a comparatively rare mixed glioneuronal tumor that occurs in the midline structures. Its morphology shows certain overlaps with other low-grade neuroepithelial tumors. Identifying the rosettes around the neuropil is critical for morphological diagnosis, and the molecular identification of FGFR1 mutations accompanied by PIK3R1 mutations can facilitate diagnosis.
Design, synthesis, and molecular dynamics simulation studies of some novel kojic acid fused 2-amino-3-cyano-4H-pyran derivatives as tyrosinase inhibitors
Authors: Najafi Zahra , Zandi Haramabadi Maryam , Chehardoli Gholamabbas , Ebadi‬ Ahmad , Iraji Aida 
Published: February 2024

AbstractA novel series of kojic acid fused 2-amino-3-cyano-4H-pyran derivatives were synthesized via a multicomponent reaction involving kojic acid, benzyloxy benzaldehyde, and malonitrile as tyrosinase inhibitors. Subsequently, the structures of the compounds were characterized using FT-IR, 1H-, and 13C-NMR spectroscopic analyses. The designed compounds fall into three series: (1) 4-benzyloxy-phenyl kojopyran 6a–e, (2) 3-benzyloxy- phenyl kojopyran derivatives 6f–j, and (3) 4-benzyloxy-3-methoxy-phenyl kojopyran derivative 6 k–o. The assessment of tyrosinase inhibition activity was conducted using L-Dopa as the substrate. Among synthesized compounds, 2-amino-4-(4-((4-fluorobenzyl)oxy)phenyl)-6-(hydroxymethyl)-8-oxo-4,8-dihydropyrano[3,2-b]pyran-3-carbonitrile (6b) demonstrated the highest antityrosinase activity with a competitive inhibition pattern (IC50 = 7.69 ± 1.99 μM) as compared to the control agent kojic acid (IC50 = 23.64 ± 2.56 µM). Since compound 6b was synthesized as a racemic mixture, in silico studies were performed for both R and S enantiomers. The R- enantiomer showed critical interactions compared with the S-enantiomer. Specifically, it established hydrogen bonds and hydrophobic interactions with crucial and highly conserved amino acids within the enzyme's binding site in the target protein. Moreover, the molecular dynamics simulations revealed that compound 6b demonstrated significant interactions with essential residues of the binding site, resulting in a stable complex throughout the entire simulation run. The drug-like and ADMET properties predictions showed an acceptable profile for compound 6b. Thus, it can serve as a drug candidate to develop more potent antityrosinase agents due to its low toxicity and its high inhibition activity.
Determination of antihistaminic drugs alcaftadine and olopatadine hydrochloride via ion-pairing with eosin Y as a spectrofluorimetric and spectrophotometric probe: application to dosage forms
Authors: Derayea Sayed M. , Badr El-din Khalid M. , Ahmed Ahmed S. , Khorshed Ahmed A. , Oraby Mohamed 
Published: February 2024

AbstractFour sensitive and fast analytical approaches relied on ion pairing with eosin Y were built up and evaluated using spectroscopy for determination of Alcaftadine and Olopatadine hydrochloride with high sensitivity and selectivity. Two spectrofluorimetric techniques were employed to observe the quenching effect of Alcaftadine or Olopatadine hydrochloride on the intrinsic fluorescence of eosin Y in a 0.1 M acetate buffer solution at pH 3.8 and 3.3 for Alcaftadine and Olopatadine hydrochloride, respectively. Those methods are considered the first spectrofluorimetric methods for Alcaftadine and Olopatadine hydrochloride assay. The fluorescence quenching effect was linear with concentration ranging from 150 to 2000 and 200 to 2000 ng mL−1 for Alcaftadine and Olopatadine hydrochloride, respectively. In the two spectrophotometric techniques, the absorbance of the produced ion-pair was monitored at 548 and 547 nm in aqueous buffered solution at pH 3.8 and 3.3 for Alcaftadine and Olopatadine hydrochloride, respectively. Beer's law was obeyed in the concentrations range of 0.8–8.0 and 1.0–10.0 µg mL−1. The four techniques were evaluated in accordance with ICH requirements and were effectively used to analyze dosage forms with a high percent recovery.
Identification of environment-insensitive genes for oil content by combination of transcriptome and genome-wide association analysis in rapeseed
Authors: Yao Min , He Dan , Li Wen , Xiong Xinghua , He Xin , Liu Zhongsong , Guan Chunyun , Qian Lunwen 
Published: February 2024

Abstract
Background
The primary objective of rapeseed breeding is to enhance oil content, which is predominantly influenced by environmental factors. However, the molecular mechanisms underlying the impact of these environmental factors on oil accumulation remain inadequately elucidated. In this study, we used transcriptome data from two higher (HOC) and two lower oil content (LOC) inbred lines at 35 days after pollination (DAP) to investigate genes exhibiting stable expression across three different environments. Meanwhile, a genome-wide association study (GWAS) was utilized to detect candidate genes exhibiting significant associations with seed oil content across three distinct environments.

Results
The study found a total of 405 stable differentially expressed genes (DEGs), including 25 involved in lipid/fatty acid metabolism and 14 classified as transcription factors. Among these genes, BnBZIP10-A09, BnMYB61-A06, BnAPA1-A08, BnPAS2-A10, BnLCAT3-C05 and BnKASIII-C09 were also found to exhibit significant associations with oil content across multiple different environments based on GWAS of 50 re-sequenced semi-winter rapeseed inbred lines and previously reported intervals. Otherwise, we revealed the presence of additive effects among BnBZIP10-A09, BnKASIII-C09, BnPAS2-A10 and BnAPA1-A08, resulting in a significant increase in seed oil content. Meanwhile, the majority of these stable DEGs are interconnected either directly or indirectly through co-expression network analysis, thereby giving rise to an elaborate molecular network implicated in the potential regulation of seed oil accumulation and stability.

Conclusions
The combination of transcription and GWAS revealed that natural variation in six environment-insensitive gene regions exhibited significant correlations with seed oil content phenotypes. These results provide important molecular marker information for us to further improve oil content accumulation and stability in rapeseed.
A knock down strategy for rapid, generic, and versatile modelling of muscular dystrophies in 3D-tissue-engineered-skeletal muscle
Authors: in ‘t Groen Stijn L. M. , Franken Marnix , Bock Theresa , Krüger Marcus , de Greef Jessica C. , Pijnappel W. W. M. Pim 
Published: February 2024

Abstract
Background
Human iPSC-derived 3D-tissue-engineered-skeletal muscles (3D-TESMs) offer advanced technology for disease modelling. However, due to the inherent genetic heterogeneity among human individuals, it is often difficult to distinguish disease-related readouts from random variability. The generation of genetically matched isogenic controls using gene editing can reduce variability, but the generation of isogenic hiPSC-derived 3D-TESMs can take up to 6 months, thereby reducing throughput.

Methods
Here, by combining 3D-TESM and shRNA technologies, we developed a disease modelling strategy to induce distinct genetic deficiencies in a single hiPSC-derived myogenic progenitor cell line within 1 week.

Results
As proof of principle, we recapitulated disease-associated pathology of Duchenne muscular dystrophy and limb-girdle muscular dystrophy type 2A caused by loss of function of DMD and CAPN3, respectively. shRNA-mediated knock down of DMD or CAPN3 induced a loss of contractile function, disruption of tissue architecture, and disease-specific proteomes. Pathology in DMD-deficient 3D-TESMs was partially rescued by a candidate gene therapy treatment using micro-dystrophin, with similar efficacy compared to animal models.

Conclusions
These results show that isogenic shRNA-based humanized 3D-TESM models provide a fast, cheap, and efficient tool to model muscular dystrophies and are useful for the preclinical evaluation of novel therapies.
Investigation of the strength behavior and failure modes of layered sedimentary rocks under Brazilian test conditions
Authors: Abdi Yasin 
Published: February 2024

AbstractAs the anisotropic behavior of sandstones and limestone along the Khorramabad-Zal expressway has not been studied, this research aims to examine the impact of layer orientation on the strength characteristics and failure patterns of layered sedimentary rocks using the Brazilian test. For this purpose, a total of 8 rock blocks were gathered from Kashkan sandstones and Sarvak limestones in three different locations along the Khorramabad-Zal highway in western Iran. The core specimens were drilled with 54 mm diameter and parallel to the laminations. Overall 150 disc-shaped specimens were subjected to Brazilian tensile strength (BTS) in ten different anisotropy angles, which refers to the angle between the loading direction and the lamination plane. The findings revealed that the highest and lowest BTS values were obtained at β = 70° and 20° for all three types of rock. After analyzing the samples that experienced the Brazilian test and examining their failure patterns, three primary modes of failure were identified: parallel to the lamination (PL), across the lamination (AL), and curved fracture (CF). Furthermore, the transitional angle, which signifies the point at which the dominant pattern of failure shifts from PL to AL or from PL to CF, was also determined.
Drawdown-based risk indicators for high-frequency financial volumes
Authors: D’Amico Guglielmo , Basilio Bice Di , Petroni Filippo 
Published: February 2024

AbstractIn stock markets, trading volumes serve as a crucial variable, acting as a measure for a security’s liquidity level. To evaluate liquidity risk exposure, we examine the process of volume drawdown and measures of crash-recovery within fluctuating time frames. These moving time windows shield our financial indicators from being affected by the massive transaction volume, a characteristic of the opening and closing of stock markets. The empirical study is conducted on the high-frequency financial volumes of Tesla, Netflix, and Apple, spanning from April to September 2022. First, we model the financial volume time series for each stock using a semi-Markov model, known as the weighted-indexed semi-Markov chain (WISMC) model. Second, we calculate both real and synthetic drawdown-based risk indicators for comparison purposes. The findings reveal that our risk measures possess statistically different distributions, contingent on the selected time windows. On a global scale, for all assets, financial risk indicators calculated on data derived from the WISMC model closely align with the real ones in terms of Kullback–Leibler divergence.
Combination of high-flow nasal oxygen and ketamine/dexmedetomidine sedation for diagnostic catheterization in a child with pulmonary arterial hypertension: a case report
Authors: Tsuboi Kaoru , Asai Misuzu , Nakamura Toshiki , Ninagawa Jun , Ono Hiroshi , Kasuya Shugo 
Published: February 2024

AbstractPulmonary hypertension is associated with significant risk of perioperative life-threatening events. We present a case of a 12-year-old child with severe pulmonary arterial hypertension who successfully underwent diagnostic cardiac catheterization under ketamine and dexmedetomidine sedation with the support of high-flow nasal oxygen. Ketamine and dexmedetomidine are reported to have minimal effect on pulmonary vasculature in children with pulmonary hypertension and can be safely used in this population along with its lack of respiratory depression. Positive pressure generated by high-flow nasal oxygen improves upper airway patency, prevents micro-atelectasis, and is shown to improve the effectiveness of ventilation and oxygenation in patients under sedation breathing spontaneously. The presented strategy may contribute to enhancing the safety and effectiveness of procedural sedation for children with life-threatening pulmonary hypertension.
Early molecular events in the interaction between Magnaporthe oryzae and rice
Authors: Zhang Haifeng , Yang Jun , Liu Muxing , Xu Xiaozhou , Yang Leiyun , Liu Xinyu , Peng Youliang , Zhang Zhengguang 
Published: February 2024

AbstractRice is a staple crop feeding more than 50% of the world’s population and, its sustainable production is crucial to the global food security. However, blast disease caused by the filamentous fungus Magnaporthe oryzae (anamorph: Pyricularia oryzae) threatens sustainable rice production as it can reduce grain yields over 30% in epidemic years. Therefore, deciphering the molecular mechanisms of the M. oryzae-rice interaction and the mechanism that how M. oryzae overcomes rice defense is crucial for developing new strategies to make green fungicides and disease-resistant rice varieties. This review provides a comprehensive overview of the latest advances in understanding the molecular mechanisms by which M. oryzae perceives host surface signals and subsequently develops specific infection structure called appressoria. In addition, the review delves into the strategies that the fungus utilizes to overcome host immunity, which in turn allows it to colonize rice tissues. Finally, we propose the perspectives for dissecting the pathogenesis of the fungus and controlling rice blast disease.
Sleep quality, anxiety, depression, and quality of life in rheumatoid arthritis patients and impact of disease activity
Authors: Abdelrahman Maha S. I. , Shaddad Ahmad M. , Khaleel Waleed Gamal Elddin , Talaat Esraa A. , Safwat Shady Mohamed , Farrag Sara 
Published: February 2024

Abstract
Background
Rheumatoid arthritis (RA) is an autoimmune lifelong disease. Systemic manifestations represent a significant aspect of the disease burden. This study aimed to assess sleep quality and psychosocial aspects among RA patients and the impact of disease duration and activity.

Results
The mean age for included RA patients was 50.00 ± 9.37 years. The median disease duration was 9.50 (Interquartile range (IQR)=5–15) years and 90% of patients were females. Disease activity score 28 was 4.65 ± 1.66. Anxiety and depression were significantly higher among RA participants. Regarding sleep quality assessment, RA group had significantly higher levels of insomnia than the control group (Insomnia Severity Index median (IQR) was 4.5 (0–15) versus 1 (0–3); p value = 0.013) and daytime sleepiness (Epworth Sleepiness Scale median (IQR) was 4 (1–11.25) versus 1 (0–3); p value = 0.002). RA patients showed significantly higher values of Pittsburgh Sleep Quality Index components as well as the global score indicating poor sleep quality. The 36-item short-form health survey domains, representing physical and mental health, were significantly lower among RA cases versus control subjects. Higher disease activity was positively correlated with anxiety, depression, insomnia, sleep quality, sleep efficiency, and daytime dysfunction, while negatively correlated with all domains of the 36-item short-form health survey.

Conclusions
RA patients have increased anxiety and depression levels in addition to poor sleep quality. High disease activity is linked to increased anxiety and depression levels, impaired quality of life, and poor sleep quality.