bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacoepidemiological assessment of off-label drug use in pediatric ambulatory departments at four tertiary care hospital in Pakistan
Authors: Sharif Rabeea , Aamir Muhammad , Shakeel Faisal , Faisal Shah , Khan Jamshaid Ali 
Published: January 2021

Purpose: To assess the frequency and possible predictors of off-label drug use in ambulatory pediatric units of four tertiary healthcare institutions in a Pakistani city.Methods: A prospective study was conducted at the pediatric ambulatory department of four tertiary care hospitals of Peshawar, Pakistan. A total 1589 patients were included in the study which to evaluate their prescriptions for off-label drug use with the aid of Thomson Healthcare Micromedex DRUGDEX database.Results: A total of 79 different drugs were prescribed 5668 times to pediatric patients. A high rate of offlabel drug use (71.8 %) was observed in this study. Compared to corresponding reference categories, infants (OR 4.134, 95 % CI 2.076-8.235) and children (OR 1.857, 95 % CI 0.967-3.568) were more likely to receive off-label prescriptions. However, pediatric patients receiving less than four drugs (OR 0.414, 95 % CI 0.312-0.548) were less likely to receive off-label prescriptions.Conclusion: A high incidence of off-label drug use has been observed in the ambulatory pediatric population studied, especially in infants. More research is needed to identify and evaluate the contributory factors to off-label use of drugs in ambulatory pediatric population in developing countries to achieve optimal drug therapy for pediatrics.
Keywords: Pediatric population, Ambulatory, Off-label drug use
MiR-28-3p enhances healing of fracture via negative regulation of the target gene Sox6 and activation of PI3K/Akt signaling pathway
Authors: Li Wei , Dong Xin , Zhao Jian 
Published: January 2021

Purpose: To investigate the effect of miR-28-3p on fracture healing, and the involvement of Sox6 gene and PI3K/Akt signaling pathway in the process.Methods: Mouse osteoblast cell lines were cultured in vitro, and miR-28-3p over-expression and inhibitory plasmids were separately added to the medium. The corresponding control groups were set up. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to measure the mRNA expressions of the osteogenesis-related genes Col1a1, Col-Ⅱ and Col-X in osteoblasts. The protein expressions of Sox6, Col1a1, Col-Ⅱ, Col-X, PI3K, p-PI3K, Akt and p-Akt in rat cartilage tissue were determined with Western blotting assay.Results: The expression of Sox6 protein in the miR-28-3p over-expression group was significantly reduced, when compared with the miR-28 overexpression control, but Sox6 protein expression in the miR-28-3p inhibition group was significantly increased, relative to inhibition control group (p < 0.05). In the miR-28-3p over-expression and Sox6 over-expression groups, Col1a1 protein expression was significantly increased, while Col-Ⅱ and Col-X protein expressions decreased, when compared with the respective over-expression control group (p < 0.05). Over-expression of miR-28-3p markedly upregulated phosphorylation levels of PI3K and Akt, relative to over-expression control group, while miR-28-3p inhibition significantly downregulated the phosphorylations of PI3K and Akt, relative to the inhibition control group (p < 0.05).Conclusion: Over-expression of miR-28-3p may enhance the healing of fractures by induction of PI3K/Akt signaling route via negative regulation of the expression of Sox6 gene.
Keywords: MiR-28-3p, Sox6, PI3K/Akt signaling pathway, Fracture healing
ARPC4 gene silencing inhibits T24 cell invasion and metastasis via a mechanism involving Arp2/3/cofilin-1 signaling pathway
Authors: Pang Shunyi , Yao Zeqin , Wang Chao , Chen Guoqiang 
Published: January 2021

Purpose: To study the influence of ARPC4 gene silencing on human urinary bladder cancer (T24) cell proliferation, invasiveness and migration, and the mechanism(s) involved.Methods: Short interfering RNA (siRNA) ARPC4 silencing fragment was transfected into T24 cells. Transfection efficiency was measured with qRT-PCR. Cell proliferation, invasiveness and migratory potential were determined with CCK-8, Transwell invasion assay, and immunofluorescence assay,respectively. Protein expressions of ARPC4 and cofilin-1 were assayed using Western blotting.Results: Short interfering RNA (siRNA) silencing of ARPC4 gene led to the downregulation of mRNA and protein expressions of ARPC4 (t = 14.898, p < 0.05; t = 7.686, p < 0.05). It also significantly downregulated cofilin-1 protein, while inhibiting proliferative capacity, invasiveness and pseudopodiaformation capacity of T24 cells (t = 8.042, p < 0.05).Conclusion: The results obtained suggest that ARPC4 gene silencing inhibits T24 cell invasion and metastasis via a mechanism involving regulation of the Arp2/3/cofilin-1 signaling route. This provides new leads for gene therapy.
Keywords: ARPC4, Bladder carcinoma, Gene silencing, Invasiveness, Cell proliferation
Crassifoside H ameliorates depressant behavior in chronic unpredictable mild stress rats by improving HPA axis dysfunction and inhibiting inflammation in hippocampus
Authors: Li Huina , Wu Kefan , Zhang Yue , Li Ning , Wang Kaijin 
Published: January 2021

Purpose: To investigate the antidepressant mechanism of action of Crassifoside H (CH) from the rhizomes of Curculigo glabrescens (Hypoxidaceae) in chronic unpredictable mild stress (CUMS)-induced rats.Methods: CUMS-induced rat depressant model was established. Behavioral tests, viz, sucrose preference test (SPT), open field test (OFT) and forced swimming test (FST) were applied to assess the antidepressant effect of CH. Enzyme linked immunosorbent assay (ELISA) was used to assess thelevels of corticosterone (CORT), TNF-α and IL-1β in serum. Protein expressions of TNF-α, IL-1β and NLRP3 in rat hippocampus were determined by Western blot.Results: Crassifoside H significantly ameliorated CUMS-induced depressant-like behavior as the serum CORT level of CUMS rats. CH remarkably decreased TNF-α and IL-1β levels in serum and hippocampus of CUMS rats. Moreover, Crassifoside H significantly inhibited NLRP3 activation inhippocampus.Conclusion: The findings demonstrate that Crassifoside H has antidepressant effect on CUMS rats. The mechanism of action of CH may be at least partly due to the improvement of hypothalamic-pituitaryadrenal (HPA) axis dysfunction by decreasing serum CORT. These findings suggest that Crassifoside H has a therapeutic potential for the management of depression.
Keywords: Crassifoside H, Antidepression, Curculigo glabrescens, Hypoxidaceae, Hypothalamicpituitary- adrenal axis, Inflammation, Corticosterone
Effect of Abelmoschus esculentus (okra)-based diet on streptozotocin-induced diabetes mellitus in adult Wistar rats
Authors: Uadia Patrick O. , Imagbovomwan Isaac O. , Oriakhi Kelly , Eze Ikechi G. 
Published: January 2021

Purpose: To evaluate the effects of an okra-based diet on streptozotocin-induced diabetes mellitus in adult Wistar rats and its mechanism of action.Methods: Wistar rats (6) were administered streptozotocin (50 mg/kg ip) after an overnight fast. Upon confirmation of diabetes mellitus, the animals were fed ad libitum for 21 days with formulated okrabased test diet in place of normal diet. The rats treated similarly with streptozotocin and fed ad libitum with the normal diet served as diabetic control while rats fed on normal diet and not treated with streptozotocin served as the negative control. Thereafter, the rats were sacrificed, fasting bloodcollected and analysed for glucose concentration and biochemical parameters. Pancreas was also excised for histopathological studies.Results: There was a significant increase in body weight, HDL-cholesterol (p< 0.05) but significant decrease in blood glucose (p < 0.05), serum total cholesterol, triglyceride, LDL-cholesterol and VLDLcholesterol concentrations in the okra-fed diabetic treated rats when compared to the diabetic control group. Furthermore, superoxide dismutase activity (SOD) was significantly higher in the diabetic control, and reduced significantly when fed with okra-based diet (p < 0.05). Catalase (CAT) activity was significantly (p < 0.05) decreased in diabetic control and treated group, whereas it was significantly (p < 0.05) increased in normal control rats. There was a significant (p < 0.05) decrease in reduced glutathione levels. The significant (p< 0.05) increase in malondialdehyde in the diabetic group was significantly decrease in the diabetic rats fed with okra-diet. Also serum insulin level was significantly (p < 0.05) increased and serum α amylase activity was significantly (p < 0.05) decrease in the diabetic treated rats. Histology results show that there was damage to the β cells of the pancreas in the diabetic control when compared to normal control, but rats fed okra diet was able to regenerate endocrine β cells.Conclusion: Okra-based diet lowers hyperglycaemia as well as regenerate/repair endocrine β-cells and exocrine tissues of the pancreas damage by streptozotocin
Keywords: Abelmoschus esculentus, Diabetes mellitus, anti-diabetic, Insulin, α-amylase, Mechanism
Inhibition of miR-665 alleviates neuropathic pain by targeting SOCS1
Authors: Lin Yongqiang , Li Mengjia , Rao Gaofeng , Zhang Wenfu , Chen Xuyan 
Published: January 2021

Purpose: To investigate the effect of miR-665 in neuropathic pain and the possible molecular mechanism involved.Methods: A neuropathic pain model was established using chronic constriction injury (CCI) methods in Sprague Dawley (SD) rats. Mechanical and thermal hyperalgesia were measured using paw withdrawal threshold (PWT) and paw withdrawal latency (PWL), respectively. The inflammation response was determined by assessing the production of inflammation factors. The target relationship of miR-665 and suppressor of cytokine signaling 1 (SOCS1) was verified by luciferase assay.Results: In the CCI rat model, PWT and PWL decreased following treatment with miR-665 (p < 0.01). MiR-665 was elevated in the spinal cord and microglia of CCI rats at different time points (p < 0.01). Down-regulation of miR-665 increased PWT and PWL and inhibited the production of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in CCI rats (p < 0.01). Luciferase assay results indicate that SOCS1 was the target of miR-665 (p < 0.01). SOCS1 decreased in CCI rats (p < 0.01) after treatment with miR-665. MiR-665 negatively regulated the expression of SOCS1 (p < 0.01). Down-regulation of SOCS1 reversed the alleviating effect of decreased miR-665 on pain sensitivity and inflammationresponse (p < 0.01).Conclusion: Down-regulation of miR-665 alleviates neuropathic pain by targeting SOCS1, and hence making miR-665 a promising therapeutic target for neuropathic pain.
Keywords: MiR-665, SOCS1, Neuropathic pain, CCI, Spinal cord
Quinolinol-platinum (II) complex suppresses survival and invasion of laryngeal cancer cells via targeting YESassociated protein expression
Authors: Xie Baotong , Li Tao 
Published: January 2021

Purpose: To investigate the anti-proliferative potential of quinolinol-platinum (II) complex {QN-Pt (II)} in laryngeal cancer cells.Methods: The inhibitory potential of QN-Pt (II) on the proliferation of laryngeal cancer cells was determined using 2H-tetrazolium, 2-(4,5-dimethyl-2-thiazolyl)-3,5-diphenyl bromide (MTT) and colony formation assays. Inhibition of cell migration was determined using wound-healing assay, while changes in LC3-II and p62 expressions were assessed by western blotting.Results: QN-Pt (II) inhibited the viability of TU212 and M4e laryngeal cancer cells in the concentration range of 2 to 10 μM (p < 0.05). Moreover, it suppressed the colony formation potential and migration of TU212 and M4e cells. The QN-Pt (II) treatment increased the proportion of TU212 and M4e cells in G1/G0 phase of the cell cycle, but decreased the cell proportion in S and G2/M phase (p < 0.05). Treatment with 10 μM QN-Pt (II) increased the expression of LC3-II, but downregulated P62 expression in TU212 and M4e cells. The expression of Yes-associated protein was inhibited in TU212 and M4e cells on treatment with QN-Pt (II). However, transfection of YAP-cDNA into TU212 and M4e cells reversed the inhibitory effect of QN-Pt (II) on cell proliferation (p < 0.05). Moreover, YAP-cDNA transfection suppressed LC3II expression, inhibited YAP phosphorylation and promoted P62 expression in QN-Pt (II)-treated TU212 and M4e cells (p < 0.05).Conclusion: QN-Pt (II) suppresses laryngeal cancer cell viability via arrest of cell cycle and activation of apoptosis. Moreover, QN-Pt (II) targets Yes-associated protein in laryngeal cancer cells. Thus, QN-Pt (II) is a potential therapeutic agent for laryngeal cancer.
Keywords: Laryngeal cancer, YAP-protein, Apoptosis, Phosphorylation, Therapeutic agent
Valores de referencia de normalidad para la prueba del nivel de disconfort para la sensación de intensidad: resultados preliminares
Authors: Baraldi Knobel Keila Alessandra , Ganz Sanchez Tanit , Nizan Pfeilsticker Leopoldo , Stoller Guita 
Published: January 2021

El Nivel de Disconfort para la Sensación de Intensidad (LDL - Loudness Disconfort Level) es una prueba audiológica utilizada para la selección del nivel de saturación de audífonos, y más recientemente también indicada para la evaluación auditiva de personas con acúfenos e hipersensibilidad auditiva. Creemos necesaria la investigación y la determinación de los valores de referencia de normalidad para el LDL en individuos sin pérdida de audición, dado que la hipersensibilidad auditiva puede darse en individuos con umbrales auditivos normales. Los niveles de disconfort para las frecuencias 0,5 a 8 KHz en los dos oídos fueron investigados en situación de test y retest en 51 individuos con edad entre 18 y 25 años y con audición normal. La mediana para todas las frecuencias varió entre 92,5 y 100 dBNA, sin diferencias entre los oídos. Esta prueba mostró una alta variabilidad inter-sujetos y una alta consistencia entre test y retest. Concluimos que el LDL puede ser un buen instrumento para evaluar la evolución de pacientes con hipersensibilidad auditiva.
Determination of the effect of functional single-nucleotide polymorphisms associated with glycerolipid synthesis on intramuscular fat deposition in Korean cattle steer
Authors: Kim Hyeongrok , Oh Dong-Yep , Lee Yoonseok 
Published: January 2021

Abstract. Intramuscular fat deposition in the longissimus dorsi
muscle (LM) of Korean cattle steer is regulated by several genes related to
lipid metabolism. One of these genes encodes the enzyme bovine
glycerol-3-phosphate acyltransferase, mitochondrial (GPAM), which is located on
the mitochondrial outer membrane and catalyzes the initial and committed
step of glycerolipid synthesis in lipid metabolism of cattle. Previous
studies have shown that the 3′-untranslated region (UTR) of the
GPAM is quite extended and contains a polyadenylation signal site, erythroid
15-lipoxygenase differentiation control elements (15-LOX-DICEs), and
cytoplasmic polyadenylation elements (CPEs) that affect the regulation of
triacylglycerol synthesis. Therefore, the aim of this study was to
identify single-nucleotide polymorphisms (SNPs) related to the regulation of
glycerolipid synthesis in the 3′-UTR of GPAM and to verify the function
of SNPs affecting the deposition of intramuscular fat in Korean cattle
steer. In the present study, 11 SNPs were discovered in the 3′-UTR
of GPAM. Among these SNPs, g.54853A>G, g.55441A>G, and
g.55930C>T were significantly associated with marbling score in
a Korean cattle steer population and were strongly correlated with each other
within the GPAM gene. Furthermore, based on the results predicted by the
RNAhybrid program, four putative microRNAs (miRNAs) were identified, and the
above SNPs were found to present in the seed region of these miRNAs. These
miRNAs have a differential binding affinity for each allele of SNPs
g.54853A>G, g.55441A>G, and g.55930C>T.
The in vivo evidence of intramuscular fat deposition in the LM tissue showed that
these SNPs affected the regulation of intramuscular fat deposition in Korean
cattle steer. Thus, the g.54853A>G, g.55441A>G, and
g.55930C>T could be considered as causal mutations regulating
intramuscular fat deposition in Korean cattle steer.
Mapping Internet Celebrity on TikTok: Exploring Attention Economies and Visibility Labours
Authors: Abidin Crystal 
Published: January 2021

Abstract
With its rapid uptake among young people around the world, it is no surprise that TikTok is buzzing with cultures and practices of internet celebrity. Most notably, the platform is becoming more commercial and professionalized with the rise of TikTok Influencers, advertising networks, and agencies dedicated to monetizing content and embedding advertising on TikTok, and top TikTok Influencers raking in millions in income annually. However, little is known about the constitution of internet celebrity on TikTok yet, and existing models of internet celebrity on predecessor apps like Instagram and YouTube do not neatly apply to the distinctive terrain of TikTok. As such, this paper is an exploratory study into the makings of internet celebrity cultures on TikTok, focused on how attention economy and visibility labour practices have emerged as a result of the app’s features. With empirical data drawn from an extended period in-depth digital ethnography, and analyses and insights informed and supported by traditional anthropological participant observation and personal interviews with TikTok Influencers and agencies, this scoping paper offers a foundation for how celebrity, attention, and visibility are constituted across TikTok’s platform norms and features.
Null arguments and the inverse problem
Authors: Brattico Pauli 
Published: January 2021

Native speakers can reconstruct null arguments from a linear string of words where they are notoriously absent. How they solve this problem remains an unsolved and largely unaddressed issue. This article argues for a unified analysis of null arguments that relies on bare sensory input. The key assumption is that antecedent recovery takes place at the syntax-semantics interface if and only if the unvalued phi-features of a lexical element cannot be valued from the information available in the sensory input. The analysis unifies the theory of finite null subject pronouns and control and furthermore interprets null argument sentences without generating phrasal null pronouns. Evidence is considered from three languages with distinct null argument profiles: English (non-pro drop), Italian (consistent pro-drop) and Finnish (partial prodrop). Finally, the model was formalized and tested by means of a computer simulation.
TECHNOLOGICAL CHARACTERIZATION OF Mezilaurus itauba WOOD: APPLICATION AND MACHINING TESTS
Authors: Rodrigues Jaime Vieira , Barbosa Felipe Manzoni , Dreyer Jaqueline Beatriz Brixner , Schorr Luís Paulo Baldissera , Cuchi Tarik , Schlickmann Monique Bohora 
Published: January 2021

Brazil has several forest species that can be used for sustainable wood production. However, finding materials with technological quality is still a challenge. Wood is an excellent building material, however, there are few studies that have investigated the technological characterization, machining and processing of these species, including Mezilaurus itauba (Meisn.) Taub. Ex Mez. Thus, this study aimed to evaluate the technical characteristics and application potential of M. itauba wood from two distinct commercial lots, by analyzing its mechanical properties and performing machining tests. For this, static bending, dynamics and machining tests were carried out. The perpendicular compression tests of the evaluated fibers presented mean values of 9899.77 Mpa and 10670.74 Mpa for the elasticity module of lot 1 and lot 2, respectively. The average value observed for the L1 rupture module was 96.02 Mpa, while for L2 it was 113.85 Mpa. For the shear tests, low variation was observed between the specimens as well as between the evaluated lots. As for machining tests, M. itauba wood was classified as excellent for manufacturing furniture and internal openings. The M. itauba lots have acceptable mechanical strength, and the density is indicated for structural works, as well as for manufacturing furniture and interiors.
Opera as Liberal Education
Authors: Cuypers Stefaan E. 
Published: January 2021

Abstract
In this paper, I forge a strong educational bond between opera and the humanities: opera as liberal education, not just additional to or exemplary of. After rehearsing the well-known present-day criticisms of liberal education, I first make the diagnosis that the trouble with liberal education as teaching and learning the humanities is not so much its theoretical justification as its practical implementation. To neutralize the criticisms and to solve the problem of how to practically realize a theoretically defensible goal, my proposal is, next, to exploit opera as the vehicle of liberal education. Finally, I detail my proposal, offering suggestions about the way opera as liberal education can function on the curriculum.
Dances and Affordances: The Relationship between Dance Training and Conceptual Problem-Solving
Authors: Kronsted Christian , Gallagher Shaun 
Published: January 2021

Abstract
It is often argued by educators and researchers that access to the arts leads to increased academic performance. However, it is not clear why such access does so. We here use autopoietic enactive embodied cognition and ecological psychology to explain the relationship between dance training and conceptual problem-solving. We investigate four features of dance training that are beneficial for conceptual problem-solving and critical thinking: empathy, affordance exploration, attention change, and habit breaking. In each case, we will see that the embodied sensorimotor skills developed through dance practice are a form of affordance exploration that can carry over into the realm of conceptual problem-solving. Hence, since some of the skills needed in conceptual problem-solving are the same ones developed and trained through dancing, when we train dance, we also train some of the relevant skills for conceptual problem-solving and critical thinking.
Aesthetics of Romanesque Architecture
Authors: Kim Nanyoung 
Published: January 2021

AbstractArchitecture is a content area in art education that is not much investigated by art educators. Even less addressed is Romanesque architectural style. Based on direct experiences of visiting hundreds of Romanesque churches in France, Italy, and Spain; many years of teaching design courses; and subsequent research and visual analyses of photos, the author discusses the aesthetic merits of Romanesque architecture through design principles: unity by repetition, variety and contrast, proportion, hierarchical forms, and articulation. Unity, variety, and contrast are found in many modern design books, proportion, less so, but it was very important in the medieval period. Hierarchical forms and articulation are uniquely Romanesque. The author demonstrates that Romanesque builders possessed a great sense of design and creativity.