bluuebunny/crossref_metadata_2025_split huggingface dataset:
Controlled release evaluation of paracetamol loaded amine functionalized mesoporous silica KCC1 compared to microcrystalline cellulose based tablets
Authors: Pishnamazi Marieh , Hafizi Hamid , Pishnamazi Mahboubeh , Marjani Azam , Shirazian Saeed , Walker Gavin M. 
Published: January 2021

AbstractIn the pharmaceutical manufacturing, drug release behavior development is remained as one of the main challenges to improve the drug effectiveness. Recently, more focus has been done on using mesoporous silica materials as drug carriers for prolonged and superior control of drug release in human body. In this study, release behavior of paracetamol is developed using drug-loaded KCC-1-NH2 mesoporous silica, based on direct compaction method for preparation of tablets. The purpose of this study is to investigate the utilizing of pure KCC-1 mesoporous silica (KCC-1) and amino functionalized KCC-1 (KCC-1-NH2) as drug carriers in oral solid dosage formulations compared to common excipient, microcrystalline cellulose (MCC), to improve the control of drug release rate by manipulating surface chemistry of the carrier. Different formulations of KCC-1 and KCC-NH2 are designed to investigate the effect of functionalized mesoporous silica as carrier on drug controlled-release rate. The results displayed the remarkable effect of KCC-1-NH2 on drug controlled-release in comparison with the formulation containing pure KCC-1 and formulation including MCC as reference materials. The pure KCC-1 and KCC-1-NH2 are characterized using different evaluation methods such as FTIR, SEM, TEM and N2 adsorption analysis.
Allele-specific expression of Parkinson’s disease susceptibility genes in human brain
Authors: Langmyhr Margrete , Henriksen Sandra Pilar , Cappelletti Chiara , van de Berg Wilma D. J. , Pihlstrøm Lasse , Toft Mathias 
Published: January 2021

AbstractGenome-wide association studies have identified genetic variation in genomic loci associated with susceptibility to Parkinson’s disease (PD), the most common neurodegenerative movement disorder worldwide. We used allelic expression profiling of genes located within PD-associated loci to identify cis-regulatory variation affecting gene expression. DNA and RNA were extracted from post-mortem superior frontal gyrus tissue and whole blood samples from PD patients and controls. The relative allelic expression of transcribed SNPs in 12 GWAS risk genes was analysed by real-time qPCR. Allele-specific expression was identified for 9 out of 12 genes tested (GBA, TMEM175, RAB7L1, NUCKS1, MCCC1, BCKDK, ZNF646, LZTS3, and WDHD1) in brain tissue samples. Three genes (GPNMB, STK39 and SIPA1L2) did not show significant allele-specific effects. Allele-specific effects were confirmed in whole blood for three genes (BCKDK, LZTS3 and MCCC1), whereas two genes (RAB7L1 and NUCKS1) showed brain-specific allelic expression. Our study supports the hypothesis that changes to the cis-regulation of gene expression is a major mechanism behind a large proportion of genetic associations in PD. Interestingly, allele-specific expression was also observed for coding variants believed to be causal variants (GBA and TMEM175), indicating that splicing and other regulatory mechanisms may be involved in disease development.
Establishment of a long-term stable β-cell line and its application to analyze the effect of Gcg expression on insulin secretion
Authors: Miyazaki Satsuki , Tashiro Fumi , Tsuchiya Takashi , Sasaki Kazuki , Miyazaki Jun-ichi 
Published: January 2021

AbstractA pancreatic β-cell line MIN6 was previously established in our lab from an insulinoma developed in an IT6 transgenic mouse expressing the SV40 T antigen in β-cells. This cell line has been widely used for in vitro analysis of β-cell function, but tends to lose the mature β-cell features, including glucose-stimulated insulin secretion (GSIS), in long-term culture. The aim of this study was to develop a stable β-cell line that retains the characteristics of mature β-cells. Considering that mice derived from a cross between C3H and C57BL/6 strains are known to exhibit higher insulin secretory capacity than C57BL/6 mice, an IT6 male mouse of this hybrid background was used to isolate insulinomas, which were independently cultured. After 7 months of continuous culturing, we obtained the MIN6-CB4 β-cell line, which stably maintains its GSIS. It has been noted that β-cell lines express the glucagon (Gcg) gene at certain levels. MIN6-CB4 cells were utilized to assess the effects of differentialGcgexpression on β-cell function. Our data show the functional importance ofGcgexpression and resulting basal activation of the GLP-1 receptor in β-cells. MIN6-CB4 cells can serve as an invaluable tool for studying the regulatory mechanisms of insulin secretion, such as the GLP-1/cAMP signaling, in β-cells.
Vision-based egg quality prediction in Pacific bluefin tuna (Thunnus orientalis) by deep neural network
Authors: Ienaga Naoto , Higuchi Kentaro , Takashi Toshinori , Gen Koichiro , Tsuda Koji , Terayama Kei 
Published: January 2021

AbstractClosed-cycle aquaculture using hatchery produced seed stocks is vital to the sustainability of endangered species such as Pacific bluefin tuna (Thunnus orientalis) because this aquaculture system does not depend on aquaculture seeds collected from the wild. High egg quality promotes efficient aquaculture production by improving hatch rates and subsequent growth and survival of hatched larvae. In this study, we investigate the possibility of a simple, low-cost, and accurate egg quality prediction system based only on photographic images using deep neural networks. We photographed individual eggs immediately after spawning and assessed their qualities, i.e., whether they hatched normally and how many days larvae survived without feeding. The proposed system predicted normally hatching eggs with higher accuracy than human experts. It was also successful in predicting which eggs would produce longer-surviving larvae. We also analyzed the image aspects that contributed to the prediction to discover important egg features. Our results suggest the applicability of deep learning techniques to efficient egg quality prediction, and analysis of early developmental stages of development.
The antimicrobial capacity of Cistus salviifolius and Punica granatum plant extracts against clinical pathogens is related to their polyphenolic composition
Authors: Álvarez-Martínez Francisco Javier , Rodríguez Juan Carlos , Borrás-Rocher Fernando , Barrajón-Catalán Enrique , Micol Vicente 
Published: January 2021

AbstractAntimicrobial resistance poses a serious threat to human health worldwide. Plant compounds may help to overcome antibiotic resistance due to their potential resistance modifying capacity. Several botanical extracts and pure polyphenolic compounds were screened against a panel of eleven bacterial isolates with clinical relevance. The two best performing agents, Cistus salviifolius (CS) and Punica granatum (GP) extracts, were tested against 100 Staphylococcus aureus clinical isolates, which resulted in average MIC50 values ranging between 50–80 µg/mL. CS extract, containing hydrolyzable tannins and flavonoids such as myricetin and quercetin derivatives, demonstrated higher activity against methicillin-resistant S. aureus isolates. GP extract, which contained mostly hydrolyzable tannins, such as punicalin and punicalagin, was more effective against methicillin-sensitive S. aureus isolates. Generalized linear model regression and multiple correspondence statistical analysis revealed a correlation between a higher susceptibility to CS extract with bacterial resistance to beta-lactam antibiotics and quinolones. On the contrary, susceptibility to GP extract was related with bacteria sensitive to quinolones and oxacillin. Bacterial susceptibility to GP and CS extracts was linked to a resistance profile based on cell wall disruption mechanism. In conclusion, a differential antibacterial activity against S. aureus isolates was observed depending on antibiotic resistance profile of isolates and extract polyphenolic composition, which may lead to development of combinatorial therapies including antibiotics and botanical extracts.
Generation of proliferating human adult hepatocytes using optimized 3D culture conditions
Authors: Rose Sophie , Ezan Frédéric , Cuvellier Marie , Bruyère Arnaud , Legagneux Vincent , Langouët Sophie , Baffet Georges 
Published: January 2021

AbstractGenerating the proliferation of differentiated normal adult human hepatocytes is a major challenge and an expected central step in understanding the microenvironmental conditions that regulate the phenotype of human hepatocytes in vitro. In this work, we described optimized 3D culture conditions of primary human hepatocytes (PHH) to trigger two waves of proliferation and we identified matrix stiffness and cell–cell interactions as the main actors necessary for this proliferation. We demonstrated that DNA replication and overexpression of cell cycle markers are modulate by the matrix stiffness while PHH cultured in 3D without prior cellular interactions did not proliferate. Besides, we showed that PHH carry out an additional cell cycle after transient inhibition of MAPK MER1/2-ERK1/2 signaling pathway. Collagen cultured hepatocytes are organized as characteristic hollow spheroids able to maintain survival, cell polarity and hepatic differentiation for long-term culture periods of at least 28 days. Remarkably, we demonstrated by transcriptomic analysis and functional experiments that proliferating cells are mature hepatocytes with high detoxication capacities. In conclusion, the advanced 3D model described here, named Hepoid, is particularly relevant for obtaining normal human proliferating hepatocytes. By allowing concomitant proliferation and differentiation, it constitutes a promising tool for many pharmacological and biotechnological applications.
Time to peak and full width at half maximum in MR perfusion: valuable indicators for monitoring moyamoya patients after revascularization
Authors: Huang Adam , Lee Chung-Wei , Liu Hon-Man 
Published: January 2021

AbstractMoyamoya disease (MMD) is a chronic, steno-occlusive cerebrovascular disorder of unknown etiology. Surgical treatment is the only known effective method to restore blood flow to affected areas of the brain. However, there are lack of generally accepted noninvasive tools for therapeutic outcome monitoring. As dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) is the standard MR perfusion imaging technique in the clinical setting, we investigated a dataset of nineteen pediatric MMD patients with one preoperational and multiple periodic DSC MRI examinations for four to thirty-eight months after indirect revascularization. A rigid gamma variate model was used to derive two nondeconvolution-based perfusion parameters: time to peak (TTP) and full width at half maximum (FWHM) for monitoring transitional bolus delay and dispersion changes respectively. TTP and FWHM values were normalized to the cerebellum. Here, we report that 74% (14/19) of patients improve in both TTP and FWHM measurements, and whereof 57% (8/14) improve more noticeably on FWHM. TTP is in good agreement with Tmax in estimating bolus delay. Our study data also suggest bolus dispersion estimated by FWHM is an additional, informative indicator in pediatric MMD monitoring.
Differential effects of sodium chloride and monosodium glutamate on kidney of adult and aging mice
Authors: Celestino Michele , Balmaceda Valdez Valeria , Brun Paola , Castagliuolo Ignazio , Mucignat-Caretta Carla 
Published: January 2021

AbstractMonosodium Glutamate (MSG) is used as flavour enhancer, with potential beneficial effects due to its nutritional value. Given the decline in kidney functions during aging, we investigated the impact of MSG voluntary intake on the kidney of male mice, aged 6 or 18 months. For 2 months, they freely consumed water (control group), sodium chloride (0.3% NaCl) or MSG (1% MSG) in addition to standard diet. Young animals consuming sodium chloride presented signs of proteinuria, hyperfiltration, enhanced expression and excretion of Aquaporin 2 and initial degenerative reactions suggestive of fibrosis, while MSG-consuming mice were similar to controls. In old mice, aging-related effects including proteinuria and increased renal corpuscle volume were observed in all groups. At an advanced age, MSG caused no adverse effects on the kidney compared to controls, despite the presence of a sodium moiety, similar to sodium chloride. These data show that prolonged MSG intake in mice has less impact on kidney compared to sodium chloride, that already in young animals induced some effects on kidney, possibly related to hypertension.
Ephrin A4-ephrin receptor A10 signaling promotes cell migration and spheroid formation by upregulating NANOG expression in oral squamous cell carcinoma cells
Authors: Chen Yu-Lin , Yen Yi-Chen , Jang Chuan-Wei , Wang Ssu-Han , Huang Hsin-Ting , Chen Chung-Hsing , Hsiao Jenn-Ren , Chang Jang-Yang , Chen Ya-Wen 
Published: January 2021

AbstractEphrin type-A receptor 10 (EPHA10) has been implicated as a potential target for breast and prostate cancer therapy. However, its involvement in oral squamous cell carcinoma (OSCC) remains unclear. We demonstrated that EPHA10 supports in vivo tumor growth and lymphatic metastasis of OSCC cells. OSCC cell migration, epithelial mesenchymal transition (EMT), and sphere formation were found to be regulated by EPHA10, and EPHA10 was found to drive expression of some EMT- and stemness-associated transcription factors. Among EPHA10 ligands, exogenous ephrin A4 (EFNA4) induced the most OSCC cell migration and sphere formation, as well as up-regulation of SNAIL, NANOG, and OCT4. These effects were abolished by extracellular signal-regulated kinase (ERK) inhibition and NANOG knockdown. Also, EPHA10 was required for EFNA4-induced cell migration, sphere formation, and expression of NANOG and OCT4 mRNA. Our microarray dataset revealed that EFNA4 mRNA expression was associated with expression of NANOG and OCT4 mRNA, and OSCC patients showing high co-expression of EFNA4 with NANOG or OCT4 mRNA demonstrated poor recurrence-free survival rates. Targeting forward signaling of the EFNA4-EPHA10 axis may be a promising therapeutic approach for oral malignancies, and the combination of EFNA4 mRNA and downstream gene expression may be a useful prognostic biomarker for OSCC.
Intermedin facilitates hepatocellular carcinoma cell survival and invasion via ERK1/2-EGR1/DDIT3 signaling cascade
Authors: Xiao Fei , Li Hongyu , Feng Zhongxue , Huang Luping , Kong Lingmiao , Li Min , Wang Denian , Liu Fei , Zhu Zhijun , Wei Yong’gang , Zhang Wei 
Published: January 2021

AbstractAs one of the most malignant cancer types, hepatocellular carcinoma (HCC) is highly invasive and capable of metastasizing to distant organs. Intermedin (IMD), an endogenous peptide belonging to the calcitonin family, has been suggested playing important roles in cancer cell survival and invasion, including in HCC. However, how IMD affects the behavior of HCC cells and the underlying mechanisms have not been fully elucidated. Here, we show that IMD maintains an important homeostatic state by activating the ERK1/2-EGR1 (early growth response 1) signaling cascade, through which HCC cells acquire a highly invasive ability via significantly enhanced filopodia formation. The inhibition of IMD blocks the phosphorylation of ERK1/2, resulting in EGR1 downregulation and endoplasmic reticulum stress (ER) stress, which is evidenced by the upregulation of ER stress marker DDIT3 (DNA damage-inducible transcript 3). The high level of DDIT3 induces HCC cells into an ER-stress related apoptotic pathway. Along with our previous finding that IMD plays critical roles in the vascular remodeling process that improves tumor blood perfusion, IMD may facilitate the acquisition of increased invasive abilities and a survival benefit by HCC cells, and it is easier for HCC cells to obtain blood supply via the vascular remodeling activities of IMD. According to these results, blockade of IMD activity may have therapeutic potential in the treatment of HCC.
CrAssphage and its bacterial host in cat feces
Authors: Li Yanpeng , Gordon Emilia , Shean Ryan C. , Idle Amanda , Deng Xutao , Greninger Alexander L. , Delwart Eric 
Published: January 2021

AbstractCrAssphages are a diverse group of related phages detected in human feces where they are the most prevalent and abundant prokaryotic virus. CrAssphages’ cellular host has been identified as the anaerobic Bacteroides intestinalis. CrAssphage has also been reported in non-human primates and environmental samples and has been proposed as a marker of human fecal contamination. Here we describe crAssphage DNA in a feline fecal sample. 95% of the ~ 100 Kb genome could be assembled and classified in genus 1 of the recently proposed Alphacrassvirinae subfamily. The cat origin of the fecal sample was confirmed by partial mitochondrial DNA sequencing. High levels of Bacteroides intestinalis DNA could also be detected in this cat’s feces. Fecal samples longitudinally collected over a 4-week period showed the continuous shedding of crAssphage DNA. We therefore report the first genome sequence-confirmed detection of crAssphage in fecal samples of a non-primate mammal.
Laser-induced melting of two-dimensional dusty plasma system in RF discharge
Authors: Vasilieva E. V. , Petrov O. F. , Vasiliev M. M. 
Published: January 2021

AbstractWe present a detailed analysis of experimental study, which shows clear evidence of a two-stage melting process of a quasi-two-dimensional dusty plasma system in a high-frequency gas discharge. We accurately calculated global parameters of the orientational and translational order, as well as their susceptibilities to determine two critical points, related to “solid-to-hexatic” and “hexatic-to-liquid” phase transitions. The nature of the emerging defects and changes in their mutual concentration, in addition to the estimate of core energy of free dislocations also counts in favor of the formation of an intermediate hexatic phase. These results are fully consistent with the Berezinsky–Kosterlitz–Thouless theory.
Serum fibroblast growth factor 21 levels after out of hospital cardiac arrest are associated with neurological outcome
Authors: Pekkarinen Pirkka T. , Skrifvars Markus B. , Lievonen Ville , Jakkula Pekka , Albrecht Laura , Loisa Pekka , Tiainen Marjaana , Pettilä Ville , Reinikainen Matti , Hästbacka Johanna 
Published: January 2021

AbstractFibroblast growth factor (FGF) 21 is a marker associated with mitochondrial and cellular stress. Cardiac arrest causes mitochondrial stress, and we tested if FGF 21 would reflect the severity of hypoxia-reperfusion injury after cardiac arrest. We measured serum concentrations of FGF 21 in 112 patients on ICU admission and 24, 48 and 72 h after out-of-hospital cardiac arrest with shockable initial rhythm included in the COMACARE study (NCT02698917). All patients received targeted temperature management for 24 h. We defined 6-month cerebral performance category 1–2 as good and 3–5 as poor neurological outcome. We used samples from 40 non-critically ill emergency room patients as controls. We assessed group differences with the Mann Whitney U test and temporal differences with linear modeling with restricted maximum likelihood estimation. We used multivariate logistic regression to assess the independent predictive value of FGF 21 concentration for neurologic outcome. The median (inter-quartile range, IQR) FGF 21 concentration was 0.25 (0.094–0.91) ng/ml in controls, 0.79 (0.37–1.6) ng/ml in patients at ICU admission (P < 0.001 compared to controls) and peaked at 48 h [1.2 (0.46–2.5) ng/ml]. We found no association between arterial blood oxygen partial pressure and FGF 21 concentrations. We observed with linear modeling an effect of sample timepoint (F 5.6, P < 0.01), poor neurological outcome (F 6.1, P = 0.01), and their interaction (F 3.0, P = 0.03), on FGF 21 concentration. In multivariate logistic regression analysis, adjusting for relevant clinical covariates, higher average FGF 21 concentration during the first 72 h was independently associated with poor neurological outcome (odds ratio 1.60, 95% confidence interval 1.10–2.32). We conclude that post cardiac arrest patients experience cellular and mitochondrial stress, reflected as a systemic FGF 21 response. This response is higher with a more severe hypoxic injury but it is not exacerbated by hyperoxia.
The impact of Pain-related emotions on migraine
Authors: Kim Seonghoon , Bae Dae-Woong , Park Sang-Gue , Park Jeong-Wook 
Published: January 2021

AbstractThe response to pain is highly individual and can be influenced by complex emotional perception. This study aims to investigate the status of the pain-related emotional response, and the influence on headache characteristics and disability in migraine. We studied the pain-related emotional response in 145 consecutive migraine patients using the Pain Anxiety Symptoms Scale (PASS), the Pain Catastrophizing Scale (PCS), and the Pain Sensitivity Questionnaire (PSQ) and compared them with 106 healthy controls. We investigated the relationship between emotional factors and migraine characteristics. The effect of pain-related emotion on migraine-related disability assessed with the Headache Impact Test-6 (HIT-6) and the Migraine Disability Assessment (MIDAS). Migraine patients showed significantly higher scores on total PASS (p < 0.001), PCS (p < 0.001) and PSQ (p = 0.002) compared to the healthy controls. The HIT-6 was weakly correlated with PASS (r = 0.390,p < 0.001) and PCS (r = 0.354,p < 0.001). PASS-Total (p = 0.001), headache frequency (p = 0.003), and HADS-Anxiety (p = 0.028) were independent variables associated with HIT-6. Headache frequency (p < 0.001) was an independent variable associated with MIDAS. The structural equation model indicated that headache severity has direct loading on emotion and subsequently influenced migraine-related disability. Disability has a significant effect on the frequency of abortive medication use. Migraine patients have altered emotional responses to pain perception. Pain-related anxiety made an important contribution to headache-related disability. The present results suggest that the management of disability by considering various pain-related emotional factors may be necessary for the therapeutic aspects of migraine.
Domain randomization-enhanced deep learning models for bird detection
Authors: Mao Xin , Chow Jun Kang , Tan Pin Siang , Liu Kuan-fu , Wu Jimmy , Su Zhaoyu , Cheong Ye Hur , Ooi Ghee Leng , Pang Chun Chiu , Wang Yu-Hsing 
Published: January 2021

AbstractAutomatic bird detection in ornithological analyses is limited by the accuracy of existing models, due to the lack of training data and the difficulties in extracting the fine-grained features required to distinguish bird species. Here we apply the domain randomization strategy to enhance the accuracy of the deep learning models in bird detection. Trained with virtual birds of sufficient variations in different environments, the model tends to focus on the fine-grained features of birds and achieves higher accuracies. Based on the 100 terabytes of 2-month continuous monitoring data of egrets, our results cover the findings using conventional manual observations, e.g., vertical stratification of egrets according to body size, and also open up opportunities of long-term bird surveys requiring intensive monitoring that is impractical using conventional methods, e.g., the weather influences on egrets, and the relationship of the migration schedules between the great egrets and little egrets.