bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nobiletin enhances the development and quality of bovine embryos in vitro during two key periods of embryonic genome activation
Authors: Cañón-Beltrán Karina , Cajas Yulia N. , Peréz-Cerezales Serafín , Leal Claudia L. V. , Agirregoitia Ekaitz , Gutierrez-Adán Alfonso , González Encina M. , Rizos Dimitrios 
Published: June 2021

AbstractIn vitro culture can alter the development and quality of bovine embryos. Therefore, we aimed to evaluate whether nobiletin supplementation during EGA improves embryonic development and blastocyst quality and if it affects PI3K/AKT signaling pathway. In vitro zygotes were cultured in SOF + 5% FCS (Control) or supplemented with 5, 10 or 25 µM nobiletin (Nob5, Nob10, Nob25) or with 0.03% dimethyl-sulfoxide (CDMSO) during minor (2 to 8-cell stage; MNEGA) or major (8 to 16-cell stage; MJEGA) EGA phase. Blastocyst yield on Day 8 was higher in Nob5 (42.7 ± 1.0%) and Nob10 (44.4 ± 1.3%) for MNEGAphase and in Nob10 (61.0 ± 0.8%) for MJEGAphase compared to other groups. Mitochondrial activity was higher and lipid content was reduced in blastocysts produced with nobiletin, irrespective of EGA phase. The mRNA abundance ofCDK2, H3-3B, H3-3A, GPX1, NFE2L2andPPARαtranscripts was increased in 8-cells, 16-cells and blastocysts from nobiletin groups. Immunofluorescence analysis revealed immunoreactive proteins for p-AKT forms (Thr308 and Ser473) in bovine blastocysts produced with nobiletin. In conclusion, nobiletin supplementation during EGA has a positive effect on preimplantation bovine embryonic development in vitro and corroborates on the quality improvement of the produced blastocysts which could be modulated by the activation of AKT signaling pathway.
Estimated glomerular filtration rate and cardiometabolic risk factors in a longitudinal cohort of children
Authors: Xargay-Torrent Sílvia , Puerto-Carranza Elsa , Marcelo Irene , Mas-Parés Berta , Gómez-Vilarrubla Ariadna , Martínez-Calcerrada Jose-Maria , de Zegher Francis , Ibáñez Lourdes , López-Bermejo Abel , Bassols Judit 
Published: June 2021

AbstractAssociations between glomerular filtration rate (GFR) and cardiometabolic risk factors have been reported in adult and pediatric patients with renal disease. We aimed to assess the relationship between the estimated GFR (eGFR) and cardiometabolic risk factors in apparently healthy children. A longitudinal study in 401 asymptomatic Caucasian children (mean age 8 years) followed up after 4 years (mean age 12 years). GFR was estimated using the pediatric form of the FAS-equation. Children were classified at baseline according to their obesity status (normal weight and overweight) and according to eGFR levels (lower, average, and higher). The association of eGFR with anthropometric data [body mass index (BMI) and waist], blood pressure [systolic (SBP) and diastolic (DBP)], metabolic parameters [glucose, insulin resistance (HOMA-IR) and serum lipids], and renal ultrasonography measurements were assessed at baseline and follow-up. Baseline eGFR associated with several cardiometabolic risk factors at follow-up including higher waist, SBP, HOMA-IR, and kidney size (all p < 0.0001) in both normal weight and overweight children. In multivariate analysis, baseline eGFR was independently associated with follow-up HOMA-IR and SBP in both normal weight and overweight subjects (model R2: 0.188–0.444), and with follow-up BMI and waist in overweight subjects (model R2: 0.367–0.477). Moreover, children with higher filtration rates at baseline showed higher waist, SBP, DBP, HOMA-IR and renal size both at baseline and follow-up. eGFR is related to insulin resistance, blood pressure and adiposity measures in school-age children. eGFR may help to profile the cardiometabolic risk of children.
In vitro assessment and phase I randomized clinical trial of anfibatide a snake venom derived anti-thrombotic agent targeting human platelet GPIbα
Authors: Li Benjamin Xiaoyi , Dai Xiangrong , Xu Xiaohong Ruby , Adili Reheman , Neves Miguel Antonio Dias , Lei Xi , Shen Chuanbin , Zhu Guangheng , Wang Yiming , Zhou Hui , Hou Yan , Ni Tiffany , Pasman Yfke , Yang Zhongqiang , Qian Fang , Zhao Yanan , Gao Yongxiang , Liu Jing , Teng Maikun , Marshall Alexandra H. , Cerenzia Eric G. , Li Mandy Lokyee , Ni Heyu 
Published: June 2021

AbstractThe interaction of platelet GPIbα with von Willebrand factor (VWF) is essential to initiate platelet adhesion and thrombosis, particularly under high shear stress conditions. However, no drug targeting GPIbα has been developed for clinical practice. Here we characterized anfibatide, a GPIbα antagonist purified from snake (Deinagkistrodon acutus) venom, and evaluated its interaction with GPIbα by surface plasmon resonance and in silico modeling. We demonstrated that anfibatide interferds with both VWF and thrombin binding, inhibited ristocetin/botrocetin- and low-dose thrombin-induced human platelet aggregation, and decreased thrombus volume and stability in blood flowing over collagen. In a single-center, randomized, and open-label phase I clinical trial, anfibatide was administered intravenously to 94 healthy volunteers either as a single dose bolus, or a bolus followed by a constant rate infusion of anfibatide for 24 h. Anfibatide inhibited VWF-mediated platelet aggregation without significantly altering bleeding time or coagulation. The inhibitory effects disappeared within 8 h after drug withdrawal. No thrombocytopenia or anti-anfibatide antibodies were detected, and no serious adverse events or allergic reactions were observed during the studies. Therefore, anfibatide was well-tolerated among healthy subjects. Interestingly, anfibatide exhibited pharmacologic effects in vivo at concentrations thousand-fold lower than in vitro, a phenomenon which deserves further investigation.Trial registration: Clinicaltrials.gov NCT01588132.
Capicua regulates the development of adult-born neurons in the hippocampus
Authors: Hourigan Brenna , Balay Spencer D. , Yee Graydon , Sharma Saloni , Tan Qiumin 
Published: June 2021

AbstractNew neurons continuously arise from neural progenitor cells in the dentate gyrus of the adult hippocampus to support ongoing learning and memory formation. To generate functional adult-born neurons, neural progenitor cells proliferate to expand the precursor cell pool and differentiate into neurons. Newly generated cells then undergo postmitotic maturation to migrate to their final destination and develop elaborate dendritic branching, which allows them to receive input signals. Little is known about factors that regulate neuronal differentiation, migration, and dendrite maturation during adult hippocampal neurogenesis. Here, we show that the transcriptional repressor protein capicua (CIC) exhibits dynamic expression in the adult dentate gyrus. Conditional deletion of Cic from the mouse dentate gyrus compromises the adult neural progenitor cell pool without altering their proliferative potential. We further demonstrate that the loss of Cic impedes neuronal lineage development and disrupts dendritic arborization and migration of adult-born neurons. Our study uncovers a previously unrecognized role of CIC in neurogenesis of the adult dentate gyrus.
Development of a prediction model for mortality and cardiovascular outcomes in older adults taking into account AZGP1
Authors: Huscher Dörte , Ebert Natalie , Soerensen-Zender Inga , Mielke Nina , Schaeffner Elke , Schmitt Roland 
Published: June 2021

AbstractZinc-alpha 2-glycoprotein (AZGP1) is a serum protein with postulated functions in metabolism, cancer and cardiovascular disease. We developed new prediction models for mortality or cardiovascular events investigating the predictive potential of serum AZGP1 in a community-based cohort of older adults. We measured AZGP1 (μg/ml) in stored serum samples of 930 individuals of the Berlin Initiative Study, a prospective, population-based cohort of adults aged ≥ 70. We determined the prognostic potential of 20 knowledge-based predictors including AZGP1 for the outcomes of mortality or the composite endpoint of death and cardiovascular events (stroke, myocardial infarction (MI)) using Cox models; their model fit was evaluated with calibration plots, goodness-of-fit tests and c-indices. During median follow-up of 48.3 months, 70 incident strokes, 38 incident MI and 234 deaths occurred. We found no associations or correlations between AZGP1 and other candidate variables. After multivariable Cox regression with backward-selection AZGP1 remained in both models for mortality (HR = 0.44, 95%CI: 0.24–0.80) and for the composite endpoint (HR = 0.43, 95%CI: 0.23–0.82). Within newly built prediction models, we found that increased AZGP1 levels were predictive for lower risk of mortality and the composite endpoint in older adults. AZGP1 as a predictor warrants further validation in older adults.
Pirfenidone modifies hepatic miRNAs expression in a model of MAFLD/NASH
Authors: Escutia-Gutiérrez Rebeca , Rodríguez-Sanabria J. Samael , Monraz-Méndez C. Alejandra , García-Bañuelos Jesús , Santos-García Arturo , Sandoval-Rodríguez Ana , Armendáriz-Borunda Juan 
Published: June 2021

AbstractmiRNAs are involved in the development of metabolic associated fatty liver disease (MAFLD) and nonalcoholic steatohepatitis (NASH). We aimed to evaluate modifications by prolonged-release pirfenidone (PR-PFD) on key hepatic miRNAs expression in a MAFLD/NASH model. First, male C57BL/6J mice were randomly assigned into groups and fed with conventional diet (CVD) or high fat and carbohydrate diet (HFD) for 16 weeks. At the end of the eighth week, HFD mice were divided in two and only one half was treated with 300 mg/kg/day of PR-PFD mixed with food. Hepatic expression of miRNAs and target genes that participate in inflammation and lipid metabolism was determined by qRT-PCR and transcriptome by microarrays. Increased hepatic expression of miR-21a-5p, miR-34a-5p, miR-122-5p and miR-103-3p in MAFLD/NASH animals was reduced with PR-PFD. Transcriptome analysis showed that 52 genes involved in lipid and collagen biosynthesis and inflammatory response were downregulated in PR-PFD group. The expression of Il1b, Tnfa, Il6, Tgfb1, Col1a1, and Srebf1 were decreased in PR-PFD treated animals. MAFLD/NASH animals compared to CVD group showed modifications in gene metabolic pathways implicated in lipid metabolic process, inflammatory response and insulin resistance; PR-PFD reversed these modifications.
Effects of emission trading schemes on corporate carbon productivity and implications for firm-level responses
Authors: Jung Hail , Song Seyeong , Ahn Young-Hwan , Hwang Ha , Song Chang-Keun 
Published: June 2021

AbstractSince the South Korean government enacted the Emission Trading Scheme (ETS), companies have been striving to simultaneously improve productivity and reduce carbon emissions, which represent conflicting goals. We used firm-level emissions and corporate variables to investigate how ETS enactment has affected carbon productivity, which is a firm-level revenue created per unit of carbon emission. Results showed that firm-level carbon productivity increased significantly under the ETS, and such a trend was more evident for high-emission industries. We also found that companies with high carbon productivity were (1) profitable, (2) innovative, and (3) managed by CEOs with experience in environmental fields. These findings suggest that to achieve the conflicting goals of increasing corporate profits while reducing emissions, firms have to invest in green technologies, and such decisions are supported by green leadership. Our findings also have implications for corporate leadership; data highlight the importance of managing human resources and deploying investment policies to respond to ETS.
Glaucoma and mortality risk: findings from a prospective population-based study
Authors: Kühn Tilman , Rohrmann Sabine , Karavasiloglou Nena , Friedman David S. , Cassidy Aedin , Bärnighausen Till , Schuster Alexander K. , Nickels Stefan 
Published: June 2021

AbstractGlaucoma is a neurodegenerative disease with a structural change of the optic nerve head, leading to visual field defects and ultimately blindness. It has been proposed that glaucoma is associated with increased mortality, but previous studies had methodological limitations (selective study samples, lack of data on potential confounders, self-reported or secondary data on glaucoma diagnoses). We evaluated the association between diagnosed glaucoma and mortality in the population-based National Health and Nutrition Examination Survey (NHANES), a representative health survey in the United States. The survey cycles 2005–2006 and 2007–2008 included an extensive ophthalmic examination with fundus photography, which were used to derive standardized glaucoma diagnoses. Risk of all-cause mortality was assessed with multivariable Cox proportional hazards regression models accounting for the complex survey design of NHANES. Time to death was calculated from the examination date to date of death or December 31, 2015 whichever came first. 5385 participants (52.5% women) were eligible, of which 138 had glaucoma at baseline, and 833 died during follow-up. Participants with glaucoma were more likely to be older than those without glaucoma (mean age 69.9 vs. 56.0 years). Mean follow-up time was 8.4 years for participants with glaucoma, and 8.6 years for participants without glaucoma. Glaucoma was associated with increased mortality in an unadjusted Cox regression model (hazard ratio 2.06, 95% confidence interval 1.16 to 3.66), but the association was no longer statistically significant after adjusting for age and sex (hazard ratio 0.74, 95% confidence interval 0.46 to 1.17). Additional adjustment for a range of potential confounders did not significantly change the results. In this representative population-based study, we found no evidence of increased mortality risk in glaucoma patients.
Molecular simulation of gases competitive adsorption in lignite and analysis of original CO desorption
Authors: Zhang Jing , Wang Jiren , Zhang Chunhua , Li Zongxiang , Zhu Jinchao , Lu Bing 
Published: June 2021

AbstractTo study the adsorption characteristics of CO, CO2, N2, O2, and their binary-components in lignite coal, reveal the influence of CO2 or N2 injection and air leakage on the desorption of CO in goafs, a lignite model (C206H206N2O44) was established, and the supercell structure was optimized under temperatures of 288.15–318.15 K for molecular simulation. Based on molecular dynamics, the Grand Canonical Monte Carlo method was used to simulate the adsorption characteristics and the Langmuir equation was used to fit the adsorption isotherms of gases. The results show that for single-components, the order of adsorption capacity is CO2 > CO > O2 > N2. For binary-components, the competitive adsorption capacities of CO2 and CO are approximate. In the low-pressure zone, the competitive adsorption capacity of CO2 is stronger than that of CO, and the CO is stronger than N2 or O2. From the simulation, it can be seen that CO2, N2 or O2 will occupy adsorption sites, causing CO desorption. Therefore, to prevent the desorption of the original CO in the goaf, it is not suitable to use CO2 or N2 injection for fire prevention, and the air leakage at the working faces need to be controlled.
Longer DNA exhibits greater potential for cell-free gene expression
Authors: Nishio Takashi , Yoshikawa Yuko , Yoshikawa Kenichi , Sato Shin-ichi 
Published: June 2021

AbstractCell-free gene expression systems have been valuable tools for understanding how transcription/translation can be regulated in living cells. Many studies have investigated the determining factors that affect gene expression. Here we report the effect of the length of linearized reporter DNAs encoding the firefly luciferase gene so as to exclude the influence of supercoiling. It is found that longer DNA molecules exhibit significantly greater potency in gene expression; for example, the expression level for DNA with 25.7 kbp is 1000-times higher than that for DNA of 1.7 kbp. AFM observation of the DNA conformation indicates that longer DNA takes shrunken conformation with a higher segment density in the reaction mixture for gene expression, in contrast to the stiff conformation of shorter DNA. We propose an underlying mechanism for the favorable effect of longer DNA on gene expression in terms of the enhancement of access of RNA polymerase to the shrunken conformation. It is expected that the enhancement of gene expression efficiency with a shrunken DNA conformation would also be a rather general mechanism in living cellular environments.
Football and team handball training postpone cellular aging in women
Authors: Hagman Marie , Fristrup Bjørn , Michelin Rémi , Krustrup Peter , Asghar Muhammad 
Published: June 2021

AbstractSeveral hallmarks of aging have been identified and examined separately in previous exercise studies. For the first time, this study investigates the effect of lifelong regular exercise in humans on two of the central aging hallmarks combined. This cross-sectional study involved 129 healthy, non-smoking women, including young elite football players (YF, n = 29), young untrained controls (YC, n = 30), elderly team handball players (EH, n = 35) and elderly untrained controls (EC, n = 35). From a resting blood sample, mononuclear cells (MNCs) were isolated and sorted into monocytes and lymphocytes. Telomere length, mitochondrial (mtDNA) copy number and key regulators of mitochondrial biogenesis and function (PGC-1α and PGC-1β expression) were measured using quantitative polymerase chain reaction (qPCR). Overall, young women showed significantly longer telomeres and higher PGC-1α and PGC-1β expression, but lower mtDNA copy number compared to elderly subjects. A multivariate analysis showed that YF had 22–24% longer telomeres in lymphocytes and MNCs compared to YC. In addition, YF showed 19–20% higher mtDNA copy number in lymphocytes and MNCs compared to YC. The two young groups did not differ in PGC-1α and PGC-1β expression. EH showed 14% lower mtDNA copy number in lymphocytes compared to EC, but 3.4-fold higher lymphocyte PGC-1α expression compared to EC. In MNCs, EH also showed 1.4–1.6-fold higher PGC-1α and PGC-1β expression. The two elderly groups did not differ in telomere length. Elite football training and lifelong team handball training are associated with anti-aging mechanisms in leukocytes in women, including maintenance of telomere length and superior mitochondrial characteristics.
Differences in plasma microRNA content impair microRNA-based signature for breast cancer diagnosis in cohorts recruited from heterogeneous environmental sites
Authors: Uyisenga Jeanne P. , Debit Ahmed , Poulet Christophe , Frères Pierre , Poncin Aurélie , Thiry Jérôme , Mutesa Leon , Jerusalem Guy , Bours Vincent , Josse Claire 
Published: June 2021

AbstractCirculating microRNAs are non-invasive biomarkers that can be used for breast cancer diagnosis. However, differences in cancer tissue microRNA expression are observed in populations with different genetic/environmental backgrounds. This work aims at checking if a previously identified diagnostic circulating microRNA signature is efficient in other genetic and environmental contexts, and if a universal circulating signature might be possible. Two populations are used: women recruited in Belgium and Rwanda. Breast cancer patients and healthy controls were recruited in both populations (Belgium: 143 primary breast cancers and 136 healthy controls; Rwanda: 82 primary breast cancers and 73 healthy controls; Ntot = 434), and cohorts with matched age and cancer subtypes were compared. Plasmatic microRNA profiling was performed by RT-qPCR. Random Forest was used to (1) evaluate the performances of the previously described breast cancer diagnostic tool identified in Belgian-recruited cohorts on Rwandan-recruited cohorts and vice versa; (2) define new diagnostic signatures common to both recruitment sites; (3) define new diagnostic signatures efficient in the Rwandan population. None of the circulating microRNA signatures identified is accurate enough to be used as a diagnostic test in both populations. However, accurate circulating microRNA signatures can be found for each specific population, when taken separately.
Potential adverse drug events and its predictors among hospitalized patients at medical center in Ethiopia: a prospective observational study
Authors: Sahilu Tamiru , Getachew Mestawet , Melaku Tsegaye , Sheleme Tadesse , Abu Duresa , Zewdu Tesfu 
Published: June 2021

AbstractPotential adverse drug event (PADE) is a medication error with the potential to cause associate degree injury however that does not cause any injury, either due to specific circumstances, chance, or as a result of the error being intercepted and corrected. This study aimed to assess the incidence, contributing factors, predictors, severity, and preventability of PADEs among hospitalized adult patients at Jimma Medical Center. A prospective observational study was conducted among hospitalized adult patients at a tertiary hospital in Ethiopia. Logistic regression was performed to identify factors predicting PADE occurrence. P-value < 0.05 was considered for statistical significance. A total of 319 patients were included. About 50.5% of them were females. The mean ± SD age of the participants was 43 ± 17.6 years. Ninety-four PADEs were identified. Number of medications (adjusted OR = 5.12; 95% CI: 2.01–13.05; p = 0.001), anticoagulants (adjusted OR = 2.51; 95% CI: 1.22–5.19; p = 0.013), anti-seizures (adjusted OR = 21.96; 95% CI: 6.57–73.39; p < 0.0001), anti-tuberculosis (adjusted OR = 2.2; 95% CI: 1.002–4.59, p = 0.049), and Elixhauser comorbidity Index ≤ 15 (adjusted OR = 6.24; 95% CI: 1.48–26.25, p = 0.013) were independent predictors of PADEs occurrence. About one-third of patients admitted to the hospital experienced PADEs.
BET inhibitor suppresses migration of human hepatocellular carcinoma by inhibiting SMARCA4
Authors: Choi Hae In , An Ga Yeong , Baek Mina , Yoo Eunyoung , Chai Jin Choul , Lee Young Seek , Jung Kyoung Hwa , Chai Young Gyu 
Published: June 2021

AbstractHepatocellular carcinoma (HCC) is one of the most prevalent and poorly responsive cancers worldwide. Bromodomain and extraterminal (BET) inhibitors, such as JQ1 and OTX-015, inhibit BET protein binding to acetylated residues in histones. However, the physiological mechanisms and regulatory processes of BET inhibition in HCC remain unclear. To explore BET inhibitors’ potential role in the molecular mechanisms underlying their anticancer effects in HCC, we analyzed BET inhibitor-treated HCC cells’ gene expression profiles with RNA-seq and bioinformatics analysis. BET inhibitor treatment significantly downregulated genes related to bromodomain-containing proteins 4 (BRD4), such as ACSL5, SLC38A5, and ICAM2. Importantly, some cell migration-related genes, including AOC3, CCR6, SSTR5, and SCL7A11, were significantly downregulated. Additionally, bioinformatics analysis using Ingenuity Knowledge Base Ingenuity Pathway Analysis (IPA) revealed that SMARCA4 regulated migration response molecules. Furthermore, knockdown of SMARCA4 gene expression by siRNA treatment significantly reduced cell migration and the expression of migration-related genes. In summary, our results indicated that BET inhibitor treatment in HCC cell lines reduces cell migration through the downregulation of SMARCA4.