bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of gene targets of developmental neurotoxicity focusing on DNA hypermethylation involved in irreversible disruption of hippocampal neurogenesis in rats
Authors: Kikuchi Satomi , Takahashi Yasunori , Ojiro Ryota , Takashima Kazumi , Okano Hiromu , Tang Qian , Woo Gye‐Hyeong , Yoshida Toshinori , Shibutani Makoto 
Published: November 2020

AbstractWe have previously found that maternal exposure to 6‐propyl‐2‐thiouracil (PTU), valproic acid (VPA), or glycidol (GLY) has a sustained or late effect on hippocampal neurogenesis at the adult stage in rat offspring. Herein, we searched for genes with hypermethylated promoter region and downregulated transcript level to reveal irreversible markers of developmental neurotoxicity. The hippocampal dentate gyrus of male rat offspring exposed maternally to PTU, VPA, or GLY was subjected to Methyl‐Seq and RNA‐Seq analyses on postnatal day (PND) 21. Among the genes identified, 170 were selected for further validation analysis of gene expression on PND 21 and PND 77 by real‐time reverse transcription‐PCR. PTU and GLY downregulated many genes on PND 21, reflecting diverse effects on neurogenesis. Furthermore, genes showing sustained downregulation were found after PTU or VPA exposure, reflecting a sustained or late effect on neurogenesis by these compounds. In contrast, such genes were not observed with GLY, probably because of the reversible nature of the effects. Among the genes showing sustained downregulation, Creb, Arc, and Hes5 were concurrently downregulated by PTU, suggesting an association with neuronal mismigration, suppressed synaptic plasticity, and reduction in neural stem and progenitor cells. Epha7 and Pvalb were also concurrently downregulated by PTU, suggesting an association with the reduction in late‐stage progenitor cells. VPA induced sustained downregulation of Vgf and Dpysl4, which may be related to the aberrations in synaptic plasticity. The genes showing sustained downregulation may be irreversible markers of developmental neurotoxicity.
Advanced fully integrated radiofrequency/optical‐coherence‐tomography irrigated catheter for atrial fibrillation ablation
Authors: Tiporlini Valentina , Ahderom Selam , Pratten Peter , Alameh Kamal 
Published: November 2020

AbstractThe inability of current catheter ablation procedures to accurately monitor lesion formation limits their safety and efficacy. An advanced fully integrated radiofrequency (RF)/optical coherence tomography (OCT) ablation catheter is developed, which enables real‐time monitoring during ablation. An OCT fiber array is especially designed, developed and integrated into an off‐the‐shelf irrigated RF ablation catheter. In‐vitro experimental studies performed on poultry and ovine hearts demonstrate the ability of the integrated RF/OCT system to provide information on the quality and orientation of catheter/wall contact. Experimental results show that adipose tissue can be accurately identified from normal myocardial tissue with 94% accuracy and lesion formation is monitored with an overall accuracy of 93%. The ability to predict pop events is also demonstrated, with an accuracy of 86%.
Upregulated microRNA‐126 induces apoptosis of dental pulp stem cell via mediating PTEN‐regulated Akt activation
Authors: Ge Rucun , Lv Yongtao , Li Peipei , Xu Lin , Feng Xiaoya , Qi Hongshun 
Published: November 2020

AbstractIntroductionHuman dental pulp stem cells (DPSCs) have potential applications in regenerative medicine. The molecular mechanisms underlying DPSCs viability and apoptosis are not completely understood. Here, we investigated the role of miR‐126 in DPSCs viability and apoptosis.Material and methodsSenescent DPSCs were compared with early passage DPSCs. real‐time PCR and microARRAY were performed to identify the differential expression of miR‐126, and western blot was performed to detect the expression of PTEN. MTT assay was utilized to reveal the proliferative rate of both senescent and early passage DPSCs. Flow cytometry was used to examine the apoptotic rate of DPSCs. Dual‐luciferase reporter assay was carried out to detect the interaction of miR‐126 and PTEN.ResultsSenescent DPSCs showed a high level of apoptosis. Further study showed that miR‐126 is upregulated in senescent DPSCs and its overexpression in early passaged DPSCs induced apoptosis. Phosphatase and tensin homolog gene (PTEN) was identified as a target of miR‐126. PTEN was downregulated in senescent DPSCs, whereas miR‐126 inhibition upregulated PTEN level, and subsequently activated Akt pathway and suppressed the apoptotic phenotype of senescent DPSCs. In addition, PTEN overexpression rescued apoptosis of DPSCs at later stage.ConclusionOur results demonstrate that the miR‐126‐PTEN‐Akt axis plays a key role in the regulation of DPSCs apoptosis and provide a candidate target to improve the functional and therapeutic potential of DPSCs.
The first report of covalently grafted semiconductors; n‐TiO2‐P25@ECH@WO3 as a new, efficient, robust and visible‐light‐responsive photocatalyst
Authors: Bitaraf Mehrnoosh , Amoozadeh Ali 
Published: November 2020

AbstractBACKGROUNDSemiconductor nanomaterials have gained great attention as potential photocatalysts to promote environmentally benign organic reactions. Degussa P25, known as commercial TiO2, is the most applicable semiconductor photocatalyst. However, the wide band‐gap of TiO2 limits its application. A simple way to address this issue is to form heterojunction structures.RESULTSIn the present work, n‐TiO2‐P25@ECH@WO3 heterostructure photocatalyst was synthesized for the first time by a two‐step covalent grafting strategy. In this photocatalyst, two nano‐semiconductors, TiO2‐P25 and WO3 were anchored with epichlorohydrin (ECH) as the covalent linker. The properties of n‐TiO2‐P25@ECH@WO3 were investigated through Fourier‐transform infrared spectroscopy (FTIR), X‐ray powder diffraction (XRD), transmission electron microscopy (TEM), energy dispersive X‐Ray (EDX) and UV‐visible/DRS techniques. Under blue LED light, n‐TiO2‐P25@ECH@WO3 oxidized benzyl alcohol to benzaldehyde with excellent selectivity and high yield.CONCLUSIONIn this study, n‐TiO2‐P25@ECH@WO3 heterostructure photocatalyst was successfully synthesized and evaluated. ECH as the organic linker stably grafted two nano‐semiconductors, n‐TiO2‐P25 and n‐WO3. The heterojunction that formed between n‐TiO2 and n‐WO3 significantly improved the light absorption performance with a considerable redshift to the visible region. Also, the photocatalyst showed an increased activity compared to individual semiconductors. © 2020 Society of Chemical Industry (SCI)
Short‐duration treatment with the novel non‐nucleoside inhibitor CDI‐31244 plus sofosbuvir/velpatasvir for chronic hepatitis C: An open‐label study
Authors: Chua Joel V. , Ntem‐Mensah Afua , Abutaleb Ameer , Husson Jennifer , Mutumbi Lydiah , Lam Ka Wing , Ghosh Alip , Romani Sara , Poonia Bhawna , Lee Sam , Luz Pascual M. , Frumkin Lyn R. , Kottilil Shyamsundaran 
Published: November 2020

AbstractCombination regimens of direct‐acting antiviral agents (DAAs) for chronic genotype 1 hepatitis C virus (HCV) infection given for 8 or 12 weeks have high cure rates. Shortened treatment durations that maintain high cure rates may lessen treatment barriers related to affordability and drug adherence. We enrolled 12 treatment‐naïve adults with chronic genotype 1 HCV infection without cirrhosis in a single‐center, open‐label trial to receive 2 weeks of the highly potent and selective non‐nucleoside inhibitor (NNI) CDI‐31244 concurrent with 6 weeks of sofosbuvir/velpatasvir. The main efficacy endpoints were sustained virologic response at 12 (SVR12) and 24 (SVR24) weeks after treatment completion. In all patients, plasma HCV RNA levels rapidly decreased during the first 2 days of treatment and were below the lower limit of quantification by the end of the 6‐week treatment period. Eight of 12 (67%) patients achieved both SVR12 and SVR24. Four patients had virological relapse at Week 10, 4 weeks after end of treatment. The most common adverse event was headache, occurring in five (42%) patients. Pharmacokinetic analysis showed no relevant drug interactions between CDI‐31244, sofosbuvir, and velpatasvir. In this pilot study of short‐duration combination therapy involving a novel NNI with a fixed‐combination DAA, 8 of 12 treatment‐naïve patients with chronic genotype 1 HCV infection without cirrhosis achieved virologic cure. Future trials might evaluate whether extending the NNI duration beyond 2 weeks with combination DAAs results in higher cure rates comparable with currently approved longer duration therapy.
Real‐world effectiveness of direct‐acting antiviral agents for chronic hepatitis C patients with genotype‐2 infection after completed treatment
Authors: Cheng Tzu‐Sheng , Liang Po‐Cheng , Huang Chung‐Feng , Yeh Ming‐Lun , Huang Ching‐I , Lin Zu‐Yau , Chen Shinn‐Cherng , Huang Jee‐Fu , Dai Chia‐Yen , Hsieh Ping‐Hsin , Chuang Wan‐Long , Yu Ming‐Lung 
Published: November 2020

AbstractChronic hepatitis C (CHC) is a major cause of cirrhosis, hepatocellular carcinoma (HCC), and mortality. Eliminating hepatitis C virus (HCV) can greatly improve long‐term outcomes. Several direct‐acting antiviral agents (DAAs), including sofosbuvir (SOF) plus different NS5A inhibitors, as well as non‐SOF‐based DAAs, including glecaprevir/pibrentasvir (GLE/PIB), have been approved for treating CHC genotype‐2 (GT‐2) patients in Taiwan. However, there is limited real‐world effectiveness data regarding these different regimens. Thus, we aimed to evaluate the real‐world efficacy in CHC GT‐2 patients who underwent these DAA regimens. We retrospectively enrolled CHC GT‐2 patients who were treated with SOF‐based DAAs or GLE/PIB at a single medical center. A total of 704 enrolled patients were treated with either SOF + ribavirin (RBV), SOF/daclatasvir (DCV) ± RBV, SOF/ledipasvir (LDV) ± RBV, SOF/velpatasvir (VEL) ± RBV, or with GLE/PIB. The overall sustained virological response (SVR) rate was 97.9%. The SVR rate was significantly lower in the SOF + RBV group (95.6%) than in the non‐SOF + RBV (98.9%) group, especially compared to the SOF/DCV (100%) and GLE/PIB groups (99.5%). Among patients treated with SOF + RBV, cirrhotic patients had significantly lower SVR rates than noncirrhotic patients (89.4% vs 98.2%). Multivariate analysis showed that patients with a younger age, hepatitis B virus coinfection, baseline cirrhosis, or those who received SOF + RBV were less likely to achieve SVR. In conclusion, for CHC GT‐2 patients, SOF in combination with DCV, LDV, or VEL, as well as GLE/PIB, achieved similar high efficacies, regardless of cirrhosis, treatment experience, or chronic kidney disease status. Therefore, the use of DAA therapy to eradicate HCV should not be delayed in these populations.
MiR‐483‐5p downregulation contributed to cell proliferation, metastasis, and inflammation of clear cell renal cell carcinoma
Authors: Wang Xue‐Gang , Zhu Yong‐Wu , Wang Tao , Chen Bin , Xing Jin‐Chun , Xiao Wen 
Published: November 2020

AbstractInflammation status are especially for tumor growth, and microRNAs (miRNAs) confirmed to participate in cancer occurrence and progression. However, the role of miR‐483‐5p and the relation with inflammation have not been elucidated in renal cell cancer (RCC). In this study, we intended to explore miR‐483‐5p expression and the relationship of inflammation status in clear cell renal cell cancer (ccRCC). Using microarray and qRT‐PCR (Quantitative Real‐time Polymerase Chain Reaction), we investigated the miR‐483‐5p expression in plasma and ccRCC cancer tissues. Then, we analyzed the correlation of miR‐483‐5p with clinicopathological parameters and inflammation status in ccRCC. Receiver operator characteristic (ROC) curves analysis was used to analyze the discrimination efficiency of miR‐483‐5p. in vitro experiments explored the biological role of miR‐483‐5p in renal cancer cells. miR‐483‐5p expression was upregulated in plasma of 5 patients with microarray and 12 patients with qRT‐PCR in ccRCC at day 7 postoperatively. In addition, low expression of miR‐483‐5p was found in 58 ccRCC cancer tissues when compared with non‐cancerous tissues. miR‐483‐5p could sufficiently discriminate ccRCC with the area under the curve (AUC) of 0.739 (P < .0001) from normal tissues. Higher expression of miR‐483‐5p was positively related to lower tumor stage and higher relative expression of miR‐483‐5p was inversely related to neutrophil‐to‐lymphocyte ratio (NLR) (P = .03) and lymphocyte‐to‐monocyte ratio (LMR) (P = .026). Overexpression of miR‐483‐5p lead to reverse epithelial‐mesenchymal transition (EMT) process, restrain cell proliferation and metastasis of renal cancer cells. Our findings suggest that miR‐483‐5p expression is negatively correlation with inflammation status and may be a potential plasma biomarker for ccRCC.
Microbial structure of carbon source utilization in rice rhizosphere and non‐rhizosphere soils with different short‐term tillage management
Authors: Tang Haiming , Li Chao , Li Weiyan , Wen Li , Shi Lihong , Cheng Kaikai , Xiao Xiaoping , Wang Ke 
Published: November 2020

AbstractCarbon (C) plays an important role in the activity and diFversity of soil microbial community, but there is still limited information about how C source utilization soil microbial structure responds to soil organic carbon changes under the double‐cropping rice (Oryza sativa L.) system in southern China's paddy fields. Therefore, the effects of short‐term (5‐year) tillage treatments on characteristics of C source utilization microbial structure in both rhizosphere and non‐rhizosphere soils under double‐cropping were investigated by using metagenome sequencing technology. The experiment included four tillage treatments: conventional tillage with crop residue incorporation (return), rotary tillage with crop residue return, no‐tillage (zero‐tilllage) with crop residue return, and rotary tillage with crop residue removed as control. The results showed that relative abundance of Firmicutes, Alphaproteobacteria and Deltaproteobacteria in both rhizosphere and non‐rhizosphere soils was increased by combined application of tillage with crop residue return practice. Regarding the cluster of orthologous groups of proteins categories, the largest group was 'amino acid transport and metabolism' with 0.223% unigenes, followed by 'general function prediction only' (0.205%), and 'nuclear structure' (0.005%) was the smallest group. And the gene ontology categories with different tillage treatments in following decreasing order: biological process (144,229, 42.4%) > cellular component (104,981, 30.8%) > molecular function (91,284, 26.8%). The principal coordinate analysis indicated that different parts of root zone and tillage treatments were the most and the second most important factors affecting the variation of C source utilization bacteria community, respectively. Therefore, the results showed that combined application of tillage with crop residue return practice significantly increased the C source utilization of soil microorganisms in the double‐cropped rice fields.
Leveraging Shape Memory Coupled Piezoelectric Properties in Melt Extruded Composite Filament Based on Polyvinylidene Fluoride and Polyurethane
Authors: Chowdhury Anupam , Bairagi Satyaranjan , Ali Syed Wazed , Kumar Bipin 
Published: November 2020

AbstractMultifunctional piezoelectric nanocomposites are promising in terms of strain sensors and actuators having ability to switch their dimensional states in a programmed temperature depending on their chemical compositions. In this research work, the effect of immiscible blends of polyurethane and polyvinylidene fluoride to induce polar β‐phase in the melt extruded composite filament and the effect of reduced graphene oxide (r‐GO) in combined properties of piezoelectricity and shape memory behavior are studied with the aid of different characterization techniques. The thermal analysis by differential scanning calorimetry also reiterates the similar behavior of crystalline phases in melting transitions and compatibilization effect of r‐GO is well supported by field emission scanning electron microscopy. Moreover, some of these filaments possess promising shape memory behavior with recovery ratios up to 100%. One of the nanocomposite filament‐based energy harvesters generates average open circuit maximum voltage of ≈349 mV. These types of melt extruded nanocomposite filament‐based energy harvesters are promising in terms of miniaturized power sources fitting into different conformed surfaces having varied contours.
A Chlorzoxazone‐Baclofen Combination Improves Cerebellar Impairment in Spinocerebellar Ataxia Type 1
Authors: Bushart David D. , Huang Haoran , Man Luke J. , Morrison Logan M. , Shakkottai Vikram G. 
Published: November 2020

ABSTRACTBackgroundA combination of central muscle relaxants, chlorzoxazone and baclofen (chlorzoxazone‐baclofen), has been proposed for treatment of cerebellar symptoms in human spinocerebellar ataxia. However, central muscle relaxants can worsen balance. The optimal dose for target engagement without toxicity remains unknown. Using the genetically precise Atxn1154Q/2Q model of spinocerebellar ataxia type 1, we aimed to determine the role of cerebellar dysfunction in motor impairment. We also aimed to identify appropriate concentrations of chlorzoxazone‐baclofen needed for target engagement without toxicity to plan for human clinical trials.MethodsWe use patch clamp electrophysiology in acute cerebellar slices and immunostaining to identify the specific ion channels targeted by chlorzoxazone‐baclofen. Behavioral assays for coordination and grip strength are used to determine specificity of chlorzoxazone‐baclofen for improving cerebellar dysfunction without off‐target effects in Atxn1154Q/2Q mice.ResultsWe identify irregular Purkinje neuron firing in association with reduced expression of ion channels Kcnma1 and Cacna1g in Atxn1154Q/2Q mice. Using in vitro electrophysiology in brain slices, we identified concentrations of chlorzoxazone‐baclofen that improve Purkinje neuron spike regularity without reducing firing frequency. At a disease stage in Atxn1154Q/2Q mice when motor impairment is due to cerebellar dysfunction, orally administered chlorzoxazone‐baclofen improves motor performance without affecting muscle strength.ConclusionWe identify a tight relationship between baclofen‐chlorzoxazone concentrations needed to engage target and levels above which cerebellar function will be compromised. We propose to use this information for a novel clinical trial design, using sequential dose escalation within each subject, to identify dose levels that are likely to improve ataxia symptoms while minimizing toxicity. © 2020 International Parkinson and Movement Disorder Society
A New MRI Measure to Early Differentiate Progressive Supranuclear Palsy From De Novo Parkinson's Disease in Clinical Practice: An International Study
Authors: Quattrone Andrea , Antonini Angelo , Vaillancourt David E. , Seppi Klaus , Ceravolo Roberto , Strafella Antonio P. , Morelli Maurizio , Nigro Salvatore , Vescio Basilio , Bianco Maria G. , Vasta Roberta , Arcuri Pier Paolo , Weis Luca , Fiorenzato Eleonora , Biundo Roberta , Burciu Roxana G. , Krismer Florian , McFarland Nikolaus R. , Mueller Christoph , Gizewski Elke R. , Cosottini Mirco , Del Prete Eleonora , Mazzucchi Sonia , Quattrone Aldo 
Published: November 2020

ABSTRACTBackgroundEnlargement of the third ventricle has been reported in atypical parkinsonism. We investigated whether the measurement of third ventricle width could distinguish Parkinson's disease (PD) from progressive supranuclear palsy (PSP).MethodsWe assessed a new MR T1‐weighted measurement (third ventricle width/internal skull diameter) in a training cohort of 268 participants (98 PD, 73 PSP, 98 controls from our center) and in a testing cohort of 291 participants (82 de novo PD patients and 133 controls from the Parkinson's Progression Markers Initiative, 76 early‐stage PSP from an international research group). PD diagnosis was confirmed after a 4‐year follow‐up. Diagnostic performance of the third ventricle/internal skull diameter was assessed using receiver operating characteristic curve with bootstrapping; the area under the curve of the training cohort was compared with the area under the curve of the testing cohort using the De Long test.ResultsIn both cohorts, third ventricle/internal skull diameter values did not differ between PD and controls but were significantly lower in PD than in PSP patients (P < 0.0001). In PD, third ventricle/internal skull diameter values did not change significantly between baseline and follow‐up evaluation. Receiver operating characteristic analysis accurately differentiated PD from PSP in the training cohort (area under the curve, 0.94; 95% CI, 91.1–97.6; cutoff, 5.72) and in the testing cohort (area under the curve, 0.91; 95% CI, 87.0–97.0; cutoff,: 5.88), validating the generalizability of the results.ConclusionOur study provides a new reliable and validated MRI measurement for the early differentiation of PD and PSP. The simplicity and generalizability of this biomarker make it suitable for routine clinical practice and for selection of patients in clinical trials worldwide. © 2020 International Parkinson and Movement Disorder Society
Implementation of inkjet‐printed 3 dB coupler with equal power division and 45° output phase difference
Authors: Babale S.A. , Rahim S.K.A. , Himdi M. , Lawan S.H. , Sani F.D. , Usman A.D. 
Published: November 2020

AbstractImplementation of a 3 dB coupler with flexible phase difference was presented in this paper. The coupler has equal power division and output phase difference of 45° as against the conventional coupler. It has advantage in many applications that require phase delay like phased antenna array, and beamforming network without necessarily requiring additional phase shifters. It was designed and implemented using the instant inkjet printing technique on a transparent Polyethylene terephthalate (PET) substrate specially coated with resin. The coupler's response shows very good return loss and isolation of −28 and −48 dB, respectively. A bandwidth of 31.33% was achieved around the center frequency. However, an output phase difference of 45° was recorded with a slight phase variation of about ±1° within the specified bandwidth.
Improved body quantitative susceptibility mapping by using a variable‐layer single‐min‐cut graph‐cut for field‐mapping
Authors: Boehm Christof , Diefenbach Maximilian N. , Makowski Marcus R. , Karampinos Dimitrios C. 
Published: November 2020

PurposeTo develop a robust algorithm for field‐mapping in the presence of water–fat components, large field inhomogeneities and MR signal voids and to apply the developed method in body applications of quantitative susceptibility mapping (QSM).MethodsA framework solving the cost‐function of the water–fat separation problem in a single‐min‐cut graph‐cut based on the variable‐layer graph construction concept was developed. The developed framework was applied to a numerical phantom enclosing an MR signal void, an air bubble experimental phantom, 14 large field of view (FOV) head/neck region in vivo scans and to 6 lumbar spine in vivo scans. Field‐mapping and subsequent QSM results using the proposed algorithm were compared to results using an iterative graph‐cut algorithm and a formerly proposed single‐min‐cut graph‐cut.ResultsThe proposed method was shown to yield accurate field‐map and susceptibility values in all simulation and in vivo datasets when compared to reference values (simulation) or literature values (in vivo). The proposed method showed improved field‐map and susceptibility results compared to iterative graph‐cut field‐mapping especially in regions with low SNR, strong field‐map variations and high values.ConclusionsA single‐min‐cut graph‐cut field‐mapping method with a variable‐layer construction was developed for field‐mapping in body water–fat regions, improving quantitative susceptibility mapping particularly in areas close to MR signal voids.