bluuebunny/crossref_metadata_2025_split huggingface dataset:
A circadian clock regulates efflux by the blood-brain barrier in mice and human cells
Authors: Zhang Shirley L. , Lahens Nicholas F. , Yue Zhifeng , Arnold Denice M. , Pakstis Peter P. , Schwarz Jessica E. , Sehgal Amita 
Published: January 2021

AbstractThe blood-brain barrier (BBB) is critical for neural function. We report here circadian regulation of the BBB in mammals. Efflux of xenobiotics by the BBB oscillates in mice, with highest levels during the active phase and lowest during the resting phase. This oscillation is abrogated in circadian clock mutants. To elucidate mechanisms of circadian regulation, we profiled the transcriptome of brain endothelial cells; interestingly, we detected limited circadian regulation of transcription, with no evident oscillations in efflux transporters. We recapitulated the cycling of xenobiotic efflux using a human microvascular endothelial cell line to find that the molecular clock drives cycling of intracellular magnesium through transcriptional regulation of TRPM7, which appears to contribute to the rhythm in efflux. Our findings suggest that considering circadian regulation may be important when therapeutically targeting efflux transporter substrates to the CNS.
NiH-catalyzed asymmetric hydroarylation of N-acyl enamines to chiral benzylamines
Authors: He Yuli , Song Huayue , Chen Jian , Zhu Shaolin 
Published: January 2021

AbstractEnantiomerically pure chiral amines and related amide derivatives are privilege motifs in many pharmacologically active molecules. In comparison to the well-established hydroamination, the transition metal-catalysed asymmetric hydrofunctionalization of enamines provides a complementary approach for their construction. Here we report a NiH-catalysed enantio- and regioselective reductive hydroarylation of N-acyl enamines, allowing for the practical access to a broad range of structurally diverse, enantioenriched benzylamines under mild, operationally simple reaction conditions.
Interactions of plasma-activated water with biofilms: inactivation, dispersal effects and mechanisms of action
Authors: Mai-Prochnow Anne , Zhou Renwu , Zhang Tianqi , Ostrikov Kostya , Mugunthan Sudarsan , Rice Scott A. , Cullen Patrick J. 
Published: January 2021

AbstractBiofilms have several characteristics that ensure their survival in a range of adverse environmental conditions, including high cell numbers, close cell proximity to allow easy genetic exchange (e.g., for resistance genes), cell communication and protection through the production of an exopolysaccharide matrix. Together, these characteristics make it difficult to kill undesirable biofilms, despite the many studies aimed at improving the removal of biofilms. An elimination method that is safe, easy to deliver in physically complex environments and not prone to microbial resistance is highly desired. Cold atmospheric plasma, a lightning-like state generated from air or other gases with a high voltage can be used to make plasma-activated water (PAW) that contains many active species and radicals that have antimicrobial activity. Recent studies have shown the potential for PAW to be used for biofilm elimination without causing the bacteria to develop significant resistance. However, the precise mode of action is still the subject of debate. This review discusses the formation of PAW generated species and their impacts on biofilms. A focus is placed on the diffusion of reactive species into biofilms, the formation of gradients and the resulting interaction with the biofilm matrix and specific biofilm components. Such an understanding will provide significant benefits for tackling the ubiquitous problem of biofilm contamination in food, water and medical areas.
High-throughput systematic topological generation of low-energy carbon allotropes
Authors: Blatov Vladislav A. , Yang Changhao , Tang Dingyi , Zeng Qingfeng , Golov Andrey A. , Kabanov Artem A. 
Published: January 2021

AbstractThe search for new materials requires effective methods for scanning the space of atomic configurations, in which the number is infinite. Here we present an extensive application of a topological network model of solid-state transformations, which enables one to reduce this infinite number to a countable number of the regions corresponding to topologically different crystalline phases. We have used this model to successfully generate carbon allotropes starting from a very restricted set of initial structures; the generation procedure has required only three steps to scan the configuration space around the parents. As a result, we have obtained all known carbon structures within the specified set of restrictions and discovered 224 allotropes with lattice energy ranging in 0.16–1.76 eV atom−1 above diamond including a phase, which is denser and probably harder than diamond. We have shown that this phase has a quite different topological structure compared to the hard allotropes from the diamond polytypic series. We have applied the tiling approach to explore the topology of the generated phases in more detail and found that many phases possessing high hardness are built from the tiles confined by six-membered rings. We have computed the mechanical properties for the generated allotropes and found simple dependences between their density, bulk, and shear moduli.
Low-temperature dielectric anomaly arising from electronic phase separation at the Mott insulator-metal transition
Authors: Pustogow A. , Rösslhuber R. , Tan Y. , Uykur E. , Böhme A. , Wenzel M. , Saito Y. , Löhle A. , Hübner R. , Kawamoto A. , Schlueter J. A. , Dobrosavljević V. , Dressel M. 
Published: January 2021

AbstractCoulomb repulsion among conduction electrons in solids hinders their motion and leads to a rise in resistivity. A regime of electronic phase separation is expected at the first-order phase transition between a correlated metal and a paramagnetic Mott insulator, but remains unexplored experimentally as well as theoretically nearby T = 0. We approach this issue by assessing the complex permittivity via dielectric spectroscopy, which provides vivid mapping of the Mott transition and deep insight into its microscopic nature. Our experiments utilizing both physical pressure and chemical substitution consistently reveal a strong enhancement of the quasi-static dielectric constant ε1 when correlations are tuned through the critical value. All experimental trends are captured by dynamical mean-field theory of the single-band Hubbard model supplemented by percolation theory. Our findings suggest a similar ’dielectric catastrophe’ in many other correlated materials and explain previous observations that were assigned to multiferroicity or ferroelectricity.
Molecular dynamics simulations and experimental studies reveal differential permeability of withaferin-A and withanone across the model cell membrane
Authors: Wadhwa Renu , Yadav Neetu Singh , Katiyar Shashank P. , Yaguchi Tomoko , Lee Chohee , Ahn Hyomin , Yun Chae-Ok , Kaul Sunil C. , Sundar Durai 
Published: January 2021

AbstractPoor bioavailability due to the inability to cross the cell membrane is one of the major reasons for the failure of a drug in clinical trials. We have used molecular dynamics simulations to predict the membrane permeability of natural drugs—withanolides (withaferin-A and withanone) that have similar structures but remarkably differ in their cytotoxicity. We found that whereas withaferin-A, could proficiently transverse through the model membrane, withanone showed weak permeability. The free energy profiles for the interaction of withanolides with the model bilayer membrane revealed that whereas the polar head group of the membrane caused high resistance for the passage of withanone, the interior of the membrane behaves similarly for both withanolides. The solvation analysis further revealed that the high solvation of terminal O5 oxygen of withaferin-A was the major driving force for its high permeability; it interacted with the phosphate group of the membrane that led to its smooth passage across the bilayer. The computational predictions were tested by raising and recruiting unique antibodies that react to withaferin-A and withanone. The time-lapsed analyses of control and treated cells demonstrated higher permeation of withaferin-A as compared to withanone. The concurrence between the computation and experimental results thus re-emphasised the use of computational methods for predicting permeability and hence bioavailability of natural drug compounds in the drug development process.
Placental and maternal sFlt1/PlGF expression in gestational diabetes mellitus
Authors: Nuzzo Anna Maria , Giuffrida Domenica , Moretti Laura , Re Paola , Grassi Giorgio , Menato Guido , Rolfo Alessandro 
Published: January 2021

AbstractGestational diabetes mellitus (GDM) and preeclampsia (PE) are both characterized by endothelial dysfunction and GDM women have higher incidence of PE. The placenta plays a key role in PE pathogenesis but its contribution to PE during GDM remains unclear. Herein, we compared placental and maternal blood anti-angiogenic soluble fms-like tyrosine kinase-1 (sFlt1) and pro-angiogenic Placental Growth Factor (PlGF) expressions in GDM and GDM-PE pregnancies compared to controls (CTRL) and PE cases. Electrochemiluminescence immunoassays showed a significantly higher maternal blood sFlt1/PlGF values in GDM-PE relative to CTRL and GDM pregnancies. We reported that placental PlGF gene expression was significantly decreased in GDM, PE and GDM-PE relative to CTRL. However, PlGF protein levels were significantly increased in GDM and GDM-PE relative to CTRL and PE placentae. Finally, sFlt1 gene expression was significantly increased in PE relative to CTRL, GDM and GDM-PE placentae. In contrast, sFlt1 protein expression was significantly decreased in GDM-PE relative to CTRL, GDM and PE placentae. Finally, higher sFlt1/PlGF ratio in GDM-PE maternal blood suggest that sFlt1 overproduction is related to PE onset also in GDM pregnancies even though characterized by a less severe endothelial dysfunction in terms of angiogenic biomarkers.
The resting coronal and sagittal stance position of the torso in adolescents with and without spinal deformity
Authors: Gardner Adrian , Archer James , Berryman Fiona , Pynsent Paul 
Published: January 2021

AbstractThe purpose of this work is to identify the resting stance of the torso, defined as the position of the C7 vertebral body relative to the sacrum in a ‘birds eye view’, as the coronal and sagittal offset, in those without spinal deformity, those with pre and post-operative AIS, and those with Scheuermann's kyphosis (SK). Using ISIS2 surface topography, the coronal and sagittal offset were measured in a prospective manner in all groups. With bivariate ellipses, a mean and 95% confidence ellipse of the data was developed. Statistical analyses was performed to examine the distribution of the data from the groups. A graphical representation of the data was developed. There were 829 without spinal deformity, 289 in both the pre and post-operative with AIS and 59 with SK. The results showed that the mean coronal offset for all groups was between 2 and 6 mm and the sagittal offset was 12 and 26 mm. Statistically significance was seen for both measures between the non-scoliotic and both AIS groups, along with the pre-operative AIS coronal offset and post-operative AIS sagittal offset and the SK measures. However, all mean values were within the 95% confidence ellipse for all of the groups. Regardless of the size or type of spinal deformity, the position of the C7 vertebral body and sacrum remain within the 95% confidence ellipse of that seen in those without spinal deformity. This work defines the Minimally Clinically Important Difference for all of the groups.
Gene co-expression network analysis reveals immune cell infiltration as a favorable prognostic marker in non-uterine leiomyosarcoma
Authors: Darzi Mohammad , Gorgin Saeid , Majidzadeh-A Keivan , Esmaeili Rezvan 
Published: January 2021

AbstractThe present study aimed to improve the understanding of non-uterine leiomyosarcoma (NULMS) prognostic genes through system biology approaches. This cancer is heterogeneous and rare. Moreover, gene interaction networks have not been reported in NULMS yet. The datasets were obtained from the public gene expression databases. Seven co-expression modules were identified from 5000 most connected genes; using weighted gene co-expression network analysis. Using Cox regression, the modules showed favorable (HR = 0.6, 95% CI = 0.4–0.89, P = 0.0125), (HR = 0.65, 95% CI = 0.44–0.98, P = 0.04) and poor (HR = 1.55, 95% CI = 1.06–2.27, P = 0.025) prognosis to the overall survival (OS) (time = 3740 days). The first one was significant in multivariate HR estimates (HR = 0.4, 95% CI = 0.28–0.69, P = 0.0004). Enriched genes through the Database for Annotation, Visualization, and Integrated Discovery (DAVID) revealed significant immune-related pathways; suggesting immune cell infiltration as a favorable prognostic factor. The most significant protective genes were ICAM3, NCR3, KLRB1, and IL18RAP, which were in one of the significant modules. Moreover, genes related to angiogenesis, cell–cell adhesion, protein glycosylation, and protein transport such as PYCR1, SRM, and MDFI negatively affected the OS and were found in the other related module. In conclusion, our analysis suggests that NULMS might be a good candidate for immunotherapy. Moreover, the genes found in this study might be potential candidates for targeted therapy.
Nitric oxide regulates perylenequinones biosynthesis in Shiraia bambusicola S4201 induced by hydrogen peroxide
Authors: Zhao Ning , Yu Yingying , Yue Yunxia , Dou Mingzhu , Guo Bingjing , Yan Shuzhen , Chen Shuanglin 
Published: January 2021

AbstractShiraia bambusicola has been used as a traditional Chinese medicine for a long history. Its major medicinal active metabolites are perylenequinones, including hypocrellin A, elsinochrome A and so on. At present, the fermentation yield of perylenequinones is low, and its complex biosynthesis and regulatory pathways are still unclear. In this study, nitric oxide, as a downstream signal molecule of hydrogen peroxide, regulates the biosynthesis of perylenequinones. Exogenous addition of 0.01 mM sodium nitroprusside (nitric oxide donor) can promote perylenequinones production by 156% compared with the control. Further research found that hydrogen peroxide and nitric oxide increased the transcriptional level of the biosynthetic genes of hypocrellin A. The results showed that nitric oxide is involved in the biosynthesis and regulation of perylenequinones in Shiraia bambusicola as a signal molecule. In the future, the yield of perylenequinones can be increased by adding exogenous nitric oxide in fermentation.
Serum iron: a new predictor of adverse outcomes independently from serum hemoglobin levels in patients with acute decompensated heart failure
Authors: Ueda Tomoya , Kawakami Rika , Nogi Kazutaka , Nogi Maki , Ishihara Satomi , Nakada Yasuki , Nakano Tomoya , Hashimoto Yukihiro , Nakagawa Hitoshi , Nishida Taku , Onoue Kenji , Soeda Tsunenari , Okayama Satoshi , Watanabe Makoto , Saito Yoshihiko 
Published: January 2021

AbstractIron is an essential trace element in the body. However, in heart failure (HF), iron is only recognized as the cause of anemia. Actually, iron itself affects myocardial exercise tolerance and cardiac function via mitochondrial function. Therefore, it is necessary to clarify the pathological significance of iron in acute HF, irrespective of concomitant anemia. We investigated the impact of serum iron level at discharge on the prognosis of 615 patients emergently admitted with acute decompensated HF (ADHF). Patients were divided into two groups according to the median level of serum iron (62 µg/dL). The endpoint was the composite outcome, which included all-cause mortality and readmission for HF. During the mean follow-up period of 32.1 months, there were 333 events. Kaplan–Meier analysis showed that the incidence of the composite outcome was significantly higher in the Low iron group (P < 0.0001). In the multivariate analysis adjusted with factors including hemoglobin and ferritin levels, low serum iron was an independent predictor for the composite outcome (hazard ratio, 1.500; 95% confidence interval, 1.128–1.976; P = 0.0044). Low serum iron was an independent predictor of poor prognosis in ADHF, irrespective of hemoglobin or ferritin level, providing a new concept that iron may play a role in the pathophysiology of ADHF via non-hematopoietic roles.
Thermal-stress analysis of a damaged solid sphere using hyperbolic two-temperature generalized thermoelasticity theory
Authors: Youssef Hamdy M. , El-Bary Alaa A. , Al-Lehaibi Eman A. N. 
Published: January 2021

AbstractThis work aims to study the influence of the rotation on a thermoelastic solid sphere in the context of the hyperbolic two-temperature generalized thermoelasticity theory based on the mechanical damage consideration. Therefore, a mathematical model of thermoelastic, homogenous, and isotropic solid sphere with a rotation based on the mechanical damage definition has been constructed. The governing equations have been written in the context of hyperbolic two-temperature generalized thermoelasticity theory. The bounding surface of the sphere is thermally shocked and without volumetric deformation. The singularities of the studied functions at the center of the sphere have been deleted using L’Hopital’s rule. The numerical results have been represented graphically with various mechanical damage values, two-temperature parameters, and rotation parameter values. The two-temperature parameter has significant effects on all the studied functions. Damage and rotation have a major impact on deformation, displacement, stress, and stress–strain energy, while their effects on conductive and dynamical temperature rise are minimal. The thermal and mechanical waves propagate with finite speeds on the thermoelastic body in the hyperbolic two-temperature theory and the one-temperature theory (Lord-Shulman model).
Connective tissue growth factor promotes chemotaxis of preosteoblasts through integrin α5 and Ras during tensile force-induced intramembranous osteogenesis
Authors: Jiang Wei , Takeshita Nobuo , Maeda Toshihiro , Sogi Chisumi , Oyanagi Toshihito , Kimura Seiji , Yoshida Michiko , Sasaki Kiyo , Ito Arata , Takano-Yamamoto Teruko 
Published: January 2021

AbstractIn vertebrates, new bone formation via intramembranous osteogenesis is a critical biological event for development, remodeling, and fracture healing of bones. Chemotaxis of osteoblast lineage cells is an essential cellular process in new bone formation. Connective tissue growth factor (CTGF) is known to exert chemotactic properties on various cells; however, details of CTGF function in the chemotaxis of osteoblast lineage cells and underlying molecular biological mechanisms have not been clarified. The aim of the present study was to evaluate the chemotactic properties of CTGF and its underlying mechanisms during active bone formation through intramembranous osteogenesis. In our mouse tensile force-induced bone formation model, preosteoblasts were aggregated at the osteogenic front of calvarial bones. CTGF was expressed at the osteogenic front, and functional inhibition of CTGF using a neutralizing antibody suppressed the aggregation of preosteoblasts. In vitro experiments using μ-slide chemotaxis chambers showed that a gradient of CTGF induced chemotaxis of preosteoblastic MC3T3-E1 cells, while a neutralizing integrin α5 antibody and a Ras inhibitor inhibited the CTGF-induced chemotaxis of MC3T3-E1 cells. These findings suggest that the CTGF-integrin α5-Ras axis is an essential molecular mechanism to promote chemotaxis of preosteoblasts during new bone formation through intramembranous osteogenesis.
Optogenetic therapy: high spatiotemporal resolution and pattern discrimination compatible with vision restoration in non-human primates
Authors: Gauvain Gregory , Akolkar Himanshu , Chaffiol Antoine , Arcizet Fabrice , Khoei Mina A. , Desrosiers Mélissa , Jaillard Céline , Caplette Romain , Marre Olivier , Bertin Stéphane , Fovet Claire-Maelle , Demilly Joanna , Forster Valérie , Brazhnikova Elena , Hantraye Philippe , Pouget Pierre , Douar Anne , Pruneau Didier , Chavas Joël , Sahel José-Alain , Dalkara Deniz , Duebel Jens , Benosman Ryad , Picaud Serge 
Published: January 2021

AbstractVision restoration is an ideal medical application for optogenetics, because the eye provides direct optical access to the retina for stimulation. Optogenetic therapy could be used for diseases involving photoreceptor degeneration, such as retinitis pigmentosa or age-related macular degeneration. We describe here the selection, in non-human primates, of a specific optogenetic construct currently tested in a clinical trial. We used the microbial opsin ChrimsonR, and showed that the AAV2.7m8 vector had a higher transfection efficiency than AAV2 in retinal ganglion cells (RGCs) and that ChrimsonR fused to tdTomato (ChR-tdT) was expressed more efficiently than ChrimsonR. Light at 600 nm activated RGCs transfected with AAV2.7m8 ChR-tdT, from an irradiance of 1015 photons.cm−2.s−1. Vector doses of 5 × 1010 and 5 × 1011 vg/eye transfected up to 7000 RGCs/mm2 in the perifovea, with no significant immune reaction. We recorded RGC responses from a stimulus duration of 1 ms upwards. When using the recorded activity to decode stimulus information, we obtained an estimated visual acuity of 20/249, above the level of legal blindness (20/400). These results lay the groundwork for the ongoing clinical trial with the AAV2.7m8 - ChR-tdT vector for vision restoration in patients with retinitis pigmentosa.
Preoperative Embolization Facilitates Segmental Resection of Pulmonary Sequestration in an Infant
Authors: Prasad Dilan , Pennell Christopher , Arthur Lindsay Grier , Prasad Rajeev 
Published: January 2021

AbstractThe most common congenital lung malformations are congenital pulmonary airway malformations and pulmonary sequestrations. Many surgeons advocate resection to prevent complications of infection, malignancy, and pneumothorax. The standard of care is lobectomy, but segmentectomy and embolization alone have been reported. These methods avoid the complications of lobectomy but are not widely practiced due to concerns about incomplete resection or involution of the lesion. We present a novel approach to the treatment of a pulmonary sequestration in a 7-month-old male using preoperative embolization followed by a sublobar pulmonary resection. The embolization clearly demarcated the affected lung intraoperatively, thereby facilitating complete removal of the lesion with a segmental lung resection rather than complete lobectomy.
Advantage of Using 8K Ultra-High-Definition Television System for Kasai Portoenterostomy for Biliary Atresia
Authors: Miyagi Hisayuki , Ishii Daisuke , Hirasawa Masatoshi , Shonaka Tatsuya , Sumi Yasuo , Azuma Nobuyoshi 
Published: January 2021

AbstractKasai portoenterostomy (KPE) is currently the first-line treatment for biliary atresia. Many pediatric surgeons have reported that the dissection of the fibrous remnant at the porta hepatis is one of the most important components of this procedure. Furthermore, laparoscopic portoenterostomy is being increasingly used to treat biliary atresia.An advantage of laparoscopic surgery is that surgeons can more easily identify microbiliary ducts, owing to the magnification. We report the case of a 61-day-old girl on whom we performed an exploratory laparotomy and diagnosed type III biliary atresia using intraoperative cholangiography. For the first time, we performed an open KPE using an 8K ultra-high-definition television system. This allowed us to clearly view the porta hepatis and to successfully perform the portoenterostomy.