bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extracting backbones in weighted modular complex networks
Authors: Ghalmane Zakariya , Cherifi Chantal , Cherifi Hocine , El Hassouni Mohammed 
Published: September 2020

AbstractNetwork science provides effective tools to model and analyze complex systems. However, the increasing size of real-world networks becomes a major hurdle in order to understand their structure and topological features. Therefore, mapping the original network into a smaller one while preserving its information is an important issue. Extracting the so-called backbone of a network is a very challenging problem that is generally handled either by coarse-graining or filter-based methods. Coarse-graining methods reduce the network size by grouping similar nodes, while filter-based methods prune the network by discarding nodes or edges based on a statistical property. In this paper, we propose and investigate two filter-based methods exploiting the overlapping community structure in order to extract the backbone in weighted networks. Indeed, highly connected nodes (hubs) and overlapping nodes are at the heart of the network. In the first method, called “overlapping nodes ego backbone”, the backbone is formed simply from the set of overlapping nodes and their neighbors. In the second method, called “overlapping nodes and hubs backbone”, the backbone is formed from the set of overlapping nodes and the hubs. For both methods, the links with the lowest weights are removed from the network as long as a backbone with a single connected component is preserved. Experiments have been performed on real-world weighted networks originating from various domains (social, co-appearance, collaboration, biological, and technological) and different sizes. Results show that both backbone extraction methods are quite similar. Furthermore, comparison with the most influential alternative filtering method demonstrates the greater ability of the proposed backbones extraction methods to uncover the most relevant parts of the network.
Biodistribution of 131I in mice is influenced by circadian variations
Authors: Andersson Charlotte K. , Elvborn Mikael , Spetz Johan K. E. , Langen Britta , Forssell-Aronsson Eva B. 
Published: September 2020

AbstractEffects of radiation and biodistribution of radionuclides are often studied in animal models. Circadian rhythm affects many biological functions and may influence the biokinetics of radionuclides and observed responses. The aim of this study was to investigate if the time during the day of 131I injection affects the biodistribution and absorbed dose to tissues in mice. Biodistribution studies were conducted on male C57BL/6 N mice for three diurnal time-series: the animals were i.v. injected with 160 kBq 131I at 8 am, 12 pm or 4 pm. The activity concentration in organs and tissues was measured at 1 h to 7 days after administration and absorbed dose at day 7 was determined. Comparison between the three time-series showed statistically significant differences in activity concentration in all investigated tissues and organs. Administration performed at 12 pm resulted in general in higher absorbed dose to the organs than injection performed at 8 am and 4 pm. Time of day of administration affects the biodistribution of 131I in mice and consequently the absorbed dose to individual organs. These findings advocate that subsequent biodistribution studies and dosimetry calculations should consider time-point of administration as a variable that could influence the results.
Modulation of CYP2C9 activity and hydrogen peroxide production by cytochrome b5
Authors: Gómez-Tabales Javier , García-Martín Elena , Agúndez José A. G. , Gutierrez-Merino Carlos 
Published: September 2020

AbstractCytochromes P450 (CYP) play a major role in drug detoxification, and cytochrome b5 (cyt b5) stimulates the catalytic cycle of mono-oxygenation and detoxification reactions. Collateral reactions of this catalytic cycle can lead to a significant production of toxic reactive oxygen species (ROS). One of the most abundant CYP isoforms in the human liver is CYP2C9, which catalyzes the metabolic degradation of several drugs including nonsteroidal anti-inflammatory drugs. We studied modulation by microsomal membrane-bound and soluble cyt b5 of the hydroxylation of salicylic acid to gentisic acid and ROS release by CYP2C9 activity in human liver microsomes (HLMs) and by CYP2C9 baculosomes. CYP2C9 accounts for nearly 75% of salicylic acid hydroxylation in HLMs at concentrations reached after usual aspirin doses. The anti-cyt b5 antibody SC9513 largely inhibits the rate of salicylic acid hydroxylation by CYP2C9 in HLMs and CYP2C9 baculosomes, increasing the KM approximately threefold. Besides, soluble human recombinant cyt b5 stimulates the Vmax nearly twofold while it decreases nearly threefold the Km value in CYP2C9 baculosomes. Regarding NADPH-dependent ROS production, soluble recombinant cyt b5 is a potent inhibitor both in HLMs and in CYP2C9 baculosomes, with inhibition constants of 1.04 ± 0.25 and 0.53 ± 0.06 µM cyt b5, respectively. This study indicates that variability in cyt b5 might be a major factor underlying interindividual variability in the metabolism of CYP2C9 substrates.
Physiologic blood flow is turbulent
Authors: Saqr Khalid M. , Tupin Simon , Rashad Sherif , Endo Toshiki , Niizuma Kuniyasu , Tominaga Teiji , Ohta Makoto 
Published: September 2020

AbstractContemporary paradigm of peripheral and intracranial vascular hemodynamics considers physiologic blood flow to be laminar. Transition to turbulence is considered as a driving factor for numerous diseases such as atherosclerosis, stenosis and aneurysm. Recently, turbulent flow patterns were detected in intracranial aneurysm at Reynolds number below 400 both in vitro and in silico. Blood flow is multiharmonic with considerable frequency spectra and its transition to turbulence cannot be characterized by the current transition theory of monoharmonic pulsatile flow. Thus, we decided to explore the origins of such long-standing assumption of physiologic blood flow laminarity. Here, we hypothesize that the inherited dynamics of blood flow in main arteries dictate the existence of turbulence in physiologic conditions. To illustrate our hypothesis, we have used methods and tools from chaos theory, hydrodynamic stability theory and fluid dynamics to explore the existence of turbulence in physiologic blood flow. Our investigation shows that blood flow, both as described by the Navier–Stokes equation and in vivo, exhibits three major characteristics of turbulence. Womersley’s exact solution of the Navier–Stokes equation has been used with the flow waveforms from HaeMod database, to offer reproducible evidence for our findings, as well as evidence from Doppler ultrasound measurements from healthy volunteers who are some of the authors. We evidently show that physiologic blood flow is: (1) sensitive to initial conditions, (2) in global hydrodynamic instability and (3) undergoes kinetic energy cascade of non-Kolmogorov type. We propose a novel modification of the theory of vascular hemodynamics that calls for rethinking the hemodynamic–biologic links that govern physiologic and pathologic processes.
Effects of early ketamine exposure on cerebral gray matter volume and functional connectivity
Authors: Hung Chia-Chun , Liu Yi-Hsuan , Huang Chu-Chung , Chou Cheng-Ying , Chen Chun-Ming , Duann Jeng-Ren , Li Chiang-Shan R. , Lee Tony Szu-Hsien , Lin Ching-Po 
Published: September 2020

AbstractKetamine has been used for medical purposes, most typically as an anesthetic, and recent studies support its use in the treatment of depression. However, ketamine tends to be abused by adolescents and young adults. In the current study, we examined the effects of early ketamine exposure on brain structure and function. We employed MRI to assess the effects of ketamine abuse on cerebral gray matter volume (GMV) and functional connectivity (FC) in 34 users and 19 non-users, employing covariates. Ketamine users were categorized as adolescent-onset and adult-onset based on when they were first exposed to ketamine. Imaging data were processed by published routines in SPM and AFNI. The results revealed lower GMV in the left precuneus in ketamine users, with a larger decrease in the adolescent-onset group. The results from a seed-based correlation analysis show that both ketamine groups had higher functional connectivity between left precuneus (seed) and right precuneus than the control group. Compared to controls, ketamine users showed decreased GMV in the right insula, left inferior parietal lobule, left dorsolateral prefrontal cortex/superior frontal gyrus, and left medial orbitofrontal cortex. These preliminary results characterize the effects of ketamine misuse on brain structure and function and highlight the influence of earlier exposure to ketamine on the development of the brain. The precuneus, a structure of central importance to cerebral functional organization, may be particularly vulnerable to the influences of early ketamine exposure. How these structural and functional brain changes may relate to the cognitive and affective deficits remains to be determined with a large cohort of participants.
Effect of cholecalciferol on serum hepcidin and parameters of anaemia and CKD-MBD among haemodialysis patients: a randomized clinical trial
Authors: Obi Yoshitsugu , Yamaguchi Satoshi , Hamano Takayuki , Sakaguchi Yusuke , Shimomura Akihiro , Namba-Hamano Tomoko , Mikami Satoshi , Nishi Osamu , Tanaka Motoko , Kamoto Akihito , Obi Yasue , Tomosugi Naohisa , Tsubakihara Yoshiharu , Isaka Yoshitaka 
Published: September 2020

AbstractIn this multicentre double-blind randomized clinical trial, we investigated the effects of oral cholecalciferol supplementation on serum hepcidin and parameters related to anaemia and CKD-MBD among haemodialysis patients. Participants were assigned in a 2:2:1:1 ratio to either (1) thrice-weekly 3,000-IU cholecalciferol, (2) once-monthly cholecalciferol (equivalent to 9,000 IU/week), (3) thrice-weekly placebo, or (4) once-monthly placebo. We also examined the effect modifications by selected single nucleotide polymorphisms in vitamin D-related genes. Out of 96 participants, 94 were available at Month 3, and 88 completed the 6-month study. After adjustment for baseline values, serum hepcidin levels were higher at Day 3 in the combined cholecalciferol (vs. placebo) group, but were lower at Month 6 with increased erythropoietin resistance. Cholecalciferol increased serum 1,25(OH)2D levels, resulting in a greater proportion of patients who reduced the dose of active vitamin D at Month 6 (31% vs. 10% in the placebo group). Cholecalciferol also suppressed intact PTH only among patients with severe vitamin D deficiency. In conclusion, cholecalciferol supplementation increases serum hepcidin-25 levels in the short term and may increase erythropoietin resistance in the long term among haemodialysis patients. Both thrice-weekly and once-monthly supplementation effectively increases serum 1,25(OH)2D levels, and hence, reduces active vitamin D drugs.Clinical Trial Registry: This study was registered at ClinicalTrials.gov and University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) as NCT02214563 (registration date: 12/08/2014) and UMIN000011786 (registration date: 15/08/2014), respectively (please refer to the links below). ClinicalTrials.gov: https://clinicaltrials.gov/ct2/show/record/NCT02214563. UMIN-CTR: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000017152&language=E.
Evolution of outcome and complications in TAVR: a meta-analysis of observational and randomized studies
Authors: Winter Max-Paul , Bartko Philipp , Hofer Felix , Zbiral Martin , Burger Achim , Ghanim Bahil , Kastner Johannes , Lang Irene M. , Mascherbauer Julia , Hengstenberg Christian , Goliasch Georg 
Published: September 2020

AbstractAim of the present analysis was to collect and pool all available data currently in the literature regarding outcomes and complications of all approved TAVR prosthesis and to assess the transition from first to next generation TAVR devices by directly comparing both in regard of procedure related complications. Transcatheter aortic valve replacement is a well established treatment modality in patients with severe aortic stenosis deemed to be inoperable or at unacceptable risk for open heart surgery. First generation prostheses were associated with a high rate of peri-procedural complications like paravalvular regurgitation, valve malpositioning, vascular complications and conduction disorders. Refinement of the available devices incorporate features to address the limitations of the first-generation devices. A PRISMA checklist-guided systematic review and meta-analysis of prospective observational studies, national and device specific registries or randomized clinical trials was conducted. Studies were identified by searching PUBMED, SCOPUS, Cochrane Central Register of Controlled Trials and LILACs from January 2000 to October 2017. We extracted and pooled data on both mortality and complications from 273 studies for twelve different valves prostheses in a total of 68,193 patients. In second generation prostheses as compared to first generation devices, we observed a significant decrease in mortality (1.47 ± 1.73% vs. 5.41 ± 4.35%; p < 0.001), paravalvular regurgitation (1.75 ± 2.43vs. 12.39 ± 9.38, p < 0.001) and MACE. TAVR with contemporary next generation devices has led to an impressive improvement in TAVR safety driven by refined case selection, improved procedural techniques and increased site experience.
Boundary sequences flanking the mouse tyrosinase locus ensure faithful pattern of gene expression
Authors: Seruggia Davide , Fernández Almudena , Cantero Marta , Fernández-Miñán Ana , Gomez-Skarmeta José Luis , Pelczar Pawel , Montoliu Lluis 
Published: September 2020

AbstractControl of gene expression is dictated by cell-type specific regulatory sequences that physically organize the structure of chromatin, including promoters, enhancers and insulators. While promoters and enhancers convey cell-type specific activating signals, insulators prevent the cross-talk of regulatory elements within adjacent loci and safeguard the specificity of action of promoters and enhancers towards their targets in a tissue specific manner. Using the mouse tyrosinase (Tyr) locus as an experimental model, a gene whose mutations are associated with albinism, we described the chromatin structure in cells at two distinct transcriptional states. Guided by chromatin structure, through the use of Chromosome Conformation Capture (3C), we identified sequences at the 5′ and 3′ boundaries of this mammalian gene that function as enhancers and insulators. By CRISPR/Cas9-mediated chromosomal deletion, we dissected the functions of these two regulatory elements in vivo in the mouse, at the endogenous chromosomal context, and proved their mechanistic role as genomic insulators, shielding the Tyr locus from the expression patterns of adjacent genes.
Second wave COVID-19 pandemics in Europe: a temporal playbook
Authors: Cacciapaglia Giacomo , Cot Corentin , Sannino Francesco 
Published: September 2020

AbstractA second wave pandemic constitutes an imminent threat to society, with a potentially immense toll in terms of human lives and a devastating economic impact. We employ the epidemic Renormalisation Group (eRG) approach to pandemics, together with the first wave data for COVID-19, to efficiently simulate the dynamics of disease transmission and spreading across different European countries. The framework allows us to model, not only inter and extra European border control effects, but also the impact of social distancing for each country. We perform statistical analyses averaging on different level of human interaction across Europe and with the rest of the World. Our results are neatly summarised as an animation reporting the time evolution of the first and second waves of the European COVID-19 pandemic. Our temporal playbook of the second wave pandemic can be used by governments, financial markets, the industries and individual citizens, to efficiently time, prepare and implement local and global measures.
Structural and vibrational properties of agrellite
Authors: Kaneva Ekaterina , Bogdanov Alexandr , Shendrik Roman 
Published: September 2020

AbstractAgrellite, NaCa2Si4O10F, is a tubular silicate mineral which crystal structure is characterized by extended [Si8O20]8– tubes and has a two-dimensional channel system. The mineral is a representative of a complex silicate family which contains some structural voids but cannot be considered as microporous because of small channel widths. However, the channel system of such minerals is able to host single guest atoms, molecules or radicals which can affect their physical properties. Presently, the exact mechanism of such hosting is undetermined. However, such information could be quite useful for materials’ application as zeolites as well as for a better understanding of their formation mechanisms. In this work we couple X-ray diffraction, infrared (IR) spectroscopy and ab initio calculations to identify structural features in agrellite from Malyy Murun massif (Russia) caused by incorporation of either H2O or OH− into the channel system. We construct structural models of water-containing NaCa2Si4O10F and identified H2O positions. The derivation of H2O sites is based on simulation of IR-spectra. Infrared spectroscopy in combination with the ab initio calculation has proven to be an effective tool for the identification of the structural positions of hydroxyl anions (OH−) and neutral water groups (H2O) in minerals.
How to do quantile normalization correctly for gene expression data analyses
Authors: Zhao Yaxing , Wong Limsoon , Goh Wilson Wen Bin 
Published: September 2020

AbstractQuantile normalization is an important normalization technique commonly used in high-dimensional data analysis. However, it is susceptible to class-effect proportion effects (the proportion of class-correlated variables in a dataset) and batch effects (the presence of potentially confounding technical variation) when applied blindly on whole data sets, resulting in higher false-positive and false-negative rates. We evaluate five strategies for performing quantile normalization, and demonstrate that good performance in terms of batch-effect correction and statistical feature selection can be readily achieved by first splitting data by sample class-labels before performing quantile normalization independently on each split (“Class-specific”). Via simulations with both real and simulated batch effects, we demonstrate that the “Class-specific” strategy (and others relying on similar principles) readily outperform whole-data quantile normalization, and is robust-preserving useful signals even during the combined analysis of separately-normalized datasets. Quantile normalization is a commonly used procedure. But when carelessly applied on whole datasets without first considering class-effect proportion and batch effects, can result in poor performance. If quantile normalization must be used, then we recommend using the “Class-specific” strategy.
Visualization of the distribution of nanoparticle-formulated AZD2811 in mouse tumor model using matrix-assisted laser desorption ionization mass spectrometry imaging
Authors: Ryu Shoraku , Ohuchi Mayu , Yagishita Shigehiro , Shimoi Tatsunori , Yonemori Kan , Tamura Kenji , Fujiwara Yasuhiro , Hamada Akinobu 
Published: September 2020

AbstractPenetration of nanoparticles into viable tumor regions is essential for an effective response. Mass spectrometry imaging (MSI) is a novel method for evaluating the intratumoral pharmacokinetics (PK) of a drug in terms of spatial distribution. The application of MSI for analysis of nanomedicine PK remains in its infancy. In this study, we evaluated the applicability of MALDI-MSI for nanoparticle-formulated drug visualization in tumors and biopsies, with an aim toward future application in clinical nanomedicine research. We established an analytic method for the free drug (AZD2811) and then applied it to visualize nanoparticle-formulated AZD2811. MSI analysis demonstrated heterogeneous intratumoral drug distribution in three xenograft tumors. The intensity of MSI signals correlated well with total drug concentration in tumors, indicating that drug distribution can be monitored quantitatively. Analysis of tumor biopsies indicated that MSI is applicable for analyzing the distribution of nanoparticle-formulated drugs in tumor biopsies, suggesting clinical applicability.
Omega-3 fatty acid prevents the development of heart failure by changing fatty acid composition in the heart
Authors: Toko Haruhiro , Morita Hiroyuki , Katakura Masanori , Hashimoto Michio , Ko Toshiyuki , Bujo Satoshi , Adachi Yusuke , Ueda Kazutaka , Murakami Haruka , Ishizuka Masato , Guo Jiaxi , Zhao Chunxia , Fujiwara Takayuki , Hara Hironori , Takeda Norifumi , Takimoto Eiki , Shido Osamu , Harada Mutsuo , Komuro Issei 
Published: September 2020

AbstractSome clinical trials showed that omega-3 fatty acid (FA) reduced cardiovascular events, but it remains unknown whether omega-3 FA supplementation changes the composition of FAs and their metabolites in the heart and how the changes, if any, exert beneficial effects on cardiac structure and function. To clarify these issues, we supplied omega-3 FA to mice exposed to pressure overload, and examined cardiac structure and function by echocardiography and a proportion of FAs and their metabolites by gas chromatography and liquid chromatography-tandem mass spectrometry, respectively. Pressure overload induced cardiac hypertrophy and dysfunction, and reduced concentration of all FAs’ components and increased free form arachidonic acid and its metabolites, precursors of pro-inflammatory mediators in the heart. Omega-3 FA supplementation increased both total and free form of eicosapentaenoic acid, a precursor of pro-resolution mediators and reduced free form arachidonic acid in the heart. Omega-3 FA supplementation suppressed expressions of pro-inflammatory cytokines and the infiltration of inflammatory cells into the heart and ameliorated cardiac dysfunction and fibrosis. These results suggest that omega-3 FA-induced changes of FAs composition in the heart have beneficial effects on cardiac function via regulating inflammation.
The fatty-acid amide hydrolase inhibitor URB597 inhibits MICA/B shedding
Authors: Sekiba Kazuma , Otsuka Motoyuki , Seimiya Takahiro , Tanaka Eri , Funato Kazuyoshi , Miyakawa Yu , Koike Kazuhiko 
Published: September 2020

AbstractMICA/B proteins are expressed on the surface of various types of stressed cells, including cancer cells. Cytotoxic lymphocytes expressing natural killer group 2D (NKG2D) receptor recognize MICA/B and eliminate the cells. However, cancer cells evade such immune recognition by inducing proteolytic shedding of MICA/B proteins. Therefore, preventing the shedding of MICA/B proteins could enhance antitumor immunity. Here, by screening a protease inhibitor library, we found that the fatty-acid amide hydrolase (FAAH) inhibitor, URB597, suppresses the shedding of MICA/B. URB597 significantly reduced the soluble MICA level in culture medium and increased the MICA level on the surface of cancer cells. The effect was indirect, being mediated by increased expression of tissue inhibitor of metalloproteinases 3 (TIMP3). Knockdown of TIMP3 expression reversed the effect of URB597, confirming that TIMP3 is required for the MICA shedding inhibition by URB597. In contrast, FAAH overexpression reduced TIMP3 expression and the cell-surface MICA level and increased the soluble MICA level. These results suggest that inhibition of FAAH could prevent human cancer cell evasion of immune-mediated clearance.