bluuebunny/crossref_metadata_2025 huggingface dataset:
Time-course of tissue factor plasma level in patients with acute coronary syndrome
Authors: Bis J , Vojáček J , Dušek J , Pecka M , Palička V , Šťásek J , Malý J
Published: February 2021

Enhanced expression of tissue factor (TF) may result in
thrombosis contributing to acute clinical consequences of
coronary artery disease. Several studies demonstrated elevated
plasma levels of TF in patients with acute coronary syndrome
(ACS). The aim of our study was to compare the concentrations
of TF in coronary sinus (CS), proximal part of the left coronary
artery (LCA) and peripheral vein (PV) of patients with ACS and
stable coronary artery disease (SCAD). Time course of the TF
plasma levels in PV was followed on day 1 and day 7 after index
event of ACS presentation and was compared to day 0 values. No
heparin was given prior to the blood sampling. Twenty-nine
patients in the ACS group (age 63.6±10.8 years, 20 males,
9 females) and 24 patients with SCAD (age 62.3±8.1 years,
21 males, 3 females) were examined. TF plasma level was
significantly higher in patients with ACS than in those with SCAD
(239.0±99.3 ng/ml vs. 164.3±114.2 ng/ml; p=0.016). There was
no difference in TF plasma levels in PV, CS and LCA (239.0± 99.3
ng/ml vs. 253.7±131.5 ng/ml vs. 250.6±116.4 ng/ml,
respectively). TF plasma levels tended to decrease only nonsignificantly on the day 7 (224.4±109.8 ng/ml). Significant linear
correlation between TF and high sensitivity CRP (hs-CRP) levels
on day 0 was found. In conclusion, TF plasma levels are elevated
in patients with ACS not only locally in CS but also in systematic
circulation. Our data support the relationship between TF
production and proinflammatory mediators.
Regionally-selective cell colonization of micropatterned surfaces prepared by plasma polymerization of acrylic acid and 1,7-octadiene
Authors: Filová E , Bullett NA , Bačáková L , Grausová Ľ , Haycock JW , Hlučilová J , Klíma J , Shard A
Published: February 2021

Micropatterned surfaces have been used as a tool for controlling
the extent and strength of cell adhesion, the direction of cell
growth and the spatial distribution of cells. In this study,
chemically micropatterned surfaces were prepared by successive
plasma polymerization of acrylic acid (AA) and 1,7-octadiene
(OD) through a mask. Rat vascular smooth muscle cells (VSMC),
bovine endothelial cells (EC), porcine mesenchymal stem cells
(MSC) or human skeletal muscle cells (HSKMC) were seeded on
these surfaces in densities from 9,320 cells/cm2 to 31,060
cells/cm2. All cell types adhered and grew preferentially on the
strip-like AA domains. Between day 1 and 7 after seeding, the
percentage of cells on AA domains ranged from 84.5 to 63.3 %
for VSMC, 85.3 to 73.5 % for EC, 98.0 to 90.0 % for MSC, and
93.6 to 55.0 % for HSKMC. The enzyme-linked immunosorbent
assay (ELISA) revealed that the concentration of alpha-actin per
mg of protein was significantly higher in VSMC on AA. Similarly,
immunofluorescence staining of von Willebrand factor showed
more apparent Weibel-Palade bodies in EC on AA domains. MSC
growing on AA had better developed beta-actin cytoskeleton,
although they were less stained for hyaluronan receptor (CD44).
In accordance with this, MSC on AA contained a higher
concentration of beta-actin, although the concentration of CD44
was lower. HSKMC growing on AA had a better developed alphaactin cytoskeleton. These results based on four cell types suggest
that plasma polymerization is a suitable method for producing
spatially defined patterned surfaces for controlled cell adhesion,
proliferation and maturation.
Mechanism of action of homocysteine and its thiolactone in hemostasis system
Authors: Karolczak K , Olas B
Published: February 2021

In the article, the actions of homocysteine (Hcys) and its
metabolite - cyclic thioester – homocysteine thiolactone (HTL) on
complex process of hemostasis, which regulates the flowing
properties of blood, are described. Possible interaction of Hcys
and HTL with endothelial cells, blood platelets, plasmatic
fibrinogen and plasminogen, as the important major components
of hemostasis are also discussed. The modification of hemostatic
proteins (N-homocysteinylated or S-homocysteinylated proteins)
induced by Hcys or its thiolactone, and links of homocysteine or
homocysteine thiolactone to •NO metabolism seem to be the
main reason of biotoxicty of homocysteine in cardiovascular
diseases.
The effect of rosiglitazone on the expression of thrombogenic markers on leukocytes in type 2 diabetes mellitus
Authors: Svobodová H , Štulc T , Kasalová Z , Doležalová R , Marinov I , Čapek P , Česka R
Published: February 2021

Diabetes mellitus is associated with a number of prothrombotic
abnormalities, and correction of these abnormalities might
translate into the reduction of cardiovascular risk. Glitazones
improve endothelial function and reduce inflammation, but much
less is known about their effect on thrombogenic factors. We
have therefore studied the effect of rosiglitazone on leukocyte
and soluble thrombogenic markers in patients with type 2
diabetes mellitus. Thirty-three subjects with type 2 diabetes and
32 normal controls were included; patients were examined at
baseline and after 5 months of rosiglitazone treatment
(4 mg/day). We measured leukocyte-platelet aggregates and
leukocyte expression of either P-selectin glycoprotein ligand 1
(PSGL-1) or receptor for urokinase-type plasminogen activator
(uPAR) using flow cytometry, as well as several circulating
soluble thrombogenic markers by ELISA method. Leukocyte
expression of uPAR and PSGL-1 was significantly higher in
patients than in controls. Leukocyte-platelet aggregates and
leukocyte expression of uPAR and PSGL-1 significantly decreased
after rosiglitazone. There was also significant decrease in CRP
and fibrinogen levels, but there was no effect of diabetes and/or
rosiglitazone on other circulating molecules. In conclusions, we
observed a substantial improvement in the expression of
thrombogenic markers on leukocytes after rosiglitazone
treatment, suggesting the novel antithrombotic effects of
rosiglitazone.
Beta 2-band synchronization during a visual oddball task
Authors: Kukleta M , Bob P , Brázdil M , Roman R , Rektor I
Published: February 2021

The study investigated whether specific changes in phase
synchrony in the beta 2 frequency band of EEG (25-35 Hz)
occurred during a recognition task. The level of synchrony was
examined between one hundred and eighty loci in the frontal and
temporal lobes of eight epileptic patients with intracerebral
electrodes; the EEG records were obtained during a visual
oddball task. In each pair of records, the correlation curves were
created from the sequence of correlation coefficients calculated.
These curves consisted of irregular oscillations between the
maximal and minimal r-values. Transient highly synchronized
activity was observed during the whole time course of the
experiment in all record pairs investigated and a significant
relationship was found between the number of such episodes
and the mean correlation coefficient (Spearman R 0.84; N 3240;
p<0.001). On averaged curves, which were calculated using
stimulus onsets as the trigger of averaging, a significant increase
of the mean correlation coefficient in the post-stimulus epoch
was found (p<0.01 after both target and non-target stimuli;
t-test for dependent samples). As the cognitive demand
significantly increases after stimulus presentation, the results are
considered to be the first evidence from intracranial recording of
increased synchronization in the beta 2 frequency band related to
the cognitive activity.
Investigation of the tip injection for stall control in a transonic compressor with inlet distortion
Authors: Zhang Wenqiang , Vahdati Mehdi
Published: February 2021

Experimental studies have shown that tip injection upstream of the rotor can extend its operational range when subjected to circumferential inlet distortion. Typically, injectors are placed uniformly around the annulus. However, such arrangement consumes a large amount of high-pressure air and decreases the overall efficiency of the compression system. The aim of this paper is to minimise the amount of the injected air by determining the most effective circumferential location for the injector. In this study, NASA stage 35 was used as the test case. The experiment was conducted with a circumferential total pressure distortion of 120 degrees. In the first part of this paper, numerical simulations were compared against the experimental data and good match was obtained. In the second part, tip injection at three different positions were tested: the clean flow region (Position 1), the distorted region (Position 2) and the border between the clean and distorted regions (Position 3). It was found that a mild injection (0.66% of the main flow) at Position 2 and Position 3 can extend the stall margin by 1.8% and 2.7%, respectively. No obvious improvement was observed for the injection at Position 1. With a larger injection of 1.5% of main flow at Position 3, the stall margin improved further with no efficiency loss.
pCysMod: Prediction of Multiple Cysteine Modifications Based on Deep Learning Framework
Authors: Li Shihua , Yu Kai , Wu Guandi , Zhang Qingfeng , Wang Panqin , Zheng Jian , Liu Ze-Xian , Wang Jichao , Gao Xinjiao , Cheng Han
Published: February 2021

Thiol groups on cysteines can undergo multiple post-translational modifications (PTMs), acting as a molecular switch to maintain redox homeostasis and regulating a series of cell signaling transductions. Identification of sophistical protein cysteine modifications is crucial for dissecting its underlying regulatory mechanism. Instead of a time-consuming and labor-intensive experimental method, various computational methods have attracted intense research interest due to their convenience and low cost. Here, we developed the first comprehensive deep learning based tool pCysMod for multiple protein cysteine modification prediction, including S-nitrosylation, S-palmitoylation, S-sulfenylation, S-sulfhydration, and S-sulfinylation. Experimentally verified cysteine sites curated from literature and sites collected by other databases and predicting tools were integrated as benchmark dataset. Several protein sequence features were extracted and united into a deep learning model, and the hyperparameters were optimized by particle swarm optimization algorithms. Cross-validations indicated our model showed excellent robustness and outperformed existing tools, which was able to achieve an average AUC of 0.793, 0.807, 0.796, 0.793, and 0.876 for S-nitrosylation, S-palmitoylation, S-sulfenylation, S-sulfhydration, and S-sulfinylation, demonstrating pCysMod was stable and suitable for protein cysteine modification prediction. Besides, we constructed a comprehensive protein cysteine modification prediction web server based on this model to benefit the researches finding the potential modification sites of their interested proteins, which could be accessed at http://pcysmod.omicsbio.info. This work will undoubtedly greatly promote the study of protein cysteine modification and contribute to clarifying the biological regulation mechanisms of cysteine modification within and among the cells.
Establishment of Novel DNA Methylation-Based Prostate Cancer Subtypes and a Risk-Predicting Eight-Gene Signature
Authors: Zhang Enchong , Shiori Fujisawa , Mu Oscar YongNan , He Jieqian , Ge Yuntian , Wu Hongliang , Zhang Mo , Song Yongsheng
Published: February 2021

Prostate cancer (PCa) is the most common malignant tumor affecting males worldwide. The substantial heterogeneity in PCa presents a major challenge with respect to molecular analyses, patient stratification, and treatment. Least absolute shrinkage and selection operator was used to select eight risk-CpG sites. Using an unsupervised clustering analysis, called consensus clustering, we found that patients with PCa could be divided into two subtypes (Methylation_H and Methylation_L) based on the DNA methylation status at these CpG sites. Differences in the epigenome, genome, transcriptome, disease status, immune cell composition, and function between the identified subtypes were explored using The Cancer Genome Atlas database. This analysis clearly revealed the risk characteristics of the Methylation_H subtype. Using a weighted correlation network analysis to select risk-related genes and least absolute shrinkage and selection operator, we constructed a prediction signature for prognosis based on the subtype classification. We further validated its effectiveness using four public datasets. The two novel PCa subtypes and risk predictive signature developed in this study may be effective indicators of prognosis.
Prognostic Signatures of Metabolic Genes and Metabolism-Related Long Non-coding RNAs Accurately Predict Overall Survival for Osteosarcoma Patients
Authors: Chao-yang Gong , Rong Tang , Yong-qiang Shi , Tai-cong Liu , Kai-sheng Zhou , Wei Nan , Hai-hong Zhang
Published: February 2021

In this study, we identified eight survival-related metabolic genes in differentially expressed metabolic genes by univariate Cox regression analysis based on the therapeutically applicable research to generate effective treatments (n = 84) data set and genotype tissue expression data set (n = 396). We also constructed a six metabolic gene signature to predict the overall survival of osteosarcoma (OS) patients using least absolute shrinkage and selection operator (Lasso) Cox regression analysis. Our results show that the six metabolic gene signature showed good performance in predicting survival of OS patients and was also an independent prognostic factor. Stratified correlation analysis showed that the metabolic gene signature accurately predicted survival outcomes in high-risk and low-risk OS patients. The six metabolic gene signature was also verified to perform well in predicting survival of OS patients in an independent cohort (GSE21257). Then, using univariate Cox regression and Lasso Cox regression analyses, we identified an eight metabolism-related long noncoding RNA (lncRNA) signature that accurately predicts overall survival of OS patients. Gene set variation analysis showed that the apical surface and bile acid metabolism, epithelial mesenchymal transition, and P53 pathway were activated in the high-risk group based on the eight metabolism-related lncRNA signature. Furthermore, we constructed a competing endogenous RNA (ceRNA) network and conducted immunization score analysis based on the eight metabolism-related lncRNA signature. These results showed that the six metabolic gene signature and eight metabolism-related lncRNA signature have good performance in predicting the survival outcomes of OS patients.
Identification and Analysis of An Epigenetically Regulated Five-lncRNA Signature Associated With Outcome and Chemotherapy Response in Ovarian Cancer
Authors: Yang Hao , Gao Lin , Zhang Meiling , Ning Ning , Wang Yan , Wu Di , Li Xiaomei
Published: February 2021

The deregulation of long non-coding RNAs (lncRNAs) by epigenetic alterations has been implicated in cancer initiation and progression. However, the epigenetically regulated lncRNAs and their association with clinical outcome and therapeutic response in ovarian cancer (OV) remain poorly investigated. This study performed an integrative analysis of DNA methylation data and transcriptome data and identified 419 lncRNAs as potential epigenetically regulated lncRNAs. Using machine-learning and multivariate Cox regression analysis methods, we identified and developed an epigenetically regulated lncRNA expression signature (EpiLncRNASig) consisting of five lncRNAs from the list of 17 epigenetically regulated lncRNAs significantly associated with outcome. The EpiLncRNASig could stratify patients into high-risk groups and low-risk groups with significantly different survival and chemotherapy response in different patient cohorts. Multivariate Cox regression analyses, after adjusted by other clinical features and treatment response, demonstrated the independence of the DEpiLncSig in predicting survival. Functional analysis for relevant protein-coding genes of the DEpiLncSig indicated enrichment of known immune-related or cancer-related biological pathways. Taken together, our study not only provides a promising prognostic biomarker for predicting outcome and chemotherapy response but also will improve our understanding of lncRNA epigenetic regulation mechanisms in OV.
Development and Evaluation of Real-Time Reverse Transcription Recombinase Polymerase Amplification Assay for Rapid and Sensitive Detection of West Nile Virus in Human Clinical Samples
Authors: Tomar Priyanka Singh , Kumar Sanjay , Patel Sapan , Kumar Jyoti S.
Published: February 2021

West Nile virus (WNV) causes West Nile fever and encephalitis worldwide. Currently, there are no effective drugs or vaccines available in the market to treat WNV infection in humans. Hence, it is of paramount importance to detect WNV early for the success of the disease control programs and timely clinical management in endemic areas. In the present paper, we report the development of real-time reverse transcription recombinase polymerase amplification (RT-RPA) assay for rapid and real-time detection of WNV targeting the envelope (env) gene of the virus. The RPA reaction was performed successfully at 39°C for 15 min in a real-time thermal cycler. The sensitivity of this assay was found similar to that of the quantitative real-time RT PCR (RT-qPCR) assay, which could detect 10 copies of the gene. The efficacy of the assay was evaluated with a panel of 110 WN suspected human samples showing the signs of retinitis, febrile illness and acute posterior uveitis. In comparison with RT-qPCR, RT-RPA showed a specificity of 100% (CI, 95.07–100%) and sensitivity of 96.15% (CI, 80.36–99.90%) with a negative (NPV) and positive predictive value (PPV) of 98.65 and 100%, respectively. The level of agreement between RT-RPA and reference RT-qPCR assay was shown to be very high. The turnaround time of real-time RPA assay is about 10-20 times faster than the RT-qPCR, which confirms its utility in the rapid and sensitive diagnosis of WNV infection. To the best of our knowledge, this is the first report which deals with the development of real-time RT-RPA assay for simple, rapid, sensitive, and specific detection of WNV in human clinical samples. The present RT-RPA assay proves to be a powerful tool that can be used for the rapid diagnosis of a large number of patient samples in endemic settings.
Circular RNA Involvement in the Protective Effect of Human Umbilical Cord Mesenchymal Stromal Cell-Derived Extracellular Vesicles Against Hypoxia/Reoxygenation Injury in Cardiac Cells
Authors: Zhang Changyi , Wang Hongwu , Li Jilin , Ma Lian
Published: February 2021

Human umbilical cord mesenchymal stromal cell-derived extracellular vesicles (HuMSC-EVs) can repair damaged tissues. The expression profile of circular RNAs (circRNAs) provides valuable insights into the regulation of the repair process and the exploration of the repair mechanism. AC16 cardiomyocytes were exposed to hypoxia/reoxygenation (H/R) injury and subsequently cultured with or without HuMSC-EVs (Group T and Group C, respectively). High-throughput RNA sequencing was implemented for the two groups. On the basis of the transcriptome data, gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and network analyses were carried out to determine the differential gene expression profiles between the two groups. After screening the circRNA database, the results were proved by quantitative real-time polymerase chain reaction. The survival rate of cardiomyocytes exposed to H/R was increased by treatment with HuMSC-EVs. RNA-seq analysis showed that 66 circRNAs were differentially expressed in cardiomyocytes in the co-cultured group. The cellular responses to hypoxia and to decreased oxygen levels were at the top of the GO upregulated list for the two groups, while the vascular endothelial growth factor signaling pathway, long-term potentiation, and the glucagon signaling pathway were at the top of the KEGG pathway upregulated list for the two groups. In the same samples, the 10 most aberrantly upregulated circRNAs were chosen for further verification of their RNA sequences. Seven of the 10 most aberrant circRNAs were significantly upregulated in the co-cultured group and in the HuMSC-EVs. Our results revealed that upregulated circRNAs were abundant during the repair of damaged cardiomyocytes by HuMSC-EVs, which provides a new perspective for the repair of H/R by HuMSC-EVs.
Updated Role of Neuropeptide Y in Nicotine-Induced Endothelial Dysfunction and Atherosclerosis
Authors: Zheng Yan-li , Wang Wan-da , Li Mei-mei , Lin Shu , Lin Hui-li
Published: February 2021

Cardiovascular disease is the leading cause of death worldwide. Endothelial dysfunction of the arterial vasculature plays a pivotal role in cardiovascular pathogenesis. Nicotine-induced endothelial dysfunction substantially contributes to the development of arteriosclerotic cardiovascular disease. Nicotine promotes oxidative inflammation, thrombosis, pathological angiogenesis, and vasoconstriction, and induces insulin resistance. However, the exact mechanism through which nicotine induces endothelial dysfunction remains unclear. Neuropeptide Y (NPY) is widely distributed in the central nervous system and peripheral tissues, and it participates in the pathogenesis of atherosclerosis by regulating vasoconstriction, energy metabolism, local plaque inflammatory response, activation and aggregation of platelets, and stress and anxiety-related emotion. Nicotine can increase the expression of NPY, suggesting that NPY is involved in nicotine-induced endothelial dysfunction. Herein, we present an updated review of the possible mechanisms of nicotine-induced atherosclerosis, with a focus on endothelial cell dysfunction associated with nicotine and NPY.
Observational Evidence of Distinguishable Weather Patterns for Three Types of Sudden Stratospheric Warming During Northern Winter
Authors: Choi Hyesun , Kim Joo-Hong , Kim Baek-Min , Kim Seong-Joong
Published: February 2021

Sudden stratospheric warming (SSW) events often lead to a cold surface air temperature anomaly over the extratropical regions. In this study, we propose, through observational evidence, that the types of SSW determine the severity of the cold anomaly. Based on the three-type classification of SSW, it is found that the surface air temperature drops notably over central to eastern North America following an SSW-type transition, especially from displacement to split. Note, however, that the differences in mean surface air temperature anomalies between SSW types are not statistically significant, even though after SSW-type transition from displacement to split, surface air temperature anomalies are colder than the other two types. The development of an anomalous tropospheric ridge in the North Pacific Arctic sector, associated with the difference in the vertical and zonal propagation of planetary waves, characterizes the post-warming period of the displacement–split type. After the occurrence of the displacement–split type transition of SSW events, upward propagation of planetary waves of zonal wavenumber 1 is suppressed, whereas planetary waves of zonal wavenumber 2 increase in the troposphere. Accompanying the ridge in the North Pacific, a trough developed downstream over North America that carries cold polar air therein. The results in this study are relevant for the subseasonal time scale, within 20 days after an SSW occurrence.
Study of Rheological Property and Flow Behavior for Nanoparticles Enhanced VES System in Porous Media
Authors: Liu Zhaoxia , Wang Qiang , Gao Ming , Luo Wenli , Cai Hongyan
Published: February 2021

In this paper, a composite sample (VES and SiO2 nanoparticle) was used to overcome the deficiencies of polymer. The rheological character of the VES/nanoparticles hybrid and flow behavior in porous media were examined. It was found that SiO2 nanoparticles exhibited viscosifying action and improved the oil tolerance. In addition, the VES solution without nanoparticles showed a lower capacity to recover oil, which might be attributed to the fact that wormlike micelles would be destroyed in crude oil. On the contrary, an enhanced oil recovery of 9.68% was achieved in the composited experiment for the VES sample with nanoparticles which is relatively stable with oil.
Convective Heat Transfer and Pumping Power Analysis of MWCNT + Fe3O4/Water Hybrid Nanofluid in a Helical Coiled Heat Exchanger with Orthogonal Rib Turbulators
Authors: Irandoost Shahrestani Misagh , Houshfar Ehsan , Ashjaee Mehdi , Allahvirdizadeh Payam
Published: February 2021

Utilizing nanofluids in heat exchangers can lead to improved thermal performance. Nanofluids with suspended carbon nanotubes are specifically desirable in thermal systems because of their unique capabilities. In this study, convective heat transfer and required pumping power are studied simultaneously for a helical coiled heat exchanger with laminar water flow while incorporating 0.1 and 0.3 percent volume fraction of the hybrid nanofluid MWCNT + Fe3O4/water. Two different geometries of bare and ribbed tubes are used for the heat exchanger part. The ribs are chosen to be orthogonal, i.e., 90° with respect to the inclined ones. Three different Reynolds numbers are selected for investigation, all in laminar flow regime based on the non-dimensional M number defined in coiled tubes. Computational fluid dynamics is used to study thermal and fluid behavior of the problem. The convective heat transfer coefficient can serve as a criterion to measure the effectiveness of utilizing nanofluids in heat exchangers by taking the pressure drop and pumping power of the system into consideration. Finally, the artificial neural network curve fitting tool of MATLAB is used to make a good fit in the data range of the problem. It is shown that for most cases of the study, the pumping power ratio is less than 1 that can be considered appropriate from energy consumption viewpoint.
Evaluation on the Cost of Energy Transition: A Case Study of Fujian, China
Authors: Lin Changyong , Li Yuanfei , Cai Qiyuan , Shi Pengjia , Song Malin , Wu Wei
Published: February 2021

The development of renewable energy in Fujian province has entered a bottleneck period in recent years. Considering the impact of COVID-19, how to formulate the provincial energy development strategy based on the 14th Five-year Plan is an important issue that need to be addressed for Fujian. This paper constructs a provincial Computable General Equilibrium model to analyze the cost of energy transition to renewable resources and tries to find a better pathway that integrated into account social efficiency and cost. The simulation results show that after the implementation of energy substitution, the actual electricity price will increase by about 1.6% and the electricity consumption in various sectors will also decrease, especially in the secondary industry. Overall, the marginal impact of energy substitution on the economy is significant.
Effects of DNA Methylation on TFs in Human Embryonic Stem Cells
Authors: Luo Ximei , Zhang Tianjiao , Zhai Yixiao , Wang Fang , Zhang Shumei , Wang Guohua
Published: February 2021

DNA methylation is an important epigenetic mechanism for gene regulation. The conventional view of DNA methylation is that DNA methylation could disrupt protein-DNA interactions and repress gene expression. Several recent studies reported that DNA methylation could alter transcription factors (TFs) binding sequence specificityin vitro. Here, we took advantage of the large sets of ChIP-seq data for TFs and whole-genome bisulfite sequencing data in many cell types to perform a systematic analysis of the protein-DNA methylationin vivo. We observed that many TFs could bind methylated DNA regions, especially in H1-hESC cells. By locating binding sites, we confirmed that some TFs could bind to methylated CpGs directly. The different proportion of CpGs at TF binding specificity motifs in different methylation statuses shows that some TFs are sensitive to methylation and some could bind to the methylated DNA with different motifs, such as CEBPB and CTCF. At the same time, TF binding could interactively alter local DNA methylation. The TF hypermethylation binding sites extensively overlap with enhancers. And we also found that some DNase I hypersensitive sites were specifically hypermethylated in H1-hESC cells. At last, compared with TFs’ binding regions in multiple cell types, we observed that CTCF binding to high methylated regions in H1-hESC were not conservative. These pieces of evidence indicate that TFs that bind to hypermethylation DNA in H1-hESC cells may associate with enhancers to regulate special biological functions.
Gentamicin Induced Microbiome Adaptations Associate With Increased BCAA Levels and Enhance Severity of Influenza Infection
Authors: Sun Yakun , He Zhili , Li Jiajia , Gong Saisai , Yuan Shunzong , Li Tao , Ning Nianzhi , Xing Li , Zhang Liangyan , Chen Fanghong , Li Zhan , Wang Jianxin , Luo Deyan , Wang Hui
Published: February 2021

Involvement of gut microbiota in pulmonary disease by the gut-lung axis has been widely observed. However, the cross-talk messengers between respiratory mucosal immunity and gut microbiota are largely unknown. Using selective pharmacologic destruction of gut microenvironment mouse models, we found gut microbiota displayed significantly lower alpha diversity and relative abundance of bacteria in Gentamicin treated mice. Metagenomic studies revealed functional differences in gut bacteria in altering metabolic profiles in mice blood. Branched-chain amino acids (BCAAs) are the essential factors linked between gut and lung. During this process, selective destruction of gut microbiota by Gentamicin induced high levels of BCAAs, and the high levels of BCAAs impacted the lung immunity against influenza virus.In vivo, Gentamicin-treated mice or mice fed with high BCAAs diets displayed reduced survival. At the sites of infection, the number of CD11b+Ly6G+cells decreased, and CD8+T cells increased accompanied by exuberant expression of pro-inflammatory cytokines could result in tissue damage. CD11b+Ly6G+cells transplantation conferred remarkable protection from influenza virus infections.In vitro, BCAAs promoted bone marrow-derived cells differentiation to dendritic cells. Taken together, these findings demonstrate that Gentamicin induced disruption of the gut microbiota leads to increased BCAA levels that suppress CD11b+Ly6c+cell development in association with overactive CD8+T responses which may contribute to enhanced severity of the viral infection.
High Resolution Spatial Distribution for the Hexactinellid Sponges Asconema setubalense and Pheronema carpenteri in the Central Cantabrian Sea
Authors: Rodríguez-Basalo Augusto , Prado Elena , Sánchez Francisco , Ríos Pilar , Gómez-Ballesteros María , Cristobo Javier
Published: February 2021

In the present work we focus on the distribution of two species of sponges. One of these is Asconema setubalense, a sponge found in rocky substrate that was sampled with a photogrammetric vehicle through georeferenced images. The other is Pheronema carpenteri, which inhabits soft bottoms and was sampled by beam trawl. For the spatial distribution modeling of both sponges, the geomorphological variables of depth, slope, broad and fine scale bathymetric position index (BPI), aspect, and types of bottoms were used, all with a resolution of 32 m. Additionally, layers of silicates and currents near the bottom were extracted from Copernicus Marine Environment Monitoring Service (CMEMS), with a resolution of ∼4 and ∼9 km, respectively. Due to the low resolution of the layers, it was considered necessary to validate their use by model comparison, where those that included these variables turned out to be more explanatory than the others. The models were developed in a complex continental break of the Central Cantabrian Sea, which comprises several submarine canyons and a seamount (Le Danois Bank). On the one hand, a very high resolution (32 m) spatial distribution model based on A. setubalense presence was developed using the MaxEnt maximum entropy model. On the other, depending on the availability of density data, generalized additive models (GAMs) were developed for P. carpenteri distribution, although in this case the sampler only allowed a maximum resolution of almost 1 Km. For the A. setubalense, the variables that best explained their distribution were ground types and depth, and for P. carpenteri, silicates, slope, northness, and eastward seawater velocity. The final model scores obtained were an AUC of 0.98 for the MaxEnt model, and an R squared of 0.87 for the GAM model.
Ten Commandments for Sustainable, Safe, and W/Healthy Sandy Coasts Facing Global Change
Authors: Silva Rodolfo , Oumeraci Hocine , Martínez M. Luisa , Chávez Valeria , Lithgow Debora , van Tussenbroek Brigitta I. , van Rijswick Helena F. M. W. , Bouma Tjeerd J.
Published: February 2021

Sandy coasts represent about one-third of the global coastline and are among the most valuable and most vulnerable areas for humans and many other species. Socio-economic development and climate change impacts, together with traditional engineering for shore protection, have pervasively resulted in coastal squeeze, thereby threatening coastal life and economic activities, and the very survival of coastal ecosystems. In the past, the responses to problems such as land loss, coastal erosion and flooding were primarily reactive, through gray engineering solutions, with little interest shown in the ecosystem processes impacted by coastal armoring. In recent decades, coastal management strategies have become more diverse, embracing traditional engineering solutions alongside ecosystem-based measures. Even so, many of these new strategies still fail to meet sustainability criteria. Inspired by Per Bruun’s “The Ten Demands for Coastal Protection” from 1972, this article attempts to consider these changes and knowledge acquired since the 1970s, in order to tentatively formulate “Ten Commandments” for the sustainability of sandy coasts in face of climate change and socio-economic development. As such, the paper offers a new vision and briefly summarizes good practices for the management of sandy coasts, particularly useful for those who, at whatever level of influence, could contribute to the long-term realization of this new vision.
Coastal Fishers Livelihood Behaviors and Their Psychosocial Explanations: Implications for Fisheries Governance in a Changing World
Authors: Andrews Evan J. , Wolfe Sarah , Nayak Prateep K. , Armitage Derek
Published: February 2021

This research is a critical examination of the behavioral foundations of livelihood pathways over a 50-year time period in a multispecies fishery in Newfoundland and Labrador, Canada. Fishers make difficult decisions to pursue, enjoy, and protect their livelihoods in times of change and uncertainty, and the resultant behaviors shape efforts to advance sustainability through coastal and marine fisheries governance. However, there is limited evidence about fishers’ behavioral changes over long time periods, and the psychosocial experiences that underpin them, beyond what is assumed using neoclassical economic and rational choice framings. Our analysis draws on 26 narrative interviews with fishers who have pursued two or more fish species currently or formerly. Fishers were asked about their behavioral responses to change and uncertainty in coastal fisheries across their entire lifetimes. Their narratives highlighted emotional, perceptual, and values-oriented factors that shaped how fishers coped and adapted to change and uncertainty. The contributions to theory and practice are two-fold. First, findings included variation in patterns of fisher behaviors. Those patterns reflected fishers prioritizing and trading-off material or relational well-being. With policy relevance, prioritizations and trade-offs of forms of well-being led to unexpected outcomes for shifting capacity and capitalization for fishers and in fisheries more broadly. Second, findings identified the influence of emotions as forms of subjective well-being. Further, emotions and perceptions functioned as explanatory factors that shaped well-being priorities and trade-offs, and ultimately, behavioral change. Research findings emphasize the need for scientists, policy-makers, and managers to incorporate psychosocial evidence along with social science about fisher behavior into their models, policy processes, and management approaches. Doing so is likely to support efforts to anticipate impacts from behavioral change on capacity and capitalization in fleets and fisheries, and ultimately, lead to improved governance outcomes.
Fecal Microbiota Transplantation Shows Marked Shifts in the Multi-Omic Profiles of Porcine Post-weaning Diarrhea
Authors: Su Yuan , Li Xiaolei , Li Diyan , Sun Jing
Published: February 2021

Weaning is the most critical phase in pig production and is generally associated with significant impacts on intestinal morphology, structure, physiology, and immune responses, which can lead to subsequent production inefficiencies such as decreases in growth and intake and increases in morbidity and mortality. In the present study, we attempted to explore the effects of fecal microbiota transplantation (FMT) on the fecal microbiota, fecal metabolites, and transcriptome in the jejunum, colon, liver, spleen, and oral mucosa in piglets with post-weaning diarrhea and to evaluate the therapeutic potential of FMT in piglets with post-weaning diarrhea. We found that FMT partially relieved the symptoms of diarrhea in piglets, and microbiota analysis results indicated that unclassified_f_Prevotellaceae was identified as an FMT-associated bacterial family at 66 day and that the Shannon index in the healthy group at 34, 38, and 66 days were higher than that at 21 day. Functional enrichment analysis of the oral mucosa, liver, jejunum, and colon showed that most of the differentially expressed genes (DEGs) were enriched in the terms metabolic process, immune response, and inflammatory response. Moreover, the enriched fecal metabolites focused mostly on apoptosis, beta-alanine metabolism, glutathione metabolism, and sphingolipid metabolism. We tried to detect specific “metabolite-bacterium” pairs, such as “g_Catenisphaera-stigmastentriol,” “p_Bacteroidetes-(6beta,22E)-6-hydroxystigmasta-4,22-dien-3-one,” and “g_Prevotellaceae_NK3B31_group-stenocereol.” Overall, the present study provides a theoretical basis for the alleviation of weaning stress and contributes to the realization of effective and sustainable application of FMT in the pig production industry in the future.
Functional Connectivity Derived From Electroencephalogram in Pharmacoresistant Epileptic Encephalopathy Using Cannabidiol as Adjunctive Antiepileptic Therapy
Authors: Morales Chacón Lilia Maria , Galan García Lidice , Berrillo Batista Sheyla , González González Judith , Sánchez Coroneaux Abel
Published: February 2021

To explore brain function using functional connectivity and network topology derived from electroencephalogram (EEG) in patients with pharmacoresistant epileptic encephalopathy with cannabidiol as adjunctive antiepileptic treatment. Sixteen epileptic patients participated in the study, six of whom had epileptic encephalopathy with a stable dose of cannabidiol Epidiolex (CBD) as adjunctive therapy. Functional connectivity derived from EEG was analyzed based on the synchronization likelihood (SL). The analysis also included reconstructing graph-theoretic measures from the synchronization matrix. Comparison of functional connectivity data between each pathological group with the control group was carried out using a nonparametric permutation test applied to SL values between pairs of electrodes for each frequency band. To compare the association patterns between graph-theoretical properties of each pathological group with the control group, Z Crawford was calculated as a measure of distance. There were differences between pairs of electrodes in all frequency bands evaluated in encephalopathy epileptic patients with CBD adjunctive therapy compared with the control (p < 0.05, permutation test). In the epileptic encephalopathy group without CBD therapy, the SL values were higher than in the control group for the beta, theta, and delta EEG frequency bands, and lower for the alpha frequency band. Interestingly, patients who had CBD as adjunctive therapy demonstrated greater synchronization for all frequency bands, showing less spatial distribution for alpha frequency compared with the control. When comparing both epileptic groups, those patients who had adjunctive CBD treatment also showed increased synchronization for all frequency bands. In epileptic encephalopathy with adjunctive CBD therapy, the pattern of differences for graph-theoretical measures according to Z Crawford indicated less segregation and greater integration suggesting a trend towards the random organization of the network principally for alpha and beta EEG bands. This exploratory study revealed a tendency to an overconnectivity with a random network topology mainly for fast EEG bands in epileptic encephalopathy patients using CBD adjunctive therapy. It can therefore be assumed that the CBD treatment could be related to inhibition of the transition of the interictal to ictal state and/or to the improvement of EEG organization and brain function.
Prognostic Factors Predict Oncological Outcome in Older Patients With Head and Neck Cancer Undergoing Chemoradiation Treatment
Authors: Stromberger Carmen , Yedikat Berna , Coordes Annekatrin , Tinhofer Ingeborg , Kalinauskaite Goda , Budach Volker , Zschaeck Sebastian , Raguse Jan-Dirk , Kofla Grzegorz , Heiland Max , Stsefanenka Aksana , Beck-Broichsitter Benedicta , Dommerich Steffen , Senger Carolin , Beck Marcus
Published: February 2021

Purpose

Older patients with head and neck cancer (HNC) represent a challenging group, as frailty and comorbidities need to be considered. This study aimed to evaluate the efficacy and side effects of curative and palliative (chemo) radiation ([C]RT) with regard to basic geriatric screening in older patients.

Methods

This study included HNC patients aged ≥70 years who were treated with curative or palliative (C)RT. Clinicopathological data including Charlson Comorbidity Index (CCI), Karnofsky performance status (KPS), and treatment data were analyzed as predictors of overall survival (OS).

Results

A total of 271 patients (median age, 74 years) were enrolled. The majority had UICC stage III/IV (90%) and underwent curative treatment (85.2%). A total of 144 (53.1%) patients received definitive and 87 (32.1%) had adjuvant (C)RT. Overall, 40 patients (14.8%) received palliative (C)RT. Median follow-up duration (curative setting) was 87 months, and the 2- and 5-year OS rates were 57.8 and 35.9%, respectively. Median OS was significantly different for age ≤75 vs. >75 years, CCI <6 vs. ≥6, KPS ≥70 vs. <70%, Tx/T1/T2 vs. T3/T4, and adjuvant vs. definitive (C)RT, respectively. Age 70–75 years (p = 0.004), fewer comorbidities when CCI < 6 (p = 0.014), good KPS ≥ 70% (p = 0.001), and adjuvant (C)RT (p = 0.008) independently predicted longer survival. Palliative RT resulted in a median OS of 4 months.

Conclusion

Older age, lower KPS, higher CCI, and definitive (C)RT are indicators of worse survival in older patients with HNC treated curatively. Without a comprehensive geriatric assessment in patients aged >75 years, the KPS and CCI can be useful tools to account for “fitness, vulnerability or frailty” to help in treatment decision-making.
Patient-Derived Nasopharyngeal Cancer Organoids for Disease Modeling and Radiation Dose Optimization
Authors: Lucky Sasidharan Swarnalatha , Law Martin , Lui Ming Hong , Mong Jamie , Shi Junli , Yu Sidney , Yoon Do Kun , Djeng Shih Kien , Wang Jiguang , Lim Chwee Ming , Tan Min Han
Published: February 2021

Effective radiation treatment (RT) for recurrent nasopharyngeal cancers (NPC), featuring an intrinsic hypoxic sub-volume, remains a clinical challenge. Lack of disease‐specificin-vitromodels of NPC, together with difficulties in establishing patient derived xenograft (PDX) models, have further hindered development of personalized therapeutic options. Herein, we established two NPC organoid lines from recurrent NPC PDX models and further characterized and compared these models with original patient tumors using RNA sequencing analysis. Organoids were cultured in hypoxic conditions to examine the effects of hypoxia and radioresistance. These models were then utilized to determine the radiobiological parameters, such as α/β ratio and oxygen enhancement ratio (OER), characteristic to radiosensitive normoxic and radioresistant hypoxic NPC, using simple dose-survival data analytic tools. The results were further validatedin-vitroandin-vivo, to determine the optimal boost dose and fractionation regimen required to achieve effective NPC tumor regression. Despite the differences in tumor microenvironment due to the lack of human stroma, RNA sequencing analysis revealed good correlation of NPC PDX and organoid models with patient tumors. Additionally, the established models also mimicked inter-tumoral heterogeneity. Hypoxic NPC organoids were highly radioresistant and had high α/β ratio compared to its normoxic counterparts.In-vitroandin-vivofractionation studies showed that hypoxic NPC was less sensitive to RT fractionation scheme and required a large bolus dose or 1.4 times of the fractionated dose that was effective against normoxic cells in order to compensate for oxygen deficiency. This study is the first direct experimental evidence to predict optimal RT boost dose required to cause sufficient damage to recurrent hypoxic NPC tumor cells, which can be further used to develop dose-painting algorithms in clinical practice.
Fractional-Order Investigation of Diffusion Equations via Analytical Approach
Authors: Liu Haobin , Khan Hassan , Mustafa Saima , Mou Lianming , Baleanu Dumitru
Published: February 2021

This research article is mainly concerned with the analytical solution of diffusion equations within a Caputo fractional-order derivative. The motivation and novelty behind the present work are the application of a sophisticated and straight forward procedure to solve diffusion equations containing a derivative of a fractional-order. The solutions of some illustrative examples are calculated to confirm the closed contact between the actual and the approximate solutions of the targeted problems. Through analysis it is shown that the proposed solution has a higher rate of convergence and provides a closed-form solution. The small number of calculations is the main advantage of the proposed method. Due to a comfortable and straight forward implementation, the suggested method can be utilized to nonlinear fractional-order problems in various applied science branches. It can be extended to solve other physical problems of fractional-order in multiple areas of applied sciences.
Conditional Neutral Reward Promotes Cooperation in the Spatial Prisoner’s Dilemma Game
Authors: Tang Yunxuan , Jing Ming , Yu Yong
Published: February 2021

Reward is an effective mechanism that promotes cooperation. However, an individual usually reward her opponents in certain cases. Inspired by this, a conditional neutral reward mechanism has been introduced. In detail, an individual will reward his or her neighbors with the same strategy when the payoff of the focal one is higher than that of his or her neighbors. And simulations are conducted to investigate the impact of our mechanism on the evolution of cooperation. Interestingly, cooperation can survive and dominate the system. Nominal antisocial reward that defectors reward each other is rarely because of the greed of defectors. By contrast, cooperators inside the cooperative clusters share the payoff with cooperators on the boundary so that the latter can form shields to protect cooperators.