bluuebunny/crossref_metadata_2025_split huggingface dataset:
Beneficial effects of elafibranor on NASH in E3L.CETP mice and differences between mice and men
Authors: van den Hoek Anita M. , Verschuren Lars , Caspers Martien P. M. , Worms Nicole , Menke Aswin L. , Princen Hans M. G. 
Published: March 2021

AbstractNon-alcoholic steatohepatitis (NASH) is the most rapidly growing liver disease that is nevertheless without approved pharmacological treatment. Despite great effort in developing novel NASH therapeutics, many have failed in clinical trials. This has raised questions on the adequacy of preclinical models. Elafibranor is one of the drugs currently in late stage development which had mixed results for phase 2/interim phase 3 trials. In the current study we investigated the response of elafibranor in APOE*3Leiden.CETP mice, a translational animal model that displays histopathological characteristics of NASH in the context of obesity, insulin resistance and hyperlipidemia. To induce NASH, mice were fed a high fat and cholesterol (HFC) diet for 15 weeks (HFC reference group) or 25 weeks (HFC control group) or the HFC diet supplemented with elafibranor (15 mg/kg/d) from week 15–25 (elafibranor group). The effects on plasma parameters and NASH histopathology were assessed and hepatic transcriptome analysis was used to investigate the underlying pathways affected by elafibranor. Elafibranor treatment significantly reduced steatosis and hepatic inflammation and precluded the progression of fibrosis. The underlying disease pathways of the model were compared with those of NASH patients and illustrated substantial similarity with molecular pathways involved, with 87% recapitulation of human pathways in mice. We compared the response of elafibranor in the mice to the response in human patients and discuss potential pitfalls when translating preclinical results of novel NASH therapeutics to human patients. When taking into account that due to species differences the response to some targets, like PPAR-α, may be overrepresented in animal models, we conclude that elafibranor may be particularly useful to reduce hepatic inflammation and could be a pharmacologically useful agent for human NASH, but probably in combination with other agents.
Multi-criteria of PV solar site selection problem using GIS-intuitionistic fuzzy based approach in Erzurum province/Turkey
Authors: Türk Seda , Koç Ahmet , Şahin Gökhan 
Published: March 2021

AbstractRenewable energy sources have been placed as the key to facilitating to provide source of electricity generation. Solar power is one of the most preferable one among renewable energy sources due to the easy to generate in suitable environment. However, there are concerns with the location of solar power plants installation which causes low efficiency and ineffective use. Hence, determining the location for the usage of solar power sources is critical to mitigating those concerns. In addition, Turkey has been focused on investments on sustainable renewable energy sources and there are few studies which work on cities to reveal potential sources. In this study, GIS and intuitionistic fuzzy set based multi-criteria decision-making method is proposed for determining the most suitable areas for solar energy power plant potential site selection in Erzurum province, Turkey. Firstly, a solar energy power plant potential site selection map is made using a GIS program along with considering ecological risks and ecological criteria. Secondly, 20 districts of Erzurum are investigated in terms of 10 criteria (slope, aspect, solar irradiation, land use, wind speed, air temperature, air pressure, air humidity, land surface temperature and transmission line) using intuitionistic fuzzy sets. In these parameters the first time we looked the land use surface. The land use surface is affected the efficiency of the solar power plant. Finally, the comparisons of two methods are done to check consistency of results obtained. The results indicate that both approaches achieve same areas as the most suitable locations for solar power plants installations for Erzurum province in Turkey. The aim of this work is first to investigate possible locations for solar power plant installation using a mapping method, GIS, and then, Intuitionistic Fuzzy is applied to the problem to obtain optimum areas for solar energy. Also, more accurate results are provided comparing results of two methods, GIS and Intuitionistic Fuzzy. The results expose that 25,065.3 km2 for solar power plant suitable for solar power plan installation.
Functional analysis of the cotton CLE polypeptide signaling gene family in plant growth and development
Authors: Wan Ke , Lu Kening , Gao Mengtao , Zhao Ting , He Yuxin , Yang Dong-Lei , Tao Xiaoyuan , Xiong Guosheng , Guan Xueying 
Published: March 2021

AbstractThe CLAVATA3 (CLV3)/EMBRYO SURROUNDING REGION (ESR)–RELATED (CLE) gene family encodes a large number of polypeptide signaling molecules involved in the regulation of shoot apical meristem division and root and vascular bundle development in a variety of plants. CLE family genes encode important short peptide hormones; however, the functions of these signaling polypeptides in cotton remain largely unknown. In the current work, we studied the effects of the CLE family genes on growth and development in cotton. Based on the presence of a conserved CLE motif of 13 amino acids, 93 genes were characterized as GhCLE gene family members, and these were subcategorized into 7 groups. A preliminary analysis of the cotton CLE gene family indicated that the activity of its members tends to be conserved in terms of both the 13-residue conserved domain at the C-terminus and their subcellular localization pattern. Among the 14 tested genes, the ectopic overexpression of GhCLE5::GFP partially mimicked the phenotype of the clv3 mutant in Arabidopsis. GhCLE5 could affect the endogenous CLV3 in binding to the receptor complex, comprised of CLV1, CLV2, and CRN, in the yeast two-hybrid assay and split-luciferase assay. Silencing GhCLE5 in cotton caused a short seedling phenotype. Therefore, we concluded that the cotton GhCLE gene family is functionally conserved in apical shoot development regulation. These results indicate that CLE also plays roles in cotton development as a short peptide hormone.
Microbial carbon source utilization in rice rhizosphere soil with different tillage practice in a double cropping rice field
Authors: Tang Haiming , Xiao Xiaoping , Li Chao , Shi Lihong , Cheng Kaikai , Li Weiyan , Wen Li , Xu Yilan , Wang Ke 
Published: March 2021

AbstractCarbon (C) plays an important role in maintaining soil fertility and increasing soil microbial community, but there is still limited information about how source utilization characteristics respond to soil fertility changes under double-cropping rice (Oryza sativa L.) system in southern China paddy field. Therefore, the effects of different short-term (5-years) tillage management on characteristics of C utilization in rice rhizosphere and non-rhizosphere soils under double-cropping rice field in southern China were investigated by using 18O incorporation into DNA. Therefore, a field experiment were included four tillage treatments: conventional tillage with crop residue incorporation (CT), rotary tillage with crop residue incorporation (RT), no-tillage with crop residue retention (NT), rotary tillage with crop residue removed as control (RTO). The results showed that soil microbial biomass C content with CT, RT, NT treatments were increased by 29.71–47.27% and 3.77–21.30% in rhizosphere and non-rhizosphere soils, compared with RTO treatment, respectively. Compared with RTO treatment, soil microbial basal respiration and microbial growth rate with CT treatment were increased 30.56%, 30.94% and 11.91%, 12.34% in rhizosphere and non-rhizosphere soils, respectively. The soil microbial C utilization efficiency were promoted with NT treatment. Compared with RTO treatment, the metabolic capacity of soil microorganism to exogenous C source with CT, RT and NT treatments were increased. The largest type of exogenous C source was saccharides, followed by amino acid and polymers, and complex compounds was the smallest. The redundancy analysis results indicated that tillage treatments significantly changed the utilization characteristics of soil microorganism to exogenous C source. Compared with RTO treatment, the grain yield of early rice and late rice with CT treatment were increased by 409.5 kg ha−1 and 387.0 kg ha−1, respectively. Therefore, the CT and RT treatments could significantly increase soil microbial biomass C content, but the NT treatment promote microbial C utilization efficiency in the double-cropping paddy field of southern China.
Brain injury after 50 h of lung-protective mechanical ventilation in a preclinical model
Authors: Bassi Thiago G. , Rohrs Elizabeth C. , Fernandez Karl C. , Ornowska Marlena , Nicholas Michelle , Gani Matt , Evans Doug , Reynolds Steven C. 
Published: March 2021

AbstractMechanical ventilation is the cornerstone of the Intensive Care Unit. However, it has been associated with many negative consequences. Recently, ventilator-induced brain injury has been reported in rodents under injurious ventilation settings. Our group wanted to explore the extent of brain injury after 50 h of mechanical ventilation, sedation and physical immobility, quantifying hippocampal apoptosis and inflammation, in a normal-lung porcine study. After 50 h of lung-protective mechanical ventilation, sedation and immobility, greater levels of hippocampal apoptosis and neuroinflammation were clearly observed in the mechanically ventilated group, in comparison to a never-ventilated group. Markers in the serum for astrocyte damage and neuronal damage were also higher in the mechanically ventilated group. Therefore, our study demonstrated that considerable hippocampal insult can be observed after 50 h of lung-protective mechanical ventilation, sedation and physical immobility.
Synthesis of titanium nitride via hybrid nanocomposites based on mesoporous TiO2/acrylonitrile
Authors: Locovei Claudiu , Chiriac Anita-Laura , Miron Andreea , Iftimie Sorina , Antohe Vlad-Andrei , Sârbu Andrei , Dumitru Anca 
Published: March 2021

AbstractIn the present study, the synthesis of titanium nitride (TiN) by carbothermal reduction nitridation (CRN) reaction using nanocomposites made of mesoporous TiO2/acrylonitrile with different content of inorganic phase were explored. The choice of hybrid nanocomposite as precursor for the synthesis of TiN was made due to the possibility of having an intimate interface between the organic and inorganic phases in the mixture that can favours CRN reaction. Subsequently, the hybrid composites have been subjected to four-step thermal treatments at 290 °C, 550 °C, 1000 °C and 1400 °C under nitrogen atmosphere. The XRD results after thermal treatment at 1000 °C under nitrogen flow show the coexistence of two crystalline phases of TiO2, i.e. anatase and rutile, as well as TiN phase, together with the detection of amorphous carbon that proved the initiation of CRN reaction. Furthermore, the observations based on XRD patterns of samples thermally treated at 1400 °C in nitrogen atmosphere were in agreement with SEM analysis, that shows the formation of TiN by CRN reaction via hybrid nanocomposites mesoporous TiO2/acrylonitrile.
Non-monotonic kilohertz frequency neural block thresholds arise from amplitude- and frequency-dependent charge imbalance
Authors: Peña Edgar , Pelot Nicole A. , Grill Warren M. 
Published: March 2021

AbstractReversible block of nerve conduction using kilohertz frequency electrical signals has substantial potential for treatment of disease. However, the ability to block nerve fibers selectively is limited by poor understanding of the relationship between waveform parameters and the nerve fibers that are blocked. Previous in vivo studies reported non-monotonic relationships between block signal frequency and block threshold, suggesting the potential for fiber-selective block. However, the mechanisms of non-monotonic block thresholds were unclear, and these findings were not replicated in a subsequent in vivo study. We used high-fidelity computational models and in vivo experiments in anesthetized rats to show that non-monotonic threshold-frequency relationships do occur, that they result from amplitude- and frequency-dependent charge imbalances that cause a shift between kilohertz frequency and direct current block regimes, and that these relationships can differ across fiber diameters such that smaller fibers can be blocked at lower thresholds than larger fibers. These results reconcile previous contradictory studies, clarify the mechanisms of interaction between kilohertz frequency and direct current block, and demonstrate the potential for selective block of small fiber diameters.
Deep learning systems detect dysplasia with human-like accuracy using histopathology and probe-based confocal laser endomicroscopy
Authors: Guleria Shan , Shah Tilak U. , Pulido J. Vincent , Fasullo Matthew , Ehsan Lubaina , Lippman Robert , Sali Rasoul , Mutha Pritesh , Cheng Lin , Brown Donald E. , Syed Sana 
Published: March 2021

AbstractProbe-based confocal laser endomicroscopy (pCLE) allows for real-time diagnosis of dysplasia and cancer in Barrett’s esophagus (BE) but is limited by low sensitivity. Even the gold standard of histopathology is hindered by poor agreement between pathologists. We deployed deep-learning-based image and video analysis in order to improve diagnostic accuracy of pCLE videos and biopsy images. Blinded experts categorized biopsies and pCLE videos as squamous, non-dysplastic BE, or dysplasia/cancer, and deep learning models were trained to classify the data into these three categories. Biopsy classification was conducted using two distinct approaches—a patch-level model and a whole-slide-image-level model. Gradient-weighted class activation maps (Grad-CAMs) were extracted from pCLE and biopsy models in order to determine tissue structures deemed relevant by the models. 1970 pCLE videos, 897,931 biopsy patches, and 387 whole-slide images were used to train, test, and validate the models. In pCLE analysis, models achieved a high sensitivity for dysplasia (71%) and an overall accuracy of 90% for all classes. For biopsies at the patch level, the model achieved a sensitivity of 72% for dysplasia and an overall accuracy of 90%. The whole-slide-image-level model achieved a sensitivity of 90% for dysplasia and 94% overall accuracy. Grad-CAMs for all models showed activation in medically relevant tissue regions. Our deep learning models achieved high diagnostic accuracy for both pCLE-based and histopathologic diagnosis of esophageal dysplasia and its precursors, similar to human accuracy in prior studies. These machine learning approaches may improve accuracy and efficiency of current screening protocols.
Health-related quality of life and its related factors in coronary heart disease patients: results from the Henan Rural Cohort study
Authors: Mei Yong-xia , Wu Hui , Zhang Huan-yun , Hou Jian , Zhang Zhen-xiang , Liao Wei , Liu Xiao-tian , Sang Sheng-xiang , Mao Zhen-xing , Yang Dong-bin , Wang Chong-jian , Zhang Wei-hong 
Published: March 2021

AbstractThe aims were to identify the possible influencing factors of health-related quality of life (HRQoL) and its domain-specific scores in patients with coronary heart disease (CHD). A total of 1247 patients with CHD from the Henan Rural Cohort Study (n = 39,259) were included in this study. The Chinese version of the European Quality of Life Five Dimension Five level scale (EQ-5D-5L) and Visual Analogue Scale (VAS) were used to evaluate HRQoL in patients with CHD. Tobit regression, generalized linear models and binary logistic regression were applied to determine the potential factors influencing the EQ-5D utility, as well as each domain, and the VAS. CHD patients had lower per capita monthly actual income, and higher rates of diabetes mellitus, stroke, anxiety and poor sleep quality, which significantly decreased EQ-5D index and VAS scores. In addition, sex, older age, education, not having a spouse, ever drinking alcohol, a high-fat diet, physical activity, hypertension and depression affected the various domain-specific EQ-5D scores in CHD patients. CHD patients in rural areas have a lower HRQoL. Factors associated with the EQ-5D index, including each domain, and the VAS need attention. CHD patients in rural areas need to be managed systematically.
Neuroinflammatory changes of the normal brain tissue in cured mice following combined radiation and anti-PD-1 blockade therapy for glioma
Authors: Clausi Mariano Guardia , Stessin Alexander M. , Zhao Zirun , Tsirka Stella E. , Ryu Samuel 
Published: March 2021

AbstractThe efficacy of combining radiation therapy with immune checkpoint inhibitor blockade to treat brain tumors is currently the subject of multiple investigations and holds significant therapeutic promise. However, the long-term effects of this combination therapy on the normal brain tissue are unknown. Here, we examined mice that were intracranially implanted with murine glioma cell line and became long-term survivors after treatment with a combination of 10 Gy cranial irradiation (RT) and anti-PD-1 checkpoint blockade (aPD-1). Post-mortem analysis of the cerebral hemisphere contralateral to tumor implantation showed complete abolishment of hippocampal neurogenesis, but neural stem cells were well preserved in subventricular zone. In addition, we observed a drastic reduction in the number of mature oligodendrocytes in the subcortical white matter. Importantly, this observation was evident specifically in the combined (RT + aPD-1) treatment group but not in the single treatment arm of either RT alone or aPD-1 alone. Elimination of microglia with a small molecule inhibitor of colony stimulated factor-1 receptor (PLX5622) prevented the loss of mature oligodendrocytes. These results identify for the first time a unique pattern of normal tissue changes in the brain secondary to combination treatment with radiotherapy and immunotherapy. The results also suggest a role for microglia as key mediators of the adverse treatment effect.
A suitable RNA preparation methodology for whole transcriptome shotgun sequencing harvested from Plasmodium vivax-infected patients
Authors: Bourgard Catarina , Lopes Stefanie C. P. , Lacerda Marcus V. G. , Albrecht Letusa , Costa Fabio T. M. 
Published: March 2021

AbstractPlasmodium vivax is a world-threatening human malaria parasite, whose biology remains elusive. The unavailability of in vitro culture, and the difficulties in getting a high number of pure parasites makes RNA isolation in quantity and quality a challenge. Here, a methodological outline for RNA-seq from P. vivax isolates with low parasitemia is presented, combining parasite maturation and enrichment with efficient RNA extraction, yielding ~ 100 pg.µL−1 of RNA, suitable for SMART-Seq Ultra-Low Input RNA library and Illumina sequencing. Unbiased coding transcriptome of ~ 4 M reads was achieved for four patient isolates with ~ 51% of transcripts mapped to the P. vivax P01 reference genome, presenting heterogeneous profiles of expression among individual isolates. Amongst the most transcribed genes in all isolates, a parasite-staged mixed repertoire of conserved parasite metabolic, membrane and exported proteins was observed. Still, a quarter of transcribed genes remain functionally uncharacterized. In parallel, a P. falciparum Brazilian isolate was also analyzed and 57% of its transcripts mapped against IT genome. Comparison of transcriptomes of the two species revealed a common trophozoite-staged expression profile, with several homologous genes being expressed. Collectively, these results will positively impact vivax research improving knowledge of P. vivax biology.
Computed tomography based measurements to evaluate lung density and lung growth after congenital diaphragmatic hernia
Authors: Stoll-Dannenhauer Timm , Schwab Gregor , Zahn Katrin , Schaible Thomas , Wessel Lucas , Weiss Christel , Schoenberg Stefan O. , Henzler Thomas , Weis Meike 
Published: March 2021

AbstractEmphysema-like-change of lung is one aspect of lung morbidity in children after congenital diaphragmatic hernia (CDH). This study aims to evaluate if the extent of reduced lung density can be quantified through pediatric chest CT examinations, if side differences are present and if emphysema-like tissue is more prominent after CDH than in controls. Thirty-seven chest CT scans of CDH patients (mean age 4.5 ± 4.0 years) were analyzed semi-automatically and compared to an age-matched control group. Emphysema-like-change was defined as areas of lung density lower than − 950 HU in percentage (low attenuating volume, LAV). A p-value lower than 0.05 was regarded as statistically significant. Hypoattenuating lung tissue was more frequently present in the ipsilateral lung than the contralateral side (LAV 12.6% vs. 5.7%; p < 0.0001). While neither ipsilateral nor contralateral lung volume differed between CDH and control (p > 0.05), LAV in ipsilateral (p = 0.0002), but not in contralateral lung (p = 0.54), was higher in CDH than control. It is feasible to quantify emphysema-like-change in pediatric patients after CDH. In the ipsilateral lung, low-density areas are much more frequently present both in comparison to contralateral and to controls. Especially the ratio of LAV ipsilateral/contralateral seems promising as a quantitative parameter in the follow-up after CDH.
Radioiodine labeling and in vivo trafficking of extracellular vesicles
Authors: Hong Chae Moon , Gangadaran Prakash , Oh Ji Min , Rajendran Ramya Lakshmi , Gopal Arunnehru , Zhu Liya , Ahn Byeong-Cheol 
Published: March 2021

AbstractBiodistribution and role of extracellular vesicles (EVs) are still largely unknown. Reliable tracking methods for EVs are needed. In this study, nuclear imaging using radioiodine were developed and applied for tracking EVs derived from cell lines. EVs were obtained from supernatant of thyroid cancer cell (Cal62) and natural killer cells (NK92-MI) using sequential ultracentrifuges. Sulfosuccinimidyl-3-(4-hydroxypheynyl) propionate were labeled to membrane of Cal62 and NK92-MI cell derived EVs, then the EVs were labeled with radioiodine (I-131 and I-125) using pre-coated iodination tubes (RI-EVs). In vivo gamma camera images were obtained after intravenous injection of the RI-EVs, and ex vivo biodistribution study was also performed. EVs were labeled with radioiodine and radiochemical purity of the RI-EV was more than 98%. Results of nanoparticle tracking analysis and electron microscopy showed that there was no significant difference in EVs before and after the radioiodine labeling. After intravenous injection of RI-EVs to mice, gamma camera imaging well visualized the real-time biodistribution of the RI-EVs. RI-EVs were mainly visualized at liver, spleen, and lung. Nuclear imaging system of EVs derived from thyroid cancer and NK cells using radioiodine labeling of the EVs was established. Thus, this system might be helpful for in vivo tracking of EVs.