bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance Analysis of Internal Heat Exchanger‐Based Quasi‐Two‐Stage Vapor Compression Heat Pump System for High‐Temperature Steam Production
Authors: Hao Zhang , Yanting Zhang , Jingyu Xu , Lin Wang , Zheng Huang
Published: October 2020

The thermodynamic performance of a high‐temperature heat pump steam (HTHPS) system is determined mainly by its different cycle configurations. The present study involves improving the thermodynamic performance of a quasi‐two‐stage vapor compression high‐temperature heat pump based on a front internal heat exchanger (IHX) cycle and a rear, and analyzing the influence of an IHX. The present study establishes thermodynamic models for front reheating structure (FRS) and rear reheating structure (RRS) models on the basis of conservation of mass and energy. The system is compared to the traditional quasi‐two‐stage compression cycle system in terms of thermodynamic parameters. The results demonstrated that the RRS system exhibits an increase of 4.87% in the coefficient of performance when the exhaust superheats is maintained under 5 K. With an increase in the condensation temperature, the required mass flow of the refrigerant in the traditional system is 9.94–12.36% higher compared to the RRS system, the power consumption of the compressor is increased by 3.9–5.6%, and the steam output per unit refrigerant is decreased by 1.04–5.07%. Furthermore, the Aspen Plus simulation verifies that the reason for the change in the exhaust superheats is the different pressure ratios in the theoretical calculation.
Lignin Depolymerization by Catalytic Hydrodeoxygenation Performed with Smectitic Clay‐Based Materials
Authors: Borsella Elisabetta , De Bari Isabella , Colucci Pietro , Mastrolitti Silvio , Liuzzi Federico , De Stefanis Adriana , Valentini Veronica , Gallese Fortunata , Perez Giorgio
Published: October 2020

The present investigation aims at exploring the application of low‐cost catalysts based on smectitic clays to the hydrodeoxygenation (HDO) of Cynara cardunculus derived lignin. Two types of clay minerals, montmorillonite and saponite, are pillared and decorated with suitable metals by means of an optimized process and characterized by X‐ray powder diffraction (XRPD), porosity, scanning electron microscopy (SEM), energy dispersive X‐ray spectroscopy (EDX), Fourier‐transform infrared spectroscopy (FTIR), UV–vis–NIR, Raman, and thermogravimetric analysis (TGA). Alkaline lignin is obtained from steam‐treated cardoon. Lignin depolymerization is conducted in a bench‐scale apparatus under subcritical conditions, at relatively low temperature (320 °C), for 3 h, under 5‐6 MPa of total pressure. Four catalysts are tested, namely, Fe/Al‐pillared montmorillonite (FAMO) and saponite (FASA), and Ni‐exchanged Ni/Al‐pillared montmorillonite (Ni–Ni/AMO) and saponite (Ni–Ni/ASA). Results indicate that mineral clay–based catalysts result effectively in the hydrogenolysis of lignin, producing several low molecular weight aromatics and other species, with overall conversions in the range 60–70%. Montmorillonite‐based catalysts yield the highest substrate conversion, with a prevalence of phenols and substituted phenols, whereas only Ni–Ni/ASA generates a higher abundance of aliphatic hydrocarbons. Overall, data indicate that smectitic clays are promising catalyst supports for products‐oriented HDO of lignin.
Three‐Dimensional Numerical Simulations on the Effect of Particle Porosity of Lithium‐Nickel–Manganese–Cobalt–Oxide on the Performance of Positive Lithium‐Ion Battery Electrodes
Authors: Cernak Susanne , Schuerholz Florian , Kespe Michael , Nirschl Hermann
Published: October 2020

A spatially resolved electrochemical model is applied to single porous lithium–nickel–manganese–cobalt‐oxide (NMC) particles to evaluate the effect of particle porosity on the half‐cell performance. The arrangement of the primary particles within the investigated secondary particles is computer‐generated by means of the Fibonacci lattice method and is therefore identical. By varying the thickness of the sintering bridges between the primary particles, the different particle porosities are obtained. The numerical results reveal that transport limitations decrease with increasing particle porosity. This becomes evident in lower local overpotentials and more homogeneous lithium concentrations in the solid, leading to higher utilizable capacities. To find optimum particle porosities for different load conditions, a utility value analysis of two assessment approaches is performed. The volume‐based evaluation shows that nonporous particles are most suitable for high‐energy applications ≪1 C, whereas for medium to high‐power applications (1 to 10 C), particles with porosities between 10% and 20% perform best. Interestingly, the latter show even higher utilizable energy densities compared with the nonporous and the highly porous particles. In contrast to that, the gravimetric results show that the electrochemical performance increases with the particle porosity. Thus, the optimum inner porosity of NMC particles depends on the desired application.
Surfactant‐Directed Engineering of Hierarchical Porous Heteroatom‐Doped Carbons for High‐Energy Supercapacitors
Authors: Liu Xufei , Luo Rui , Mei Peng , Zhang Xiaofang , Yang Yingkui
Published: October 2020

Hierarchical porous heteroatom–doped carbons (HDCs) are readily fabricated through direct carbonization of polyimide precursors obtained in the presence of cetyltrimethylammonium bromide as a structure‐directing agent, showcasing tunable morphologies and porosities. The symmetric supercapacitor assembled by the optimized HDC electrodes with an aqueous electrolyte delivers a high specific capacitance (168 F g−1 at 0.5 A g−1), excellent rate capability (83.3% retention from 0.5 to 20 A g−1), and outstanding cycling stability (almost no capacitance fading after 10 000 cycles). Furthermore, the cell possesses a remarkable energy density of 8.4 Wh kg−1 at a power density of 150 W kg−1 and still maintains an energy density of 7 Wh kg−1 even at a high power density of 6000 W kg−1. Such exceptional supercapacitive performance shall be credited to the enlarged accessible surface area and pore volume for sufficient electrolyte contact and reservoir, chemically doped carbon skeleton for refined wettability, and high electronic conductivity as well as additional pseudocapacitive behavior. This work may open up a new possibility for fabricating low‐cost, lightweight, and durable supercapacitors with balanced energy and power delivery.
Why P2X must be the part of the energy solution?
Authors: Erdem Emre
Published: October 2020

In this contribution, the terms “clean energy,” “green energy” has been revisited in terms of their toxic components. A state of art energy concept Power‐to‐X (P2X) technology and its prospects were discussed from a very general perspective. The problems, in particular, the limits of renewable energy technologies such as solar and wind have been introduced and the integration of P2X systems has been suggested as one of the promising solutions for not only the storage problems of renewables but also the key issue for overcoming the difficulties for decarbonization. Hence, low‐carbon processes and direct energy conversions can be achieved in industrial scales. The main advantage of P2X methods is their potential to create long term storage possibilities and that they can be replaced fossil fuels by H, CH4, or other useful chemicals. Also, the answer to two important questions has been found an answer in this contribution: (a) Can P2X technology be a promising alternative for replacing industrial combustion? (b) Which countries will be the key player for applying such technologies?
Contribution of total dry matter and harvest index to maize grain yield—A multisource data analysis
Authors: Liu Wanmao , Hou Peng , Liu Guangzhou , Yang Yunshan , Guo Xiaoxia , Ming Bo , Xie Ruizhi , Wang Keru , Liu Yuee , Li Shaokun
Published: October 2020

Understanding the contribution of aboveground dry matter (DM) production and harvest index (HI) to maize grain yield is essential to further improve grain yield to ensure future food growing requirements. In this study, we collected 548 sets of data of DM, HI, and grain yield from a multisite (40 sites) and multiyear (2009–2016) experiment conducted in major maize‐growing regions across China and 615 sets of data from 40 published papers distributed from 1988 to 2018 to assess the performance of DM, HI, and their contributions to grain yield. It was found that the average contribution rate of DM was 73.71%, which was much higher than those of HI (26.28%) across China. For the five different modern hybrids, the contribution rates of DM to grain yield (ranged from 71.36% to 89.10%) were also significantly higher than those of HI (ranged from 10.79% to 28.64%) on a large spatial scale. The significant differences in grain yields between cultivars were mainly due to the differences in HI. Among the four maize‐growing regions, the contribution rates of DM in both NW (57.34%) and NM (64.46%) were higher than those of HI (42.66% and 35.54%, respectively). In contrast, the contribution rates of HI in HM (52.67%) and SW (50.92%) were slightly higher than those of DM (47.33% and 49.08%, respectively). The interregional differences in grain yield were mainly attributed to the differences in DM between regions. Additionally, combining the data of this study and data collected from previous studies, we found that the increase in maize grain yield under lower yield levels (<15 Mg/ha) was mainly attributed to the increase in both DM and HI, while that under higher yield levels (>15 Mg/ha) was mainly dependent on the increase in DM.
Improving gelatin‐based emulsion films with cold plasma using different gases
Authors: Ledari Shahrbanoo Ahmadi , Milani Jafar Mohammadzadeh , Lanbar Farshad Sohbatzadeh
Published: October 2020

In this research, the effects of cold plasma treatment on the properties of gelatin‐based emulsion films (GEFs) using different gases were investigated. The gases used include O2, N2, air, Ar, and ethanol‐argon (EtOH‐Ar). Surface hydrophobicity, morphology, water vapor permeability (WVP), and mechanical, thermal, and antifungal properties after plasma application on the film were analyzed. The results revealed that surface hydrophilicity significantly increased after cold plasma, while the contact angle significantly decreased (p < .05). Furthermore, atomic force microscopy results showed that the argon gas plasma significantly increased roughness of the GEFs surface. Besides, plasma did not decrease WVP. Different gases had no significant effect on the mechanical properties of the GEFs (p > .05). Oxygen permeability after plasma application was significantly different from the control sample; consequently, the permeability after plasma application decreased and the lowest level 55.7 (cm3μm m−2 day−1 Pa−1) was seen for oxygen gas. Plasma treatment caused etching effects and lessened the surface moisture of the polymer film. Antimicrobial activity was observed in the cold plasma‐treated samples, especially under air and nitrogen atmosphere. Cold plasma treatment is an effective method for surface modification, expanding the application of emulsion films in the packing industry with improved performance properties.
Effect of foliar application of selenium on morphological and physiological indices of savory (Satureja hortensis) under cadmium stress
Authors: Azizi Iraj , Esmaielpour Behrooz , Fatemi Hamideh
Published: October 2020

Cadmium is a heavy metal that pollutes the environment and affects plants physiologically and morphologically. Selenium is considered as a beneficial element, with effective roles in increasing plant tolerance to environmental stresses. A greenhouse factorial pot experiment was conducted to study the impact of selenium on traits of Savory plants under Cd stress. Experimental factors included soil contamination with cadmium (0, 75, 100, and 150 μM) and foliar spraying of selenium (0, 10, 20, and 40 μM of Sodium Selenate). Biomass, photosynthetic pigments including chlorophyll a, chlorophyll b, total chlorophyll, proline, total soluble solids, cell membrane leakage, relative water content of leaves antioxidant enzymes, and Cd and Zn concentration in shoot and root were recorded. Results revealed that Cd stress decreased vegetative growth criteria, photosynthetic pigments include chlorophyll a, chlorophyll b, total chlorophyll, and carotenoid almost, 55%, 57%, 57%, and 68%, respectively, while poline, cell membrane leakage, peroxidase (POD), and catalase (CAT) antioxidant enzymes were increased with increasing Cd concentrations. Foliar spray of selenium reduced the toxic effects of Cd stress on savory plants via enhancing of proline content and stimulation of CAT and POD enzymes and limitation of cell membrane leakage. Also, selenium foliar spray improved chlorophyll content under Cd stress condition and decreased cadmium accumulation 29% in root, respectively. In general, these results suggest that foliar application of selenium could mitigate Cd toxicity and improve growth and antioxidant capacity of savory under different level of cadmium heavy metal stress.
Beaver dam analogues drive heterogeneous groundwater–surface water interactions
Authors: Wade Jeffrey , Lautz Laura , Kelleher Christa , Vidon Philippe , Davis Julianne , Beltran Julio , Pearce Casey
Published: October 2020

Beaver dam analogues (BDAs) are a cost‐effective stream restoration approach that leverages the recognized environmental benefits of natural beaver dams on channel stability and local hydrology. Although natural beaver dams are known to exert considerable influence on the hydrologic conditions of a stream system by mediating geomorphic processes, nutrient cycling, and groundwater–surface water interactions, the impacts of beaver‐derived restoration methods on groundwater–surface water exchange are poorly characterized. To address this deficit, we monitored hyporheic exchange fluxes and streambed porewater biogeochemistry across a sequence of BDAs installed along a central Wyoming stream during the summer of 2019. Streambed fluxes were quantified by heat tracing methods and vertical hydraulic gradients. Biogeochemical activity was evaluated using major ion porewater chemistry and principal component analysis. Vertical fluxes of approximately 1.0 m/day were observed around the BDAs, as was the development of spatially heterogeneous zones of nitrate production, groundwater upwelling, and anaerobic reduction. Strong contrasts in hyporheic zone processes were observed across BDAs of differing sizes. This suggests that structures may function with size‐dependent behaviour, only altering groundwater–surface water interactions after a threshold hydraulic step height is exceeded. Patterns of hyporheic exchange and biogeochemical cycling around the studied BDAs resemble those around natural beaver dams, suggesting that BDAs may provide comparable benefits to channel complexity and near‐stream function over a 1‐year period.
Attendance at early recall and colposcopy in routine cervical screening with human papillomavirus testing
Authors: Green Leonardo I. , Mathews Christopher S. , Waller Jo , Kitchener Henry , Rebolj Matejka ,   The HPV Pilot Steering Committee
Published: October 2020

Attendance at early recall and colposcopy is crucial to attaining the benefits of primary high‐risk human papillomavirus (HR‐HPV)‐based screening. Within the English HPV pilot, we analysed deprivation‐ and age‐related patterns of attendance at colposcopy and 12‐ and 24‐month early recall of HR‐HPV positive women screened in 2013 to 2015 (N = 36 466). We fitted logistic regression models for adjusted odds ratios (OR). Despite high overall attendance, area deprivation had a small but significant impact at both early recalls, for example, attendance at 24 months was 86.3% and 83.0% in less vs more deprived areas, respectively (ORadj: 0.76; 95% CI: 0.67‐0.87). Older women (≥30 years) were more likely to attend early recall than younger women (<30 years), for example, attendance at 24 months was 86.1% vs 82.3%, respectively (ORadj: 1.32, 95% CI: 1.16‐1.51). Most women attended colposcopy following a baseline referral, with 96.9% attendance among more deprived and 97.8% among less deprived areas (ORadj: 0.70; 95% CI: 0.55‐0.88). Differences in colposcopy attendance by deprivation level at 12 and 24 months were of approximately the same magnitude. In conclusion, attendance at early recall and colposcopy was reassuringly high. Although there were statistically significant differences by deprivation and age group, these were small in absolute terms.
Everolimus after failure of one prior VEGF‐targeted therapy in metastatic renal cell carcinoma: Final results of the MARC‐2 trial
Authors: Staehler Michael , Stöckle Michael , Christoph Daniel C. , Stenzl Arnulf , Potthoff Karin , Grimm Marc‐Oliver , Klein Dunja , Harde Johanna , Brüning Fabian , Goebell Peter J. , Augustin Marinela , Roos Frederik , Benz‐Rüd Iris , Marschner Norbert , Grünwald Viktor
Published: October 2020

MARC‐2, a prospective, multicenter phase IV trial, aimed to investigate clinical outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with everolimus after failure of one initial vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR‐TKI) therapy and to identify subgroups benefiting most, based on clinical characteristics and biomarkers. Patients with clear cell mRCC failing one initial VEGFR‐TKI received everolimus until progression or unacceptable toxicity. Primary endpoint was 6‐month progression‐free survival rate (6moPFS). Secondary endpoints were overall response rate (ORR), PFS, overall survival (OS), and safety. Between 2011 and 2015, 63 patients were enrolled. Median age was 65.4 years (range 43.3‐81.1). 6moPFS was 39.3% (95% confidence interval [CI], 27.0‐51.3) overall, 54.4% (95% CI, 35.2‐70.1) vs 23.7% (95% CI, 10.5‐39.9) for patients aged ≥65 vs <65 years and 51.4% (95% CI, 34.7‐65.7) vs 18.2% (95% CI, 5.7‐36.3) for patients with body mass index (BMI) >25 vs ≤25 kg/m2. A Cox proportional hazards model confirmed a longer PFS for patients aged ≥65 years (hazard ratio [HR] 0.46; 95% CI, 0.26‐0.80) and a longer OS for patients with BMI >25 kg/m2 (HR 0.36; 95% CI, 0.18‐0.71). Median PFS and median OS were 3.8 months (95% CI, 3.2‐6.2) and 16.8 months (95% CI, 14.3‐24.3). ORR was 7.9% and disease control rate was 60.3%. No new safety signals emerged. Most common adverse events were stomatitis (31.7%), fatigue (31.7%), and anemia (30.2%). One patient died from treatment‐related upper gastrointestinal hemorrhage. Everolimus remains a safe and effective treatment option for mRCC patients after one prior VEGFR‐TKI therapy. Patients aged ≥65 years and patients with BMI >25 kg/m2 benefited most.
International travel to obtain medical treatment for primary retinoblastoma: A global cohort study
Authors: Bowman Richard J. C. , Foster Allen , Stacey Andrew , Keren‐Froim Naama , Bascaran Cova , Kivelä Tero T. , Munier Francis , Fabian Ido Didi
Published: October 2020

Early diagnosis and treatment of retinoblastoma (Rb), the most common intraocular malignancy, can save both the child's life and vision. However, access to services and hence chances for survival and preserving the eye and its vision vary widely across the globe. Some families have to, or make a choice to, leave their home country to seek planned medical treatment abroad. We aimed to investigate how frequently this cross‐border travel occurs and the factors associated with it. A total of 278 Rb centres in 153 countries were recruited to participate in a global cross‐sectional analysis of newly diagnosed Rb patients in 2017. Number and proportions of children who travelled from their home country for treatment were analysed by country, continent, socioeconomic stratum and clinical and demographic features. The cohort included 4351 new patients of whom 223 [5.1%, 95% confidence interval 4.5‐5.8] were taken across country borders for planned medical treatment. Independently significant predictors of travelling across borders included: being from a country with a smaller population, being from a country classified as low socioeconomic status, having bilateral Rb and having intraocular disease without extraocular spread. The factors that determine international travel for Rb treatment are complex and deserve further investigation. We may need to rethink the way services are delivered in the light of the threat of severe curtailment of international travel from pandemics like corona virus disease 2019.
Effect of bioactive Biosilicate®/F18 glass scaffolds on osteogenic differentiation of human adipose stem cells
Authors: Marin Claudia P. , Santana Geovana L. , Robinson Meghan , Willerth Stephanie M. , Crovace Murilo C. , Zanotto Edgar D.
Published: October 2020

This study evaluated the gene expression profile of the human adipose‐derived stem cells (hASCs) grown on the Biosilicate®/F18 glass (BioS‐2P/F18) scaffolds. hASCs were cultured using the osteogenic medium (control), the scaffolds, and their ionic extract. We observed that ALP activity was higher in hASCs grown on the BioS‐2P/F18 scaffolds than in hASCs cultured with the ionic extract or the osteogenic medium on day 14. Moreover, the dissolution product group and the control exhibited deposited calcium, which peaked on day 21. Gene expression profiles of cell cultured using the BioS‐2P/F18 scaffolds and their extract were evaluated in vitro using the RT2 Profiler polymerase chain reaction (PCR) microarray on day 21. Mineralizing tissue‐associated proteins, differentiation factors, and extracellular matrix enzyme expressions were measured using quantitative PCR. The gene expression of different proteins involved in osteoblast differentiation was significantly up‐regulated in hASCs grown on the scaffolds, especially BMP1, BMP2, SPP1, BMPR1B, ITGA1, ITGA2, ITGB1, SMAD1, and SMAD2, showing that both the composition and topographic features of the biomaterial could stimulate osteogenesis. This study demonstrated that gene expression of hASCs grown on the scaffold surface showed significantly increased gene expression related to hASCs cultured with the ionic extract or the osteogenic medium, evidencing that the BioS‐2P/F18 scaffolds have a substantial effect on cellular behavior of hASCs.
Virulence factors impair epithelial junctions during bacterial infection
Authors: Zheng Manxi , Sun Shuang , Zhou Jun , Liu Min
Published: October 2020

Epithelial cells are typically connected through different types of cell junctions that are localized from the apical membrane to the basal surface. In this way, epithelium cells form the first barrier against pathogenic microorganisms and prevent their entry into internal organs and the circulatory system. Recent studies demonstrate that bacterial pathogens disrupt epithelial cell junctions through targeting junctional proteins by secreted virulence factors. In this review, we discuss the diverse strategies used by common bacterial pathogens, includingPseudomonas aeruginosa,Helicobacter pylori, and enteropathogenicEscherichia coli, to disrupt epithelial cell junctions during infection. We also discuss the potential of targeting the pathogenic mechanisms in the treatment of pathogen‐associated diseases.
Cytokine profiles and clinical characteristics in primary Sjögren´s syndrome patient groups
Authors: López‐Villalobos Erika Fabiola , Muñoz‐Valle José Francisco , Palafox‐Sánchez Claudia Azucena , García‐Arellano Samuel , Martínez‐Fernández Diana Emilia , Orozco‐Barocio Gerardo , García‐Espinoza José Antonio , Oregon‐Romero Edith
Published: October 2020

Background

Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by a lymphocytic infiltrate in salivary glands driving to epithelial damage. The pSS patients present heterogenic clinical and serological characteristics. This heterogenicity could be due to the cytokine microenvironment. Cytokine levels have been analyzed and reported individually, showing controversial results; for that reason, we considered essential to evaluate a cluster of cytokines and relate them with antibody levels and clinical characteristics to find pSS subgroups.

Methods

Ninety‐nine pSS patients, diagnosed by the 2016 ACR/EULAR classification criteria, and 76 control subjects (CS) were included. Cytokine quantification was performed by Multiplex assay. Principal component analysis (PCA) was realized, and the K‐mean test was used to identify clusters/groups. Groups were analyzed by the Kruskal‐Wallis test and the Bonferroni test.

Results

Higher IFN‐γ, IL‐17F, IL‐21, IL‐23, IL‐4, and IL‐31 levels were observed in pSS patients in comparison with control subjects. PCA analysis showed three groups. The severe group was characterized by higher cytokine concentrations as well as an increase in clinical parameters such as antibody levels, damage index score, and others. The moderate group presented intermediate severity; meanwhile, the mild group presented the lowest severity.

Conclusion

Cluster analysis revealed three groups that were different in cytokine levels and clinical parameters in which the mild group was defined by lower severity, the moderate group with intermediate severity, and the severe group with higher severity. This analysis could help subclassify the primary Sjögren syndrome patients for a better understanding of the clinical phenotype that impacts the treatment approach.
Peripheral leptin signaling persists in innate immune cells during diet-induced obesity
Authors: Souza-Almeida Glaucia , Palhinha Lohanna , Liechocki Sally , da Silva Pereira Jéssica Aparecida , Reis Patrícia Alves , Dib Paula Ribeiro Braga , Hottz Eugenio D , Gameiro Jacy , Vallochi Adriana Lima , de Almeida Cecília Jacques , Castro-Faria-Neto Hugo , Bozza Patrícia T , Maya-Monteiro Clarissa Menezes
Published: October 2020

Leptin is a pleiotropic adipokine that regulates immunometabolism centrally and peripherally. Obese individuals present increased levels of leptin in the blood and develop hypothalamic resistance to this adipokine. Here we investigated whether leptin effects on the periphery are maintained despite the hypothalamic resistance. We previously reported that leptin injection induces in vivo neutrophil migration and peritoneal macrophage activation in lean mice through TNF-α- and CXCL1-dependent mechanisms. However, leptin effects on leukocyte biology during obesity remain unclear. In this study, we investigated the in vivo responsiveness of leukocytes to i.p. injected leptin in mice with diet-induced obesity (DIO). After 14–16 wk, high-sucrose, high-fat diet (HFD)-fed mice showed hyperglycemia, hyperleptinemia, and dyslipidemia compared to normal-sucrose, normal-fat diet (ND). Exogenous leptin did not reduce food intake in DIO mice in contrast to control mice, indicating that DIO mice were centrally resistant to leptin. Regardless of the diet, we found increased levels of TNF-α and CXCL1 in the animals injected with leptin, alongside a pronounced neutrophil migration to the peritoneal cavity and enhanced biogenesis of lipid droplets in peritoneal macrophages. Supporting our in vivo results, data from ex vivo leptin stimulation experiments confirmed hypothalamic resistance in DIO mice, whereas bone marrow cells responded to leptin stimulation through mTOR signaling despite obesity. Altogether, our results show that leukocytes responded equally to leptin in ND- or HFD-fed mice. These results support a role for leptin in the innate immune response also in obesity, contributing to the inflammatory status that leads to the development of metabolic disease.
Frontline Science: Extracellular CIRP generates a proinflammatory Ly6G+CD11bhi subset of low-density neutrophils in sepsis
Authors: Takizawa Satoshi , Murao Atsushi , Ochani Mahendar , Aziz Monowar , Wang Ping
Published: October 2020

Extracellular cold-inducible RNA-binding protein (eCIRP) is a damage-associated molecular pattern. Neutrophils present in the mononuclear cell fraction of Ficoll gradient separation are called low-density neutrophils (LDNs). Here we report the novel role of eCIRP on LDNs’ heterogeneity in sepsis. Sepsis was induced in male C57BL/6 wild-type (WT) and CIRP−/− mice by cecal ligation and puncture (CLP). At 20 h after CLP, LDNs in the blood were isolated by Ficoll gradient separation, followed by staining the cells with anti-Ly6G and anti-CD11b Abs and detection by flow cytometry. Sepsis or recombinant murine CIRP (rmCIRP) injection in mice resulted in significant increase in the frequency (%) and number of Ly6G+CD11bhi and Ly6G+CD11blo LDNs in the blood compared to sham- or vehicle-treated mice. At 20 h of CLP, CIRP−/− mice had significantly lower frequency and number of Ly6G+CD11bhi and Ly6G+CD11blo LDNs in the blood compared to WT mice. In sepsis mice or rmCIRP-injected mice, compared to Ly6G+CD11blo LDNs, the expression of CXCR4, ICAM-1, and iNOS and formation of reactive oxygen species, and neutrophil extracellular traps in Ly6G+CD11bhi LDNs in the blood were significantly increased. Treatment of WT bone marrow-derived neutrophils (BMDNs) with rmCIRP increased Ly6G+CD11bhi LDN frequency, whereas treatment of TLR4−/− BMDNs with rmCIRP significantly decreased the frequency of Ly6G+CD11bhi LDNs. BMDNs’ stimulation with rmCIRP increased the expression of transcription factors in LDNs. eCIRP induces the formation of a proinflammatory phenotype Ly6G+CD11bhi of LDNs through TLR4. Targeting eCIRP may provide beneficial outcomes in sepsis by decreasing proinflammatory Ly6G+CD11bhi LDNs.
Hypoxia-inducible factors not only regulate but also are myeloid-cell treatment targets
Authors: Kling Lovis , Schreiber Adrian , Eckardt Kai-Uwe , Kettritz Ralph
Published: October 2020

Hypoxia describes limited oxygen availability at the cellular level. Myeloid cells are exposed to hypoxia at various bodily sites and even contribute to hypoxia by consuming large amounts of oxygen during respiratory burst. Hypoxia-inducible factors (HIFs) are ubiquitously expressed heterodimeric transcription factors, composed of an oxygen-dependent α and a constitutive β subunit. The stability of HIF-1α and HIF-2α is regulated by oxygen-sensing prolyl-hydroxylases (PHD). HIF-1α and HIF-2α modify the innate immune response and are context dependent. We provide a historic perspective of HIF discovery, discuss the molecular components of the HIF pathway, and how HIF-dependent mechanisms modify myeloid cell functions. HIFs enable myeloid-cell adaptation to hypoxia by up-regulating anaerobic glycolysis. In addition to effects on metabolism, HIFs control chemotaxis, phagocytosis, degranulation, oxidative burst, and apoptosis. HIF-1α enables efficient infection defense by myeloid cells. HIF-2α delays inflammation resolution and decreases antitumor effects by promoting tumor-associated myeloid-cell hibernation. PHDs not only control HIF degradation, but also regulate the crosstalk between innate and adaptive immune cells thereby suppressing autoimmunity. HIF-modifying pharmacologic compounds are entering clinical practice. Current indications include renal anemia and certain cancers. Beneficial and adverse effects on myeloid cells should be considered and could possibly lead to drug repurposing for inflammatory disorders.
Single-cell transcriptomics uncover distinct innate and adaptive cell subsets during tissue homeostasis and regeneration
Authors: Yang Kevin Y , Ku Manching , Lui Kathy O
Published: October 2020

Recently, immune cell-mediated tissue repair and regeneration has been an emerging paradigm of regenerative medicine. Immune cells form an essential part of the wound as induction of inflammation is a necessary step to elicit tissue healing. Rapid progress in transcriptomic analyses by high-throughput next-generation sequencing has been developed to study gene regulatory network and establish molecular signatures of immune cells that could potentially predict their functional roles in tissue repair and regeneration. However, the identification of cellular heterogeneity especially on the rare cell subsets has been limited in transcriptomic analyses of bulk cell populations. Therefore, genome-wide, single-cell RNA sequencing (scRNA-Seq) has offered an unprecedented approach to unravel cellular diversity and to study novel immune cell populations involved in tissue repair and regeneration through unsupervised sampling of individual cells without the need to rely on prior knowledge about cell-specific markers. The analysis of gene expression patterns at a single-cell resolution also holds promises to uncover the mechanisms and therefore the development of therapeutic strategy promoting immunoregenerative medicine. In this review, we will discuss how scRNA-Seq facilitates the characterization of immune cells, including macrophages, innate lymphoid cells and T and B lymphocytes, discovery of immune cell heterogeneity, identification of novel subsets, and tracking of developmental trajectories of distinct immune cells during tissue homeostasis, repair, and regeneration.
Pivots and pirouettes: adapting a robust departmental CPD and training program to the COVID‐19 crisis
Authors: Besson Jacqueline , McNamara Clare , Brown Elizabeth
Published: October 2020

The onset of the COVID‐19 pandemic caused swift change in society, affecting both personal and professional lives. In radiation therapy (RT), professional and social interactions are highly important to maintaining team culture and effective patient care. Continuing Professional Development (CPD) is also an integral part of maintaining professional and personal competence and growth for healthcare professionals. This article examines the rationale for and methods of swiftly adapting a robust CPD program and training calendar to an online offering for radiation therapists (RTs) at the Princess Alexandra Hospital Radiation Oncology Department, Brisbane, Australia. Reasons for the change, how it was achieved quickly, and the opportunity to build resilience in the staff group are discussed. Successes and challenges of achieving meaningful change in a short timeframe are described, ensuring RTs maintained access to both CPD and social support during the crisis. Initial feedback suggested a positive response from RTs, but the situation remains dynamic and will need to be monitored and adapted as the pandemic continues.
Cardiovascular risk factors and APOE‐ε4 status affect memory functioning in aging via changes to temporal stem diffusion
Authors: McKinnon Andrew C. , Stickel Ariana , Ryan Lee
Published: October 2020

Prior research investigating associations between hypertension, obesity, and apolipoprotein (APOE) genotype status with memory performance among older adults has yielded inconsistent results. This may reflect, in part, a lack of first accounting for the effects these variables have on structural brain changes, that in turn contribute to age‐related memory impairment. The current study sought to clarify the relationships between these factors via path modeling. We hypothesized that higher body mass index (BMI), hypertension, and being an APOE‐ε4 allele carrier would predict poorer memory scores, with much of these effects accounted for by indirect effects operating via differences in the integrity of temporal stem white matter. Participants included 125 healthy older adults who underwent neuropsychological assessment and diffusion‐weighted MRI scanning. Direct effects were found for hypertension and demographic variables including age, sex, and education. Importantly, indirect effects were found for BMI, hypertension, APOE‐ε4 status, age, and sex, where these factors predicted memory scores via their impact on temporal stem diffusion measures. There was also a dual effect of sex, with a direct effect indicating that females had better memory performance overall, and an indirect effect indicating that females with greater temporal stem diffusion had poorer memory performance. Results suggest that changes to the integrity of temporal white matter in aging may underpin reduced memory performance. These results highlight that accounting for variables that not only directly impact cognition, but also for those that indirectly impact cognition via structural brain changes, is crucial for understanding the impact of risk factors on cognition.
Time‐to‐contact perception in the brain
Authors: Baurès Robin , Fourteau Marie , Thébault Salomé , Gazard Chloé , Pasquio Léa , Meneghini Giulia , Perrin Juliette , Rosito Maxime , Durand Jean‐Baptiste , Roux Franck‐Emmanuel
Published: October 2020

Time‐to‐contact (TTC) perception refers to the ability of an observer to estimate the remaining time before an object reaches a point in the environment, and is of crucial importance in daily life. Noninvasive correlational approaches have identified several brain areas sensitive to TTC information. Here we report the results of two studies, including one during an awake brain surgery, that aimed to identify the specific areas causally engaged in the TTC estimation process. In Study 1, we tested 40 patients with brain tumor in a TTC estimation task. The results showed that four of the six patients with impaired performance had tumors in right upper parietal cortex, although this tumoral location represented only six over 40 patients. In Study 2, 15 patients underwent awake brain surgery electrostimulation mapping to examine the implication of various brain areas in the TTC estimation process. We acquired and normalized to MNI space the coordinates of the functional areas that influenced task performance. Our results seem to demonstrate that the early stage of the TTC estimation process involved specific cortical territories in the ventral region of the right intraparietal sulcus. Downstream processing of TTC could also involve the frontal eye field (middle frontal gyrus) related to ocular search. We also found that deactivating language areas in the left hemisphere interfered with the TTC estimation process. These findings demonstrate a fine grained, cortical representation of TTC processing close to the ventral right intraparietal sulcus and complement those described in other human studies.
Network meta‐analysis results against a fictional treatment of average performance: Treatment effects and ranking metric
Authors: Nikolakopoulou Adriani , Mavridis Dimitris , Chiocchia Virginia , Papakonstantinou Theodoros , Furukawa Toshi A. , Salanti Georgia
Published: October 2020

Background

Network meta‐analysis (NMA) produces complex outputs as many comparisons between interventions are of interest. The estimated relative treatment effects are usually displayed in a forest plot or in a league table and several ranking metrics are calculated and presented.

Methods

In this article, we estimate relative treatment effects of each competing treatment against a fictional treatment of average performance using the “deviation from the means” coding that has been used to parametrize categorical covariates in regression models. We then use this alternative parametrization of the NMA model to present a ranking metric (PreTA: Preferable Than Average) interpreted as the probability that a treatment is better than a fictional treatment of average performance.

Results

We illustrate the alternative parametrization of the NMA model using two networks of interventions, a network of 18 antidepressants for acute depression and a network of four interventions for heavy menstrual bleeding. We also use these two networks to highlight differences among PreTA and existing ranking metrics. We further examine the agreement between PreTA and existing ranking metrics in 232 networks of interventions and conclude that their agreement depends on the precision with which relative effects are estimated.

Conclusions

A forest plot with NMA relative treatment effects using “deviation from means” coding could complement presentation of NMA results in large networks and in absence of an obvious reference treatment. PreTA is a viable alternative to existing probabilistic ranking metrics that naturally incorporates uncertainty.
Agricultural practices modulate the bacterial communities, and nitrogen cycling bacterial guild in rhizosphere: field experiment with soybean
Authors: Singh Upma , Choudhary Anil K , Sharma Shilpi
Published: October 2020

BACKGROUND

Modern agricultural management approaches are often dependent on the application of chemicals, resulting in adverse impacts on human and environmental health. Therefore, for sustainable agriculture, there is a need to implement integrated agriculture practices that can maintain natural soil microbiome and enhance crop production. Various agricultural approaches influence crop production by impacting the functional bacterial community entailed in biogeochemical cycles, for example, nitrogen (N) cycle. This study aimed to assess the rhizospheric N cycling community of soybean under three agricultural practices, namely, conservation agriculture (CA), conventional treatment (CT), and organic agriculture (OA) for two consecutive years (2017 and 2018).

RESULTS

A field experiment was designed under soybean–wheat cropping system employing CA, CT, and OA modules that included different practices of tillage, crop bedding pattern, crop residue retention, and nutrient application. Assessment of bacterial communities contributing to N transformation was performed with quantitative polymerase chain reaction (qPCR) of important markers (nifH, amoA, narG, and nirK).

CONCLUSION

Results concluded that the practice of conservation agriculture comprising of raised bed, zero tillage, crop residue retention, and application of NPK (nitrogen, phosphorus, potassium) nutrients favorably affected the plant attributes and the abundance of N cycling bacterial community over the two consecutive years. The outcome revealed the mechanistic principle behind enhanced plant growth under conservation agriculture, and opened up the possibility of regulating the N cycling bacterial community to develop sustainable and productive agro‐ecosystems. © 2020 Society of Chemical Industry
The association between Norton scale gain and functional outcome among older hip fracture patients
Authors: Mizrahi Eliyahu H. , Lubart Emilia , Stambler Ilia , Adunsky Abraham
Published: October 2020

Aim

This study examines interrelations between gains of Norton Scale Score (NSS) and functional outcome measured by Functional Independence Measurement (FIM) among older hip fracture patients.

Design

Retrospective study.

Methods

We examined 227 patients consecutively hospitalized in a geriatric postacute rehabilitation ward. The data were collected during 2012‐2017. Data were analysed using Student's t test, chi‐square test, Pearson's correlation coefficient and linear regression.

Results

Patients with positive NSS gains demonstrated statistically significant higher total FIM, motor FIM and total FIM gain scores at hospital discharge, compared with patients showing no NSS gains or negative NSS. Multiple regression analysis indicated that positive NSS gains were independently predictive for higher total FIM and motor FIM scores at hospital discharge and higher motor FIM gains at discharge.

Conclusion

Our results suggest that positive NSS gains are associated with higher FIM scores at hospital discharge and may assist in predicting the functional outcome of hospitalized older hip fracture patients.
Population Pharmacokinetic Study of Vancomycin in Chinese Pediatric Patients with Hematological Malignancies
Authors: Wang Huijuan , Huang Lingfei , Wang Junyan , Ni Yinghua , Zhu Zhengyi , Gao Peng , Hu Yan , Zhang Liwen , Yang Jufei , Fang Luo
Published: October 2020

Study Objectives

Vancomycin is a primary antibiotic for the treatment of severe infections in children with malignant hematological disease. However, precise dosing of vancomycin is difficult in children because of high interindividual variability and limited data of pharmacokinetic profiles. The present study aims to develop a population pharmacokinetic (PPK) model for vancomycin in Chinese pediatric patients with hematological malignancies.

Design

This was a retrospective pharmacokinetic study.

Setting

The setting for this study was a tertiary‐care children's hospital.

Patients

This study included 92 pediatric patients with hematological malignancies who received vancomycin and experienced therapeutic drug monitoring from February 2017 to December 2018.

Measurements and Main Results

A PPK model was generated with a nonlinear mixed effects model. In addition, required doses to achieve target therapeutic concentrations were simulated based on the final model. A one‐compartment model with first‐order elimination fit the concentration data best. Actual body weight (BW) and glomerular filtration rate (GFR) were the significant influential factors on the clearance (CL) of vancomycin. The final PPK model for CL was CL (L/h) = 4.18 , K = , and the volume of distribution was 22.3 L. The model proved to be robust and reliable. Reference dosing regimens were proposed based on the final model.

Conclusions

A PPK model of vancomycin was established for Chinese pediatric patients with hematological malignancies using a nonlinear mixed effects model, which provided a reference for the clinical application of vancomycin.
Ligand binding and global adaptation of the GlnPQ substrate binding domain 2 revealed by molecular dynamics simulations
Authors: Kienlein Maximilian , Zacharias Martin
Published: October 2020

Substrate‐binding domains (SBD) are important structural elements of substrate transporters mediating the transport of essential molecules across the cell membrane. The SBD2 domain of the glutamine (GLN) transporter from bacteria consists of two domains D1 and D2 that bind GLN in the space between the domains in a closed conformation. In the absence of ligand, SBD2 adopts an open conformation with increased domain distance. In molecular dynamics (MD) simulations in the absence of ligands, no closing of the open conformation was observed on the MD time scale. Addition of GLN resulted in several reversible binding and unbinding events of GLN at the binding site on the D1 domain but did not induce domain closing indicating that binding and global domain closing do not occur simultaneously. The SBD2 structure remained in a closed state when starting from the GLN‐bound closed crystal structure and opened quickly to reach the open state upon removal of the GLN ligand. Free energy simulations to induce opening to closing indicated a barrier for closing in the absence and presence of ligand and a significant penalty for closing without GLN in the binding pocket. Simulations of a Leu480Ala mutation also indicate that an interaction of a C‐terminal D1‐tail471‐484 with a D2‐helix418‐427 (not contacting the substrate‐binding region) plays a decisive role for controlling the barrier of conformational switching in the SBD2 protein. The results allow us to derive a model of the molecular mechanism of substrate binding to SBD2 and associated conformational changes.