bluuebunny/crossref_metadata_2025 huggingface dataset:
The oxygen sensor Prolyl hydroxylase domain 2 regulates the in vivo suppressive capacity of regulatory T cells
Authors: Ajouaou Yousra , Azouz Abdulkader , Taquin Anaelle , Hussein Hind , Andris Fabienne , Moser Muriel , Goriely Stanislas , Leo Oberdan
Published: April 2021

The oxygen sensor PHD2 (prolyl hydroxylase domain 2) plays an important role in cell hypoxia adaptation by regulating the stability of HIF proteins (HIF1α and HIF2α) in numerous cell types including T lymphocytes. The role of oxygen sensor on immune cells, in particular on regulatory T cell (Treg) function, has not been fully elucidated. The purpose of our study was to evaluate the role of PHD2 in the regulation of Treg phenotype and function. We demonstrate herein that selective ablation of PHD2 expression in Treg (PHD2ΔTreg mice) leads to a spontaneous systemic inflammatory syndrome, as evidenced by weight loss, development of a rectal prolapse, splenomegaly, shortening of the colon and elevated expression of IFN-γ in the mesenteric lymph nodes, intestine and spleen. PHD2 deficiency in Tregs led to an increased number of activated CD4 conventional T cells expressing an effector/Th1-like phenotype. Concomitantly, the expression of innate-type cytokines such as IL1-β, IL-12p40, IL-12p35 and TNF-α was found to be elevated in peripheral (gut) tissues and spleen. PHD2ΔTreg mice also displayed an enhanced sensitivity to DSS-induced colitis and to toxoplasmosis, suggesting that PHD2-deficient Tregs do not efficiently control inflammatory response in vivo, in particular immune responses characterized by IFN-γ production. Further analysis revealed that Treg dysregulation is largely prevented in PHD2-HIF2α (PHD2-HIF2αΔTreg mice), but not in PHD2-HIF1α (PHD2-HIF1αΔTreg mice) double KOs, suggesting an important and possibly selective role of the PHD2-HIF2α axis in the control of Treg function. Finally, the transcriptomic analysis of PHD2-deficient Tregs revealed an altered expression of several chemokine receptors including CXCR3, a finding corroborated by the altered in vivo localization of PHD2-deficient Tregs in splenic tissues. Collectively, these findings uncover an important role of the PHD2-HIF2α axis in regulatory T cell positioning and trafficking.
Deterministic and Stochastic Principles to Convert Discrete Water Quality Data into Continuous Time Series
Authors: Ferreira Danieli Mara , Coelho Marcelo , Fernandes Cristovão Vicente Scapulatempo , Kaviski Eloy , Detzel Daniel Henrique Marco
Published: April 2021

Limited water quality data is often responsible for incorrect model description and misleading interpretation in water resources planning and management scenarios. This study compares two hybrid strategies to convert discrete concentration data into continuous daily values for one year in different river sections. Model A is based on an autoregressive process, accounting for serial correlation, water quality historical characteristics (mean and standard deviation) and random variability; the second approach (model B) is a regression model, based on the relationship between monitoring flow and concentrations, plus an error term. The generated series (here referred to as synthetic series) are propagated in time and space by a full deterministic model (SihQual), that solves the Saint-Venant and advection-dispersion-reaction equations. Results reveal that both approaches are appropriate to reproduce the variability of biochemical oxygen demand and organic nitrogen concentrations, leading to the conclusion that the combination of deterministic/empirical and stochastic components are compatible. A second outcome arises from the comparison of results in different time scales, supporting the need for further assessment of statistical characteristics of water quality data - which relies on monitoring plans. Nonetheless, the proposed methods are suitable to estimate multiple scenarios of interest in water resources planning and management.
Phospho-proteomic analysis of the effect of merecidin inhibiting the human lung adenocarcinoma A549 cells
Authors: Wang Xiuqing , Jia Qinqin , Zhang Qiannan , Yang Tingting , Song Jinxuan , Wang Yarong
Published: April 2021

Background: Merecidin induced A549 cells apoptosis. The present study aimed to assess the differentially phosphorylated proteins in lung cancer A549 cells treated with antibacterial peptide merecidin. Methods: TMT/iTRAQ labeling, LC-MS/MS analysis, HPLC grading, IMAC modification and enrichment, and liquid chromatography-mass spectrometry of peptide. The data of proteins were filtered according to the localization probability >0.75 standard. The phosphorylated proteomics data were analyzed using GO, KEGG, and STRING databases. Western blots examined the changes in phosphorylated protein expression. Results: Protein function enrichment showed significant changes in the phosphorylation level with respect to protein binding, metabolic activity, molecular function regulation, cell process, and biological function regulation. Integrated pathway bioinformatics results showed that differential proteins are associated with several pathways, including mTOR and AMPK etc. Screening of the COG database revealed differentiated phosphorylated proteins in cell signal transduction, RNA transcription, translation processing and modification, ribosome synthesis of proteins, cytoskeleton protein formation, intracellular material transport, secretion, and vesicle transport. Protein interaction level analysis identified an interaction network with HDAC1, RPL23A, SRSF3H, and NCBP1.etc. The phosphorylated proteomics data and showed that after merecidin treatment, ATG2B and ULK1s were significantly upregulated, while MAPK1 and AKT were significantly downregulated. In addition, Western blot also showed the upregulated level of ATG13,ULK1;MAPK1 downregulated. Conclusion: The results verified the feasibility of phosphorylated proteomics analysis, confirmed the signaling pathways, and suggested that merecidin may induce autophagy of lung adenocarcinoma A549 cells.
Internet memes related to the COVID-19 pandemic as a potential coping mechanism for anxiety
Authors: Akram Umair , Irvine Kamila , Allen Sarah , Ellis Jason , Drabble Jennifer , Stevenson Jodie C
Published: April 2021

This study examined whether significantly anxious individuals differed from non-anxious individuals in their perceptual ratings of internet memes related to the Covid-19 pandemic, whilst considering the mediating role of emotion regulation. Eighty individuals presenting clinically significant anxiety symptoms (indicating ≥15 on the GAD-7) and 80 non-anxious controls (indicating ≤4) rated the emotional valance, humour, relatability, shareability, and offensiveness of 45 Covid-19 internet memes. A measure of emotion regulation difficulties was also completed. The perception of humour, relatability, and shareability were all greater amongst anxious individuals relative to non-anxious controls. These differences were not mediated by emotion regulation deficits. Internet memes related to the current Covid-19 pandemic may serve as beneficial coping mechanism for individuals experiencing severe symptoms of anxiety.
Shotgun Metagenomics evaluation of soil fertilization effect on the rhizosphere viral community of maize plants
Authors: Nwokolo Nwabunwanne Lilian , ENEBE MATTHEW Chekwube
Published: April 2021

The need for sustainability in food supply has led to progressive increase in soil nutrient enrichment. Fertilizer application affect both biological and abiotic processes in the soil, of which bacterial community that support viral multiplication are equally influenced. Soil viral community composition and dynamics are affected by soil fertilization with less exploration on organic and inorganic fertilizer application. In this study, we evaluated the influence of soil fertilization on the maize rhizosphere viral community growing in Luvisolic soil. The highest abundance of bacteriophages were detected in soil treated with high compost manure (Cp8), low inorganic fertilizer (N1), low compost (Cp4) and control (Cn0). Our result showed higher frequency of Myoviridae (47%), Podoviridae (46%) and Siphoviridae (90%) in high organic manure (Cp8) fertilized compared to others. While Inoviridae (98%) and Microviridae (74%) were the most abundant phage families in low organic (Cp4) fertilized soil. This demonstrate that soil fertilization with organic manure increases the abundance and diversity of viruses in the soil due to its soil conditioning effects.
A Consensus Time for Performing Quality Control of 225Ac-Labeled Radiopharmaceuticals
Authors: Kelly James M. , Amor-Coarasa Alejandro , Sweeney Elizabeth , Wilson Justin J. , Causey Patrick W. , Babich John
Published: April 2021

Background: As 225Ac-labeled radiopharmaceuticals continue to show promise as targeted alpha therapeutics, there is a growing need to standardize quality control (QC) testing procedures. The determination of radiochemical purity (RCP) is an essential QC test. A significant obstacle to RCP testing is the disruption of the secular equilibrium between actinium-225 and its daughter radionuclides during labeling and analysis. In order to accelerate translation of actinium-225 targeted alpha therapy, we aimed to determine the earliest time point at which the RCP of an 225Ac-labeled radiopharmaceutical can be accurately calculated. Results: Six ligands were conjugated to macrocyclic metal chelators and labeled with actinium-225 under conditions designed to generate diverse incorporation yields. RCP was determined by radio thin layer chromatography (radioTLC) followed by exposure of the TLC plate on a phosphor screen either 0.5, 2, 3.5, 5, 6.5, or 26 h after the plate was developed. The dataset was used to create models for predicting the true RCP using pre-equilibrium measurements at early time points. The 585 TLC measurements span RCP values of 1.8% to 99.5%. The statistical model created from these data predicted an independent data set with high accuracy. Predictions made at 0.5 h are more uncertain than predictions made at later time points. This is primarily due to the decay of bismuth-213. At 2 h the mean average error is < 3%. A measurement of RCP > 90% at this time point predicts a true RCP > 97%. These findings were independently validated using NaI(Tl) scintillation counting and high resolution gamma spectroscopy on a smaller set of samples with 10% ≤ RCP ≤ 100%. Conclusions: RCP of 225Ac-labeled radiopharmaceuticals can be quantified with acceptable accuracy at least 2 h after radioTLC using various methods of quantifying particle emissions. This time point best balances the need to accurately quantify RCP with the need to safely release the batch as quickly as possible.
Phosphate removal from aqueous solution by Fe-La binary (hydr)oxides: A study of batch experiments and mechanisms
Authors: Duan Haijing , Zhang Lin , Wang Yu-long , Liu Yanhong , Wang Yangyang
Published: April 2021

In this study, Fe-La binary (hydr)oxides were prepared by a co-precipitation method for phosphate removal. Various techniques, including secondary electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX), powder X-ray diffraction (p-XRD) and Brunauer-Emmett-Teller (BET) surface area analysis, were employed to characterize the synthesized Fe-La binary (hydr)oxides. Batch experiments indicated that the performance of phosphate removal by Fe-La binary (hydr)oxides was excellent and increased with increasing La contents. The kinetics study showed that the adsorption was rapid and described better by the pseudo-second-order equation. The maximum adsorption capacities of Fe/La 3:1, Fe/La 1:1 and Fe/La 1:3 binary (hydr)oxides at pH 4.0 calculated by Langmuir model were 49.02, 69.44 and 136.99 mg/g, respectively. The uptake of phosphate was highly affected by solution pH and significantly reduced with the increase of pH value. The analyses of p-XRD, Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) suggested that the predominant mechanisms of phosphate removal involved surface hydroxyl exchange reactions and co-precipitation of released La3+ and phosphate ions, which resulted into the formation of amorphous phase of rhabdophane (LaPO4∙0.5H2O). The results show great potential for the application on the treatment of phosphate decontamination for their high efficiency of phosphate removal.
The total factor productivity index of freshwater aquaculture in China: based on regional heterogeneity
Authors: Zhong Shen , Li Aizhi , Wu Jing
Published: April 2021

Continuously improving freshwater aquaculture efficiency will help promote the sustainable development of freshwater aquaculture, which is crucial to ensure fish food supply. In particular, finding ways to improve the freshwater aquaculture efficiency, by measuring and analyzing the total factor productivity (TFP) of freshwater aquaculture, is of great significance to the sustainable development of freshwater aquaculture industry. Therefore, this paper constructs a meta-frontier Malmquist index (MMI) model by considering the regional heterogeneity to evaluate the TFP of freshwater aquaculture of China from 2004 to 2019. The results show that: (1) From 2004 to 2019, the TFP of freshwater aquaculture shows dynamic fluctuations and spatial differences. Compared with coastal regions, there are obvious advantages in TFP of freshwater aquaculture in inland regions. (2) The change of TFP in freshwater aquaculture is driven by the combined effect of technology change (TC) and technical efficiency change (EC). (3) The technology gap in freshwater aquaculture of coastal regions is tiny, while that of inland regions is large. This paper finally gives some policy suggestions to improve the TFP to ensure the sustainable development of freshwater aquaculture.
Characteristics and Outcomes In Patients With Left-Sided Infective Endocarditis Undergoing Left-Sided Valve Surgery With or Without Concomitant Tricuspid Annuloplasty
Authors: Wu Zexuan , Zhou Yuanyuan , Chen Yili , Wei Fangfei , Ye Zi , He Xin , Liang Weihao , Zhao Jingjing , Xue Ruicong , Wu Yuzhong , Zhu Wengen , Dong Yugang , Liu Chen
Published: April 2021

Background: In patients with left-sided infective endocarditis (LSIE) undergoing left-sided valve surgery (LVS), the effects of concomitant tricuspid annuloplasty (TA) on clinical features and prognosis remain unknown. Methods: This is a single-center retrospective study conducted in a tertiary hospital in China. A total of 207 consecutive patients ≥18 years with a definite LSIE diagnosis who underwent LVS between 2008 and 2017 were included. Patients were divided into two groups: LVS alone (n=157) and LVS+TA group (n=50), to identify differences between the clinical features, echocardiogdraphic parameters and outcomes.Results: The mean age was 44.6±15.6 years and 150 (72.5%) were male. Of the 207 patients, 71 (34.3%) patients had aortic valve involved alone, 115 (55.6%) had mitral valve involved alone and 21 (10.1%) had both valved involved. The average hospital stays were 38±16 days and the median follow-up duration was 34.4 (IQR 19.8-56.3) months. Demographic and baseline characteristics were comparable between the two groups, except that the renal function in LVS alone group was better than LVS +TA group (eGFR 97.2±28.8 vs. 87.6±30.7, P=0.046). Significant reductions in left and right atrial diameter, left ventricular diameter, mitral and tricuspid regurgitation (TR) degree, and pulmonary arterial systolic pressure were reported in both groups, of which the differences were more prominent in LVS+ TA group than LVS alone group (P<0.05). The rate of postoperative complications was higher in LVS+ TA group than that in LVS group (44.0% vs. 23.6%, P=0.005). However, the in-hospital mortality and long-term mortality was similar in both groups. After multi-factor adjustment, concomitant TA was not significantly associated with in-hospital and long-term mortality.Conclusions: Concomitant TA at the time of LVS significantly improved cardiac diameter but increased postoperative complications. It might not be associated with improved survival in LSIE patients.
Coffee Intake and Trace Element Blood Concentrations in Association with Renal Cell Cancer Among Smokers
Authors: Wu Hongke , Weinstein Stephanie J. , Moore Lee E. , Albanes Demetrius , Wilson Robin Taylor
Published: April 2021

Purpose: Determine whether higher coffee intake may reduce the risk of renal cell cancer (RCC) associated with lead (Pb) and other heavy metals with known renal toxicity. Methods: We conducted a nested case-control study of male smokers (136 RCC cases and 304 controls) within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Cases diagnosed with RCC at five or more years following cohort enrollment, were matched to controls on age (±7 years) and whole blood draw date (± 30 days). Conditional logistic regression (using two-sided tests) was used to test for main effects and additive models of effect modification. Results: After a mean follow-up of 16.3 years, coffee consumption was not significantly associated with renal cell cancer risk, when adjusting for blood concentrations of Cd, Hg and Pb and RCC risk factors (age, smoking, BMI, and systolic blood pressure) (p-trend, 0.134). The association with above median blood Pb and RCC (HR = 1.69, 95% CI: 1.06, 2.85) appeared to be modified by coffee consumption, such that RCC risk among individuals with both increased coffee intake and higher blood lead concentration was more than 3-fold higher (HR=3.40, 95% CI: 1.62, 7.13; p-trend 0.003). Conclusion: Contrary to our initial hypothesis, this study suggests that heavy coffee consumption may increase the previously identified association between higher circulating lead (Pb) concentrations and increased RCC risk. Improved assessment of exposure, including potential trace element contaminants in coffee, are needed.
Metabolic Engineering of Moorella Thermoacetica for Thermophilic Bioconversion of Gaseous Substrates to a Volatile Chemical
Authors: Kato Junya , Takemura Kaisei , Kato Setsu , Fujii Tatsuya , Wada Keisuke , Iwasaki Yuki , Aoi Yoshiteru , Matsushika Akinori , Murakami Katsuji , Nakashimada Yutaka
Published: April 2021

Gas fermentation is one of the promising bioprocesses to convert CO2 or syngas to important chemicals. Thermophilic gas fermentation of volatile chemicals has the potential for the development of consolidated bioprocesses that can simultaneously separate products during fermentation. This study reports the production of acetone from CO2 and H2, CO, or syngas by introducing the acetone production pathway using acetyl–coenzyme A (Ac-CoA) and acetate produced via the Wood–Ljungdahl pathway in Moorella thermoacetica. Reducing the carbon flux from Ac-CoA to acetate through genetic engineering successfully enhanced acetone productivity, which varied on the basis of the gas composition. The highest acetone productivity was obtained with CO–H2, while autotrophic growth collapsed with CO2–H2. By adding H2 to CO, the acetone productivity from the same amount of carbon source increased compared to CO gas only, and the maximum specific acetone production rate also increased from 0.04 to 0.09 g-acetone/g-dry cell/h. Our development of the engineered thermophilic acetogen M. thermoacetica, which grows at a temperature higher than the boiling point of acetone (58°C), would pave the way for developing a consolidated process with simplified and cost-effective recovery via condensation following gas fermentation.
Engineering Immunomodulatory and Osteoinductive Implant Surfaces via Mussel Adhesion-Mediated Ion Coordination and Molecular Clicking
Authors: Wang Tao , Bai Jiaxiang , Lu Min , Huang Chenglong , Geng Dechun , Chen Gang , Wang Lei , Qi Jin , Cui Wenguo , Deng Lianfu
Published: April 2021

Immune action and new tissue formation are two distinct but overlapping stages involved in tissue regeneration process. However, current biomaterial design is trapped into a one-sided consideration with either focusing on the regulation of immune response or paying attention to induction of new tissue formation. Bone implants also face the same problem. In this work, we designed a dual-effect bone implant with immunomodulatory activity with direct osteogenicity by a mussel adhesion-mediated ion coordination and molecular clicking strategy. The mussel-inspired chemistry for surface adhesion, bioclickable way for molecular conjugation, and coordination means for ion loading led to an immunoactive Zn2+ ion and osteoinductive BMP-2 peptide co-modified coating on bone implants. We demonstrated that the dual-effect coating could better improve cytocompatibility and promote the polarization of macrophages to M2 phenotype in vitro and in vivo. Moreover, the Zn2+ ion and BMP-2 peptide co-modified bone implants showed optimal osteogenicity and osseointegration, thus improving implant stability in vivo. We anticipate this study would provide new ideas and solutions for engineering implants with immunoactivity and tissue inductivity to precisely adapt tissue regeneration microenvironment.
Optimizing Cellulose Microfibrillation With NaOH Pretreatments for Unbleached Eucalyptus Pulp
Authors: Martins Caio Cesar Nemer , Dias Matheus Cordazzo , Mendonça Maressa Carvalho , Durães Alisson Farley Soares , Silva Luiz Eduardo , Felix Jefferson Resende , Damasio Renato Augusto Pereira , Tonoli Gustavo Henrique Denzin
Published: April 2021

This study aimed to assess the effect of drying unbleached Eucalyptus cellulose fibers after the application of pretreatments in order to optimize the microfibrillation process, as well as to evaluate the efficiency of NaOH pretreatments in reducing energy consumption for production of microfibrillated cellulose (MFC). Pretreatments with 0 wt% (untreated), 5 wt% and 10 wt% NaOH were evaluated. The length and width of the fibers pretreated with NaOH decreased significantly, mainly with hasher pretreatments. The removal of hemicellulose from the fiber cell wall was an important factor concerning the degree of fibrillation of the fibers. Pretreating fibers with 5 wt% NaOH for 2 h increased the water retention value (WRV), in addition to presenting the lowest energy consumption for fibrillation, promoting energy savings of up to 48%. Pulps that were not dried after the NaOH pretreatments incurred in easier microfibrillation and lower energy consumption when comparing to the dried pulp, which shows the negative impact of drying on the fibers to obtain the MFC.
Experimental Investigation on Mechanical Behavior of Anchor and Shotcrete Support System Under Axial Pull-out Action
Authors: Liu Xiliang , Sun Feiyue , Kong Fuli , GUO Jiaqi
Published: April 2021

Based on axial pull-out performance tests of anchor and shotcrete support system with three types of plates and two kinds of shotcretes (plain and steel fiber reinforced concrete) conducted by use of the multi-functional testing system. The mechanical behavior of the anchor and shotcrete support system with the different plate and shotcrete such as the pull-out performance of support system, deformation and failure properties of shotcrete was studied and analyzed. Experimental results showed that the relationship curves between elongation and drawing force has three stages, which are elastic, yielding and strengthening. Different plate types have obvious influence on the tensile stiffness during the elastic stage. The steel fiber reinforced concrete spray layer can improve the yield strength of rockbolt under the coupling effect by the support system. The strain at the interface between the initial shotcrete layer and surrounding rock mass is greater than that of the external surface of the resprayed shotcrete layer, though they are equal far away from the rockbolt hole. The shotcrete strain values of steel fiber reinforced concrete is lower than that of plain concrete, and the shotcrete strain values decreases with the improvement of steel fiber content. For shotcrete strain values on the same position, the higher they are the steel fiber content, the lower their strain will be. The failure of plain shotcrete usually begins around of rockbolt hole, when the interfacial stress between the initial shotcrete layer and surround rock is higher than that in the initial shotcrete layer and resprayed shotcrete layer. The steel fiber can effectively improves the toughness, anti-cracking performance and prevent fracture of shotcrete from failure properties.
Climatology of Ionospheric Amplitude Scintillation on GNSS Signals at South American Sector During Solar Cycle 24
Authors: Macho Eduardo Perez , Correia Emilia , Spogli Luca , Muella Marcio Tadeu de Assis Honorato
Published: April 2021

Scintillations are caused by ionospheric irregularities and can affect the propagation of trans-ionospheric radio signals. One way to understand and predict the impact of such irregularities on Global Navigation Satellite System (GNSS) signals is through the climatological behavior of the ionospheric scintillation indexes during the different phases of a solar cycle. In this work, we investigate the amplitude scintillation index S4 during the full solar cycle 24 at South American (SA) sector, that is featured by the Ionospheric Anomaly (EIA) and by the South Atlantic Magnetic Anomaly (SAMA). We also investigate the daily variation of S4 and two case studies during geomagnetic storms. The results show a significant intensification of amplitude scintillations at northern and southern crest of EIA, especially during the southern hemisphere’s spring/summer seasons, with a higher increase during solar maximum, and after sunset. And particularly at the SAMA region, where the intensity of magnetic field lines is lower, the S4 fluctuations are much higher.
Properties Of Cellulose Nanofibers Extracted From Eucalyptus And Their Emulsifying Role In The Oil-In-Water Pickering Emulsions
Authors: Martins Lilian S. , Santos Ronaldo Gonçalves dos , Spinacé Márcia A. Silva
Published: April 2021

In this work, nanocellulose particles were obtained from eucalyptus fibers by high-pressure homogenization (CNF) and by high-intensity ultrasound (SCNF). The nanocellulose was applied as a solid emulsifier for soybean oil in water (O/W) emulsions. The adding of 0.25 - 1 wt.% of both CNF and SCNF produced stable O/W emulsions without conventional surfactants. SCNF emulsions showed the highest stability and displayed the narrowest size distribution. Zeta potential values (-40 to -70 mV) indicated an electrical barrier to the droplet coalescence. The rheological behavior of O/W emulsions stabilized with CNF and SCNF was described by the Herschel-Buckley model. O/W emulsions produced with nanocellulose particles behave as shear thinning fluid, and their behavior index ranged from 0.33 to 0.68. Both CNF and SCNF emulsions displayed maximum yield stress at a particle concentration of 0.5wt.% and 0.75wt.%, respectively. Besides, the prepared O/W emulsions using 0.5 to 1.00 wt.% CNF or SCNF did not showed phase separation until 30 days of rest. The data point out to the feasibility of using nanocellulose as a natural emulsifier, which can replace conventional surfactants.
An epigenetic GPI anchor defect impairs TLR4 signaling in the B cell transdifferentiation model for primary human monocytes BLaER1
Authors: Wegner Julia , Zillinger Thomas , Schlee-Guimaraes Thais , Bartok Eva , Schlee Martin
Published: April 2021

Antigen-presenting myeloid cells like monocytes detect invading pathogens via pattern recognition receptors (PRRs) and initiate adaptive and innate immune responses. As analysis of PRR signaling in primary human monocytes is hampered by their restricted expandability, human monocyte models like THP-1 cells are commonly used for loss-of-function studies, such as with CRISPR-Cas9 editing. A recently developed transdifferentiation cell culture system, BLaER1, enables lineage conversion from malignant B cells to monocytes and was found superior to THP1 in mimicking PRR signaling, thus being the first model allowing TLR4 and inflammasome pathway analysis. Here, we identified an important caveat when investigating TLR4-driven signaling in BLaER1 cells. We show that this model contains glycosylphosphatidylinositol (GPI) anchor-deficient cells, which lack CD14 surface expression when differentiated to monocytes, resulting in diminished LPS/TLR4 but not TLR7/TLR8 responsiveness. This GPI anchor defect is caused by epigenetic silencing of PIGH, leading to a random distribution of intact and PIGH-deficient clones after single-cell cloning. Overexpressing PIGH or 5-aza-2'-deoxycytidine treatment restored GPI-anchored protein (including CD14) expression and LPS responsiveness. When studying CD14- or other GPI-anchored protein-dependent pathways, researchers should consider this anomaly and ensure equal GPI-anchored protein expression when comparing cells that have undergone single-cell cloning, e. g. after CRISPR-Cas9 editing.
A Panel of DNA Methylation Biomarkers for Detection and Improving Diagnostic Efficiency of Lung Cancer
Authors: Wei Bing , Wu Fengxin , Xing Wenqun , Sun Haibo , Yan Chi , Zhao Chengzhi , Wang Dongqing , Chen Xiaobing , Chen Yanli , Li Mingming , Ma Jie
Published: April 2021

Lung cancer remains the leading cause of cancer deaths worldwide. Although low-dose spiral computed tomography (LDCT) screening is used for the detection of lung cancer in a high-risk population, false-positive results of LDCT remain a clinical problem. Here, we developed a blood test of a novel three gene methylation panel and validated the diagnostic efficiency from a total of 351 subjects (197 controls, 154 cases). DNA methylation of short stature homeobox 2 gene (SHOX2), ras association domain family 1A gene (RASSF1A), and prostaglandin E receptor 4 gene (PTGER4) could be used as a panel of biomarkers to distinguish between malignant and benign lung disease at high sensitivity and specificity: 87.0% sensitivity [95% CI 80.2-91.5%], 98.0% specificity [95% CI 94.9-99.4%]. Sensitivity in adenocarcinoma, squamous cell carcinoma, small cell lung cancer, and other lung cancer was 89.0%, 87.5%, 85.7%, and 77.8%, respectively. Notably, cancer patients in stage I and II showed high diagnostic sensitivity at 82.5% and 90.5%, respectively. Moreover, the diagnostic efficiency did not show bias toward age, gender, smoking, and the presence of other (nonlung) cancers. These findings clearly showed that this panel of DNA methylation biomarkers was effective in detecting lung cancer noninvasively and may provide clinical utility in stand-alone or in combination with current imaging techniques to improve the diagnosis of lung cancer.
Frequency and component analysis of contaminants generated in preparation of anticancer agents using Closed system drug transfer devices (CSTDs)
Authors: Sumikawa Satomi , Yakushijin Yoshihiro , Aogi Kenjiro , Yano Takuya , Hashimoto Hiroki , Tsukui Chiyuki , Noguchi Tadashi , Shiraishi Taro , Horikawa Yasuhiro , Yasuoka Yasuo , Tanaka Akihiro , Hidaka Noriaki , Tanaka Mamoru
Published: April 2021

Occupational exposure of anticancer agents during their preparation has been recognized as a serious hazard. Closed system drug transfer devices (CSTDs) enable “safe” preparation of agents for medical personnel and ensure a safe hospital environment. However, artificial particles of infusion materials have been reported during CSTD use. Here, the incidence of insoluble fine particles during preparation of anticancer agents using CSTDs was examined. Visible insoluble fine particles were found in 465 (9.4%) of 4,948 treatment cases at Ehime University Hospital with CSTD use. Contaminants occurred more frequently during preparation of monoclonal antibodies than cytotoxic anticancer agents (19.4% versus 4.1%, respectively, P<0.01). A similar survey was conducted at nine hospitals to investigate the incidence of insoluble fine particles with or without CSTDs. Insoluble fine particles were detected in 113 (15.4%) of 732 treatment cases during preparation of monoclonal antibodies with CSTD use. In contrast, the occurrence of insoluble fine particles without CSTDs was found in only 3 (0.073%) of 4,113 treatment cases. Contamination with CSTDs might cause harmful effects on patients 4 during cancer therapy. We strongly recommend the use of in-line filters combined with infusion routes after CSTD use to avoid contamination-associated adverse events.
Outpatient Stereotactic Brain Biopsies
Authors: MATHON Bertrand , MARIJON Pauline , RICHE Maximilien , DEGOS Vincent , CARPENTIER Alexandre
Published: April 2021

BackgroundOutpatient neurosurgery is rising popularity leading to patients’ satisfaction and cost-savings. Although several North-American teams have shown the safety of outpatient stereotactic brain biopsies, few data from other countries with different health care systems are available. ObjectiveWe therefore conducted a feasibility and safety study on the outpatient stereotactic brain biopsies. MethodsWe prospectively examined all the consecutive stereotactic brain biopsies performed in an outpatient setting at our tertiary medical center, between June 2018 and September 2020.ResultsAmong the 437 patients who underwent stereotactic brain biopsy during the study period, 40 (9.2%) patients were enrolled for an outpatient management. The sex ratio was 1 and the median age on biopsy day was 55 [41-66] years. The median distance from patients’ home to hospital was 17 kms [3-47]. 95% of patients had prebiopsy ASA score of 1 or 2 and mRs equal to 2 or less. The rate of same-day discharge was 100%. No patient experienced post-biopsy symptomatic complication necessitating readmission within the month following the biopsy. One patient (2.5%) resorted to an unplanned consultation. Histological findings obtained from brain biopsy led to a diagnosis in all patients; the most frequently found were neoplastic lesions (77.5%)ConclusionStereotactic brain biopsies can therefore be safely achieved on an outpatient setting in carefully selected patients. This process could be more widely adopted in other neurosurgical centers, without affecting the quality of patient’s health care and safety. In this article, we propose management guidelines and pre-biopsy checklist for performing ambulatory stereotactic brain biopsies.
Differences in Somatosensory Function During Premenopause and Early and Late Postmenopause in Patients With Burning Mouth Syndrome
Authors: Ozasa Kana , Noma Noboru , Watanabe Kosuke , Young Andrew , Eliav Eli , Imamura Yoshiki
Published: April 2021

Background: This study aimed to examine the association between somatosensory dysfunction and burning mouth syndrome (BMS) in premenopausal, early postmenopausal, and late postmenopausal patients, using a standardized Quantitative Sensory Testing (QST) protocol, and to determine the predictive value of thermal or mechanical perception by QST for detecting BMS.Methods: The study included 36 female participants with BMS (12 premenopausal, 10 early postmenopausal, and 14 late postmenopausal) and 42 age- and sex- matched healthy volunteers (21 premenopausal, 10 early postmenopausal, and 11 late postmenopausal). Neurophysiological tests were used to evaluate somatosensory dysfunction at the tongue.Results: Z-scores in the late postmenopausal BMS group revealed a gain of function for the cold pain threshold and heat pain threshold (Z=2.08 and 3.38, respectively). In the multiple regression analysis with the Visual Analogue Scale as the dependent variable, the vibration detection threshold predicted severity of burning mouth sensation in the premenopausal group.Conclusions: Late postmenopausal patients with BMS showed an increased response of the tongue to noxious thermal stimuli. This supports the theory that changes in sex hormones may affect trigeminal somatosensory function in particular, during the late postmenopausal stage in patients with BMS.
Smart Healthcare Management Evaluation using Fuzzy Decision Making Method
Authors: Quasim Mohammad Tabrez , Shaikh Asadullah , Shuaib Mohammed , Sulaiman Adel , Alam Shadab , Asiri Yousef
Published: April 2021

Smart healthcare has become a health policy services that utilize technologies including wearables, the Internet of things, smartphones, etc., to access information continuously and to link patients, equipment and medical facilities, and then effectively handles and responds in an intelligent way to the needs of medical ecosystems. The smart healthcare management system digitally helps the patient to have used medical assistance and services like emergency response, diagnostic service, and surveillance services at any time and in any location. The evaluation of such a management system must be studied for innovative ideas similar to direct healthcare services. Therefore, this study proposes a Smart Healthcare Management Evaluation using Fuzzy Decision Making (SHME-FDM) method to assess the technological integration efficiency. This study thus evaluates the privacy protection of healthcare data of the smart healthcare management system using the Fuzzy Analytical Hierarchy Process- Technique for Order of Preference by Similarity to Ideal Solution (Fuzzy AHP-TOPSIS). Here, this study uses the fuzzy-based neural network for healthcare predictions. The experimental analysis evaluates the accuracy, reliability and error rate of the fuzzy results. The security risk analysis findings show that the proposed fuzzy model can give the highest risk evaluation performance compared to existing models.
Reduction of Viral Load in Patients With Acute Sore Throats: Results From an Observational Clinical Trial With Echinacea and Salvia Lozenges
Authors: Weishaupt Ramon , Buchkov Alexandar , Kolev Emil , Klein Peter , Schoop Roland
Published: April 2021

Background: Acute tonsillopharyngitis or sore throat is an initial and frequent sign of viral respiratory tract infection (RTI) and represents an optimal occasion for early and effective treatment. Most sore throats are caused by a multiplicity of viruses that are highly contagious (e.g., rhinoviruses or coronaviruses). Thus, therapeutic intervention should not only aim to reduce symptoms (anti-inflammatory and anesthetic), but also the viral load and transmission (anti-viral). Both of these actions have been attributed to Echinacea purpurea and Salvia officinalis. The goal of this clinical study was to assess the safety and acute treatment effects of the Echinacea/Salvia lozenges for the treatment of early symptoms of sore throat, associated common cold symptoms, and viral shedding from the very beginning.Methods: A total of 74 patients (age 13-69 years) with acute sore throat symptoms (<48 h) were treated with five Echinacea/Salvia lozenges per day (4000 mg Echinacea purpurea extract [Echinaforce®] and 1893 mg Salvia officinalis extract [A. Vogel Switzerland] daily) for 4 days. Patients recorded throat pain, tonsillopharyngitis, and common cold symptoms and provided throat swab samples to assess the viral load before, during and after therapy.Results: The lozenges had 99% (very) good ratings and were exceptionally well-tolerated according to the physician and patients. A single lozenge significantly reduced viral load by 62% (p<0.03), and a 4-day treatment by 96% (p<0.02). Ninety minutes after the first dose, throat pain was reduced by 48% (p<0.001) and tonsillopharyngitis symptoms, such as difficulty of swallowing, salivation, and reddening, by 34% (p<0.001). At the end of treatment, pain, sore throat, and additional common cold symptoms, such as nasal and systemic complaints, were reduced by more than 83% (p<0.001). The physician’s assessment of throat status ultimately confirmed the patient-reported positive treatment outcome. Finally, no complicated RTI developed during therapy, and no antibiotic treatment was required (0%).Conclusions: Echinacea/Salvia lozenges represent an effective option for the early treatment of acute sore throats with a wide safety margin. Importantly, antiviral effects immediately reduce viral shedding and potentially the transmission of RTIs from the very start of treatment.
Raman Spectroscopic and Advanced Signal Processing analyses for Real Time Standoff Detection and Identification of Explosives
Authors: Abdallah Adel , Mahmoud Alaaeldin , Mokhtar Mohamed , Mousa Aiman , Elbashar Yahia , Ayoub H. S.
Published: April 2021

Laser Raman spectroscopy is a powerful instrument commonly used for detection of bulk and trace amounts of explosives. The work carried out in this paper is divided into two phases; the first phase is to propose a real time standoff explosive detection and identification system based on Raman spectroscopy that can be deployed in static checkpoints. The measurement is performed for samples placed in contact and at distances up to 1 meter in ambient light conditions. The second phase is to propose a novel sophisticated signal processing and pattern recognition techniques for accurate identification and classification of the investigated materials.
Haematopoietic and Cardiac GPR55 Synchronize Post-myocardial Infarction Remodelling
Authors: Puhl Sarah-Lena , Hilby Michael , Kohlhaas Michael , Keidel Linus M. , Jansen Yvonne , Hristov Michael , Schindler Jakob , Maack Christoph , Steffens Sabine
Published: April 2021

Background and purpose: While classical cannabinoid receptors are known to crucially impact on myocardial infarction (MI) repair, a function of the cannabinoid-sensitive receptor GPR55 herein is poorly understood. We investigated the role of GPR55 in cardiac physiology and post-MI inflammation and remodelling. Methods and results: Global GPR55-/- and wildtype (WT) mice were basally characterized or assigned to 1, 3 or 28 days permanent MI and subsequently analysed via pro-inflammatory and pro-hypertrophic parameters. GPR55-/- deficiency was basally associated with bradycardia, increased diastolic LV volume and sarcomere length and a subtle inflammatory phenotype. While infarct size and myeloid cell infiltration were unaffected by GPR55 depletion, acute cardiac chemokine production was prolonged post-MI. Concurrently, GPR55-/- hearts exhibited a premature expansion of pro-reparative and phagocytic macrophages paralleled by early up regulation of extracellular matrix (ECM) factors 3 days post-MI, which could be mimicked by sole haematopoietic GPR55 depletion. Moreover, global GPR55 deficiency mitigated MI-induced foetal gene re-programming and cardiomyocyte hypertrophy, culminating in aggravated LV dilatation and infarct expansion. Conclusions: GPR55 regulates cardiac homeostasis and ischaemia responses by maintaining adequate LV filling and modulating three crucial processes post-MI: wound healing kinetics, cardiomyocyte hypertrophy and maladaptive remodelling.
VEGF-targeted multispectral optoacoustic tomography and fluorescence molecular imaging in human carotid atherosclerotic plaques
Authors: Steinkamp Pieter J. , Vonk Jasper , Huisman Lydian A. , Meersma Gert-Jan , Diercks Gilles F.H. , Hillebrands Jan-Luuk , Nagengast Wouter B. , Zeebregts Clark J. , Slart Riemer H.J.A. , Boersma Hendrikus H. , Dam Gooitzen M. van
Published: April 2021

Background: Vulnerable atherosclerotic carotid plaques are prone to rupture resulting in ischemic strokes. Molecular imaging techniques have the potential to assess plaque vulnerability by visualizing molecular markers. Bevacizumab-800CW is a near-infrared fluorescent contrast agent antibody targeting vascular endothelial growth factor-A (VEGF-A). Here, we study if administration of bevacizumab-800CW is safe and can be visualized using multispectral optoacoustic tomography (MSOT) to evaluate atherosclerotic carotid plaques in vivo by visualizing intra-plaque neovascularization.Methods: Healthy volunteers were imaged with MSOT to determine the technical feasibility of human carotid imaging with MSOT. Patients with symptomatic carotid artery stenosis scheduled for carotid artery endarterectomy were intravenously administered with a bolus injection of 4.5 mg bevacizumab-800CW. Before and two days after tracer administration, in vivo non-invasive MSOT was performed. For validation, ex vivo fluorescence molecular imaging of the surgically removed plaque specimen was performed and correlated with histopathology.Results: Administration of 4.5 mg bevacizumab-800CW was safe in five patients. MSOT achieved accurate visualization of the carotid bifurcation area and assessment of the plaque in all five patients. Bevacizumab-800CW-resolved signal could not be detected with MSOT prior to surgery. However, ex vivo analysis of the carotid plaque showed accumulation of bevacizumab-800CW.Conclusions: These first-in-human MSOT and fluorescence molecular imaging results in carotid artery plaques suggest that bevacizumab is a potential tracer for imaging of vulnerable plaques. However, the microdose used here cannot be detected with MSOT. A subsequent phase I dose-finding study is needed to evaluate bevacizumab-800CW in higher doses as a useful optoacoustic imaging agent. Moreover, the development of dedicated optoacoustic contrast agents for signal attenuation of the targeting moiety is advisable for carotid atherosclerotic plaque assessment using MSOT.
Are Exclusion Fences Effective in Protecting Threatened Plants?
Authors: Lorite Juan , Salazar-Mendías Carlos , Pawlak Roza , Cañadas Eva
Published: April 2021

Overgrazing stands out as threat factors on biodiversity, being especially harmful in the Mediterranean, due to strong human pressure and an accelerated climate change acting synergistically. Fencing is one of the most used tools in conservation biology to tackle this problem. Advantages of fences are usually fast, intuitive, and easy to evaluate. However, disadvantages could also arise (increasing interspecific competition, disturbing habitat structure, limiting pollination, reducing dispersion). Together with management issues (maintenance, conflicts with stakeholders, and pulling effect). Effectiveness of fencing for conservation has been frequently assessed for animals, while it is almost a neglected topic in plants. We evaluated the outcome of fencing three threatened and narrow-endemic plants. Selected 5 populations were only partly fenced, which allowed comparing different variables inside and outside the fence. For evaluating the fencing effects, we sampled several habitats (vegetation cover, composition, density of target species), and target-species features (individual size, neighbouring species, and fruit-set). Fencing had strong effects on the habitat and on target-species individuals, showing contrasting responses at species and population level. Particularly, for Erodium cazorlanum, fence had a positive effect in one case, and negative in another. In Hormathophylla baetica effect was positive in all populations. Finally, fencing negatively affected Solenanthus reverchonii by increasing competition and limiting seed-dispersal. Fencing outcome was different in assessed species, highlighting the need to a case-by-case evaluation to determine the net balance (pros vs. cons), also its suitability and most favourable option (i.e. permanent vs. temporary fences).