bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Acute Inflammation on Cytochromes P450 Activity Assessed by the Geneva Cocktail
Authors: Lenoir Camille , Daali Youssef , Rollason Victoria , Curtin François , Gloor Yvonne , Bosilkovska Marija , Walder Bernhard , Gabay Cem , Nissen Michael John , Desmeules Jules Alexandre , Hannouche Didier , Samer Caroline Flora 
Published: December 2020

Cytochromes P450 (CYP) are subject to important interindividual variability in their activity due to genetic and environmental factors and some diseases. Limited human data support the idea that inflammation downregulates CYP activities. Our study aimed to evaluate the impact of orthopedic surgery (acute inflammation model) on the activity of six human CYP. This prospective observational study was conducted in 30 patients who underwent elective hip surgery at the Geneva University Hospitals in Switzerland. The Geneva phenotyping cocktail containing caffeine, bupropion, flurbiprofen, omeprazole, dextromethorphan, and midazolam as probe drugs respectively assessing CYP1A2, 2B6, 2C9, 2C19, 2D6, and 3A activities was administered orally before surgery, day 1 (D1) and 3 (D3) postsurgery and at discharge. Capillary blood samples were collected 2 hours after cocktail intake to assess metabolic ratios (MRs). Serum inflammatory markers (CRP, IL‐6, IL‐1β, TNF‐α, and IFN‐γ) were also measured in blood. CYP1A2 MRs decreased by 53% (P < 0.0001) between baseline and the nadir at D1. CYP2C19 and CYP3A activities (MRs) decreased by 57% (P = 0.0002) and 61% (P < 0.0001), respectively, with the nadir at D3. CYP2B6 and CYP2C9 MRs increased by 120% (P < 0.0001) and 79% (P = 0.018), respectively, and peaked at D1. Surgery did not have a significant impact on CYP2D6 MR. Hip surgery was a good acute inflammation model as CRP, IL‐6, and TNF‐α peak levels were reached between D1 and day 2 (D2). Acute inflammation modulated CYP activity in an isoform‐specific manner, with different magnitudes and kinetics. Acute inflammation may thus have a clinically relevant impact on the pharmacokinetics of these CYP substrates.
Upgrading of Bio‐Oil Model Compounds and Bio‐Crude into Biofuel by Electrocatalysis: A Review
Authors: Chen Guanyi , Liang Lan , Li Ning , Lu Xukai , Yan Beibei , Cheng Zhanjun 
Published: December 2020

AbstractLimited availability of fossil energy and serious environmental pollution have caused the emergence of bio‐oil, which can serve as an alternative and promising green energy source. However, bio‐oil generated from the rapid pyrolysis of biomass cannot be utilized immediately owing to its corrosivity, instability, and low heating value. Herein, the electrocatalytic hydrogenation (ECH) process towards bio‐oil upgrading is reviewed. Specifically, the ECH integrates the advantages of mild operating conditions, no petrochemically derived hydrogen and good controllability. The influence of different factors on the conversion of bio‐oil components and product selectivity in the ECH process are presented comprehensively. In addition, various reaction mechanisms are discussed in the designed ECH systems. Finally, some challenges need to be further overcome for real bio‐oil reduction in the ECH process: exploration of efficient multifunctional electrocatalysts for specific bio‐oil components and determination of the dominant steps in the complicated reaction path network.
Origins and diversity of macrophages in health and disease
Authors: Sreejit Gopalkrishna , Fleetwood Andrew J , Murphy Andrew J , Nagareddy Prabhakara R 
Published: December 2020

AbstractMacrophages are the first immune cells in the developing embryo and have a central role in organ development, homeostasis, immunity and repair. Over the last century, our understanding of these cells has evolved from being thought of as simple phagocytic cells to master regulators involved in governing a myriad of cellular processes. A better appreciation of macrophage biology has been matched with a clearer understanding of their diverse origins and the flexibility of their metabolic and transcriptional machinery. The understanding of the classical mononuclear phagocyte system in its original form has now been expanded to include the embryonic origin of tissue‐resident macrophages. A better knowledge of the intrinsic similarities and differences between macrophages of embryonic or monocyte origin has highlighted the importance of ontogeny in macrophage dysfunction in disease. In this review, we provide an update on origin and classification of tissue macrophages, the mechanisms of macrophage specialisation and their role in health and disease. The importance of the macrophage niche in providing trophic factors and a specialised environment for macrophage differentiation and specialisation is also discussed.
Ab initio spillover compensation in mass cytometry data
Authors: Miao Qi , Wang Fang , Dou Jinzhuang , Iqbal Ramiz , Muftuoglu Muharrem , Basar Rafet , Li Li , Rezvani Katy , Chen Ken 
Published: December 2020

AbstractSignal intensity measured in a mass cytometry (CyTOF) channel can often be affected by the neighboring channels due to technological limitations. Such signal artifacts are known as spillover effects and can substantially limit the accuracy of cell population clustering. Current approaches reduce these effects by using additional beads for normalization purposes known as single‐stained controls. While effective in compensating for spillover effects, incorporating single‐stained controls can be costly and require customized panel design. This is especially evident when executing large‐scale immune profiling studies. We present a novel statistical method, named CytoSpill that independently quantifies and compensates the spillover effects in CyTOF data without requiring the use of single‐stained controls. Our method utilizes knowledge‐guided modeling and statistical techniques, such as finite mixture modeling and sequential quadratic programming, to achieve optimal error correction. We evaluated our method using five publicly available CyTOF datasets obtained from human peripheral blood mononuclear cells (PBMCs), C57BL/6J mouse bone marrow, healthy human bone marrow, chronic lymphocytic leukemia patient, and healthy human cord blood samples. In the PBMCs with known ground truth, our method achieved comparable results to experiments that incorporated single‐stained controls. In datasets without ground‐truth, our method not only reduced spillover on likely affected markers, but also led to the discovery of potentially novel subpopulations expressing functionally meaningful, cluster‐specific markers. CytoSpill (developed in R) will greatly enhance the execution of large‐scale cellular profiling of tumor immune microenvironment, development of novel immunotherapy, and the discovery of immune‐specific biomarkers. The implementation of our method can be found at https://github.com/KChen-lab/CytoSpill.git.
Silver‐Catalyzed [3+1+1] Annulation of Nitrones with Isocyanoacetates as an Approach to 1,4,5‐Trisubstituted Imidazoles
Authors: Lv Lanlan , Chen Yan , Shatskiy Andrey , Liu Jian‐Quan , Liu Xiaoyi , Kärkäs Markus D. , Wang Xiang‐Shan 
Published: December 2020

AbstractA silver‐catalyzed protocol for [3+1+1] annulation of nitrones and isocyanoacetates is reported. The reaction is proposed to proceed through sequential [3+2] cycloaddition, ring‐opening, cyclization‐oxidation, and dealkylation, allowing access to a broad scope of valuable polysubstituted imidazoles in high yields.
Oxidative stress, DNA damage, inflammation and gene expression in occupationally exposed university hospital anesthesia providers
Authors: Souza Kátina Meneghetti , De Vivo Immaculata , Chen Chung‐Yen , Nogueira Flávia Ribeiro , Aun Aline Garcia , Arruda Nayara Micarelli , Lara Juliana Rodrigues , Silva Mariane Aparecida P. , Figueiredo Drielle Baptista S. , Corrêa Camila Renata , de Carvalho Lídia Raquel , Braz José Reinaldo C. , Braz Leandro Gobbo , Braz Mariana Gobbo 
Published: December 2020

AbstractConsidering the importance and lack of data of toxicogenomic approaches on occupational exposure to anesthetics, we evaluated possible associations between waste anesthetic gases (WAGs) exposure and biological effects including oxidative stress, DNA damage, inflammation, and transcriptional modulation. The exposed group was constituted by anesthesia providers who were mainly exposed to the anesthetics sevoflurane and isoflurane (10 ppm) and to a lesser degree to nitrous oxide (150 ppm), and the control group was constituted by physicians who had no exposure to WAGs. The oxidative stress markers included oxidized DNA bases (comet assay), malondialdehyde (high‐performance liquid chromatography [HPLC]), nitric oxide metabolites (ozone‐chemiluminescence), and antioxidative markers, including individual antioxidants (HPLC) and antioxidant defense marker (ferric reducing antioxidant power by spectrophotometry). The inflammatory markers included high‐sensitivity C‐reactive protein (chemiluminescent immunoassay) and the proinflammatory interleukins IL‐6, IL‐8 and IL‐17A (flow cytometry). Telomere length and gene expression related to DNA repair (hOGG1 and XRCC1), antioxidant defense (NRF2) and inflammation (IL6, IL8 and IL17A) were evaluated by real‐time quantitative polymerase chain reaction. No significant differences (p > .0025) between the groups were observed for any parameter evaluated. Thus, under the conditions of the study, the findings suggest that occupational exposure to WAGs is not associated with oxidative stress or inflammation when evaluated in serum/plasma, with DNA damage evaluated in lymphocytes and leucocytes or with molecular modulation assessed in peripheral blood cells in university anesthesia providers. However, it is prudent to reduce WAGs exposure and to increase biomonitoring of all occupationally exposed professionals.
Relationships between the response of the sweet taste receptor, salivation toward sweeteners, and sweetness intensity
Authors: Kusakabe Yuko , Shindo Yumiko , Kawai Takayuki , Maeda‐Yamamoto Mari , Wada Yuji 
Published: December 2020

AbstractSweeteners are widely used in food products, and their sweetness potency is usually evaluated by comparing it with that of sucrose. This, however, has led to confusion as some sweeteners are evaluated based on their maximum value of sweet taste response, while others are evaluated by their threshold value. Here, we aimed to develop a novel nonverbal sweetness evaluation system through the sweet taste signal transduction by comparing the responses of the sweet taste receptor, salivation, taste intensity, and preference among six sweeteners. The hT1r2/hT1r3 sweet taste receptor responses represented the input signal of the sweet taste signal transduction, while salivation, sweet taste intensity, and participants' preferences represented the output signals by the gustatory–salivary reflex, primary gustatory cortex area, and the secondary gustatory cortex, respectively. Our results showed that the sweet taste receptor, sweet intensity, and salivary secretion responses were concentration‐dependent and expressed exponentially. Moreover, the results comparing coefficients showed 15–35 times more sensitivity between the response of hT1r2/hT1r3 and the salivation or the sweet taste intensity in non‐nutrient sweeteners. The preference graph curve was not exponential, suggesting that the sweetener preference was not related to the sweet taste receptor, salivation, or sweet taste intensity. These results may suggest that the sweet taste signal of the non‐nutritive sweeteners might be maintained by taste reception by hT1r2/hT1r3 to taste recognition in the primary gustatory area and that receptor responses and salivation could be used as indicators of sweetness intensity.
Unique deficit in embodied simulation in autism: An fMRI study comparing autism and developmental coordination disorder
Authors: Kilroy Emily , Harrison Laura , Butera Christiana , Jayashankar Aditya , Cermak Sharon , Kaplan Jonas , Williams Marian , Haranin Emily , Bookheimer Susan , Dapretto Mirella , Aziz‐Zadeh Lisa 
Published: December 2020

AbstractA deficit in pre‐cognitively mirroring other people's actions and experiences may be related to the social impairments observed in autism spectrum disorder (ASD). However, it is unclear whether such embodied simulation deficits are unique to ASD or instead are related to motor impairment, which is commonly comorbid with ASD. Here we aim to disentangle how, neurologically, motor impairments contribute to simulation deficits and identify unique neural signatures of ASD. We compare children with ASD (N = 30) to children with Developmental Coordination Disorder (DCD; N = 23) as well as a typically developing group (N = 33) during fMRI tasks in which children observe, imitate, and mentalize about other people's actions. Results indicate a unique neural signature in ASD: during action observation, only the ASD group shows hypoactivity in a region important for simulation (inferior frontal gyrus, pars opercularis, IFGop). However, during a motor production task (imitation), the IFGop is hypoactive for both ASD and DCD groups. For all tasks, we find correlations across groups with motor ability, even after controlling for age, IQ, and social impairment. Conversely, across groups, mentalizing ability is correlated with activity in the dorsomedial prefrontal cortex when controlling for motor ability. These findings help identify the unique neurobiological basis of ASD for aspects of social processing. Furthermore, as no previous fMRI studies correlated brain activity with motor impairment in ASD, these findings help explain prior conflicting reports in these simulation networks.
Hippocampal neurogenesis and memory in adolescence following intrauterine growth restriction
Authors: Gilchrist Courtney P. , Cumberland Angela L. , Kondos‐Devcic Delphi , Hill Rachel A. , Khore Madhavi , Quezada Sebastian , Reichelt Amy C. , Tolcos Mary 
Published: December 2020

AbstractIntrauterine growth restriction (IUGR) is associated with hippocampal alterations that can increase the risk of short‐term memory impairments later in life. Despite the role of hippocampal neurogenesis in learning and memory, research into the long‐lasting impact of IUGR on these processes is limited. We aimed to determine the effects of IUGR on neuronal proliferation, differentiation and morphology, and on memory function at adolescent equivalent age. At embryonic day (E) 18 (term ∼E22), placental insufficiency was induced in pregnant Wistar rats via bilateral uterine vessel ligation to generate IUGR offspring (n = 10); control offspring (n = 11) were generated via sham surgery. From postnatal day (P) 36–44, spontaneous location recognition (SLR), novel object location and recognition (NOL, NOR), and open field tests were performed. Brains were collected at P45 to assess neurogenesis (immunohistochemistry), dendritic morphology (Golgi staining), and brain‐derived neurotrophic factor expression (BDNF; Western blot analysis). In IUGR versus control rats there was no difference in object preference in the NOL or NOR, the similar and dissimilar condition of the SLR task, or in locomotion and anxiety‐like behavior in the open field. There was a significant increase in the linear density of immature neurons (DCX+) in the subgranular zone (SGZ) of the dentate gyrus (DG), but no difference in the linear density of proliferating cells (Ki67+) in the SGZ, nor in areal density of mature neurons (NeuN+) or microglia (Iba‐1+) in the DG in IUGR rats compared to controls. Dendritic morphology of dentate granule cells did not differ between groups. Protein expression of the BDNF precursor (pro‐BDNF), but not mature BDNF, was increased in the hippocampus of IUGR compared with control rats. These findings highlight that while the long‐lasting prenatal hypoxic environment may impact brain development, it may not impact hippocampal‐dependent learning and memory in adolescence.
Impacts of couple stress with magnetic field and heat absorption on peristaltic flow of a power‐law fluid containing nanoparticles
Authors: Eldabe Nabil T. , Kamel Kawther A. , Ramadan Shaimaa F. , Saad Rabab A. 
Published: December 2020

AbstractThis paper deals with the mathematical examination of the arrangement of incomplete differential conditions which depict the peristaltic movement of a non‐Newtonian nanofluid with couple stress through a symmetric channel with flexible walls. The fluid used obeys a power‐law model. The system of the nondimensional form of momentum, heat, and concentration of the fluid flow is solved numerically by using a Rung–Kutta–Merson method with the appropriate boundary conditions after using the approximations of long wavelength and low Reynolds number. The obtained arrangements are elements of the physical boundaries of the problem. In this manner, the impacts of these boundaries on the velocity, temperature, and nanoconcentration distributions are concentrated mathematically and shown graphically through many figures. It is discovered that the physical boundaries play a significant role in controlling the arrangements, where the speed field diminishes with expansion of the attractive boundary, while it increments with expanding couple pressure and the non‐Newtonian parameter of the non‐Newtonian liquid. Additionally, the temperature and nanoconcentration changes with the Brownian parameter and thermophoresis. Moreover, the temperature distribution increases with increase of the magnetic parameter, Prandtl number, Eckert number, and heat source.
Oncometabolite L‐2‐hydroxyglurate directly induces vasculogenic mimicry through PHLDB2 in renal cell carcinoma
Authors: Wang Huan , Wang Liya , Zheng Qiming , Lu Zeyi , Chen Yuanlei , Shen Danyang , Xue Dingwei , Jiang Minxiao , Ding Lifeng , Zhang Jie , Wu Haiyang , Xia Liqun , Qian Jun , Li Gonghui , Lu Jieyang 
Published: December 2020

AbstractMetabolism reprograming is a hallmark of cancer and plays an important role in tumor progression. The aberrant metabolism in renal cell carcinoma (RCC) leads to accumulation of the oncometabolite L‐2‐hydroxyglurate (L‐2HG). L‐2HG has been reported to inhibit the activity of some α‐ketoglutarate‐dependent dioxygenases such as TET enzymes, which mediate epigenetic alteration, including DNA and histone demethylation. However, the detailed functions of L‐2HG in renal cell carcinoma have not been investigated thoroughly. In our study, we found that L‐2HG was significantly elevated in tumor tissues compared to adjacent tissues. Furthermore, we demonstrated that L‐2HG promoted vasculogenic mimicry (VM) in renal cancer cell lines through reducing the expression of PHLDB2. A mechanism study revealed that activation of the ERK1/2 pathway was involved in L‐2HG‐induced VM formation. In conclusion, these findings highlighted the pathogenic link between L‐2HG and VM and suggested a novel therapeutic target for RCC.
Evaluation of the lifetime brain/central nervous system cancer risk associated with childhood head CT scanning in Japan
Authors: Kadowaki Yuko , Hamada Nobuyuki , Kai Michiaki , Furukawa Kyoji 
Published: December 2020

AbstractThe use of computed tomography (CT) scanning has increased worldwide over the decades, and Japan is one of the leading countries in annual frequency of diagnostic CT. Although benefits of CT scan are undisputable, concerns have been raised about potential health effects of ionizing radiation exposure from CT, particularly among children who are likely more susceptible to radiation than adults. Our study aims to evaluate the cumulated lifetime risk of the brain/central nervous system (CNS) cancer due to head CT examinations performed on Japanese children at age 0 to 10 years in 2012, 2015 and 2018. The frequency and dose distribution of head CT examinations were estimated based on information from recent national statistics and nationwide surveys. The lifetime risk attributable to exposure was calculated by applying risk models based on the study of Japanese atomic‐bomb survivors. In contrast to the overall increasing trend, the frequency of childhood CT, especially at age < 5, was decreasing, reflecting a growing awareness for efforts to reduce childhood CT exposure over the past decade. In 2018, 138 532 head CT examinations were performed at age 0 to 10, which would consequently induce a lifetime excess of 22 cases (1 per 6300 scans) of brain/CNS cancers, accounting for 5% of the total cases. More excess cases were estimated among men than among women, and excess cases could emerge at relatively young ages. These results would have useful implications as scientific basis for future large‐scale epidemiological studies and also as quantitative evidence to justify the benefits of CT vs risks in Japan.
Effects of screening for colorectal cancer: Development, documentation and validation of a multistate Markov model
Authors: Heisser Thomas , Hoffmeister Michael , Brenner Hermann 
Published: December 2020

AbstractSimulation models are a powerful tool to overcome gaps of evidence needed to inform medical decision‐making. Here, we present development and application of COSIMO, a Markov‐based Colorectal Cancer (CRC) Multi‐state Simulation Model to simulate effects of CRC screening, along with a thorough assessment of the model's ability to reproduce real‐life outcomes. Firstly, we provide a comprehensive documentation of COSIMO’s development, structure and assumptions. Secondly, to assess the model's external validity, we compared model‐derived cumulative incidence and prevalences of colorectal neoplasms to (a) results from KolosSal, a study in German screening colonoscopy participants, (b) registry‐based estimates of CRC incidence in Germany, and (c) outcome patterns of randomized sigmoidoscopy screening studies. We found that (a) more than 90% of observed prevalences in the KolosSal study were within the 95% confidence intervals of the model‐predicted neoplasm prevalences; (b) the 15‐year cumulative CRC incidences estimated by simulations for the German population deviated by 0.0% to 0.2% units in men and 0.0% to 0.3% units in women when compared to corresponding registry‐derived estimates; and (c) the time course of cumulative CRC incidence and mortality in the modeled intervention group and control group closely resembles the time course reported from sigmoidoscopy screening trials. Overall, COSIMO adequately predicted colorectal neoplasm prevalences and incidences in a German population for up to 25 years, with estimated patterns of the effect of screening colonoscopy resembling those seen in registry data and real‐world studies. This suggests that the model may represent a valid tool to assess the comparative effectiveness of CRC screening strategies.