bluuebunny/crossref_metadata_2025 huggingface dataset:
Racial/Ethnic Disparities in Patient Care Experiences among Prostate Cancer Survivors: A SEER-CAHPS Study
Authors: Pandit Ambrish A. , Gressler Laura E. , Halpern Michael T. , Kamel Mohamed , Payakachat Nalin , Li Chenghui
Published: November 2022

Purpose: To evaluate racial/ethnic disparities in patient care experiences (PCEs) among prostate cancer (PCa) survivors. Methods: This retrospective study used 2007–2015 National Cancer Institute Surveillance, Epidemiology and End Results registry data linked to Consumer Assessment of Healthcare Providers and Systems surveys. First survey ≥ 6 months post-PCa diagnosis was analyzed. We performed multivariable linear regression, adjusting for demographic and clinical covariates, to evaluate the association of race/ethnicity (non-Hispanic Whites (NHWs), non-Hispanic Black (NHBs), Hispanic, non-Hispanic Asian (NHAs), and other races) with PCE composite measures: getting needed care, doctor communication, getting care quickly, getting needed prescription drugs (Rx), and customer service. Results: Among 7319 PCa survivors, compared to NHWs, Hispanics, NHBs and NHAs reported lower scores for getting care quickly (ß = −3.69; p = 0.002, ß = −2.44; p = 0.021, and ß = −6.44; p < 0.001, respectively); Hispanics scored worse on getting needed care (ß = −2.16; p = 0.042) and getting needed Rx (ß = −2.93; p = 0.009), and NHAs scored worse on customer service (ß = −7.60; p = 0.003), and getting needed Rx (ß = −3.08; p = 0.020). However, NHBs scored better than NHWs on doctor communication (ß = 1.95, p = 0.006). No statistically significant differences were found between other races and NHWs. Conclusions: Comparing to NHWs, Hispanics and NHAs reported worse experiences on several PCE composite measures, while NHBs reported worse scores on one but better scores on another PCE composite measure. Further research is needed to understand the reasons behind these disparities and their influence on healthcare utilization and health outcomes among PCa survivors.
Recent HIV Infection: Diagnosis and Public Health Implications
Authors: Nikolopoulos Georgios K. , Tsantes Andreas G.
Published: November 2022

The early period of infection with human immunodeficiency virus (HIV) has been associated with higher infectiousness and, consequently, with more transmission events. Over the last 30 years, assays have been developed that can detect viral and immune biomarkers during the first months of HIV infection. Some of them depend on the functional properties of antibodies including their changing titers or the increasing strength of binding with antigens over time. There have been efforts to estimate HIV incidence using antibody-based assays that detect recent HIV infection along with other laboratory and clinical information. Moreover, some interventions are based on the identification of people who were recently infected by HIV. This review summarizes the evolution of efforts to develop assays for the detection of recent HIV infection and to use these assays for the cross-sectional estimation of HIV incidence or for prevention purposes.
Changing the Patient’s Position: Pitfalls and Benefits for Radiation Dose and Image Quality of Computed Tomography in Polytrauma
Authors: Graef Jessica , Bressem Keno K. , Asbach Patrick , Hamm Bernd , Niehues Stefan M.
Published: November 2022

For computed tomography (CT), representing the diagnostic standard for trauma patients, image quality is essential. The positioning of the patient’s arms next to the abdomen causes artifacts and is also considered to increase radiation exposure. The aim of this study was to evaluate the effect of various positionings during different CT examination steps on the extent of artifacts as well as radiation dose using iterative reconstruction (IR). 354 trauma-CTs were analyzed retrospectively. All datasets were reconstructed using IR and three different examination protocols were applied. Arm elevation led to a significant improvement of the image quality across all examination protocols (p < 0.001). Variation in arm positioning during image acquisition did not lead to a reduction of radiation dose (p = 0.123). Only elevation during scout acquisition resulted in the reduction of radiation exposure (p < 0.001). To receive high-quality CT images, patients should be placed with elevated arms for the trunk scan, as artifacts remain even with the IR. Arm repositioning during the examination itself had no effect on the applied radiation dose because its modulation refers to the initial scout obtained. In order to achieve a dose effect by different positioning, a two-scout protocol (dual scout) should be used.
Research on Insulator Defect Detection Based on an Improved MobilenetV1-YOLOv4
Authors: Xu Shanyong , Deng Jicheng , Huang Yourui , Ling Liuyi , Han Tao
Published: November 2022

Insulator devices are important for transmission lines, and defects such as insulator bursting and string loss affect the safety of transmission lines. In this study, we aim to investigate the problems of slow detection speed and low efficiency of traditional insulator defect detection algorithms, and to improve the accuracy of insulator fault identification and the convenience of daily work; therefore, we propose an insulator defect detection algorithm based on an improved MobilenetV1-YOLOv4. First, the backbone feature extraction network of YOLOv4 ‘Backbone’ is replaced with the lightweight module Mobilenet-V1. Second, the scSE attention mechanism is introduced in stages of preliminary feature extraction and enhanced feature extraction, sequentially. Finally, the depthwise separable convolution substitutes the 3 × 3 convolution of the enhanced feature extraction network to reduce the overall number of network parameters. The experimental results show that the weight of the improved algorithm is 57.9 MB, which is 62.6% less than that obtained by the MobilenetV1-YOLOv4 model; the average accuracy of insulator defect detection is improved by 0.26% and reaches 98.81%; and the detection speed reaches 190 frames per second with an increase of 37 frames per second.
Three Terminal Perovskite/Silicon Solar Cell with Bipolar Transistor Architecture
Authors: Giliberti Gemma , Di Giacomo Francesco , Cappelluti Federica
Published: November 2022

Solar photovoltaic energy is the most prominent candidate to speed up the transition from the existing non-renewable energy system to a more efficient and environmentally friendly one. Currently, silicon cells dominate the photovoltaic market owing to their cost-effectiveness and high efficiency, nowadays approaching the theoretical limit. Higher efficiency can be achieved by tandem devices, where a wide bandgap semiconductor is stacked on top of the silicon cell. Thin-film perovskite technology has emerged as one of the most promising for the development of silicon-based tandems because of the optimal perovskite opto-electronic properties and the fast progress achieved in the last decade. While most of the reported perovskite/silicon tandem devices exploit a two-terminal series connected structure, three-terminal solutions have recently drawn significant attention due to their potential for higher energy yield. In this work, we report for the first time a theoretical study, based on validated optical and electrical simulations, of three-terminal perovskite/silicon solar cells employing a hetero-junction bipolar transistor structure. With respect to other three-terminal tandems proposed so far, the transistor structure can be implemented with rear-contact silicon cells, which are simpler and more common than interdigitated back-contact ones.
Orderliness in Mining 4.0
Authors: Zhironkin Sergey , Gasanov Magerram , Suslova Yulia
Published: November 2022

Mining of minerals is an important part of the technical sciences, for which the certainty and unambiguity of terms and the correct application of definitions is an absolute requirement. At the same time, the expansion of Industry 4.0 technologies, both in practice and in scientific discussions, brings new terms to mining that are far from the original meaning. These terms include Data Mining and Mining 4.0, which, having a common digital core, refer to fundamentally different areas of human activity, and have the opposite meaning in relation to the use of resources (digital ones—endless, and the natural ones—finite). The indiscriminate use of the term “mining” is especially dangerous in the context of Mining 4.0, in which digital technologies allow the intensification of the exploitation of natural resources. This brief Perspective paper will show the role of terminology in Mining 4.0 and offer an interpretation of its relationship with Data Mining.
Study on the Slurry Diffusion Law of Fluidized Filling Gangue in the Caving Goaf of Thick Coal Seam Fully Mechanized Caving Mining
Authors: Li Liang , Huang Qingxiang , Zuo Xiao , Wu Jie , Wei Baoning , He Yanpeng , Zhang Weilong , Zhang Jie
Published: November 2022

Because of the problem of gangue discharge and surface subsidence during coal mining, the current research on underground filling mainly focuses on the paste filling, solid filling, and grouting filling of the overburden separation layer after scaffolding. We proposed the technology of fluidization gangue grouting for filling the collapse area based on our previous research. The prediction method of residual space in the collapse area and the diffusion law of gangue fluidization filling slurry are two essential points for successfully implementing the technology and maximizing the use of goaf for gangue backfilling and reducing overburden settlement. To further explore the remaining space distribution law of the collapsed goaf in thick seam fully mechanized top coal caving mining and the effect of coal gangue fluidization filling, the caving goaf of the 3307 fully mechanized top coal caving face in Sangshuping No. 2 coal mine in the Weibei mining area was detected by the transient electromagnetic method. We studied the distribution law of the measured abnormal area in the caving goaf, which reflects the distribution law of the remaining space from one aspect. The coefficient of the remaining space was calculated to be 19.5%. Then, we applied COMSOL simulation software. The diffusion law of coal gangue fluidized slurry in the caving goaf was simulated and analyzed. It shows that the most obvious diffusion direction of the coal gangue slurry is the trend of the gradual expansion of the “cavity pore” multi-type residual space, indicating that with the increase in the diffusion distance, the diffusion resistance gradually increases, and the slurry morphology gradually presents the “claw” form. According to the space theory and fractal dimension theory, the prediction method of the remaining space in the caving goaf is given, and the design basis of the filling drilling parameters is determined. Finally, the field-filling test was carried out. The results show that the high- and low-level fluidized filling in the caving goaf can safely and efficiently handle the gangue in the mine, and the residual space characteristics and slurry diffusion law in the caving goaf are consistent with the above. The research results provide theoretical support for the fluidization filling technology of coal gangue in thick seam fully mechanized top coal caving areas.
A Novel Denoising Method for Partial Discharge Signal Based on Improved Variational Mode Decomposition
Authors: Yang Jingjie , Yan Ke , Wang Zhuo , Zheng Xiang
Published: November 2022

Partial discharge (PD) online monitoring is a common technique for high-voltage equipment diagnosis. However, due to field interference, the monitored PD signal contains a lot of noise. Therefore, this paper proposes a novel method by integrating the flower pollination algorithm, variational mode decomposition, and Savitzky–Golay filter (FPA-VMD-SG) to effectively suppress white noise and narrowband noise in the PD signal. Firstly, based on the mean envelope entropy (MEE), the decomposition number and quadratic penalty term of the VMD were optimized by the FPA. The PD signal containing noise was broken down into intrinsic mode functions (IMFs) by optimized parameters. Secondly, the IMFs were classified as the signal component, the noise dominant component, and the noise component according to the kurtosis value. Thirdly, the noise dominant component was denoised using the SG filter, and the denoised signal was mixed with the signal component to reconstruct a new signal. Finally, threshold denoising was used to eliminate residual white noise. To verify the performance of the FPA-VMD-SG method, compared with empirical mode decomposition with wavelet transform (EMD-WT) and adaptive singular value decomposition (ASVD), the denoising results of simulated and real PD signals indicated that the FPA-VMD-SG method had excellent performance.
Toward the Application of Pulse Width Modulated (PWM) Inverter Drive-Based Electric Propulsion to Ice Capable Ships
Authors: Renz Eric Christopher , Turso James
Published: November 2022

The current world geopolitical state has driven significant interest in expanding influence in the polar regions. In order to develop new trade routes and defense of these areas, specialized ice-capable vessels are needed. Traditional propulsion technology utilized for these vessels has featured diesel and turbo electric drives with cycloconverter based technology used for speed regulation. Cycloconverter technology has the major disadvantage of characteristic output voltage waveforms that are very non-sinusoidal which induce harmonic rich currents with their resulting negative effects on total power factor and efficiency. There is also the potential to induce harmonic currents that may increase heat production in power cables, stressing insulation and reducing overall component life. Furthermore, sensitive loads such as control system power supplies may also be affected. The output waveform of a PWM drive has harmonic content that is both less severe, and more easily analyzed with current modeling tools. There are significant technical challenges that need to be assessed when considering PWM drive deployment in ice-capable vessels. This is due to the severe load torques, and torque variation imposed on propeller blades during ice-milling operations. To the authors’ knowledge, an analysis of the behavior of vector-controlled PWM drives to this type of service has not been published in the open literature. This paper presents an initial modeling and simulation study that investigates whether such a PWM drive and associated controller may be effective for ice milling and other operational evolutions for these types of ships.
Study on the Complex Dynamical Behavior of the Fractional-Order Hopfield Neural Network System and Its Implementation
Authors: Ma Tao , Mou Jun , Li Bo , Banerjee Santo , Yan Huizhen
Published: November 2022

The complex dynamics analysis of fractional-order neural networks is a cutting-edge topic in the field of neural network research. In this paper, a fractional-order Hopfield neural network (FOHNN) system is proposed, which contains four neurons. Using the Adomian decomposition method, the FOHNN system is solved. The dissipative characteristics of the system are discussed, as well as the equilibrium point is resolved. The characteristics of the dynamics through the phase diagram, the bifurcation diagram, the Lyapunov exponential spectrum, and the Lyapunov dimension of the system are investigated. The circuit of the system was also designed, based on the Multisim simulation platform, and the simulation of the circuit was realized. The simulation results show that the proposed FOHNN system exhibits many interesting phenomena, which provides more basis for the study of complex brain working patterns, and more references for the design, as well as the hardware implementation of the realized fractional-order neural network circuit.
Partially Explore the Differences and Similarities between Riemann-Liouville Integral and Mellin Transform
Authors: Zhou Zhibiao , Xiao Wei , Liang Yongshun
Published: November 2022

At present many researchers devote themselves to studying the relationship between continuous fractal functions and their fractional integral. But little attention is paid to the relationship between Mellin transform and fractional integral. This paper aims to partially explore the differences and similarities between Riemann-Liouville integral and Mellin transform, then a 1-dimensional continuous and unbounded variational function defined on the closed interval [0,1] needs to be constructed. Through describing the image of the constructed function and its transformed function and proving the relevant properties, we obtain that Box dimension of its Riemann–Liouville integral of arbitrary order and its Mellin transformed function are also one. The smoothness of its Riemann–Liouville integral can only be improved, and its Mellin transformed function is differentiable.
A Plasma Circular RNA Profile Differentiates Subjects with Alzheimer’s Disease and Mild Cognitive Impairment from Healthy Controls
Authors: Piscopo Paola , Manzini Valeria , Rivabene Roberto , Crestini Alessio , Le Pera Loredana , Pizzi Elisabetta , Veroni Caterina , Talarico Giuseppina , Peconi Martina , Castellano Anna Elisa , D’Alessio Carmelo , Bruno Giuseppe , Corbo Massimo , Vanacore Nicola , Lacorte Eleonora
Published: November 2022

The most frequently used biomarkers to support the diagnosis of Alzheimer’s Disease (AD) are Aβ42, total-Tau, and phospho-tau protein levels in CSF. Moreover, magnetic resonance imaging is used to assess hippocampal atrophy, 18F-FDG PET to identify abnormal brain metabolism, and PET imaging for amyloid deposition. These tests are rather complex and invasive and not easily applicable to clinical practice. Circulating non-coding RNAs, which are inherently stable and easy to manage, have been reported as promising biomarkers for central nervous system conditions. Recently, circular RNAs (circRNAs) as a novel class of ncRNAs have gained attention. We carried out a pilot study on five participants with AD and five healthy controls (HC) investigating circRNAs by Arraystar Human Circular RNA Microarray V2.0. Among them, 26 circRNAs were differentially expressed (FC ≥ 1.5, p < 0.05) in participants with AD compared to HC. From a top 10 of differentially expressed circRNAs, a validation study was carried out on four up-regulated (hsa_circRNA_050263, hsa_circRNA_403959, hsa_circRNA_003022, hsa_circRNA_100837) and two down-regulated (hsa_circRNA_102049, hsa_circRNA_102619) circRNAs in a larger population. Moreover, five subjects with mild cognitive impairment (MCI) were investigated. The analysis confirmed the upregulation of hsa_circRNA_050263, hsa_circRNA_403959, and hsa_circRNA_003022 both in subjects with AD and in MCI compared to HCs. We also investigated all microRNAs potentially interacting with the studied circRNAs. The GO enrichment analysis shows they are involved in the development of the nervous system, and in the cellular response to nerve growth factor stimuli, protein phosphorylation, apoptotic processes, and inflammation pathways, all of which are processes related to the pathology of AD.
Systemic CD4 Immunity and PD-L1/PD-1 Blockade Immunotherapy
Authors: Escors David , Bocanegra Ana , Chocarro Luisa , Blanco Ester , Piñeiro-Hermida Sergio , Garnica Maider , Fernandez-Rubio Leticia , Vera Ruth , Arasanz Hugo , Kochan Grazyna
Published: November 2022

PD-L1/PD-1 blockade immunotherapy has changed the therapeutic approaches for the treatment of many cancers. Nevertheless, the mechanisms underlying its efficacy or treatment failure are still unclear. Proficient systemic immunity seems to be a prerequisite for efficacy, as recently shown in patients and in mouse models. It is widely accepted that expansion of anti-tumor CD8 T cell populations is principally responsible for anti-tumor responses. In contrast, the role of CD4 T cells has been less studied. Here we review and discuss the evidence supporting the contribution of CD4 T cells to anti-tumor immunity, especially recent advances linking CD4 T cell subsets to efficacious PD-L1/PD-1 blockade immunotherapy. We also discuss the role of CD4 T cell memory subsets present in peripheral blood before the start of immunotherapies, and their utility as predictors of response.
Rapid Detection of Fusarium oxysporum Using Insulated Isothermal PCR and a Rapid, Simple DNA Preparation Protocol
Authors: Chang Tsai-De , Huang Li-Nian , Lin Yi-Jia , Wu Zhong-Bin , Tsai Shang-Han , Lin Ying-Hong
Published: November 2022

We developed an insulated isothermal PCR (iiPCR) method for the efficient and rapid detection of Fusarium oxysporum (Fo), which is a fungus that infects various hosts and causes severe crop losses. The Fo iiPCR method was sensitive enough to detect up to 100 copies of standard DNA template and 10 fg of Fo genomic DNA. In addition, it could directly detect 1 pg of mycelium and 10 spores of Fo without DNA extraction. Our study compared the performance of Fo iiPCR to that of three published in planta molecular detection methods—conventional PCR, SYBR green-based real-time PCR, and hydrolysis probe-based real-time PCR—in field detection of Fo. All diseased field samples yielded positive detection results with high reproducibility when subjected to an Fo iiPCR test combined with a rapid DNA extraction protocol compared to Fo iiPCR with an automated magnetic bead-based DNA extraction protocol. Intraday and interday assays were performed to ensure the stability of this new rapid detection method. The results of detection of Fo in diseased banana pseudostem samples demonstrated that this new rapid detection method was suitable for field diagnosis of Fusarium wilt and had high F1 scores for detection (the harmonic mean of precision and recall of detection) for all asymptomatic and symptomatic Fo-infected banana samples. In addition, banana samples at four growth stages (seedling, vegetative, flowering and fruiting, and harvesting) with mild symptoms also showed positive detection results. These results indicate that this new rapid detection method is a potentially efficient procedure for on-site detection of Fo.
Crosstalk between Tumor-Associated Macrophages and MicroRNAs: A Key Role in Tumor Microenvironment
Authors: Zhou Xianghong , Chen Bo , Zhang Zilong , Huang Yin , Li Jinze , Wei Qiang , Cao Dehong , Ai Jianzhong
Published: November 2022

As an in-depth understanding of immunotherapy continues to grow, current anticancer therapy research is increasingly focused on the tumor microenvironment (TME). MicroRNAs (miRNAs) play crucial roles in the regulation of genetic information and expression and mediate interactions between tumor cells and components in the TME, such as tumor-associated macrophages (macrophages). Macrophages are abundant in the TME, and their different polarization directions can promote or inhibit tumor growth and progression. By regulating biological behaviors, such as macrophage recruitment, infiltration, and polarization, miRNAs can affect various molecular pathways to regulate tumor progression and treatment response. In this review, we discuss in detail the effects of macrophages on tumors and the multifaceted effects of miRNAs on macrophages. We also discuss the potential clinical applications and prospects of targeted therapy based on miRNAs, novel clinical biomarkers, and drug delivery systems.
APP Knock-In Mice Produce E22P-Aβ Exhibiting an Alzheimer’s Disease-like Phenotype with Dysregulation of Hypoxia-Inducible Factor Expression
Authors: Maki Takahito , Sawahata Masahito , Akutsu Ichiro , Amaike Shohei , Hiramatsu Genki , Uta Daisuke , Izuo Naotaka , Shimizu Takahiko , Irie Kazuhiro , Kume Toshiaki
Published: November 2022

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that requires further pathological elucidation to establish effective treatment strategies. We previously showed that amyloid β (Aβ) toxic conformer with a turn at positions 22–23 is essential for forming highly toxic oligomers. In the present study, we evaluated phenotypic changes with aging in AD model AppNL-P-F/NL-P-F (NL-P-F) mice with Swedish mutation (NL), Iberian mutation (F), and mutation (P) overproducing E22P-Aβ, a mimic of toxic conformer utilizing the knock-in technique. Furthermore, the role of the toxic conformer in AD pathology was investigated. NL-P-F mice produced soluble toxic conformers from an early age. They showed impaired synaptic plasticity, glial cell activation, and cognitive decline, followed by the accumulation of Aβ plaques and tau hyperphosphorylation. In addition, the protein expression of hypoxia-inducible factor (HIF)-1α was increased, and gene expression of HIF-3α was decreased in NL-P-F mice. HIF dysregulation due to the production of soluble toxic conformers may be involved in AD pathology in NL-P-F mice. This study could reveal the role of a highly toxic Aβ on AD pathogenesis, thereby contributing to the development of a novel therapeutic strategy targeting the toxic conformer.
Serum SELENBP1 and VCL Are Effective Biomarkers for Clinical and Forensic Diagnosis of Coronary Artery Spasm
Authors: Lin Xinyi , Lin Zijie , Zhao Xin , Liu Zheng , Xu Chenchao , Yu Bokang , Gao Pan , Wang Zhimin , Ge Junbo , Shen Yiwen , Li Liliang
Published: November 2022

Coronary artery spasm (CAS) plays an important role in the pathogenesis of many ischemic heart entities; however, there are no established diagnostic biomarkers for CAS in clinical and forensic settings. This present study aimed to identify such serum biomarkers by establishing a rabbit CAS provocation model and integrating quantitative serum proteomics, parallel reaction monitoring/mass spectrometry-based targeted proteomics, and partial least-squares discriminant analysis (PLS-DA). Our results suggested that SELENBP1 and VCL were potential candidate biomarkers for CAS. In independent clinical samples, SELENBP1 and VCL were validated to be significantly lower in serum but not blood cells from CAS patients, with the reasons for this possibly due to the decreased secretion from cardiomyocytes. The areas under the curve of the receiver operating characteristics (ROC) analysis were 0.9384 for SELENBP1 and 0.9180 for VCL when diagnosing CAS. The CAS risk decreased by 32.3% and 53.6% for every 10 unit increases in the serum SELENBP1 and VCL, respectively. In forensic samples, serum SELENBP1 alone diagnosed CAS-induced deaths at a sensitivity of 100.0% and specificity of 72.73%, and its combination with VCL yielded a diagnostic specificity of 100.0%, which was superior to the traditional biomarkers of cTnI and CK-MB. Therefore, serum SELENBP1 and VCL could be effective biomarkers for both the clinical and forensic diagnosis of CAS.
Adenosine A3 Receptor (A3AR) Agonist for the Treatment of Bleomycin-Induced Lung Fibrosis in Mice
Authors: Sgambellone Silvia , Marri Silvia , Catarinicchia Stefano , Pini Alessandro , Tosh Dilip K. , Jacobson Kenneth A. , Masini Emanuela , Salvemini Daniela , Lucarini Laura
Published: November 2022

Adenosine receptors (ARs) are involved in the suppression and development of inflammatory and fibrotic conditions. Specifically, AR activation promotes differentiation of lung fibroblasts into myofibroblasts, typical of a fibrotic event. Pulmonary fibrosis is a severe disease characterized by inflammation and fibrosis of unknown etiology and lacking an effective treatment. The present investigation explored the action of MRS5980, a new, highly potent and selective A3AR agonist, in an established murine model of lung fibrosis. The effects of either vehicle or MRS5980 were studied in mice following intratracheal bleomycin administration. We evaluated the role of the A3AR agonist on lung stiffness, studying the airway resistance to inflation, oxidative stress (8-OHdG and MDA), inflammation, pro- and anti-inflammatory marker levels (IL-1β, IL-6, TNF-α, IL-10 and IL-17A) and fibrosis establishment, evaluating transforming growth factor (TGF)-β expression and α-smooth muscle actin (α-SMA) deposition in lungs. Bleomycin administration increased lung stiffness, TGF-β levels, α-SMA deposition, and inflammatory and oxidative stress markers. The treatment with MRS5980 attenuated all the analyzed functional, biochemical and histopathological markers in a dose-dependent manner. Our findings support the therapeutic potential of A3AR agonists in lung fibrosis by demonstrating reduced disease progression, as indicated by decreased inflammation, TGF-β expression and fibrotic remodeling.
Hybrid Carbon Supports Composed of Small Reduced Graphene Oxide and Carbon Nanotubes for Durable Oxygen Reduction Catalysts in Proton Exchange Membrane Fuel Cells
Authors: Bak Su-Jeong , Son Mingyu , Shin Jeehoon , Kim Sun-I , Lee Jung Woo , Lee Duck Hyun
Published: November 2022

We demonstrated highly active and durable hybrid catalysts (HCs) composed of small reduced graphene oxide (srGO) and carbon nanotubes (CNTs) for use as oxygen reduction reaction (ORR) catalysts in proton exchange membrane fuel cells. Pt/srGO and Pt/CNTs were prepared by loading Pt nanoparticles onto srGO and CNTs using a polyol process, and HCs with different Pt/CNT and Pt/srGO ratios were prepared by mechanically mixing the two components. The prepared HCs consisted of Pt/CNTs well dispersed on Pt/srGO, with catalyst HC55, which was prepared using Pt/srGO and Pt/CNTs in a 5:5 ratio, exhibiting excellent oxygen reduction performance and high stability over 1000 cycles of the accelerated durability test (ADT). In particular, after 1000 cycles of the ADT, the normalized electrochemically active surface area of Pt/HC55 decreased by 11.9%, while those of Pt/srGO and Pt/C decreased by 21.2% and 57.6%, respectively. CNTs have strong corrosion resistance because there are fewer defect sites on the surface, and the addition of CNTs in rGO further improved the durability and the electrical conductivity of the catalyst. A detailed analysis of the structural and electrochemical properties of the synthesized catalysts suggested that the synergetic effects of the high specific surface area of srGO and the excellent electrical conductivity of CNTs were responsible for the enhanced efficiency and durability of the catalysts.
Liver Brain Interactions: Focus on FGF21 a Systematic Review
Authors: Prida Eva , Álvarez-Delgado Sara , Pérez-Lois Raquel , Soto-Tielas Mateo , Estany-Gestal Ana , Fernø Johan , Seoane Luisa María , Quiñones Mar , Al-Massadi Omar
Published: November 2022

Fibroblast growth factor 21 is a pleiotropic hormone secreted mainly by the liver in response to metabolic and nutritional challenges. Physiologically, fibroblast growth factor 21 plays a key role in mediating the metabolic responses to fasting or starvation and acts as an important regulator of energy homeostasis, glucose and lipid metabolism, and insulin sensitivity, in part by its direct action on the central nervous system. Accordingly, pharmacological recombinant fibroblast growth factor 21 therapies have been shown to counteract obesity and its related metabolic disorders in both rodents and nonhuman primates. In this systematic review, we discuss how fibroblast growth factor 21 regulates metabolism and its interactions with the central nervous system. In addition, we also state our vision for possible therapeutic uses of this hepatic-brain axis.
Extracellular Vesicles in Diffuse Large B Cell Lymphoma: Characterization and Diagnostic Potential
Authors: Matthiesen Rune , Gameiro Paula , Henriques Andreia , Bodo Cristian , Moraes Maria Carolina Strano , Costa-Silva Bruno , Cabeçadas José , Gomes da Silva Maria , Beck Hans Christian , Carvalho Ana Sofia
Published: November 2022

Diffuse large B cell lymphoma (DLBCL) is an aggressive B cell lymphoma characterized by a heterogeneous behavior and in need of more accurate biological characterization monitoring and prognostic tools. Extracellular vesicles are secreted by all cell types and are currently established to some extent as representatives of the cell of origin. The present study characterized and evaluated the diagnostic and prognostic potential of plasma extracellular vesicles (EVs) proteome in DLBCL by using state-of-the-art mass spectrometry. The EV proteome is strongly affected by DLBCL status, with multiple proteins uniquely identified in the plasma of DLBCL. A proof-of-concept classifier resulted in highly accurate classification with a sensitivity and specificity of 1 when tested on the holdout test data set. On the other hand, no proteins were identified to correlate with non-germinal center B-cell like (non-GCB) or GCB subtypes to a significant degree after correction for multiple testing. However, functional analysis suggested that antigen binding is regulated when comparing non-GCB and GCB. Survival analysis based on protein quantitative values and clinical parameters identified multiple EV proteins as significantly correlated to survival. In conclusion, the plasma extracellular vesicle proteome identifies DLBCL cancer patients from healthy donors and contains potential EV protein markers for prediction of survival.
Immobilization and Application of the Recombinant Xylanase GH10 of Malbranchea pulchella in the Production of Xylooligosaccharides from Hydrothermal Liquor of the Eucalyptus (Eucalyptus grandis) Wood Chips
Authors: Alnoch Robson C. , Alves Gabriela S. , Salgado Jose C. S. , de Andrades Diandra , Freitas Emanuelle N. de , Nogueira Karoline M. V. , Vici Ana C. , Oliveira Douglas P. , Carvalho-Jr Valdemiro P. , Silva Roberto N. , Buckeridge Marcos S. , Michelin Michele , Teixeira José A. , Polizeli Maria de Lourdes T. M.
Published: November 2022

Xylooligosaccharides (XOS) are widely used in the food industry as prebiotic components. XOS with high purity are required for practical prebiotic function and other biological benefits, such as antioxidant and inflammatory properties. In this work, we immobilized the recombinant endo-1,4-β-xylanase of Malbranchea pulchella (MpXyn10) in various chemical supports and evaluated its potential to produce xylooligosaccharides (XOS) from hydrothermal liquor of eucalyptus wood chips. Values >90% of immobilization yields were achieved from amino-activated supports for 120 min. The highest recovery values were found on Purolite (142%) and MANAE-MpXyn10 (137%) derivatives, which maintained more than 90% residual activity for 24 h at 70 °C, while the free-MpXyn10 maintained only 11%. In addition, active MpXyn10 derivatives were stable in the range of pH 4.0–6.0 and the presence of the furfural and HMF compounds. MpXyn10 derivatives were tested to produce XOS from xylan of various sources. Maximum values were observed for birchwood xylan at 8.6 mg mL−1 and wheat arabinoxylan at 8.9 mg mL−1, using Purolite-MpXyn10. Its derivative was also successfully applied in the hydrolysis of soluble xylan present in hydrothermal liquor, with 0.9 mg mL−1 of XOS after 3 h at 50 °C. This derivative maintained more than 80% XOS yield after six cycles of the assay. The results obtained provide a basis for the application of immobilized MpXyn10 to produce XOS with high purity and other high-value-added products in the lignocellulosic biorefinery field.
PSEN2 Thr421Met Mutation in a Patient with Early Onset Alzheimer’s Disease
Authors: Yang YoungSoon , Bagyinszky Eva , An Seong Soo A. , Kim SangYun
Published: November 2022

Presenilin-2 (PSEN2) mutation Thr421Met was identified from a 57-years old patient with early onset Alzheimer’s disease (EOAD) for the first time in Korea. Previously, this mutation was discovered in an EOAD patient in Japan without a change on amyloid production from the cellular study. Both Korean and Japanese patients developed the disease in their 50s. Memory loss was prominent in both cases, but no additional clinical information was available on the Japanese patient. Magnetic resonance imaging (MRI) images of the Korean patient revealed asymmetric atrophies in both temporo-parietal lobes. In addition, amyloid positron emission tomography (PET) also revealed amyloid deposits in the gray matter of the temporo-parietal lobes asymmetrically. PSEN2 Thr421 was conserved among a majority of vertebrates (such as zebras, elephants, and giant pandas); hence, Thr421 could play an important role in its functions and any mutations could cause detrimental ramifications in its interactions. Interestingly, PSEN2 Thr421 could have homology with PSEN1 Thr440, as PSEN1 T440del mutations were reported from patients with AD or dementia with Lewy bodies. Hence, the changed amino acid from threonine to methionine of PSEN2 Thr421 could cause significant structural alterations in causing local protein dynamics, leading to its pathogenicity in EOAD. Lastly, PSEN2 Thr421Met may interact with other mutations in neurodegenerative disease related genes, which were found in the proband patient, such as ATP binding cassette subfamily A member 7 (ABCA7), Notch Receptor 3 (NOTCH3), or Leucine-rich repeat kinase 2 (LRRK2). These interactions of pathway networks among PSEN2 and other disease risk factors could be responsible for the disease phenotype through other pathways. For example, PSEN2 and ABCA7 may impact amyloid processing and reduce amyloid clearance. Interaction between PSEN2 and NOTCH3 variants may be associated with abnormal NOTCH signaling and a lower degree of neuroprotection. Along with LRRK2 variants, PSEN2 Thr421Met may impact neurodegeneration through Wnt related pathways. In the future, cellular studies of more than one mutation by CRISPR-Cas9 method along with biomarker profiles could be helpful to understand the complicated pathways.
Complement System Inhibition Modulates the Inflammation Induced by the Venom of Premolis semirufa, an Amazon Rainforest Moth Caterpillar
Authors: Gabrili Joel J. M. , Villas-Boas Isadora Maria , Pidde Giselle , Squaiella-Baptistão Carla Cristina , Woodruff Trent M. , Tambourgi Denise V.
Published: November 2022

The caterpillar of the Premolis semirufa moth, commonly called Pararama, is found in the Brazilian Amazon region. Contact with the hairs can cause a chronic inflammatory reaction, termed “pararamosis”. To date, there is still no specific treatment for pararamosis. In this study, we used a whole human blood model to evaluate the involvement of the complement in the proinflammatory effects of P. semirufa hair extract, as well as the anti-inflammatory potential of complement inhibitors in this process. After treatment of blood samples with the P. semirufa hair extract, there was a significant increase in the generation of soluble terminal complement complex (sTCC) and anaphylatoxins (C3a, C4a, and C5a), as well as the production of the cytokines TNF-α and IL-17 and the chemokines IL-8, RANTES, MIG, MCP-1, and IP-10. The inhibition of C3 with compstatin significantly decreased IL-17, IL-8, RANTES, and MCP-1 production. However, the use of the C5aR1 antagonist PMX205 promoted a reduction in the production of IL-8 and RANTES. Moreover, compstatin decreased CD11b, C5aR1, and TLR2 expression induced by P. semirufa hair extract in granulocytes and CD11b, TLR4, and TLR2 in monocytes. When we incubated vascular endothelial cells with extract-treated human plasma, there was an increase in IL-8 and MCP-1 production, and compstatin was able to decrease the production of these chemokines. C5aR1 antagonism also decreased the production of MCP-1 in endothelial cells. Thus, these results indicate that the extract of the Pararama bristles activates the complement system and that this action contributes to the production of cytokines and chemokines, modulation of the expression of surface markers in leukocytes, and activation of endothelial cells.
Cardioprotection by Hypothyroidism Is Not Mediated by Favorable Hemodynamics—Role of Canonical Thyroid Hormone Receptor Alpha Signaling
Authors: Pape Janina , Kerp Helena , Lieder Helmut R. , Geist Daniela , Hönes Georg Sebastian , Moeller Lars C. , Kleinbongard Petra , Führer Dagmar
Published: November 2022

Hypothyroidism has been shown to reduce infarct size in rats, but the underlying mechanisms are unclear. We used isolated pressure-constant perfused hearts of control, hypothyroid and hyperthyroid mice and measured infarct size, functional parameters and phosphorylation of key molecules in cardioprotective signaling with matched heart rate. Compared with controls, hypothyroidism was cardioprotective, while hyperthyroidism was detrimental with enlarged infarct size. Next, we asked how thyroid hormone receptor α (TRα) affects ischemia/reperfusion (IR) injury. Thus, canonical and noncanonical TRα signaling was investigated in the hearts of (i) mice lacking TRα (TRα0), (ii) with a mutation in TRα DNA-binding domain (TRαGS) and (iii) in hyperthyroid TRα0 (TRα0hyper) and TRαGS mice (TRαGShyper). TRα0 mouse hearts were protected against IR injury. Furthermore, infarct size was reduced in the hearts of TRαGS mice that lack canonical TRα signaling but maintain noncanonical TRα action. Hyperthyroidism did not increase infarct size in TRα0 and TRαGS mouse hearts. These cardioprotective effects were not associated with increased phosphorylation of key proteins of RISK, SAFE and eNOS pathways. In summary, chronic hypothyroidism and the lack of canonical TRα signaling are cardioprotective in IR injury and protection is not due to favorable changes in hemodynamics.
Accurate Prediction of Epigenetic Multi-Targets with Graph Neural Network-Based Feature Extraction
Authors: Wang Yishu , Qi Juan , Chen Xiaomin
Published: November 2022

Epigenetics, referring to genetic modifications that change gene expression, but which are not encoded in DNA, has been shown to be related to oncology, with the potential to influence associated treatments. As such, epigenetic drugs comprise an important new field in cancer therapy; however, drug development is a high-cost and time-consuming procedure. Different epigenetic modifications, such as mutations in DNA methyltransferase and somatic mutations in core histone genes that lead to a global loss of the histone modifications, have innumerable relationships. In this article, we propose a graph neural network-based model for the extraction of molecular features, thus reducing the computational requirements. Through integration with a popular and efficient supervised learner, our model achieves higher prediction accuracy in both single- and multi-target tasks and can determine the pleiotropy associated with drugs, providing theoretical support for drug combination and discovery research.
Running from Stress: Neurobiological Mechanisms of Exercise-Induced Stress Resilience
Authors: Nowacka-Chmielewska Marta , Grabowska Konstancja , Grabowski Mateusz , Meybohm Patrick , Burek Malgorzata , Małecki Andrzej
Published: November 2022

Chronic stress, even stress of a moderate intensity related to daily life, is widely acknowledged to be a predisposing or precipitating factor in neuropsychiatric diseases. There is a clear relationship between disturbances induced by stressful stimuli, especially long-lasting stimuli, and cognitive deficits in rodent models of affective disorders. Regular physical activity has a positive effect on the central nervous system (CNS) functions, contributes to an improvement in mood and of cognitive abilities (including memory and learning), and is correlated with an increase in the expression of the neurotrophic factors and markers of synaptic plasticity as well as a reduction in the inflammatory factors. Studies published so far show that the energy challenge caused by physical exercise can affect the CNS by improving cellular bioenergetics, stimulating the processes responsible for the removal of damaged organelles and molecules, and attenuating inflammation processes. Regular physical activity brings another important benefit: increased stress robustness. The evidence from animal studies is that a sedentary lifestyle is associated with stress vulnerability, whereas a physically active lifestyle is associated with stress resilience. Here, we have performed a comprehensive PubMed Search Strategy for accomplishing an exhaustive literature review. In this review, we discuss the findings from experimental studies on the molecular and neurobiological mechanisms underlying the impact of exercise on brain resilience. A thorough understanding of the mechanisms underlying the neuroprotective potential of preconditioning exercise and of the role of exercise in stress resilience, among other things, may open further options for prevention and therapy in the treatment of CNS diseases.
Mass Spectrometry, Ion Mobility Separation and Molecular Modelling: A Powerful Combination for the Structural Characterisation of Substituted Cyclodextrins Mixtures
Authors: Rigaud Sébastien , Dosso Abdouramane , Lesur David , Cailleu Dominique , Mathiron David , Pilard Serge , Cézard Christine , Djedaini-Pilard Florence
Published: November 2022

When working on the synthesis of substituted cyclodextrins (CDs), the main challenge remains the analysis of the reaction media content. Our objective in this study was to fully characterise a complex isomers mixture of Lipidyl-βCDs (LipβCD) obtained with a degree of substitution 1 (DS = 1) from a one-step synthesis pathway. The benefit of tandem mass spectrometry (MS/MS) and ion mobility separation hyphenated with mass spectrometry (IM-MS) was investigated. The MS/MS fragment ion‘s relative intensities were analysed by principal component analysis (PCA) to discriminate isomers. The arrival time distribution (ATD) of each isomer was recorded using a travelling wave ion mobility (TWIM) cell allowing the determination of their respective experimental collision cross section (CCSexp). The comparison with the predicted theoretical CCS (CCSth) obtained from theoretical calculations propose a regioisomer assignment according to the βCD hydroxyl position (2, 3, or 6) involved in the reaction. These results were validated by extensive NMR structural analyses of pure isomers combined with molecular dynamics simulations. This innovative approach seems to be a promising tool to elucidate complex isomer mixtures such as substituted cyclodextrin derivatives.
Interplay between the DNA Damage Response and Immunotherapy Response in Cancer
Authors: Lee Elizabeth Chun Yong , Kok Jessica Sook Ting , Teh Bin Tean , Lim Kah Suan
Published: November 2022

Genome instability and immune evasion are both defining hallmarks of cancer. Tumorigenesis is frequently initiated when there is DNA damage to a proto-oncogene or tumor suppressor gene and DNA repair mechanisms are lost or insufficient to correct the damage; immune evasion then prevents the host immune system from recognizing these transformed cells. Therapies targeting genomic instability and immune evasion have been effectively used to treat cancer. Genotoxic therapies such as chemoradiation have been employed in cancer treatments for several decades, while immunotherapy is a relatively new class of cancer therapy that has led to disease regression even in patients with advanced cancer. Several recent studies have shown synergy between both classes of therapy targeting these two defining hallmarks of cancer, and different mechanisms are proposed to be involved. Here, we review the different classes of DNA damage, their links to cancer, and their contribution to immunotherapy responses, as well as the different models that are currently being used to study tumor–immune interactions.