bluuebunny/crossref_metadata_2025 huggingface dataset:
CC-90001, a c-Jun N-terminal kinase (JNK) inhibitor, in patients with pulmonary fibrosis: design of a phase 2, randomised, placebo-controlled trial
Authors: Popmihajlov Zoran , Sutherland Donna J , Horan Gerald S , Ghosh Atalanta , Lynch David A , Noble Paul W , Richeldi Luca , Reiss Theodore F , Greenberg Steven
Published: January 2022

Introduction

Idiopathic pulmonary fibrosis (IPF) is a progressive and often fatal interstitial lung disease (ILD); other ILDs have a progressive, fibrotic phenotype (PF-ILD). Antifibrotic agents can slow but not stop disease progression in patients with IPF or PF-ILD. c-Jun N-terminal kinases (JNKs) are stress-activated protein kinases implicated in the underlying mechanisms of fibrosis, including epithelial cell death, inflammation and polarisation of profibrotic macrophages, fibroblast activation and collagen production. CC-90001, an orally administered (PO), one time per day, JNK inhibitor, is being evaluated in IPF and PF-ILD.

Methods and analysis

This is a phase 2, randomised, double-blind, placebo-controlled study evaluating efficacy and safety of CC-90001 in patients with IPF (main study) and patients with PF-ILD (substudy). Both include an 8-week screening period, a 24-week treatment period, up to an 80-week active-treatment extension and a 4-week post-treatment follow-up. Patients with IPF (n=165) will be randomised 1:1:1 to receive 200 mg or 400 mg CC-90001 or placebo administered PO one time per day; up to 25 patients/arm will be permitted concomitant pirfenidone use. Forty-five patients in the PF-ILD substudy will be randomised 2:1 to receive 400 mg CC-90001 or placebo. The primary endpoint is change in per cent predicted forced vital capacity from baseline to Week 24 in patients with IPF.

Ethics and dissemination

This study will be conducted in accordance with Good Clinical Practice guidelines, Declaration of Helsinki principles and local ethical and legal requirements. Results will be reported in a peer-reviewed publication.

Trial registration number

NCT03142191.
Combination of ultrasound-based mechanical disruption of tumor with immune checkpoint blockade modifies tumor microenvironment and augments systemic antitumor immunity
Authors: Abe Shinya , Nagata Hiroshi , Crosby Erika J , Inoue Yoshiyuki , Kaneko Kensuke , Liu Cong-Xiao , Yang Xiao , Wang Tao , Acharya Chaitanya R , Agarwal Pankaj , Snyder Joshua , Gwin William , Morse Michael A , Zhong Pei , Lyerly Herbert Kim , Osada Takuya
Published: January 2022

Background

Despite multimodal adjuvant management with radiotherapy, chemotherapy and hormonal therapies, most surgically resected primary breast cancers relapse or metastasize. A potential solution to late and distant recurrence is to augment systemic antitumor immunity, in part by appropriately presenting tumor antigens, but also by modulating the immunosuppressive tumor microenvironment (TME). We previously validated this concept in models of murine carcinoma treated with a novel predominately microcavitating version of high-intensity focused ultrasound (HIFU), mechanical high-intensity focused ultrasound (M-HIFU). Here we elucidated the mechanisms of enhanced antitumor immunity by M-HIFU over conventional thermal high-intensity focused ultrasound (T-HIFU) and investigated the potential of the combinatorial strategy with an immune checkpoint inhibitor, anti-PD-L1 antibody.

Methods

The antitumor efficacy of treatments was investigated in syngeneic murine breast cancer models using triple-negative (E0771) or human ErbB-2 (HER2) expressing (MM3MG-HER2) tumors in C57BL/6 or BALB/c mice, respectively. Induction of systemic antitumor immunity by the treatments was tested using bilateral tumor implantation models. Flow cytometry, immunohistochemistry, and single-cell RNA sequencing were performed to elucidate detailed effects of HIFU treatments or combination treatment on TME, including the activation status of CD8 T cells and polarization of tumor-associated macrophages (TAMs).

Results

More potent systemic antitumor immunity and tumor growth suppression were induced by M-HIFU compared with T-HIFU. Molecular characterization of the TME after M-HIFU by single-cell RNA sequencing demonstrated repolarization of TAM to the immunostimulatory M1 subtype compared with TME post-T-HIFU. Concurrent anti-PD-L1 antibody administration or depletion of CD4+ T cells containing a population of regulatory T cells markedly increased T cell-mediated antitumor immunity and tumor growth suppression at distant, untreated tumor sites in M-HIFU treated mice compared with M-HIFU monotherapy. CD8 T and natural killer cells played major roles as effector cells in the combination treatment.

Conclusions

Physical disruption of the TME by M-HIFU repolarizes TAM, enhances T-cell infiltration, and, when combined with anti-PD-L1 antibody, mediates superior systemic antitumor immune responses and distant tumor growth suppression. These findings suggest M-HIFU combined with anti-PD-L1 may be useful in reducing late recurrence or metastasis when applied to primary tumors.
CD161 expression and regulation defines rapidly responding effector CD4+ T cells associated with improved survival in HPV16-associated tumors
Authors: Duurland Chantal L , Santegoets Saskia J , Abdulrahman Ziena , Loof Nikki M , Sturm Gregor , Wesselink Tom H , Arens Ramon , Boekestijn Sanne , Ehsan Ilina , van Poelgeest Mariette I E , Finotello Francesca , Hackl Hubert , Trajanoski Zlatko , ten Dijke Peter , Braud Veronique M , Welters Marij J P , van der Burg Sjoerd H
Published: January 2022

Background

Expression of killer cell lectin-like receptor B1 (KLRB1), the gene encoding the cell surface molecule CD161, is associated with favorable prognosis in many cancers. CD161 is expressed by several lymphocyte populations, but its role and regulation on tumor-specific CD4+ T cells is unknown.

Methods

We examined the clinical impact of CD4+CD161+ T cells in human papillomavirus (HPV)16+ oropharyngeal squamous cell carcinoma (OPSCC), analyzed their contribution in a cohort of therapeutically vaccinated patients and used HPV16-specific CD4+CD161+ tumor-infiltrating lymphocytes and T cell clones for in-depth mechanistic studies.

Results

Central and effector memory CD4+ T cells express CD161, but only CD4+CD161+ effector memory T cells (Tem) are associated with improved survival in OPSCC. Therapeutic vaccination activates and expands type 1 cytokine-producing CD4+CD161+ effector T cells. The expression of CD161 is dynamic and follows a pattern opposite of the checkpoint molecules PD1 and CD39. CD161 did not function as an immune checkpoint molecule as demonstrated using multiple experimental approaches using antibodies to block CD161 and gene editing to knockout CD161 expression. Single-cell transcriptomics revealedKLRB1expression in many T cell clusters suggesting differences in their activation. Indeed, CD4+CD161+ effector cells specifically expressed the transcriptional transactivatorSOX4,known to enhance T cell receptor (TCR) signaling via CD3ε. Consistent with this observation, CD4+CD161+ cells respond more vigorously to limiting amounts of cognate antigen in presence of interleukin (IL)-12 and IL-18 compared to their CD161- counterparts. The expression of CD161/KLRB1andSOX4was downregulated upon TCR stimulation and this effect was boosted by transforming growth factor (TGF)β1.

Conclusion

High levels of CD4+CD161+ Tem are associated with improved survival and our data show that CD161 is dynamically regulated by cell intrinsic and extrinsic factors. CD161 expressing CD4+ T cells rapidly respond to suboptimal antigen stimulation suggesting that CD161, similar to SOX4, is involved in the amplification of TCR signals in CD4+ T cells.
Chemsex and incidence of sexually transmitted infections among Canadian pre-exposure prophylaxis (PrEP) users in the l’Actuel PrEP Cohort (2013–2020)
Authors: Flores Anato Jorge Luis , Panagiotoglou Dimitra , Greenwald Zoë R , Blanchette Maxime , Trottier Claire , Vaziri Maliheh , Charest Louise , Szabo Jason , Thomas Réjean , Maheu-Giroux Mathieu
Published: January 2022

Objectives

Use of illicit substances during sex (chemsex) may increase transmission of HIV and other STIs. Pre-exposure prophylaxis (PrEP) is highly effective at preventing HIV transmission, providing an important prevention tool for those who practise chemsex. However, it does not prevent acquisition of other STIs. We aim to examine the impact of chemsex on STI incidence among gay, bisexual and other men who have sex with men (gbMSM), and transgender women using PrEP in Montréal, Canada.

Methods

We linked baseline sociodemographic and behavioural data with follow-up STI testing from 2013 to 2020 among PrEP users in the l’Actuel PrEP Cohort (Canada). Focusing on the 24 months following PrEP initiation, we estimated the effect of chemsex reported at baseline on cumulative incidence of gonorrhoea and chlamydia using Kaplan-Meier curves and survival analyses. We investigated the role of polysubstance use and effect modification by sociodemographic factors.

Results

There were 2086 clients (2079 cisgender gbMSM, 3 transgender gbMSM, 4 transgender women) who initiated PrEP, contributing 1477 years of follow-up. There were no incident HIV infections among clients on PrEP. Controlling for sociodemographic confounders, clients reporting chemsex at baseline had a 32% higher hazard of gonorrhoea/chlamydia diagnosis (adjusted HR=1.32; 95% CI: 1.10 to 1.57), equivalent to a risk increase of 8.9 percentage points (95% CI: 8.5 to 9.4) at 12 months. The effect was greater for clients who reported polysubstance use (adjusted HR=1.51; 95% CI: 1.21 to 1.89). The strength of the effect of chemsex on STI incidence varied by age, education and income.

Conclusion

Among PrEP users, chemsex at baseline was linked to increased incidence of gonorrhoea and chlamydia. This effect was stronger for people reporting multiple chemsex substances. The high STI incidence among gbMSM who report chemsex highlights the importance of PrEP for this population and the need for integrated services that address the complexities of sexualised substance use.
Potential of Bayesian formalism for the fusion and assimilation of sequential forestry data in time and space
Authors: Mohamedou Cheikh , Kangas Annika , Hamedianfar Alireza , Vauhkonen Jari
Published: January 2022

Forest resource assessments based on multi-source and multi-temporal data have become more common. Therefore, enhancing the prediction capabilities of forestry dynamics by efficiently pooling and analyzing time-series and spatial sequential data is now more pivotal. Bayesian filtering and smoothing provide a well-defined formalism for the fusion or assimilation of various data. We ascertained how often the generic, standardized Bayesian framework is used in the scientific literature and whether such an approach is beneficial for forestry applications. A review of the literature showed that the use of Bayesian methods appears to be less common in forestry than in other disciplines, particularly remote sensing. Specifically, time-series analyses were found to favor ad hoc methods. Our review did not reveal strong numeric evidence for better performance by the various Bayesian approaches, but this result may be partly due to the challenge in comparing a variety of methods for different prediction tasks. We identified methodological challenges related to assimilating predictions of forest development; in particular, combining modelled growth with disturbances due to both forest operations and natural phenomena. Nevertheless, the Bayesian frameworks provide possibilities to efficiently combine and update prior and posterior predictive distributions and derive related uncertainty measures that appear under-utilized in forestry.
LARGE PLATONIC MARKETS WITH DELAYS
Authors: LIMMER YANNICK , MEYER-BRANDIS THILO
Published: January 2022

The objective is to develop a general stochastic approach to delays on financial markets. We suggest such a concept in the context of large Platonic markets, which allow infinitely many assets and incorporate a restricted information setting. The discussion is divided into information delays and order execution delays. The former enables modeling of markets, where the observed information is delayed, while the latter provides the opportunity to defer the indexed time of a received asset price. Both delays may be designed randomly and inhomogeneously over time. We show that delayed markets are equipped with a fundamental theorem of asset pricing and our main result is inheritance of the no asymptotic Lp-free lunch condition under both delay types. Eventually, we suggest an approach to verify absence of Lp-free lunch on markets with multiple brokers endowed with deviating trading speeds.
Query Processing on Heterogeneous CPU/GPU Systems
Authors: Rosenfeld Viktor , Breß Sebastian , Markl Volker
Published: January 2022

Due to their high computational power and internal memory bandwidth,
graphic processing units (GPUs)
have been extensively studied by the database systems research community. A heterogeneous query processing system that employs CPUs and GPUs at the same time has to solve many challenges, including how to distribute the workload on processors with different capabilities; how to overcome the data transfer bottleneck; and how to support implementations for multiple processors efficiently. In this survey we devise a classification scheme to categorize techniques developed to address these challenges. Based on this scheme, we categorize query processing systems on heterogeneous CPU/GPU systems and identify open research problems.
Scaling High-Quality Pairwise Link-Based Similarity Retrieval on Billion-Edge Graphs
Authors: Yu Weiren , McCann Julie , Zhang Chengyuan , Ferhatosmanoglu Hakan
Published: January 2022

SimRank is an attractive link-based similarity measure used in fertile fields of Web search and sociometry. However, the existing deterministic method by Kusumoto et al. [24] for retrieving SimRank does not always produce high-quality similarity results, as it fails to accurately obtain diagonal correction matrix D. Moreover, SimRank has a “connectivity trait” problem: increasing the number of paths between a pair of nodes would decrease its similarity score. The best-known remedy, SimRank++ [1], cannot completely fix this problem, since its score would still be zero if there are no common in-neighbors between two nodes.

In this article, we study fast high-quality link-based similarity search on billion-scale graphs. (1) We first devise a “varied-D” method to accurately compute SimRank in linear memory. We also aggregate duplicate computations, which reduces the time of [24] from quadratic to linear in the number of iterations. (2) We propose a novel “cosine-based” SimRank model to circumvent the “connectivity trait” problem. (3) To substantially speed up the partial-pairs “cosine-based” SimRank search on large graphs, we devise an efficient dimensionality reduction algorithm,PSR#, with guaranteed accuracy. (4) We give mathematical insights to the semantic difference between SimRank and its variant, and correct an argument in [24] that “ifDis replaced by a scaled identity matrix (1-Ɣ)I, their top-K rankings will not be affected much”. (5) We propose a novel method that can accurately convert from Li et al.  SimRank ~{S} to Jeh and Widom’s SimRankS. (6) We proposeGSR#, a generalisation of our “cosine-based” SimRank model, to quantify pairwise similarities across two distinct graphs, unlike SimRank that would assess nodes across two graphs as completely dissimilar. Extensive experiments on various datasets demonstrate the superiority of our proposed approaches in terms of high search quality, computational efficiency, accuracy, and scalability on billion-edge graphs.
The LiNiO2 Cathode Active Material: A Comprehensive Study of Calcination Conditions and their Correlation with Physicochemical Properties Part II. Morphology
Authors: Riewald Felix , Kurzhals Philipp , Bianchini Matteo , Sommer Heino , Janek Jürgen , Gasteiger Hubert A.
Published: January 2022

A better understanding of the cathode active material (CAM) plays a crucial role in the improvement of lithium-ion batteries. We have previously reported the structural properties of the model cathode material LiNiO2 (LNO) in dependence of its calcination conditions and found that the deviation from the ideal stoichiometry in LiNiO2 (Ni excess) shows no correlation to the 1st cycle capacity loss. Rather, the morphology of LNO appears to be decisive. As CAM secondary agglomerates fracture during battery operation, the surface area in contact with the electrolyte changes during cycle life. Thus, particle morphology and especially the primary particle size become critical and are analyzed in detail in this report for LNO, using an automated SEM image segmentation method. It is shown that the accessible surface area of the pristine CAM powder measured by physisorption is close to the secondary particle geometric surface area. The interface area between CAM and electrolyte is measured by an in situ capacitance method and approaches a value proportional to the estimated primary particle surface area determined by SEM image analysis after just a few cycles. This interface area is identified to be the governing factor determining the 1st cycle capacity loss and long-term cycling behavior.
Electrochemical Estimations of the Gold Nanoparticle Size Effect on Cysteine-Gold Oxidation
Authors: Romanovskaia Elena , Slovenský Peter , Kalantarian S. Marzieh , Laundry-Mottiar Lila , Romanovski Valentin , Halama Maroš , Auinger Michael , Hedberg Yolanda S.
Published: January 2022

Gold nanoparticles are interesting for nanobiomedical applications, such as for drug delivery and as diagnostic imaging contrast agents. However, their stability and reactivity in-vivo are influenced by their surface properties and size. Here, we investigate the electrochemical oxidation of differently sized citrate-coated gold nanoparticles in the presence and absence of L-cysteine, a thiol-containing amino acid with high binding affinity to gold. We found that smaller sized (5, 10 nm) gold nanoparticles were significantly more susceptible to electrochemical L-cysteine interactions and/or L-cysteine-facilitated gold oxidation than larger (20, 50 nm) sized gold nanoparticles, both for the same mass and nominal surface area, under the conditions investigated (pH 7.4, room temperature, stagnant solutions, and scan rates of 0.5 to 450 mV s−1). The electrochemical measurements of drop-casted gold nanoparticle suspensions on paraffin-impregnated graphite electrodes were susceptible to the quality of the electrode. Increased cycling resulted in irreversible oxidation and detachment/oxidation of gold into solution. Our results suggest that L-cysteine-gold interactions are stronger for smaller nanoparticles.
Distribution of Relaxation Times: Debye Length Distribution vs Electrode Polarization by a Cole−Cole Relaxation Model
Authors: Compañ Vicente , Diaz-Calleja Ricardo , Diaz-Boils Joaquín , Escorihuela Jorge
Published: January 2022

Mobility, diffusivity and charge density in polyelectrolytes, are generally determined from electrochemical impedance spectroscopy following the electrode polarization analysis, in which at a given temperature the peaks in tan δ are fitted based on a model. These results can be different depending on the model used in the fitting of the curves. Generally, the models are based on a single Debye model or on the existence of an overlap in relaxation times (Cole–Cole model). In this work, we propose the alternative use of the distribution of the relaxation times by a distribution of the Debye length (LD), which allows the calculation of parameters such as mobility, diffusivity, and charge density as a function of LD in a more concise approach.
Electrochemical Filter-Press Reactors
Authors: Walsh Frank C. , Robinson David
Published: January 2022

Electrolytic processes have traditionally been used on a large scale for the manufacture of chlorine and caustic soda, for the extraction of aluminum from its ores and for the production of adiponitrile. Over the last 15-20 years, the applications of industrial electrochemistry have diversified in terms of both the scale of operation and the nature of the electrode reactions involved.
Daily protein-polyphenol ingestion increases daily myofibrillar protein synthesis rates and promotes early muscle functional gains during resistance training
Authors: Pavis George F. , Jameson Tom S. O. , Blackwell Jamie R. , Fulford Jonathan , Abdelrahman Doaa R. , Murton Andrew J. , Alamdari Nima , Mikus Catherine R. , Wall Benjamin T. , Stephens Francis B.
Published: January 2022

Using a unilateral model of resistance training, we show for the first time that a protein-polyphenol beverage increases initial rates of myofibrillar protein synthesis and promotes early functional improvements. Following a prolonged period of training, this strategy also increases type II fiber hypertrophy and causes large individual variation in gains in quadricep muscle cross-sectional area.
Metabolic reprogramming in a slowly developing orthologous model of polycystic kidney disease
Authors: Hopp Katharina , Kleczko Emily K. , Gitomer Berenice Y. , Chonchol Michel , Klawitter Jost , Christians Uwe , Klawitter Jelena
Published: January 2022

This report delineates the evolution of metabolic changes occurring during autosomal dominant polycystic kidney disease (ADPKD) progression. Using an orthologous model, we performed kidney metabolomics and confirmed dysregulation of metabolic pathways previously found altered in nonorthologous or rapidly progressive PKD models. Importantly, we identified novel alterations, including augmentation of kynurenines, polyamines, and indoles, suggesting increased inflammation and microbial dysbiosis that provide insights into PKD pathomechanisms and may prove helpful for diagnosing, monitoring, and treating ADPKD.
Novel Application of Eupatilin for Effectively Attenuating Cisplatin-Induced Auditory Hair Cell Death via Mitochondrial Apoptosis Pathway
Authors: Lu Xiaochan , Deng Tingting , Dong Hongsong , Han Jinghong , Yu Yanping , Xiang Deng , Nie Guohui , Hu Bing
Published: January 2022

Eupatilin (5,7-dihydroxy-3

′

,4

′

,6-trimethoxyflavone) is a pharmacologically active flavone that has been isolated from a variety of medicinal plants and possesses a number of pharmacological properties. This study evaluates the antioxidant and antiapoptotic effects of eupatilin on cisplatin-induced ototoxicity using in vitro and in vivo models including HEI-OC1 cells, cochlear hair cells, and zebrafish. Employing a CCK8 assay and Annexin V-FITC/PI double staining, we found that eupatilin significantly alleviated cisplatin-induced apoptosis and increased hair cell viability. The level of reactive oxygen species (ROS) was evaluated by CellROX green and MitoSOX Red staining. The results showed that eupatilin possesses antioxidant activity. MitoTracker Red staining indicated that eupatilin remarkably decreased mitochondrial damage. Furthermore, we demonstrated that eupatilin protects hair cells from cisplatin-induced damage. Mechanistic studies in cisplatin-induced HEI-OC1 cells revealed that eupatilin promoted Bcl-2 expression, downregulated Bax expression, reversed the increase in caspase-3 and PARP activity, and reduced the expression of phosphorylated p38 and JNK. Our data suggest a novel role for eupatilin as a protective agent against ototoxic drug-induced hair cell apoptosis by inhibiting ROS generation and modulating mitochondrial-related apoptosis.
Study on the High Accuracy and Fast Acquisition of Satellite Signals Based on the Blind Source Separation Technique
Authors: Li Bo , Xie Kan , Bai Yulei , Wu Zongze , Xie Shengli
Published: January 2022

To address the problems of slow acquisition speed and low accuracy faced by existing grid search-based satellite acquisition methods in complex scenarios, this study proposes a high accuracy and fast satellite signal acquisition method based on blind source separation. The proposed method first adopts wavelet threshold denoising to reduce the noise in the overlapped satellite signal received by the receiver so as to improve the signal-to-noise ratio of the satellite signal. On this basis, a subspace estimation method is introduced to construct a blind acquisition algorithm for satellite signals, which achieves high accuracy and fast solution for the Doppler frequency shift and code phase shift of satellite carrier signals and is able to recover the unobservable individual source signals. The effectiveness of the proposed method is verified through experiments and compared against the traditional grid search type acquisition method, which confirmed that the method is suitable for the acquisition requirements of weak signals and has a good engineering application value.
Adaptive Channel Estimation for Underwater Acoustic OFDM System in Impulsive Noise Environment
Authors: Wu Yaohui , Shao Pengfei , Zhang Shaozhong , Li Youming
Published: January 2022

Applying the orthogonal matching pursuit (OMP) to estimate the underwater acoustic (UWA) orthogonal frequency division multiplexing (OFDM) channels is attractive because of its high estimation accuracy and low computational cost. However, most existing OMP-based algorithms suffer the limited estimation accuracy in impulsive noise (IN) cases. Through the studies can be found, only part of channels’ estimation is affected due to the random IN which appears transient and intermittent in time and frequency. Based on this observation, joint time-frequency OMP (JTF-OMP) method is proposed, where the estimation of the affected channels benefits adaptively from that of adjacent channels in time or frequency. It is well known that preliminary Doppler scale estimation is key to the subsequent OMP algorithm, which is difficult to deal with due to the IN. To solve this problem, an adaptive Doppler scale estimation (ADSE) method is proposed. It involves generating two shorter identical cyclic prefixes (CPs) for each OFDM symbol, placed before two adjacent OFDM symbols. The repetition pattern can adaptively defend the IN which appears randomly and shortly in time. Simulation results show that the proposed algorithms integrating JTF-OMP with ADSE can achieve much higher estimation accuracy and better system reliability than the OMP in the IN environment.
Copy Number Variation and Frequency of rs179008 in TLR7 Gene Associated with Systemic Lupus Erythematosus in Two Mexican Populations
Authors: Pacheco Guillermo Valencia , Nakazawa Ueji Yumi E. , Bello Julián Ramírez , Barbosa Cobos Rosa E. , Jiménez Becerra Eduardo D. , González Herrera Lizbeth J. , Pérez Mendoza Gerardo J. , Rivero Cárdenas Nubia A. , Angulo Ramírez Angélica V. , López Villanueva Ricardo F.
Published: January 2022

Systemic Lupus Erythematosus (SLE) is an autoimmune disease in which genetic factors play a role in the susceptibility to develop it. Genes related to the synthesis of interferons such as TLR7 and genetics factors such as single nucleotide polymorphisms (SNPs) or copies number variation (CNV) in the gene have been involved with the development of the disease. The genetic differences between the populations contribute to the complexity of LES. Mexico has a mestizo population with a genetic load of at least three origins: Amerindian, Caucasian, and African. The mestizo of Yucatán is the only group whose contribution Amerindian is mainly Mayan, geographically distant from other Mexican Amerindians. We analyzed the CNV and the frequency of SNP rs179008 of the TLR7 as genetic risk factors in developing the disease in patients from Yucatán and Central Mexico. Results show that 14% of the cases of the Yucatecan population showed significantly >2 CNV and a higher risk of developing the disease (OR: 34.364), concerning 4% of those coming from Central Mexico (OR: 10.855). T allele and the A/T and T/T risk genotypes of rs179008 were more frequent in patients of Central Mexico than in those of Yucatán (50% vs. 30%, 93% vs. 30%, 4% vs. 1%), and association with susceptibility to develop SLE was observed (OR: 1.5 vs. 0.58, 9.54 vs. 0.66, 12 vs. 0.14). Data support the genetic differences between and within Mexican mestizo populations and the role of the TLR7 in the pathogenesis of SLE.
Effect of Sodium Selenosulfate Concentration on Microstructural, Morphological, and Luminescence Characteristics of Cadmium Selenide Nanoparticles
Authors: Abel Saka , Tesfaye Jule Leta , Shanmugam R. , Dwarampudi L. Priyanka , Nagaprasad N. , Gudata Lamessa , Krishnaraj Ramaswamy
Published: January 2022

CBD‐deposited cadmium selenide nanoparticles in acidic medium production at pH value of bath solution was stayed constant at 6.5 using EDTA as complexing agents; sodium selenosulfite acts as a source of Se2- ion and cadmium acetate as source of Cd2+ ion. The nanoparticles of binary compound CdSe were also grown at different concentrations of sodium selenosulfite, and the influence of this parameter on the behaviours of the nanoparticles was studied. The as‐synthesized cadmium selenide nanoparticles are investigated by scanning electron microscopy (SEM), X‐ray diffraction (XRD), and PL absorption spectroscopy. Cadmium‐selenide nanoparticles were produced using various concentrations as 10, 15, and 20 milliliters on a microscopic glass plate by chemical technique at a growth temperature of 90 degree Celsius. Microstructural constraints realized from the X‐ray diffraction pattern decrease in grain size with an increase of concentration (8.25 nm–0.01 nm). It witnessed that the synthesized nanoparticle has a cubic crystal structure with favoured direction towards the (111) Miller indices’ plane. The oriented peak was investigated from the planes (311) and (111). From patterns of PL emissions, it was detected that in increasing concentration of sodium selenosulfate intensity, the nanoparticles with small crystal size could represent maximum luminescence intensity associated with the larger crystal size. This is due to the fact that the amount of ions on the nanoparticle surface rapidly increases as the crystal size of the nanoparticles reduces. Additionally, the transporter recombination ratio was increased as the size of the transporter reduces resulting in an increase in the overlap between the electron and hole wave functions. SEM inspection of produced nanoparticles reveals that the surface is free of cracks and that the grains are spherically formed. The surface is coated with granules of consistent size and shape. There are no fractures or holes visible inside the thin films under examination.
The Effects of RBP4 and Vitamin D on the Proliferation and Migration of Vascular Smooth Muscle Cells via the JAK2/STAT3 Signaling Pathway
Authors: Zhou Wan , Wang Wei , Yuan Xiao-Jing , Xiao Chun-Chun , Xing Yan , Ye Shan-Dong , Liu Qiang
Published: January 2022

Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are one of the main causes of the development of diabetic atherosclerotic process. The aim of our study was to assess the role of RBP4 in the proliferation and migration of VSMCs and the inhibitory effect of vitamin D on the mechanisms. In an in vivo experiment, rats were randomly classified into 6 groups: the control group, diabetic rats, diabetic atherosclerotic rats (diabetic rats intraperitoneally injected with RBP4), diabetic atherosclerotic rats treated with 0.075 μg kg-1 d-1 vitamin D, 0.15 μg kg-1 d-1 vitamin D and 0.3 μg kg-1 d-1 vitamin D. We found that the levels of JAK2, STAT3, cylinD1, and Bcl-2 were increased in diabetic atherosclerotic rats, and these increases were improved after vitamin D supplementation. Furthermore, to investigate the underlying molecular mechanisms, cells were cultured with glucose in the presence of RBP4 and the absence of RBP4, respectively, and vitamin D of different concentrations and different intervention times was simultaneously adopted. The proliferation and migration of VSMCs was enhanced and the levels of JAK2, STAT3, cyclinD1, and Bcl-2 were increased in the cells transfected with RBP4 overexpression plasmid. Moreover, vitamin D supplementation was detected to lower the expressions of JAK2, STAT3, cyclinD1, and Bcl-2 and inhibit the abnormal proliferation of VSMCs caused by the RBP4/JAK2/STAT3 signaling pathway. RBP4 can promote the proliferation and migration of VSMCs and contributes to the development of diabetic macroangiopathy via regulating the JAK2/STAT3 signaling pathway. This mechanism of RBP4 can be inhibited by vitamin D supplementation.
Combination of Colchicine and Ticagrelor Inhibits Carrageenan-Induced Thrombi in Mice
Authors: Zhang BuChun , Huang Rong , Yang DaiGang , Chen GuiLan , Chen YuanLi , Han Jihong , Zhang Shuang , Ma LiKun , Yang XiaoXiao
Published: January 2022

The formation of a thrombus is closely related to oxidative stress and inflammation. Colchicine is one of the most commonly prescribed medication for gout treatment, with anti-inflammation and antioxidative stress properties. Therefore, we speculated that it is possible for colchicine to treat thrombosis. In this study, we used carrageenan to induce thrombosis in BALB/c mice and fed mice with colchicine, ticagrelor, and their combination, respectively. We found colchicine inhibited carrageenan-induced thrombi in mouse tail, and the inhibition was enhanced by ticagrelor. In vitro, colchicine inhibited thrombin-induced retraction of human platelet clots. Mechanically, colchicine inhibited platelet activation by reducing the expression of platelet receptors, protease-activated receptor 4 (PAR4) and CD36, and inactivating of AKT and ERK1/2 pathways. Furthermore, in human umbilical vein endothelial cells (HUVECs), colchicine showed antioxidative stress effects through increasing protein expression of glutathione peroxidase-1 (GPx-1), and mRNA levels of forkhead box O3 (FOXO3a) and superoxide dismutase 2 (SOD2). In RAW264.7 cells, colchicine reduced LPS-enhanced inflammatory response through attenuating toll-like receptor 4 (TLR4) activation. In addition, colchicine reduced LPS or ox-LDL-induced monocyte adhesion to HUVECs by inhibiting intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) levels. Taken together, our study demonstrates that colchicine exerts antithrombotic function by attenuating platelet activation and inhibiting oxidative stress and inflammation. We also provide a potential new strategy for clinical treatment.
A Numerical Method for the Variable-Order Time-Fractional Wave Equations Based on the H2N2 Approximation
Authors: Liu Xiao , Bo Yu , Jin Yuanfeng
Published: January 2022

Aiming at the initial boundary value problem of variable-order time-fractional wave equations in one-dimensional space, a numerical method using second-order central difference in space and H2N2 approximation in time is proposed. A finite difference scheme with second-order accuracy in space and

3
−

γ

∗

order accuracy in time is obtained. The stability and convergence of the scheme are further discussed by using the discrete energy analysis method. A numerical example shows the effectiveness of the results.
Information Dissemination and Control of NIMBY Projects under Stigmatization
Authors: Zhang Changzheng , Zhu Yun , Xu Lianyan
Published: January 2022

NIMBY (Not in My Backyard) projects are easily stigmatized due to their environmental risk. Stigmatization enlarges residents’ risk perception, urges residents to spread information, and takes actions to resist project implementation, causing environmental mass emergency. Taking paraxylene (PX) project as an example, information dissemination model of NIMBY project under stigmatization based on SEIR model in small world network was established, and the information dissemination process and characteristics of NIMBY project under stigmatization were simulated and analysed. The results show that (1) the public risk perception deviation caused by stigmatization promotes residents to disseminate information; (2) stigmatization has a greater impact on the information dissemination of NIMBY project with low environmental risk; (3) stigmatization accelerates the speed of information dissemination and increases the number of residents participating in information dissemination in different dissemination environment. The contribution of this paper is that SEIR model in small world network is used to verify the role of stigmatization in promoting information dissemination of NIMBY project by comparing the information dissemination before and after stigmatization.
Recognition of Ocular Artifacts in EEG Signal through a Hybrid Optimized Scheme
Authors: Sahoo Santosh Kumar , Mohapatra Sumant Kumar
Published: January 2022

Brain computer interface (BCI) requires an online and real‐time processing of EEG signals. Hence, the accuracy of the recording system is improved by nullifying the developed artifacts. The goal of this proposal is to develop a hybrid model for recognizing and minimizing ocular artifacts through an improved deep learning scheme. The discrete wavelet transform (DWT) and Pisarenko harmonic decomposition are used for decomposing the signals. Then, the features are extracted by principal component analysis (PCA) and independent component analysis (ICA) techniques. After collecting the features, an optimized deformable convolutional network (ODCN) is used for the recognition of ocular artifacts from EEG input signals. When artifacts are sensed, the moderation method is executed by applying the empirical mean curve decomposition (EMCD) followed by ODCN for noise optimization in EEG signals. Conclusively, the spotless signal is reconstructed by an application of inverse EMCD. The proposed method has achieved a higher performance than that of conventional methods, which demonstrates a better ocular artifact reduction by the proposed method.
Performance Prediction of Refractured Wells Based on Embedded Discrete-Fracture Modeling Method
Authors: Du Yawen , Cao Xiaolu , Teng Bailu
Published: January 2022

In unconventional reservoirs, the production rate of the initially fractured well will decrease rapidly as the development proceeds. In order to maintain economic well productivity of the initial fracture, the industries can create refractures to prevent the well production rate from decreasing. However, the production of the initial fracture can induce the stress field to reorientate, which will cause the refracture to propagate along a different direction from the initial fracture. Thus, the refracturing treatment can result in a complex fracture system which raises a stringent challenge for one to evaluate the performance of the refractured well. In this paper, the authors utilize the embedded discrete fracture model (EDFM) to characterize the performance of the refractured wells. The calculated results in this paper show that, for the same equivalent matrix permeability, a larger permeability component parallel to the initial fracture can lead to a higher increase ratio of the refracturing treatment but lower cumulative production. If the reoriented section of the refracture is orthogonal to the initial fracture, the productivity of the refracture system can be the highest. The length of the reoriented section plays a more important role than the length of the initially oriented section in influencing the refracturing treatment. The refracturing treatment can lead to a higher increase of cumulative production if the initial fracture has a lower permeability.
The Tribological Behavior of Nanocrystalline TiO2 Coating Produced by Plasma Electrolytic Oxidation
Authors: Abbasi S. , Mahboob A. , Bakhtiari Zamani H. , Bilesan M. R. , Repo E. , Hakimi A.
Published: January 2022

Nanocrystalline TiO2 coatings were produced on titanium substrates using the plasma electrolytic oxidation technique. The effects of frequency, duty cycle, and type of applied current (pulse and direct) were evaluated on the microstructure of the coatings and the tribological behavior of the samples. Morphological evaluations demonstrated that the pancake structure was developed from coatings created with a unipolar pulsed current. However, a volcano‐like surface morphology resulted from a constant current. The XRD analysis results showed that the coatings were composed mainly of the rutile phase by 77.80‐96.34 wt. %. In comparison, 22.20 wt. % of the anatase phase was identified in samples produced with direct current. These phases were determined to be nanocrystalline (29.5‐48.3 nm), which led to significant improvements in the tribological properties. The sample produced with direct current had larger pores, greater roughness, and a four‐times higher thickness than samples created with unipolar current. Furthermore, the tribological study results showed that wear resistance was significantly higher in the unipolar pulsed current coatings than in those obtained with direct current. Moreover, samples made at a higher frequency and lower duty cycle showed better tribological behavior.
Analysis of Multipath Fading and Doppler Effect with Multiple Reconfigurable Intelligent Surfaces in Mobile Wireless Networks
Authors: Wu Guilu , Li Fan , Jiang Huilin
Published: January 2022

The multipath fading and Doppler effect are well-known phenomena affecting channel quality in mobile wireless communication systems. Within this context, the emergence of reconfigurable intelligence surfaces (RISs) brings a chance to achieve this goal. RISs as a potential solution are considered to be proposed in sixth generation (6G). The core idea of RISs is to change the channel characteristic from uncontrollable to controllable. This is reflected by some novel functionalities with wave absorption and abnormal reflection. In this paper, the multipath fading and Doppler effect are characterized by establishing a mathematical model from the perspective of reflectors and RISs in different mobile wireless communication processes. In addition, the solutions that improve the multipath fading and Doppler effect stemming from the movement of mobile transmitter are discussed by utilizing multiple RISs. A large number of experimental results demonstrate that the received signal strength abnormal fluctuations due to Doppler effect can be eliminated effectively by real-time control of RISs. Meanwhile, the multipath fading is also mitigated when all reflectors deployed are coated with RISs.
Mechanical Behavior of Cracked Rock in Cold Region Subjected to Step Cyclic Loading
Authors: Zhang Liang , Niu Fujun , Liu Minghao , Luo Jing , Ju Xin
Published: January 2022

In order to analyze the mechanical behavior of cracked rock in cold region subjected to cyclic loading, step cyclic loading and unloading (SCLU) triaxial tests with different stress paths have been designed. The mechanical responses such as strength, deformation, and failure mode were analyzed. The test results show that limestone has obvious strengthening effect under cyclic loading due to local crushing and filling of internal structural plane. The strengthening effect and fatigue damage effect caused by cyclic loading and the impact damage effect caused by the upgraded of stress level have an effect on mechanical response of cracked rock, and the degree of influence is related to the stress path. Under the stress path of constant stress lower limit (CSLL), the strengthening effect of rock was more prominent and its strength was enhanced. It was mainly subjected to progressive fatigue damage and had a buffering effect in the failure process. However, under the stress path of increasing the stress lower limit (ISLL), the rock suffered significant impact damage and entered the fatigue damage stage in advance, which led to its strength reduction and sudden failure when entering the next stress level. In addition, during the loading process, larger initial stress amplitudes led to more obvious cyclic strengthening effects, while smaller initial stress amplitudes led to greater plastic deformation and energy dissipation, and the rock was more prone to progressive damage.
Ferric Ammonium Citrate Upregulates PD-L1 Expression through Generation of Reactive Oxygen Species
Authors: Choi Eun Jung , Jeon Chang Hyun , Lee In-Kyu
Published: January 2022

Iron plays an important role in macrophage polarization by altering metabolic and redox status. However, the impact of iron on the immune status of macrophages is still controversial. In this study, we report that ferric ammonium citrate (FAC) upregulates PD-L1 expression in macrophages. FAC not only altered the phenotype of macrophages but also led to enriching immune-modulatory T cell subsets. Since iron is known to be a constituent of coenzymes facilitating metabolic processes in mitochondria, we examined the metabolic status of FAC-overloaded macrophages by measuring the oxygen consumption rate (OCR) and the represented coenzyme, aconitase. In addition to enhancement of metabolic processes, FAC accelerated the Fenton reaction in macrophages, which also contributed to the facilitation of oxygen consumption. We reasoned that the enhancement of the OCR leads to the production of reactive oxygen species (ROS), which are directly linked to PD-L1 induction. Using ferrostatin, rotenone, and N-acetyl-L-cysteine, we confirmed that metabolic and redox regulation is responsible for FAC-mediated PD-L1 expression. Furthermore, we suggested that FAC-induced ROS production may explain FAC-mediated pro- and anti-inflammatory responses in macrophages. These findings may extend our understanding of regulating iron concentration during immune checkpoint therapy in cancer patients.
Research Help-Seeking in Residents of Ophthalmology in Mashhad University of Medical Sciences: A Cross-Sectional Study
Authors: Gholami Hasan , Hosseini Seyed Masoud , Rezvani Talieh Saeidi , Zamani Ghodsieh , Abrishami Mojtaba
Published: January 2022

Background and Objectives. Considering the undeniable role of the help-seeking strategy in learning research skills, this study aimed to examine the situation of research help-seeking among ophthalmology residents of Mashhad University of Medical Sciences (MUMS), Mashhad, Iran. Materials and Methods. This descriptive cross-sectional study was performed on all ophthalmology residents of MUMS (n = 46). A validated research help-seeking scale was used to collect the required data. The scale consisted of 29 items and assessed the three dimensions of avoidance of help-seeking, adaptive help-seeking, and perceived benefit of help-seeking. The answers were scored based on a six-point Likert scale. Results. In total, 41 residents who responded to the electronic version of the research help-seeking scale were selected through convenience sampling. In the axes of help-seeking avoidance and perceived benefit of help-seeking, indexes were in the upper-middle level, while in the adaptive help-seeking axis, it was in the lower-middle level. Based on the results, gender and academic year of residency had no effect on research help-seeking aspects in the participants. However, age had a positive and significant correlation with the perceived benefit of help-seeking. Conclusion. Research help-seeking in residents of ophthalmology of MUMS in all three axes was around the middle level, and it is recommended that university officials and professors encourage residents use adaptive help-seeking strategy during their residency to improve their research skills.