bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blocking Jak/STAT signalling using tofacitinib inhibits angiogenesis in experimental arthritis
Authors: Di Benedetto Paola , Ruscitti Piero , Berardicurti Onorina , Panzera Noemi , Grazia Nicolò , Di Vito Nolfi Mauro , Di Francesco Barbara , Navarini Luca , Maurizi Antonio , Rucci Nadia , Teti Anna Maria , Zazzeroni Francesca , Guggino Giuliana , Ciccia Francesco , Dolo Vincenza , Alesse Edoardo , Cipriani Paola , Giacomelli Roberto 
Published: August 2021

Abstract
Objective
During rheumatoid arthritis (RA), the angiogenic processes, occurring with pannus-formation, may be a therapeutic target. JAK/STAT-pathway may play a role and the aim of this work was to investigate the inhibiting role of a JAK-inhibitor, tofacitinib, on the angiogenic mechanisms occurring during RA.

Methods
After ethical approval, JAK-1, JAK-3, STAT-1, STAT-3 and VEGF expression was evaluated on RA-synovial-tissues. In vitro, endothelial cells (ECs), stimulated with 20 ng/ml of VEGF and/or 1 μM of tofacitinib, were assessed for tube formation, migration and proliferation, by Matrigel, Boyden chamber assay and ki67 gene-expression. In vivo, 32 mice received collagen (collagen-induced arthritis (CIA)) and 32 mice PBS (control). At day 19, CIA and controls mice were divided: 16 mice receiving vehicle and 16 mice receiving tofacitinib. At day 35, the arthritis score, the thickness of paw joints and the serum levels of VEGF and Ang-2 were evaluated.

Results
The expression of JAK-1, JAK-3, STAT-1, STAT-3 and VEGF in synovial tissue of RA-patients were significantly higher than healthy controls. In vitro, tofacitinib inhibited the ECs ability to form vessels, to proliferate and to migrate. In vivo, administration of tofacitinib prevented the increase of the arthritis score, the paw thickness, the synovial vessels and VEGF and Ang-2 serum-accumulation, when compared to CIA without tofacitinib.

Conclusions
We explored the anti-angiogenic role of tofacitinib, reporting its ability to inhibit in vitro the angiogenic mechanisms of ECs and in vivo the formation of new synovial vessels, occurring in CIA model. These findings suggest that the therapeutic effect of tofacitinib during RA may be also related to its anti-angiogenic activity.
Pathogenic roles and therapeutic potential of the CCL8–CCR8 axis in a murine model of IgG4-related sialadenitis
Authors: Honda Fumika , Tsuboi Hiroto , Ono Yuko , Abe Saori , Takahashi Hiroyuki , Ito Kiyoaki , Yamada Kazunori , Kawano Mitsuhiro , Kondo Yuya , Asano Kenichi , Tanaka Masato , Malissen Marie , Malissen Bernard , Matsumoto Isao , Sumida Takayuki 
Published: August 2021

Abstract
Background
Our previous studies reveal that CCL18-CCR8 chemokine axis is upregulated in patients of immunoglobulin G4-related disease (IgG4-RD), suggesting that the CCL18–CCR8 axis is implicated in the etiology of IgG4-RD, although whether this axis has a potential as a therapeutic target remains unclear. Our purpose was to clarify the pathogenic roles and therapeutic potential of the murine CCL8 (analog of human CCL18)–CCR8 axis by using an animal model of IgG4-RD (LAT Y136F knockin mice; LAT mice).

Methods
We compared the infiltration of inflammatory cells and the fibrosis of the salivary glands of 6-week-old LAT mice and littermate mice. The expressions of Ccl8 and Ccr8 were also compared. Next, we investigated the therapeutic effects of intravenous administration of anti-CCL8 neutralizing antibody in LAT mice against inflammation and fibrosis of the salivary glands. We also investigated the effects of stimulation with recombinant mouse CCL8 on the collagen production in a mouse fibroblast cell line (NIH/3 T3) in vitro.

Results
When compared with the littermates, the LAT mice showed apparent infiltration of inflammatory cells and fibrosis in the salivary glands. The focus and fibrosis score in the salivary glands were significantly higher in the LAT mice than in the littermates. The expression levels of Ccl8 in the spleen and of Ccr8 in the salivary glands were significantly higher in the LAT mice than in the littermates. Anti-CCL8 antibody significantly improved the focus and fibrosis score in the salivary glands of the LAT mice. In vitro, stimulation with recombinant mouse CCL8 significantly increased the expression of collagen and ERK1/2 phosphorylation in NIH/3 T3.

Conclusion
We clarified the overexpression and therapeutic potential of the mouse CCL8–CCR8 axis in LAT mice, which could play a crucial role in fibrosis via ERK1/2 phosphorylation, as well as the chemotaxis of inflammatory cells. The human CCL18–CCR8 axis might be a novel therapeutic target for IgG4-RD.
Success rate to complete optimal 20 + 2 ISUOG planes for foetal ultrasonographic structural screening during early second trimester pregnancy in Thailand
Authors: Chaichanalap Ravita , Hanprasertpong Tharangrut 
Published: August 2021

Abstract
Objective
To compare the success rates of obtaining optimal 20 + 2 (2 overview + 20 planes) International Society of Ultrasound in Obstetrics and Gynaecology (ISUOG) planes for foetal ultrasound structural screening between pregnant women at gestational age (GA) 18–20 weeks and 20–22 weeks 6 days

Methods
A prospective descriptive study was conducted. Singleton pregnant women at GA 18–22 weeks + 6 days attending antenatal clinic between December 2019 and March 2020 were invited to participate in the study. Women whose foetuses had obvious structural anomalies were excluded. The ultrasound screening using 20 + 2 ISUOG protocol was performed by 21 operators who had completed the online ISUOG basic training programme with an experience of ultrasound scanning of at least 30 cases. The success rates of achieving optimal planes between GA 18–20 weeks and 20–22 weeks 6 days were compared using Chi-square test. Common suboptimal planes in the ultrasound scan were also presented.

Results
Optimal 20 + 2 ISUOG planes were successfully assessed in 97/126 (77%) and 112/126 (88.9%) patients in the group with a GA < 20 weeks and in the group with a GA ≥ 20 weeks, respectively. Overall success rate was 82.9%. The success rate for the GA < 20 weeks group was significantly lower than that for the GA ≥ 20 weeks group. The group with a GA ≥ 20 weeks had a 1.2 times higher success rate than the group with a GA < 20 weeks. The most common suboptimal planes were the facial planes, especially the median facial profile, and foetal thoracic planes.

Conclusions
We prefer to perform foetal structural screening using US with the 20 + 2 ISUOG protocol at a GA 20 to 22 weeks and 6 days with the aim reducing the need for repeat scans.
Dock2 affects the host susceptibility to Citrobacter rodentium infection through regulating gut microbiota
Authors: Xie Yuan , Chen Jun , Wu Bing , He Tiansheng , Xie Lu , Liu Zhiping 
Published: August 2021

Abstract
Background
Dysregulated gut microbiota is one of major pathogenic factors in the development of colitis. Dock2 acts as a guanine nucleotide exchange factor (GEF) and activates small G protein RAC1. Our previous study showed that, compared to wild type (WT) mice, Dock2−/− mice were more susceptible to colitis induced by Citrobacter rodentium infection. However, it is not clear whether gut microbiota affects the host susceptibility to enteric bacterial infection in Dock2−/− mice.

Results
In this study, we demonstrated that Dock2 regulated the gut microbiota and affected the host susceptibility to C. rodentium infection by co-housing, fecal microbiota transfer and antibiotic treatment methods. Microbiota analysis by 16 S rRNA gene sequencing showed that Dock2 increased the abundance of prevotellaceae-NK3B31-group and Lactobacillus but decreased that of Helicobacter.

Conclusions
These results suggest that Dock2 regulates the composition of gut microbiota and affects the host susceptibility to C. rodentium infection.
The effects of cocoa flavanols on indices of muscle recovery and exercise performance: a narrative review
Authors: Corr Liam D. , Field Adam , Pufal Deborah , Clifford Tom , Harper Liam D. , Naughton Robert J. 
Published: August 2021

AbstractExercise-induced muscle damage (EIMD) is associated with oxidative stress and inflammation, muscle soreness, and reductions in muscle function. Cocoa flavanols (CF) are (poly)phenols with antioxidant and anti-inflammatory effects and thus may attenuate symptoms of EIMD. The purpose of this narrative review was to collate and evaluate the current literature investigating the effect of CF supplementation on markers of exercise-induced oxidative stress and inflammation, as well as changes in muscle function, perceived soreness, and exercise performance. Acute and sub-chronic intake of CF reduces oxidative stress resulting from exercise. Evidence for the effect of CF on exercise-induced inflammation is lacking and the impact on muscle function, perceived soreness and exercise performance is inconsistent across studies. Supplementation of CF may reduce exercise-induced oxidative stress, with potential for delaying fatigue, but more evidence is required for any definitive conclusions on the impact of CF on markers of EIMD.Graphic abstract
Non-verbal IQ and change in restricted and repetitive behavior throughout childhood in autism: a longitudinal study using the Autism Diagnostic Interview-Revised
Authors: Courchesne V. , Bedford R. , Pickles A. , Duku E. , Kerns C. , Mirenda P. , Bennett T. , Georgiades S. , Smith I. M. , Ungar W. J. , Vaillancourt T. , Zaidman-Zait A. , Zwaigenbaum L. , Szatmari P. , Elsabbagh M. ,   Pathways Team
Published: August 2021

AbstractBackgroundRestricted and repetitive behavior (RRB) is one of the characteristic features of Autism Spectrum Disorder. This domain of symptoms includes a broad range of behaviors. There is a need to study each behavior individually to better understand the role of each in the development of autistic children. Moreover, there are currently no longitudinal studies investigating change in these behaviors over development.MethodsThe goal of the present study was to explore the association between age and non-verbal IQ (NVIQ) on 15 RRB symptoms included in the Autism Diagnostic Interview-Revised (ADI-R) over time. A total of 205 children with ASD were assessed using the ADI-R at time of diagnosis, at age 6 years, and at age 11 years, and with the Wechsler Intelligence Scales for Children—Fourth Edition (WISC-IV) at age 8 years.ResultsThe proportion of children showing each RRB tended to diminish with increasing age, except forsensitivity to noiseandcircumscribed interests,where the proportion increased over time. Although there was no significant main effect of NVIQ, there was a significant interaction between age and NVIQ. This was mainly driven byDifficulties with change in routine, for which higher NVIQ was associated with the behavior remaining relatively stable with age, while lower NVIQ was associated with the behavior becoming more prevalent with age.LimitationsThe study focused on the presence/absence of each RRB but did not account for potential changes in frequency or severity of the behaviors over development. Furthermore, some limitations are inherent to the measures used. The ADI-R relies on parent report and hence has some level of subjectivity, while the Wechsler intelligence scales can underestimate the intellectual abilities of some autistic children.ConclusionsThese results confirm that specific RRB are differentially linked to age and NVIQ. Studying RRB individually is a promising approach to better understanding how RRB change over the development of autistic children and are linked to other developmental domains.
Prospect of cell penetrating peptides in stem cell tracking
Authors: Zhang Xiaoshuang , Lei Tong , Du Hongwu 
Published: August 2021

AbstractStem cell therapy has shown great efficacy in many diseases. However, the treatment mechanism is still unclear, which is a big obstacle for promoting clinical research. Therefore, it is particularly important to track transplanted stem cells in vivo, find out the distribution and condition of the stem cells, and furthermore reveal the treatment mechanism. Many tracking methods have been developed, including magnetic resonance imaging (MRI), fluorescence imaging, and ultrasound imaging (UI). Among them, MRI and UI techniques have been used in clinical. In stem cell tracking, a major drawback of these technologies is that the imaging signal is not strong enough, mainly due to the low cell penetration efficiency of imaging particles. Cell penetrating peptides (CPPs) have been widely used for cargo delivery due to its high efficacy, good safety properties, and wide delivery of various cargoes. However, there are few reports on the application of CPPs in current stem cell tracking methods. In this review, we systematically introduced the mechanism of CPPs into cell membranes and their advantages in stem cell tracking, discussed the clinical applications and limitations of CPPs, and finally we summarized several commonly used CPPs and their specific applications in stem cell tracking. Although it is not an innovation of tracer materials, CPPs as a powerful tool have broad prospects in stem cell tracking.
Graphic abstract
Activation of G protein-coupled estradiol receptor 1 in the dorsolateral striatum enhances motivation for cocaine and drug-induced reinstatement in female but not male rats
Authors: Quigley Jacqueline A. , Logsdon Molly K. , Graham Brianna C. , Beaudoin Kendra G. , Becker Jill B. 
Published: August 2021

Abstract
Background
Estradiol potentiates drug-taking behaviors, including motivation to self-administer cocaine and reinstatement of drug-seeking after extinction in females, but not males. The dorsolateral stratum (DLS) is a region of the brain implicated in mediating drug-seeking behaviors and, more specifically, is a target brain area to study how estradiol regulates these behaviors. The estradiol receptors α, β, and G protein-coupled estradiol receptor 1 (GPER1) are all present in the DLS. In this study, the effects of activating GPER1 in the DLS on drug-seeking are investigated.

Methods
Gonad-intact male and female rats were trained to self-administer cocaine (0.4 mg/kg/inf) on a fixed-ratio 1 schedule of reinforcement. For 4 weeks, animals underwent testing on a progressive ratio schedule of reinforcement to determine their motivation to attain cocaine. Halfway through progressive ratio testing, a selective agonist targeting GPER1 (G1) was administered intra-DLS to determine the contribution of GPER1 activation on motivation for cocaine. The effects of intra-DLS GPER1 activation on drug-induced reinstatement after extinction were subsequently determined.

Results
Activation of GPER1, via intra-DLS G1 administration, potentiated females’ motivation to self-administer cocaine. There was no effect of prior G1 treatment on extinction of cocaine-taking in females; however, G1 treatment resulted in greater drug-induced reinstatement (10 mg/kg cocaine, i.p.). There were no effects of intra-DLS GPER1 activation observed on motivation for cocaine or cocaine-induced reinstatement of responding in males.

Conclusions
These results support the conclusion that activation of GPER1 in the DLS enhances cocaine-seeking behaviors for female, but not male rats.
Generation of equine enteroids and enteroid-derived 2D monolayers that are responsive to microbial mimics
Authors: Hellman Stina 
Published: August 2021

AbstractEnteroid cultures are three-dimensional in vitro models that reflect the cellular composition and architecture of the small intestine. One limitation with the enteroid conformation is the enclosed lumen, making it difficult to expose the apical surface of the epithelium to experimental treatments. The present study was therefore conducted to generate cultures of equine enteroids and to develop methods for culture of enteroid-derived cells on a two-dimensional plane, enabling easy access to the apical surface of the epithelium. Equine enteroids were established from small intestinal crypts within 7–9 days of culture. Transcriptional analysis of cell type markers confirmed the presence of enterocytes, stem-, Paneth-, proliferative-, enteroendocrine-, goblet- and tuft cells. This cellular composition was maintained over multiple passages, showing that the enteroids can be kept for prolonged periods. The transfer from 3D enteroids to 2D monolayers slightly modified the relative expression levels of the cell type markers, indicating a decrease of goblet- and Paneth cells in the monolayers. Stimulation with the TLR2, 3 and 4 agonists Pam3CSK4, Poly I:C and LPS, respectively, induced the pro-inflammatory cytokines TNF-α and IL-8, while the TLR5 agonist FliC only induced TNF-α. In addition, an up-regulation of TGF-β, IL-33 and IFN-β was recorded after exposure to lipofected Poly I:C that also affected the monolayer integrity. Thus, the equine enteroid-derived 2D monolayers described in the present study show both genetic and functional similarities with the equine intestine making it an interesting in vitro model for studies demanding access to the apical surface, e.g. in studies of host-microbe interactions.
Aerial intelligent reflecting surface-enhanced cell-free massive MIMO for high-mobility communication: joint Doppler compensation and power optimization
Authors: Zhou Tao , Xu Kui , Xie Wei , Shen Zhexian , Wei Chen , Liu Jie , Sun Linpu 
Published: August 2021

AbstractIntelligent reflecting surfaces (IRSs) are considered one of the core technologies in sixth-generation (6G) mobile communication. In this paper, we investigate an aerial IRS (AIRS)-enhanced cell-free (CF) massive multiple-input-multiple-output (MIMO)system where multiple APs serve a high-speed mobile user simultaneously. The mobility of the user leads to fast time-varying and nonnegligible Doppler frequency offsets (DFOs), which cause a serious threat to link performance. To overcome the influence of the Doppler effect and reduce the energy consumption of the system, we propose a Doppler compensation and transmission method by using the AIRS. Specifically, we divide the AIRS reflection phase shift vector into two parts: one part is used for Doppler compensation, and the other is used for transmission. First, we propose an angle-sensing algorithm to obtain the user angle in each coherent time (CT) and use it to design a Doppler compensation vector. Then, we propose an angle information-aided transmission strategy to design the transmission reflecting vector, the beamforming vector, and the power allocation coefficient of each AP to minimize the transmission power of all APs at a required achievable rate. The simulation results show that we can significantly reduce the total transmission power by using the proposed method.
A noise PSD estimation algorithm using derivative-based high-pass filter in non-stationary noise conditions
Authors: Roy Sujan Kumar , Paliwal Kuldip K. 
Published: August 2021

AbstractThe minimum mean-square error (MMSE)-based noise PSD estimators have been used widely for speech enhancement. However, the MMSE noise PSD estimators assume that the noise signal changes at a slower rate than the speech signal— which lacks the ability to track the highly non-stationary noise sources. Moreover, the performance of the MMSE-based noise PSD estimator largely depends upon the accuracy of the a priori SNR estimation in practice. In this paper, we introduce a noise PSD estimation algorithm using a derivative-based high-pass filter in non-stationary noise conditions. The proposed method processes the silent and speech frames of the noisy speech differently to estimate the noise PSD. It is due to the non-stationary noise that can be mixed with silent and speech-dominated frames non-uniformly. We first introduce a spectral-flatness-based adaptive thresholding technique to detect the speech activity of the noisy speech frames. Since the silent frame of the noisy speech is completely filled with noise, the noise periodogram is directly computed from it without applying any filtering. Conversely, a 4th order derivative-based high-pass filter is applied during speech activity of the noisy speech frame to filter out the clean speech components while leaving behind mostly the noise. The noise periodogram is computed from the filtered signal—which counteracts the leaking of clean speech power. The noise PSD estimate is obtained by recursively averaging the previously estimated noise PSD and the current estimate of the noise periodogram. The proposed method is found to be effective in tracking the rapidly changing as well as the slowly varying noise PSD than the competing methods in non-stationary noise conditions for a wide range of signal-to-noise ratio (SNR) levels. Extensive objective and subjective scores on the NOIZEUS corpus demonstrate that the application of the proposed noise PSD with MMSE-based speech enhancement methods produce higher quality and intelligible enhanced speech than the competing methods.
ToAM: a task-oriented authentication model for UAVs based on blockchain
Authors: Chen Aiguo , Peng Kun , Sha Zexin , Zhou Xincen , Yang Zhen , Lu Guoming 
Published: August 2021

AbstractThe pervasive cooperation of a group of UAVs has attracted increasing attention due to the reduced cost and widespread availability. When working in an untrusted or adversarial environment, the mutual authentication of UAVs in the cooperative process is imperative. However, there are some major challenges, including changes in the network environment before and during task performing, and the weak connection network state faced by UAVs. Therefore, a novel task-oriented authentication model for UAVs based on blockchain (ToAM) is proposed, which divides UAVs authentication into group building authentication and intra-group authentication with a two-stage authentication framework. And two lightweight authentication protocols are presented, respectively, corresponding to two stages. Finally, analyses demonstrate that our model realizes secure and lightweight authentication function for the whole process of UAVs requisition and task performing.