bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between hypertension and coffee drinking based on CYP1A2 rs762551 single nucleotide polymorphism in Taiwanese
Authors: Hou Chien-Chou , Tantoh Disline Manli , Lin Chuan-Chao , Chen Pei-Hsin , Yang Hao-Jan , Liaw Yung-Po
Published: August 2021

Background

Hypertension increases the likelihood of cardiovascular diseases (CVDs). Cytochrome P450 1A2 (CYP1A2) single nucleotide polymorphism (SNP) is related to caffeine metabolism and the risk of CVD among coffee drinkers. CYP1A2 rs762551 influenced the risk of stroke among hypertensive patients. We examined the relationship between hypertension and coffee drinking based on CYP1A2 rs762551 SNP in Taiwanese adults.

Methods

We used data contained in the Taiwan Biobank database (2011–2018) and included 19,133 participants having complete information on hypertension, rs762551 polymorphism, coffee intake, etc. The risk of hypertension was determined using multiple logistic regression.

Results

Coffee intake was significantly associated with a lower risk of hypertension. The odds ratio (OR), 95% confidence interval (CI), and p-value were 0.877, 0.807–0.954, and 0.0032, respectively. CYP1A2 rs762551 was not significantly associated with the risk of hypertension, but it had a significant interactive association with coffee drinking (p value = 0.0303). After stratification by rs762551 genotypes, the inverse coffee drinking-hypertension association was retained, but significant results were observed only in those with the AC + CC genotype (OR 0.678, 95% CI 0.722–900, p value = 0.0001). According to the combination of coffee drinking and rs762551 genotypes (reference group: no coffee drinking and rs762551 AA), the coffee drinking-AC + CC group had a lower risk of hypertension (OR 0.888, 95% CI 0.789–0.999, p value = 0.0483).

Conclusion

Coffee drinking, particularly among individuals with the CYP1A2 rs762551 AC + CC genotype was associated with lower odds of hypertension.
Does a preoperative cone beam CT reduce complication rates in the surgical removal of complex lower third molars? A retrospective study including 486 cases
Authors: Klatt Jan C. , Sorowka Tony , Kluwe Lan , Smeets Ralf , Gosau Martin , Hanken Henning
Published: August 2021

Backround

This study was designed to analyse the value of preoperative Cone Beam CTs (CBCT) prior to the surgical removal of complex lower third molars. Furthermore, the aim was to assess injuries to the inferior alveolar nerve (IAN) bundle and postoperative neurological disorders depending on the position of the lower third molar and the inferior alveolar nerve bundle.

Methods

In this retrospective examination preoperative Cone Beam CTs and Orthopantomographs (OPT) of 324 patients were analysed concerning the location of the lower third molars in relation to the mandible and the inferior alveolar nerve bundle. Surgery protocols of all patients who underwent the surgical removal of at least one complex lower third molar were analysed concerning patient data, length of surgery, intraoperative haemorrhage, intraoperative exposure of the inferior alveolar nerve bundle, postoperative swelling and postoperative neurological disorders. The data was then compared to data from international studies.

Results

In all 324 patients a permanent neurological damage was not found. Temporary neurological damage was recorded in 13 cases (2.6%). A caudal nerve position with no measurable distance to the root of the lower third molar was associated with the highest risk of a temporal neurological damage. A vestibular touching nerve route also correlated with postoperative sensitivity impairment. If a mesioangulation (Winter) or a Pell and Gregory Type IIIC appears in the OPT, risk of neurological damage is at its highest.

Conclusions

Three-dimensional radiographic imaging, in our patient group, does not significantly affect the risk for complications during the surgical removal of complex lower third molars. Therefore, it should only be utilized for risk assessment, especially in cases of symptom-free lower third molars.

A preoperative orthopantomogram still can be accepted as standard for radiographic imaging.

An intraoperative exposure of the IAN bundle does not necessarily predict simultaneous neurological damage. Exposure of the IAN bundle is no indication for a discontinuation of the surgery.
Comparison of stereotactic body radiation therapy versus fractionated radiation therapy for primary liver cancer with portal vein tumor thrombus
Authors: Zhang Sujing , He Li , Bo Changwen , Yang Shufang , An Yonghui , Li Na , Zhao Yingchun , Zhao Liping , Ma Wenhua , Zheng Zheng
Published: August 2021

Background

To compare the clinical outcomes of stereotactic body radiation therapy (SBRT) and fractionated radiation therapy (FRT) for primary liver cancer with portal vein tumor thrombus (PVTT).

Methods

This retrospective study included 36 patients who underwent SBRT and 36 patients who underwent FRT from August 2016 to June 2018. Patients were evaluated for short-term efficacy, long-term efficacy, AEs, and quality of life before and after treatment.

Results

With a median follow-up of 28.8 months (26–36 months), 27 patients survived in the SBRT group while 19 patients survived in the FRT group. The survival rate in the SBRT group was statistically higher than that of the FRT group after 6 months (80.56% vs. 58.33%; P = 0.041), 12 months (77.78% vs. 55.56%; P = 0.046) and 24 months 75.00% vs. 52.78%; P = 0.049). The median whole survival time of the SBRT group was 13.3 months (95% CI 12.83–13.97), which was statistically longer than 9.8 months in the FRT group (95% CI 8.83–10.97, P < 0.05) based on the Kaplan–Meier method. The SBRT group had better survival quality and fewer adverse events than the FRT group.

Conclusion

SBRT had better clinical outcomes than FRT for primary liver cancer with PVTT.
A novel method for inference of acyclic chemical compounds with bounded branch-height based on artificial neural networks and integer programming
Authors: Azam Naveed Ahmed , Zhu Jianshen , Sun Yanming , Shi Yu , Shurbevski Aleksandar , Zhao Liang , Nagamochi Hiroshi , Akutsu Tatsuya
Published: August 2021

Analysis of chemical graphs is becoming a major research topic in computational molecular biology due to its potential applications to drug design. One of the major approaches in such a study is inverse quantitative structure activity/property relationship (inverse QSAR/QSPR) analysis, which is to infer chemical structures from given chemical activities/properties. Recently, a novel two-phase framework has been proposed for inverse QSAR/QSPR, where in the first phase an artificial neural network (ANN) is used to construct a prediction function. In the second phase, a mixed integer linear program (MILP) formulated on the trained ANN and a graph search algorithm are used to infer desired chemical structures. The framework has been applied to the case of chemical compounds with cycle index up to 2 so far. The computational results conducted on instances withnnon-hydrogen atoms show that a feature vector can be inferred by solving an MILP for up to$$n=40$$n=40, whereas graphs can be enumerated for up to$$n=15$$n=15. When applied to the case of chemical acyclic graphs, the maximum computable diameter of a chemical structure was up to 8. In this paper, we introduce a new characterization of graph structure, called “branch-height” based on which a new MILP formulation and a new graph search algorithm are designed for chemical acyclic graphs. The results of computational experiments using such chemical properties as octanol/water partition coefficient, boiling point and heat of combustion suggest that the proposed method can infer chemical acyclic graphs with around$$n=50$$n=50and diameter 30.
Potential genes and pathways associated with heterotopic ossification derived from analyses of gene expression profiles
Authors: Yang Zhanyu , Liu Delong , Guan Rui , Li Xin , Wang Yiwei , Sheng Bin
Published: August 2021

Background

Heterotopic ossification (HO) represents pathological lesions that refer to the development of heterotopic bone in extraskeletal tissues around joints. This study investigates the genetic characteristics of bone marrow mesenchymal stem cells (BMSCs) from HO tissues and explores the potential pathways involved in this ailment.

Methods

Gene expression profiles (GSE94683) were obtained from the Gene Expression Omnibus (GEO), including 9 normal specimens and 7 HO specimens, and differentially expressed genes (DEGs) were identified. Then, protein–protein interaction (PPI) networks and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed for further analysis.

Results

In total, 275 DEGs were differentially expressed, of which 153 were upregulated and 122 were downregulated. In the biological process (BP) category, the majority of DEGs, including EFNB3, UNC5C, TMEFF2, PTH2, KIT, FGF13, and WISP3, were intensively enriched in aspects of cell signal transmission, including axon guidance, negative regulation of cell migration, peptidyl-tyrosine phosphorylation, and cell-cell signaling. Moreover, KEGG analysis indicated that the majority of DEGs, including EFNB3, UNC5C, FGF13, MAPK10, DDIT3, KIT, COL4A4, and DKK2, were primarily involved in the mitogen-activated protein kinase (MAPK) signaling pathway, Ras signaling pathway, phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) signaling pathway, and Wnt signaling pathway. Ten hub genes were identified, including CX3CL1, CXCL1, ADAMTS3, ADAMTS16, ADAMTSL2, ADAMTSL3, ADAMTSL5, PENK, GPR18, and CALB2.

Conclusions

This study presented novel insight into the pathogenesis of HO. Ten hub genes and most of the DEGs intensively involved in enrichment analyses may be new candidate targets for the prevention and treatment of HO in the future.
Posterior pericardiotomy to prevent new-onset atrial fibrillation after coronary artery bypass grafting: a systematic review and meta-analysis of 10 randomized controlled trials
Authors: Xiong Tao , Pu Lei , Ma Yuan-Feng , Zhu Yun-Long , Li Hua , Cui Xu , Li Ya-Xiong
Published: August 2021

Background

Atrial fibrillation (AF) is associated with adverse events after cardiac surgery. Multiple studies have reported that posterior pericardiotomy (PP) may be effective for preventing AF after coronary artery bypass grafting (CABG), but some conflicting results have been reported and the quality of evidence from previous meta-analyses has been limited. The present study aimed to systematically evaluate the safety and efficacy of PP for preventing AF after CABG in adults.

Methods

We conducted a quantitative meta-analysis of randomized controlled trials (RCTs) published before May 31, 2021. The primary outcome was AF after CABG under cardiopulmonary bypass. Secondary outcomes included early pericardial effusion, late pericardial effusion, pericardial tamponade, pleural effusion, length of hospital stay, length of intensive care unit (ICU) stay, pulmonary complications, intra-aortic balloon pump use, revision surgery for bleeding, and mortality.

Results

Ten RCTs with 1829 patients (910 in the PP group and 919 in the control group) were included in the current meta-analysis. The incidence of AF was 10.3% (94/910) in the PP group and 25.7% (236/919) in the control group. A random-effects model indicated that incidence of AF after CABG significantly lower in the PP group than in the control group (risk ratio = 0.45, 95% confidence interval 0.29–0.64, P < 0.0001). PP also effectively reduced the post-CABG occurrence of early pericardial effusion (RR = 0.28, 95% CI 0.15–0.50; P < 0.05), late pericardial effusion (RR = 0.06, 95% CI 0.02–0.16; P < 0.05), and pericardial tamponade (RR = 0.08, 95% CI 0.02–0.33; P < 0.05) as well as the length of ICU stay (weighted mean difference [WMD] = 0.91,95% CI 0.57–1.24; P < 0.05), while increasing the occurrence pleural effusion (RR = 1.51, 95% CI 1.19–1.92; P < 0.05). No significant differences length of hospital stay (WMD =  − 0.45, 95% CI − 2.44 to 1.54, P = 0.66), pulmonary complications (RR = 0.99, 95% CI 0.71–1.39, P = 0.97), revision surgery for bleeding (RR = 0.84, 95% CI 0.43–1.63, P = 0.60), use of IABP (RR = 1, 95% CI 0.61–1.65, P = 1.0), or death (RR = 0.45, 95% CI 0.07–3.03, P = 0.41) were observed between the PP and control groups.

Conclusions

PP may be a safe, effective, and economical method for preventing AF after CABG in adult patients.
Chaihu-Shugan-San (Shihosogansan) alleviates restraint stress-generated anxiety and depression in mice by regulating NF-κB-mediated BDNF expression through the modulation of gut microbiota
Authors: Han Sang-Kap , Kim Jeon-Kyung , Park Hee-Seo , Shin Yeun-Jeong , Kim Dong-Hyun
Published: August 2021

Background

Chaihu-Shugan-San (CSS, named Shihosogansan in Korean), a Chinese traditional medicine, is frequently used to treat anxiety and depression. Psychiatric disorders including depression are associated with gut dysbiosis. Therefore, to comprehend gut microbiota-involved anti-depressive effect of CSS, we examined its effect on restraint stress (RS)-induced depression and gut dysbiosis in mice

Methods

CSS was extracted with water in boiling water bath and freeze-dried. Anxiety and depression was induced in C57BL/6 mice by exposure to RS. Anxiety- and depression-like behaviors were measured in the light/dark transition and elevated plus maze tasks, forced swimming test, and tail suspension test. Biomarkers were assayed by using the enzyme-linked immunosorbent assay and immunoblotting. The gut microbiota composition was analyzed by Illumina iSeq sequencer.

Results

CSS significantly reduced the RS-induced anxiety- and depression-like behaviors in mice. CSS suppressed the RS-induced activation of NF-κB and expression of interleukin (IL)-6 and increased the RS-suppressed expression of brain-derived neurotrophic factor (BDNF). Furthermore, CSS suppressed the RS-induced IL-6 and corticosterone level in the blood and IL-6 expression and myeloperoxidase activity in the colon. CSS decreased the RS-induced γ-Proteobacteria population in gut microbiota, while the RS-suppressed Lactobacillaceae, Prevotellaceae, and AC160630_f populations increased. Fecal transplantation of vehicle-treated control or RS/CSS-treated mice into RS-exposed mice significantly mitigated RS-induced anxity- and depression-like behaviors, suppressed the NF-κB activation in the hippocampus and colon, and reduced the IL-6 and corticosterone levels in the blood. These fecal microbiota transplantations suppressed RS-induced Desulfovibrionaceae and γ-Proteobacteria populations and increased RS-suppressed Lactobacillaceae and Prevotellaceae poulation in the gut microbiota.

Conclusions

CSS alleviated anxiety and depression by inducing NF-κB-involved BDNF expression through the regulation of gut inflammation and microbiota.
Simultaneous external validation of various cardiac arrest prognostic scores: a single-center retrospective study
Authors: Tsuchida Takumi , Ono Kota , Maekawa Kunihiko , Wada Takeshi , Katabami Kenichi , Yoshida Tomonao , Hayakawa Mineji
Published: August 2021

Background

This study aimed to compare and validate the out-of-hospital cardiac arrest (OHCA); cardiac arrest hospital prognosis (CAHP); non-shockable rhythm, unwitnessed arrest, long no-flow or long low-flow period, blood pH < 7.2, lactate > 7.0 mmol/L, end-stage chronic kidney disease, age ≥ 85 years, still resuscitation, and extracardiac cause (NULL-PLEASE) clinical; post-cardiac arrest syndrome for therapeutic hypothermia (CAST); and revised CAST (rCAST) scores in OHCA patients treated with recent cardiopulmonary resuscitation strategies.

Methods

We retrospectively collected data on adult OHCA patients admitted to our emergency department between February 2015 and July 2018. OHCA, CAHP, NULL-PLEASE clinical, CAST, and rCAST scores were calculated based on the data collected. The predictive abilities of each score were tested using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve.

Results

We identified 236 OHCA patients from computer-based medical records and analyzed 189 without missing data. In OHCA patients without bystander witnesses, CAHP and OHCA scores were not calculated. Although the predictive abilities of the scores were not significantly different, the NULL-PLEASE score had a large AUC of ROC curve in various OHCA patients. Furthermore, in patients with bystander-witnessed OHCA, the NULL-PLEASE score had large partial AUCs of ROC from sensitivity 0.8–1.0 and specificity 0.8–1.0.

Conclusions

The NULL-PLEASE score had a high, comprehensive predictive ability in various OHCA patients. Furthermore, the NULL-PLEASE score had a high predictive ability for good and poor neurological outcomes in patients with bystander-witnessed OHCA.
Efficacy and central mechanism of acupuncture treatment in patients with neck pain: study protocol for a randomized controlled trial
Authors: Gao Zhen , Yin Tao , Lan Lei , Li Dehua , Sun Ruirui , Ha Guodong , Jiang Caili , Shao Xin , He Zhaoxuan , Ji Laixi , Zeng Fang
Published: August 2021

Background

Acupuncture is effective for reducing the symptoms of neck pain (NP). However, the underlying mechanisms are not fully elucidated. Based on evaluating the efficacy of two acupuncture prescriptions for treating NP, this study aims to investigate the potential central mechanism of acupuncture treatment for NP by functional magnetic resonance imaging (fMRI).

Methods

This is a randomized controlled trial; 86 patients will be randomly assigned into two acupuncture treatment groups at a ratio of 1:1. The whole study period includes 2 weeks baseline, 2 weeks treatments, and 12 weeks follow-up (4 and 12 weeks after treatment). The pain severity, the neck disability index, the cervical range of motion, and the pressure pain threshold, etc., will be used to evaluate the clinical efficacy of two acupuncture prescriptions for NP treatment. The MRI scans will be performed to detect cerebral activity changes of 20 patients in each group. The clinical data and MRI data will be analyzed, respectively.Pearsoncorrelation coefficient will be used to evaluate the association between changes of cerebral activity features and improvement of clinical symptoms.

Discussion

The results will provide further evidence for the clinical application of acupuncture in the treatment of NP.

Trial registration

Chinese Clinical Trial RegistryChiCTR2000040930. Registered on 16 December 2020.
Prevalence of arbovirus antibodies in young healthy adult population in Brazil
Authors: Salgado Bárbara Batista , de Jesus Maués Fábio Carmona , Pereira Renato Lemos , Chiang Jannifer Oliveira , de Oliveira Freitas Maria Nazaré , Ferreira Milene Silveira , Martins Lívia Caricio , da Costa Vasconcelos Pedro Fernando , Ganoza Christian , Lalwani Pritesh
Published: August 2021

Background

The emergence and re-emergence of infectious diseases are a cause for worldwide concern. The introduction of Zika and Chikungunya diseases in the Americas has exposed unforeseen medical and logistical challenges for public health systems. Moreover, the lack of preventive measures and vaccination against known and emerging mosquito-transmitted pathogens, and the occurrence of unanticipated clinical complications, has had an enormous social and economic impact on the affected populations. In this study, we aimed to measure the seroprevalence of endemic and emerging viral pathogens in military personnel stationed in Manaus, Amazonas state.

Methods

We measured the seropositivity of antibodies against 19 endemic and emerging viruses in a healthy military personnel group using a hemagglutination inhibition assay (HIA).

Results

Overall, DENV positivity was 60.4%, and 30.9% of the individuals reacted against ZIKV. Also, 46.6%, 54.7%, 51.3% and 48.7% individuals reacted against West Nile virus (WNV), Saint Louis encephalitis virus (SLEV), Ilheus virus (ILHV) and Rocio virus (ROCV), respectively. Individuals with high DENV HIA titer reacted more frequently with ZIKV or WNV compared to those with low HIA titers. Observed cross-reactivity between Flaviviruses varied depending on the virus serogroup. Additionally, 0.6% and 0.3% individuals were seropositive for Oropouche virus (OROV) and Catu virus (CATUV) from the family Peribunyaviridae, respectively. All samples were negative for Eastern Equine Encephalitis virus (EEEV), Western Equine Encephalomyelitis virus (WEEV), Mayaro virus (MAYV), Mucambo virus (MUCV) and CHIKV from the family Togaviridae.

Conclusions

A high proportion of individuals in our high-risk population (~ 60%) lacked antibodies against major endemic and emerging viruses, which makes them susceptible for further infections. Military personnel serving in the Amazon region could serve as sentinels to strengthen global infectious disease surveillance, particularly in remote areas.

Graphical abstract
Equine attachment site preferences and seasonality of common North American ticks: Amblyomma americanum, Dermacentor albipictus, and Ixodes scapularis
Authors: Sundstrom Kellee D. , Lineberry Megan W. , Grant Amber N. , Duncan Kathryn T. , Ientile Michelle M. , Little Susan E.
Published: August 2021

Background

Ticks are common on horses, but recent publications characterizing equine tick infestations in North America are lacking.

Methods

To further understand attachment site preferences of common ticks of horses, and to document the seasonality of equine tick infestation in northeastern Oklahoma, horses from eight farms were evaluated twice a month over a 1-year period. Each horse was systematically inspected beginning at the head and moving caudally to the tail. Attachment sites of ticks were recorded and all ticks collected were identified to species and stage.

Results

Horses (26 males and 62 females) enrolled in the study ranged in age from 1 to 23 years (mean = 12, 95% CI 11–13). A total of 2731 ticks were collected; 84.1% (74/88) of the horses were infested (median = 3 ticks) at one or more examinations. Five tick species were identified, including Amblyomma americanum (78.2%; 2136/2731), Ixodes scapularis (18.2%; 497/2731), Dermacentor albipictus brown variant (2.6%; 71/2731), Dermacentor variabilis (0.7%; 20/2731), and Amblyomma maculatum (0.3%; 7/231). Most ticks were adults (83.6%; 2282/2731), but immature A. americanum (436/2136; 20.4%), D. albipictus (12/71; 16.9%), and A. maculatum (n = 1) were occasionally recovered. Amblyomma americanum were most often attached to the inguinal area, and I. scapularis and D. albipictus were most commonly found on the chest and axillary region (P < 0.0001). Ticks were found on horses in every month of the year. The largest number of ticks (638/2731; 23.4%) were collected in May (P < 0.0001). Amblyomma americanum, primarily immature, was the only tick recovered in September, I. scapularis and D. albipictus predominated October through February, and both A. americanum and I. scapularis were common in March. In the warmer months, April through August, A. americanum was the most common tick, followed by D. variabilis and A. maculatum.

Conclusions

This research confirms that ticks common on horses in North America have attachment site preferences and that ticks infest horses in Oklahoma throughout the year, including during the winter. Additional research is warranted to fully understand the risk these infestations pose to equine health.

Graphical abstract
The role of lung ultrasound B-lines and serum KL-6 in the screening and follow-up of rheumatoid arthritis patients for an identification of interstitial lung disease: review of the literature, proposal for a preliminary algorithm, and clinical application to cases
Authors: Wang Yukai , Chen Shaoqi , Zheng Shaoyu , Lin Jianqun , Hu Shijian , Zhuang Jinghua , Lin Qisheng , Xie Xuezhen , Zheng Kedi , Zhang Weijin , Du Guangzhou , Zhang Guohong , Hoffmann-Vold Anna-Maria , Matucci-Cerinic Marco , Furst Daniel E.
Published: August 2021

Screening and follow-up of interstitial lung disease associated with rheumatoid arthritis (RA-ILD) is a challenge in clinical practice. In fact, the majority of RA-ILD patients are asymptomatic and optimal tools for early screening and regular follow-up are lacking. Furthermore, some patients may remain oligosymptomatic despite significant radiological abnormalities. In RA-ILD, usual interstitial pneumonia (UIP) is the most frequent radiological and pathological pattern, associated with a poor prognosis and a high risk to develop acute exacerbations and infections. If RA-ILD can be identified early, there may be an opportunity for an early treatment and close follow-up that might delay ILD progression and improve the long-term outcome.

In connective tissue disease–associated interstitial lung disease (CTD-ILD), lung ultrasound (LUS) with the assessment of B-lines and serum Krebs von den Lungen-6 antigen (KL-6) has been recognized as sensitive biomarkers for the early detection of ILD. B-line number and serum KL-6 level were found to correlate with high-resolution computed tomography (HRCT), pulmonary function tests (PFTs), and other clinical parameters in systemic sclerosis–associated ILD (SSc-ILD). Recently, the significant correlation between B-lines and KL-6, two non-ionizing and non-invasive biomarkers, was demonstrated. Hence, the combined use of LUS and KL-6 to screen and follow up ILD in RA patients might be useful in clinical practice in addition to existing tools. Herein, we review relevant literature to support this concept, propose a preliminary screening algorithm, and present 2 cases where the algorithm was used.
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

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

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

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

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

Exercise-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

Background

Restricted 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.

Methods

The 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.

Results

The 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.

Limitations

The 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.

Conclusions

These 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

Stem 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

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

Enteroid 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

Intelligent 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

The 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

The 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.