bluuebunny/crossref_metadata_2025 huggingface dataset:
Construction and verification of a novel hypoxia-related lncRNA signature related with survival outcomes and immune microenvironment of bladder urothelial carcinoma by weighted gene co-expression network analysis
Authors: Cai Dawei , Zhou Zhongbao , Wei Guangzhu , Wu Peishan , Kong Guangqi
Published: August 2022

Background: Bladder urothelial carcinoma (BLCA) is a common malignant tumor with the greatest recurrence rate of any solid tumor. Hypoxia is crucial in the growth and immune escape of malignant tumors. To predict clinical outcomes and immunological microenvironment of patients with BLCA, a hypoxia-related long non-coding RNA (HRlncRNA) signature was established.

Methods: The Cancer Genome Atlas (TCGA) provided us with the differentially expressed profile of HRlncRNAs as well as clinical data from patients with BLCA, and we used weighted gene co-expression network analysis (WGCNA) to identify gene modules associated with malignancies.

Results: Finally, Cox analysis revealed that HRlncRNAs, which comprised 13 lncRNAs, were implicated in the predictive signature. The training, testing, and overall cohorts of BLCA patients were divided into the low-risk group and high-risk group based on the median of the risk score. The Kaplan–Meier curves revealed that BLCA patients with a high-risk score had a poor prognosis, and the difference between subgroups was statistically significant. The receiver operating characteristic curves revealed that this signature outperformed other strategies in terms of predicting ability. Multivariate analysis revealed that the risk score was an independent prognostic index for overall survival (HR = 1.411; 1.259–1.582; p < 0.001). Then, a nomogram with clinicopathological features and risk score was established. This signature could effectively enhance the capacity to predict survival, according to the calibration plots, stratification, and clinical analysis. The majority of Kyoto Encyclopedia of Genes and Genomes (KEGG) were WNT, MAPK, and ERBB signaling pathways. Two groups had different immune cell subtypes, immune checkpoints, immunotherapy response, and anti-tumor drug sensitivity, which might result in differing survival outcomes. We then validated the differential expression of signature-related genes between tumor and normal tissues using TCGA paired data.

Conclusion: This prognostic signature based on 13 HRlncRNAs may become a novel and potential prognostic biomarker, providing more accurate clinical decision-making and effective treatment for BLCA patients.
Liver transplantation combined with tyrosine kinase inhibitors for the treatment of hepatic metastatic giant gastrointestinal stromal tumors: A case report and literature review
Authors: Qian Jun Lin , Hu Ze Min , He Kun , He Yong Zhu
Published: August 2022

Background

Surgical resection combined with oral tyrosine kinase inhibitors(TKI) is the most effective treatment for gastrointestinal stromal tumor(GIST) liver metastases. Liver transplantation (LT) is the last resort for the treatment of terminal liver malignancy. Whether it can be a potential treatment option for liver metastases from unresectable GIST is worth exploring.

Case presentation

We report a 38-year-old woman who underwent jejunal stromal tumor resection and TKI(imatinib) therapy 15 years ago for jejunal stromal tumor liver metastases. During the period from 2015 to 2018, the liver metastases continued to grow after the patient stopped taking imatinib voluntarily, and the patient subsequently underwent multiple interventional surgeries and drug treatments, which were still poorly curative. The tumor was deemed unresectable because it filled the entire liver, and the patient subsequently underwent LT and was treated with imatinib post-operatively, which resulted in no recurrence of the tumor within 18 months of follow-up.

Literature review

There are few reports in the literature on LT for the treatment of liver metastases from GIST. A systematic review and summary of the current literature by literature search revealed that LT as a last resort for metastatic GIST of the liver remains a major challenge.

Conclusions

LT combined with TKI-targeted therapy is a potential therapy worth exploring for patients with unresectable metastatic GIST.
The molecular subtypes of triple negative breast cancer were defined and a ligand-receptor pair score model was constructed by comprehensive analysis of ligand-receptor pairs
Authors: Pan Weijun , Song Kai , Zhang Yunli , Yang Ciqiu , Zhang Yi , Ji Fei , Zhang Junsheng , Shi Jian , Wang Kun
Published: August 2022

Background

Intercellular communication mediated by ligand-receptor interactions in tumor microenvironment (TME) has a profound impact on tumor progression. This study aimed to explore the molecular subtypes mediated by ligand-receptor (LR) pairs in triple negative breast cancer (TNBC), identify the most important LR pairs to construct a prognostic risk model, and study their effect on TNBC immunotherapy.

Methods

LR pairs subclasses of TNBC were categorized by consensus clustering based on LR Pairs in METABRIC dataset. Least absolute shrinkage and selection operator (LASSO) Cox regression and stepwise Akaike information criterion (stepAIC) were conducted to build a LR pairs score model. The relationship between LR pairs score and immune cell infiltration, stromal score and immune score associated with TME was analyzed, and the prediction of drug therapy and immunotherapy efficacy by LR pairs score was evaluated.

Results

According to the expression pattern of 145 TNBC prognostic LR pairs, the samples were divided into three subclasses with different survival outcomes, copy number variation (CNV), TME immune cell infiltration, stromal score and immune score. The LR pairs score model constructed in the METABRIC dataset was composed of four LR pairs, and its predictive significance for TNBC prognosis was verified in GSE58812 and GSE21653 cohorts. In addition, LR pairs score was negatively correlated with several immune pathways regulating immunity and immune score, and related to the sensitivity of anti-neoplastic drugs and the effect of anti-PD-L1 therapy.

Conclusion

Our study confirmed the impact of LR pairs on the molecular heterogeneity of TNBC, characterized three LR pairs subtypes with different survival outcomes and TME patterns, and proposed a LR pairs score system with predictive significance for TNBC prognosis and anti-PD-L1 therapeutic effect, which provides a potential evaluation scheme for TNBC management.
Flexural behavior of composite beams with concrete filled steel tube flanges and honeycombed steel webs
Authors: Ji Jing , Li Yunhao , Jiang Liangqin , Ren Hongguo , Wang Qingqin , Zhang Lei , He Lingjie , Zhang Zhanbin
Published: August 2022

Honeycombed beams are widely used because they are conducive to the layout of pipelines and circuits, and the traditional honeycombed beams are generally H-shaped steel beams and concrete-encased upper flange composite beams. In this paper, a composite beam with concrete-filled steel tube as both upper and lower flanges and steel plate with circular openings as web is proposed. The effective constraint of steel tube on concrete strengthens the deformation ability of concrete. In order to study the flexural behavior of composite beams with concrete filled steel tube flanges and honeycombed steel webs (SHC), 25 simply-supported SHC beams were designed to carry out the four-point bending load simulation analysis. By reasonable modeling method. The main parameters of SHC concluding the compression strength of concrete (fck), yield strength of steel (fyfk), height-to-span ratio (H/L), ratio of space to height of web (s/hw), thickness of steel tube flange (t1), thickness of web (t2) and ratio of hole to height of web (a/hw) were discussed, and the whole loading process of the beam was analyzed. The results showed that the SHC specimens could be divided into elastic stage, elastic-plastic stage and plastic stage under four-point bending load. Steel tube in the tensile zone yielded firstly before specimens failed, and the failure mode of the specimens was that the concrete at the loading point was crushed. Though the steel tube in lower flange at the support, loading point and mid-span yielded, the web did not buckle. SHC could meet the requirements of Chinese code in the normal use stage, and the cross-section deformation basically conformed to the plane assumption. Finally, based on the unified strength theory, a prediction formula of ultimate bending moment is established, which is in good agreement with experiment and can lay the foundation for the popularization and application of this kind of beams.
Application of chitosan-based materials in surgical or postoperative hemostasis
Authors: Xia Yuanliang , Yang Ruohan , Wang Hengyi , Li Yuehong , Fu Changfeng
Published: August 2022

Uncontrolled bleeding from trauma or surgery remains an important factor affecting the survival and prognosis of surgical patients. Failure to timeously stop bleeding will not only prolong the operative time but also threaten the patient’s life. Timely hemostasis after bleeding has become the most concerned event for surgeons. At present, the most commonly used hemostasis methods in the operating room include ligation of blood vessels, electrocautery, and gauze compression to stop bleeding. However, These hemostatic methods do great harm to surrounding tissues while achieving hemostasis. Based on tissue engineering repair strategies, the use of natural polymer materials as hemostatic agents has achieved clinical success. Gelatin sponge and cellulose gauze have been used clinically with good results. However, gelatin sponges are very expensive and place enormous financial pressure on patients. Therefore, there is an urgent need for new hemostatic materials for surgical hemostasis. Chitosan is a natural polysaccharide with biocompatibility and biodegradability, which plays an important role in tissue engineering and regenerative medicine. Chitosan gauze has been proven to have good hemostatic effects. The positive charge on the surface of chitosan can adsorb red blood cells and platelets at the bleeding site to form platelet thrombosis. However, chitosan is not easily soluble in water and has poor adsorption, which makes it a weak local hemostatic agent. Therefore, it is important to improve chitosan-based hemostatic material such that it l has an excellent hemostatic effect. In this review, we introduce the physiological coagulation process and discuss the physicochemical properties of chitosan and its role in hemostasis. Furthermore, we discuss the advantages and disadvantages of chitosan-based hemostatic materials. Finally, we summarize and discuss chitosan-based hemostatic materials.
Improvement of an interobserver agreement of ARDS diagnosis by adding additional imaging and a confidence scale
Authors: Hagens Laura A. , Van der Ven Fleur L. I. M. , Heijnen Nanon F. L. , Smit Marry R. , Gietema Hester A. , Gerretsen Suzanne C. , Schultz Marcus J. , Bergmans Dennis C. J. J. , Schnabel Ronny M. , Bos Lieuwe D. J.
Published: August 2022

Acute respiratory distress syndrome (ARDS) often is not recognized in clinical practice, largely due to variation in the interpretation of chest x-ray (CXR) leading to poor interobserver reliability. We hypothesized that the agreement in the interpretation of chest imaging for the diagnosis of ARDS in invasively ventilated intensive care unit patients between experts improves when using an 8-grade confidence scale compared to using a dichotomous assessment and that the agreement increases after adding chest computed tomography (CT) or lung ultrasound (LUS) to CXR. Three experts scored ARDS according to the Berlin definition based on case records from an observational cohort study using a dichotomous assessment and an 8-grade confidence scale. The intraclass correlation (ICC), imaging modality, and the scoring method were calculated per day and compared using bootstrapping. A consensus judgement on the presence of ARDS was based on the combined confidence grades of the experts, followed by a consensus meeting for conflicting scores. In total, 401 patients were included in the analysis. The best ICC was found using an 8-grade confidence scale for LUS (ICC: 0.49; 95%-CI: 0.29–0.63) and CT evaluation (ICC: 0.49; 95%-CI: 0.34–0.61). The ICC of CXR increased by 0.022 and of CT by 0.065 when 8-grade scoring was used instead of the dichotomous assessment. Adding information from LUS or chest CT increased the ICC by 0.25 when using the 8-grade confidence assessment. An agreement on the diagnosis of ARDS can increase substantially by adapting the scoring system from a dichotomous assessment to an 8-grade confidence scale and by adding additional imaging modalities such as LUS or chest CT. This suggests that a simple assessment of the diagnosis of ARDS with a chart review by one assessor is insufficient to define ARDS in future studies.

Clinical trial registration

Trialregister.nl (identifier NL8226).
The antifungal activity and mechanism of silver nanoparticles against four pathogens causing kiwifruit post-harvest rot
Authors: Li Li , Pan Hui , Deng Lei , Qian Guoliang , Wang Zupeng , Li Wenyi , Zhong Caihong
Published: August 2022

Post-harvest rot causes enormous economic loss to the global kiwifruit industry. Currently, there are no effective fungicides to combat the disease. It is unclear whether silver nanoparticles (AgNPs) are effective in controlling post-harvest rot and, if so, what the underlying antifungal mechanism is. Our results indicated that 75 ppm AgNPs effectively inhibited the mycelial growth and spore germination of four kiwifruit rot pathogens: Alternaria alternata, Pestalotiopsis microspora, Diaporthe actinidiae, and Botryosphaeria dothidea. Additionally, AgNPs increased the permeability of mycelium’s cell membrane, indicating the leakage of intracellular substance. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) observations revealed that AgNPs induced pathogen hypha shrinkage and distortion, as well as vacuolation in hypha cells, implying that AgNPs caused cellular and organelle structural degradation. The transcriptome sequencing of mycelium treated with AgNPs (24 h / 48 h) was performed on the Illumina Hiseq 4000 sequencing (RNA-Seq) platform. For the time points of 24 h and 48 h, AgNPs treatment resulted in 1,178 and 1,461 differentially expressed genes (DEGs) of A. alternata, 517 and 91 DEGs of P. microspora, 1,287 and 65 DEGs of D. actinidiae, 239 and 55 DEGs of B. dothidea, respectively. The DEGs were found to be involved in “catalytic activity,” “small molecule binding,” “metal ion binding,” “transporter activity,” “cellular component organization,” “protein metabolic process,” “carbohydrate metabolic process,” and “establishment of localization.” Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis also revealed that “carbohydrate metabolism,” “amino acid metabolism,” “energy metabolism,” and “xenobiotics biodegradation and metabolism” of “metabolism processes” were the most highly enriched pathways for these DEGs in four pathogens, with “cellular processes” being particularly enriched for B. dothidea. Furthermore, quantitative polymerase chain reactions (qPCRs) were used to validate the RNA-seq results. It was also confirmed that AgNPs could significantly reduce the symptoms of kiwifruit rot without leaving any Ag+ residue on the peel and flesh of kiwifruit. Our findings contributed to a better understanding of the antifungal effect and molecular mechanisms of AgNPs against pathogens causing kiwifruit post-harvest rot, as well as a new perspective on the application of this novel antifungal alternative to fruit disease control.
EEG-fNIRS-based hybrid image construction and classification using CNN-LSTM
Authors: Mughal Nabeeha Ehsan , Khan Muhammad Jawad , Khalil Khurram , Javed Kashif , Sajid Hasan , Naseer Noman , Ghafoor Usman , Hong Keum-Shik
Published: August 2022

The constantly evolving human–machine interaction and advancement in sociotechnical systems have made it essential to analyze vital human factors such as mental workload, vigilance, fatigue, and stress by monitoring brain states for optimum performance and human safety. Similarly, brain signals have become paramount for rehabilitation and assistive purposes in fields such as brain–computer interface (BCI) and closed-loop neuromodulation for neurological disorders and motor disabilities. The complexity, non-stationary nature, and low signal-to-noise ratio of brain signals pose significant challenges for researchers to design robust and reliable BCI systems to accurately detect meaningful changes in brain states outside the laboratory environment. Different neuroimaging modalities are used in hybrid settings to enhance accuracy, increase control commands, and decrease the time required for brain activity detection. Functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG) measure the hemodynamic and electrical activity of the brain with a good spatial and temporal resolution, respectively. However, in hybrid settings, where both modalities enhance the output performance of BCI, their data compatibility due to the huge discrepancy between their sampling rate and the number of channels remains a challenge for real-time BCI applications. Traditional methods, such as downsampling and channel selection, result in important information loss while making both modalities compatible. In this study, we present a novel recurrence plot (RP)-based time-distributed convolutional neural network and long short-term memory (CNN-LSTM) algorithm for the integrated classification of fNIRS EEG for hybrid BCI applications. The acquired brain signals are first projected into a non-linear dimension with RPs and fed into the CNN to extract essential features without performing any downsampling. Then, LSTM is used to learn the chronological features and time-dependence relation to detect brain activity. The average accuracies achieved with the proposed model were 78.44% for fNIRS, 86.24% for EEG, and 88.41% for hybrid EEG-fNIRS BCI. Moreover, the maximum accuracies achieved were 85.9, 88.1, and 92.4%, respectively. The results confirm the viability of the RP-based deep-learning algorithm for successful BCI systems.
Residue, dissipation, and dietary intake evaluation of fenpyroximate acaricide in/on guava, orange, and eggplant under open field condition
Authors: Malhat Farag , Abdallah Osama , Anagnostopoulos Chris , Hussien Mohamed , Purnama Indra , Helmy Rania M. A. , Soliman Hanim , El-Hefny Dalia
Published: August 2022

Fenpyroximate is a widely used acaricide applicable in many crops. In this study, the residue behavior of fenpyroximate on eggplant, orange, and guava was investigated. The chronic and acute dietary intake was calculated at several sampling points, and preharvest intervals (PHI) were proposed to ensure compliance with the existing maximum residue levels. A simple extraction protocol combined with ultrahigh-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) was employed to quantify residue levels. The method was successfully validated according to the European Union (EU) guidelines, and a limit of quantification of 0.01 mg/kg was set. The dissipation patterns in all crops could be described by the first-order kinetics model with half-lives of 1.7, 2.2, and 1.9 days for eggplants, guavas, and oranges, respectively. The dietary risk assessment at the authorized or more critical application patterns was acceptable for the consumers. For oranges and eggplant, a PHI of 3 and 7 days, respectively, can be proposed; however, a proposal was not possible for guava due to the absence of maximum residue limits (MRLs) and quantitative residue findings at all sampling points tested. The current work not only contributes to the practical application of fenpyroximate related to residue management in dryland areas, such as Egypt, but can also be used to estimate the appropriate PHIs and support the authorization of plant protection products as supplementary information.
Role of arginine supplementation on muscular metabolism and flesh quality of Pacific white shrimp (Litopenaeus vannamei) reared in freshwater
Authors: Li Meifeng , Wen Hua , Huang Feng , Wu Meili , Yu Lijuan , Jiang Ming , Lu Xing , Tian Juan
Published: August 2022

It is no doubt that the improvement of flesh quality of Pacific white shrimp (Litopenaeus vannamei) reared in freshwater contributes to its development potential in aquaculture. In this study, we aimed to explore the effect of arginine supplementation on the flesh quality of L. vannamei reared in freshwater and its mechanism. L. vannamei were randomly fed with three diets for 56 days, of which arginine level was 10.15 g kg–1 (arginine-deficient diet), 21.82 g kg–1 (arginine-optimal diet), and 32.46 g kg–1 (arginine-excessive diet), respectively. Each diet was randomly assigned to triplicate tanks, and each tank was stocked with 35 shrimps (initial weight: 1.70 ± 0.02 g). Results showed the arginine-optimal diet increased the weight gain, flesh percentage, crude protein and flavor amino acid contents in muscle, and improved the flesh hardness by conversing fast myofibers to slow myofibers, increasing myofiber density and myofibrillar length, and promoting ornithine and collagen synthesis. The arginine-optimal diet influenced the purine metabolic pathway by reducing hypoxanthine, xanthine, and inosine contents. Ornithine, citrulline, and glutamate were identified as the key metabolites affecting flesh quality traits after arginine treatments. Only increasing the levels of dietary arginine did not result in an increase in endogenous creatine synthesis in muscle and hepatopancreas. Overall, the arginine-optimal diet improved the flesh quality traits of L. vannamei reared in freshwater due to the enhanced muscular hardness, protein deposition, and flavor, which may be contributing to the transformation of muscle fiber type and increase in protein synthesis by the metabolites of arginine (ornithine, citrulline, and glutamate).
Dynamic monitoring revealed a slightly prolonged waiting time for total gastrectomy during the COVID-19 pandemic without increasing the short-term complications
Authors: Zheng Xiaohao , Ding Shikang , Wu Ming , Sun Chunyang , Wu Yunzi , Wang Shenghui , Du Yongxing , Yang Lin , Xue Liyan , Wang Bingzhi , Wang Chengfeng , Cui Wei , Xie Yibin
Published: August 2022

We aimed to determine the pattern of delay and its effect on the short-term outcomes of total gastrectomy before and during the coronavirus disease 2019 (COVID-19) pandemic. Overlaid line graphs were used to visualize the dynamic changes in the severity of the pandemic, number of gastric cancer patients, and waiting time for a total gastrectomy. We observed a slightly longer waiting time during the pandemic (median: 28.00 days, interquartile range: 22.00–34.75) than before the pandemic (median: 25.00 days, interquartile range: 18.00–34.00; p = 0.0071). Moreover, we study the effect of delayed surgery (waiting time > 30 days) on short-term outcomes using postoperative complications, extreme value of laboratory results, and postoperative stay. In patients who had longer waiting times, we did not observe worse short-term complication rates (grade II–IV: 15% vs. 19%, p = 0.27; grade III–IV: 7.3% vs. 9.2%, p = 0.51, the short waiting group vs. the prolonged waiting group) or a higher risk of a longer POD (univariable: OR 1.09, 95% CI 0.80–1.49, p = 0.59; multivariable: OR 1.10, 95% CI 0.78–1.55, p = 0.59). Patients in the short waiting group, rather than in the delayed surgery group, had an increased risk of bleeding in analyses of laboratory results (plasma prothrombin activity, hemoglobin, and hematocrit). A slightly prolonged preoperative waiting time during COVID-19 pandemic might not influence the short-term outcomes of patients who underwent total gastrectomy.
Combined proton radiography and irradiation for high-precision preclinical studies in small animals
Authors: Schneider Moritz , Bodenstein Elisabeth , Bock Johanna , Dietrich Antje , Gantz Sebastian , Heuchel Lena , Krause Mechthild , Lühr Armin , von Neubeck Cläre , Nexhipi Sindi , Schürer Michael , Tillner Falk , Beyreuther Elke , Suckert Theresa , Müller Johannes Richard
Published: August 2022

Background and purpose

Proton therapy has become a popular treatment modality in the field of radiooncology due to higher spatial dose conformity compared to conventional radiotherapy, which holds the potential to spare normal tissue. Nevertheless, unresolved research questions, such as the much debated relative biological effectiveness (RBE) of protons, call for preclinical research, especially regarding in vivo studies. To mimic clinical workflows, high-precision small animal irradiation setups with image-guidance are needed.

Material and methods

A preclinical experimental setup for small animal brain irradiation using proton radiographies was established to perform planning, repositioning, and irradiation of mice. The image quality of proton radiographies was optimized regarding the resolution, contrast-to-noise ratio (CNR), and minimal dose deposition in the animal. Subsequently, proof-of-concept histological analysis was conducted by staining for DNA double-strand breaks that were then correlated to the delivered dose.

Results

The developed setup and workflow allow precise brain irradiation with a lateral target positioning accuracy of<0.26mm for in vivo experiments at minimal imaging dose of<23mGy per mouse. The custom-made software for image registration enables the fast and precise animal positioning at the beam with low observer-variability. DNA damage staining validated the successful positioning and irradiation of the mouse hippocampus.

Conclusion

Proton radiography enables fast and effective high-precision lateral alignment of proton beam and target volume in mouse irradiation experiments with limited dose exposure. In the future, this will enable irradiation of larger animal cohorts as well as fractionated proton irradiation.
Myricitrin inhibits fibroblast-like synoviocyte-mediated rheumatoid synovial inflammation and joint destruction by targeting AIM2
Authors: Shen Chuyu , Xu Meilin , Xu Siqi , Zhang Shuoyang , Lin Wei , Li Hao , Zeng Shan , Qiu Qian , Liang Liuqin , Xiao Youjun , Xu Hanshi
Published: August 2022

Objective: To explore the effect and underlying mechanism of Myricitrin (Myr) in regulating fibroblast-like synoviocyte (FLS)-mediated synovitis and joint destruction in RA.

Methods: FLSs were isolated from synovial tissues from patients with RA. Gene expression was measured using quantitative RT-qPCR. Protein expression was detected by immunohistochemistry or Western blot. Cell apoptosis was performed by an Annexin-PI staining assay. EdU incorporation was used to assess the proliferation of RA FLS. Transwell assay was used to characterize the cell migration and invasion ability of RA FLS. The potential target of Myr was identified by RNA sequencing analysis. The in vivo effect of Myr was assessed in a collagen-induced arthritis (CIA) model.

Results: Myr treatment inhibited the lamellipodia formation, migration, and invasion, but not the apoptosis and proliferation, of RA FLSs. Myr also reduced the expression of CCL2, IL-6, IL-8, MMP-1, MMP-3, and MMP-13 induced by TNF-α. The RNA-seq results indicated that AIM2 may be a target gene of Myr in RA FLSs. Furthermore, compared to healthy controls, AIM2 expression showed higher levels in synovial tissues and FLSs from RA patients. AIM2 knockdown also inhibited RA FLS migration, invasion, cytokine, and MMP expression. In addition, either Myr treatment or AIM2 knockdown reduced the phosphorylation of AKT induced by TNF-α stimulation. Importantly, Myr administration relieved arthritis symptoms and inhibited AIM2 expression in the synovium of CIA mice.

Conclusion: Our results indicate that Myr exerts an anti-inflammatory and anti-invasion effect in RA FLSs and provide evidence of the therapeutic potential of Myr for RA.
Preclinical evidence and possible mechanisms of β-asarone for rats and mice with Alzheimer’s disease: A systematic review and meta-analysis
Authors: Du Xin-Yuan , Cao Yu-Shuang , Yang Juan , Guo Li-Chen , Zhang Tong , Yuan Qing , Chen Xi , Hu Li-min
Published: August 2022

Background: Currently, there are many different drugs to improve Alzheimer’s disease (AD) from different pathways. As a supplement and alternative medicine, traditional Chinese medicine (TCM) targets multiple pathways which may be different from classical Western medicine, which may be orchestrated with Western medicine to materialize multiplying efficacy in AD patients.

Objective: To investigate the therapeutic effect and assess the available preclinical evidence and possible mechanisms of β-asarone which was extracted from Acorus gramineus Soland (Araceae, AGS) for AD based on rat and mouse animal models.

Methods: PubMed, Embase, Scopus, Cochrane Library, BIOSIS Previews, Web of Science, EBSCO, and Google Scholar were searched from inception to 5 May 2022. Rat and mouse experiments assessing the therapeutic effects of β-asarone for AD were included. Primary outcomes were neuroethology, including escape latency and times of crossing platform. Second outcomes were cell apoptosis, including Bax and Bcl-2. The weighted mean difference (WMD) was generated for continuous variables. The relative outcomes were analyzed with the aid of Get Data Graph Digitizer 2.26 and software STATA version 16.0 MP.

Results: For the primary endpoint, compared with the modeling group, β-asarone significantly decreased the escape latency (WMD = -12.61, 95% CI: -18.66 to -6.57) and increased the times of crossing platform (WMD = 1.50, 95% CI: 0.31–2.70). For the secondary endpoint, β-asarone remarkably reduced the relative expression of the amyloid precursor protein (APP) (WMD = −2.25, 95% CI: −2.49 to −2.01), decreased the expression of the apoptosis-related protein, associated X protein (Bax) (WMD = −2.40, 95% CI: −3.51 to −1.29), lowered the expression of apoptosis-related protein, B-cell lymphoma-2 (Bcl-2) (WMD = 0.42, 95% CI: 0.38–0.46), and decreased the signal pathway-related proteins, phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) (WMD = −0.70, 95% CI: −0.93 to −0.47) over the control group.

Conclusion: β-asarone spectacularly improved the learning ability and memory in rats and mice, which might be correlated with its potential neuroprotective effect through multiple signaling pathways.
Trends in orphan drug use and spending among children and adolescents during 2010–2020 in Korea
Authors: Oh Jung Yeon , Lee Jin Yong , Kim Dong-Sook
Published: August 2022

Background: Since 2014 in Korea, the Ministry of Food and Drug Safety has designated orphan drugs (ODs) for the treatment of rare diseases. This study investigated the market share and 20 most frequently prescribed therapeutic subgroups of ODs among children and adolescents in Korea.

Methods: This study referenced the Korean national health insurance database from January 2010 through December 2020. The outcome measures were the number of prescriptions and expenditures on ODs.

Results: Among children aged 0–12 years, the number of patients using ODs increased from 11,264 in 2010 to 14,017 in 2020. Expenditures on ODs and their proportion of total pharmaceutical expenditures also tripled from 13.3 million USD (1.2%) in 2010 to 46.4 million USD (6.2%) in 2020. Among the overall population and adolescents aged 13–17 years, the percentage of total pharmaceutical expenditures for ODs increased from 0.4% in 2010 to 3.2% in 2020 and from 2.1% in 2010 to 11.2% in 2020, respectively. The highest numbers and drug costs of child patients were for H01 (pituitary and hypothalamic hormones and analogues, 44,839) and A16 (other alimentary tract and metabolism products, 160 million USD). The individual ODs with the highest drug costs were A16AB09 (idursulfase, 82.4 million USD) and M09AX07 (nusinersen, 36.2 million USD).

Conclusion: Although the market size of ODs remained small in Korea, both the number of approved ODs and the proportion of total pharmaceutical expenditures for ODs have increased. Additional policies related to designation and reimbursement should be put in place to ensure timely access to ODs.
Metastructure with integrated internal oscillators of constant, linearly and nonlinearly varying natural frequency
Authors: Kovacic Ivana , Rakaric Zvonko , Kanovic Zeljko , Rajs Vladimir
Published: August 2022

This research focuses on the analysis of the model and performance of lightweight metastructures encompassing a distributed array of internal homogenous oscillators, integrated into the host structure to create a single-piece element. This metastructure performs longitudinal vibrations, whose axis is colinear with the direction of the transverse vibration of the internal oscillators. First, the mechanical models of the separate elements of the metastructure and the metastructure as a whole are created and considered. The first modal frequencies of longitudinal vibrations of the metastructure with blocked and free internal oscillators are tuned to the first modal frequency of transverse vibration of one internal oscillator, yielding the optimal number of internal oscillators for this to be achieved, which is a new result for the proposed design. This theoretical result is then checked experimentally with the metastructures produced by 3D printing technology, comprising a different number of internal oscillators, all of which have the same natural frequency. Besides validating the theoretical results, experimental investigations with blocked and freely vibrating internal oscillators of the constant natural frequency are used to explore other performance characteristics, such as the width of the regions where the reduced amplitude is achieved. Finally, based on the theoretical and additional numerical results, the internal oscillators are modified in two ways, which is an original approach: their natural frequency is increased linearly and nonlinearly along the metastructure in accordance with the previous new theoretical results. The benefits of such new redesigns for the multi-modal performance characteristics of the metastructure are discussed.
Large scale text mining for deriving useful insights: A case study focused on microbiome
Authors: Ahmed Syed Ashif Jardary Al , Bapatdhar Nishad , Kumar Bipin Pradeep , Ghosh Samik , Yachie Ayako , Palaniappan Sucheendra K.
Published: August 2022

Text mining has been shown to be an auxiliary but key driver for modeling, data harmonization, and interpretation in bio-medicine. Scientific literature holds a wealth of information and embodies cumulative knowledge and remains the core basis on which mechanistic pathways, molecular databases, and models are built and refined. Text mining provides the necessary tools to automatically harness the potential of text. In this study, we show the potential of large-scale text mining for deriving novel insights, with a focus on the growing field of microbiome. We first collected the complete set of abstracts relevant to the microbiome from PubMed and used our text mining and intelligence platform Taxila for analysis. We drive the usefulness of text mining using two case studies. First, we analyze the geographical distribution of research and study locations for the field of microbiome by extracting geo mentions from text. Using this analysis, we were able to draw useful insights on the state of research in microbiome w. r.t geographical distributions and economic drivers. Next, to understand the relationships between diseases, microbiome, and food which are central to the field, we construct semantic relationship networks between these different concepts central to the field of microbiome. We show how such networks can be useful to derive useful insight with no prior knowledge encoded.
LEAFY COTYLEDONs: Connecting different stages of plant development
Authors: Chen Chen , Du Xinglin
Published: August 2022

The life of higher plants progresses successively through embryonic, juvenile, adult, and reproductive stages. LEAFY COTYLEDON (LEC) transcription factors, first discovered in Arabidopsis thaliana several decades ago, play a key role in regulating plant embryonic development, seed maturation, and subsequent growth. Existing studies have demonstrated that LECs together with other transcription factors form a huge and complex regulatory network to regulate many aspects of plant growth and development and respond to environmental stresses. Here, we focus on the role that has received little attention about the LECs linking different developmental stages and generational cycles in plants. We summarize the current fragmented research progress on the LECs role and molecular mechanism in connecting embryonic and vegetative growth periods and the reproductive stage. Furthermore, the possibility of LECs controlling the maintenance and transition of plant growth stages through epigenetic modifications is discussed.
Differential influence of cortex and stele components on root tip diameter in different types of tropical climbing plants
Authors: Xu Haiwu , Wang Siyuan , Tang Liang , Wang Yan , Li Zhongyue , Wang Wenna
Published: August 2022

Climbing plants are an abundant and taxonomically diverse plant group that competes intensely with trees and thus substantially affects forest diversity and structure. The growth and physiology of climbing plants largely depend on their root tip structure and function. However, little is known regarding the mechanisms through which anatomical traits regulate root tip diameter in climbing plants. Therefore, our study sought to explore the relationships between root tip diameter and seven anatomical traits (e.g., cortex thickness and stele diameter) in three lianas and three vine species sampled from a tropical forest in Hainan. Root tip diameter was significantly positively correlated with cortex thickness (r = 0.94–0.99) and stele diameter (r = 0.72–0.94) within species, especially with cortex thickness. Cortex thickness was significantly positively correlated with mean cortical cell diameter in six species (r = 0.72–0.93), but was only correlated with the number of cortical cell layers in three species (r = 0.42–0.66). Stele diameter displayed significant positive correlations with mean conduit diameter (r = 0.58–0.88) and the number of conduits per stele (r = 0.50–0.66, except for Cyclea hypoglauca), and was negatively correlated with conduit density in all species (r = −0.65 to –0.77). The correlations between cortical cells and conduit traits and root tip diameter were similar to that with cortex thickness and stele diameter, respectively. Compared with vines, liana root tips showed closer relationships between root diameter and cortex thickness and stele diameter, and between cortex thickness and mean diameter of cortical cells. Moreover, the root tip of lianas possesses significantly higher stele proportion and denser conduits, significantly lower cortex proportion, and smaller conduit size than those of vines. However, the specific conductivity was similar. Overall, these results suggest that the cortex is the main driver for the change in root tip diameter rather than the stele. Nevertheless, both factors were responsible for variations in diameter-related traits when compared with number-related traits, with lianas and vines exhibiting distinct regulatory mechanisms.
Transcriptome analysis of tea (Camellia sinensis) leaves in response to ammonium starvation and recovery
Authors: Wang Yu , Ouyang Jia-Xue , Fan Dong-Mei , Wang Shu-Mao , Xuan Yi-Min , Wang Xiao-Chang , Zheng Xin-Qiang
Published: August 2022

The tea plant is a kind of ammonium-preferring crop, but the mechanism whereby ammonium (NH4+) regulate its growth is not well understood. The current study focused on the effects of NH4+ on tea plants. Transcriptomic analysis was performed to investigate the early- and late-stage NH4+ deprivation and resupply in tea plants shoots. Through short- and long-term NH4+ deficiency, the dynamic response to NH4+ stress was investigated. The most significant effects of NH4+ deficiency were found to be on photosynthesis and gene ontology (GO) enrichment varied with the length of NH4+ deprivation. Enriched KEGG pathways were also different when NH4+ was resupplied at different concentrations which may indicate reasons for tolerance of high NH4+ concentration. Using weighted gene co-expression network analysis (WGCNA), modules related to significant tea components, tea polyphenols and free amino acids, were identified. Hence, NH4+ could be regarded as a signaling molecule with the response of catechins shown to be higher than that of amino acids. The current work represents a comprehensive transcriptomic analysis of plant responses to NH4+ and reveals many potential genes regulated by NH4+ in tea plants. Such findings may lead to improvements in nitrogen efficiency of tea plants.
Applications and prospects of genome editing in plant fatty acid and triacylglycerol biosynthesis
Authors: Park Mid-Eum , Kim Hyun Uk
Published: August 2022

Triacylglycerol (TAG), which is a neutral lipid, has a structure in which three molecules of fatty acid (FA) are ester-bonded to one molecule of glycerol. TAG is important energy source for seed germination and seedling development in plants. Depending on the FA composition of the TAG, it is used as an edible oil or industrial material for cosmetics, soap, and lubricant. As the demand for plant oil is rising worldwide, either the type of FA must be changed or the total oil content of various plants must be increased. In this review, we discuss the regulation of FA metabolism by Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9, a recent genome-editing technology applicable to various plants. The development of plants with higher levels of oleic acid or lower levels of very long-chain fatty acids (VLCFAs) in seeds are discussed. In addition, the current status of research on acyltransferases, phospholipases, TAG lipases, and TAG synthesis in vegetative tissues is described. Finally, strategies for the application of CRISPR/Cas9 in lipid metabolism studies are mentioned.
Analysis of internal processes of conflict behavior among Iranian rangeland exploiters: Application of environmental psychology
Authors: Haji Latif , Hayati Dariush
Published: August 2022

Conflicts over rangeland exploitation have been a serious challenge in Iran, rooted in human behavior. Accordingly, this study aimed to provide a comprehensive theoretical framework in the field of analyzing conflict behavior among rangeland exploiters. This research is a descriptive-correlational and causal-relational study conducted using a cross-sectional survey. The statistical population of the study was rangeland exploiters in one of the northwest provinces of Iran (N= 66,867) of whom 384 people were selected as a sample and stratified random sampling method with proportional assignment. The research instrument was a questionnaire, the validity of which was confirmed by a panel of academic experts and the reliability of its items was verified using Cronbach’s alpha coefficient. The results showed that the variables of personal norms (PN) and the perceived behavioral control were able to predict 25.9% of the variance in terms of the conflicting behavior of rangeland exploiters; besides, ascription of responsibility, PN, perceived behavioral control, and awareness of consequences, which have been proposed as activators of PN, were able to explain a significant percentage (63.5%) of the variance in terms of PN. Furthermore, analysis of the effects of environmental and cultural values showed that conflict behaviors of exploiters were mostly affected by their underlying values. Generally, the results of this study would help in the development of more integrated and comprehensive models in the field of exploiters’ conflict behavior. Eventually, to change and improve the environmental behavior of exploiters to better management of conflict in rangelands, providing a list of considerations and competencies for agricultural extension and education, this article comes to the end.
Improving consumer stickiness in livestream e-commerce: A mixed-methods study
Authors: Shen Lihong , Zhang Yuning , Fan Ying , Chen Yiduo , Zhao Yi
Published: August 2022

With the continuous development and improvement of Internet media technologies in China, the influence of livestream e-commerce is becoming increasingly prominent, and an increasing number of people are engaging in consumption activities in this field. It is important to study consumer stickiness in livestream e-commerce to promote economic structure adjustment and innovation-driven development. Therefore, in this study, we adopted the expectation confirmation theory (ECT) as the theoretical framework and analyzed the ECT and stickiness. The study considered satisfaction as the previous influencing factor of user and consumer stickiness, replaced the continuance intention in the expectation confirmation model with consumer stickiness as the explanatory variable, introduced the variable of perceived playfulness as the value perception after user experience, and established a consumer stickiness factors model. A total of 262 valid questionnaires were collected in this study, and SmartPLS analysis along with interviews were used to justify the limitations of data analysis. The results of the study demonstrated a significant effect of perceived usefulness and confirmation on satisfaction, a significant effect of confirmation on perceived usefulness, a significant effect of satisfaction on stickiness, and a significant effect of confirmation on perceived playfulness. Based on findings from the data analysis and interviews, we further proposed rationalized recommendations, and aimed to provide some theoretical guidance for future research on live streaming.
Mental health problems among healthcare professionals following the workplace violence issue-mediating effect of risk perception
Authors: Zhong Deping , Liu Chengcheng , Luan Chunna , Li Wei , Cui Jiuwei , Shi Hanping , Zhang Qiang
Published: August 2022

Although there have been numerous studies on mental wellbeing impairment or other negative consequences of Workplace Violence (WPV) against healthcare professionals, however, the effects of WPV are not limited to those who experience WPV in person, but those who exposed to WPV information indirectly. In the aftermath of “death of Dr. Yang Wen,” a cross-sectional study was conducted to explore the psychological status of healthcare professionals. A total of 965 healthcare professionals from 32 provinces in China participated in our research. The prevalence rates of Post-Traumatic Stress Disorder (PTSD) symptoms, depression, anxiety among healthcare professional in the current study were 25.60, 46.01, and 27.88%, respectively. Moreover, our research suggested that the awareness of WPV-incident had a significant association with PTSD symptoms. In addition, risk perception was shown to mediate the effect of WPV awareness on PTSD symptoms. Furthermore, the present research also found a U-shaped relationship between issue salience and PTSD symptoms, and the relationship between issue salience and anxiety, indicating that higher awareness of WPV issue was negatively related to mental health status (including PTSD and anxiety) but only to the points at which there were no additional effects of more issue salience. This study highlighted that more protective measures for healthcare professionals need to be implemented in response to potential WPV events. More importantly, risk perception was found to mediate the effect of WPV issue salience on PTSD symptoms, it is critical to reduce the mental health burden through intervening in risk perception.