bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circular RNA hsa_circ_0001874 is an indicator for gastric cancer
Authors: Ye Qihua , Qi Changlei , Xi Mengting , Ye Guoliang 
Published: May 2021

AbstractBackgroundRecent studies have indicated that circular RNAs (circRNAs) are novel endogenous RNAs whose 5′ and 3′ ends are covalently linked and play critical roles in gastric carcinogenesis. However, the significance of circRNA hsa_circ_0001874 in gastric cancer (GC) is still unclear.MethodsTherefore, we first detected hsa_circ_0001874 levels in GC cell lines and tissues and analyzed their potential correlation with clinicopathological factors. Then, a receiver operating characteristic (ROC) curve was established to evaluate its clinical value. Finally, we further predicted the biological functions of this molecule by bioinformatics analysis.ResultsOur data showed that as an indicator, hsa_circ_0001874 expression was significantly decreased in 78.02% (71/91) of the GC patients. Combined with clinicopathological factors, the hsa_circ_0001874 level was strongly associated with cell differentiation (p < 0.001), tumor stage (p = 0.005), invasion (p = 0.024), lymphatic metastasis (p = 0.023), and CEA level (p < 0.001) in GC tissues. The area under the curve (AUC) was up to 0.673, with a sensitivity and specificity of 61.54% and 68.13%, respectively. Bioinformatics analysis showed that hsa_circ_0001874 harbors miR‐593‐5p, miR‐103a‐3p, and miR‐107 seed sequences to regulate these three miRNAs and downstream target genes and exert its various biological functions in the carcinogenesis and progression of GC.ConclusionIn summary, these data suggest that hsa_circ_0001874 is an indicator of GC and plays a significant role in gastric carcinogenesis and progression.
Effect of necrotrophic fungus and PGPR on the comparative histochemistry of Vigna radiata by using multiple microscopic techniques
Authors: Javed Sidra , Javaid Arshad , Hanif Uzma , Bahadur Saraj , Sultana Shazia , Shuaib Muhammad , Ali Sajjad 
Published: May 2021

AbstractRapid advances in the field of pathogen detection have opened new opportunities and better understanding for their management approaches. Aim of this study was to elucidate histopathological observations of different tissues affected by Macrophomina phaseolina and to observe the defense responses of plant growth promoting rhizobacteria (PGPR) in mungbean plants. Sections of the stem and root were prepared and stained with ferric chloride, Lugol's iodine and Wiesner's reagent and were then observed under multiple microscopic techniques. Results revealed that both pathogen and PGPR produce responses on the plant that include colonization of xylem vessels by hyphae and sclerotia, hypertrophy and hyperplasia of the cells, destruction of xylem fibers and amyloplasts in parenchymatous cells; and production of gels by the plant were observed. There was a significant increase in lignin and phenolic compounds deposition in stem and root sections of PGPR treated and non‐treated mungbean plants. Whereas the soil amended with PGPR showed very less to no starch production. Moreover, production of gels and gums were also observed in both stem and root sections. Compared to light microscopy, scanning electron microscope provided greater depth of focus and resolution of the pathogen attack on plant tissues, associated bacteria. As a whole, the data demonstrated that inoculation of PGPR can be an effective strategy to stimulate plant growth and they could significantly activate disease resistance against M. phaseolina.
Acetyl-CoA carboxylase-1/2 blockade locks dendritic cells in the semimature state associated with FA deprivation by favoring FAO
Authors: Nguyen-Phuong Thuy , Chung Hyunwoo , Jang Jiyun , Kim Jung-Sik , Park Chung-Gyu 
Published: May 2021

AbstractImmunometabolism is rising as an intriguing topic that reveals the connection between immune cell function and metabolic processes. Especially, fatty acid metabolism plays an essential role in the dendritic cells (DCs) during the differentiation and maturation period. We questioned whether regulation of acetyl-CoA carboxylases 1 and 2-(ACC1/2), the core enzymes of fatty acid synthesis (FAS), would control DC function. Here, we report that blocking ACC1/2 to prevent FAS during DC maturation switched their cellular metabolism into fatty acid oxidation to fuel oxidative phosphorylation. This action turned DCs to utilize exogenous fatty acids to sustain their basal energy demand and maintain a stable cellular respiration rate. Coincidentally, under the ACC1/2 inhibitor treatment, LPS-treated DCs exhibited a semimaturation phenotype with a maturation-resistance feature, with decreased expression of costimulatory molecules including CD86 and CD40, along with the reduction of IL-12 and IL-6. The migratory capability of DCs has been known to relate to the glycolysis pathway, and here we showed that the ACC1/2 blockade did not affect the expression of CCR7 and DC migration. Furthermore, we found that under the ACC1/2 blocking condition, DCs pulsed with OVA failed to activate OVA-specific CD4+ T cell proliferation even though their antigen uptake capacity was intact. Together, our data suggest ACC1/2 as a promising target to control DC fate.
GABAergic signaling in human and murine NK cells upon challenge withToxoplasma gondii
Authors: Bhandage Amol K , Friedrich Laura M , Kanatani Sachie , Jakobsson-Björkén Simon , Escrig-Larena J Ignacio , Wagner Arnika K , Chambers Benedict J , Barragan Antonio 
Published: May 2021

AbstractProtective cytotoxic and proinflammatory cytokine responses by NK cells impact the outcome of infections by Toxoplasma gondii, a common parasite in humans and other vertebrates. However, T. gondii can also sequester within NK cells and downmodulate their effector functions. Recently, the implication of GABA signaling in infection and inflammation-related responses of mononuclear phagocytes and T cells has become evident. Yet, the role of GABAergic signaling in NK cells has remained unknown. Here, we report that human and murine NK cells synthesize and secrete GABA in response to infection challenge. Parasitized NK cells secreted GABA, whereas activation stimuli, such as IL-12/IL-18 or parasite lysates, failed to induce GABA secretion. GABA secretion by NK cells was associated to a transcriptional up-regulation of GABA synthesis enzymes (glutamate decarboxylases [GAD65/67]) and was abrogated by GAD inhibition. Further, NK cells expressed GABA-A receptor subunits and GABA signaling regulators, with transcriptional modulations taking place upon challenge with T. gondii. Exogenous GABA and GABA-containing supernatants from parasitized dendritic cells (DCs) impacted NK cell function by reducing the degranulation and cytotoxicity of NK cells. Conversely, GABA-containing supernatants from NK cells enhanced the migratory responses of parasitized DCs. This enhanced DC migration was abolished by GABA-A receptor antagonism or GAD inhibition and was reconstituted by exogenous GABA. Jointly, the data show that NK cells are GABAergic cells and that GABA hampers NK cell cytotoxicity in vitro. We hypothesize that GABA secreted by parasitized immune cells modulates the immune responses to T. gondii infection.
Densely connected U‐Net retinal vessel segmentation algorithm based on multi‐scale feature convolution extraction
Authors: Du Xinfeng , Wang Jiesheng , Sun Weizhen 
Published: May 2021

PurposeThe segmentation results of retinal blood vessels have a significant impact on the automatic diagnosis of various ophthalmic diseases. In order to further improve the segmentation accuracy of retinal vessels, we propose an improved algorithm based on multiscale vessel detection, which extracts features through densely connected networks and reuses features.MethodsA parallel fusion and serial embedding multiscale feature dense connection U‐Net structure are designed. In the parallel fusion method, features of the input images are extracted for Inception multiscale convolution and dense block convolution, respectively, and then the features are fused and input into the subsequent network. In serial embedding mode, the Inception multiscale convolution structure is embedded in the dense connection network module, and then the dense connection structure is used to replace the classical convolution block in the U‐Net network encoder part, so as to achieve multiscale feature extraction and efficient utilization of complex structure vessels and thereby improve the network segmentation performance.ResultsThe experimental analysis on the standard DRIVE and CHASE_DB1 databases shows that the sensitivity, specificity, accuracy, and AUC of the parallel fusion and serial embedding methods reach 0.7854, 0.9813, 0.9563, 0.9794; 0.7876, 0.9811, 0.9565, 0.9793 and 0.8110, 0.9737, 0.9547, 0.9667; 0.8113, 0.9717, 0.9574, 0.9750, respectively.ConclusionsThe experimental results show that multiscale feature detection and feature dense connection can effectively enhance the network model's ability to detect blood vessels and improve the network segmentation performance, which is superior to U‐Net algorithm and some mainstream retinal blood vessel segmentation algorithms at present.
A systematic review of the effectiveness of Pilates on pain, disability, physical function, and quality of life in older adults with chronic musculoskeletal conditions
Authors: Denham‐Jones Laura , Gaskell Lynne , Spence Nicola , Pigott Tim 
Published: May 2021

AbstractObjectivesThis systematic review aims to evaluate the effectiveness and delivery of Pilates to reduce pain and disability and to improve physical function and quality of life in middle‐aged to older adults with a range of chronic musculoskeletal conditions.MethodsSearches were conducted using CENTRAL, CINAHL, SCOPUS, Pubmed, PsycInfo, Web of Science Core Collection and Google Scholar. Inclusion criteria were controlled trials and observational studies, population mean age 50 years and over with chronic musculoskeletal conditions, using mat‐based Pilates exercise. Outcomes included pain, disability, physical function and quality of life.ResultsSeven studies were included, with a combined total sample of 397 participants (73% female). Pilates was significantly effective (p ≤ 0.05) for reducing back pain, neck pain and pain associated with knee osteoarthritis and osteoporosis. Additional significant disability, physical functioning and quality of life effects were found for back pain, osteoporosis, and knee OA. Overall Pilates was as effective as other exercise. Adherence to group exercise was good, but poor for home exercise. No significant adverse effects were reported.ConclusionPilates is a safe and effective exercise intervention for adults over 50 with a diverse range of musculoskeletal conditions which may otherwise put them at risk of becoming sedentary. Although no overall significant superiority was found over other exercise, participants reported psychosocial benefits particular to the Pilates group exercise, with enjoyment a possible positive factor in adherence. Further research on Pilates exercises for various pathologies could inform teaching and improve engagement with older adults, including those with chronic conditions.
A complex variable solution for a non‐circular tunnel in an elastic half‐plane
Authors: Lu Ai‐zhong , Zeng Gui‐sen , Zhang Ning 
Published: May 2021

AbstractAn analytical solution for a non‐circular tunnel excavated in an elastic homogeneous half‐plane is obtained, which considers gravity and different lateral pressure coefficients. The solution is deduced using the complex variable method, mapping the region containing a non‐circular tunnel onto a circular ring. The basic equations for the analytic functions are established using the stress boundary conditions at the ground surface and the edges of the tunnel and the analytical functions are solved by the power series method. In the process of solving, the Fourier series was used. To elaborate the solution process clearly and verify the correctness of the solution, a shallow quasi‐ellipse tunnel was analyzed as a computational example, and the results obtained using the presented analytical method are compared with that obtained by the numerical software ANSYS.
A systematic review on distributed denial of service attack defense mechanisms in programmable networks
Authors: Dalmazo Bruno L. , Marques Jonatas A. , Costa Lucas R. , Bonfim Michel S. , Carvalho Ranyelson N. , da Silva Anderson S. , Fernandes Stenio , Bordim Jacir L. , Alchieri Eduardo , Schaeffer‐Filho Alberto , Paschoal Gaspary Luciano , Cordeiro Weverton 
Published: May 2021

SummaryDesign flaws and vulnerabilities inherent to network protocols, devices, and services make Distributed Denial of Service (DDoS) a persisting threat in the cyberspace, despite decades of research efforts in the area. The historical vertical integration of traditional IP networks limited the solution space, forcing researchers to tweak network protocols while maintaining global compatibility and proper service to legitimate flows. The advent of Software‐Defined Networking (SDN) and advances in Programmable Data Planes (PDP) changed the state of affairs and brought novel possibilities to deal with such attacks. In summary, the ability of bringing together network intelligence to a control plane, and offloading flow processing tasks to the forwarding plane, opened up interesting opportunities for network security researchers unlike ever. In this article, we dive into recent research that relies on SDN and PDP to detect, mitigate, and prevent DDoS attacks. Our literature review takes into account the SDN layered view as defined in RFC7426 and focuses on the data, control, and application planes. We follow a systematic methodology to capture related articles and organize them into a taxonomy of DDoS defense mechanisms focusing on three facets: activity level, deployment location, and cooperation degree. From the analysis of existing work, we also highlight key research gaps that may foster future research in the field.
Metabolomic Profiles of Shift Workers and Day Workers: A Cross‐Sectional Study
Authors: Huang Xinru , Chen Xiaoyi , Zhao Shiyu , Hou Jiaojiao , Huang Li , Xu Jie , Wang Wei , He Mengting , Shen Ouxi , Zhang Jie 
Published: May 2021

ObjectiveThe purpose of this study was to characterize the metabolomic profiles of shift workers and day workers and to discover the effect of shift work on workers’ metabolic health.MethodsA total of 824 participants aged 25 to 55 years were recruited, and 485 (275 shift workers and 210 day workers) completed the study. The mean age of the shift workers was 37.32 (5.53) years old, and that of day workers was 36.50 (7.83) years old. Serum and salivary samples were collected for the detection of key biochemical indicators (melatonin, cholesterol, and low‐density lipoprotein cholesterol) and for metabolome profile analyses.ResultsCompared with female day workers, female shift workers had a higher BMI, waist circumference, and hip circumference. Correspondingly, we identified 76 significant metabolites (false discovery rate < 0.05) in shift workers, including L‐tryptophan, acylcarnitines, and several fatty acids. Three pathways that presented significant differences were biosynthesis of unsaturated fatty acids, linoleic acid metabolism, and ubiquinone and other terpenoid‐quinone biosynthesis.ConclusionsCompared with day workers, shift workers were more prone to weight gain and central obesity and were at a higher risk for impaired lipid metabolism with disrupted circadian rhythms.
The Rapidly Evolving Landscape of First-Line Targeted Therapy in Metastatic Urothelial Cancer: A Systematic Review
Authors: Lavoie Jean-Michel , Sridhar Srikala S. , Ong Michael , North Scott , Alimohamed Nimira , McLeod Deanna , Eigl Bernhard J. 
Published: May 2021

Abstract

Background
Metastatic urothelial carcinoma (mUC) historically is treated with first-line platinum-based combination chemotherapy, preferably cisplatin plus gemcitabine whenever possible. In recent years, multiple classes of targeted therapy have demonstrated benefit, with some receiving approval in mUC. This review will summarize phase III efficacy and safety data for targeted agents, principally immune checkpoint inhibitors (ICIs), as either first-line or first-line switch-maintenance therapy for mUC and interpret these findings in the context of the current treatment landscape.

Materials and Methods
Published and presented phase III data on targeted therapy for the first-line or first-line switch-maintenance treatment of mUC were identified using the key search terms “targeted therapy” AND “urothelial carcinoma” AND “advanced” OR respective aliases according to the guidelines for Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).

Results
Of the six eligible phase III targeted therapy trials, two assessing ICIs met their primary endpoints in platinum-eligible patients. First-line ICI plus chemotherapy combinations have not improved overall survival (OS), although final OS results of the IMVigor 130 trial are pending. Switch-maintenance using an ICI in patients achieving at least stable disease following platinum-based chemotherapy statistically significantly improved OS (21.4 vs. 14.3 months, hazard ratio, 0.69; 95% confidence interval, 0.56–0.86; p = .001). Current sequencing options for mUC include first-line platinum-based chemotherapy with a switch to ICI either immediately or upon disease progression.

Conclusion
Recent targeted therapy trials have expanded ICI sequencing options for mUC. The treatment landscape is likely to evolve rapidly, with results from multiple phase III trials expected in the next 5 years.

Implications for Practice
Multiple classes of targeted agents are approved for use in metastatic urothelial carcinoma (mUC). Six phase III trials have recently provided insight on the benefit of these agents in the first-line setting. In platinum-eligible patients, immune checkpoint inhibitors (ICIs) combined with first-line platinum-based chemotherapy failed to demonstrate improved survival, although ICI monotherapy as switch-maintenance significantly improved overall survival in patients with mUC who had achieved at least stable disease following first-line platinum-based chemotherapy. In patients ineligible for any chemotherapy, pembrolizumab, atezolizumab, or pembrolizumab in combination with enfortumab vedotin may be options.
Dynamic association between perceived conflict and communication behavior in intimate relationships: The moderating effect of traumatic experience
Authors: Liu Xiaoyan , Chen Sicheng , Zhang Qian , Wen Xue , Xu Wei 
Published: May 2021

AbstractMany individuals may face traumatic events throughout their lives. For intimate relationship partners, early traumatic experiences can have a specific effect on their interpersonal communication. This study examined the moderating effect of traumatic experiences at early ages between perceived conflict and communication behavior among individuals in an intimate relationship. A total of 186 college students in intimate relationships reported their perceived conflict and communication behaviors with their partners three times a day for 14 days using ambulatory assessment. Findings from the multilevel model showed that a higher level of perceived conflict significantly positively associated with negative communication and negatively correlated with positive communication at the within‐person level. Traumatic experiences at the between‐person level moderated the within‐person level associations between the dynamic perceived conflict and negative and positive communication behavior. However, the moderating effect of traumatic experiences on the association between perceived conflict and positive communication was contrary to the hypothesis. Daily perceived conflict was associated with daily communication behavior. For those with early traumatic experiences, the relationship between negative communication and conflict was stronger than for those who had not experienced such trauma.
Heat-stable enterotoxin inhibits intestinal stem cell expansion to disrupt the intestinal integrity by downregulating the Wnt/β-catenin pathway
Authors: Zhou Jia-yi , Huang Deng-gui , Gao Chun-qi , Yan Hui-chao , Zou Shi-geng , Wang Xiu-qi 
Published: May 2021

Abstract
Enterotoxigenic Escherichia coli causes severe infectious diarrhea with high morbidity and mortality in newborn and weanling pigs mainly through the production of heat-stable enterotoxins (STs). However, the precise regulatory mechanisms involved in ST-induced intestinal epithelium injury remain unclear. Consequently, we conducted the experiments in vivo (mice), ex vivo (mouse and porcine enteroids), and in vitro (MODE-K and IPEC-J2 cells) to explore the effect of STp (one type of STa) on the integrity of the intestinal epithelium. The results showed that acute STp exposure led to small intestinal edema, disrupted intestinal integrity, induced crypt cell expansion into spheroids, and downregulated Wnt/β-catenin activity in the mice. Following a similar trend, the enteroid-budding efficiency and the expression of Active β-catenin, β-catenin, Lgr5, PCNA, and KRT20 were significantly decreased after STp treatment, as determined ex vivo. In addition, STp inhibited cell proliferation, induced cell apoptosis, destroyed cell barriers, and reduced Wnt/β-catenin activity by downregulating its membrane receptor Frizzled7 (FZD7). In contrast, Wnt/β-catenin reactivation protected the IPEC-J2 cells from STp-induced injury. Taking these findings together, we conclude that STp inhibits intestinal stem cell expansion to disrupt the integrity of the intestinal mucosa through the downregulation of the Wnt/β-catenin signaling pathway.
Robust parameter design of human induced pluripotent stem cell differentiation protocols defines lineage-specific induction of anterior-posterior gut tube endodermal cells
Authors: Yasui Ryota , Sekine Keisuke , Yamaguchi Kiyoshi , Furukawa Yoichi , Taniguchi Hideki 
Published: May 2021

AbstractTissues and cells derived from pluripotent stem cells (PSC) are likely to become widely used in disease modeling, drug screening, and regenerative medicine. For these applications, the in vitro PSC differentiation process must be elaborately investigated and controlled to reliably obtain the desired end products. However, because traditional experimental methods, such as one factor at a time or brute-force approaches, are impractical for detailed screening of complex PSC cultivation conditions, more strategic and effective screening based on statistical design of experiments (DOE) ought to be indispensable. Among various DOE approaches, we regard robust parameter design (RPD) as particularly suited for differentiation protocol optimization due to its suitability for multifactorial screening. We confirmed the adaptability of RPD for investigating human induced PSC lineage specification toward anterior-posterior gut tube endodermal cells and clarified both the contribution of each cell signaling pathway and the effect of cell signaling condition alteration on marker RNA expression levels, while increasing the efficiency of the screening in 243-fold (18 vs 4374) compared with that of a brute-force approach. Specific induction of anterior foregut, hepatic, pancreatic, or mid-hindgut cells was achieved using seven iPSC strains with the optimal culture protocols established on the basis of RPD analysis. RPD has the potential to enable efficient construction and optimization of PSC differentiation protocols, and its use is recommended from fundamental research to mass production of PSC-derived products.