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Composite visualization represents a widely embraced design that combines multiple visual representations to create an integrated view. However, the traditional approach of creating composite visualizations in immersive environments typically occurs asynchronously outside of the immersive space and is carried out by experienced experts. In this work, we aim to empower users to participate in the creation of composite visualization within immersive environments through embodied interactions. This could provide a flexible and fluid experience with immersive visualization and has the potential to facilitate understanding of the relationship between visualization views. We begin with developing a design space of embodied interactions to create various types of composite visualizations with the consideration of data relationships. Drawing inspiration from people's natural experience of manipulating physical objects, we design interactions based on the combination of 3D manipulations in immersive environments. Building upon the design space, we present a series of case studies showcasing the interaction to create different kinds of composite visualizations in virtual reality. Subsequently, we conduct a user study to evaluate the usability of the derived interaction techniques and user experience of creating composite visualizations through embodied interactions. We find that empowering users to participate in composite visualizations through embodied interactions enables them to flexibly leverage different visualization views for understanding and communicating the relationships between different views, which underscores the potential of several future application scenarios.

Data transformation is an essential step in data science. While experts primarily use programming to transform their data, there is an increasing need to support non-programmers with user interface-based tools. With the rapid development in interaction techniques and computing environments, we report our empirical findings about the effects of interaction techniques and environments on performing data transformation tasks. Specifically, we studied the potential benefits of direct interaction and virtual reality (VR) for data transformation. We compared gesture interaction versus a standard WIMP user interface, each on the desktop and in VR. With the tested data and tasks, we found time performance was similar between desktop and VR. Meanwhile, VR demonstrates preliminary evidence to better support provenance and sense-making throughout the data transformation process. Our exploration of performing data transformation in VR also provides initial affirmation for enabling an iterative and fully immersive data science workflow.

Triple-negative breast cancer (TNBC) is currently the type of breast cancer with the worst prognosis; it lacks specific treatments, such as ER/PR antagonistic endocrine and anti-HER2 targeted therapies. Although immunotherapy with immune checkpoints has shown some efficacy in many solid tumors, clinical data in TNBC suggest significant limitations. The essence of ferroptosis is the impaired metabolism of intracellular lipid oxides, which in turn causes the activation and abnormalities of the immune system, including ROS, and not only plays an important role in liver injury and organ aging but also a large amount of data points to the close correlation between the ferroptosis process and tumor development. In this study, through the analysis of large-throughput biological data of breast tumors, combined with the characteristics of the biological process of ferroptosis, the specific gene IDH2 was found to be significantly highly expressed in TNBC and functionally correlated with ferroptosis. Through clinical specimens validated at the gene and protein levels, in vitro tumor cell line validation, and in vivo mouse models, we found that the high expression of IDH2 in TNBC has a role in inhibiting the ferroptosis process in TNBC, thus promoting the proliferation of TNBC cells and other malignant features., (© 2024. The Author(s).)

Context: Anaplastic thyroid cancer (ATC) is a relatively rare and extensively malignant kind of thyroid carcinoma. The poor prognosis and high mortality rate of ATC can be attributed to its invasive features and undifferentiated phenotype. At present, there is a lack of efficacious therapeutic options. In light of the elevated fatality rate, it is vital to possess a comprehensive comprehension of the scientific terrain pertaining to ATC. To gather the perspectives of different researchers about the topic of ATC treatment, we did a bibliometric network analysis, which offers a comprehensive view of the scholarly literature., Methodology: A systematic search was conducted on the WoSCC database to identify publications pertaining to ATC treatment between the years 2000 and 2023. In this bibliometric investigation, the tools VOSviewers, CiteSpace, and the R package "bibliometrix" were employed to investigate the general attributes, developmental framework, and academic frontiers of the subject matter., Results: 1223 publications in total, written by 6937 scholars from 53 areas and 1402 institutions and published in 358 scholarly journals, were analyzed. There has been a gradual increase in the quantity of publications pertaining to ATC treatment. The United States and China emerged as the most prominent nations. The University of Texas MD Anderson Cancer Center and Memorial Sloan Kettering Cancer Counseling Center are prominent research institutions in highly productive countries. The journal Thyroid holds a prominent position within its discipline, being widely recognized as both the most popular and highly co-cited publication. According to the available data, Maria Cabanillas has authored the highest number of published articles, while RC Smallridge has received the highest number of co-citations. It turned out that the prevailing keywords encompassed expression, therapy, apoptosis, survival, activation, proliferation, metastasis, and other related terms. Immunotherapy, targeted therapy, and prognostic factors are the emerging research hotspots and trends., Conclusions: This paper presents a complete overview of research trends and advancements in the treatment of ATC using bibliometric analysis. The acquisition of information will offer vital insights for funding and potential creative strategies in researching the treatment of ATC, which indicates the research frontiers as well as prevalent directions in recent years., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Yan, Yang, Xia and Zhang.)

Testicular macrophages (TM) are critical for the function of the testis by regulating homeostasis and inflammatory responses. However, the mechanisms by which TM fulfil these roles remain elusive. In this study, we explored the impact of two key testicular microenvironmental factors, namely 25-hydroxycholesterol (25HC), an oxysterol related to sex hormones and macrophage colony-stimulating factor (M-CSF), a factor crucial for macrophage survival and differentiation, on the regulation of the TM phenotype. Specifically, we examined their role in controlling the expression of the transcription factor interferon regulatory factor 7 (Irf7), a factor critical for maintaining the alternative macrophage phenotype. To achieve this, we used an in vitro bone marrow-derived macrophage (BMDM) model as a surrogate for TM to investigate the roles of 25HC and M-CSF in regulating the expression of Irf7 during the polarization of murine TM. M-CSF was identified as the main regulator of Irf7 expression, while 25HC production is a consequence of Irf7 activation in BMDM. In turn, 25HC plays a role in a negative feedback loop on the expression levels of Irf7 in BMDM. Using flow cytometry in Irf7 -/- mouse testis the CD64 lo MHC hi TM subpopulation was found to be decreased. Together with lower IL-10 protein levels in Irf7 -/- TM this indicates a shift towards an M1-like macrophage profile. In summary, our data indicates that M-CSF could act as an inducer of high Irf7 expression levels in the mouse testis. However, the exact role of the high 25HC concentration in the testis in maintaining the local immune milieu still needs further study., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sudhanshu Bhushan reports financial support was provided by Deutsche Forschungsgemeinschaft (DFG), Germany. Sudhanshu Bhushan reports a relationship with Deutsche Forschungsgemeinschaft (DFG) that includes: funding grants. Sudhanshu Bhushan has patent Not applicable pending to Not applicable. Not applicable., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Two probe-based quantitative PCR (qPCR) systems, namely P-Xtt and P-Xtu, were developed to diagnose cereal bacterial leaf streak pathogens Xanthomonas translucens pv. translucens and pv. undulosa , respectively. P-Xtt is specific to pv. translucens , and P-Xtu is specific to pv. undulosa , pv. cerealis , pv. secalis , and pv. pistaciae . P-Xtt and P-Xtu worked on all accessible strains of pv. translucens and pv. undulosa , respectively. Both systems could detect 100 copies of the target gBlock DNA. The two systems could be used in both singleplex qPCR and duplex qPCR with similar efficiencies. On genomic DNA from strains of various X. translucens pathovars, both singleplex and duplex qPCR could specifically detect and differentiate pv. translucens and pv. undulosa . The duplex qPCR could detect pv. translucens and pv. undulosa from genomic DNA of 1,000 bacterial cells. On infected barley and wheat grain samples and on one infected wheat leaf sample, the duplex qPCR showed similar efficiency compared to a previously published qPCR system but with the additional capability of pathovar differentiation. The duplex qPCR system developed in this study will be useful in studies on bacterial leaf streak and detection/differentiation of the pathogens., Competing Interests: The author(s) declare no conflict of interest.

Background: Lung ultrasound (LUS) is recommended as a reliable diagnostic alternative to chest X-ray (CXR) for detecting pneumonia in children., Methods: PubMed, Embase, and Cochrane Library databases were used to identify eligible studies from their inception until April 2023. The investigated diagnostic parameters included sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the receiver operating characteristic curves (AUC)., Results: Twenty-six studies involving 3,401 children were selected for meta-analysis. The sensitivity, specificity, PLR, NLR, DOR, and AUC of LUS for detecting pneumonia in children were 0.95, 0.92, 12.31, 0.05, 108.53, and 0.98, respectively, while the sensitivity, specificity, PLR, NLR, DOR, and AUC of CXR were 0.92, 0.93, 24.63, 0.08, 488.54, and 0.99, respectively. The sensitivity of LUS was higher than that of CXR for detecting pneumonia in children (ratio: 1.03; 95% CI: 1.01-1.06; P = 0.018), whereas the DOR of LUS was significantly lower than that of CXR (ratio: 0.22; 95% CI: 0.06-0.85; P = 0.028)., Conclusions: This study found that the diagnostic performance of LUS was comparable to that of CXR for detecting pneumonia, and the sensitivity of LUS was superior to that of CXR., (© 2024. The Author(s).)

Purpose: This study adapted the Chinese version of the Couple Skills Training intervention program to couples of young breast cancer patients in China and investigated its effects on fear of cancer recurrence (FCR), cancer-related communication, and level of hope among the couples., Methods: Ninety young breast cancer patients and their spouses were recruited and randomly assigned to the intervention group (45 couples) and the control group (45 couples). Couples in the intervention group received skills training and were assessed at baseline, post-intervention, and 3 months post-intervention to measure outcomes. Differences in scores between the two groups were analyzed using two-sample t-tests and generalized estimating equations (GEE) controlling for demographic and health-related variables., Results: Couples' skills training intervention effectively reduced FCR and improved cancer-related communication in young breast cancer patients compared to the control group (both p < 0.001). Spouses' expectations significantly increased (p < 0.001). At 3 months post-intervention, couples in the intervention group showed significant improvements in FCR, cancer-related communication, and hope (all p < 0.001)., Conclusion: Couples' skills training interventions are beneficial for helping young breast cancer patients cope with FCR. Couples-based interventions play a crucial role in addressing FCR in these patients and their spouses. Future research should consider larger samples and longer follow-up periods to enhance intervention effectiveness., Clinical Trial Center Registration Number: This study has also been registered with the Chinese Clinical Trial Registry (No: ChiCTR2200063327)., Competing Interests: Declaration of competing interest All authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this study., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Labels are widely used in augmented reality (AR) to display digital information. Ensuring the readability of AR labels requires placing them in an occlusion-free manner while keeping visual links legible, especially when multiple labels exist in the scene. Although existing optimization-based methods, such as force-based methods, are effective in managing AR labels in static scenarios, they often struggle in dynamic scenarios with constantly moving objects. This is due to their focus on generating layouts optimal for the current moment, neglecting future moments and leading to sub-optimal or unstable layouts over time. In this work, we present RL-LABEL, a deep reinforcement learning-based method intended for managing the placement of AR labels in scenarios involving moving objects. RL-LABEL considers both the current and predicted future states of objects and labels, such as positions and velocities, as well as the user's viewpoint, to make informed decisions about label placement. It balances the trade-offs between immediate and long-term objectives. We tested RL-LABEL in simulated AR scenarios on two real-world datasets, showing that it effectively learns the decision-making process for long-term optimization, outperforming two baselines (i.e., no view management and a force-based method) by minimizing label occlusions, line intersections, and label movement distance. Additionally, a user study involving 18 participants indicates that, within our simulated environment, RL-LABEL excels over the baselines in aiding users to identify, compare, and summarize data on labels in dynamic scenes.

Introduction: To compare the overall morbidity and recurrence of papillary thyroid cancer (PTC) after total thyroidectomy (TT) with or without prophylactic central compartment neck dissection (CCND) in cases of both preoperative and intraoperative nonsuspicious central lymph nodes (CLNs)., Methods: A total of 570 PTC patients who harbored no preoperative and intraoperative suspicious CLNs at two institutions were enrolled. They were randomly assigned to TT alone or TT with prophylactic CCND (pCCND) after intraoperative assessment of CLNs during the surgery. Lymph nodes that were hard or large enough to be palpated were regarded as suspicious metastatic lymph nodes during the surgery. The characteristics, postoperative complications, and locoregional recurrence of the two groups were recorded and compared., Results: With a median follow-up of 5 y, the rates of lymph node recurrence in the TT alone and TT with pCCND groups were similar (7.3% versus 4.6%, P = 0.247), but there were significantly higher rates of overall morbidity (6.6% versus 19.1%, P < 0.001) when pCCND was performed., Conclusions: pCCND is not recommended for patients with clinically node-negative PTC preoperatively and intraoperatively because of the high complication rate and lack of benefit of reducing recurrence., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Macrophages are the major type of immune cell in the testis of both humans and rodents. Testicular macrophages (TMs) play critical roles in maintaining the testicular microenvironment, such as Leydig cell-dependent hormone production, spermatogenesis, and immune balance. A substantial number of studies have used rodent models to investigate the functions of TMs with various methods and harvest macrophages from the testis. Studies have demonstrated that enzyme digestion, an essential part of these methods, can improve the number and purity of TMs while unavoidably altering the immunoprofile of macrophages, which is detrimental for further study in terms of immune investigation. Here, we modified the existing method of microglia isolation and set up a novel method without the enzyme digestion step to isolate TMs. According to the characteristics of testicular tissue looseness and the physical and biological characteristics of macrophages, by combining mechanical separation, gradient centrifugation, and immuno-magnetic bead selection, we can effectively avoid the enzymatic digestion of testis tissue and maintain the immune characteristics of macrophages. Additionally, we verified the purity of TM with flow cytometry (FC) at approximately 91-95%, and the production of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) was lower than that isolated with enzyme digestion. In contrast to the traditional method, this novel protocol can assist those who have no convenient access to fluorescence-activated cell sorting (FACS) to isolate a sufficient number of TMs and, most importantly, avoid altering the immunoprofile of TMs without enzyme digestion., Competing Interests: Declaration of Competing Interest We declare that we have no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Two probe-based qPCR systems, namely P-Lb and P-Lm, specific to the canola blackleg pathogens Leptosphaeria biglobosa and L. maculans , respectively, were developed, and their efficiencies were tested. Each of the two systems targets a single-copy gene exclusively present in the corresponding species. The specificities of the two systems on the species level and their ubiquities on the subspecies level were confirmed by in silico sequence analyses and testing on L. biglobosa (17 strains), L. maculans (10 strains), and other plant pathogens (31 species). For sensitivities, the two systems were tested on synthesized DNA fragments (gBlock) of the targeted regions, from which a standard curve was generated for each system. In addition, standard curves were also generated on gBlocks for duplex qPCR in which the two systems were used in the same reaction. The two systems were further tested in both singleplex and duplex qPCR on DNA samples extracted from fungal spores, inoculated canola cotyledons, and naturally infected canola stubble samples collected from commercial fields. Our data indicated that the two systems are specific to L. biglobosa and L. maculans , respectively, and one reaction could detect as few as 200 spores of either species. When used in duplex qPCR on DNA samples with various origins, the two systems generated similar results as in singleplex qPCR. The duplex qPCR system, along with the sample preparation and DNA extraction specified in this study, constituted a first-reported duplex qPCR protocol for detection and quantification of the two blackleg pathogens from field samples., Competing Interests: The author(s) declare no conflict of interest.

Background: Breast cancer (BRCA) has become the most diagnosed cancer worldwide for female and seriously endanger female health. The epithelial-mesenchymal transition (EMT) process is associated with metastasis and drug resistance in BRCA patients. However, the prognostic value of EMT-related lncRNA in BRCA still needs to be revealed. The aim of this study is to construct an EMT-related lncRNA (ERL) signature with accuracy predictive ability for the prognosis of BRCA patients., Methods: RNA-seq expression data and Clinical characteristics obtained from the TCGA (The Cancer Genome Atlas) were used in the study. First, we identified the EMT-related lncRNA by the Pearson correlation analysis. An EMT-related lncRNAs prognostic risk signature was constructed using univariate Cox regression and Lasso-penalized Cox regression analyses. The model's performance was validated using Kaplan-Meier (KM) survival analysis, ROC curve and C-index. Finally, a nomogram was constructed for clinical practice in evaluating the patients with BRCA and validated by calibration curve and decision curve analysis (DCA). We also evaluated the drug sensitivity of signature lncRNA and the tumor immune cell infiltration in breast cancer., Results: We constructed a 10-lncRNA risk score signature based on the lncRNAs associated with the EMT process. We could assign BRCA patients to the high- and low-risk group according to the median risk score. The prognostic risk signature showed excellent accuracy and demonstrated sufficient independence from other clinical characteristics. The immune cell infiltration analysis showed that the prognostic risk signature was related to the infiltration of the immune cell subtype. Drug sensitivity analysis proved ERLs signature could effectively predict the sensitivity of patients to common chemotherapy drugs in BRCA and provide guidance for chemotherapy drugs for high-risk and low-risk patients., Conclusion: Our ERL signature and nomogram have excellent prognostic value and could become reliable tools for clinical guidance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Zheng, Xu, Yuan, Di, Yang, Dong, Hou and Wu.)

Automated pavement crack image segmentation presents a significant challenge due to the difficulty in detecting slender cracks on complex pavement backgrounds, as well as the significant impact of lighting conditions. In this paper, we propose a novel approach for automated pavement crack detection using a multi-scale feature fusion network based on the Transformer architecture, leveraging an encoding-decoding structure. In the encoding phase, the Transformer is leveraged as a substitute for the convolution operation, which utilizes global modeling to enhance feature extraction capabilities and address long-distance dependence. Then, dilated convolution is employed to increase the receptive field of the feature map while maintaining resolution, thereby further improving context information acquisition. In the decoding phase, the linear layer is employed to adjust the length of feature sequence output by different encoder block, and the multi-scale feature map is obtained after dimension conversion. Detailed information of cracks can be restored by fusing multi-scale features, thereby improving the accuracy of crack detection. Our proposed method achieves an F1 score of 70.84% on the Crack500 dataset and 84.50% on the DeepCrack dataset, which are improvements of 1.42% and 2.07% over the state-of-the-art method, respectively. The experimental results show that the proposed method has higher detection accuracy, better generalization and better crack detection results can be obtained under both high and low brightness conditions.

Innate immune signaling in macrophages during viral infection is regulated by ISGylation, the covalent attachment of the ubiquitin-like protein interferon-stimulated gene 15 (ISG15) to protein targets. Here, we explored the role of ISGylation in the macrophage response to infection with Mycobacterium tuberculosis . In human and mouse macrophages, the E3 ubiquitin ligases HERC5 and mHERC6, respectively, mediated the ISGylation of the phosphatase PTEN, which promoted its degradation. The decreased abundance of PTEN led to an increase in the activity of the PI3K-AKT signaling pathway, which stimulated the synthesis of proinflammatory cytokines. Bacterial growth was increased in culture and in vivo when human or mouse macrophages were deficient in the major E3 ISG15 ligase. The findings expand the role of ISGylation in macrophages to antibacterial immunity and suggest that HERC5 signaling may be a candidate target for adjunct host-directed therapy in patients with tuberculosis.

Background: 5-Methylcytosine (m5C) methylation is a major epigenetic RNA modification and is closely related to tumorigenesis in various cancers. This study aimed to explore the prognostic value of m5C-related lncRNAs in breast cancer., Methods: Clinical characteristics and RNA-seq expression data from TCGA (The Cancer Genome Atlas) were used in the study. First, we performed differentially expressed gene (DEG) analysis and constructed a PPI network for the 12 m5C regulators. Then, we identified the m5C-related LncRNAs by the "cor. test." An m5C-related lncRNA prognostic risk signature was developed using univariate Cox regression and Lasso-penalized Cox regression analyses. The model's performance was determined using Kaplan-Meier (KM) survival analysis and ROC curves. Finally, a nomogram was constructed for clinical application in evaluating patients with BRCA. We also researched the drug sensitivity of signature lncRNAs and immune cell infiltration. Finally, we validated the expression of the signature lncRNAs through qRT-PCR in a breast cancer cell line and a breast epithelial cell line., Results: Overall, we constructed an 11-lncRNA risk score signature based on the lncRNAs associated with m5C regulators. According to the median risk score, we divided BRCA patients into high- and low-risk groups. The prognostic risk signature displayed excellent accuracy and demonstrated sufficient independence from other clinical characteristics. The immune cell infiltration analysis showed that the prognostic risk signature was related to the infiltration of immune cell subtypes. Drug sensitivity proved that our prognostic risk signature potentially has therapeutic value., Conclusions: The m5C-related lncRNA signature reliably predicted the prognosis of breast cancer patients and may provide new insight into the breast cancer tumor immune microenvironment., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Augmented Reality (AR) embeds digital information into objects of the physical world. Data can be shown in-situ, thereby enabling real-time visual comparisons and object search in real-life user tasks, such as comparing products and looking up scores in a sports game. While there have been studies on designing AR interfaces for situated information retrieval, there has only been limited research on AR object labeling for visual search tasks in the spatial environment. In this article, we identify and categorize different design aspects in AR label design and report on a formal user study on labels for out-of-view objects to support visual search tasks in AR. We design three visualization techniques for out-of-view object labeling in AR, which respectively encode the relative physical position (height-encoded), the rotational direction (angle-encoded), and the label values (value-encoded) of the objects. We further implement two traditional in-view object labeling techniques, where labels are placed either next to the respective objects (situated) or at the edge of the AR FoV (boundary). We evaluate these five different label conditions in three visual search tasks for static objects. Our study shows that out-of-view object labels are beneficial when searching for objects outside the FoV, spatial orientation, and when comparing multiple spatially sparse objects. Angle-encoded labels with directional cues of the surrounding objects have the overall best performance with the highest user satisfaction. We discuss the implications of our findings for future immersive AR interface design.

Most sports visualizations rely on a combination of spatial, highly temporal, and user-centric data, making sports a challenging target for visualization. Emerging technologies, such as augmented and mixed reality (AR/XR), have brought exciting opportunities along with new challenges for sports visualization. We share our experience working with sports domain experts and present lessons learned from conducting visualization research in SportsXR. In our previous work, we have targeted different types of users in sports, including athletes, game analysts, and fans. Each user group has unique design constraints and requirements, such as obtaining real-time visual feedback in training, automating the low-level video analysis workflow, or personalizing embedded visualizations for live game data analysis. In this article, we synthesize our best practices and pitfalls we identified while working on SportsXR. We highlight lessons learned in working with sports domain experts in designing and evaluating sports visualizations and in working with emerging AR/XR technologies. We envision that sports visualization research will benefit the larger visualization community through its unique challenges and opportunities for immersive and situated analytics.

Purpose: The prognostication for the injured recurrent laryngeal nerve (RLN) with incomplete loss of signal (LOS) and its function outcome have not been well unified. A warning criterion was proposed to predict RLN injury during monitored thyroidectomy., Methods: A retrospective review of prospectively collected data from consecutive 357 patients with 560 nerves at risk was conducted. Vocal cords mobility with laryngoscope was performed preoperatively, on the second day, and once a month postoperatively until complete recovery. Different cutoff values of the percentage reduction in sum of the amplitude of left and right channel at the end of the surgery, for postoperative vocal cord paralysis (VCP) prediction were compared., Results: Percentage reduction in sum of the amplitude of left and right channel at the end of operation ranged from 30.2 to 63.6% in 27 nerves with incomplete LOS (absolute amplitude value of final R 2  > 100 μV with reduction > 50% of R 1 ). Seven (1.25%) nerves experienced transient postoperative VCP, in which one nerve with postoperative VCP showed no amplitude reduction. The positive predictive value of VCP for the sum amplitude reduction exceeding 30, 40, 50, and 60% was 22.2, 40, 85.7, and 100%, respectively. Accuracy was 96.1, 98.2, 99.6, 99.4%, respectively., Conclusion: Percentage reduction in sum of the amplitude of left and right channel is a meaningful method to improve the accuracy of VCP prediction. When the sum amplitude reduction ≥ 50%, surgeons should consider the possibility of postoperative VCP and correct some surgical maneuvers., (© 2022. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)

Background: Anaplastic thyroid carcinoma (ATC) is a rare but extremely malignant tumor, with a rapid growth rate and early metastasis thus leading to poor survival of patients. The molecular mechanisms underlying these aggressive traits of ATC remain unknown, which impedes the substantial progress in treatment to prolong ATC patient survival., Methods: We applied weighted gene co-expression network analysis (WGCNA) to identify ATC-specific modules. The Metascape web and R package clusterProfiler were employed to perform enrichment analysis. Combined with differentially expressed gene analysis, we screened out the most potential driver genes and validated them using receiver operator characteristic (ROC) analysis, quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blotting, immunohistochemistry (IHC), and triple immunofluorescence staining., Results: A gene expression matrix covering 75 normal samples, 83 papillary thyroid carcinoma (PTC), 26 follicular thyroid carcinoma (FTC), 19 poor-differentiated thyroid carcinoma (PDTC), and 41 ATC tissue samples were integrated, based on which we detected three most potential ATC-specific modules and found that hub genes of these modules were enriched in distinct biological signals. Hub genes in the turquoise module were mainly enriched in mitotic cell cycle, tube morphogenesis, and cell differentiation, hub genes in the magenta module were mainly clustered in the extracellular matrix organization, positive regulation of cell motility, and regulation of Wnt signaling pathway, while hub genes in the blue module primarily participated in the inflammatory response, innate immune response, and adaptive immune response. We showed that 9 top genes, 8 transcription factors (TFs), and 4 immune checkpoint genes (ICGs) were differentially expressed in ATC compared to other thyroid samples and had high diagnostic values for ATC, among which, 9 novel ATC-specific genes ( ADAM12, RNASE2, CASP5, KIAA1524, E2F7, MYBL1, SRPX2, HAVCR2 , and TDO2 ) were validated with our clinical samples. Furthermore, we illustrated that ADAM12, RNASE2, and HAVCR2 were predominantly present in the cytoplasm., Conclusion: Our study identified a set of novel ATC-specific genes that were mainly related to cell proliferation, invasion, metastasis, and immunosuppression, which might throw light on molecular mechanisms underlying aggressive phenotypes of ATC and provide promisingly diagnostic biomarkers and therapeutic targets., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dong, Yang, Hou, Chen, Yuan, Xu, Liu, Li and Wu.)

A probe-based quantitative PCR (qPCR) protocol was developed for detection and evaluation of the wheat bacterial leaf streak pathogen Xanthomonas translucens pathovar (pv.) undulosa . The protocol can also detect X. translucens pv. translucens and X. translucens pv. secalis but can't differentiate the three pathovars. When tested on nontarget DNA (i.e., from plant; bacteria other than X. translucens pv. undulosa , X. translucens pv. translucens , and X. translucens pv. secalis ; and culture of microorganisms from wheat grains), the qPCR showed a high specificity. On purified X. translucens pv. undulosa DNA, the qPCR was more sensitive than a loop-mediated isothermal amplification assay. When DNA samples from a set of serial dilutions of X. translucens pv. undulosa cells were tested, the qPCR method could repeatedly generate quantification cycle (Cq) values from the dilutions containing ≥1,000 cells. Since 2 µl of the total 50 µl of DNA was used in one reaction, one qPCR reaction could detect the presence of the bacteria in samples containing as few as 40 bacterial cells. The qPCR could detect the bacteria from both infected grain and leaf tissues. For seed testing, a protocol for template preparation was standardized, which allowed one qPCR reaction to test DNA from the surface of one wheat grain. Thus, the qPCR system could detect X. translucens pv. undulosa , X. translucens pv. translucens , and/or X. translucens pv. secalis in samples where the bacteria had an average concentration of ≥40 cells per grain.

Since immune system and internal environment in vivo are large and complex, the interpretation of the observed immune effect from the perspective of a single immune cell or antibody seems a little feeble. Many studies have shown that specific antibodies against " former" viruses have a reduced ability to neutralize "new" mutant strains. However, there is no comprehensive and clear view of whether there will be Antibody-dependent enhancement (ADE). We review the latest relevant studies, hoping to explain the ADE of SARS-CoV-2 infection sometimes observed in some patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yang and Xu.)

Sports game data is becoming increasingly complex, often consisting of multivariate data such as player performance stats, historical team records, and athletes' positional tracking information. While numerous visual analytics systems have been developed for sports analysts to derive insights, few tools target fans to improve their understanding and engagement of sports data during live games. By presenting extra data in the actual game views, embedded visualization has the potential to enhance fans' game-viewing experience. However, little is known about how to design such kinds of visualizations embedded into live games. In this work, we present a user-centered design study of developing interactive embedded visualizations for basketball fans to improve their live game-watching experiences. We first conducted a formative study to characterize basketball fans' in-game analysis behaviors and tasks. Based on our findings, we propose a design framework to inform the design of embedded visualizations based on specific data-seeking contexts. Following the design framework, we present five novel embedded visualization designs targeting five representative contexts identified by the fans, including shooting, offense, defense, player evaluation, and team comparison. We then developed Omnioculars, an interactive basketball game-viewing prototype that features the proposed embedded visualizations for fans' in-game data analysis. We evaluated Omnioculars in a simulated basketball game with basketball fans. The study results suggest that our design supports personalized in-game data analysis and enhances game understanding and engagement.

Background: Compound aluminum sulfate injection (CASI) originated from a Chinese traditional medicine, "Kuzhiye", and has been used in treating non-muscle invasive bladder cancer (NMIBC). Previous studies suggested that CASI was a potential monotherapeutic drug for NMIBC. However, the efficacy and safety of CASI in the treatment of NMIBC, as well as the long-term recurrence after treatment, need to be further evaluated., Methods: A multicenter retrospective single-arm cohort study was conducted. From 2006 to 2009, 101 patients (74 men and 27 women, aged 58.9±11.9 years) with T1 or benign NMIBC were enrolled. Each patient was directly injected with CASI through catheter needle into the root of NMIBC. Vital signs, electrocardiography, blood count, blood biochemistry, and urine analysis were re-examined on day 2 and day 14 after CASI injection, together with a cystoscopic examination 4 weeks after CASI treatment was performed for all patients to assess the clinical activity and safety of CASI. To study long-term efficacy, patients in center 2 were followed up for recurrence with a median follow-up time of 13.8 years., Results: For the 101 patients enrolled in this study, demographic characteristics in the 3 centers showed no significant differences. After CASI, 2 patients showed administration site-dependent, but not dose-dependent, increase in their aluminum concentration in 24 hours without obvious abnormality in blood biochemistry. The overall effective rate was 97.03%, including complete tumor necrosis in 94 patients. Treatment-related adverse events occurred in 20 patients (19.80%), including 9 drug-related and 11 cystoscopy-related adverse events (AEs). All AEs were endurable and disappeared within 2 weeks without any treatment. The maximum tolerated single dose of CASI was 21 mL. Among the 43 patients at center 2, 3 patients were excluded because they changed to other treatment regimen. As of April 2022, of the 40 patients enrolled, 22 had no recurrence and 7 relapsed. The follow-up time was 2-16.2 years. The other 11 patients were lost to follow up., Conclusions: CASI may be an effective and safe option for the treatment of NMIBC and is expected to be a potential monotherapy regimen for NMIBC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-22-483/coif). The authors have no conflicts of interest to declare., (2022 Translational Andrology and Urology. All rights reserved.)

Macrophage is the important sentinel cell type of innate immune system, and bridge with the adaptive immune response via antigen presentation. Tissue-resident macrophages are universal in almost all organs and play essential roles in maintaining specific organ homeostasis, inflammation responses, and disease genesis, including tumorigenesis. Macrophage is generally divided into two extreme statuses, M1 and M2, with sophisticated continuous subtypes due to different stimuli and microenvironments. Tumor-associated macrophage (TAM) is regarded as the key factor related to the prognosis, staging, classification, and treatment strategy of various cancers. However, emerging evidence indicated potential opposite functions of TAM in different tumor models. Recent studies found that different originated resident macrophages show notably different profiles in the same tissue niche. More evidence pointed out that the strategies to repolarize the subtypes of TAM or resident macrophages are valuable in carcinoma treatments. In the breast cancer model, studies pointed that macrophages located differently in histology show obvious different cell markers and functions. In this review, we will illustrate the profiles of resident macrophages in breast cancer with various aspects, including origination, polarization, tumoricidal activity, tumorigenesis, and the factors that could regulate the functions of macrophages., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

In this paper, the traditional, silicate-based Portland cement (PC) was employed as the control to explore the impact of adding varying amounts of metakaolin (MK) on the mechanical properties of cement mortar. In fact, as a mineral admixture, metakaolin (MK) has the ability to significantly improve the early strength and sulfate resistance of cement mortar in traditional, silicate-based Portland cement (PC). In addition to this, the performance of Portland cement mortar is greatly affected by the curing mode. The previous research mainly stays in the intermittent curing and alkaline excitation mode, and there are few studies on the influence of relatively humidity on it. Moreover, the paper investigated the impact of four different curing methods about humidity on the mechanical properties and sulfate resistance. The results show that the best content of metakaolin in Portland cement is 10% (M10), and the best curing method is 95% humidity in the first three days followed by 60% humidity in the later period (3#). Based on previous literature that suggests that adding MK thickens water film layer on the surface of mortar, the mechanism of MK increasing the early strength of cement was analyzed. The compressive strength of the Portland cement containing 10% MK (M10) after 1 day curing is 3.18 times that of pristine PC mortar, and is comparable if PC is cured for three days under the same curing conditions. The traditional PC mortar is highly dependent on the wet curing time, and normally requires a curing time of at least seven days. However, the incorporation of MK can greatly reduce the sensitivity of Portland cement to water; MK cement mortar with only three days wet curing (3#M10) can reach 49.12 MPa after 28 days, which can greatly shorten the otherwise lengthy wet curing time. Lastly, the cement specimens with MK also demonstrated excellent resistance against sulfate corrosion. The work will provide a strong theoretical basis for the early demolding of cement products in construction projects. At the same time, this study can also provide a theoretical reference for the construction of climate drought and saline land areas, which has great reference value.

Background: Breast cancer (BC) is the leading malignancy among women worldwide., Aim: This work aimed to present a comprehensively bioinformatic analysis of gene expression profiles and to identify the hub genes during BC tumorigenesis, providing potential biomarkers and targets for the diagnosis and therapy of BC., Materials & Methods: In this study, multiple public databases, bioinformatics approaches, and online analytical tools were employed and the real-time reverse transcription polymerase chain reaction was implemented., Results: First, we identified 10, 107, and 3869 differentially expressed genes (DEGs) from three gene expression datasets (GSE9574, GSE15852, and GSE42568, covering normal, para-cancerous, and BC samples, respectively), and investigated different biological functions and pathways involved. Then, we screened out 8, 16, and 29 module genes from these DEGs, respectively. Next, 10 candidate genes were determined through expression and survival analyses. We noted that seven candidate genes JUN, FOS, FOSB, EGR1, ZFP36, CFD, and PPARG were downregulated in BC compared to normal tissues and lower expressed in aggressive types of BC (basal, HER2 + , and luminal B), TP53 mutation group, younger patients, higher stage BC, and lymph node metastasis BC, while CD27, PSMB9, and SELL were upregulated. The present study discovered that the expression levels of these candidate genes were correlated with the infiltration of immune cells (CD8 + T cell, macrophage, natural killer [NK] cell, and cancer-associated fibroblast) in BC, as well as biomarkers of immune cells and immune checkpoints. We also revealed that promoter methylation, amplification, and deep deletion might contribute to the abnormal expressions of candidate genes. Moreover, we illustrated downstream-targeted genes of JUN, FOS, FOSB, EGR1, and ZFP36 and demonstrated that these targeted genes were involved in "positive regulation of cell death", "pathways in cancer", "PI3K-Akt signaling pathway", and so on., Discussion & Conclusion: We presented differential gene expression profiles among normal, para-cancerous, and BC tissues and further identified candidate genes that might contribute to tumorigenesis and progression of BC, as potential diagnostic and prognostic targets for BC patients., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: As deubiquitinases (DUBs), ubiquitin C-terminal hydrolase (UCH)-L1 has been shown to play a crucial role in regulating diverse biological processes. However, its function in macrophage polarization remains unclear., Methods: We performed in vivo and in vitro experiments to investigate the role of ubiquitin carboxyl-terminal hydrolase L1 (UCHL1), a kind of DUBs, in macrophage differentiation by using UCHL1-deficiency mice., Results: We demonstrated that LPS stimulation induced UCHL1 expression in macrophages. The deficiency of UCHL1 expression decreased the expression of CD80 and CD86 but increased the expression of CD206. The expression of TNF-α, IL-6, iNOS, and IL-10 was downregulated, while that of Arg1, Ym1, and Fizz1 was upregulated in UCHL1 deficient macrophages. Moreover, we observed that UCHL1 promoted the degradation of p110α through autophagy, but paradoxically increased the activity of AKT, thereby promoting polarization of macrophages into pro-inflammatory states., Conclusion: In this study, we identified UCHL1 as a positive regulator of M1 macrophage polarization. Our findings may help in developing therapeutic interventions for the treatment of inflammatory diseases and pathogenic infections., Competing Interests: The authors declare no competing financial/non-financial interests., (© 2022 Huang et al.)

Cell migration-inducing hyaluronidase 1 (CEMIP), a Wnt-related protein and also known as KIAA1199, is implicated in the process of metastatic colonization in a variety of malignant tumors, including breast cancer (BC), which is one of the most frequently diagnosed tumors in women worldwide. In this study, multiple public databases, online analytical tools, and bioinformatics approaches were applied to explore the expression levels, regulatory mechanisms, and biological functions of CEMIP in BC. We illustrated that CEMIP was highly expressed in various kinds of carcinomas, including BC, especially advanced subtypes, and predicted less favorable prognosis (negatively associated with overall survival) in BC patients, which might be an independent prognostic factor. Then, we revealed that the mutation and high expression of CEMIP might lead to it as an oncogene. We also demonstrated that TP53 mutation, DNA hypo-methylation, and the expression changes of three potential upstream transcription factors ( EZH2, EGR1 , and JUN ) of CEMIP were likely to cause the hyperexpression of CEMIP in BC . Moreover, our findings suggested that CEMIP might exert its carcinogenic roles in the tumor microenvironment via participation in the extracellular matrix formation, increasing cancer-associated fibroblast (CAF), M2 macrophage, and neutrophil infiltration and decreasing CD8 + T cell infiltration. In summary, our study provided more solid evidence for CEMIP as a prognostic and metastatic biomarker and a potential therapeutic target in BC. Of course, these findings also need more confirmations of basic experiments and further clinical trials in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Dong, Yang, Yuan, Hou and Wu.)

We introduce Tilt Map, a novel interaction technique for intuitively transitioning between 2D and 3D map visualisations in immersive environments. Our focus is visualising data associated with areal features on maps, for example, population density by state. Tilt Map transitions from 2D choropleth maps to 3D prism maps to 2D bar charts to overcome the limitations of each. Our article includes two user studies. The first study compares subjects' task performance interpreting population density data using 2D choropleth maps and 3D prism maps in virtual reality (VR). We observed greater task accuracy with prism maps, but faster response times with choropleth maps. The complementarity of these views inspired our hybrid Tilt Map design. Our second study compares Tilt Map to: a side-by-side arrangement of the various views; and interactive toggling between views. The results indicate benefits for Tilt Map in user preference; and accuracy (versus side-by-side) and time (versus toggle).

We present how to integrate Design Sprints and project-based learning into introductory visualization courses. A design sprint is a unique process based on rapid prototyping and user testing to define goals and validate ideas before starting costly development. The well-defined, interactive, and time-constrained design cycle makes design sprints a promising option for teaching project-based and active-learning-centered courses to increase student engagement and hands-on experience. Over the past five years, we have adjusted the design sprint methodology for teaching a range of visualization courses. We present a detailed guide on incorporating design sprints into large undergraduate and small professional development courses in both online and on-campus settings. Design sprint results, including quantitative and qualitative student feedback, show that design sprints engage students and help practice and apply visualization and design skills. We provide design sprint teaching materials, show examples of student-created work, and discuss limitations and lessons learned.

Deubiquitinases (DUBs) regulate diverse biological processes and represent a novel class of drug targets. However, the biological function of only a small fraction of DUBs, especially in adaptive immune response regulation, is well-defined. In this study, we identified DUB ubiquitin-specific peptidase 12 (USP12) as a critical regulator of CD4 + T cell activation. USP12 plays an intrinsic role in promoting the CD4 + T cell phenotype, including differentiation, activation, and proliferation. Although USP12-deficient CD4 + T cells protected mice from autoimmune diseases, the immune response against bacterial infection was subdued. USP12 stabilized B cell lymphoma/leukemia 10 (BCL10) by deubiquitinating, and thereby activated the NF-κB signaling pathway. Interestingly, this USP12 regulatory mechanism was identified in CD4 + T cells, but not in CD8 + T cells. Our study results showed that USP12 activated CD4 + T cell signaling, and targeting USP12 might help develop therapeutic interventions for treating inflammatory diseases or pathogen infections., (© 2021. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.)

Clubroot caused by Plasmodiophora brassicae is an important disease on cruciferous crops worldwide. Management of clubroot is challenging, largely because of the millions of resting spores produced within an infected root that can survive dormant in the soil for many years. This study was conducted to investigate some of the environmental conditions that may affect the survival of resting spores in the soil. Soil samples containing clubroot resting spores (1 × 10 7 spores/g soil) were stored at various temperatures for 2 years. Additionally, other samples were buried in soil or kept on the soil surface in the field. The content of P. brassicae DNA and the numbers of viable spores in the samples were assessed by quantitative PCR (qPCR) and pathogenicity bioassays, respectively. The results indicated that 4°C, 20°C, and being buried in the soil were more conductive conditions for spore survival than -20°C, 30°C, and at the soil surface. Most (99.99%) of the spores kept on the soil surface were nonviable, suggesting a negative effect of light on spore viability. Additional experiments confirmed the negative effect of ultraviolet light on spore viability because spores receiving 2 and 3 h ultraviolet light exhibited lower disease potential and contained less DNA content than the nontreated control. Finally, this work confirmed that DNA-based quantification methods such as qPCR can be poor predictors of P. brassicae disease potential because of the presence and persistence of DNA from dead spores.

Node-link diagrams are widely used to visualise networks. However, even the best network layout algorithms ultimately result in 'hairball' visualisations when the graph reaches a certain degree of complexity, requiring simplification through aggregation or interaction (such as filtering) to remain usable. Until now, there has been little data to indicate at what level of complexity node-link diagrams become ineffective or how visual complexity affects cognitive load. To this end, we conducted a controlled study to understand workload limits for a task that requires a detailed understanding of the network topology-finding the shortest path between two nodes. We tested performance on graphs with 25 to 175 nodes with varying density. We collected performance measures (accuracy and response time), subjective feedback, and physiological measures (EEG, pupil dilation, and heart rate variability). To the best of our knowledge this is the first network visualisation study to include physiological measures. Our results show that people have significant difficulty finding the shortest path in high density node-link diagrams with more than 50 nodes and even low density graphs with more than 100 nodes. From our collected EEG data we observe functional differences in brain activity between hard and easy tasks. We found that cognitive load increased up to certain level of difficulty after which it decreased, likely because participants had given up. We also explored the effects of global network layout features such as size or number of crossings, and features of the shortest path such as length or straightness on task difficulty. We found that global features generally had a greater impact than those of the shortest path.

data has no natural scale and so interactive data visualizations must provide techniques to allow the user to choose their viewpoint and scale. Such techniques are well established in desktop visualization tools. The two most common techniques are zoom+pan and overview+detail. However, how best to enable the analyst to navigate and view abstract data at different levels of scale in immersive environments has not previously been studied. We report the findings of the first systematic study of immersive navigation techniques for 3D scatterplots. We tested four conditions that represent our best attempt to adapt standard 2D navigation techniques to data visualization in an immersive environment while still providing standard immersive navigation techniques through physical movement and teleportation. We compared room-sized visualization versus a zooming interface, each with and without an overview. We find significant differences in participants' response times and accuracy for a number of standard visual analysis tasks. Both zoom and overview provide benefits over standard locomotion support alone (i.e., physical movement and pointer teleportation). However, which variation is superior, depends on the task. We obtain a more nuanced understanding of the results by analyzing them in terms of a time-cost model for the different components of navigation: way-finding, travel, number of travel steps, and context switching.

Macrophages are the principal immune cells of the epididymis and testis, but their origins, heterogeneity, development, and maintenance are not well understood. Here, we describe distinct populations of epididymal and testicular macrophages that display an organ-specific cellular identity. Combining in vivo fate-mapping, chimeric and parabiotic mouse models with in-depth cellular analyses, we found that CD64 hi MHCII lo and CD64 lo MHCII hi macrophage populations of epididymis and testis arise sequentially from yolk sac erythro-myeloid progenitors, embryonic hematopoiesis, and nascent neonatal monocytes. While monocytes were the major developmental source of both epididymal and testicular macrophages, both populations self-maintain in the steady-state independent of bone marrow hematopoietic precursors. However, after radiation-induced macrophage ablation or during infection, bone marrow-derived circulating monocytes are recruited to the epididymis and testis, giving rise to inflammatory macrophages that promote tissue damage. These results define the layered ontogeny, maintenance and inflammatory response of macrophage populations in the male reproductive organs., Competing Interests: The authors declare no competing interest.

Vitamin B6 is necessary to maintain normal metabolism and immune response, especially the anti-inflammatory immune response. However, the exact mechanism by which vitamin B6 plays the anti-inflammatory role is still unclear. Here, we report a novel mechanism of preventing excessive inflammation by vitamin B6 via reduction in the accumulation of sphingosine-1-phosphate (S1P) in a S1P lyase (SPL)-dependent manner in macrophages. Vitamin B6 supplementation decreased the expression of pro-inflammatory cytokines by suppressing nuclear factor-κB and mitogen-activated protein kinases signalling pathways. Furthermore, vitamin B6-reduced accumulation of S1P by promoting SPL activity. The anti-inflammatory effects of vitamin B6 were inhibited by S1P supplementation or SPL deficiency. Importantly, vitamin B6 supplementation protected mice from lethal endotoxic shock and attenuated experimental autoimmune encephalomyelitis progression. Collectively, these findings revealed a novel anti-inflammatory mechanism of vitamin B6 and provided guidance on its clinical use., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Lighting condition is essential to human performance. With the widespread use of computer-based learning, the performance measurements become difficult, and the effects of artificial lighting conditions towards the new learning forms are not investigated extensively. The current study conducts a subject-within experiment with a 45-min-long online learning along with electroencephalogram (EEG)-based measurements, and a post-interview under five lighting setups respectively (300 lx, 3000 K; 300 lx, 4000 K; 300 lx, 6500 K; 500 lx, 4000 K; 1000 lx, 4000 K). Attention is chosen as the key factor to represent the learning performance. The results show that the attention of people aged in the 20s is not affected by the experimental lighting conditions. The results also demonstrate that people in high illumination at 1000 lx are more inclined to sustain attention despite the discomfort and dissatisfaction. Taking the EEG-based attention measurements and post-interview answers into consideration, lighting conditions at 300 lx, 4000 K are the recommended set points for university architectures among the investigated conditions, providing a practical basis when adjusting the lighting standard for its advantage in energy saving.

Clubroot, caused by Plasmodiophora brassicae , is an important disease on canola in Alberta, Canada. The pathogen is grouped into pathotypes according to their virulence reaction on differential hosts. Multiple pathotypes or strains are known exist in one field, one plant, or even one gall. This study was conducted with the objective of testing the prevalence of the coexistence of multiple strains in a single gall. In all, 79 canola clubroot galls were collected from 22 fields across Northern Alberta in 2018. Genomic DNA extracted from these single galls was analyzed using RNase H-dependent PCR (rhPCR). The rhPCR primers were designed to amplify a partial sequence of a dimorphic gene, with one primer pair specific to one sequence and the other primer pair specific to the alternative sequence. The amplification of both sequences from DNA obtained from a single gall would indicate that it contains two different P. brassicae strains. The rhPCR analyses indicated that the P. brassicae populations in 50 of the 79 galls consisted of more than one strain. This result emphasizes the need for cautious interpretation of results when a single-gall population is subject to pathotyping or being used as inoculum in plant pathology research. It also confirms that the maintenance of pathotype diversity within single root galls is a common occurrence which has implications for the durability, and stewardship, of single-gene host resistance.

NOD-like receptor (NLR) family CARD domain containing 3 (NLRC3), an intracellular member of NLR family, is a negative regulator of inflammatory signaling pathways in innate and adaptive immune cells. Previous reports have shown that NLRC3 is expressed in dendritic cells (DCs). However, the role of NLRC3 in DC activation and immunogenicity is unclear. In the present study, we find that NLRC3 attenuates the antigen-presenting function of DCs and their ability to activate and polarize CD4 + T cells into Th1 and Th17 subsets. Loss of NLRC3 promotes pathogenic Th1 and Th17 responses and enhanced experimental autoimmune encephalomyelitis (EAE) development. NLRC3 negatively regulates the antigen-presenting function of DCs via p38 signaling pathway. Vaccination with NLRC3-overexpressed DCs reduces EAE progression. Our findings support that NLRC3 serves as a potential target for treating adaptive immune responses driving multiple sclerosis and other autoimmune disorders., (© 2019 The Authors.)

To develop genetic markers for differentiation between pathotypes of the clubroot pathogen Plasmodiophora brassicae, DNA polymorphisms of 85 P. brassicae genes were investigated by comparing the sequences of these genes from published expressed sequence tag libraries to their sequences in the two released whole genomes. A significant portion of the identified sequence differences across all polymorphic genes are between an isolate from New Zealand and the two whole-genome sequenced isolates. Four genes with a high density of polymorphisms were selected and their partial sequences were amplified by polymerase chain reaction (PCR) from the old pathotypes 2, 3, 5, 6, and 8 (based on the Williams differential set) and the new virulent populations 3-like and 5-like. On the sequences of two of the four genes, the old pathotypes are all identical to the two whole-genome sequenced isolates and all of the new virulent populations are identical to the New Zealand isolate. Based on the dimorphism on the sequence of these two genes, an RNase H-dependent PCR protocol was developed. This protocol was demonstrated to be useful for virulent pathotype identification and may also be used to study the population dynamics of P. brassicae and the in planta interaction of different pathotypes.

NLRC3, a member of the NLR family, has been reported as a negative regulator of inflammatory signaling pathways in innate immune cells. However, the direct role of NLRC3 in modulation of CD4+ T-cell responses in infectious diseases has not been studied. In the present study, we showed that NLRC3 plays an intrinsic role by suppressing the CD4+ T cell phenotype in lung and spleen, including differentiation, activation, and proliferation. NLRC3 deficiency in CD4+ T cells enhanced the protective immune response against Mycobacterium tuberculosis infection. Finally, we demonstrated that NLRC3 deficiency promoted the activation, proliferation, and cytokine production of CD4+ T cells via negatively regulating the NF-κB and MEK-ERK signaling pathways. This study reveals a critical role of NLRC3 as a direct regulator of the adaptive immune response and its protective effects on immunity during M. tuberculosis infection. Our findings also suggested that NLRC3 serves as a potential target for therapeutic intervention against tuberculosis., Competing Interests: The authors have declared that no competing interests exist.

Immersive virtual- and augmented-reality headsets can overlay a flat image against any surface or hang virtual objects in the space around the user. The technology is rapidly improving and may, in the long term, replace traditional flat panel displays in many situations. When displays are no longer intrinsically flat, how should we use the space around the user for abstract data visualisation? In this paper, we ask this question with respect to origin-destination flow data in a global geographic context. We report on the findings of three studies exploring different spatial encodings for flow maps. The first experiment focuses on different 2D and 3D encodings for flows on flat maps. We find that participants are significantly more accurate with raised flow paths whose height is proportional to flow distance but fastest with traditional straight line 2D flows. In our second and third experiment we compared flat maps, 3D globes and a novel interactive design we call MapsLink, involving a pair of linked flat maps. We find that participants took significantly more time with MapsLink than other flow maps while the 3D globe with raised flows was the fastest, most accurate, and most preferred method. Our work suggests that careful use of the third spatial dimension can resolve visual clutter in complex flow maps.

It is known that vitamin B1 (VB1) has a protective effect against oxidative retinal damage induced by anti-tuberculosis drugs. However, it remains unclear whether VB1 regulates immune responses during Mycobacterium tuberculosis (MTB) infection. We report here that VB1 promotes the protective immune response to limit the survival of MTB within macrophages and in vivo through regulation of peroxisome proliferator-activated receptor γ (PPAR-γ). VB1 promotes macrophage polarization into classically activated phenotypes with strong microbicidal activity and enhanced tumor necrosis factor-α and interleukin-6 expression at least in part by promoting nuclear factor-κB signaling. In addition, VB1 increases mitochondrial respiration and lipid metabolism and PPAR-γ integrates the metabolic and inflammatory signals regulated by VB1. Using both PPAR-γ agonists and deficient mice, we demonstrate that VB1 enhances anti-MTB activities in macrophages and in vivo by down-regulating PPAR-γ activity. Our data demonstrate important functions of VB1 in regulating innate immune responses against MTB and reveal novel mechanisms by which VB1 exerts its function in macrophages.

A commonly used protocol for DNA extraction from Plasmodiophora brassicae was modified by adding an alkaline treatment step to increase the purity of resting spores. The quality of DNA extracted by the modified protocol was improved due to the removal of DNA contamination from host plant cells and other microorganisms., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Showing flows of people and resources between multiple geographic locations is a challenging visualisation problem. We conducted two quantitative user studies to evaluate different visual representations for such dense many-to-many flows. In our first study we compared a bundled node-link flow map representation and OD Maps [37] with a new visualisation we call MapTrix. Like OD Maps, MapTrix overcomes the clutter associated with a traditional flow map while providing geographic embedding that is missing in standard OD matrix representations. We found that OD Maps and MapTrix had similar performance while bundled node-link flow map representations did not scale at all well. Our second study compared participant performance with OD Maps and MapTrix on larger data sets. Again performance was remarkably similar.

Background: In recent years, drug resistant tuberculosis (DR-TB) particularly the emergence of multi-drug-resistant tuberculosis (MDR-TB) has become a major public health issue. The most recent study regarding the prevalence of drug-resistant tuberculosis in mainland China was a meta-analysis published in 2011, and the subjects from the included studies were mostly enrolled before 2008, thus making it now obsolete. Current data on the national prevalence of DR-TB is needed. This review aims to provide a comprehensive and up-to-date assessment of the status of DR-TB epidemic in mainland China., Methods: A systematic review and meta-analysis of studies regarding the prevalence of drug-resistant tuberculosis in mainland China was performed. Pubmed/MEDLINE, EMBASE, the Cochrane central database, the Chinese Biomedical Literature Database and the China National Knowledge Infrastructure Database were searched for studies relevant to drug-resistant tuberculosis that were published between January 1, 2012 and May 18, 2015. Comprehensive Meta-Analysis (V2.2, Biostat) software was used to analyse the data., Results: A total of fifty-nine articles, published from 2012 to 2015, were included in our review. The result of this meta-analysis demonstrated that among new cases, the rate of resistance to any drug was 20.1% (18.0%-22.3%; n/N = 7203/34314) and among retreatment cases, the rate was 49.8% (46.0%-53.6%; n/N = 4155/8291). Multi-drug resistance among new and retreatment cases was 4.8% (4.0%-5.7%; n/N = 2300/42946) and 26.3% (23.1%-29.7%; n/N = 3125/11589) respectively. The results were significantly heterogeneous (p<0.001, I2 tests). Resistance to isoniazid was the most common resistance observed, and HRSE (H: isoniazid; R: rifampicin; S: streptomycin; E: ethambutol) was the most common form for MDR among both new and retreatment cases. Different drug resistance patterns were found by subgroup analysis according to geographic areas, subject enrolment time, and methods of drug susceptibility test (DST)., Conclusions: The prevalence of resistance to any drug evidently dropped for both new and retreatment cases, and multi-drug resistance declined among new cases but became more prevalent among retreatment cases compared to the data before 2008. Therefore, drug-resistant tuberculosis, particularly multi-drug-resistant tuberculosis among retreatment TB cases is a public health issue in China that requires a constant attention in order to prevent increase in MDR-TB cases.