bluuebunny/crossref_metadata_2025 huggingface dataset:
Smart Ambulance Traffic Control System
Authors: KRISHNAN SUREN , THANGAVELOO RAJAN , BIN ABD RAHMAN SHAPI-EE , SINDIRAMUTTY SIVA RAJA
Published: June 2021

The traffic lights control system is broadly implemented to track and control the flow of vehicles through the intersection of multiple roads. Nevertheless, the synchronization of traffic light system at adjacent junctions is an intricate issue given the different parameters involved. Existing traffic light control systems do not control many flows approaching the same junctions. This results in traffic jams and congestion at urban areas or major cities with high volume traffic consisting of various types of vehicles. This includes emergency ambulances travelling on the same traffic junction during peak hour traffic. Thus, an enhanced traffic light control system is imperative to provide a smooth and free flow for an ambulance on the way to its destination. The Smart Ambulance Traffic Control System proposed in this paper is an integrated system of traffic light control for emergency ambulance service. The traffic lights can be controlled in a timely and efficient manner every time an emergency ambulance is approaching. The Radio-Frequency Identification (RFID) is used as an instrument to communicate with traffic lights during traffic congestion. The emergency ambulance driver needs to activate the RFID tag to allow the detection of RFID readers to control the traffic light operation at the upcoming traffic light junctions. The traffic lights in the path of the ambulance are forced to be green to allow the emergency ambulance to pass through the junction with top priority. Immediately after the ambulance has passed the junction, the control system will reset and return to normal operations.
Quality of Service and Brand Trust Against Decisions Using Indihome in Ciputat Area of South Tangerang
Authors: Santoso Senen , Wulandari Siswi
Published: June 2021

The purpose of this study is to know the influence between sales promotion to purchase decisions, to know the influence between the quality of service to purchasing decisions, to know the influence between brand trusts on purchasing decisions. The analysis method used is multiple linear regression using SPSS 25 analysis tool. The object of the research in this study was indihome customers of Ciputat region as many as 100 people with random sampling techniques (probability sampling). The results of the analysis stated that partially sales promotion affects purchasing decisions, partially the quality of service services affects purchasing decisions and partially brand trusts affect purchasing decisions, simultaneously (sales promotion, service quality and brand trust) affect purchasing decisions. Concluded in this study is sales promotion influences the decision to use Indihome, the quality of service influences the decision to use Indihome, brand trust influences the decision to use Indihome, simultaneously the promotion of sales of services and brand trust influences the decision to use Indihome.
Kurtosis and Skewness on Lagged Market Risk Premium in Indonesian Market During Covid 19 Pandemic
Authors: Lubis Iman
Published: June 2021

This study investigates the impact of return distribution such as skewness and kurtosis on lagged market risk premium to risk premium in Indonesia capital market during COVID-19 pandemic. Data are monthly, from january to December 2020, and 674 firms. Panel data predictive regression is used The method  For this study, I first looked for market risk premium and risk premium desripitives. Second, I used monthly panel data predictive regression from lagged market risk premium and risk premium in 2020. Third, I incorporate skewness and kurtosis simultaneously. Fourth, I exclude kurtosis or skewness in previous model. The results are market risk premium and risk premium having negative return. Risk premium has lower returns than market risk premium. The beta lagged market risk premium is significant to risk premium. The skewness and kurtosis market risk premium do not signify to risk premium together but significant separately. I can clonclude that the movement market risk premim and risk premium during COVID-19 pandemic are average negative. Beta lagged market risk premium can explain the future monthly risk premium. Contrary skewness and kurtosis, those can not be run together. When the model used to beta lagged market risk premium and skewness, partially the skewness was significant and the direction was positive. However, only beta lagged market risk premium and kurtosis were staying negative to the previous model. Incorporating lagged assumptive distribution only explain the risk premium under 1 % about 0.24%.
Group Salience, Inflammatory Rhetoric, and the Persistence of Hate Against Religious Minorities
Authors: Hobbs William , Lajevardi Nazita , Li Xinyi , Lucas Caleb
Published: June 2021

Hate crimes surged at several points during and after the 2016 U.S. presidential election. Observers argued that hate crimes, especially against Muslims, increased due to inflammatory rhetoric. Did anti-Muslim hate crimes decline after the salience of Muslims receded? Or did emboldening and organizational effects on hate crimes endure? Here, we show that a sudden mid-2017 decline in media discussion of Muslims and in online communities was associated with a large and sustained drop in anti-Muslim hate. At nearly the same time as these shifts, however, we observe an increase in violent hate crimes committed against Jews, and Granger causality tests demonstrate that week-to-week changes in online extremist speech targeting one group versus another also predicted subsequent shifts in hate crimes and bias incidents. Platform-level and within-individual analyses of online social media users suggest that increased anti-Jewish speech was partly driven by far-right communities and extremists who previously promoted anti-Muslim speech.
Building a Bigger Table: Networking 101 For Graduate Students
Authors: Kim Seo-young Silvia , Lebovits Hannah , Shugars Sarah
Published: June 2021

Although the importance of networking is often emphasized to graduate students, straightforward guidance on how to approach this task is typically reliant on individual advisors both knowing and demystifying the discipline's hidden and informal practices. This article provides concrete, point-by-point tips for both junior scholars and their supporters, building on our experiences creating an online communication forum for early-career scholars on the market. Specifically, we suggest a model of community networking focused on robust, cross-rank engagement along dimensions of similar experiences and similar interests. Community networking aims to move beyond individuals angling to get a seat at the table and instead builds a bigger, more inclusive table. While junior scholars must primarily focus on their research rather than expansive service commitments, community networking is ultimately both a service to the discipline and a fruitful strategy for raising one's profile and finding coauthors, colleagues, friends, and allies.
The Effect of Vitamin B12, Physical and Cognitive Activity on Idiopathic Forgetfulness
Authors: Mistik Selcuk , Agadayi Emine , Koseoglu Emel
Published: June 2021

Aim: In this study, we aimed to evaluate the effect of physical activity, vitamin B supplementation and mental activity on cognitive functions in middle-aged individuals with subjective forgetfulness.

Methods: We included 82 people between 40-65 years of age who were admitted to Erciyes University Faculty of Medicine, Family Medicine and Neurology Departments polyclinics with the complaint of subjective forgetfulness between May 2017 and May 2018. General physical examination, blood tests including B12, folic acid level and thyroid functions were performed. In addition to the socio-demographic questionnaire, Beck Anxiety and Beck Depression Scale, Montreal Cognitive Assessment Test, Visual and Verbal Memory Tests were performed. Sixty-eight subjects were randomly allocated to 3 groups as cognitive activity, physical activity and vitamin B supplementation. The physical activity group made a minimum of half-hour brisk walk daily. The cognitive activity group was asked to solve a hooked puzzle every day. Vitamin supplement group used daily vitamin B complex. At the end of the third month, cognitive tests and B12 blood level test were repeated.

Results: Improvement in cognitive functions was found only in the walking group. Long-term visual memory and verbal memory sub-test scores improved significantly in all groups. There were some differences between the groups in terms of verbal memory subtest scores.

Conclusion: In people with forgetfulness, walking, puzzle and vitamin B supplementation seem to have positive effects even after a period of three months in terms of cognitive functions and memory.

Keywords: dementia, cognitive activity, exercise, physical, B vitamins
Sensitive Detection of Single-Nucleotide Polymorphisms by Solid Nanopores Integrated With DNA Probed Nanoparticles
Authors: Wu Ling Zhi , Ye Yuan , Wang Zhi Xuan , Ma Die , Li Li , Xi Guo Hao , Bao Bi Qing , Weng Li Xing
Published: June 2021

Single-nucleotide polymorphisms (SNPs) are the abundant forms of genetic variations, which are closely associated with serious genetic and inherited diseases, even cancers. Here, a novel SNP detection assay has been developed for single-nucleotide discrimination by nanopore sensing platform with DNA probed Au nanoparticles as transport carriers. The SNP of p53 gene mutation in gastric cancer has been successfully detected in the femtomolar concentration by nanopore sensing. The robust biosensing strategy offers a way for solid nanopore sensors integrated with varied nanoparticles to achieve single-nucleotide distinction with high sensitivity and spatial resolution, which promises tremendous potential applications of nanopore sensing for early diagnosis and disease prevention in the near future.
HNRNPA2B1 Affects the Prognosis of Esophageal Cancer by Regulating the miR-17-92 Cluster
Authors: Li Kexin , Chen Jiongyu , Lou Xiaoying , Li Yiling , Qian Benheng , Xu Danfei , Wu Yue , Ma Shaohui , Zhang Donghong , Cui Wei
Published: June 2021

N6-methyladenosine (m6A) is the most abundant RNA modification in eukaryotes. Accumulating evidence suggests that dysregulation of m6A modification significantly correlates with tumorigenesis and progression. In this study, we observed an increased expression and positive correlations of all 25 m6A regulators in esophageal cancer (ESCA) data obtained from the TCGA database. Through expression profiling of these regulators, a prognostic score model containing HNRNPA2B1, ALKBH5, and HNRNPG was established, and the high-risk subgroup exhibited strong positive correlations with ESCA progression and outcome. The risk score obtained from this model may represent an independent predictor of ESCA prognosis. Notably, the gene most frequently associated with increased risk was HNRNPA2B1; in ESCA, the increased expression of this gene alone predicted poor prognosis by affecting tumor-promoting signaling pathways through miR-17-92 cluster. An experimental study demonstrated that elevated HNRNPA2B1 expression was positively associated with distant metastasis and lymph node stage, and predicted the poor outcomes of ESCA patients. Knockdown of HNRNPA2B1 significantly decreased the expression of miR-17, miR-18a, miR-20a, miR-93, and miR-106b and inhibited the proliferation of ESCA cells. Therefore, our study indicated that the dynamic changes in 25 m6A regulators were associated with the clinical features and prognosis of patients with ESCA. Importantly, HNRNPA2B1 alone may affect the prognosis of patients with ESCA by regulating the miR-17-92 cluster.
EGF-Induced miR-223 Modulates Goat Mammary Epithelial Cell Apoptosis and Inflammation via ISG15
Authors: Zhang Yue , Wu Qiong , Niu Guanglin , Liu Jidan , Cao Fangjun , An Xiaopeng , Cao Binyun
Published: June 2021

The health of mammary gland is essential for lactation. Epidermal growth factor (EGF) is reported to play an important role in lactation initiation and miR-223 is a conserved microRNA in anti-inflammation. In this study, EGF was found to induce a higher expression of miR-223 in goat mammary epithelial cell (gMEC). The downstream genes of miR-223 were screened by RNA sequencing, including Interferon-stimulated gene product 15 (ISG15), a pivotal immune responder, which was detected to be downregulated by EGF and miR-223. Due to the correlation between inflammation and apoptosis, the gMEC apoptosis modulated by EGF, miR-223, and ISG15 was investigated, and the protein expressions of Bcl-2/Bax, Caspase 3 and p53 were examined to evaluate the apoptosis of gMEC. The protein expressions of p-STAT3/STAT3, PR, FOXC1, and HOXA10, which had been shown to be related to inflammation, were detected to assess the inflammation of gMEC. This study provided a regulation axis, EGF/miR-223/ISG15, and illustrated its regulation to gMEC apoptosis and inflammation.
Targeting Protein Kinases Degradation by PROTACs
Authors: Yu Fei , Cai Ming , Shao Liang , Zhang Jihong
Published: June 2021

Kinase dysregulation is greatly associated with cell proliferation, migration and survival, indicating the importance of kinases as therapeutic targets for anticancer drug development. However, traditional kinase inhibitors binding to catalytic or allosteric sites are associated with significant challenges. The emergence of resistance and targeting difficult-to-degrade and multi-domain proteins are significant limiting factors affecting the efficacy of targeted anticancer drugs. The next-generation treatment approaches seem to have overcome these concerns, and the use of proteolysis targeting chimera (PROTAC) technology is one such method. PROTACs bind to proteins of interest and recruit E3 ligase for degrading the whole target protein via the ubiquitin-proteasome pathway. This review provides a detailed summary of the most recent signs of progress in PROTACs targeting different kinases, primarily focusing on new chemical entities in medicinal chemistry.
Fictive Deixis, Direct Discourse, and Viewpoint Networks
Authors: Dancygier Barbara
Published: June 2021

This paper proposes a renewed and more textured understanding of the relation between deixis and direct discourse, grounded in a broader range of genres and reflecting contemporary multimodal usage. I re-consider the phenomena covered by the concept of deixis in connection to the speech situation, and, by extension, to the category of Direct Discourse, in its various functions. I propose an understanding of Direct Discourse as a construction which is a correlate of Deictic Ground. Relying on Mental Spaces Theory and the apparatus it makes available for a close analysis of viewpoint networks, I analyze examples from a range of discourse genres - textual, visual and multimodal, such as literature, political campaigns, internet memes and storefront signs. These discourse contexts use Direct Discourse Constructions but usually lack a fully profiled Deictic Ground. I propose that in such cases the Deictic Ground is not a pre-existing conceptual structure, but rather is set up ad hoc to construe non-standard uses of Direct Discourse–I refer to such construals as Fictive Deictic Grounds. In that context, I propose a re-consideration of the concept of Direct Discourse, to explain its tight correlation with the concept of deixis. I also argue for a treatment of Deictic Ground as a composite structure, which may not be fully profiled in each case, while participating in the construction of viewpoint configurations.
Meta-Analysis on the Safety and Cardiorenal Efficacy of SGLT2 Inhibitors in Patients Without T2DM
Authors: Li Lu-Feng , Ding Liang-Liang , Zhan Ze-Lin , Qiu Mei
Published: June 2021

The cardiorenal benefits of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus (T2DM) are established, whereas those in patients without T2DM are not established. We sought to assess the cardiorenal efficacy and safety of SGLT2 inhibitors in non-T2DM patients by performing a meta-analysis based on the subgroup data of non-T2DM patients from relevant secondary analysis articles in which subgroup analyses were done according to the status of diabetes. Compared to placebo, SGLT2 inhibitors significantly reduced heart failure hospitalization [risk ratio (RR) 0.70, 95% confidence interval (CI) 0.59–0.83] and kidney-specific composite outcome (RR 0.55, 95% CI 0.40–0.75) and increased Kansas City Cardiomyopathy Questionnaire total score by 1.15 (95% CI 1.05–1.25) in patients without T2DM with heart failure (HF) or chronic kidney disease (CKD), whereas gliflozins did not significantly affect cardiovascular death, all-cause mortality, volume depletion, fracture, and amputation in this vulnerable population. There was no event of major hypoglycemia or diabetic ketoacidosis observed in the non-T2DM subgroup in included trials. These findings will further prompt gliflozins to be used for the prevention of HF and renal failure events and for the improvement of life quality in patients without T2DM with HF or CKD.
Nanomedicine in Oncocardiology: Contribution and Perspectives of Preclinical Studies
Authors: Borges Gabriel Silva Marques , Lages Eduardo Burgarelli , Sicard Pierre , Ferreira Lucas Antônio Miranda , Richard Sylvain
Published: June 2021

Cancer and cardiovascular diseases are the leading causes of death and morbidity worldwide. Strikingly, cardiovascular disorders are more common and more severe in cancer patients than in the general population, increasing incidence rates. In this context, it is vital to consider the anticancer efficacy of a treatment and the devastating heart complications it could potentially cause. Oncocardiology has emerged as a promising medical and scientific field addressing these aspects from different angles. Interestingly, nanomedicine appears to have great promise in reducing the cardiotoxicity of anticancer drugs, maintaining or even enhancing their efficacy. Several studies have shown the benefits of nanocarriers, although with some flaws when considering the concept of oncocardiology. Herein, we discuss how preclinical studies should be designed as closely as possible to clinical protocols, considering various parameters intrinsic to the animal models used and the experimental protocols. The sex and age of the animals, the size and location of the tumors, the doses of the nanoformulations administered, and the acute vs. the long-term effects of treatments are essential aspects. We also discuss the perspectives offered by non-invasive imaging techniques to simultaneously assess both the anticancer effects of treatment and its potential impact on the heart. The overall objective is to accelerate the development and validation of nanoformulations through high-quality preclinical studies reproducing the clinical conditions.
Rediscovering, Reevaluating, and Restoring Lost River-Wetland Corridors
Authors: Wohl Ellen , Castro Janine , Cluer Brian , Merritts Dorothy , Powers Paul , Staab Brian , Thorne Colin
Published: June 2021

River-wetland corridors form where a high degree of connectivity between the surface (rheic) and subsurface (hyporheic) components of streamflow creates an interconnected system of channels, wetlands, ponds, and lakes. River-wetland corridors occur where the valley floor is sufficiently wide to accommodate a laterally unconfined river planform that may feature morphologically complex, multi-threaded channels with vegetated bars, islands, and floodplains. River-wetland corridors can develop anywhere there is valley expansion along a drainage network, from the headwaters to estuaries or deltas, and they are found across all latitudes and within all biomes and hydroclimates. River-wetland corridors may be longitudinally continuous but are commonly interspersed with single-thread reaches in narrower portions of the valley. The development and persistence of river-wetland corridors is driven by combinations of geologic, biotic, and geomorphic processes that create a river environment that is diverse, heterogeneous, patchy, and dynamically stable, and within which patterns of flow, sediment features, and habitats shift continually. Hence, we describe these polydimensional river corridors as “kaleidoscope rivers.” Historically, river-wetland corridors were pervasive in wide, alluvial valley reaches, but their presence has been so diminished worldwide (due to a diverse range of anthropogenic activities and impacts) that the general public and even most river managers are unaware of their former pervasiveness. Here, we define river-wetland corridors as a river type; review paleoenvironmental and historical records to establish their past ubiquity; describe the geologic, biotic, and geomorphic processes responsible for their formation and persistence; and provide examples of river-wetland corridor remnants that still survive. We close by highlighting the significance of the diverse river functions supported by river-wetland corridors, the consequences of diminution and neglect of this river type, and the implications for river restoration.
Changes in Cave Sedimentation Mechanisms During the Late Quaternary: An Example From the Lower Cerovačka Cave, Croatia
Authors: Kurečić Tomislav , Bočić Neven , Wacha Lara , Bakrač Koraljka , Grizelj Anita , Tresić Pavičić Dinko , Lüthgens Christopher , Sironić Andreja , Radović Siniša , Redovniković Loris , Fiebig Markus
Published: June 2021

During archeological excavations in the Lower Cerovačka Cave (Mt. Velebit, Croatia), the test trench penetrated to a depth of 1.8 m. An undisturbed sequence of sediments was exposed. Considering that caves represent highly efficient sediment traps it was possible to recognize changes in the depositional mechanisms during the Pleistocene–Holocene period. Using the multiproxy approach, the mineralogical, petrographic, and biostratigraphic characterization of the cave sediments was performed. Facies analysis revealed several stages in the development of the clastic filling of cave channels. Allochthonous origin of the sediment was assumed. Sedimentation took place under various conditions from pronounced cold and dry climate during Pleistocene stages in the base of the profile, to humid periods with anthropogenic influence during the Holocene at the very top of the profile. Although traditionally these sediments were believed to be of a Pleistocene age, here for the first time a stratigraphic calibration of the profile has been performed based on luminescence dating of detrital cave sediments and radiometric dating of speleothems.
Playing Entropy Mastermind can Foster Children’s Information-Theoretical Intuitions
Authors: Özel Elif , Nelson Jonathan D. , Bertram Lara , Martignon Laura
Published: June 2021

Conceptual descriptions and measures of information and entropy were established in the twentieth century with the emergence of a science of communication and information. Today these concepts have come to pervade modern science and society, and are increasingly being recommended as topics for science and mathematics education. We introduce a set of playful activities aimed at fostering intuitions about entropy and describe a primary school intervention that was conducted according to this plan. Fourth grade schoolchildren (8–10 years) played a version of Entropy Mastermind with jars and colored marbles, in which a hidden code to be deciphered was generated at random from an urn with a known, visually presented probability distribution of marble colors. Children prepared urns according to specified recipes, drew marbles from the urns, generated codes and guessed codes. Despite not being formally instructed in probability or entropy, children were able to estimate and compare the difficulty of different probability distributions used for generating possible codes.
Non-Symbolic Numerosity and Symbolic Numbers are not Processed Intuitively in Children: Evidence From an Event-Related Potential Study
Authors: van Hoogmoed Anne H. , Huijsmans Marije D. E. , Kroesbergen Evelyn H.
Published: June 2021

The approximate number system (ANS) theory and the ANS mapping account have been the most prominent theories on non-symbolic numerosity processing and symbolic number processing respectively, over the last 20 years. Recently, there is a growing debate about these theories, mainly based on research in adults. However, whether the ANS theory and ANS mapping account explain the processing of non-symbolic numerosity and symbolic number in childhood has received little attention. In the current ERP study, we first examined whether non-symbolic numerosity processing in 9-to-12-year-old children (N = 34) is intuitive, as proposed by the ANS theory. Second, we examined whether symbolic number processing is rooted in non-symbolic numerosity processing, as proposed the ANS mapping account. ERPs were measured during four same-different match-to-sample tasks with non-symbolic numerosities, symbolic numbers, and combinations of both. We found no evidence for intuitive processing of non-symbolic numerosity. Instead, children processed the visual features of non-symbolic stimuli more automatically than the numerosity itself. Moreover, children do not seem to automatically activate non-symbolic numerosity when processing symbolic numbers. These results challenge the ANS theory and ANS mapping account in 9-to-12-year-old children.
Estimating Smart Grid’s Carbon Emission Reduction Potential in China’s Manufacturing Industry Based on Decomposition Analysis
Authors: Fu Hua , Shi Yingying , Zeng Yongchao
Published: June 2021

China has a large manufacturing industry and shoulders the responsibility of reducing carbon emissions. Smart grid technologies can integrate multiple renewable energy technologies, which possess significant potential in reducing carbon emissions. To estimate the carbon emission reduction potential of the smart grid in China’s manufacturing industry, this paper applies a temporal logarithmic mean Divisia index (LMDI) method to analyze the driving forces of carbon emission changes in the whole manufacturing industry and 28 sub-industries from 2000 to 2017, respectively. The results reveal that industrial activity and energy intensity are the key factors leading to the increase and mitigation of carbon emissions, respectively. Sub-industries with high emission intensity are crucial for the reduction of carbon emissions in the manufacturing industry. By applying a smart grid, the carbon emissions could be reduced by 27.51% in the optimistic scenario.
Reliable Estimation of CD8 T Cell Inhibition of In Vitro HIV-1 Replication
Authors: Xu Yinyan , Weideman Ann Marie , Abad-Fernandez Maria , Mollan Katie R. , Kallon Sallay , Samir Shahryar , Warren Joanna A. , Clutton Genevieve , Roan Nadia R. , Adimora Adaora A. , Archin Nancie , Kuruc JoAnn , Gay Cynthia , Hudgens Michael G. , Goonetilleke Nilu
Published: June 2021

The HIV-1 viral inhibition assay (VIA) measures CD8 T cell-mediated inhibition of HIV replication in CD4 T cells and is increasingly used for clinical testing of HIV vaccines and immunotherapies. The VIA has multiple sources of variability arising from in vitro HIV infection and co-culture of two T cell populations. Here, we describe multiple modifications to a 7-day VIA protocol, the most impactful being the introduction of independent replicate cultures for both HIV infected-CD4 (HIV-CD4) and HIV-CD4:CD8 T cell cultures. Virus inhibition was quantified using a ratio of weighted averages of p24+ cells in replicate cultures and the corresponding 95% confidence interval. An Excel template is provided to facilitate calculations. Virus inhibition was higher in people living with HIV suppressed on antiretroviral therapy (n=14, mean: 40.0%, median: 43.8%, range: 8.2 to 73.3%; p < 0.0001, two-tailed, exact Mann-Whitney test) compared to HIV-seronegative donors (n = 21, mean: -13.7%, median: -14.4%, range: -49.9 to 20.9%) and was stable over time (n = 6, mean %COV 9.4%, range 0.9 to 17.3%). Cross-sectional data were used to define 8% inhibition as the threshold to confidently detect specific CD8 T cell activity and determine the minimum number of culture replicates and p24+ cells needed to have 90% statistical power to detect this threshold. Last, we note that, in HIV seronegative donors, the addition of CD8 T cells to HIV infected CD4 T cells consistently increased HIV replication, though the level of increase varied markedly between donors. This co-culture effect may contribute to the weak correlations observed between CD8 T cell VIA and other measures of HIV-specific CD8 T cell function.
Association of Immune and Inflammatory Gene Polymorphism With the Risk of IgA Nephropathy: A Systematic Review and Meta-Analysis of 45 Studies
Authors: Ding Xiaonan , Mei Yan , Mao Zhi , Long Lingling , Han Qiuxia , You Yanqin , Zhu Hanyu
Published: June 2021

IgA nephropathy is the most prevalent primary glomerulonephritis worldwide, with identical immunopathological characteristics caused by multiple etiologies as well as influenced by geographical and ethnical factors. To elucidate the role of immunologic and inflammatory mechanisms in the susceptibility to IgA nephropathy, we explored single nucleotide polymorphisms of related molecules in the immune pathways. We searched the PubMed database for studies that involved all gene variants of molecules in the 20 immunologic and inflammatory pathways selected from the Kyoto Encyclopedia of Genes and Genomes database. The odds ratios with their corresponding 95% confidence intervals in six genetic models (allele model, dominant model, homozygote model, heterozygote model, overdominant model, and recessive model) were summarized using fixed or random effect models. Subgroup analysis was conducted based on different ethnicities with generalized odds ratios. Heterogeneity was evaluated using the Q and I2 tests. Begg’s funnel plot and Egger’s linear regression test were used to evaluating possible publication bias among the included studies, and sensitivity analysis was used to test the stability of the overall results. A total of 45 studies met our selection criteria and eight related genetic association studies were retrieved, including 320 single-nucleotide polymorphisms from 20 candidate pathways, ranging from 2000 to 2021. A total of 28,994 healthy people versus 20,600 IgA nephropathy patients were enrolled. Upon meta-analyzed results that TGFB1 (rs1800469, rs1982073, rs1800471), IL-1B (rs1143627), IL-18 (rs1946518), and TLR1 (rs5743557) showed effect with or without ethnicity difference. And 10 variants presented stable and robust related to IgA nephropathy. This research showed that genetic variants are related to the immunologic and inflammatory effects of IgA nephropathy pathogenesis. The meta-analysis results supported the previous researches, and may help deepen the understanding of pathogenesis and explore new targets for IgA nephropathy-specific immunotherapy.
Enhanced Expression of Autoantigens During SARS-CoV-2 Viral Infection
Authors: Saheb Sharif-Askari Narjes , Saheb Sharif-Askari Fatemeh , Ahmed Samrein B. M. , Hannawi Suad , Hamoudi Rifat , Hamid Qutayba , Halwani Rabih
Published: June 2021

Immune homeostasis is disturbed during severe viral infections, which can lead to loss of tolerance to self-peptides and result in short- or long-term autoimmunity. Using publicly available transcriptomic datasets, we conducted an in-silico analyses to evaluate the expression levels of 52 autoantigens, known to be associated with 24 autoimmune diseases, during SAR-CoV-2 infection. Seven autoantigens (MPO, PRTN3, PADI4, IFIH1, TRIM21, PTPRN2, and TSHR) were upregulated in whole blood samples. MPO and TSHR were overexpressed in both lung autopsies and whole blood tissue and were associated with more severe COVID-19. Neutrophil activation derived autoantigens (MPO, PRTN3, and PADI4) were prominently increased in blood of both SARS-CoV-1 and SARS-CoV-2 viral infections, while TSHR and PTPRN2 autoantigens were specifically increased in SARS-CoV-2. Using single-cell dataset from peripheral blood mononuclear cells (PBMCs), we observed an upregulation of MPO, PRTN3, and PADI4 autoantigens within the low-density neutrophil subset. To validate our in-silico analysis, we measured plasma protein levels of two autoantigens, MPO and PRTN3, in severe and asymptomatic COVID-19. The protein levels of these two autoantigens were significantly upregulated in more severe COVID-19 infections. In conclusion, the immunopathology and severity of COVID-19 could result in transient autoimmune activation. Longitudinal follow-up studies of confirmed cases of COVID-19 could determine the enduring effects of viral infection including development of autoimmune disease.
Pathogenic Role of Circulating Citrullinated Antigens and Anti-Cyclic Monoclonal Citrullinated Peptide Antibodies in Rheumatoid Arthritis
Authors: Won Pureun , Kim Youngkyun , Jung Hyerin , Rim Yeri Alice , Sohn Dong Hyun , Robinson William H. , Moon Su-Jin , Ju Ji Hyeon
Published: June 2021

We examined whether it is possible to directly detect citrullinated antigens in the serum of rheumatoid arthritis (RA) patients using a monoclonal antibody (mAb) designed to be specific for citrullinated peptides. In order to confirm the potential of the mAb as a direct arthritis-inducing substance through experimental model of RA, a monoclonal antibody (mAb) 12G1 was generated using by immunization of mice with a challenging cyclic citrullinated peptide. Immunohistochemical analysis of RA-affected synovial tissue showed that our mAb 12G1 could indeed detect citrullinated proteins in target tissues. Subsequently, serum levels of citrullinated type II collagen and filaggrin were measured in healthy volunteers, patients with RA, ankylosing spondylitis (AS), and systemic lupus erythematosus (SLE) using a 12G1-based sandwich ELISA. This showed that citrullinated filaggrin showed 78.9% sensitivity and 85.9% specificity for RA diagnosis with a cutoff optical density (OD) value of 1.013, comparable with the results from a second-generation anti-citrullinated protein antibody (ACPA) test. Circulating citrullinated collagen and filaggrin were detected even in sera of RA patients who were negative for both rheumatoid factor (RF) and ACPA. ELISA results also showed that RF and ACPA titers showed significantly positive correlation with both citrullinated collagen and filaggrin OD values in sera of RA patients. 12G1 challenging aggravated the severity of murine arthritis. In summary, mAb 12G1 can directly detect citrullinated proteins in RA target tissue and in sera of RA patients and 12G1 showed direct arthritogenic potentialin vivo. This, 12G1 might be useful for diagnosis of RA including seronegative RA and may help to elucidate the pathophysiological role of citrullination in RA.
Erythropoietin Receptor/β Common Receptor: A Shining Light on Acute Kidney Injury Induced by Ischemia-Reperfusion
Authors: Wu Yuanyuan , Yang Bin
Published: June 2021

Acute kidney injury (AKI) is a health problem worldwide, but there is a lack of early diagnostic biomarkers and target-specific treatments. Ischemia-reperfusion (IR), a major cause of AKI, not only induces kidney injury, but also stimulates the self-defense system including innate immune responses to limit injury. One of these responses is the production of erythropoietin (EPO) by adjacent normal tissue, which is simultaneously triggered, but behind the action of its receptors, either by the homodimer EPO receptor (EPOR)2 mainly involved in erythropoiesis or the heterodimer EPOR/β common receptor (EPOR/βcR) which has a broad range of biological protections. EPOR/βcR is expressed in several cell types including tubular epithelial cells at low levels or absent in normal kidneys, but is swiftly upregulated by hypoxia and inflammation and also translocated to cellular membrane post IR. EPOR/βcR mediates anti-apoptosis, anti-inflammation, pro-regeneration, and remodeling via the PI3K/Akt, STAT3, and MAPK signaling pathways in AKI. However, the precise roles of EPOR/βcR in the pathogenesis and progression of AKI have not been well defined, and its potential as an earlier biomarker for AKI diagnosis and monitoring repair or chronic progression requires further investigation. Here, we review biological functions and mechanistic signaling pathways of EPOR/βcR in AKI, and discuss its potential clinical applications as a biomarker for effective diagnosis and predicting prognosis, as well as directing cell target drug delivery.
Updating the NLRC4 Inflammasome: from Bacterial Infections to Autoimmunity and Cancer
Authors: Wen Jiexia , Xuan Bin , Liu Yang , Wang Liwei , He Li , Meng Xiangcai , Zhou Tao , Wang Yimin
Published: June 2021

Inflammasomes comprise a family of cytosolic multi-protein complexes that modulate the activation of cysteine-aspartate-specific protease 1 (caspase-1) and promote the maturation and secretion of interleukin (IL)-1β and IL-18, leading to an inflammatory response. Different types of inflammasomes are defined by their sensor protein which recognizes pathogenic ligands and then directs inflammasome assembly. Although the specific molecular mechanisms underlying the activation of most inflammasomes are still unclear, NLRC4 inflammasomes have emerged as multifaceted agents of the innate immune response, playing important roles in immune defense against a variety of pathogens. Other studies have also expanded the scope of NLRC4 inflammasomes to include a range of inherited human autoimmune diseases as well as proposed roles in cancer. In this review article, we provide an updated overview of NLRC4 inflammasomes, describing their composition, activation mechanisms and roles in both microbial infections and other disease conditions.
Underwhelming or Misunderstood? Genetic Variability of Pattern Recognition Receptors in Immune Responses and Resistance to Mycobacterium tuberculosis
Authors: Dubé Jean-Yves , Fava Vinicius M. , Schurr Erwin , Behr Marcel A.
Published: June 2021

Human genetic control is thought to affect a considerable part of the outcome of infection withMycobacterium tuberculosis(Mtb). Most of us deal with the pathogen by containment (associated with clinical “latency”) or sterilization, but tragically millions each year do not. After decades of studies on host genetic susceptibility toMtbinfection, genetic variation has been discovered to play a role in tuberculous immunoreactivity and tuberculosis (TB) disease. Genes encoding pattern recognition receptors (PRRs) enable a consistent, molecularly direct interaction between humans andMtbwhich suggests the potential for co-evolution. In this review, we explore the roles ascribed to PRRs duringMtbinfection and ask whether such a longstanding and intimate interface between our immune system and this pathogen plays a critical role in determining the outcome ofMtbinfection. The scientific evidence to date suggests that PRR variation is clearly implicated in altered immunity toMtbbut has a more subtle role in limiting the pathogen and pathogenesis. In contrast to ‘effectors’ like IFN-γ, IL-12, Nitric Oxide and TNF that are critical forMtbcontrol, ‘sensors’ like PRRs are less critical for the outcome ofMtbinfection. This is potentially due to redundancy of the numerous PRRs in the innate arsenal, such thatMtbrarely goes unnoticed. Genetic association studies investigating PRRs duringMtbinfection should therefore be designed to investigate endophenotypes of infection – such as immunological or clinical variation – rather than just TB disease, if we hope to understand the molecular interface between innate immunity andMtb.
Leaving the Dark Side? Insights Into the Evolution of Luciferases
Authors: Delroisse Jérôme , Duchatelet Laurent , Flammang Patrick , Mallefet Jérôme
Published: June 2021

Bioluminescence—i.e., the emission of visible light by living organisms—is defined as a biochemical reaction involving, at least, a luciferin substrate, an oxygen derivative, and a specialised luciferase enzyme. In some cases, the enzyme and the substrate are durably associated and form a photoprotein. While this terminology is educatively useful to explain bioluminescence, it gives a false idea that all luminous organisms are using identical or homologous molecular tools to achieve light emission. As usually observed in biology, reality is more complex. To date, at least 11 different luciferins have indeed been discovered, and several non-homologous luciferases lato sensu have been identified which, all together, confirms that bioluminescence emerged independently multiple times during the evolution of living organisms. While some phylogenetically related organisms may use non-homologous luciferases (e.g., at least four convergent luciferases are found in Pancrustacea), it has also been observed that phylogenetically distant organisms may use homologous luciferases (e.g., parallel evolution observed in some cnidarians, tunicates and echinoderms that are sharing a homologous luciferase-based system). The evolution of luciferases then appears puzzling. The present review takes stock of the diversity of known “bioluminescent proteins,” their evolution and potential evolutionary origins. A total of 134 luciferase and photoprotein sequences have been investigated (from 75 species and 11 phyla), and our analyses identified 12 distinct types—defined as a group of homologous bioluminescent proteins. The literature review indicated that genes coding for luciferases and photoproteins have potentially emerged as new genes or have been co-opted from ancestral non-luciferase/photoprotein genes. In this latter case, the homologous gene’s co-options may occur independently in phylogenetically distant organisms.
Physiological and Transcriptomic Variability Indicative of Differences in Key Functions Within a Single Coral Colony
Authors: Drake Jeana L. , Malik Assaf , Popovits Yotam , Yosef Oshra , Shemesh Eli , Stolarski Jarosław , Tchernov Dan , Sher Daniel , Mass Tali
Published: June 2021

Polyps in different locations on individual stony coral colonies experience variation in numerous environmental conditions including flow and light, potentially leading to transcriptional and physiological differences across the colony. Here, we describe high-resolution tissue and skeleton measurements and differential gene expression from multiple locations within a single colony ofStylophora pistillata, aiming to relate these to environmental gradients across the coral colony. We observed broad transcriptional responses in both the host and photosymbiont in response to height above the substrate, cardinal direction, and, most strongly, location along the branch axis. Specifically, several key physiological processes in the host appear more active toward branch tips including several metabolic pathways, toxin production for prey capture or defense, and biomolecular mechanisms of biomineralization. Further, the increase in gene expression related to these processes toward branch tips is conserved betweenS. pistillataandAcroporaspp. The photosymbiont appears to respond transcriptionally to relative light intensity along the branch and due to cardinal direction. These differential responses were observed across the colony despite its genetic homogeneity and likely inter-polyp communication. While not a classical division of labor, each part of the colony appears to have distinct functional roles related to polyps’ differential exposure to environmental conditions.
Development and Validation of a Prognostic Classifier Based on Lipid Metabolism–Related Genes in Gastric Cancer
Authors: Wei Xiao-Li , Luo Tian-Qi , Li Jia-Ning , Xue Zhi-Cheng , Wang Yun , Zhang You , Chen Ying-Bo , Peng Chuan
Published: June 2021

Background: Dysregulation of lipid metabolism plays important roles in the tumorigenesis and progression of gastric cancer (GC). The present study aimed to establish a prognostic model based on the lipid metabolism–related genes in GC patients.

Materials and Methods: Two GC datasets from the Gene Expression Atlas, GSE62254 (n = 300) and GSE26942 (n = 217), were used as training and validation cohorts to establish a risk predictive scoring model. The efficacy of this model was assessed by ROC analysis. The association of the risk predictive scores with patient characteristics and immune cell subtypes was evaluated. A nomogram was constructed based on the risk predictive score model and other prognostic factors.

Results: A risk predictive score model was established based on the expression of 19 lipid metabolism–related genes (LPL, IPMK, PLCB3, CDIPT, PIK3CA, DPM2, PIGZ, GPD2, GPX3, LTC4S, CYP1A2, GALC, SGMS1, SMPD2, SMPD3, FUT6, ST3GAL1, B4GALNT1, and ACADS). The time-dependent ROC analysis revealed that the risk predictive score model was stable and robust. Patients with high risk scores had significantly unfavorable overall survival compared with those with low risk scores in both the training and validation cohorts. A higher risk score was associated with more aggressive features, including a higher tumor grade, a more advanced TNM stage, and diffuse type of Lauren classification of GC. Moreover, distinct immune cell subtypes and signaling pathways were found between the high–risk and low–risk score groups. A nomogram containing patients’ age, tumor stage, adjuvant chemotherapy, and the risk predictive score could accurately predict the survival probability of patients at 1, 3, and 5 years.

Conclusion: A novel 19-gene risk predictive score model was developed based on the lipid metabolism–related genes, which could be a potential prognostic indicator and therapeutic target of GC.
The Role of Indoor Plants in air Purification and Human Health in the Context of COVID-19 Pandemic: A Proposal for a Novel Line of Inquiry
Authors: El-Tanbouly Rania , Hassan Ziad , El-Messeiry Sarah
Published: June 2021

The last two decades have seen the discovery of novel retroviruses that have resulted in severe negative consequences for human health. In late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged with a high transmission rate and severe effects on human health, with 5% infected persons requiring hospitalisation and 3.81 million deaths to date globally. Aerosol particles containing virions are considered the main source of SARS CoV-2 transmission in this pandemic, with increased infection rates in confined spaces. Consequently, public and private institutions had to institute mitigation measures including the use of facial masks and social distancing to limit the spread of the virus. Moreover, the role of air purification and bio-decontamination is understood as being essential to mitigate viral spread. Various techniques can be applied to bio-decontaminate the air such as the use of filtration and radiation; however, these methods are expensive and not feasible for home use. Another method of air purification is where indoor plants can purify the air by the removal of air pollutants and habituated airborne microbes. The use of indoor plants could prove to be a cost-efficient way of indoor air-purification that could be adapted for a variety of environments with no need for special requirements and can also add an aesthetic value that can have an indirect impact on human health. In this review, we discuss the emergence of the COVID-19 pandemic and the currently used air purification methods, and we propose the use of indoor plants as a new possible eco-friendly tool for indoor air purification and for reducing the spread of COVID-19 in confined places.