bluuebunny/crossref_metadata_2025 huggingface dataset:
Open data policy, e-commerce connectivity and catalog size predict a global brand’s online popularity rank
Authors: Hoogeveen Martijn
Published: September 2022

Content marketing is increasingly important for online branding. However, brand popularity is not yet well-understood form a content marketing perspective. We used brand popularity and catalog data in combination with product reviews (n = 333 brands). Backward stepwise multiple linear regression was used to develop a predictive model of the brand popularity rank. We identified highly significant predictive factors for brand rank in our content marketing model: the brand’s data syndication policy, the number of connected e-commerce platforms, and a brand’s catalog size. Our model explains 78% of the variance of Global Brand Rank and has a good and highly significant fit: F (5, 327) = 233.5, p < 0.00001. We conclude that a content marketing model can adequately predict a global brand's popularity. In this model an open content syndication policy, more connected e-commerce platforms, and catalog size are each related to a better (lower) Global Brand Rank score.
Ring Field and Vector Space on Combinatorial Geometric Series and Binomial Coefficients
Authors: Annamalai Chinnaraji
Published: September 2022

This paper discusses an abelian group, ring, field, vector space under addition and multiplication of the binomial coefficients in combinatorial geometric series. The coefficient for each term in combinatorial geometric series refers to a binomial coefficient. This idea can enable the scientific researchers to solve the real life problems.
A Very Brief Note on the Riemann Hypothesis
Authors: Vega Frank
Published: September 2022

Robin's criterion states that the Riemann Hypothesis is true if and only if the inequality $\sigma(n) < e^{\gamma} \cdot n \cdot \log \log n$ holds for all natural numbers $n > 5040$, where $\sigma(n)$ is the sum-of-divisors function of $n$ and $\gamma \approx 0.57721$ is the Euler-Mascheroni constant. We require the properties of superabundant numbers, that is to say left to right maxima of $n \mapsto \frac{\sigma(n)}{n}$. In this note, using Robin's inequality on superabundant numbers, we prove that the Riemann Hypothesis is true. This proof is an extension of the article ``Robin's criterion on divisibility'' published by The Ramanujan Journal on May 3rd, 2022.
Production of secondary metabolites in stirred tank bioreactor co-cultures of Streptomyces noursei and Aspergillus terreus
Authors: Boruta Tomasz , Ścigaczewska Anna , Bizukojć Marcin
Published: September 2022

The focus of the study was to characterize the bioprocess kinetics and secondary metabolites production in the novel microbial co-cultivation system involving Streptomyces noursei ATCC 11455 (the producer of an antifungal substance known as nystatin) and Aspergillus terreus ATCC 20542 (the source of lovastatin, a cholesterol-lowering drug). The investigated “A. terreus vs. S. noursei” stirred tank bioreactor co-cultures allowed for the concurrent development and observable biosynthetic activity of both species. In total, the production profiles of 50 secondary metabolites were monitored over the course of the study. The co-cultures were found to be effective in terms of enhancing the biosynthesis of several metabolic products, including mevinolinic acid, an acidic form of lovastatin. This work provided a methodological example of assessing the activity of a given strain in the co-culture by using the substrates which can be metabolized exclusively by this strain. Since S. noursei was shown to be incapable of lactose utilization, the observed changes in lactose levels were attributed to A. terreus and thus confirmed its viability. The study was complemented with the comparative microscopic observations of filamentous morphologies exhibited in the co-cultures and corresponding monocultures.
Development of functional hydroxyethyl cellulose-based composite films for food packaging applications
Authors: Zhang Xueqin , Guo Haoqi , Luo Wenhan , Chen Guojian , Xiao Naiyu , Xiao Gengsheng , Liu Chuanfu
Published: September 2022

Cellulose-based functional composite films can be a good substitute for conventional plastic packaging to ensure food safety. In this study, the semi-transparent, mechanical strengthened, UV-shielding, antibacterial and biocompatible films were developed from hydroxyethyl cellulose Polyvinyl alcohol (PVA) and ε-polylysine (ε-PL) were respectively used as reinforcing agent and antibacterial agent, and chemical cross-linking among these three components were constructed using epichlorohydrin The maximum tensile strength and elongation at break were 95.9 ± 4.1 MPa and 148.8 ± 2.6%, respectively. TG-FTIR and XRD analyses indicated that chemical structure of the composite films could be well controlled by varying component proportion. From UV-Vis analysis, the optimum values of the percentage of blocking from UV-A and UV-B and ultraviolet protection factor values were 98.35%, 99.99% and 60.25, respectively. Additionally, the composite films exhibited good water vapor permeability, swelling behavior, antibacterial activity and biocompatibility. In terms of these properties, the shelf life of grapes could be extended to 6 days after packing with the composite film.
Micro/mesoporous LTL derived materials for catalytic transfer hydrogenation and acid reactions of bio-based levulinic acid and furanics
Authors: Antunes Margarida M. , Silva Andreia F. , Fernandes Auguste , Ribeiro Filipa , Neves Patrícia , Pillinger Martyn , Valente Anabela A.
Published: September 2022

The biomass-derived platform chemicals furfural and 5-(hydroxymethyl)furfural (HMF) may be converted to α-angelica lactone (AnL) and levulinic acid (LA). Presently, LA (synthesized from carbohydrates) has several multinational market players. Attractive biobased oxygenated fuel additives, solvents, etc., may be produced from AnL and LA via acid and reduction chemistry, namely alkyl levulinates and γ-valerolactone (GVL). In this work, hierarchical hafnium-containing multifunctional Linde type L (LTL) related zeotypes were prepared via top-down strategies, for the chemical valorization of LA, AnL and HMF via integrated catalytic transfer hydrogenation (CTH) and acid reactions in alcohol medium. This is the first report of CTH applications (in general) of LTL related materials. The influence of the post-synthesis treatments/conditions (desilication, dealumination, solid-state impregnation of Hf or Zr) on the material properties and catalytic performances was studied. AnL and LA were converted to 2-butyl levulinate (2BL) and GVL in high total yields of up to ca. 100%, at 200°C, and GVL/2BL molar ratios up to 10. HMF conversion gave mainly the furanic ethers 5-(sec-butoxymethyl)furfural and 2,5-bis(sec-butoxymethyl)furan (up to 63% total yield, in 2-butanol at 200°C/24 h). Mechanistic, reaction kinetics and material characterization studies indicated that the catalytic results depend on a complex interplay of different factors (material properties, type of substrate). The recovered-reused solids performed steadily.
High efficient room temperature phosphorescent materials constructed with methylene molecular configuration
Authors: Wang Jian
Published: September 2022

In this work, we have investigated several pure organic room temperature phosphorescent materials with donor-methylene acceptor configurations with relatively different quantum efficiency. The results show that the introduction of methylene functional group in room temperature phosphorescent materials based on donor-acceptor configuration is more favorable for obtaining higher phosphorescent quantum efficiency in crystal phase environment. More importantly, our calculations reveal the root cause of the excellent quantum efficiency performance after the introduction of methylene groups. The results show that the introduction of methylene can inhibit the structural deformation of molecules during the excited state transition process and give them higher interaction. Moreover, in the donor-acceptor configuration, the heavy atom effect is more favorable to the formation of π-x (X = Br) interaction to accelerate the occurrence of intersystem crossing and achieve a higher intersystem crossing rate. Therefore, the donor-methylene-acceptor molecule is expected to improve the quantum efficiency of room temperature phosphorescence, and the addition of heavy atoms is more conducive to prolong the life of room temperature phosphorescence. This work provides a useful reference for rational design of room temperature phosphorescent materials with high efficiency and long life.
Significant difference of differential expression pyroptosis-related genes and their correlations with infiltrated immune cells in sepsis
Authors: Wang Li , Zhang Jiting , Zhang Li , Hu Lingli , Tian Jianhui
Published: September 2022

Background

Sepsis is regarded as a life-threatening organ dysfunction syndrome that responds to infection. Pyroptosis, a unique form of programmed cell death, is characterized by inflammatory cytokine secretion. Recently, an increasing number of studies have investigated the relationship between sepsis and pyroptosis. Appropriate pyroptosis can help to control infection during sepsis, but an immoderate one may cause immune disorders. The present study aimed to identify pyroptosis-related gene biomarkers and their relationship with the immune microenvironment using the genome-wide technique.

Methods

The training dataset GSE154918 and the validation dataset GSE185263 were downloaded for bioinformatics analysis. Differentially expressed pyroptosis-related genes (DEPRGs) were identified between sepsis (including septic shock) and healthy samples. Gene Set Enrichment Analysis (GSEA) was performed to explore gene function. CIBERSORT tools were applied to quantify infiltrating immune cells, and the correlation between differentially infiltrating immune cells and DEPRG expression was investigated. Furthermore, based on multivariable Cox regression, the study also utilized a random forest (RF) model to screen biomarkers.

Results

In total, 12 DEPRGs were identified. The expression level of PLCG1 was continuously significantly decreased, while the expression level of NLRC4 was elevated from control to sepsis and then to septic shock. GSEA found that one DEPRG (PLCG1) was involved in the T-cell receptor signaling pathway and that many T cell-related immunologic signature gene sets were enriched. The proportions of plasma cells, T cells CD4 memory activated, and some innate cells in the sepsis group were significantly higher than those in the healthy group, while the proportions of T cells CD8, T cells CD4 memory resting, T cells regulatory (Tregs), and NK cells were lower. Additionally, CASP4 was positively correlated with Neutrophils and negatively correlated with T cells CD4 memory resting and Tregs. Lastly, two biomarkers (CASP4 and PLCG1) were identified, and a nomogram model was constructed for diagnosis with area under the curve (AUC) values of 0.998.

Conclusion

This study identified two potential pyroptosis-related diagnostic genes, CASP4 and PLCG1, and explored the correlation between DEPRGs and the immune microenvironment. Also, our study indicated that some DEPRGs were satisfactorily correlated with several representative immune cells that can regulate pyroptosis.
Dynamic electrophysiological mechanism in patients with long-standing persistent atrial fibrillation
Authors: Osorio-Jaramillo Emilio , Cox James L. , Klenk Sarah , Kaider Alexandra , Angleitner Philipp , Werner Paul , Strassl Andreas , Mach Markus , Laufer Guenther , Ehrlich Marek P. , Ad Niv
Published: September 2022

Background

Improved understanding of the mechanisms that sustain persistent and long-standing persistent atrial fibrillation (LSpAF) is essential for providing better ablation solutions. The findings of traditional catheter-based electrophysiological studies can be impacted by the sedation required for these procedures. This is not required in non-invasive body-surface mapping (ECGI). ECGI allows for multiple mappings in the same patient at different times. This would expose potential electrophysiological changes over time, such as the location and stability of extra-pulmonary vein drivers and activation patterns in sustained AF.

Materials and methods

In this electrophysiological study, 10 open-heart surgery candidates with LSpAF, without previous ablation procedures (6 male, median age 73 years), were mapped on two occasions with a median interval of 11 days (IQR: 8–19) between mappings. Bi-atrial epicardial activation sequences were acquired using ECGI (CardioInsight™, Minneapolis, MN, United States).

Results

Bi-atrial electrophysiological abnormalities were documented in all 20 mappings. Interestingly, the anatomic location of focal and rotor activities changed between the mappings in all patients [100% showed changes, 95%CI (69.2–100%), p < 0.001]. Neither AF driver type nor their number varied significantly between the mappings in any patient (median total number of focal activities 8 (IQR: 1–16) versus 6 (IQR: 2–12), p = 0.68; median total number of rotor activities 48 (IQR: 44–67) versus 55 (IQR: 44–61), p = 0.30). However, individual zones showed a high number of quantitative changes (increase/decrease) of driver activity. Most changes of focal activity were found in the left atrial appendage, the region of the left lower pulmonary vein and the right atrial appendage. Most changes in rotor activity were found also at the left lower pulmonary vein region, the upper half of the right atrium and the right atrial appendage.

Conclusion

This clinical study documented that driver location and activation patterns in patients with LSpAF changes constantly. Furthermore, bi-atrial pathophysiology was demonstrated, which underscores the importance of treating both atria in LSpAF and the significant role that arrhythmogenic drivers outside the pulmonary veins seem to have in maintaining this complex arrhythmia.
Severe flood probability on the middle Changjiang (Yangtze River) after completion of the Three Gorges Dam
Authors: Shankman David , Lai Xijun
Published: September 2022

A major justification for building the Three Gorges Dam on the Changjiang is flood control. The dam can reduce peak discharge during severe floods. These floods, however, cannot be prevented by operation of the Three Gorges Dam alone. During the most severe floods abnormally high rainfall occurs throughout the Changjiang basin. The Three Gorges Dam can only affect discharge from the upper basin. Large tributaries on the middle Changjiang are unaffected by the dam. The cumulative impact of high discharge from large tributaries on the middle Changjiang increase flood severity with distance downstream. Also, Changjiang-lake interaction is affected by decreasing volume of Poyang and Dongting Lakes that occurred during the past few decades. These are the largest freshwater lakes in China. As a result of reduced floodwater storage capacity during summer high discharge periods, tributaries flow into the lakes with a higher base level than previously occurred. Instead of Changjiang back flowing into the lakes as previously expected during major floods, high Changjiang discharge occurs at the same time as high tributary discharge that increases peak river stage.
The self-efficacy of private school teachers toward the implementation of inclusive education in Ghana: A mixed-methods study
Authors: Opoku Maxwell Peprah , Nketsia William , Mohamed Ahmed H.
Published: September 2022

Background

Although efforts toward practicing inclusive education have stalled in countries such as Ghana, the available data have mainly centred on enacting inclusive education in public schools. With private schools being notable alternative service providers to public schools, understanding private school teachers’ perceived self-efficacy toward teaching students with disabilities in the classroom is essential.

Method

To develop insights into inclusive practices, a two-phase mixed-methods design was adopted for this study. In the first phase, 82 teachers from six private schools responded to the self-reported Teacher Efficacy for Inclusive Practice (TEIP) scale. In the second phase, there were 10 participants, including principals (n= 3), heads of department (n= 4) and teachers (n= 3). While the quantitative data were subjected to confirmatory factor analysis,t-tests, analysis of variance and linear regression, the qualitative data were analysed thematically using the components of the TEIP scale asa priorithemes.

Result

The study confirmed the structural validity of the TEIP scale in measuring teachers’ self-efficacy and the correlations and covariances between efficacy in managing behaviour and performing instruction and collaboration. There was divergence between the quantitative and qualitative data and background variables, such as educational qualifications, pre-service training in inclusive education and participation in professional development, which provided additional insights into the teachers’ self-efficacy.

Conclusion

The findings show that some private school teachers teach students with disabilities despite having no confidence in their capabilities. The study findings underscore the need to create more training opportunities for private school teachers to enhance their confidence in practicing inclusive education in schools.
Current insights of applying MRI in Graves’ ophthalmopathy
Authors: Song Cheng , Luo Yaosheng , Yu Genfeng , Chen Haixiong , Shen Jie
Published: September 2022

Graves’ ophthalmopathy (GO) is an autoimmune disease related to Grave’s disease (GD). The therapeutic strategies for GO patients are based on precise assessment of the activity and severity of the disease. However, the current assessment systems require development to accommodate updates in treatment protocols. As an important adjunct examination, magnetic resonance imaging (MRI) can help physicians evaluate GO more accurately. With the continuous updating of MRI technology and the deepening understanding of GO, the assessment of this disease by MRI has gone through a stage from qualitative to precise quantification, making it possible for clinicians to monitor the microstructural changes behind the eyeball and better integrate clinical manifestations with pathology. In this review, we use orbital structures as a classification to combine pathological changes with MRI features. We also review some MRI techniques applied to GO clinical practice, such as disease classification and regions of interest selection.
Pore-scale phenomena in carbon geological storage (Saline aquifers—Mineralization—Depleted oil reservoirs)
Authors: Liu Qi , Benitez Marcelo D. , Xia Zhao , Santamarina J. Carlos
Published: September 2022

The injection of CO2 into geological formations triggers inherently coupled thermo-hydro-chemo-mechanical processes. The reservoir pressure and temperature determine the CO2 density, the CO2-water interfacial tension, and the solubility of CO2 in water (hindered by salts and competing gases). The CO2-water interface experiences marked pinning onto mineral surfaces, and contact angles can range from the asymptotic advancing to receding values, in contrast to the single contact angle predicted by Young’s equation. CO2 dissolves in water to form carbonic acid and the acidified water dissolves minerals; mineral dissolution enhances porosity and permeability, triggers settlement, may couple with advection to form “wormholes”, produces stress changes and may cause block sliding and shear bands. Convective currents can emerge beneath the CO2 plume and sustain CO2 and mineral dissolution processes. On the other hand, mineralization is a self-homogenizing process in advective regimes. The crystallization pressure can exceed the tensile capacity of the host rock and create new surfaces or form grain-displacive lenses. Within the rock matrix, coupled reactive-diffusion-precipitation results in periodic precipitation bands. Adequate seal rocks for CO2 geological storage must be able to sustain the excess capillary pressure in the buoyant CO2 plume without experiencing open-mode discontinuities or weakening physico-chemical interactions. CO2 injection into depleted oil reservoirs benefits from time-proven seals; in addition, CO2 can mobilize residual oil to simultaneously recover additional oil through oil swelling, ganglia destabilization, the reduction in oil viscosity and even miscible displacement. Rapid CO2 depressurization near the injection well causes cooling under most anticipated reservoir conditions; cooling can trigger hydrate and ice formation, and reduce permeability. In some cases, effective stress changes associated with the injection pressure and cooling thermoelasticity can reactivate fractures. All forms of carbon geological storage will require large reservoir volumes to hold a meaningful fraction of the CO2 that will be emitted during the energy transition.
Variation in the VLF signal noise amplitude during the period of intense seismic activity in Central Italy from 25 October to 3 November 2016
Authors: Nina Aleksandra , Biagi Pier Francesco , Pulinets Sergey , Nico Giovanni , Mitrović Srđan T. , Čadež Vladimir M. , Radovanović Milan , Urošev Marko , Popović Luka Č.
Published: September 2022

Recent research shows reductions in the VLF signal noise amplitude that begin before particular earthquakes whose epicentres are more than 100 km away from the signal propagation path. In this paper, we extend this research to studying the noise amplitude during periods of intense seismic activity in a localized area. We analyse variations in the VLF signal noise amplitude over a period of 10 days (25 October–3 November 2016) when 981 earthquakes with the minimum magnitude of 2 occurred in Central Italy. Out of these events, 31 had the magnitude equal or greater than 4, while the strongest one had the magnitude of 6.5. We observe the VLF signal emitted by the ICV transmitter located in Sardinia (Italy) and recorded in Belgrade (Serbia). Bearing in mind that the trajectory of this signal crosses the area in which the observed earthquakes occurred, we extend the existing research to study of variations in the noise amplitude of the signal propagating at short distances from the epicentres of the considered earthquakes. In addition, we analyse the impact of a large number earthquakes on characteristics of the noise amplitude and its reductions before particular events. In order to examine the localization of the recorded changes, we additionally analysed the noise amplitude of two reference signals emitted in Germany and Norway. The obtained results show the existence of the noise amplitude reduction preceding individual strong or relatively strong earthquakes, and earthquakes followed by others that occurred in a shorter time interval. However, the additional noise amplitude reductions are either not pronounced or they do not exist before the considered events in periods of the reduced noise amplitude remain from previous earthquakes. Reductions in noise amplitudes for all observed signals indicate a larger perturbed area through which they spread or its closer location to the receiver. The analysis of daily values of parameters describing the noise amplitude reveals their variations start up to 2 weeks before the seismically active period occurs.
Effects of dissolved black carbon bound with goethite on physicochemical properties and adsorption capacity for imidacloprid: Adsorption versus coprecipitation
Authors: Zhang Peng , Ma Mingming , Meng Xingying , Shao Yifei , Liu Aiju
Published: September 2022

Dissolved black carbon (DBC) is an important component of natural dissolved organic matter and can bind to iron minerals to form DBC-mineral complexes by adsorption and coprecipitation. However, reports regarding the difference in physicochemical properties between adsorbed and coprecipitated DBC-mineral complexes and their sorption capacity for polar organic pollutants are limited. Herein, goethite (Gt) and the adsorbed and coprecipitated complexes of DBC with Gt (SGt-DBC and CGt-DBC) were prepared, and their physicochemical properties and adsorption capacity for polar imidacloprid (IMI) were determined. The results showed that DBC could efficiently bind to Gt by coprecipitation or adsorption, leading to the aggregation of Gt particles, decreasing SSA, and increasing microporous volume, O-containing functional groups and negative charges. A greater effect was observed in CGt-DBC samples than SGt-DBC samples. CGt-DBC samples could more efficiently adsorb IMI than SGt-DBC samples, and CGt-DBC samples obtained the greatest Qmax with 68.4 mg/kg. The sorption mechanisms mainly involved hydrophobic partitioning, H-bonding, cation-π and p/π-π electron donor-acceptor interactions and electrostatic interactions. Additionally, the greater solution pH and Na+ concentration facilitated IMI adsorption on Gt and Gt-DBC samples; however, the Ca2+ solution obtained the opposite result. This effect on IMI adsorption was more pronounced for CGt-DBC samples. Therefore, the findings of this study provide a deep understanding of the interactions between Gt and DBC by adsorption and coprecipitation and their effect on the sorption of organic pollutants in natural soil and water environments.
Computational approaches for predicting variant impact: An overview from resources, principles to applications
Authors: Liu Ye , Yeung William S. B. , Chiu Philip C. N. , Cao Dandan
Published: September 2022

One objective of human genetics is to unveil the variants that contribute to human diseases. With the rapid development and wide use of next-generation sequencing (NGS), massive genomic sequence data have been created, making personal genetic information available. Conventional experimental evidence is critical in establishing the relationship between sequence variants and phenotype but with low efficiency. Due to the lack of comprehensive databases and resources which present clinical and experimental evidence on genotype-phenotype relationship, as well as accumulating variants found from NGS, different computational tools that can predict the impact of the variants on phenotype have been greatly developed to bridge the gap. In this review, we present a brief introduction and discussion about the computational approaches for variant impact prediction. Following an innovative manner, we mainly focus on approaches for non-synonymous variants (nsSNVs) impact prediction and categorize them into six classes. Their underlying rationale and constraints, together with the concerns and remedies raised from comparative studies are discussed. We also present how the predictive approaches employed in different research. Although diverse constraints exist, the computational predictive approaches are indispensable in exploring genotype-phenotype relationship.
An immunogenic cell death-related regulators classification patterns and immune microenvironment infiltration characterization in intracranial aneurysm based on machine learning
Authors: Turhon Mirzat , Maimaiti Aierpati , Gheyret Dilmurat , Axier Aximujiang , Rexiati Nizamidingjiang , Kadeer Kaheerman , Su Riqing , Wang Zengliang , Chen Xiaohong , Cheng Xiaojiang , Zhang Yisen , Aisha Maimaitili
Published: September 2022

Background

Immunogenic Cell Death (ICD) is a novel way to regulate cell death and can sufficiently activate adaptive immune responses. Its role in immunity is still emerging. However, the involvement of ICD in Intracranial Aneurysms (IA) remains unclear. This study aimed to identify biomarkers associated with ICDs and determine the relationship between them and the immune microenvironment during the onset and progression of IA

Methods

The IA gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) in IA were identified and the effects of the ICD on immune microenvironment signatures were studied. Techniques like Lasso, Bayes, DT, FDA, GBM, NNET, RG, SVM, LR, and multivariate analysis were used to identify the ICD gene signatures in IA. A consensus clustering algorithm was used for conducting the unsupervised cluster analysis of the ICD patterns in IA. Furthermore, enrichment analysis was carried out for investigating the various immune responses and other functional pathways. Along with functional annotation, the weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) network and module construction, identification of the hub gene, and co-expression analysis were also carried out.

Results

The above techniques were used for establishing the ICD gene signatures of HMGB1, HMGN1, IL33, BCL2, HSPA4, PANX1, TLR9, CLEC7A, and NLRP3 that could easily distinguish IA from normal samples. The unsupervised cluster analysis helped in identifying three ICD gene patterns in different datasets. Gene enrichment analysis revealed that the IA samples showed many differences in pathways such as the cytokine-cytokine receptor interaction, regulation of actin cytoskeleton, chemokine signaling pathway, NOD-like receptor signaling pathway, viral protein interaction with the cytokines and cytokine receptors, and a few other signaling pathways compared to normal samples. In addition, the three ICD modification modes showed obvious differences in their immune microenvironment and the biological function pathways. Eight ICD-regulators were identified and showed meaningful associations with IA, suggesting they could severe as potential prognostic biomarkers.

Conclusions

A new gene signature for IA based on ICD features was created. This signature shows that the ICD pattern and the immune microenvironment are closely related to IA and provide a basis for optimizing risk monitoring, clinical decision-making, and developing novel treatment strategies for patients with IA.
cGAS/STING and innate brain inflammation following acute high-fat feeding
Authors: Elzinga Sarah E. , Henn Rosemary , Murdock Benjamin J. , Kim Bhumsoo , Hayes John M. , Mendelson Faye , Webber-Davis Ian , Teener Sam , Pacut Crystal , Lentz Stephen I. , Feldman Eva L.
Published: September 2022

Obesity, prediabetes, and diabetes are growing in prevalence worldwide. These metabolic disorders are associated with neurodegenerative diseases, particularly Alzheimer’s disease and Alzheimer’s disease related dementias. Innate inflammatory signaling plays a critical role in this association, potentially via the early activation of the cGAS/STING pathway. To determine acute systemic metabolic and inflammatory responses and corresponding changes in the brain, we used a high fat diet fed obese mouse model of prediabetes and cognitive impairment. We observed acute systemic changes in metabolic and inflammatory responses, with impaired glucose tolerance, insulin resistance, and alterations in peripheral immune cell populations. Central inflammatory changes included microglial activation in a pro-inflammatory environment with cGAS/STING activation. Blocking gap junctions in neuron-microglial co-cultures significantly decreased cGAS/STING activation. Collectively these studies suggest a role for early activation of the innate immune system both peripherally and centrally with potential inflammatory crosstalk between neurons and glia.
PD-1 inhibition plus platinum-based chemotherapy (PBC) or PBC alone in the first-line treatment of locally advanced or metastatic pulmonary lymphoepithelioma-like carcinoma
Authors: Zhang Xuanye , Zhou Yixin , Chen Hualin , Chen Chen , Lin Zuan , He Li-na , Du Wei , Chen Tao , Hong Shaodong , Fu Sha
Published: September 2022

Background

Pulmonary lymphoepithelioma-like carcinoma (PLELC) is a distinctive subtype of non-small cell lung carcinoma that was not well presented in clinical studies. The management of advanced PLELC remains an important, unmet need due to the paucity of high-grade evidence. Herein, we carried out a multicenter, retrospective study to assess the effectiveness and tolerability of PD-1/PD-L1 inhibitor plus chemotherapy versus chemotherapy alone for patients with advanced PLELC in the first-line setting.

Patients and Methods

This retrospective study enrolled patients with advanced PLELC receiving first-line treatment with PD-1 inhibition plus chemotherapy (IO-Chemo group) or chemotherapy alone (Chemo group) in three medical centers in China. The survival outcomes, efficacy, and safety profile were investigated. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), overall survival (OS), and adverse events (AEs).

Results

A total of 133 patients were enrolled. PFS was significantly longer in the IO-Chemo group (median 12.8 months [95% CI 5.2-20.4]) than that in the Chemo group (median 7.7 months [95% CI 6.8-8.6]; hazard ratio [HR] 0.48 [95% CI 0.31-0.74]; P=0.001). ORR was 74.5% (95% CI, 63.0-86.1) in the IO-Chemo group and 34.6% (95% CI, 24.1-45.2) in the Chemo group (P<0.001). The median OS was not reached in the IO-Chemo group versus 35.7 months (95% CI 26.7-44.8) in the Chemo group (HR 0.47 [95% CI 0.20-1.07]; P=0.065). Multivariate analysis revealed that PD-1/PD-L1 inhibitor combination was independently associated with longer PFS (HR 0.40 [95% CI 0.25-0.63]; P<0.001). Grade 3 or higher AEs occurred in 36 (65.5%) patients in the IO-Chemo group and 56 (71.8%) patients in the Chemo group, respectively.

Conclusions

In patients with advanced PLELC, adding PD-1/PD-L1 inhibitor to platinum-based chemotherapy significantly increased PFS and ORR with a tolerable safety profile.
Type 2 autoimmune hepatitis: Genetic susceptibility
Authors: Lapierre Pascal , Alvarez Fernando
Published: September 2022

Two types of autoimmune hepatitis (AIH) are recognized; AIH-1 is characterized by the presence of anti-nuclear and/or anti-smooth muscle autoantibodies, while AIH-2 is associated with the presence of anti-Liver kidney microsome and/or anti-Liver Cytosol antibodies. The autoantigens targeted by AIH-2 autoantibodies are the cytochrome P450 2D6 and Formiminotransferase-cyclodeaminase for anti-LKM1 and anti-LC1 respectively. Both autoantigens are expressed in hepatocytes at higher levels than in any other cell type. Therefore, compared to AIH-1, the autoantigens targeted in AIH-2 are predominantly tissue-specific. Distinct clinical features are specific to AIH-2 compared to AIH-1, including diagnosis in younger patients (mean age 6.6 years), onset as fulminant hepatitis in very young patients (3 years of age or less), higher frequency in children than in adults and is frequently associated with extrahepatic T cell-mediated autoimmune diseases. AIH-2 is also often diagnosed in patients with primary immunodeficiency. AIH-2 is associated with specific HLA class II susceptibility alleles; DQB1*0201 is considered the main determinant of susceptibility while DRB1*07/DRB1*03 is associated with the type of autoantibody present. HLA DQB1*0201 is in strong linkage disequilibrium with both HLA DRB1*03 and DRB1*07. Interestingly, as in humans, MHC and non-MHC genes strongly influence the development of the disease in an animal model of AIH-2. Altogether, these findings suggest that AIH-2 incidence is likely dependent on specific genetic susceptibility factors combined with distinct environmental triggers.
P2X7 purinergic receptor plays a critical role in maintaining T-cell homeostasis and preventing lupus pathogenesis
Authors: Mellouk Amine , Hutteau-Hamel Tom , Legrand Julie , Safya Hanaa , Benbijja Mohcine , Mercier-Nomé Françoise , Benihoud Karim , Kanellopoulos Jean M. , Bobé Pierre
Published: September 2022

The severe lymphoproliferative and lupus diseases developed by MRL/lprmice depend on interactions between the Faslprmutation and MRL genetic background. Thus, the Faslprmutation causes limited disease in C57BL/6 mice. We previously found that accumulating B220+CD4–CD8–double negative (DN) T cells in MRL/lprmice show defective P2X7 receptor ( P2X7)-induced cellular functions, suggesting that P2X7 contributes to T-cell homeostasis, along with Fas. Therefore, we generated a B6/lprmouse strain (called B6/lpr-p2x7KO) carrying homozygous P2X7 knockout alleles. B6/lpr-p2x7KO mice accumulated high numbers of FasL-expressing B220+DN T cells of CD45RBhighCD44higheffector/memory CD8+T-cell origin and developed severe lupus, characterized by leukocyte infiltration into the tissues, high levels of IgG anti-dsDNA and rheumatoid factor autoantibodies, and marked cytokine network dysregulation. B6/lpr-p2x7KO mice also exhibited a considerably reduced lifespan. P2X7 is therefore a novel regulator of T-cell homeostasis, of which cooperation with Fas is critical to prevent lymphoaccumulation and autoimmunity.
Case report: Bilateral panuveitis resembling Vogt-Koyanagi-Harada disease after second dose of BNT162b2 mRNA COVID-19 vaccine
Authors: Sato Tomohito , Nihei Ryotaro , Sora Daisuke , Nishio Yoshiaki , Takeuchi Masaru
Published: September 2022

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a serious pandemic. COVID-19 vaccination is urgent needed for limiting SARS-CoV-2 outbreaks by herd immunity. Simultaneously, post-marketing surveillance to assess vaccine safety is important, and collection of vaccine-related adverse events has been in progress. Vision-threatening ophthalmic adverse events of COVID-19 vaccines are rare but are a matter of concern. We report a 45-year-old Japanese male with positive for HLA-DR4/HLA-DRB1*0405, who developed bilateral panuveitis resembling Vogt-Koyanagi-Harada (VKH) disease after the second dose of Pfizer-BioNTech COVID-19 mRNA (BNT162b2) vaccine. Glucocorticosteroid (GC) therapy combined with cyclosporine A (CsA) readily improved the panuveitis. The immune profile at the time of onset was analyzed using CyTOF technology, which revealed activations of innate immunity mainly consisting of natural killer cells, and acquired immunity predominantly composed of B cells and CD8+ T cells. On the other hand, the immune profile in the remission phase was altered by GC therapy with CsA to a profile composed primarily of CD4+ cells, which was considerably similar to that of the healthy control before the vaccination. Our results indicate that BNT162b2 vaccine may trigger an accidental immune cross-reactivity to melanocyte epitopes in the choroid, resulting in the onset of panuveitis resembling VKH disease.
Comparative efficacy and safety of JAK inhibitors as monotherapy and in combination with methotrexate in patients with active rheumatoid arthritis: A systematic review and meta-analysis
Authors: Liu Li , Yan Yi-Dan , Shi Fang-Hong , Lin Hou-Wen , Gu Zhi-Chun , Li Jia
Published: September 2022

Background

We aim to evaluate the efficacy and tolerability of Janus kinase inhibitors (JAKi) as monotherapy and in combination with methotrexate (MTX) in active rheumatoid arthritis (RA).

Methods

Medline, EMBASE, and Cochrane Library were systematically searched to identify relevant randomized controlled trials (RCTs). Pooled analysis was conducted using random-effects model, along with the risk difference (RD) and 95% confidence intervals (CIs).

Results

Three RCTs, including 2,290 patients, were included. JAKi (tofacitinib, baricitinib, and filgotinib) plus MTX displayed a higher proportion of patients meeting the American College of Rheumatology (ACR) criteria than JAKi alone at week 52 (ACR20 RD 0.032; 95% CI −0.027 to 0.091; ACR50 RD 0.050; 95% CI 0.003 to 0.097; ACR70 RD 0.056; 95% CI 0.012 to 0.100). Similar results were observed for ACR20/50/70 at week 24. No significant difference was found between two regimens for the proportion of patients achieving Health Assessment Questionnaire disability index (HAQ-DI) improvement ≥ 0.22 at weeks 24 and 52. Regarding low disease activity and remission achievement, JAKi in combination with MTX, contributed higher response rates than JAKi alone at weeks 24 and 52. Compared with JAKi monotherapy, combination therapy had a higher risks of treatment-emergent adverse events (TEAEs) and adverse events (AEs) leading to study discontinuation.

Conclusion

JAKi combined with MTX demonstrated superiority to JAKi monotherapy in terms of ACR responses, low disease activity and remission achievement. The two regimens presented comparable physical functioning measured by HAQ-DI improvement and similar tolerability, except for high risks of TEAEs and AEs leading to study discontinuation in combination therapy.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021288907.
Effects of ecological restoration on soil biogenic elements and their ecological stoichiometry in the Yellow River Delta, China
Authors: Li Dongxue , Li Yi’na , Xie Yiliang , Cui Baoshan , Ning Zhonghua , Zhang Shuyan , Bi Zhenggang , Fu Shouqiang , Che Chunguang
Published: September 2022

Coastal wetlands serve as sources and sinks of carbon, nitrogen, phosphorus, and sulfur, and their ecological stoichiometry intuitively indicates the biogeochemical cycle process of the region. This study investigated the changing trend of the contents of soil organic carbon (i.e., SOC), total nitrogen (i.e., TN), total phosphorus (i.e., TP), and total sulfur (i.e., TS) and their ecological stoichiometric ratios in 2019-2021 in the Yellow River Delta (including north and south banks) under the Internationally Important Wetland Biodiversity Conservation Project by conducting field surveys and experiments. The results showed that SOC, TN, and TP showed the highest content in the North Unrestoration, while the TS content appeared highest in the North Restoration. In addition, ecological restoration improved the biogenic element stability in both banks and improved the stability of ecological stoichiometry on the north bank while decreasing the ecological stoichiometry stability on the south bank. Notably, the changing trend of soil C/S in the North Unrestoration exhibited a considerably different profile similarity from the North Restoration, which indicates that the ecological restoration changed the wetland ecosystem from the perspective of soil C/S. Furthermore, the high content of soil biogenic elements SOC and high ratio of soil ecological stoichiometry C/N and C/S in the Yellow River Delta induce that they are more sensitive to environmental change. Over the three years, the contributions of soil moisture content, soil salinity, and pH to soil biogenic element contents and their stoichiometric ratios were 32.20%, 49.30%, and 18.50% on the north bank, respectively, and 85.70%, 8.50%, and 5.80% on the south bank, respectively. This study implies that ecological restoration generally has a positive effect on the soil biogenic element contents and their ecological stoichiometry in the Yellow River Delta and provides a reference for delta restoration.
Exposure to silica and systemic sclerosis: A retrospective cohort study based on the Canadian Scleroderma Research Group
Authors: Muntyanu Anastasiya , Milan Raymond , Rahme Elham , LaChance Avery , Ouchene Lydia , Cormier Maxime , Litvinov Ivan V. , Hudson Marie , Baron Murray , Netchiporouk Elena ,   the Canadian Scleroderma Research Group
Published: September 2022

Introduction

Systemic sclerosis (SSc) is thought to be induced by an environmental trigger in genetically predisposed individuals. This study assessed the demographic and clinical characteristics and disease severity of silica exposed SSc patients.

Methods

Data was obtained from the Canadian Scleroderma Research Group (CSRG) cohort, containing 1,439 patients (2004–2019). Univariate and multivariate logistic regression analyses were performed, to determine the phenotype and severity of silica-exposed SSc patients. Mortality was assessed using Cox Survival Regression and Kaplan-Meier analyses.

Results

Among 1,439 patients (86.7% females), 95 patients reported exposure to silica. Those exposed were younger, of male sex and with more severe disease. Sex differences were observed where male patients exposed to silica were more likely to be Caucasian and smokers whereas female patients were younger at SSc diagnosis compared to unexposed. Multivariate regression, controlled for multiple confounders, showed that silica exposure was associated with a younger age at diagnosis and worse disease severity and mortality.

Conclusion

Exposure to silica was reported in ∼7% of CSRG cohort and ∼20% of male patients and was associated with a worse prognosis in terms of age of diagnosis, organ involvement and mortality. Hence, screening for silica exposure among higher risk individuals may be beneficial and these patients may require closer monitoring for systemic disease.
Long-term cultivation alter soil bacterial community in a forest-grassland transition zone
Authors: Bai Zhenyin , Zheng Lingbo , Bai Zhenjian , Jia Aomei , Wang Mingjun
Published: September 2022

Changes in land use types can significantly affect soil porperties and microbial community composition in many areas. However, the underlying mechanism of shift in bacterial communities link to soil properties is still unclear. In this study, Illumina high-throughput sequencing was used to analyze the changes of soil bacterial communities in different land use types in a forest-grassland transition zone, North China. There are two different land use types: grassland (G) and cultivated land (CL). Meanwhile, cultivated land includes cultivated of 10 years (CL10) or 20 years (CL20). Compared with G, CL decreased soil pH, SOC and TN, and significantly increased soil EC, P and K, and soil properties varied significantly with different cultivation years. Grassland reclamation increases the diversity of bacterial communities, the relative abundance of Proteobacteria, Gemmatimonadetes and Bacteroidetes increased, while that of Actinobacteria, Acidobacteria, Rokubacteria and Verrucomicrobia decreased. However, the relative abundance of Proteobacteria decreased and the relative abundance of Chloroflexi and Nitrospirae increased with the increase of cultivated land years. Mantel test and RDA analysis showed that TP, AP, SOC and EC were the main factors affecting the diversity of composition of bacterial communities. In conclusion, soil properties and bacterial communities were significantly altered after long-term cultivation. This study provides data support for land use and grassland ecological protection in this region.
Activation of TLR4 by viral glycoproteins: A double-edged sword?
Authors: Halajian Emily A. , LeBlanc Emmanuelle V. , Gee Katrina , Colpitts Che C.
Published: September 2022

Recognition of viral infection by pattern recognition receptors is paramount for a successful immune response to viral infection. However, an unbalanced proinflammatory response can be detrimental to the host. Recently, multiple studies have identified that the SARS-CoV-2 spike protein activates Toll-like receptor 4 (TLR4), resulting in the induction of proinflammatory cytokine expression. Activation of TLR4 by viral glycoproteins has also been observed in the context of other viral infection models, including respiratory syncytial virus (RSV), dengue virus (DENV) and Ebola virus (EBOV). However, the mechanisms involved in virus-TLR4 interactions have remained unclear. Here, we review viral glycoproteins that act as pathogen-associated molecular patterns to induce an immune response via TLR4. We explore the current understanding of the mechanisms underlying how viral glycoproteins are recognized by TLR4 and discuss the contribution of TLR4 activation to viral pathogenesis. We identify contentious findings and research gaps that highlight the importance of understanding viral glycoprotein-mediated TLR4 activation for potential therapeutic approaches.