bluuebunny/crossref_metadata_2025 huggingface dataset:
Stratification of diabetic kidney diseases via data-independent acquisition proteomics–based analysis of human kidney tissue specimens
Authors: Huang Qinghua , Fei Xianming , Zhong Zhaoxian , Zhou Jieru , Gong Jianguang , Chen Yuan , Li Yiwen , Wu Xiaohong
Published: November 2022

Aim

The aims of this study were to analyze the proteomic differences in renal tissues from patients with diabetes mellitus (DM) and diabetic kidney disease (DKD) and to select sensitive biomarkers for early identification of DKD progression.

Methods

Pressure cycling technology–pulse data-independent acquisition mass spectrometry was employed to investigate protein alterations in 36 formalin-fixed paraffin-embedded specimens. Then, bioinformatics analysis was performed to identify important signaling pathways and key molecules. Finally, the target proteins were validated in 60 blood and 30 urine samples.

Results

A total of 52 up- and 311 down-regulated differential proteins were identified as differing among the advanced DKD samples, early DKD samples, and DM controls (adjusted p<0.05). These differentially expressed proteins were mainly involved in ion transport, apoptosis regulation, and the inflammatory response. UniProt database analysis showed that these proteins were mostly enriched in signaling pathways related to metabolism, apoptosis, and inflammation. NBR1 was significantly up-regulated in both early and advanced DKD, with fold changes (FCs) of 175 and 184, respectively (both p<0.01). In addition, VPS37A and ATG4B were significantly down-regulated with DKD progression, with FCs of 0.140 and 0.088, respectively, in advanced DKD and 0.533 and 0.192, respectively, in early DKD compared with the DM control group (both p<0.01). Bioinformatics analysis showed that NBR1, VPS37A, and ATG4B are closely related to autophagy. We also found that serum levels of the three proteins and urine levels of NBR1 decreased with disease progression. Moreover, there was a significant difference in serum VPS37A and ATG4B levels between patients with early and advanced DKD (both p<0.05). The immunohistochemistry assaay exhibited that the three proteins were expressed in renal tubular cells, and NBR1 was also expressed in the cystic wall of renal glomeruli.

Conclusion

The increase in NBR1 expression and the decrease in ATG4B and VPS37 expression in renal tissue are closely related to inhibition of the autophagy pathway, which may contribute to DKD development or progression. These three proteins may serve as sensitive serum biomarkers for early identification of DKD progression.
Urban functional zone classification based on self-supervised learning: A case study in Beijing, China
Authors: Lu Weipeng , Qi Ji , Feng Huihui
Published: November 2022

Urban functional zones (UFZs) are the fundamental units for urban management and operation. The advance in earth observation and deep learning technology provides chances for automatically and intelligently classifying UFZs via remote sensing images. However, current methods based on deep learning require numerous high-quality annotations to train a well-performed model, which is time-consuming. Thus, how to train a reliable model using a few annotated data is a problem in UFZ classification. Self-supervised learning (SSL) can optimize models using numerous unannotated data. In this paper, we introduce SSL into UFZ classification to use the instance discrimination pretext task for guiding a model to learn useful features from over 50,000 unannotated remote sensing images and fine tune the model using 700 to 7,000 annotated data. The validation experiment in Beijing, China reveals that 1) using a few annotated data, SSL can achieve a kappa coefficient and an overall accuracy 2.1–11.8% and 2.0–10.0% higher than that of supervised learning (SL), and 2) can also gain results comparable to that got by the SL paradigm using two times annotated data for training. The less the data used for finetuning the more obvious the advantage of SSL to SL. Besides, the comparison experiment between the model pretrained on the research region and that pretrained on the benchmark reveals that the objects with displacement and incompleteness are more difficult for models to classify accurately.
Carbon emission reduction pathways under carbon neutrality targets in Gansu province of China
Authors: Xie Mingjun , Liu Xinyuan , Yan Wenshan , Li Yongjun , Liu Xinwei , Zhang Gexiang , Sun Jianyun
Published: November 2022

Gansu province will fulfill the carbon reduction target under the national carbon neutrality strategy. As a developing province in China, Gansu will have to trade off carbon reduction targets and economic development. This study adopts a computable general equilibrium model to simulate the carbon reduction pathway and estimate the possible impacts on the economy, output and environment under a carbon-neutral target. Our results show carbon emission will peak around 2033 in the baseline scenario and decline slowly after the peak. While carbon emissions will peak around 2023 in the carbon neutral scenario and decline very fast from 154 million tons in 2023 to 40 million ton in 2060. The economy will continue to increase from 734 billion CNY in 2017–3375 billion CNY in 2050 under a carbon reduction target, which means the carbon neutral target will have very limited economic impacts by 2060. At the sector level, economic outputs vary among different sectors. The output will increase significantly, such as power generation 14%, water supply 8% and nonmental 4%. Some other sectors will decrease quickly, paper 15% and textile industry 7%. Carbon reduction will also contribute to air pollutants reduction, which is a benefit to air quality. Carbon neutral targets will bring more opportunities in Gansu due to green energy potential without economic burden. Proper carbon mitigation policy would avoid the adverse impact but bring more potential to the economy in Gansu.
Effects of landscape restoration on migration of lead and cadmium at an abandoned mine site
Authors: Zhang Feiying , Li Hepeng
Published: November 2022

Abandoned lead and zinc (Pb/Zn) mining wastes represent a serious environmental hazard because heavy metals (e.g., Pb and Cd) are continuously released into the environment, threatening ecological and human health. This study was devoted to investigate the stability of Pb and Cd in the soil at an abandoned Pb/Zn mine site after landscape restoration by five-year monitoring. Chemical extraction was applied to measure the distribution of metals. The results showed that the bioavailability of Pb and Cd in soil increased, during the accumulation of soil organic matter of about seven g/kg, and that the soil pH value decreased from 4.82 to 4.44. Soil organic matter and soil pH significantly affected the distribution of metals. Long-term afforestation can lead to continuous soil acidification. There was a significant negative correlation between the carbonate-bound state distribution and soil pH. With the decrease in pH, the decomposition of carbonates was promoted, and relative abundances of Pb and Cd in the distribution associated with the fulvic and humic complex of organic matter increased by 0.54% and 3.17%, respectively. Pb and Cd showed different migration behavior in pine. Compared with Cd, Pb was more concentrated in roots. These results have important implications for the long-term sustainable management of forests formed by the phytostabilization of contaminated soil.
Accelerated gross nitrogen cycling following garlic mustard invasion is linked with abiotic and biotic changes to soils
Authors: Edwards Joseph D. , Cook Allison M. , Yannarell Anthony C. , Yang Wendy H.
Published: November 2022

Introduction

Alliaria petiolata (garlic mustard), an invasive forest herb in North America, often alters nutrient availability in its non-native ecosystems, but the mechanisms driving these changes have yet to be determined. We hypothesized three potential mechanisms through which garlic mustard could directly influence soil nitrogen (N) cycling: by increasing soil pH, by modifying soil microbial community composition, and by altering nutrient availability through litter inputs.

Materials and methods

To test these hypotheses, we evaluated garlic mustard effects on soil pH and other soil properties; fungal and prokaryotic (bacterial and archaeal) community composition; and soil N cycling rates (gross N mineralization and nitrification rates, microbial N assimilation rates, and nitrification- versus denitrification-derived nitrous oxide fluxes); and we assessed correlations among these variables. We collected soil samples from garlic mustard present, absent, and removed treatments in eight forests in central Illinois, United States, during the rosette, flowering, and senescence phenological stages of garlic mustard life cycle.

Results

We found that garlic mustard increased soil pH, altered fungal and prokaryotic communities, and increased rates of N mineralization, nitrification, nitrification-derived net N2O emission. Significant correlations between soil pH and microbial community composition suggest that garlic mustard effects on soil pH could both directly and indirectly influence soil N cycling rates.

Discussion

Correspondence of gross rates of N mineralization and nitrification with microbial community composition suggest that garlic mustard modification of soil microbial communities could directly lead to changes in soil N cycling. We had expected that early season, nutrient-rich litter inputs from mortality of young garlic mustard could accelerate gross N mineralization and microbial N assimilation whereas late season, nutrient poorer litter inputs from senesced garlic mustard could suppress N mineralization, but we did not observe these patterns in support of the litter input mechanism. Together, our results elucidate how garlic mustard effects on soil pH and microbial community composition can accelerate soil N cycling to potentially contribute to the invasion success of garlic mustard.
Simultaneous detection of novel genes and SNPs by adaptive p-value combination
Authors: Chen Xiaohui , Zhang Hong , Liu Ming , Deng Hong-Wen , Wu Zheyang
Published: November 2022

Combining SNP p-values from GWAS summary data is a promising strategy for detecting novel genetic factors. Existing statistical methods for the p-value-based SNP-set testing confront two challenges. First, the statistical power of different methods depends on unknown patterns of genetic effects that could drastically vary over different SNP sets. Second, they do not identify which SNPs primarily contribute to the global association of the whole set. We propose a new signal-adaptive analysis pipeline to address these challenges using the omnibus thresholding Fisher’s method (oTFisher). The oTFisher remains robustly powerful over various patterns of genetic effects. Its adaptive thresholding can be applied to estimate important SNPs contributing to the overall significance of the given SNP set. We develop efficient calculation algorithms to control the type I error rate, which accounts for the linkage disequilibrium among SNPs. Extensive simulations show that the oTFisher has robustly high power and provides a higher balanced accuracy in screening SNPs than the traditional Bonferroni and FDR procedures. We applied the oTFisher to study the genetic association of genes and haplotype blocks of the bone density-related traits using the summary data of the Genetic Factors for Osteoporosis Consortium. The oTFisher identified more novel and literature-reported genetic factors than existing p-value combination methods. Relevant computation has been implemented into the R package TFisher to support similar data analysis.
Identification of RNA N6-methyladenosine regulation in epilepsy: Significance of the cell death mode, glycometabolism, and drug reactivity
Authors: Liu Xuchen , Sun Qingyuan , Cao Zexin , Liu Wenyu , Zhang Hengrui , Xue Zhiwei , Zhao Jiangli , Feng Yifei , Zhao Feihu , Wang Jiwei , Wang Xinyu
Published: November 2022

Epilepsy, a functional disease caused by abnormal discharge of neurons, has attracted the attention of neurologists due to its complex characteristics. N6-methyladenosine (m6A) is a reversible mRNA modification that plays essential role in various biological processes. Nevertheless, no previous study has systematically evaluated the role of m6A regulators in epilepsy. Here, using gene expression screening in the Gene Expression Omnibus GSE143272, we identified seven significant m6A regulator genes in epileptic and non-epileptic patients. The random forest (RF) model was applied to the screening, and seven m6A regulators (HNRNPC, WATP, RBM15, YTHDC1, YTHDC2, CBLL1, and RBMX) were selected as the candidate genes for predicting the risk of epilepsy. A nomogram model was then established based on the seven-candidate m6A regulators. Decision curve analysis preliminarily showed that patients with epilepsy could benefit from the nomogram model. The consensus clustering method was performed to divide patients with epilepsy into two m6A patterns (clusterA and clusterB) based on the selected significant m6A regulators. Principal component analysis algorithms were constructed to calculate the m6A score for each sample to quantify the m6A patterns. Patients in clusterB had higher m6A scores than those in clusterA. Furthermore, the patients in each cluster had unique immune cell components and different cell death patterns. Meanwhile, based on the M6A classification, a correlation between epilepsy and glucose metabolism was laterally verified. In conclusion, the m6A regulation pattern plays a vital role in the pathogenesis of epilepsy. The research on m6A regulatory factors will play a key role in guiding the immune-related treatment, drug selection, and identification of metabolism conditions and mechanisms of epilepsy in the future.
Unmet need for contraception and its associated factors among adolescent and young women in Guinea: A multilevel analysis of the 2018 Demographic and Health Surveys
Authors: Sidibé Sidikiba , Grovogui Fassou Mathias , Kourouma Karifa , Kolié Delphin , Camara Bienvenu Salim , Delamou Alexandre , Kouanda Seni
Published: November 2022

Despite the recent repositioning efforts to increase the use of modern contraceptives, the prevalence of unmet need for contraception remains high among adolescent and young women in Guinea. This study analyzed the individual and contextual factors associated with the unmet need for contraception among adolescent and young women in 2018 in Guinea. We conducted a secondary analysis of the 2018 Demographic and Health Survey data. Multilevel mixed-effects logistic regression models were used to assess the association between individual and contextual characteristics and unmet need for contraception among adolescents and young women. Adjusted odds ratios (AORs) with their 95% confidence intervals (CIs) were calculated, with statistical significance set at p < 0.05. The prevalence of total unmet need for contraception was 22.6% (95% CI, 18.1–27.8). Being an adolescent aged 15–19 years (AOR = 1.44; 95% CI, 1.01–2.05), unmarried (AOR = 5.19; 95% CI, 3.51–7.67), having one or two children (AOR = 3.04; 95% CI, 2.18–4.25), or more than two children (AOR = 4.79; 95% CI, 3.00–7.62) were individual factors associated with the unmet need for contraception. As for community factors, only living in Labé (AOR = 2.54; 95% CI, 1.24–5.18) or Mamou (AOR = 1.73; 95% CI, 1.21–2.48) was significantly associated with the unmet need for contraception. In conclusion, both individual and community characteristics were significantly associated with the unmet need for contraception. This highlights the need to focus and strengthen communication and counseling strategies targeting adolescents and young women and aiming to increase the uptake of family planning in Guinea.
Why vaccines fail against Piscirickettsiosis in farmed salmon and trout and how to avoid it: A review
Authors: Valenzuela-Aviles Paula , Torrealba Débora , Figueroa Carolina , Mercado Luis , Dixon Brian , Conejeros Pablo , Gallardo-Matus José
Published: November 2022

Piscirickettsiosis is the most severe, persistent, and damaging disease that has affected the Chilean salmon industry since its origins in the 1980s. As a preventive strategy for this disease, different vaccines have been developed and used over the last 30 years. However, vaccinated salmon and trout frequently die in the sea cages and the use of antibiotics is still high demonstrating the low efficiency of the available vaccines. The reasons why the vaccines fail so often are still debated, but it could involve different extrinsic and intrinsic factors. Among the extrinsic factors, mainly associated with chronic stress, we can distinguish: 1) biotic including coinfection with sea lice, sealions attacks or harmful algal blooms; 2) abiotic including low oxygen or high temperature; and 3) farm-management factors including overcrowding or chemical delousing treatments. Among the intrinsic factors, we can distinguish: 1) fish-related factors including host’s genetic variability (species, population and individual), sex or age; 2) pathogen-related factors including their variability and ability to evade host immune responses; and 3) vaccine-related factors including low immunogenicity and poor matches with the circulating pathogen strain. Based on the available evidence, in order to improve the development and the efficacy of vaccines against P. salmonis we recommend: a) Do not perform efficacy evaluations by intraperitoneal injection of pathogens because they generate an artificial protective immune response, instead cohabitation or immersion challenges must be used; b) Evaluate the diversity of pathogen strains in the field and ensure a good antigenic match with the vaccines; c) Investigate whether host genetic diversity could be improved, e.g. through selection, in favor of better and longer responses to vaccination; d) To reduce the stressful effects at the cage level, controlling the co-infection of pathogens and avoiding fish overcrowding. To date, we do not know the immunological mechanisms by which the vaccines against P. salmonis may or may not generate protection. More studies are required to identify what type of response, cellular or molecular, is required to develop effective vaccines.
In vitro systems to study inborn errors of immunity using human induced pluripotent stem cells
Authors: Nikolouli Eirini , Reichstein Janne , Hansen Gesine , Lachmann Nico
Published: November 2022

In the last two decades, the exponential progress in the field of genetics could reveal the genetic impact on the onset and progression of several diseases affecting the immune system. This knowledge has led to the discovery of more than 400 monogenic germline mutations, also known as “inborn errors of immunity (IEI)”. Given the rarity of various IEI and the clinical diversity as well as the limited available patients’ material, the continuous development of novel cell-based in vitro models to elucidate the cellular and molecular mechanisms involved in the pathogenesis of these diseases is imperative. Focusing on stem cell technologies, this review aims to provide an overview of the current available in vitro models used to study IEI and which could lay the foundation for new therapeutic approaches. We elaborate in particular on the use of induced pluripotent stem cell-based systems and their broad application in studying IEI by establishing also novel infection culture models. The review will critically discuss the current limitations or gaps in the field of stem cell technology as well as the future perspectives from the use of these cell culture systems.
M2 macrophage-related gene signature in chronic rhinosinusitis with nasal polyps
Authors: Zhu Ying , Sun Xiwen , Tan Shaolin , Luo Chunyu , Zhou Jiayao , Zhang Shiyao , Li Zhipeng , Lin Hai , Zhang Weitian
Published: November 2022

Background

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common sinonasal inflammatory disorder with high heterogeneity. Increasing evidence have indicated that the infiltration of macrophages especially M2 macrophages play pivotal roles in the pathogenesis of CRSwNP, but the underlying mechanisms remain undetermined. This study sought to identify potential biomarkers related to M2 macrophages in CRSwNP.

Methods

The expression datasets of GSE136825 and GSE179265 were download from Gene Expression Omnibus (GEO) database and merged. Then, CIBERSORT and weighted gene co-expression network analysis (WGCNA) algorithms were applied to identify M2 macrophage-related gene modules. Thereafter, differentially expressed genes (DEGs) related to M2 macrophages were selected to perform functional enrichment analyses. A protein-protein interaction (PPI) network was built to identify hub genes and quantitative real-time reverse transcriptions PCR was used to verify the bioinformatics results.

Results

A total of 92 DEGs associated with M2 macrophages were identified for further analysis. The results of Gene ontology (GO) and Kyoto Encyclopedia of genes and genomes (KEGG) analyses illustrated that M2 macrophage-associated DEGs primarily enriched in immune responses and extracellular matrix structure. PPI network analysis identified 18 hub genes related to M2 macrophages that might be pivotal in the pathogenesis of CRSwNP. After verification, AIF1, C1QA, C1QB, C3AR1, CCR1, CD163, CD4, CD53, CD86, CSF1R, CYBB, FCER1G, FCGR3A, IL10RA, ITGB2, LAPTM5, PLEK, TYROBP were identified as potential M2 macrophage-related biomarkers for CRSwNP.

Conclusion

These findings yield new insights into the hub genes and mechanisms related to M2 macrophages in the pathogenesis of CRSwNP. Further studies of these hub genes would help better understand the disease progression and identify potential treatment targets.
T cell-intrinsic protein kinase D3 is dispensable for the cells’ activation
Authors: Koutník Jiří , Leitges Michael , Siegmund Kerstin
Published: November 2022

Protein kinases D (PKDs) are implicated in T cell receptor (TCR) signaling. Of the two T cell-expressed isoforms PKD2 and PKD3, however, only the former one is rather well understood in this immune cell type. Recently, we have observed a putative hyper-phenotype of T cells from conventional PKD3-knockout mice, which we explained as a secondary effect due to a skewed T cell compartment from naïve towards effector/memory T cells already under steady state conditions. Nonetheless, to this end it is not clear whether these aberrations are mediated by a T cell-intrinsic or -extrinsic function of PKD3. To address this question, we have investigated mice lacking PKD3 specifically in the T cell compartment. We could show that T cells from CD4-Cre-driven conditional knockout mice did not phenocopy the ones from conventional PKD3-knockout mice. In brief, no skewing in the T cell compartment of peripheral lymphoid organs, no hyper-activation upon stimulation in vitro or in vivo as well as no aberrations in follicular helper T cells (TFH) upon immunization were observed. Hence, although PKD3 is strongly regulated upon TCR stimulation, in T cells this kinase seems to be dispensable for their activation. The described skewing in the T cell compartment of conventional PKD3-deficient mice seems to be mediated by T cell-extrinsic mechanisms, thus once more emphasizing the importance of cell type-specific mouse models.
Structural basis for the broad and potent cross-reactivity of an N501Y-centric antibody against sarbecoviruses
Authors: Jeong Bo-Seong , Jeon Joon Young , Lai Chih-Jen , Yun Hye-Yeoung , Jung Jae U. , Oh Byung-Ha
Published: November 2022

More than 80% of SARS-CoV-2 variants, including Alpha and Omicron, contain an N501Y mutation in the receptor-binding domain (RBD) of the spike protein. The N501Y change is an adaptive mutation enabling tighter interaction with the human ACE2 receptor. We have developed a broadly neutralizing antibody (nAb), D27LEY, whose binding affinity was intentionally optimized for Y501. This N501Y-centric antibody not only interacts with the Y501-containing RBDs of SARS-CoV-2 variants, including Omicron, with pico- or subnanomolar binding affinity, but also binds tightly to the RBDs with a different amino acid at residue 501. The crystal structure of the Fab fragment of D27LEY bound to the RBD of the Alpha variant reveals that the Y501-containing loop adopts a ribbon-like topology and serves as a small but major epitope in which Y501 is a part of extensive intermolecular interactions. A hydrophobic cleft on the most conserved surface of the RBD core serves as another major binding epitope. These data explain the broad and potent cross-reactivity of this N501Y-centric antibody, and suggest that a vaccine antigenic component composed of the RBD core and a part of receptor-binding motif (RBM) containing tyrosine at residue 501 might elicit broad and potent humoral responses across sarbecoviruses.
Hepatitis B functional cure and immune response
Authors: Zheng Jia-Rui , Wang Zi-Long , Feng Bo
Published: November 2022

Hepatitis B virus (HBV) is a hepatotropic virus, which damage to hepatocytes is not direct, but through the immune system. HBV specific CD4+ T cells can induce HBV specific B cells and CD8+ T cells. HBV specific B cells produce antibodies to control HBV infection, while HBV specific CD8+ T cells destroy infected hepatocytes. One of the reasons for the chronicity of HBV infection is that it cannot effectively activate adoptive immunity and the function of virus specific immune cells is exhausted. Among them, virus antigens (including HBV surface antigen, e antigen, core antigen, etc.) can inhibit the function of immune cells and induce immune tolerance. Long term nucleos(t)ide analogues (NAs) treatment and inactive HBsAg carriers with low HBsAg level may “wake up” immune cells with abnormal function due to the decrease of viral antigen level in blood and liver, and the specific immune function of HBV will recover to a certain extent, thus becoming the “dominant population” for functional cure. In turn, the functional cure will further promote the recovery of HBV specific immune function, which is also the theoretical basis for complete cure of hepatitis B. In the future, the complete cure of chronic HBV infection must be the combination of three drugs: inhibiting virus replication, reducing surface antigen levels and specific immune regulation, among which specific immunotherapy is indispensable. Here we review the relationship, mechanism and clinical significance between the cure of hepatitis B and immune system.
Fisetin reduces the senescent tubular epithelial cell burden and also inhibits proliferative fibroblasts in murine lupus nephritis
Authors: Ijima Shogo , Saito Yuki , Nagaoka Kentaro , Yamamoto Sena , Sato Tsukasa , Miura Norihiro , Iwamoto Taiki , Miyajima Maki , Chikenji Takako S.
Published: November 2022

Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease characterized by the involvement of multiple organs. Lupus nephritis (LN) is a major risk factor for overall morbidity and mortality in SLE patients. Hence, designing effective drugs is pivotal for treating individuals with LN. Fisetin plays a senolytic role by specifically eliminating senescent cells, inhibiting cell proliferation, and exerting anti-inflammatory, anti-oxidant, and anti-tumorigenic effects. However, limited research has been conducted on the utility and therapeutic mechanisms of fisetin in chronic inflammation. Similarly, whether the effects of fisetin depend on cell type remains unclear. In this study, we found that LN-prone MRL/lpr mice demonstrated accumulation of Ki-67-positive myofibroblasts and p15INK4B-positive senescent tubular epithelial cells (TECs) that highly expressed transforming growth factor β (TGF-β). TGF-β stimulation induced senescence of NRK-52E renal TECs and proliferation of NRK-49F renal fibroblasts, suggesting that TGF-β promotes senescence and proliferation in a cell type-dependent manner, which is inhibited by fisetin treatment in vitro. Furthermore, fisetin treatment in vivo reduced the number of senescent TECs and myofibroblasts, which attenuated kidney fibrosis, reduced senescence-associated secretory phenotype (SASP) expression, and increased TEC proliferation. These data suggest that the effects of fisetin vary depending on the cell type and may have therapeutic effects in complex and diverse LN pathologies.
Differentially induced immunity in buccal and nasal mucosae after vaccination for SARS–CoV–2: Prospects for mass scale immunity-screening in large populations
Authors: Tsamadou Chrysanthi , Ludwig Carolin , Scholz Judith , Proffen Matthias , Hägele Janina , Rode Immanuel , Körper Sixten , Fabricius Dorit , Jahrsdörfer Bernd , Neuchel Christine , Amann Elisa , Schrezenmeier Hubert , Fürst Daniel
Published: November 2022

Introduction

Humoral immunity after SARS-CoV-2 vaccination has been extensively investigated in blood. Aim of this study was to develop an ELISA method in order to determine the prevalence of IgG and IgA SARS-CoV-2 domain 1 spike-protein (S) specific antibodies (Abs) in buccal and nasal mucosal surfaces of vaccinees.

Methods

To this end, we analyzed 69 individuals who received their first vaccine dose between February and July 2021. Vaccines administered were BNT162b2, mRNA-1273 or ChAdOx1-nCoV-19. Detection of IgG and IgA Abs was performed using commercial ELISA kits for both blood and swab samples after protocol modification for the latter.

Results

Anti-spike IgG and IgA Abs in the buccal and/or nasal swabs were detectable in >81% of the study subjects after the second dose. The IgG measurements in buccal swabs appeared to correlate in a more consistent way with the respective measurements in blood with a correlation coefficient of r=0.74. It is of note that IgA Abs appeared to be significantly more prevalent in the nasal compared to the buccal mucosa. Optimal selection of the assay cut-off for the IgG antibody detection in buccal swabs conferred a sensitivity of 91.8% and a specificity of 100%. Last, individuals vaccinated with mRNA-based vaccines exhibited higher antibody levels in both blood and mucosal surfaces compared to those receiving ChAdOx1-nCoV-19 confirming previously reported results.

Conclusion

In conclusion, our findings show a differential prevalence of anti-S Abs on mucosal surfaces after vaccination for SARS-CoV-2, while they also set the basis for potential future use of IgG antibody detection in buccal swabs for extended immunity screening in large populations.
Community-wide mass drug administration for soil-transmitted helminths – risk of drug resistance and mitigation strategies
Authors: Pilotte Nils , Manuel Malathi , Walson Judd L. , Ajjampur Sitara S. R.
Published: November 2022

Mass drug administration programs for the control of soil-transmitted helminths (STH) in humans most commonly utilize a single class of drugs; the benzimidazoles. Most such programs focus on the treatment of pre-school and school aged children attending schools, although there is increasing interest in the potential utility of community-wide MDA to reduce infection intensity within communities and possibly to interrupt STH transmission. In animals, mass treatment with benzimidazoles leads to the rapid selection of parasites containing resistance-encoding single nucleotide polymorphisms (SNP) and the potential emergence of resistance in parasite species that infect humans is of major potential public health concern. As programs scale up delivery of anthelmintics and consider expanding treated populations, monitoring of drug efficacy and the potential emergence of anthelmintic resistance with sensitive diagnostic tools is critical to ensure the continued success of STH control programs. In particular, as programs consider the adoption of community-wide deworming, there is concern that such a strategy may increase the risk of drug resistance by limiting the number of untreated individuals which serve as a refugia of unexposed worm populations. We review the literature for evidence of drug resistance in human STH infections and explore risks and mitigation strategies for emergence of drug resistance in the context of community-wide deworming.
Experimental investigation on the effects of magnetic field assistance on the quality of surface finish for sustainable manufacturing of ultra-precision single-point diamond turning of titanium alloys
Authors: Hatefi Shahrokh , Abou-El-Hossein Khaled
Published: November 2022

Single-point diamond turning (SPDT) is the state-of-the-art technology for ultra-precision manufacturing of optical products with optical surface roughness down to 1 nm. The SPDT technology has an important role in advanced manufacturing of critical components in different fields of industry. In a SPDT process, different cutting mechanisms affect the optical surface generation and reduce the quality of the turned product. Different efforts have been undertaken to improve the machining conditions as well as optical surface generation mechanisms. Recently, the application of magnetic field assistance in non-conventional SPDT platforms has shown promising results in terms of improving the cutting stability as well as the quality of surface finish. The application of magnetic field assistance becomes more important in SPDT of hard-to-cut materials including titanium alloy. In this study, magnetic field assistance is used in SPDT of Ti-6Al-4V alloy. The machining results show that using this technique could significantly improve the machining conditions and the quality of optical surface generation. The magnetic field assisted SPDT with air coolant could successfully improve the quality of surface finish by 62.5% when compared to non-magnetic purely mechanical SPDT process in dry cutting conditions. Magnetic field assistance is a passive machining technique, environmentally friendly, and it can promote green manufacturing and clean production in ultra-precision SPDT applications.
Fluid overload and mortality in critically ill patients with severe heart failure and cardiogenic shock–An observational cohort study
Authors: Waskowski Jan , Michel Matthias C. , Steffen Richard , Messmer Anna S. , Pfortmueller Carmen A.
Published: November 2022

Objective

Patients with heart failure (HF) and cardiogenic shock are especially prone to the negative effects of fluid overload (FO); however, fluid resuscitation in respective patients is sometimes necessary resulting in FO. We aimed to study the association of FO at ICU discharge with 30-day mortality in patients admitted to the ICU due to severe heart failure and/or cardiogenic shock.

Methods

Retrospective, single-center cohort study. Patients with admission diagnoses of severe HF and/or cardiogenic shock were eligible. The following exclusion criteria were applied: (I) patients younger than 16 years, (II) patients admitted to our intermediate care unit, and (III) patients with incomplete data to determine FO at ICU discharge. We used a cumulative weight-adjusted definition of fluid balance and defined more than 5% as FO. The data were analyzed by univariate and adjusted univariate logistic regression.

Results

We included 2,158 patients in our analysis. 185 patients (8.6%) were fluid overloaded at ICU discharge. The mean FO in the FO group was 7.2% [interquartile range (IQR) 5.8–10%]. In patients with FO at ICU discharge, 30-day mortality was 22.7% compared to 11.7% in non-FO patients (p < 0.001). In adjusted univariate logistic regression, we did not observe any association of FO at discharge with 30-day mortality [odds ratio (OR) 1.48; 95% confidence interval (CI) 0.81–2.71, p = 0.2]. No association between FO and 30-day mortality was found in the subgroups with HF only or cardiogenic shock (all p > 0.05). Baseline lactate (adjusted OR 1.27; 95% CI 1.13–1.42; p < 0.001) and cardiac surgery at admission (adjusted OR 1.94; 95% CI 1.0–3.76; p = 0.05) were the main associated factors with FO at ICU discharge.

Conclusion

In patients admitted to the ICU due to severe HF and/or cardiogenic shock, FO at ICU discharge seems not to be associated with 30-day mortality.
Pathogenesis of giant cell arteritis with focus on cellular populations
Authors: Stamatis Pavlos , Turesson Carl , Michailidou Despina , Mohammad Aladdin J.
Published: November 2022

Giant cell arteritis (GCA), the most common non-infectious vasculitis, mainly affects elderly individuals. The disease usually affects the aorta and its main supra-aortic branches causing both general symptoms of inflammation and specific ischemic symptoms because of the limited blood flow due to arterial structural changes in the inflamed arteries. The pathogenesis of the GCA is complex and includes a dysregulated immune response that affects both the innate and the adaptive immunity. During the last two decades several studies have investigated interactions among antigen-presenting cells and lymphocytes, which contribute to the formation of the inflammatory infiltrate in the affected arteries. Toll-like receptor signaling and interactions through the VEGF-Notch-Jagged1 pathway are emerging as crucial events of the aberrant inflammatory response, facilitating among others the migration of inflammatory cells to the inflamed arteries and their interactions with the local stromal milieu. The increased use of checkpoint inhibitors in cancer immunotherapy and their immune-related adverse events has fed interest in the role of checkpoint dysfunction in GCA, and recent studies suggest a dysregulated check point system which is unable to suppress the inflammation in the previously immune-privileged arteries, leading to vasculitis. The role of B-cells is currently reevaluated because of new reports of considerable numbers of plasma cells in inflamed arteries as well as the formation of artery tertiary lymphoid organs. There is emerging evidence on previously less studied cell populations, such as the neutrophils, CD8+ T-cells, T regulatory cells and tissue residing memory cells as well as for stromal cells which were previously considered as innocent bystanders. The aim of this review is to summarize the evidence in the literature regarding the cell populations involved in the pathogenesis of GCA and especially in the context of an aged, immune system.
Case report: Antiplatelet therapy on metastatic paraganglioma-associated cutaneous vascular disease and literature review
Authors: Gao Yinjie , Cui Yunying , Hu Zhonghui , Wang Yu , Li Tianyi , Liu Yuehua , Tong Anli
Published: November 2022

Context

Tumor-associated cutaneous vascular disorder induced by PPGL was extremely rare, and the cutaneous manifestations could disappear after removal of the tumors. However, the definite pathological diagnosis and the potential mechanism remained unidentified. We presented a severe cutaneous vascular lesion manifested as diffuse erythema with ulceration and necrosis over the limbs in a female patient with metastatic paraganglioma. Skin biopsy was performed on her for defining the pathological diagnosis and potential mechanism. The patient was diagnosed as vascular disease according to the obvious angioectasia in dermis on cutaneous pathology, which might be caused by PPGL-induced hypercoagulability. We used the antiplatelet therapy with aspirin to treat the PPGL-associated cutaneous vascular disease for the first time, and the cutaneous lesions were relieved and healed gradually, further supporting the diagnosis of vascular disease.

Conclusion

For metastatic PPGL patients like the case we reported, the definite diagnosis by skin biopsy and the early antiplatelet therapy might be effective to the cutaneous lesions caused by the hypercoagulable state of PPGL.
Gamma-glutamyl transferase to high-density lipoprotein cholesterol ratio has a non-linear association with non-alcoholic fatty liver disease: A secondary prospective cohort study in non-obese Chinese adults
Authors: Li Qiming , Han Yong , Hu Haofei , Zhuge Yuzheng
Published: November 2022

Objective

The evidence for a relationship between the ratio of gamma-glutamyl transferase (GGT) to high-density lipoprotein cholesterol (HDL-c) and non-alcoholic fatty liver disease (NAFLD) is currently inadequate. This study aimed to investigate the relationship between the GGT/HDL-c ratio and NAFLD.

Materials and methods

This study is a prospective cohort study that recruited a total of 11,891 non-obese volunteers in a Chinese hospital from January 2010 to December 2014 in a non-selective manner. The Cox proportional-hazards regression model was then used to investigate the relationship between baseline GGT/HDL-c ratio and the probability of developing NAFLD. The non-linear link between the GGT/HDL-c ratio and NAFLD was identified using a Cox proportional hazards regression with cubic spline functions and smooth curve fitting (cubic spline smoothing). Furthermore, we conducted several sensitivity and subgroup analyses. Data had been uploaded to the DATADRYAD website.

Results

The mean age of study participants was 43.29 ± 14.95 years old, and 6,502 (54.68%) were male. The median (interquartile ranges) of GGT/HDL-c ratio was 15.56 (10.73–23.84). During a median follow-up of 29.35 months, 2028 (17.05%) participants were diagnosed with NAFLD. After adjusting for covariates, the results showed that GGT/HDL-c ratio was positively associated with incident NAFLD (HR = 1.014, 95% CI 1.011–1.017). There was also a non-linear relationship between GGT/HDL-c ratio and NAFLD, and the inflection point of the GGT/HDL-c ratio was 20.35. The effect sizes (HR) on the left and right sides of the inflection point were 1.113 (95% CI 1.096, 1.130) and 1.003 (95% CI 1.000–1.007), respectively. Moreover, the sensitivity analysis demonstrated the robustness of our results. Subgroup analysis showed that GGT/HDL-c ratio was more strongly associated with incident NAFLD in triglyceride (TG) < 1.7 mmol/L participants. In contrast, the weaker association was probed in those with TG ≥ 1.7 mmol/L.

Conclusion

The present study reveals a positive and non-linear relationship between the GGT/HDL-c ratio and NAFLD risk in a non-obese Chinese population. GGT/HDL-c ratio is strongly associated with NAFLD when GGT/HDL-c ratio is less than 20.35. Therefore, maintaining the GGT/HDL-c ratio lower than the inflection point is recommended from a treatment perspective.
The successional trajectory of bacterial and fungal communities in soil are fabricated by yaks’ excrement contamination in plateau, China
Authors: Shang Zhenda , Wang Yaping , An Miao , Chen Xiushuang , Kulyar Muhammad Fakhar-e-Alam , Tan Zhankun , Liu Suozhu , Li Kun
Published: November 2022

The soil microbiome is crucial in determining contemporary realistic conditions for future terrestrial ecological and evolutionary development. However, the precise mechanism between the fecal deposition in livestock grazing and changes in the soil microbiome remains unknown. This is the first in-depth study of bacterial and fungal taxonomic changes of excrement contaminated soils in the plateau (>3,500 m). This suggests the functional shifts towards a harmful-dominated soil microbiome. According to our findings, excrement contamination significantly reduced the soil bacterial and fungal diversity and richness. Furthermore, a continuous decrease in the relative abundance of microorganisms was associated with nutrient cycling, soil pollution purification, and root-soil stability with the increasing degree of excrement contamination. In comparison, soil pathogens were found to have the opposite trend in the scenario, further deteriorating normal soil function and system resilience. Such colonization and succession of the microbiome might provide an important potential theoretical instruction for microbiome-based soil health protection measures in the plateau of China.
Transcriptional factor OmpR positively regulates prodigiosin biosynthesis in Serratia marcescens FZSF02 by binding with the promoter of the prodigiosin cluster
Authors: Jia Xianbo , Zhao Ke , Liu Fangchen , Lin Junjie , Lin Chenqiang , Chen Jichen
Published: November 2022

Prodigiosin is a promising secondary metabolite mainly produced by Serratia marcescens. The production of prodigiosin by S. marcescens is regulated by different kinds of regulatory systems, including the EnvZ/OmpR system. In this study, we demonstrated that the regulatory factor OmpR positively regulated prodigiosin production in S. marcescens FZSF02 by directly binding to the promoter region of the prodigiosin biosynthesis cluster with a lacZ reporter assay and electrophoretic mobility shift assay (EMSA). The binding sequence with the pig promoter was identified by a DNase I footprinting assay. We further demonstrate that OmpR regulates its own expression by directly binding to the promoter region of envZ/ompR. For the first time, the regulatory mechanism of prodigiosin production by the transcriptional factor OmpR was revealed.
Differences in gastric microbiota and mucosal function between patients with chronic superficial gastritis and intestinal metaplasia
Authors: Li Yingxia , Jiang Libin , Li Zhichao , Liu Yali , Xiao Bo , Ding Yan , Wen Hongtao
Published: November 2022

Chronic superficial gastritis (CSG) and intestinal metaplasia (IM) can further develop into gastric cancer, which seriously endangers the health of people all over the world. In this study, the differences in gastric microbiota between CSG patients and IM patients were detected by 16S rRNA gene sequencing. As the expression levels of mucin and CDX2 are closely related to IM, the expression differences of mucin (MUC2 and MUC5AC) and CDX2 in the gastric mucosa of CSG patients and IM patients were detected by Western blot and qRT-PCR. The results showed that both Faith_pd and Observed_species indexes of microbiota in the gastric juice of CSG patients were significantly higher than those of IM patients. At the genus level, Thermus and Anoxybacillus were dominant in the gastric juice of IM patients, and Helicobacter was dominant in the gastric juice of CSG patients. Non-metric multidimensional scaling (NMDS) demonstrated that the dispersion of samples in the CSG group is greater than that in the IM group, and some samples in the CSG group are clustered with samples in the IM group. The KEGG metabolic pathway difference analysis of gastric juice microbiota in CSG and IM patients revealed that the gastric juice microbiota in the CSG and IM patients were significantly enriched in the amino acid metabolism, carbohydrate metabolism, and metabolism of cofactors and vitamins, and the functional differences between the two groups were mainly concentrated in the bacterial secretion system (VirB1, VirB2, VirB3, VirD2, and VirD4). In conclusion, there are significant differences in gastric microbiota and mucosal function between the CSG and IM patients. Moreover, the results of this study may provide a new means for the detection of CSG and IM and a new direction for the prevention and treatment of CSG and IM.