bluuebunny/crossref_metadata_2025 huggingface dataset:
Public Perceptions of Synthetic Biology Solutions for Environmental Problems
Authors: Hobman Elizabeth V. , Mankad Aditi , Carter Lucy
Published: July 2022

This study explored public attitudes towards developing synthetic biology solutions for environmental problems: 1) invasive pest management, 2) endangered species conservation, 3) bioremediation of waterways, and 4) coral reef restoration. A sample of 4,593 Australians were surveyed online. Results showed that public support for a synthetic biology solution was highest for the bioremediation of waterways using an engineered pseudo-organism. Genetically engineering endangered species, invasive pests and coral received comparatively less support than bioremediation, however, support was still moderate to high for these other applications. More proximal behavioural intentions were also rated moderately to more favourably. Our findings underscore the importance of engaging with those who are likely to be impacted by the synthetic biology solution if it were introduced. At this local level, we can then obtain a better understanding of how people are likely to respond to the synthetic biology solution, which can inform how the solution is developed, and when, where, and how it might be implemented in the future.
Urban Comprehensive Carrying Capacity and Development Order: A “Pressure-Capacity-Potential” Logical Framework
Authors: Li Bingqian , Guan Mei , Zhan Lingyun , Liu Chunqiang , Zhang Zhipeng , Jiang Huailong , Zhang Yong , Dong Guanglong
Published: July 2022

Urban comprehensive carrying capacity determines the scale and development direction of a city and is an important factor in the optimization of main function areas, the arrangement of urban development order, and the demarcation of urban development boundaries in China’s new national spatial planning system. Using the constructed “pressure-capacity-potential” model as a theoretical basis, this study combines human factors and natural factors and calculates the urban carrying capacity index by means of multi-factor weighted summation, graded assignment, stepwise correction, and subsection variable weight. From the perspective of the integration and coordination of “three forces,” urban development rules are established, and an urban development order based on the framework of “three districts and six types” is put forward. The results reveal four key findings. First, the “pressure-capability-potential” conceptual model analyzes the urban carrying capacity from the perspective of the integration of externality and internality, which can effectively support the orderly arrangement and rational layout of urban development. Second, the urban carrying pressure of Shandong province is general, and the urban carrying capacity is high. The results also showed that the urban carrying potential is low and the urban comprehensive carrying capacity is high. Third, in the “3+6” urban development pattern of Shandong province, priority development and key development zones are the main areas. For the most part, these zones are distributed in the Jiaodong Peninsula, the Jinan–Tai’an–Jining development zone, and the surrounding areas of Weifang, Linyi, Liaocheng, and Heze. Moderate development zones are concentrated in Nansi Lake and the Yellow River Delta. Fourth, the urban development in Shandong province is mainly restricted by landform, water resources, environmental capacity, and geological disasters. Under the premise of ensuring resource conservation and environmental friendliness, using policies and engineering measures to revitalize stock space is an effective way to foster urban development in the 14th Five-Year Plan period. This study can provide reference for the evaluation of urban comprehensive carrying capacity and the establishment of development order in Shandong province and other similar areas.
Interactive Effects of meteorological Factors and Ambient air Pollutants on Mumps Incidences in Ningxia, China Between 2015 and 2019
Authors: Liu Weichen , Zhao Shi , Gong Rui , Zhang Yajuan , Ding Fan , Zhang Lu , Li Xiaolong , Wang Ruonan , Ma Ning , Zhao Yu
Published: July 2022

Background: Existing evidence suggests that mumps epidemics, a global public health issue, are associated with meteorological factors and air pollutants at the population scale. However, the interaction effect of meteorological factors and air pollutants on mumps remains underexplored.

Methods: Daily cases of mumps, meteorological factors, and air pollutants were collected in Ningxia, China, from 2015 to 2019. First, a distributed lag nonlinear model (DLNM) was employed to assess the confounding-adjusted relationship between meteorological factors, ambient air pollutants, and mumps incidences. According to the results of DLNM, stratification in both air pollutants and meteorological factors was adopted to further explore the interaction effect of particulate matter less than or equal to 2.5 μm in aerodynamic diameter (PM2.5) and ground-level ozone (O3) with temperature and relative humidity (RH).

Results: We reported significant individual associations between mumps incidences and environmental factors, including temperature, relative humidity, PM2.5, and O3. Evident multiplicate and additive interactions between meteorological factors and PM2.5 were found with interaction relative risk (IRR) of 1.14 (95%CI: 1.01, 1.29) and relative excess risk due to interaction (RERI) of 0.17 (95%CI: 0.02, 0.32) for a moderate level of temperature at 12°C, and IRR of 1.37 (95%CI: 1.14, 1.66), RERI of 0.36 (95%CI: 0.11, 0.60) for a high level of temperature at 20°C, respectively. These results indicated that PM2.5 and temperature have a significant synergistic effect on the cases of mumps, while no interaction between relative humidity and PM2.5 is observed. Regarding O3 and meteorological factors (temperature = 12°C, 20°C), IRR and RERI were 1.33 (95%CI: 1.17, 1.52) and 0.30 (95%CI: 0.16, 0.45), 1.91 (95%CI: 1.46, 2.49) and 0.69 (95%CI: 0.32, 1.07), respectively. And IRR of 1.17 (95%CI: 1.06, 1.29), RERI of 0.13 (95%CI: 0.04, 0.21) for a middle level of relative humidity at 48%.

Conclusion: Our findings indicated that meteorological factors and air pollutants imposed a significantly lagged and nonlinear effect on the incidence of mumps. The interaction between low temperature and O3 showed antagonistic effects, while temperature (medium and high) with PM2.5 and O3 presented synergistic effects. For relative humidity, the interaction with O3 is synergistic. These results provide scientific evidence to relevant health authorities for the precise disease control and prevention of mumps in arid and semi-arid areas.
The Spatial-Temporal Evolution Characteristics and Driving Factors of the Green Utilization Efficiency of Urban Land in China
Authors: Zhang Lijuan , Yu Yuzhu , Chen Yongheng
Published: July 2022

With the acceleration of urbanization, the urban land area of different spatial scales in China continues to increase, the urban land use efficiency is relatively low, and there are great regional differences. Land is an important material carrier for human production, life, and socio-economic activities. Reasonable measurement of the green utilization efficiency of urban land (Glande) has important theoretical and practical significance for the realization of urban land green use and the formulation of related policies. In this context, based on the publicly available data of 282 China’s cities at prefecture-level and above from 2009 to 2019, this study measures Glande with the Super-SBM data envelopment analysis model. After analyzing the spatio-temporal evolution characteristics of Glande, we employ the spatial dynamic Durbin model to analyze the spatial spillover effects. The results showed that: 1) Glande in China shows a fluctuating and rising trend, but it has not reached the effective state; 2) the agglomeration characteristics of urban land green use efficiency are significant, and from a regional point of view, it shows the pattern of western > eastern > central; 3) Glande is the result of the interaction of many factors. In the future, measures should be taken according to urban policies and local conditions, and differential measures should be taken to improve Glande.
A Rare Phenotype of Uncommon Charcot–Marie–Tooth Genotypes Complicated With Inflammation Evaluated by Genetics and Magnetic Resonance Neurography
Authors: Su Xiaoyun , Kong Xiangquan , Lu Zuneng , Wang Lixia , Zheng Chuansheng
Published: July 2022

The pathogenesis of Charcot–Marie–Tooth (CMT) disease, an inherited peripheral neuropathy, is associated with more than 60 nuclear genes. We reported a rare phenotype of the uncommon CMT genotype complicated with neuroinflammation, that is, an MPZ mutation, NC_000001.11 (NM_000530.6): c.308G > C detected by next-generation sequencing. Moreover, we present a case of the CMT type 1B, with atypical presentation as two patterns of hypertrophy in the brachial and lumbosacral plexus, as well as enhancement in the cauda equina and nerve roots on multimodal magnetic resonance neurography (MRN). MRN assessment facilitated the identification of coexisting neuroinflammation and provided more evidence, especially for patients with atypical symptoms in hereditary sensory and motor neuropathy, who could benefit from immunotherapy.
Comprehensive Analyses of Immune Subtypes of Stomach Adenocarcinoma for mRNA Vaccination
Authors: You Weiqiang , Ouyang Jian , Cai Zerong , Chen Yufeng , Wu Xiaojian
Published: July 2022

Background

Although messenger RNA (mRNA) vaccines have unique advantages against multiple tumors, mRNA vaccine targets in stomach adenocarcinoma (STAD) remain unknown. The potential effectiveness of mRNA vaccines is closely associated with the tumor immune infiltration microenvironment. The present study aimed to identify tumor antigens of STAD as mRNA vaccine targets and systematically determine immune subtypes (ISs) of STAD that might be suitable for immunotherapy.

Methods

Gene expression profiles and clinical data of patients with gastric cancer were downloaded from The Cancer Genome Atlas (TCGA; n = 409) and the Gene Expression Omnibus (GEO; n = 433), and genomic data were extracted from cBioPortal. Differential gene expression was analyzed using the limma package, genetic alterations were visualized using maftools, and prognosis was analyzed using ToPP. Correlations between gene expression and immune infiltration were calculated using TIMER software, and potential ISs were identified using ConsensusClusterPlus. Functional enrichment was analyzed in clusterProfiler, and r co-expression networks were analyzed using the weighted gene co-expression network analysis (WGCNA) package in R.

Results

Overexpression of the prognostic and highly mutated antigens ADAMTS18, COL10A1, PPEF1, and STRA6 was associated with infiltration by antigen-presenting cells in STAD. Five ISs (IS1–IS5) in STAD with distinct prognoses were developed and validated in TCGA and GEO databases. The tumor mutational burden and molecular and clinical characteristics significantly differed among IS1–IS5. Both IS1 and IS2 were associated with a high mutational burden, massive infiltration by immune cells, especially antigen-presenting cells, and better survival compared with the other subtypes. Both IS4 and IS5 were associated with cold immune infiltration and correlated with advanced pathological stages. We analyzed the immune microenvironments of five subtypes of immune modulators and biomarkers to select suitable populations for mRNA vaccination and established four co-expressed key modules to validate the characteristics of the ISs. Finally, the correlation of these four mRNA vaccine targets with the transcription factors of DC cells, including BATF3, IRF4, IRF8, ZEB2, ID2, KLF4, E2-2, and IKZF1, were explored to reveal the underlying mechanisms.

Conclusions

ADAMTS18, COL10A1, PPEF1, and STRA6 are potential mRNA vaccine candidates for STAD. Patients with IS1 and IS2 are suitable populations for mRNA vaccination immunotherapy.
Influence of Type I Interferons in Gammaherpesvirus-68 and Its Influence on EAE Enhancement
Authors: Márquez Ana Citlali , Croft Carys , Shanina Iryna , Horwitz Marc Steven
Published: July 2022

Epstein-Barr virus (EBV) has been identified as a putative trigger of multiple sclerosis (MS). Previously, we reported that mice latently infected with murine gammaherpesvirus 68 (γHV-68), the murine homolog to EBV, and induced for experimental autoimmune encephalomyelitis (EAE), developed an enhanced disease more reminiscent of MS. These prior results showed that expression of CD40 on CD11b+CD11c+ cells in latently infected mice was required to prime the strong Th1 response driving disease as well as decreasing Treg frequencies in the periphery and CNS. Subsequent work demonstrated that transfer of B cells from latently infected mice was sufficient to enhance disease. Herein, we show that B cells from infected mice do not need type I IFN signaling to drive a strong Th1 response, yet are important in driving infiltration of the CNS by CD8+ T cells. Given the importance of type I IFNs in MS, we used IFNARko mice in order to determine if type I IFN signaling was important in the enhancement of EAE in latently infected mice. We found that while type I IFNs are important for the control of γHV-68 infection and maintenance of latency, they do not have a direct effect in the development of enhanced EAE.
The Blood Immune Cell Count, Immunoglobulin, Inflammatory Factor, and Milk Trace Element in Transition Cows and Calves Were Altered by Increasing the Dietary n-3 or n-6 Polyunsaturated Fatty Acid Levels
Authors: Sun Xiaoge , Hou Yuhuang , Wang Yue , Guo Cheng , Wang Qianqian , Zhang Yan , Yang Zhantao , Wang Zhonghan , Cao Zhijun , Wang Wei , Li Shengli
Published: July 2022

Transition dairy cows experience sudden changes in both metabolic and immune functions, which lead to many diseases in postpartum cows. Therefore, it is crucial to monitor and guarantee the nutritional and healthy status of transition cows. The objective of this study was to determine the effect of diet enriched in n-3 or n-6 polyunsaturated fatty acid (PUFA) on colostrum composition and blood immune index of multiparous Holstein cows and neonatal calves during the transition period. Forty-five multiparous Holstein dairy cows at 240 days of pregnancy were randomly assigned to receive 1 of 3 isoenergetic and isoprotein diets: 1) CON, hydrogenated fatty acid (control), 1% of hydrogenated fatty acid [diet dry matter (DM) basis] during prepartum and postpartum, respectively; 2) HN3, 3.5% of extruding flaxseed (diet DM basis, n-3 PUFA source); 3) HN6, 8% of extruding soybeans (diet DM basis, C18:2n-6 PUFA source). Diets containing n-3 and n-6 PUFA sources decreased colostrum immunoglobulin G (IgG) concentration but did not significantly change the colostrum IgG yield compared with those with CON. The commercial milk yield (from 14 to 28 days after calving) was higher in the HN3 and HN6 than that in the CON. Furthermore, the n-3 PUFA source increased neutrophil cell counts in blood during the prepartum period and increased neutrophil percentage during the postpartum period when compared with those with control treatment. Diets containing supplemental n-3 PUFA decreased the serum concentration of interleukin (IL)-1β in maternal cows compared with those in control and n-6 PUFA during prepartum and postpartum. In addition, the neonatal calf serum concentration of tumor necrosis factor (TNF) was decreased in HN3 compared with that in the HN6 treatment. The diet with the n-3 PUFA source could potentially increase the capacity of neutrophils to defend against pathogens in maternal cows by increasing the neutrophil numbers and percentage during the transition period. Meanwhile, the diet with n-3 PUFA source could decrease the pro-inflammatary cytokine IL-1β of maternal cows during the transition period and decline the content of pro-inflammatary cytokine TNF of neonatal calves. It suggested that the highest milk production in n-3 PUFA treatment may partially be due to these beneficial alterations.
Sortase A-Cleavable CD1d Identifies Sphingomyelins as Major Class of CD1d-Associated Lipids
Authors: Rudolph Maren , Wang Yuting , Simolka Theresa , Huc-Claustre Emilie , Dai Lingyun , Grotenbreg Gijsbert , Besra Gurdyal Singh , Shevchenko Anna , Shevchenko Andrej , Zeissig Sebastian
Published: July 2022

CD1d is an atypical MHC class I molecule which binds endogenous and exogenous lipids and can activate natural killer T (NKT) cells through the presentation of lipid antigens. CD1d surveys different cellular compartments including the secretory and the endolysosomal pathway and broadly binds lipids through its two hydrophobic pockets. Purification of the transmembrane protein CD1d for the analysis of bound lipids is technically challenging as the use of detergents releases CD1d-bound lipids. To address these challenges, we have developed a novel approach based on Sortase A-dependent enzymatic release of CD1d at the cell surface of live mammalian cells, which allows for single step release and affinity tagging of CD1d for shotgun lipidomics. Using this system, we demonstrate that CD1d carrying the Sortase A recognition motif shows unimpaired subcellular trafficking through the secretory and endolysosomal pathway and is able to load lipids in these compartments and present them to NKT cells. Comprehensive shotgun lipidomics demonstrated that the spectrum and abundance of CD1d-associated lipids is not representative of the total cellular lipidome but rather characterized by preferential binding to long chain sphingolipids and glycerophospholipids. As such, sphingomyelin species recently identified as critical negative regulators of NKT cell activation, represented the vast majority of endogenous CD1d-associated lipids. Moreover, we observed that inhibition of endolysosomal trafficking of CD1d surprisingly did not affect the spectrum of CD1d-bound lipids, suggesting that the majority of endogenous CD1d-associated lipids load onto CD1d in the secretory rather than the endolysosomal pathway. In conclusion, we present a novel system for the analysis of CD1d-bound lipids in mammalian cells and provide new insight into the spectrum of CD1d-associated lipids, with important functional implications for NKT cell activation.
Dynamics of Melanoma-Associated Epitope-Specific CD8+ T Cells in the Blood Correlate With Clinical Outcome Under PD-1 Blockade
Authors: Gaißler Andrea , Meldgaard Trine Sundebo , Heeke Christina , Babaei Sepideh , Tvingsholm Siri Amanda , Bochem Jonas , Spreuer Janine , Amaral Teresa , Wagner Nikolaus Benjamin , Klein Reinhild , Meier Friedegund , Garbe Claus , Eigentler Thomas K. , Pawelec Graham , Claassen Manfred , Weide Benjamin , Hadrup Sine Reker , Wistuba-Hamprecht Kilian
Published: July 2022

Immune checkpoint blockade (ICB) is standard-of-care for patients with metastatic melanoma. It may re-invigorate T cells recognizing tumors, and several tumor antigens have been identified as potential targets. However, little is known about the dynamics of tumor antigen-specific T cells in the circulation, which might provide valuable information on ICB responses in a minimally invasive manner. Here, we investigated individual signatures composed of up to 167 different melanoma-associated epitope (MAE)-specific CD8+ T cells in the blood of stage IV melanoma patients before and during anti-PD-1 treatment, using a peptide-loaded multimer-based high-throughput approach. Additionally, checkpoint receptor expression patterns on T cell subsets and frequencies of myeloid-derived suppressor cells and regulatory T cells were quantified by flow cytometry. Regression analysis using the MAE-specific CD8+ T cell populations was applied to identify those that correlated with overall survival (OS). The abundance of MAE-specific CD8+ T cell populations, as well as their dynamics under therapy, varied between patients. Those with a dominant increase of these T cell populations during PD-1 ICB had a longer OS and progression-free survival than those with decreasing or balanced signatures. Patients with a dominantly increased MAE-specific CD8+ T cell signature also exhibited an increase in TIM-3+ and LAG-3+ T cells. From these results, we created a model predicting improved/reduced OS by combining data on dynamics of the three most informative MAE-specific CD8+ T cell populations. Our results provide insights into the dynamics of circulating MAE-specific CD8+ T cell populations during ICB, and should contribute to a better understanding of biomarkers of response and anti-cancer mechanisms.
The Neuroimmune Response to Surgery – An Exploratory Study of Trauma-Induced Changes in Innate Immunity and Heart Rate Variability
Authors: Hildenborg Malin , Kåhlin Jessica , Granath Fredrik , Schening Anna , Granström Anna , Ebberyd Anette , Klevenvall Lena , Zetterberg Henrik , Han Jinming , Schlegel Todd T. , Harris Robert , Harris Helena Erlandsson , Eriksson Lars I.
Published: July 2022

Surgery triggers a systemic inflammatory response that ultimately impacts the brain and associates with long-term cognitive impairment. Adequate regulation of this immune surge is pivotal for a successful surgical recovery. We explored the temporal immune response in a surgical cohort and its associations with neuroimmune regulatory pathways and cognition, in keeping with the growing body of evidence pointing towards the brain as a regulator of peripheral inflammation. Brain-to-immune communication acts through cellular, humoral and neural pathways. In this context, the vagal nerve and the cholinergic anti-inflammatory pathway (CAP) have been shown to modify peripheral immune cell activity in both acute and chronic inflammatory conditions. However, the relevance of neuroimmune regulatory mechanisms following a surgical trauma is not yet elucidated. Twenty-five male patients undergoing elective laparoscopic abdominal surgery were included in this observational prospective study. Serial blood samples with extensive immune characterization, assessments of heart rate variability (HRV) and cognitive tests were performed before surgery and continuing up to 6 months post-surgery. Temporal immune responses revealed biphasic reaction patterns with most pronounced changes at 5 hours after skin incision and 14 days following surgery. Estimations of cardiac vagal nerve activity through HRV recordings revealed great individual variations depending on the pre-operative HRV baseline. A principal component analysis displayed distinct differences in systemic inflammatory biomarker trajectories primarily based on pre-operative HRV, with potiential consequences for long-term surgical outcomes. In conclusion, individual pre-operative HRV generates differential response patterns that associate with distinct inflammatory trajectories following surgery. Long-term surgical outcomes need to be examined further in larger studies with mixed gender cohorts.
γ9δ2 T-Cell Expansion and Phenotypic Profile Are Reflected in the CDR3δ Repertoire of Healthy Adults
Authors: Vyborova Anna , Janssen Anke , Gatti Lucrezia , Karaiskaki Froso , Yonika Austin , van Dooremalen Sanne , Sanders Jasper , Beringer Dennis X. , Straetemans Trudy , Sebestyen Zsolt , Kuball Jürgen
Published: July 2022

γ9δ2T cells fill a distinct niche in human immunity due to the unique physiology of the phosphoantigen-reactive γ9δ2TCR. Here, we highlight reproducible TCRδ complementarity-determining region 3 (CDR3δ) repertoire patterns associated with γ9δ2T cell proliferation and phenotype, thus providing evidence for the role of the CDR3δ in modulatingin vivoT-cell responses. Features that determine γ9δ2TCR binding affinity and reactivity to the phosphoantigen-induced ligandin vitroappear to similarly underpinin vivoclonotypic expansion and differentiation. Likewise, we identify a CDR3δ bias in the γ9δ2T cell natural killer receptor (NKR) landscape. While expression of the inhibitory receptor CD94/NKG2A is skewed toward cells bearing putative high-affinity TCRs, the activating receptor NKG2D is expressed independently of the phosphoantigen-sensing determinants, suggesting a higher net NKR activating signal in T cells with TCRs of low affinity. This study establishes consistent repertoire–phenotype associations and justifies stratification for the T-cell phenotype in future research on γ9δ2TCR repertoire dynamics.
In Vivo ETosis of Human Eosinophils: The Ultrastructural Signature Captured by TEM in Eosinophilic Diseases
Authors: Neves Vitor H. , Palazzi Cinthia , Bonjour Kennedy , Ueki Shigeharu , Weller Peter F. , Melo Rossana C. N.
Published: July 2022

Eosinophilic diseases, also termed eosinophil-associated diseases (EADs), are characterized by eosinophil-rich inflammatory infiltrates and extensive eosinophil degranulation with clinically relevant organ pathology. Recent evidence shows that eosinophil cytolytic degranulation, that is, the release of intact, membrane-delimited granules that arises from the eosinophil cytolysis, occurs mainly through ETosis, meaning death with a cytolytic profile and extrusion of nucleus-originated DNA extracellular traps (ETs). The ultrastructural features of eosinophil ETosis (EETosis) have been studied mostly in vitro after stimulation, but are still poorly understood in vivo. Here, we investigated in detail, by transmission electron microscopy (TEM), the ultrastructure of EETosis in selected human EADs affecting several tissues and organ systems. Biopsies of patients diagnosed with eosinophilic chronic rhinosinusitis/ECRS (frontal sinus), ulcerative colitis/UC (intestine), and hypereosinophilic syndrome/HES (skin) were processed for conventional TEM. First, we found that a large proportion of tissue-infiltrated eosinophils in all diseases (~45-65% of all eosinophils) were undergoing cytolysis with release of free extracellular granules (FEGs). Second, we compared the morphology of tissue inflammatory eosinophils with that shown by in vitro ETosis-stimulated eosinophils. By applying single-cell imaging analysis, we sought typical early and late EETosis events: chromatin decondensation; nuclear delobulation and rounding; expanded nuclear area; nuclear envelope alterations and disruption; and extracellular decondensed chromatin spread as ETs. We detected that 53% (ECRS), 37% (UC), and 82% (HES) of all tissue cytolytic eosinophils had ultrastructural features of ETosis in different degrees. Eosinophils in early ETosis significantly increased their nuclear area compared to non-cytolytic eosinophils due to excessive chromatin decondensation and expansion observed before nuclear envelope disruption. ETosis led not only to the deposition of intact granules, but also to the release of eosinophil sombrero vesicles (EoSVs) and Charcot-Leyden crystals (CLCs). Free intact EoSVs and CLCs were associated with FEGs and extracellular DNA nets. Interestingly, not all cytolytic eosinophils in the same microenvironment exhibited ultrastructure of ETosis, thus indicating that different populations of eosinophils might be selectively activated into this pathway. Altogether, our findings captured an ultrastructural signature of EETosis in vivo in prototypic EADs highlighting the importance of this event as a form of eosinophil degranulation and release of inflammatory markers (EoSVs and CLCs).
Multisystem Inflammatory Syndrome in Children and Long COVID: The SARS-CoV-2 Viral Superantigen Hypothesis
Authors: Noval Rivas Magali , Porritt Rebecca A. , Cheng Mary Hongying , Bahar Ivet , Arditi Moshe
Published: July 2022

Multisystem inflammatory syndrome in children (MIS-C) is a febrile pediatric inflammatory disease that may develop weeks after initial SARS-CoV-2 infection or exposure. MIS-C involves systemic hyperinflammation and multiorgan involvement, including severe cardiovascular, gastrointestinal (GI) and neurological symptoms. Some clinical attributes of MIS-C—such as persistent fever, rashes, conjunctivitis and oral mucosa changes (red fissured lips and strawberry tongue)—overlap with features of Kawasaki disease (KD). In addition, MIS-C shares striking clinical similarities with toxic shock syndrome (TSS), which is triggered by bacterial superantigens (SAgs). The remarkable similarities between MIS-C and TSS prompted a search for SAg-like structures in the SARS-CoV-2 virus and the discovery of a unique SAg-like motif highly similar to a Staphylococcal enterotoxin B (SEB) fragment in the SARS-CoV-2 spike 1 (S1) glycoprotein. Computational studies suggest that the SAg-like motif has a high affinity for binding T-cell receptors (TCRs) and MHC Class II proteins. Immunosequencing of peripheral blood samples from MIS-C patients revealed a profound expansion of TCR β variable gene 11-2 (TRBV11-2), which correlates with MIS-C severity and serum cytokine levels, consistent with a SAg-triggered immune response. Computational sequence analysis of SARS-CoV-2 spike further identified conserved neurotoxin-like motifs which may alter neuronal cell function and contribute to neurological symptoms in COVID-19 and MIS-C patients. Additionally, autoantibodies are detected during MIS-C, which may indicate development of post-SARS-CoV-2 autoreactive and autoimmune responses. Finally, prolonged persistence of SARS-CoV-2 RNA in the gut, increased gut permeability and elevated levels of circulating S1 have been observed in children with MIS-C. Accordingly, we hypothesize that continuous and prolonged exposure to the viral SAg-like and neurotoxin-like motifs in SARS-CoV-2 spike may promote autoimmunity leading to the development of post-acute COVID-19 syndromes, including MIS-C and long COVID, as well as the neurological complications resulting from SARS-CoV-2 infection.
Topographic Hotspots of Southern Ocean Eddy Upwelling
Authors: Yung Claire K. , Morrison Adele K. , Hogg Andrew McC.
Published: July 2022

The upwelling of cold water from the depths of the Southern Ocean to its surface closes the global overturning circulation and facilitates uptake of anthropogenic heat and carbon. Upwelling is often conceptualised in a zonally averaged framework as the result of isopycnal flattening via baroclinic eddies. However, upwelling is zonally non-uniform and occurs in discrete hotspots near topographic features. The mechanisms that facilitate topographically confined eddy upwelling remain poorly understood and thus limit the accuracy of parameterisations in coarse-resolution climate models.

Using a high-resolution global ocean sea-ice model, we calculate spatial distributions of upwelling transport and energy conversions associated with barotropic and baroclinic instability, derived from a thickness-weighted energetics framework. We find that five major topographic hotspots of upwelling, covering less than 30% of the circumpolar longitude range, account for up to 76% of the southward eddy upwelling transport. The conversion of energy into eddies via baroclinic instability is highly spatially correlated with upwelling transport, unlike the barotropic energy conversion, which is also an order of magnitude smaller than the baroclinic conversion. This result suggests that eddy parameterisations that quantify baroclinic energy conversions could be used to improve the simulation of upwelling hotspots in climate models. We also find that eddy kinetic energy maxima are found on average 110 km downstream of upwelling hotspots in accordance with sparse observations. Our findings demonstrate the importance of localised mechanisms to Southern Ocean dynamics.
A Result of Accidental Noise Pollution: Acoustic Flowmeters Emit 28 kHz Pulses That May Affect Harbor Porpoise Hearing
Authors: Schaffeld Tobias , Schnitzler Joseph G. , Ruser Andreas , Baltzer Johannes , Schuster Max , Siebert Ursula
Published: July 2022

Large rivers like the Elbe or the Weser are periodically entered by harbor porpoises of the North Sea. They may even move 97 km upstream to the port of Hamburg, where their presence is highest in spring. This migration is believed to be related to important anadromous prey species travelling upstream for spawning. An acoustic flowmeter in the port of Hamburg emits signals in the hearing range of harbor porpoises. The pulses have a duration of 0.2 ms, a peak frequency of 28 kHz, a source level of 210 dB re 1 µPa and an inter-pulse interval of 4.2 s. The signals are continuously emitted from both sides of the river at a location where the river is 400 m wide. We evaluated the potential of these signals to induce temporary threshold shift (TTS) in harbor porpoise hearing. Hearing tests with a harbor porpoise in human care were conducted to determine TTS onset. We modelled the acoustic field based on underwater noise measurements. The acoustic flowmeters emit pulses in a highly directional beam with a source level high enough for inducing TTS in harbor porpoises by a single exposure up to a distance of approximately 72 m. The received cumulative sound exposure levels for harbor porpoises travelling along the flowmeters are mainly dependent on the timing and distance to the sound source. Accordingly, a close approach to the flowmeter at the time of transmission should be prevented. This could be the case, if vessels force harbor porpoises to displace closer to the flowmeters. We therefore suggest to decrease acoustic flowmeter source levels. This case study emphasizes the need for a mandatory authorization process prior to the use of underwater sound for any purpose with potential effects on aquatic life. Such an authorization process should carefully consider potential effects for target and non-target species.
Slope Undercurrent in the Northwestern South China Sea Beneath the Winter Western Boundary Current
Authors: Shen Junqiang , Fang Wendong , Li Li , Qiu Yun , Xiao Zheng , Zhang Junpeng , Guo Xiaogang
Published: July 2022

We herein report the observation of a slope undercurrent beneath the winter western boundary current of the northwestern South China Sea (SCS), and its spatiotemporal variation. The possible underlying dynamics are also discussed. In situ observations reveal that the northeastward undercurrent is located above the upper slope with a core velocity exceeding 20 cm/s, which extends from 200 m to 800 m in depth with a width of 30–50 km and an along-slope length of approximately 200 km in deep winter of 2006-2007, and is characterized with interseasonal and interannual variabilities. The existence of this undercurrent is also supported by Hybrid Coordinate Ocean Model (HYCOM) results. We find that the slope undercurrent is probably driven by the along-slope pressure gradient associated with the sea level set-up off the continental slope of south Hainan Island and modulated by mesoscale eddies and Rossby waves. This study will renew our knowledge of the deep slope currents in the northwestern SCS.
Spatially Resolved Transcriptomes of Mammalian Kidneys Illustrate the Molecular Complexity and Interactions of Functional Nephron Segments
Authors: Raghubar Arti M. , Pham Duy T. , Tan Xiao , Grice Laura F. , Crawford Joanna , Lam Pui Yeng , Andersen Stacey B. , Yoon Sohye , Teoh Siok Min , Matigian Nicholas A. , Stewart Anne , Francis Leo , Ng Monica S. Y. , Healy Helen G. , Combes Alexander N. , Kassianos Andrew J. , Nguyen Quan , Mallett Andrew J.
Published: July 2022

Available transcriptomes of the mammalian kidney provide limited information on the spatial interplay between different functional nephron structures due to the required dissociation of tissue with traditional transcriptome-based methodologies. A deeper understanding of the complexity of functional nephron structures requires a non-dissociative transcriptomics approach, such as spatial transcriptomics sequencing (ST-seq). We hypothesize that the application of ST-seq in normal mammalian kidneys will give transcriptomic insights within and across species of physiology at the functional structure level and cellular communication at the cell level. Here, we applied ST-seq in six mice and four human kidneys that were histologically absent of any overt pathology. We defined the location of specific nephron structures in the captured ST-seq datasets using three lines of evidence: pathologist's annotation, marker gene expression, and integration with public single-cell and/or single-nucleus RNA-sequencing datasets. We compared the mouse and human cortical kidney regions. In the human ST-seq datasets, we further investigated the cellular communication within glomeruli and regions of proximal tubules–peritubular capillaries by screening for co-expression of ligand–receptor gene pairs. Gene expression signatures of distinct nephron structures and microvascular regions were spatially resolved within the mouse and human ST-seq datasets. We identified 7,370 differentially expressed genes (padj< 0.05) distinguishing species, suggesting changes in energy production and metabolism in mouse cortical regions relative to human kidneys. Hundreds of potential ligand–receptor interactions were identified within glomeruli and regions of proximal tubules–peritubular capillaries, including known and novel interactions relevant to kidney physiology. Our application of ST-seq to normal human and murine kidneys confirms current knowledge and localization of transcripts within the kidney. Furthermore, the generated ST-seq datasets provide a valuable resource for the kidney community that can be used to inform future research into this complex organ.
Secular Trends of Incidence, Prevalence, and Healthcare Economic Burden in ANCA-Associated Vasculitis: An Analysis of the 2002–2018 South Korea National Health Insurance Database
Authors: Ahn Sung Soo , Lim Hyunsun , Lee Chan Hee , Park Yong-Beom , Park Jin-Su , Lee Sang-Won
Published: July 2022

Objectives

The incidence and prevalence of AAV in Asia remain poorly understood, especially in a nationwide setting. This study investigated the incidence, prevalence, and healthcare burden of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in South Korea by analyzing a national database.

Methods

This study included patients with AAV identified from the National Health Insurance Service Database of South Korea from 2002 to 2018. Patients were diagnosed with AAV in a general or tertiary hospital and were registered in the individual payment beneficiaries program or were prescribed glucocorticoids. A calendar-based meteorological definitions were adopted to assess the differences in the incidence of AAV according to season. The average healthcare expenditure and patient outcomes of mortality and end-stage renal disease (ESRD) in patients with AAV were compared to 1:10 age, sex and residential area matched controls.

Results

A total of 2,113 patients [708, 638, and 767 with microscopic polyangiitis (MPA), granulomatosis with polyangiitis, and eosinophilic granulomatosis with polyangiitis, respectively] were identified. The annual incidence and prevalence of AAV increased continuously, and MPA being the most common disease subtype after 2015. The highest incidence and prevalence of AAV was 0.48/100,000 person-years (PY) and 2.40/100,000 PY in 2017 and 2018, respectively. There were no significant differences in monthly and seasonal incidence of AAV. The average expense of medical care, overall mortality, and ESRD rates of patients with AAV were higher in patients with AAV than in controls, especially in the case of MPA.

Conclusion

An increasing trend of AAV diagnosis observed is consistent with the evidence that AAV is more common in recent years; however, a relatively lower incidence and prevalence was observed compared to that in Western countries. The higher medical cost and rates of mortality and ESRD in AAV emphasize the early recognition and implementation of optimal treatment for these patients.
Main Pathological Changes of Benign Ureteral Strictures
Authors: Tan Jiang , Yu Zhuoyuan , Ling Xinyi , Qiu Guoping , Yang Xin , Tang Yi , Yang Dong , Yang Mei , Gao Fei
Published: July 2022

Objective

To identify the pathological classification of benign ureteral strictures according to the histological features and explore the relationship between various pathological types and inflammatory cells, fibroblasts, and collagen.

Patients and Methods

Thirty one specimens from patients diagnosed with ureteral strictures between 2013 and 2021 were included and classified according to the histopathological characteristics. The number of fibroblasts and inflammatory cells was counted, and the proportion of type I and type III collagen in ureteral stricture tissues was detected by picrosirius red staining.

Results

We identified three types of benign ureteral strictures in 31 specimens: inflammatory cell infiltration (n= 10, 32%), fibroplasia (n= 14, 45%), and hyalinization (n= 7, 23%), with significant differences in obstruction history and hydronephrosis grades among the three types. The number of inflammatory cells (lymphocytes, neutrophils and eosinophils) was significantly lower in hyalinization ureteral strictures than in the other two types (p< 0.05). The number of foreign-body giant cells associated with foreign-body reactions increased significantly in suture-induced ureteral strictures (p< 0.05). Fibroplasia type had the largest number of fibroblasts, whereas the other two types had smaller numbers. The results of type I and III collagen analysis showed that type I and III collagen were the most abundant in hyalinization among all ureteral stricture types (p< 0.05). Compared to ureteral strictures, the content of type I and III collagen in atresia increased significantly (p< 0.05).

Conclusion

Common pathological types of benign ureteral strictures include inflammatory cell infiltration, fibroplasia, and hyalinization. Changes in type I and III collagen, inflammatory cells, and fibroblasts in different pathological types may be related to the progression of ureteral strictures.
The Effect of Hydroxychloroquine on Residual Proteinuria in Patients With Immunoglobulin A Nephropathy: A Retrospective Study Based on Propensity Score Matching
Authors: Liu Mijia , Bian Xueyan , Wang Li , Li Guisen
Published: July 2022

Background

There is insufficient evidence to support the use of hydroxychloroquine (HCQ) in Immunoglobulin A nephropathy (IgAN) patients with high residual proteinuria in spite of 6-month supportive treatment combined with corticosteroids (P) and/or immunosuppressives (IM). This study aims to explore the effect of HCQ on residual proteinuria in IgAN.

Materials and Methods

This is a retrospective study. IgAN patients who had residual proteinuria ≥0.3 g/24 h after 6-month treatment by renin-angiotensin system inhibitors (RASI) + P ± IM were included. Groups were divided based on the different regimens and then matched by the propensity score matching method. The primary outcome was defined as the cumulative frequency of residual proteinuria reduction ≥30%.

Results

RASI (n = 183), HCQ + RASI (n = 59), RASI + P ± IM (n = 145), and HCQ + RASI + P ± IM (n = 38) groups were included. HCQ + RASI group had a higher level of residual proteinuria and a worse renal function than those in the RASI group. The renal function was worse in the HCQ + RASI + P ± IM group than that in the control group, but residual proteinuria levels were similar. After matching, there were 40 patients in the first two groups and 29 patients in the latter two groups, respectively. The cumulative frequency of residual proteinuria reduction ≥30% in HCQ + RASI + P ± IM group was higher than that in control group (86.2% vs. 62.1%, χ2 = 6.397, p = 0.011). HCQ combination treatment was one of independent factors.

Conclusion

The addition of HCQ treatment can effectively reduce the residual proteinuria in IgAN patients previously treated with supportive treatment combined with P and IM treatment and the cumulative frequency of effective reduction of residual proteinuria can reach 86.2%.
18F-FDG /18F-Choline Dual-Tracer PET Behavior and Tumor Differentiation in HepatoCellular Carcinoma. A Systematic Review
Authors: Ghidaglia Jérôme , Golse Nicolas , Pascale Alina , Sebagh Mylène , Besson Florent L.
Published: July 2022

Background

Post-operative recurrence remains the strongest prognostic factor of resected hepatocellular carcinoma (HCC), making the accurate selection of patients with curable HCC a crucial issue. PET imaging combining both 18F-FDG and fatty acid synthase (FAS) radiotracers—such as Choline—has shown its interest for the initial staging and therapeutic management of patients with HCC, but its use is still not consensual. Importantly, the very first dual-tracer PET studies suggested 18F-FDG/FAS PET behavior be linked to the degree of differentiation of HCC, a major predictive factor of post-operative recurrence. Although this key molecular imaging concept may impact how dual-tracer PET will be used in early-stage HCC, its level of evidence remains largely unexplored. In this study, we conducted a systematic review of the available evidence-based data to clarify the relevance of dual 18F-FDG/18F-Choline PET in characterizing the degree of differentiation of HCC tumors.

Methods

A systematic search of the PubMed/Medline and Embase databases was performed up to November 2021. A systematic review of the dual-tracer 18F-FDG/18F-Choline PET behavior of histology-proven HCC according to their degree of differentiation was conducted. The overall quality of the included studies was critically assessed based on the STROBE guidelines. Information on study date, design, patient cohort characteristics, grade of differentiation of HCC tumors, and the dual-tracer PET behavior per HCC was independently extracted and summarized.

Results

From 440 records initially available, 6 full-text articles (99 histology-proven HCC) provided dual-tracer 18F-FDG/18F-Choline PET behavior per HCC tumor grade were included in the systematic review. Based on our analysis, 43/99 HCCs were reported to be well-differentiated, and 56/99 HCCs were reported to be less-differentiated tumors. In the well-differentiated subgroup, more than half were exclusively positive for 18F-Choline (51%), whereas 39% were positive for both 18F-FDG and 18F-Choline. In the less-differentiated subgroup, 37% of HCC patients were positive exclusively for FDG, 36% were positive for both 18F-FDG and 18F-Choline, and 25% were positive exclusively for 18F-Choline.

Conclusion

The 18F-FDG/18F-Choline dual-tracer PET behavior of uptake shows high overlap between well- and less differentiated HCC, making the characterization of tumors challenging based on such PET combination alone. Given our growing knowledge of the molecular complexity of HCC, further studies are necessary to refine our understanding of radiotracers’ behavior in this field and improve the usefulness of PET imaging in the clinical decision process of HCC.