bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of chromatin data supports a role for CD14+ monocytes/macrophages in mediating genetic risk for juvenile idiopathic arthritis
Authors: Crinzi Elizabeth A. , Haley Emma K. , Poppenberg Kerry E. , Jiang Kaiyu , Tutino Vincent M. , Jarvis James N.
Published: September 2022

Introduction

Genome wide association studies (GWAS) have identified multiple regions that confer genetic risk for the polyarticular/oligoarticular forms of juvenile idiopathic arthritis (JIA). However, genome-wide scans do not identify the cells impacted by genetic polymorphisms on the risk haplotypes or the genes impacted by those variants. We have shown that genetic variants driving JIA risk are likely to affect both innate and adaptive immune functions. We provide additional evidence that JIA risk variants impact innate immunity.

Materials and methods

We queried publicly available H3K4me1/H3K27ac ChIP-seq data in CD14+ monocytes to determine whether the linkage disequilibrium (LD) blocks incorporating the SNPs that tag JIA risk loci showed enrichment for these epigenetic marks. We also queried monocyte/macrophage GROseq data, a functional readout of active enhancers. We defined the topologically associated domains (TADs) encompassing enhancers on the risk haplotypes and identified genes within those TADs expressed in monocytes. We performed ontology analyses of these genes to identify cellular processes that may be impacted by these variants. We also used whole blood RNAseq data from the Genotype-Tissue Expression (GTEx) data base to determine whether SNPs lying within monocyte GROseq peaks influence plausible target genes within the TADs encompassing the JIA risk haplotypes.

Results

The LD blocks encompassing the JIA genetic risk regions were enriched for H3K4me1/H3K27ac ChIPseq peaks (p=0.00021 and p=0.022) when compared to genome background. Eleven and sixteen JIA were enriched for resting and activated macrophage GROseq peaks, respectively risk regions (p=0.04385 and p=0.00004). We identified 321 expressed genes within the TADs encompassing the JIA haplotypes in human monocytes. Ontological analysis of these genes showed enrichment for multiple immune functions. Finally, we found that SNPs lying within the GROseq peaks are strongly associated with expression levels of plausible target genes in human whole blood.

Conclusions

These findings support the idea that both innate and adaptive immunity are impacted by JIA genetic risk variants.
Targeting hypoxia-induced tumor stemness by activating pathogen-induced stem cell niche defense
Authors: Bhuyan Seema , Pal Bidisha , Pathak Lekhika , Saikia Partha Jyoti , Mitra Shirsajit , Gayan Sukanya , Mokhtari Reza Bayat , Li Hong , Ramana Chilakamarti V. , Baishya Debabrat , Das Bikul
Published: September 2022

Tumor hypoxia and oxidative stress reprograms cancer stem cells (CSCs) to a highly aggressive and inflammatory phenotypic state of tumor stemness. Previously, we characterized tumor stemness phenotype in the ATP Binding Cassette Subfamily G Member 2 (ABCG2)–positive migratory side population (SPm) fraction of CSCs exposed to extreme hypoxia followed by reoxygenation. Here, we report that post-hypoxia/reoxygenation SPm+/ABCG2+ CSCs exerts defense against pathogen invasion that involves bystander apoptosis of non-infected CSCs. In an in vitro assay of cancer cell infection by Bacillus Calmette Guerin (BCG) or mutant Mycobacterium tuberculosis (Mtb) strain 18b (Mtb-m18b), the pathogens preferentially replicated intracellular to SPm+/ABCG2+ CSCs of seven cell lines of diverse cancer types including SCC-25 oral squamous cancer cell line. The conditioned media (CM) of infected CSCs exhibited direct anti-microbial activity against Mtb and BCG, suggesting niche defense against pathogen. Importantly, the CM of infected CSCs exhibited marked in vitro bystander apoptosis toward non-infected CSCs. Moreover, the CM-treated xenograft bearing mice showed 10- to 15-fold reduction (p < 0.001; n = 7) in the number of CSCs residing in the hypoxic niches. Our in vitro studies indicated that BCG-infected SPm+/ABCG2+ equivalent EPCAM+/ABCG2+ CSCs of SCC-25 cells underwent pyroptosis and released a high mobility group box protein 1 (HMGB1)/p53 death signal into the tumor microenvironment (TME). The death signal can induce a Toll-like receptor 2/4–mediated bystander apoptosis in non-infected CSCs by activating p53/MDM2 oscillation and subsequent activation of capase-3–dependent intrinsic apoptosis. Notably, SPm+/ABCG2+ but not SP cells undergoing bystander apoptosis amplified the death signal by further release of HMGB1/p53 complex into the TME. These results suggest that post-hypoxia SPm+/ABCG2+ CSCs serve a functional role as a tumor stemness defense (TSD) phenotype to protect TME against bacterial invasion. Importantly, the CM of TSD phenotype undergoing bystander apoptosis may have therapeutic uses against CSCs residing in the hypoxic niche.
Simultaneous genotyping for human platelet antigen systems and HLA-A and HLA-B loci by targeted next-generation sequencing
Authors: Wang Jielin , You Xuan , He Yanmin , Hong Xiaozhen , He Ji , Tao Sudan , Zhu Faming
Published: September 2022

In order to treat the alloimmunization platelet transfusion refractoriness (PTR), human leukocyte antigen (HLA)-type and/or human platelet antigen (HPA)-type matched platelets between donors and patients are usually used. Therefore, genotyping of HLA-A and HLA-B loci, as well as HPA systems, for donors and patients, is of great significance. However, there is a rare report of genotyping for HLA-A and HLA-B loci as well as HPA systems at the same time. In this study, a high-throughput method for simultaneous genotyping of HLA-A and HLA-B loci, as well as HPA genotyping, was developed. A RNA capture probe panel was designed covering all exon sequences of the GP1BA, GP1BB, ITGA2, CD109, ITGB3, and ITGA2B genes and HLA-A and HLA-B loci. The HLA-A, HLA-B, and 34 HPA systems were genotyped using a targeted next-generation sequencing (NGS) method. The genotypes of the HLA-A and HLA-B loci, as well as the HPA, were assigned based on the nucleotides in the polymorphism sites. Using the NGS method, 204 unrelated blood specimens were successfully genotyped for all 34 HPA systems as well as HLA-A and HLA-B loci. The accuracy of the NGS method was 100%. Only HPA-2, HPA-3, HPA-5, HPA-6w, HPA-15, and HPA-21w showed polymorphism with frequencies of 0.9412, 0.6863, 0.9853, 0.9779, 0.4314, and 0.9951 for a allele, respectively. Thirty-two single nucleotide variants (SNVs) were detected. Of them, 12 SNVs can lead to amino acid change. HLA-A*11:01 and HLA-B*46:01 are the most common alleles for HLA-A and HLA-B loci. A targeted next-generation sequencing method for simultaneously genotyping HPA systems and HLA-A and HLA-B loci was first established, which could be used to create a database of HLA-typed and/or HPA-typed unrelated donors.
Novel peanut-specific human IgE monoclonal antibodies enable screens for inhibitors of the effector phase in food allergy
Authors: Suber Jada , Zhang Yugen , Ye Ping , Guo Rishu , Burks A. Wesley , Kulis Michael D. , Smith Scott A. , Iweala Onyinye I.
Published: September 2022

Background

10% of US residents have food allergies, including 2% with peanut allergy. Mast cell mediators released during the allergy effector phase drive allergic reactions. Therefore, targeting sensitized mast cells may prevent food allergy symptoms.

Objective

We used novel, human, allergen-specific, IgE monoclonal antibodies (mAbs) created using human hybridoma techniques to design anin vitrosystem to evaluate potential therapeutics targeting sensitized effector cells.

Methods

Two human IgE mAbs specific for peanut, generated through human hybridoma techniques, were used to sensitize rat basophilic leukemia (RBL) SX-38 cells expressing the human IgE receptor (FcϵRI). Beta-hexosaminidase release (a marker of degranulation), cytokine production, and phosphorylation of signal transduction proteins downstream of FcϵRI were measured after stimulation with peanut. Degranulation was also measured after engaging inhibitory receptors CD300a and Siglec-8.

Results

Peanut-specific human IgE mAbs bound FcϵRI, triggering degranulation after stimulation with peanut in RBL SX-38 cells. Sensitized RBL SX-38 cells stimulated with peanut increased levels of phosphorylated SYK and ERK, signal transduction proteins downstream of FcϵRI. Engaging inhibitory cell surface receptors CD300a or Siglec-8 blunted peanut-specific activation.

Conclusion

Allergen-specific human IgE mAbs, expressed from human hybridomas and specific for a clinically relevant food allergen, passively sensitize allergy effector cells central to thein vitromodels of the effector phase of food allergy. Peanut reproducibly activates and induces degranulation of RBL SX-38 cells sensitized with peanut-specific human IgE mAbs. This system provides a unique screening tool to assess the efficacy of therapeutics that target allergy effector cells and inhibit food allergen-induced effector cell activation.
Single cell meta-analysis of EndMT and EMT state in COVID-19
Authors: Zhang Lanlan , Tang Chuang , Zhang Min , Tong Xia , Xie Yingying , Yan Ruitong , Wang Xiangjun , Zhang Xin , Liu Dan , Li Shasha
Published: September 2022

COVID-19 prognoses suggests that a proportion of patients develop fibrosis, but there is no evidence to indicate whether patients have progression of mesenchymal transition (MT) in the lungs. The role of MT during the COVID-19 pandemic remains poorly understood. Using single-cell RNA sequencing, we profiled the transcriptomes of cells from the lungs of healthy individuals (n = 45), COVID-19 patients (n = 58), and idiopathic pulmonary fibrosis (IPF) patients (n = 64) human lungs to map the entire MT change. This analysis enabled us to map all high-resolution matrix-producing cells and identify distinct subpopulations of endothelial cells (ECs) and epithelial cells as the primary cellular sources of MT clusters during COVID-19. For the first time, we have identied early and late subgroups of endothelial mesenchymal transition (EndMT) and epithelial-mesenchymal transition (EMT) using analysis of public databases for single-cell sequencing. We assessed epithelial subgroups by age, smoking status, and gender, and the data suggest that the proportional changes in EMT in COVID-19 are statistically significant. Further enumeration of early and late EMT suggests a correlation between invasive genes and COVID-19. Finally, EndMT is upregulated in COVID-19 patients and enriched for more inflammatory cytokines. Further, by classifying EndMT as early or late stages, we found that early EndMT was positively correlated with entry factors but this was not true for late EndMT. Exploring the MT state of may help to mitigate the fibrosis impact of SARS-CoV-2 infection.
Basophils activation of patients with chronic spontaneous urticaria in response to C5a despite failure to respond to IgE-mediated stimuli
Authors: Matsubara Daiki , Yanase Yuhki , Ishii Kaori , Takahagi Shunsuke , Tanaka Akio , Ozawa Koichiro , Hide Michihiro
Published: September 2022

Urticaria is characterized by the occurrence of wheals and flares in response to vasoactive mediators, such as histamine. Various studies have suggested the involvement of basophils in the pathogenesis of chronic spontaneous urticaria (CSU). However, histamine release from peripheral basophils in response to stimuli acting on the high affinity IgE receptor (FcϵRI) is impaired in many patients with CSU (non/low responders). We previously demonstrated that tissue factor (TF)s expressed on vascular endothelial cells in response to a combination of various stimuli, such as that of histamine and lipopolysaccharide (LPS), activates the extrinsic coagulation pathway and produces anaphylatoxin, complement 5a (C5a), which then activates basophils and mast cells via the C5a receptor (C5aR). We have revealed that histamine release was induced in response to C5a and formyl-l-methionyl-l-leucyl-l-phenylalanine (fMLP), regardless of the response to anti-IgE antibody, the reduced numbers of basophils and severity of urticaria. Moreover, we found that spontaneous release of histamine ex vivo from basophils of patients with CSU is higher than that from healthy individuals. These results suggest that basophils and the complement system, which could be activated by coagulation factors, may play a critical role in the pathogenesis of CSU, especially in cases refractory to treatment involving the IgE/FcϵRI pathway.
Pan-cancer analysis of AIM2 inflammasomes with potential implications for immunotherapy in human cancer: A bulk omics research and single cell sequencing validation
Authors: Qin Yan , Pan Liuxian , Qin Tianyu , Ruan Hanyi , Zhang Yujie , Zhang Yan , Li Jianli , Yang Jianrong , Li Wei
Published: September 2022

Background

The absent in melanoma 2 (AIM2) inflammasome is a multi-protein platform that recognizes aberrant cytoplasmic double-stranded DNA(dsDNA) and induces cytokine maturation, release, and pyroptosis. Some studies found that the AIM2 inflammasome was a double-edged sword in many cancers. However, there have been fewer studies on AIM2 inflammasomes in pan-cancer.

Methods

Gene expression was analyzed using The Cancer Genome Atlas (TCGA) database and The Genotype-Tissue Expression (GTEx) database. Immunohistochemistry (IHC) was used to validate the expression of the AIM2. We used the survival curve to explore the prognostic significance of the AIM2 inflammasomes in pan-cancer. Mutations and methylation of AIM2 inflammasome-related genes (AIM2i-RGs) were also comprehensively analyzed. Single sample gene set enrichment analysis was used to calculate the AIM2 inflammasomes score and explore the correlation of the AIM2 inflammasomes score with immune-related genes and immune infiltrations. The function of AIM2 inflammasomes in pan-cancer was analyzed at the single-cell level. Single-cell transcriptome sequencing (scRNA-seq) data was used to assess the activation state of the AIM2 inflammasomes in the tumor microenvironment.

Results

We found that AIM2i-RGs were aberrantly expressed in tumors and were strongly associated with prognosis. In pan-cancer, the expression of AIM2i-RGs was positively associated with copy number variation and negatively associated with methylation. In AIM2i-RGs, missense mutations were the predominant type of single nucleotide polymorphism. Moreover, we found that the drugs dimethyloxallyl glycine (DMOG) and Z-LNle-CHO may be sensitive to the AIM2 inflammasomes. The AIM2 inflammasomes score was significantly and positively correlated with the tumor immunity score and the stroma score. In most tumors, the AIM2 inflammasomes score was significantly and positively correlated with CD8+ T cell abundance in the tumor microenvironment. Additionally, the AIM2 inflammasomes score was significantly correlated with immune checkpoint genes in pan-cancer as well as immune checkpoint therapy-related markers including tumor mutational burden (TMB), microsatellite instability(MSI), and tumor immune dysfunction and exclusion(TIDE). scRNA-seq analysis suggested that AIM2 inflammasomes differ significantly among different cells in the tumor microenvironment. IHC confirmed low expression of AIM2 in colorectal cancer.

Discussion

AIM2 inflammasomes may be a new target for future tumor therapy It is likely involved in tumor development, and its high expression may serve as a predictor of tumor immunotherapy efficacy.
Surface chlorophyll anomalies induced by mesoscale eddy-wind interactions in the northern Norwegian Sea
Authors: Dong Huizi , Zhou Meng , Raj Roshin P. , Smith Walker O. , Basedow Sünnje L. , Ji Rubao , Ashjian Carin , Zhang Zhaoru , Hu Ziyuan
Published: September 2022

The substantial productivity of the northern Norwegian Sea is closely related to its strong mesoscale eddy activity, but how eddies affect phytoplankton biomass levels in the upper ocean through horizontal and vertical transport-mixing has not been well quantified. To assess mesoscale eddy induced ocean surface chlorophyll-a concentration (CHL) anomalies and modulation of eddy-wind interactions in the region, we constructed composite averaged CHL and wind anomalies from 3,841 snapshots of anticyclonic eddies (ACEs) and 2,727 snapshots of cyclonic eddies (CEs) over the period 2000-2020 using satellite altimetry, scatterometry, and ocean color products. Results indicate that eddy pumping induces negative (positive) CHL anomalies within ACEs (CEs), while Ekman pumping caused by wind-eddy interactions induces positive (negative) CHL anomalies within ACEs (CEs). Eddy-induced Ekman upwelling plays a key role in the unusual positive CHL anomalies within the ACEs and results in the vertical transport of nutrients that stimulates phytoplankton growth and elevated productivity of the region. Seasonal shoaling of the mixed layer depth (MLD) results in greater irradiance levels available for phytoplankton growth, thereby promoting spring blooms, which in combination with strong eddy activity leads to large CHL anomalies in May and June. The combined processes of wind-eddy interactions and seasonal shallowing of MLD play a key role in generating surface CHL anomalies and is a major factor in the regulation of phytoplankton biomass in the northern Norwegian Sea.
Assessment of connectivity patterns of the marbled crab Pachygrapsus marmoratus in the Adriatic and Ionian seas through combination of genetic data and Lagrangian simulations
Authors: Marino Ilaria Anna Maria , Schiavina Marcello , Aglieri Giorgio , Bevilacqua Stanislao , Boscari Elisa , Congiu Leonardo , Faggion Sara , Kruschel Claudia , Papetti Chiara , Patarnello Tomaso , Paterno Marta , Voutsinas Emanuela , Zane Lorenzo , Melià Paco
Published: September 2022

Seascape connectivity studies, informing the level of exchange of individuals between populations, can provide extremely valuable data for marine population biology and conservation strategy definition. Here we used a multidisciplinary approach to investigate the connectivity of the marbled crab (Pachygrapsus marmoratus), a high dispersal species, in the Adriatic and Ionian basins. A combination of genetic analyses (based on 15 microsatellites screened in 314 specimens), Lagrangian simulations (obtained with a biophysical model of larval dispersal) and individual-based forward-time simulations (incorporating species-specific fecundity and a wide range of population sizes) disclosed the realized and potential connectivity among eight different locations, including existing or planned Marine Protected Areas (MPAs). Overall, data indicated a general genetic homogeneity, after removing a single outlier locus potentially under directional selection. Lagrangian simulations showed that direct connections potentially exist between several sites, but most sites did not exchange larvae. Forward-time simulations indicated that a few generations of drift would produce detectable genetic differentiation in case of complete isolation as well as when considering the direct connections predicted by Lagrangian simulations.Overall, our results suggest that the observed genetic homogeneity reflects a high level of realized connectivity among sites, which might result from a regional metapopulation dynamics, rather than from direct exchange among populations of the existing or planned MPAs. Thus, in the Adriatic and Ionian basins, connectivity might be critically dependent on unsampled, unprotected, populations, even in species with very high dispersal potential like the marbled crab. Our study pointed out the pitfalls of using wide-dispersing species with broad habitat availability when assessing genetic connectivity among MPAs or areas deserving protection and prompts for the careful consideration of appropriate dispersing features, habitat suitability, reproductive timing and duration in the selection of informative species.
Seasonal variations in biochemical (biomolecular and amino acid) compositions and protein quality of particulate organic matter in the Southwestern East/Japan Sea
Authors: Jo Naeun , Youn Seok-Hyun , Joo HuiTae , Jang Hyo Keun , Kim Yejin , Park Sanghoon , Kim Jaesoon , Kim Kwanwoo , Kang Jae Joong , Lee Sang Heon
Published: September 2022

The biochemical compositions of marine particulate organic matter (POM) can provide significant information to understanding the physiological conditions of phytoplankton and food quality for their potential consumers. We investigated the seasonal variations in biomolecular and amino acid (AA) compositions of the bulk POM in the southwestern East/Japan Sea from four different sampling months (February, April, August, and October) in 2018. In terms of the biomolecular composition of the POM, overall carbohydrates (CHO) were predominant among three biomolecules accounting for 48.6% followed by lipids (LIP; 35.5%) and proteins (PRT; 15.9%) in the East/Japan Sea. However, markedly seasonal differences in the biomolecular composition of POM were found from February to October, which could be due to seasonally different conditions favorable to phytoplankton growth. Dominant AA constituents to trace POM lability were glycine (GLY), alanine (ALA), and glutamic acid (GLU), suggesting that our POM was the mixtures of decomposing and fresher materials. Furthermore, the significantly negative correlation between the proportion of total essential amino acids (EAAs) and PRT composition (r = -0.627, p< 0.01) was probably reflected by nutrient availability to phytoplankton partitioning EAAs or non-essential AAs (NEAAs). The different biomolecular compounds under un- or favorable growth conditions for phytoplankton could determine the nutritional quality of POM as potential prey as well as degradation status of POM. Therefore, the biochemical compositions of phytoplankton-originated POM hold important ecological implications in various marine ecosystems under ongoing climate changes.
Coastal sea levels and wind-waves in the Mediterranean Sea since 1950 from a high-resolution ocean reanalysis
Authors: Toomey Tim , Amores Angel , Marcos Marta , Orfila Alejandro
Published: September 2022

In the Mediterranean Sea, coastal extreme sea levels are mainly caused by storm surges driven by atmospheric pressure and surface winds from extratropical cyclones. In addition, wind-waves generated by the same atmospheric perturbations may also contribute to coastal extremes through wave setup (temporal rise above the mean sea level due to dissipation and breaking of waves in shallow waters close to the shore). This study investigates the spatial and temporal variability of coastal extreme sea levels in the Mediterranean basin, using a new ocean hindcast generated with a coupled hydrodynamic-wave model that simulates storm surges and wind-waves. The numerical simulation covers the period 1950-2021 with high temporal sampling (1h) and at unprecedented spatial resolution for a basin scale analysis, that reaches 200 m along the coastlines. Coastal storm surges and wave heights are validated with available observations (tide gauges, waves buoys and satellites). Comparison against tide gauges shows an average RMSE of 7.5 cm (7.7 cm for extreme events) and mean linear correlation of 0.64 for the whole period. Similarly, comparison of simulated and observed significant wave height shows good agreement, with RMSE lower than 0.25 m and a coefficient correlation as high as 0.95. The results confirm that coastal extreme sea levels are more likely to be located in regions with wide continental shelves favouring the wind contribution to storm surges along with shallow waters that favour wave setup induced by depth-breaking. The contribution of waves to coastal extreme sea levels has been quantified, using the hindcast in combination with an uncoupled simulation and has been shown to be significant, with an assessed wave setup spatial footprint at regional scale and observed maximum sea levels increased by up to 120% in the presence of waves.
Experimental research on statics bond performance of reinforcement-concrete interface after the combined action of corrosion and fatigue
Authors: Wang Bowen , Liu Yang , Luo Dong , Yuan Heping
Published: September 2022

Corrosion of reinforced bars and the fatigue effect in concrete structures significantly impact the bond performance of reinforced bars. The current research mainly focuses on the effect of fatigue or corrosion on the bonding properties of steel bars, which is still quite different from the service environment of the structure. The degradation law of the bond performance, failure characteristics, and changing trend of bond stress along the anchorage length of reinforced concrete specimens were analyzed under the combined action of fatigue and corrosion in this test. Under the combined action of corrosion and fatigue, the specimens’ bond stress and slip limit are significantly reduced, and the steel bars may fracture during the loading process. There are two peaks in the longitudinal distribution curve of the combined stress of the specimen under the combined action of fatigue and corrosion.
Cytokine levels as predictors of mortality in critically ill patients with severe COVID-19 pneumonia: Case-control study nested within a cohort in Colombia
Authors: Molina Francisco José , Botero Luz Elena , Isaza Juan Pablo , Cano Luz Elena , López Lucelly , Hoyos Lina Marcela , Correa Elizabeth , Torres Antoni
Published: September 2022

Background

High levels of different cytokines have been associated in COVID-19 as predictors of mortality; however, not all studies have found this association and its role to cause multi-organ failure and death has not been fully defined. This study aimed to investigate the association of the levels of 10 cytokines with mortality in patients with COVID-19 admitted to the intensive care unit (ICU).

Materials and methods

This is a case-control study nested within a cohort of patients with COVID-19 who were on mechanical ventilation and were not hospitalized for more than 48 h across nine ICUs in Medellín, Colombia. Serum samples were collected upon admission to the ICU and 7 days later and used to measure cytokine levels.

Results

Upon admission, no differences in mortality between the cytokine levels were observed when comparisons were made quantitatively. However, in the multivariate analysis, patients with median IL-1β levels <1.365 pg/ml showed an increase in mortality (OR = 3.1; 1.24<7.71; p = 0.015). On day 7 in the ICU, IL-1β median levels were lower (0.34 vs. 2.41 pg/ml, p = 0.042) and IL-10 higher (2.08 vs. 1.05 pg/ml, p = 0.009) in patients who died. However, in the multivariate analysis, only IL-12p70 was associated with mortality (OR = 0.23; 0.07<0.73; p = 0.012). The mean difference in the levels between day 1 and day 7 decreased in both IFN-γ (3.939 pg/ml, p < 0.039) and in IL-18 (16.312 pg/ml, p < 0.014) in the patients who died. A low IL-1β/IL-10 ratio was associated with mortality on both day 1 and day 7, while an IL-1β/IL-10 ratio below the cut-off on day 7 was associated with decreased survival. The lowest TNFα/IL-10 ratio was associated with mortality only on day 7.

Conclusion

At the time of admission, patients with median IL-1β levels lower than 1.365 pg/ml had increased mortality. An IL-1β/IL-10 ratio <2 at day 7 and IL-12p70 levels >1.666 pg/ml was associated with decreased survival.
Effect of fetoscopic laser surgery on the placental characteristics and birth-weight discordance of twins with twin-to-twin transfusion syndrome
Authors: Wang Xueju , Li Luyao , Yuan Pengbo , Zhao Yangyu , Wei Yuan
Published: September 2022

Objective

This study explored the effect of fetoscopic laser surgery on the placental structure and birth-weight discordance of twin-to-twin transfusion syndrome (TTTS).

Methods

A retrospective cohort study was conducted in TTTS patients who were admitted to the Peking University Third Hospital between April 2014 and April 2020. The patients were divided into two groups: laser group and control group. Placentas with twin survival were injected, and pregnancy outcomes and placental characteristics of the two groups were compared. The correlation between the birth-weight discordance and placental characteristics in each group was analyzed.

Results

The gestational age at first diagnosis in the laser group was significantly smaller than that in the control group (21.6 ± 2.8 weeks vs. 27.7 ± 3.0 weeks, p < 0.001). The proportion of patients with TTTS stage-I in the laser group was significantly lower than the control group (9.4 vs. 64.0%, p < 0.001). The gestational age at delivery in the laser group was significantly larger than that in the control group (33.6 ± 2.1 weeks vs. 31.4 ± 2.5 weeks, p = 0.001). In the laser group, the birth-weight discordance ratio was positively correlated with the placental territory discordance ratio (Spearman coefficient = 0.556; p = 0.001).

Conclusion

The birth-weight discordance is positively correlated with placental territory discordance in TTTS patients after FLS.
Using Clustered Regularly Interspaced Short Palindromic Repeats gene editing to induce permanent expression of fetal hemoglobin in β-thalassemia and sickle cell disease: A comparative meta-analysis
Authors: Quagliano Anthony , Acevedo Daniel , Hardigan Patrik , Prasad Samiksha
Published: September 2022

β-hemoglobinopathies like sickle cell disease (SCD) and β-thalassemia are characterized by differing mutations in the hemoglobin subunit beta gene (HBB). These disorders vary in phenotypic presentation and severity, with more severe manifestations leading to transfusion dependence along with associated complications such as infection and iron overload. β-hemoglobinopathies symptoms rapidly worsen after birth as the levels of fetal hemoglobin (HbF) begin to decline. To reverse this decline, current treatment plans typically involve the use of pharmacological agents such as hydroxyurea to raise expression levels of HbF. However, these treatments only result in transient effects and must be consistently administered. Gene editing technologies such as CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats- CRISPR associated protein) offer the opportunity to create novel treatments which can raise HbF expression with potential permanent effects. Two gene targets, B-cell lymphoma/leukemia 11A gene (BCL11A) and the promoter regions of gamma globin genes (HBG1/2), have been identified to significantly increase HbF protein expression. In order to differentiate the effectiveness of BCL11A and HBG1/2 editing, a meta-analysis was performed by first identifying 119 studies for inclusion based on the search terms terms “β-Thalassemia,” “beta-thal” “sickle cell disease,” “SCD,” and “CRISPR.” Following application of exclusion and inclusion criteria, we performed analysis on 8 peer-reviewed published studies from 2018 to 2021 were included in the study. Forest plots were generated using R (version 4.1.2). Primary comparative analysis shows HBG1/2 had a significantly (p < 0.01)greater impact on induction of HbF expression compared to BCL11A. This analysis leads us to conclude that HBG1/2 merits further investigation as a possible gene editing target for treatment of SCD and β-thalassemia.
Basic COVID-19 knowledge according to education level and country of residence: Analysis of twelve countries in Latin America
Authors: Mejia Christian R. , Aveiro-Robalo Telmo Raul , Garlisi Torales Luciana Daniela , Fernández Maria Fernanda , Bonilla-Rodríguez Francisco E. , Estigarribia Enrique , Coronel-Ocampos Johanna Magali , Caballero-Arzamendia Cecilia J. , Torres Renato R. , Conde-Escobar Aram , Canaviri-Murillo Yuliana , Castro-Pacoricona Diana , Serna-Alarcón Victor , Arias-Chávez Dennis
Published: September 2022

Introduction

Knowing a disease is crucial for being able to fight it, especially in a region in which COVID-19 caused so many deaths, such as Latin America.

Objective

To determine the association between basic knowledge of COVID-19 and education level according to country of residence in Latin America.

Methodology

This is an analytical cross-sectional study. Basic level of knowledge was measured through nine close-ended questions (scale validated in Peru). The score obtained was analyzed through performing a crosstab vs. gender, age, education level, and country of residence.

Results

Of a total of 9,222 respondents, almost all of them knew the common symptoms (99%), modes of transmission (93%), and knew how to recognize which was not a specific symptom (93%). Through the multivariate model, we found that there was no association with gender (p = 0.716) or age (p = 0.059), in comparison with those who had primary or a lower education level. All the other higher education levels had statistically significant scores (all p-values p < 0.001). When comparing knowledge according to countries, and using Peru as reference for comparison, Chile, Paraguay, Mexico, Bolivia, Panama, Ecuador, Costa Rica, and Colombia had a better level of knowledge (all p-values < 0.001); however, only El Salvador had a lower level (p < 0.001).

Discussion

There was lack of knowledge of some topics, difference according to academic degree and country. As Peru was one of countries that obtained the lowest level of knowledge, it could have influenced the fact that it was the most affected country in the world.
A deep learning approach for detecting liver cirrhosis from volatolomic analysis of exhaled breath
Authors: Wieczorek Mikolaj , Weston Alexander , Ledenko Matthew , Thomas Jonathan Nelson , Carter Rickey , Patel Tushar
Published: September 2022

Liver disease such as cirrhosis is known to cause changes in the composition of volatile organic compounds (VOC) present in patient breath samples. Previous studies have demonstrated the diagnosis of liver cirrhosis from these breath samples, but studies are limited to a handful of discrete, well-characterized compounds. We utilized VOC profiles from breath samples from 46 individuals, 35 with cirrhosis and 11 healthy controls. A deep-neural network was optimized to discriminate between healthy controls and individuals with cirrhosis. A 1D convolutional neural network (CNN) was accurate in predicting which patients had cirrhosis with an AUC of 0.90 (95% CI: 0.75, 0.99). Shapley Additive Explanations characterized the presence of discrete, observable peaks which were implicated in prediction, and the top peaks (based on the average SHAP profiles on the test dataset) were noted. CNNs demonstrate the ability to predict the presence of cirrhosis based on a full volatolomics profile of patient breath samples. SHAP values indicate the presence of discrete, detectable peaks in the VOC signal.
Trends in gastroesophageal reflux disease research: A bibliometric and visualized study
Authors: Zhang Tai , Zhang Beihua , Tian Wende , Wei Yuchen , Wang Fengyun , Yin Xiaolan , Wei Xiuxiu , Liu Jiali , Tang Xudong
Published: September 2022

Background

Gastroesophageal reflux disease (GERD), a disorder resulting from the retrograde flow of gastric contents into the esophagus, affects an estimated 10–30% of the Western population, which is characterized by multifactorial pathogenesis. Over the past few decades, there have been many aspects of uncertainty regarding GERD leading to an ongoing interest in the field as reflected by a large number of publications, whose heterogeneity and variable quality may present a challenge for researchers to measure their scientific impact, identify scientific collaborations, and to grasp actively researched themes in the GERD field. Accordingly, we aim to evaluate the knowledge structure, evolution of research themes, and emerging topics of GERD research between 2012 and 2022 with the help of bibliometric approaches.

Methods

The literature focusing on GERD from 2012 to 2022 was retrieved from the Science Citation Index Expanded of the Web of Science Core Collection. The overall publication performance, the most prolific countries or regions, authors, journals and resources-, knowledge- and intellectual-networking, as well as the co-citation analysis of references and keywords, were analyzed through Microsoft Office Excel 2019, CiteSpace, and VOSviewer.

Results

A total of 8,964 publications were included in the study. The USA published the most articles (3,204, 35.74%). Mayo Clin ranked first in the number of articles published (201, 2.24%). EDOARDO SAVARINO was the most productive author (86, 0.96%). The most productive journal in this field was SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES (304, 3.39%). AMERICAN JOURNAL OF GASTROENTEROLOGY had the most co-citations (4,953, 3.30%). Keywords with the ongoing strong citation bursts were transoral incision less fundoplication, eosinophilic esophagitis, baseline impedance, and functional heartburn.

Conclusion

For the first time, we obtained deep insights into GERD research through bibliometric analysis. Findings in this study will be helpful for scholars seeking to understand essential information in this field and identify research frontiers.
Untargeted plasma metabolomic fingerprinting highlights several biomarkers for the diagnosis and prognosis of coronavirus disease 19
Authors: Occelli Céline , Guigonis Jean-Marie , Lindenthal Sabine , Cagnard Alexandre , Graslin Fanny , Brglez Vesna , Seitz-Polski Barbara , Dellamonica Jean , Levraut Jacques , Pourcher Thierry
Published: September 2022

Objectives

The COVID-19 pandemic has been a serious worldwide public health crisis since 2020 and is still challenging healthcare systems. New tools for the prognosis and diagnosis of COVID-19 patients remain important issues.

Design

Here, we studied the metabolome of plasma samples of COVID-19 patients for the identification of prognosis biomarkers.

Patients

Plasma samples of eighty-six SARS-CoV-2-infected subjects and 24 healthy controls were collected during the first peak of the COVID-19 pandemic in France in 2020.

Main results

Plasma metabolome fingerprinting allowed the successful discrimination of healthy controls, mild SARS-CoV-2 subjects, and moderate and severe COVID-19 patients at hospital admission. We found a strong effect of SARS-CoV-2 infection on the plasma metabolome in mild cases. Our results revealed that plasma lipids and alterations in their saturation level are important biomarkers for the detection of the infection. We also identified deoxy-fructosyl-amino acids as new putative plasma biomarkers for SARS-CoV-2 infection and COVID-19 severity. Finally, our results highlight a key role for plasma levels of tryptophan and kynurenine in the symptoms of COVID-19 patients.

Conclusion

Our results showed that plasma metabolome profiling is an efficient tool for the diagnosis and prognosis of SARS-CoV-2 infection.
In-depth investigation of microRNA-mediated cross-kingdom regulation between Asian honey bee and microsporidian
Authors: Fan Xiaoxue , Zhang Wende , Zhang Kaiyao , Zhang Jiaxin , Long Qi , Wu Ying , Zhang Kuihao , Zhu Leran , Chen Dafu , Guo Rui
Published: September 2022

Asian honey bee Apis cerana is the original host for Nosema ceranae, a unicellular fungal parasite that causes bee nosemosis throughout the world. Currently, interaction between A. cerana and N. ceranae is largely unknown. Our group previously prepared A. c. cerana workers’ midguts at 7 days post inoculation (dpi) and 10 dpi with N. ceranae spores as well as corresponding un-inoculated workers’ midguts, followed by cDNA library construction and a combination of RNAs-seq and small RNA-seq. Meanwhile, we previously prepared clean spores of N. ceranae, which were then subjected to cDNA library construction and deep sequencing. Here, based on the gained high-quality transcriptome datasets, N. ceranae differentially expressed mRNAs (DEmiRNAs) targeted by host DEmiRNAs, and A. c. cerana DEmRNAs targeted by microsporidian DEmiRNAs were deeply investigated, with a focus on targets involved in N. ceranae glycolysis/glyconeogenesis as well as virulence factors, and A. c. cerana energy metabolism and immune response. In A. c. cerana worker’s midguts at 7 (10) dpi (days post inoculation), eight (seven) up-regulated and six (two) down-regulated miRNAs were observed to target 97 (44) down-regulated and 60 (15) up-regulated N. ceranae mRNAs, respectively. Additionally, two up-regulated miRNAs (miR-60-y and miR-676-y) in host midgut at 7 dpi could target genes engaged in N. ceranae spore wall protein and glycolysis/gluconeogenesis, indicating potential host miRNA-mediated regulation of microsporidian virulence factor and energy metabolism. Meanwhile, in N. ceranae at 7 (10) dpi, 121 (110) up-regulated and 112 (104) down-regulated miRNAs were found to, respectively, target 343 (247) down-regulated and 138 (110) down-regulated mRNAs in A. c. cerana workers’ midguts. These targets in host were relevant to several crucial cellular and humoral immune pathways, such as phagasome, endocytosis, lysosomes, regulation of autophagy, and Jak–STAT signaling pathway, indicative of the involvement of N. ceranae DEmiRNAs in regulating these cellular and humoral immune pathways. In addition, N. ceranae miR-21-x was up-regulated at 7 dpi and had a target relative to oxidative phosphorylation, suggesting that miR-21-x may be used as a weapon to modulate this pivotal energy metabolism pathway. Furthermore, potential targeting relationships between two pairs of host DEmiRNAs-microsporidian DEmRNAs and two pairs of microsporidian DEmiRNAs-host DEmRNAs were validated using RT-qPCR. Our findings not only lay a foundation for exploring the molecular mechanism underlying cross-kingdom regulation between A. c. cerana workers and N. ceranae, but also offer valuable insights into Asian honey bee-microsporidian interaction.
Silicon fertilizer mediated structural variation and niche differentiation in the rhizosphere and endosphere bacterial microbiome and metabolites of sugarcane
Authors: Yuan Zhaonian , Pang Ziqin , Fallah Nyumah , Zhou Yongmei , Dong Fei , Lin Wenxiong , Hu Chaohua
Published: September 2022

The microbiomes of plant are potential determinants of plant growth, productivity, and health. They provide plants with a plethora of functional capacities, namely, phytopathogens suppression, access to low-abundance nutrients, and resistance to environmental stressors. However, a comprehensive insight into the structural compositions of the bacterial abundance, diversity, richness, and function colonizing various microenvironments of plants, and specifically their association with bioactive compounds and soil edaphic factors under silicon (Si) amendment remains largely inconclusive. Here, high-throughput sequencing technology and nontargeted metabolite profiling method were adopted to test the hypotheses regarding microbiome niche abundance, diversity, richness, function, and their association with bioactive compounds and soil edaphic factors within different ecological niches (leaf, stem, root, rhizosphere, and bulk soils) under Si amendment during cane growth were we addressed. Our results demonstrated that Si correspondingly increased sugarcane theoretical production and yield, and remarkably enhanced soil nutrient status, especially Si, AP, and AK. It was also observed that bacterial diversity demonstrated tissue-dependent distribution patterns, with the bulk soil, rhizosphere soil, and root endosphere revealing the highest amount of bacterial diversity compared with the stem and leaf tissues. Moreover, Si exhibited the advantage of considerably promoting bacterial abundance in the various plant compartments. Co-occurrence interactions demonstrated that Si application has the potential to increase bacterial diversity maintenance, coexistence, and plant–soil systems bacteria connections, thereby increasing the functional diversity in the various plant tissues, which, in turn, could trigger positive growth effects in plants. Network analysis further revealed that metabolite profiles exhibited a strong association with bacterial community structures. It was also revealed that Si content had a considerable positive association with bacterial structures. Our findings suggest that the dynamic changes in microbe’s community composition in different plant and soil compartments were compartment-specific. Our study provides comprehensive empirical evidence of the significance of Si in agriculture and illuminated on differential metabolite profiles and soil microbe’s relationship.
CRISPR/Cas9 RNP-assisted validation of palmarumycin biosynthetic gene cluster in Lophiotrema sp. F6932
Authors: Gakuubi Martin Muthee , Ching Kuan Chieh , Munusamy Madhaiyan , Wibowo Mario , Lim Chun Teck , Ma Guang-Lei , Liang Zhao-Xun , Kanagasundaram Yoganathan , Ng Siew Bee
Published: September 2022

Lophiotrema is a genus of ascomycetous fungi within the family Lophiotremataceae. Members of this genus have been isolated as endophytes from a wide range of host plants and also from plant debris within terrestrial and marine habitats, where they are thought to function as saprobes. Lophiotrema sp. F6932 was isolated from white mangrove (Avicennia officinalis) in Pulau Ubin Island, Singapore. Crude extracts from the fungus exhibited strong antibacterial activity, and bioassay-guided isolation and structure elucidation of bioactive constituents led to the isolation of palmarumycin C8 and a new analog palmarumycin CP30. Whole-genome sequencing analysis resulted in the identification of a putative type 1 iterative PKS (iPKS) predicated to be involved in the biosynthesis of palmarumycins. To verify the involvement of palmarumycin (PAL) gene cluster in the biosynthesis of these compounds, we employed ribonucleoprotein (RNP)-mediated CRISPR-Cas9 to induce targeted deletion of the ketosynthase (KS) domain in PAL. Double-strand breaks (DSBs) upstream and downstream of the KS domain was followed by homology-directed repair (HDR) with a hygromycin resistance cassette flanked by a 50 bp of homology on both sides of the DSBs. The resultant deletion mutants displayed completely different phenotypes compared to the wild-type strain, as they had different colony morphology and were no longer able to produce palmarumycins or melanin. This study, therefore, confirms the involvement of PAL in the biosynthesis of palmarumycins, and paves the way for implementing a similar approach in the characterization of other gene clusters of interest in this largely understudied fungal strain.
An improved luciferase immunosorbent assay for ultrasensitive detection of antibodies against African swine fever virus
Authors: Wang Qiongjie , Tian Zhancheng , Yang Jifei , Gao Shandian , Du Junzheng , Zhang Hongge , Zhang Zhonghui , Guan Guiquan , Niu Qingli , Yin Hong
Published: September 2022

African swine fever (ASF), caused by African swine fever virus (ASFV), is a fatal infectious disease of pigs and causes great socioeconomic losses globally. The reliable diagnostic method is critical for prevention and control of the disease. In this study, an improved Luciferase immunosorbent assay (LISA) for detecting ASF was developed using the cell lysates containing ASFV p35 protein fused with a reporter Nano-luciferase (p35-Luc protein). The improved method avoids the complicate procedures of immobilizing the serum samples with protein G in the normal LISA method, and replaced by directly coating the serum samples with carbonate buffer, therefore reduces the productive cost and simplifies the operation procedures. The p35-Luc LISA exhibited high specificity for anti-ASFV sera while no cross-reactions with the sera against other swine viruses. The detection limit of the p35-Luc LISA was shown to be at least four times higher than that of the p35 based indirect ELISA established in our lab. The receiver operating characteristic (ROC) analysis showed the 96.36% relative specificity and 96.97% relative sensitivity of the p35-Luc LISA with the cutoff values of 3.55 as compared to the commercial Ingezim p72-ELISA kit. Furthermore, a total of 248 serum samples were tested by both the p35-Luc LISA and commercial Ingezim p72-ELISA kit, and there was a high degree of agreement (97.6%, kappa = 0.9753) in the performance of the two assays. Collectively, the improved LISA based on the p35-Luc protein could be used as a rapid, ultrasensitive, cost-effective and reliable diagnostic tool for serological survey of ASF in pig farms.