bluuebunny/crossref_metadata_2025 huggingface dataset:
Baseline Elevations of Leukotriene Metabolites and Altered Plasmalogens Are Prognostic Biomarkers of Plaque Progression in Systemic Lupus Erythematosus
Authors: Baig Sahar , Vanarsa Kamala , Ding Huihua , Titus Anto Sam Crosslee Louis Sam , McMahon Maureen , Mohan Chandra
Published: May 2022

Systemic lupus erythematosus (SLE) is associated with an increased incidence of acute and chronic cardiovascular disease as compared to the general population. This study uses a comprehensive metabolomic screen of baseline sera from lupus patients to identify metabolites that predict future carotid plaque progression, following 8–9 years of follow-up. Nine patients had SLE without plaque progression, 8 had SLE and went on to develop atherosclerotic plaques (SLEPP), and 8 patients were controls who did not have SLE. The arachidonic acid pathway metabolites, leukotriene B4 (LTB4) and 5-hydroxyeicosatetraenoic acid (5-HETE), and the oxidized lipids 9/13-hydroxyoctodecadienoic acid (HODE) were found to be significantly altered (p < 0.05 and fold-change >2) in SLEPP patients compared to SLE patients without plaque progression. SLEPP patients also exhibited significantly altered levels of branched chain amino acid (BCAA) metabolites and plasmalogens compared to the non-SLE controls. Taken together with the rich literature on these metabolites, these findings suggest that the identified metabolites may not only be prognostic of cardiovascular disease development in SLE patients, but they may also be active drivers of atheroma formation. Early identification of these high risk SLE patients may help institute preventive measures early in the disease course.
Cardiovascular Hypertension-Mediated Organ Damage in Hypertensive Urgencies and Hypertensive Outpatients
Authors: Vallelonga Fabrizio , Cesareo Marco , Menon Leonardo , Airale Lorenzo , Leone Dario , Astarita Anna , Mingrone Giulia , Tizzani Maria , Lupia Enrico , Veglio Franco , Milan Alberto
Published: May 2022

Background

The prevalence of hypertension mediated organ damage (HMOD) in patients attending the Emergency Department (ED) with symptomatic blood pressure (BP) rise is unknown, and whether HMOD varies between asymptomatic and symptomatic patients with grade 3 hypertension is unclear.

Aim

This study aimed to investigate cardiac and vascular HMOD in hypertensive urgencies (HU) and asymptomatic outpatients with grade 1–3 hypertension.

Methods

Patients attending the ED with a symptomatic BP rise ≥180/110 mmHg were prospectively enrolled (HU group), after the exclusion of acute organ damage. HMOD and BP were assessed after 72 h from ED discharge in an office setting. These patients were matched by age and sex to outpatients with grade 3 hypertension (Grade 3 group), and by age, sex, and 72 h office BP values to outpatients with any grade hypertension (Control group).

Results

A total of 304 patients were enrolled (76 patients in the HU group, 76 in the Grade 3 group, and 152 in the Control group). Grade 3 patients had increased left ventricular mass (LVMi) compared to patients with HU (106.9 ± 31.5 vs. 96.1 ± 30.7 g/m2, p = 0.035). Severe left ventricular hypertrophy (LVH) was more frequent in grade 3 (21.1 vs. 5.3%, p = 0.004), and pulse wave velocity (PWV) was similar in the two groups. There was no difference in LVMi between ED and Control patients (96.1 ± 30.7 vs. 95.2 ± 26.6 g/m2, p = 0.807). LVH prevalence was similar (43.4 vs. 35.5%, p = 0.209, respectively), but patients with HU had thicker interventricular septum (11.9 ± 2.2 vs. 11.1 ± 2.2 mm, p = 0.007). PWV was similar between these two groups. Patients with HU needed more antihypertensive drugs than Control patients (2 vs. 1, p < 0.001).

Conclusions

Patients with HU had a better cardiac HMOD profile than outpatients with grade 3 hypertension. Their cardiac and vascular HMOD is more comparable to an outpatient with similar in-office BP, although they need more antihypertensive medications.
Serum Cytokines Predict the Severity of Coronary Artery Disease Without Acute Myocardial Infarction
Authors: Liu Sheng , Wang Chenyang , Guo Jinzhu , Yang Yunxiao , Huang Mengling , Li Li , Wang Yu , Qin Yanwen , Zhang Ming
Published: May 2022

Introduction

Various cytokines were involved in the process of atherosclerosis, and their serum levels were correlated with coronary artery disease (CAD) to varying degrees. However, there were limited reports about the correlation between serum cytokines and the severity of coronary atherosclerotic lesion in patients with non-acute myocardial infarction (AMI). The purpose of this study was to investigate the relationship between serum cytokines and the severity of CAD, and identify the predictors of severe CAD in patients suspected to have CAD but AMI had been ruled out.

Methods

A total of 502 patients who had suspected CAD and underwent coronary angiography were enrolled. The serum levels of IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, TNF-α, IFN-α,and IFN-γ were determined by multiplexed particle-based flow cytometric assays technology. And the severity of CAD was evaluated by Gensini score (GS).

Results

The serum levels of IL-4, IL-12p70, IL-17, and IFN-α were significantly lower in the severe CAD group (GS≥30) than those in the non-severe CAD group (GS < 30). And IL-12p70 and IL-17 were negatively correlated with the severity of CAD. Multivariate logistic regression analyses demonstrated that two serum cytokines (IL-12p70 and IL-17), one clinical protective factor (HDL-C), and two clinical risk factors (gender and diabetes) were the independent predictors of severe CAD. ROC curve analysis showed that multivariate mode combined these predictors had a good performance in predicting severe CAD.

Conclusion

The combination of serum cytokines (IL-12p70 and IL-17) and clinical risk factors (HDL-C, gender, and diabetes) may help identify patients with more severe coronary artery lesions from those with suspected CAD but not AMI, and may contribute to guiding the risk stratification for patients with chest discomfort in health care facilities without sufficient medical resources (especially cardiac catheterization resources).
Knowledge of Symptoms of Acute Myocardial Infarction, Reaction to the Symptoms, and Ability to Perform Cardiopulmonary Resuscitation: Results From a Cross-sectional Survey in Four Regions in Germany
Authors: Kartschmit Nadja , Birnbach Benedikt , Hartwig Saskia , Mikolajczyk Rafael
Published: May 2022

Background

Ischemic heart disease affects 126 million individuals globally which illustrates the importance of finding ways to decrease mortality and morbidity in case of an acute myocardial infarction (AMI). Since knowledge of symptoms, correct reaction to symptoms, and ability to perform cardiopulmonary resuscitation (CPR) decreases the time from symptoms-onset to reperfusion, which leads to lower AMI mortality, we aimed to examine those factors and identify predicting variables in regions with low and high AMI mortality rates.

Methods

We conducted a cross-sectional online survey including 633 respondents from the general population in four federal states in Germany with low and high AMI mortality and morbidity rates. We used uni- and multivariable regressions to find health-related and sociodemographic factors associated with knowledge, reaction to symptoms, and skills in CPR.

Results

Out of 11 symptoms, the mean of correctly attributed AMI symptoms was 7.3 (standard deviation 1.96). About 93% of respondents chose to call an ambulance when witnessing an AMI. However, when confronted with the description of a real-life situation, only 35 and 65% of the participants would call an ambulance in case of abdominal and chest pain, respectively. The predicting variables for higher knowledge were being female, knowing someone with heart disease, and being an ex-smoker compared to people who never smoked. Higher knowledge was associated with adequate reaction in the description of a real-life situation and ability to perform CPR. Prevalence ratio for being able to perform CPR was lower in females, older participants, and participants with low educational level. About 38% of participants state to know how to perform CPR. Our results indicate rather no difference regarding knowledge, reaction to AMI symptoms, and ability to perform CPR among different regions in Germany.

Conclusions

Knowledge of symptoms and first responder reaction including skills in CPR is inadequate when confronted with the description of a real-life situation. Educational health campaigns should focus on conveying information close to real-life situations. Interventions for enhancing ability to perform CPR should be compulsory in regular intervals. Interestingly, we found no difference regarding the factors in regions with high and low AMI mortality rates in Germany.
Is Speech the New Blood? Recent Progress in AI-Based Disease Detection From Audio in a Nutshell
Authors: Milling Manuel , Pokorny Florian B. , Bartl-Pokorny Katrin D. , Schuller Björn W.
Published: May 2022

In recent years, advancements in the field of artificial intelligence (AI) have impacted several areas of research and application. Besides more prominent examples like self-driving cars or media consumption algorithms, AI-based systems have further started to gain more and more popularity in the health care sector, however whilst being restrained by high requirements for accuracy, robustness, and explainability. Health-oriented AI research as a sub-field of digital health investigates a plethora of human-centered modalities. In this article, we address recent advances in the so far understudied but highly promising audio domain with a particular focus on speech data and present corresponding state-of-the-art technologies. Moreover, we give an excerpt of recent studies on the automatic audio-based detection of diseases ranging from acute and chronic respiratory diseases via psychiatric disorders to developmental disorders and neurodegenerative disorders. Our selection of presented literature shows that the recent success of deep learning methods in other fields of AI also more and more translates to the field of digital health, albeit expert-designed feature extractors and classical ML methodologies are still prominently used. Limiting factors, especially for speech-based disease detection systems, are related to the amount and diversity of available data, e. g., the number of patients and healthy controls as well as the underlying distribution of age, languages, and cultures. Finally, we contextualize and outline application scenarios of speech-based disease detection systems as supportive tools for health-care professionals under ethical consideration of privacy protection and faulty prediction.
Gas Hydrate Dissociation Events During LGM and Their Potential Trigger of Submarine Landslides: Foraminifera and Geochemical Records From Two Cores in the Northern South China Sea
Authors: Huang Yi , Cheng Jun , Wang Mingmin , Wang Shuhong , Yan Wen
Published: May 2022

Although submarine slope failures and occurrence of gas hydrates are well known in the Dongsha area of the South China Sea the potential relationship between the aforementioned phenomena has not been clearly understood yet. Herein, we present carbon and oxygen isotope compositions of benthic foraminifera and sulfur isotopic composition of chromium reducible sulfur (CRS; δ34SCRS) from two cores from the Dongsha slope, aiming at identifying gas hydrate dissociation events in geological history. The geochemical data indicated that a large amount of gas hydrate dissociated at the beginning of the Last Glacial Maximum (LGM). Meanwhile, disturbances in the sedimentary strata revealed that a submarine landslide occurred at the end of the Last Glacial Maximum. Moreover, the associated abrupt increase of benthic foraminifera abundance implies that the submarine landslide was probably caused by an intense methane releasing from gas hydrate dissociation. A smaller scale submarine landslide related to gas hydrate dissociation was also recorded in core 973-5, retrieved from the flat area at the base of the slope.
Editorial: Multidisciplinary Loess Geohazard Investigations
Authors: Zhang Fanyu , Wang Gonghui , Allen Mark B. , Xu Yueren
Published: May 2022

Editorial paper
Features of the Early Hydrocarbon Accumulation and Its Effects on the Late Accumulation in Sandstone Reservoir: A Case Study of the Eocene Dongying Depression, Bohai Bay Basin
Authors: Wang Miao , Chen Yong , Song Guoqi , Liu Huimin , Wang Yongshi , Zhang Pengfei , Qiu Yibo , Chen Tao , Li Jiyan , Liu Xinjin , Liu Peng , Feng Yuelin , Zhang Hui , Huang Qian , Wang Yelei
Published: May 2022

Multi-stage hydrocarbon generation and accumulation are very common in petroliferous basins. Also, determination of hydrocarbon accumulation stages and each related diagenetic feature is important for understanding the distribution of current oil and gas resources in one individual basin. However, in the case of conventional sandstone reservoirs, few studies have focused on these resulting reservoir features (e.g., physical property and wettability) that are caused by the first accumulation of hydrocarbons and their geological implications. In this study, taking the reservoir from the Eocene Dongying Depression as an example, we investigated the features of the early hydrocarbon accumulation and its effects on the late accumulation, by analyzing the early accumulation-related paragenesis, fluid inclusions, clay minerals content, reservoir physical property, and wettability in sandstones. Our results show that the early stage accumulation of the overpressured hydrocarbon fluid could support and offset some loads of overburden, weaken the normal compaction, and preserve some original pores. Also, the early hydrocarbon accumulation resulted in an alternated, diagenetic fluid environment from the initial acidic to subsequent alkalic conditions, with the overall dissolution intensity stronger than the cementation, and formed a large number of secondary pores. As a result, the early accumulation was beneficial to reservoir space development and provided more space for the late hydrocarbons. In addition, the early hydrocarbon accumulation could cause the alteration of rock wettability and gradually formed a lipophilic migration pathway from the source rock to the reservoir. Also, the late stage of hydrocarbons would preferentially choose this dominant pathway for their migration (i.e., inheritance of migration pathway).
Experimental and Numerical Studies of Ignition Delay Time and Laminar Flame Speed of JP-10 at Elevated Temperature Conditions
Authors: Yang Junsen , Wu Yi , Zhang Zhenpeng , Shang Yanlei , Pan Lun
Published: May 2022

In this work, the laminar flame speeds of JP-10/air mixtures and ignition delay time of JP-10/O2/Ar mixtures have been studied over a wide range of experimental conditions using a premixed Bunsen flame and a shock tube. Laminar flame speed measurements of the JP-10/air mixture were measured at T = 360–453 K, φ = 0.7–1.3 and p = 1 atm. The ignition delay times of JP-10 with fuel mole fraction of 0.2% JP-10/2.8% O2/97% Ar were measured with a heated shock tube behind the reflected shock wave at 1183–1478 K and pressure of 3.4 atm. Numerical calculation and sensitivity analysis of the laminar flame speed and ignition delay time of JP-10 were performed by using published detailed and skeletal kinetic mechanisms. The comparison of experimental and numerical results showed that all models tend to overestimate the laminar flame speed under the studied conditions, especially under lower temperature conditions (360–423 K). A temperature dependency empirical correlation of laminar flame speed was then proposed by power law theory. The sensitivity analysis identified three important reactions [H+O2 = O+OH, C5H5+H (+M) = C5H6(+M), C3H3+C2H2 = C5H5] that determined the laminar flame speed and ignition delay time.
Predicting the Risk of Exotic Plant Invasions in the Orinoco Region: Importance of Distribution Models, Climatic Niche and Functional Richness
Authors: Salgado-Negret Beatriz , Urbina-Cardona Nicolás , Noguera-Urbano Elkin A. , Cruz-Rodríguez Cristian A. , Baptiste María Piedad
Published: May 2022

The process of biological invasions resulting from the introduction of exotic species is one of the most critical components of global environmental change. Although many hypotheses try to explain the processes underlying biological invasions, changes in land use are essential drivers mediating the colonization of exotic species at the landscape level. We used potential species distribution models developed in Maxent and a database of nine functional traits associated with invasion success for 18 exotic species with a high risk of establishment and difficulty of control in the Orinoco region from Colombia. We found that 67% of the species differed from the centroid in the climatic niche when comparing native and invaded localities. Overall, the native distribution localities showed a more restricted dispersal in their climatic niche, and for most species, native distribution was found within the broad environmental gradients of the invaded localities. Additionally, we found high climatic suitability for all exotic species across all the biomes and ecosystems; however, transformed ecosystems showed exotic plant species’ higher potential functional richness. Our research allowed us to identify key geographical areas that are highly susceptible to invasions and prioritize species that need control in particular ecosystems and biomes. This work provides early warnings on the potential risks of invasion of exotic species, and it will improve the monitoring and management efforts in the Orinoco region of Colombia.
Temporal Changes in Taxonomic and Functional Diversity of Fish Assemblages in the Upper Yangtze River After Impoundment of the Three Gorges Reservoir, China
Authors: Zhang Chen , Liu Fei , Liu Huanzhang , Wang Chunling , Lin Pengcheng , Gao Xin
Published: May 2022

Anthropogenic disturbances are one of the primary factors that drive biodiversity loss. Temporal changes in biodiversity respond to such disturbances. In the present study, we investigated the temporal changes in taxonomic and functional diversity of fish assemblages in different habitats (Three Gorges Reservoir, TGR; running water above the TGR, UTGR; and tributary Chishui River, CSR) in the upper Yangtze basin after impoundment of the TGR from 2008 to 2015. During the survey, the taxonomic and functional composition of fish assemblages varied among the habitats. Although taxonomic diversity increased and functional diversity decreased significantly in the entire upper Yangtze basin, no significant changes in the diversities were observed in each habitat. The habitats showed directional changes in the composition of fish species. The slope of the directional changes in the TGR was more than that in the UTGR and CSR. These results indicated that the distribution of fish species was associated with the habitat after the impoundment. The assembly of the fish assemblage was driven primarily by the neutral process in the entire survey area but was promoted by a combination of species sorting and neutral process in each habitat. The impoundment caused more effects on the TGR than on the UTGR, but it slightly affected the CSR. Regarding fishing closure, conservation measures for fish diversity should be established according to the different habitats. The study findings suggest the removal of small dams in tributaries and ecological regulation in the mainstream and continuous monitoring of fish biodiversity.
Financial Ecological Environment, Financing Constraints, and Green Innovation of Manufacturing Enterprises: Empirical Evidence From China
Authors: Zhao Linhai , Wang Yajun
Published: May 2022

In the carbon neutrality strategy, facilitating the green innovation of enterprises and promoting industrial upgradation have become a key issue. We explore the relationship between the financial ecological environment, financing constraints, and green innovation of manufacturing enterprises based on endogenous growth and stakeholder theories. Manufacturing companies listed on Shanghai Stock Exchange and Shenzhen Stock Exchange during 2010–2020 are taken as samples. With the help of principal component analysis, a comprehensive index of the annual financial ecological environment is constructed. The SA index is employed to measure the financing constraints of firms, and the number of granted green patents is used to measure the green innovation of manufacturing enterprises. We conclude that the green innovation of manufacturing enterprises will relax their financing constraints. The financial ecological environment positively moderates the relationship between green innovation and corporate financing constraints. An excellent financial ecological environment enhances the mitigation effect of green innovation of manufacturing enterprises on their financing constraints. Policy implications are given according to the conclusion.
Genetic Admixture History and Forensic Characteristics of Guizhou Sui People Inferred From Autosomal Insertion/Deletion and Genome-Wide Single-Nucleotide Polymorphisms
Authors: Yang Meiqing , Yang Xiaomin , Ren Zheng , He Guanglin , Zhang Han , Wang Qiyang , Liu Yubo , Zhang Hongling , Ji Jingyan , Chen Jing , Guo Jianxin , Huang Jiang , Wang Chuan-Chao
Published: May 2022

Insertion-deletion (Indel) serves as one of the important markers in forensic personal identification and parentage testing, especially for cases with degraded samples. However, the genetic diversity and forensic features in ethnolinguistically diverse southwestern Chinese populations remain to be explored. Sui, one Tai-Kadai-speaking population residing in Guizhou, has a complex genetic history based on linguistic, historic, and anthropological evidence. In this study, we genotyped 30 Indels from 511 Guizhou Sui individuals and obtained approximately 700,000 genome-wide single-nucleotide polymorphisms (SNPs) in 15 representative Sui individuals to comprehensively characterize the genetic diversity, forensic characteristics, and genomic landscape of Guizhou Sui people. The estimated forensic statistically allele frequency spectrum and parameters demonstrated that this Indels panel was polymorphic and informative in Tai-Kadai populations in southern China. Results of principal component analysis (PCA), STRUCTURE, and phylogenetic trees showed that Guizhou Sui had a close genetic relationship with geographically close Tai-Kadai and Hmong-Mien people. Furthermore, genomic analysis based on the Fst and f4-statistics further suggested the genetic affinity within southern Chinese Tai-Kadai-speaking populations and a close relationship with geographically adjoining Guizhou populations. Admixture models based on the ADMIXTURE, f4, three-way qpAdm, and ALDER results demonstrated the interaction between the common ancestor for Tai-Kadai/Austronesian, Hmong-Mien, and Austroasiatic speaking populations played a significant role in the formation of modern Tai-Kadai people. We observed a sex-biased influence in Sui people by finding that the dominant Y chromosomal type was a Hmong-Mien specific lineage O2a2a1a2a1a2-N5 but the mtDNA lineages were commonly found in Tai-Kadai populations. The additional southward expansion of millet farmers in the Yellow River Basin has impacted the gene pool of southern populations including Tai-Kadai. The whole-genome sequencing in the future will shed more light on the finer genetic profile of Guizhou populations.
Genome Re-Sequencing Reveals the Host-Specific Origin of Genetic Variation in Magnaporthe Species
Authors: Li Jinbin , Lu Lin , Wang Qun , Shi Zhufeng , Li Chengyun , Guo Zhixiang
Published: May 2022

Rice blast is caused by Magnaporthe oryzae (M. oryzae), which is considered one of the most serious pathogens of rice around the globe. It causes severe losses owing to its proven capability to disrupt the host resistance. Recently, its invasion of new hosts like the Musa species or banana plants has been noticed. To understand the possible level of genetic variation, we sequenced the genomes of eight different isolates of the Magnaporthe species infecting rice, Digitaria (a weed), finger millet, Elusine indica, and banana plants. Comparative genomic analysis of these eight isolates with the previously well-characterized laboratory strain M. oryzae 70-15 was made. The infectivity of the newly isolated strain from Musa species suggested that there is no resistance level in the host plants. The sequence analysis revealed that despite genome similarities, both the banana and Digitaria isolates have relatively larger genome sizes (∼38.2 and 51.1 Mb, respectively) compared to those of the laboratory reference strain M. oryzae 70-15 (∼37 Mb). The gene contraction, expansion, and InDel analysis revealed that during evolution, a higher number of gene insertions and deletions occurred in the blast fungus infecting Digitaria and banana. Furthermore, each genome shared thousands of genes, which suggest their common evolution. Overall, our analysis indicates that higher levels of genes insertion or deletions and gain in the total genome size are important factors in disrupting the host immunity and change in host selection.
Breaking the Immune Complexity of the Tumor Microenvironment Using Single-Cell Technologies
Authors: Caligola Simone , De Sanctis Francesco , Canè Stefania , Ugel Stefano
Published: May 2022

Tumors are not a simple aggregate of transformed cells but rather a complicated ecosystem containing various components, including infiltrating immune cells, tumor-related stromal cells, endothelial cells, soluble factors, and extracellular matrix proteins. Profiling the immune contexture of this intricate framework is now mandatory to develop more effective cancer therapies and precise immunotherapeutic approaches by identifying exact targets or predictive biomarkers, respectively. Conventional technologies are limited in reaching this goal because they lack high resolution. Recent developments in single-cell technologies, such as single-cell RNA transcriptomics, mass cytometry, and multiparameter immunofluorescence, have revolutionized the cancer immunology field, capturing the heterogeneity of tumor-infiltrating immune cells and the dynamic complexity of tenets that regulate cell networks in the tumor microenvironment. In this review, we describe some of the current single-cell technologies and computational techniques applied for immune-profiling the cancer landscape and discuss future directions of how integrating multi-omics data can guide a new “precision oncology” advancement.
Nomogram Model Based on Clinical Risk Factors and Heart Rate Variability for Predicting All-Cause Mortality in Stage 5 CKD Patients
Authors: Gao Xueyan , Wang Jing , Huang Hui , Ye Xiaoxue , Cui Ying , Ren Wenkai , Xu Fangyan , Qian Hanyang , Gao Zhanhui , Zeng Ming , Yang Guang , Huang Yaoyu , Tang Shaowen , Xing Changying , Wan Huiting , Zhang Lina , Chen Huimin , Jiang Yao , Zhang Jing , Xiao Yujie , Bian Anning , Li Fan , Wei Yongyue , Wang Ningning
Published: May 2022

Background: Heart rate variability (HRV), reflecting circadian rhythm of heart rate, is reported to be associated with clinical outcomes in stage 5 chronic kidney disease (CKD5) patients. Whether CKD related factors combined with HRV can improve the predictive ability for their death remains uncertain. Here we evaluated the prognosis value of nomogram model based on HRV and clinical risk factors for all-cause mortality in CKD5 patients.

Methods: CKD5 patients were enrolled from multicenter between 2011 and 2019 in China. HRV parameters based on 24-h Holter and clinical risk factors associated with all-cause mortality were analyzed by multivariate Cox regression. The relationships between HRV and all-cause mortality were displayed by restricted cubic spline graphs. The predictive ability of nomogram model based on clinical risk factors and HRV were evaluated for survival rate.

Results: CKD5 patients included survival subgroup (n = 155) and all-cause mortality subgroup (n = 45), with the median follow-up time of 48 months. Logarithm of standard deviation of all sinus R-R intervals (lnSDNN) (4.40 ± 0.39 vs. 4.32 ± 0.42; p = 0.007) and logarithm of standard deviation of average NN intervals for each 5 min (lnSDANN) (4.27 ± 0.41 vs. 4.17 ± 0.41; p = 0.008) were significantly higher in survival subgroup than all-cause mortality subgroup. On the basis of multivariate Cox regression analysis, the lnSDNN (HR = 0.35, 95%CI: 0.17–0.73, p = 0.01) and lnSDANN (HR = 0.36, 95% CI: 0.17–0.77, p = 0.01) were associated with all-cause mortality, their relationships were negative linear. Spearman’s correlation analysis showed that lnSDNN and lnSDANN were highly correlated, so we chose lnSDNN, sex, age, BMI, diabetic mellitus (DM), β-receptor blocker, blood glucose, phosphorus and ln intact parathyroid hormone (iPTH) levels to build the nomogram model. The area under the curve (AUC) values based on lnSDNN nomogram model for predicting 3-year and 5-year survival rates were 79.44% and 81.27%, respectively.

Conclusion: In CKD5 patients decreased SDNN and SDANN measured by HRV were related with their all-cause mortality, meanwhile, SDNN and SDANN were highly correlated. Nomogram model integrated SDNN and clinical risk factors are promising for evaluating their prognosis.
Association Study Between Polymorphic Loci in Cholesterol Metabolism Pathway and Gallstone in the Tibetan Population
Authors: Ma Lifeng , Chen Hui , Zhang Zhiying , Liu Lijun , Zhao Yiduo , Li Yansong , Zhao Zhipeng , Chen Haitao , Kang Longli
Published: May 2022

Background: The incidence of gallstones in the Tibetan population is increasing rapidly. Previous studies indicated that genetic variation located in the cholesterol metabolism pathway may be associated with the incidence of gallstones.

Methods: By recruiting 132 Tibetan gallstone patients and 52 normal Tibetan controls, we performed next-generation sequencing for 508 genes in the cholesterol metabolism pathway. Additionally, by integrating the sequence data of 41 normal Tibetan subjects in the public database, we finally obtained 93 normal Tibetan controls. Single nucleotide polymorphisms (SNPs) calling were performed by using the GATK pipeline. The quality control criteria for SNPs were: missing rate <0.05; minor allele frequency (MAF) > 0.01; and p value >0.001 in the Hardy-Weinberg Equilibrium (HWE) test. To eliminate the influence of population heterogeneity, Principal Component Analysis (PCA) was carried out by using the smartpca software. Association analyses were performed by Plink software. Multiple tests were adjusted by the false discovery rate (FDR) method.

Results: A total of 2,401 SNPs were obtained by analyzing 508 genes, and 2,011 SNPs left after quality control. After adjusting the eigen vectors, we found that 10 SNPs (SNV05997, rs80145081, rs80005560, rs79074685, rs748546375, rs201880593, rs142559357, rs750769471, rs869789 and rs4072341) were significantly associated with gallstone. Subsequently, by comparing the case group with our control group and the public database control group separately, we further found that the SNP rs869789 was consistently significantly associated with gallstone (p = 9.04 × 10–3 in cases vs. our controls and 5.73 × 10–3 in cases vs. public controls, respectively).

Conclusion: By systematically analyzed SNPs in the cholesterol metabolism pathway, we identified one polymorphic locus rs869789 significantly associated with the pathogenesis of gallstone in the Tibetan population. This study will provide clue for further mechanism study of gallstone in the Tibetan population.
Development of a Phagocytosis-Dependent Gene Signature to Predict Prognosis and Response to Checkpoint Inhibition in Clear-Cell Renal Cell Carcinoma
Authors: Li Kunping , Li Yuqing , Lyu Yinfeng , Tan Linyi , Zheng Xinyi , Jiang Haowen , Wen Hui , Feng Chenchen
Published: May 2022

Aim

The action of immune checkpoint inhibition (ICI) largely depends on antibody-dependent cellular phagocytosis (ADCP). We thus aim to develop ADCP-based ccRCC risk stratification as both prognostic and therapeutic markers of ICI.

Method

Genomic data from multiple public datasets (TCGA, etc.) were integrated. A cancer-intrinsic ADCP gene set for ccRCC tailored from a recent report was constructed based on the association with prognosis, immune infiltrates, and response to ICI. Therapeutic potential was profiled using genome-drug sensitivity datasets.

Results

ADCP genes were selected from a recent CRISPR/Cas9 screen report. Following a four-module panel based on clinical traits, we generated a six-gene signature (ARPC3, PHF19, FKBP11, MS4A14, KDELR3, and CD1C), which showed a strong correlation with advanced grade and stage and worsened prognosis, with a nomogram showing predictive efficacies of 0.911, 0.845, and 0.867 (AUC) at 1, 3, and 5 years, respectively. Signatures were further dichotomized, and groups with a higher risk score showed a positive correlation with tumor mutation burden, higher expressions of inhibitory checkpoint molecules, and increased antitumor immune infiltrates and were enriched for antitumor immune pathways. The high risk-score group showed better response to ICI and could benefit from TKIs of axitinib, tivozanib, or sorafenib, preferentially in combination, whereas sunitinib and pazopanib would better fit the low risk-score group.

Conclusion

Here we showed a six-gene ADCP signature that correlated with prognosis and immune modulation in ccRCC. The signature-based risk stratification was associated with response to both ICI and tyrosine kinase inhibition in ccRCC.
High-CBD Extract (CBD-X) Downregulates Cytokine Storm Systemically and Locally in Inflamed Lungs
Authors: Aswad Miran , Hamza Haya , Pechkovsky Antonina , Zikrach Anastasiia , Popov Tania , Zohar Yaniv , Shahar Eduardo , Louria-Hayon Igal
Published: May 2022

Cytokine storm refers to the dysregulated production of inflammatory mediators leading to hyperinflammation. They are often detrimental, and worsen the severity of COVID-19 and other infectious or inflammatory diseases. Cannabinoids are known to have anti-inflammatory effects but their possible therapeutic value on cytokine storms has not been fully elucidated. In vivo and ex vivo studies were carried out to investigate the effects of high-THC and high-CBD extracts on cytokine production in immune cells. Significant differences between the extracts were observed. Subsequent experiments focusing on a specific high CBD extract (CBD-X) showed significant reductions in pro-inflammatory cytokines in human-derived PBMCs, neutrophils and T cells. In vivo mouse studies, using a systemically inflamed mouse model, showed reductions in pro-inflammatory cytokines TNFα and IL-1β and a concurrent increase in the anti-inflammatory cytokine IL-10 in response to CBD-X extract treatment. Lung inflammation, as in severe COVID-19 disease, is characterized by increased T-cell homing to the lungs. Our investigation revealed that CBD-X extract impaired T-cell migration induced by the chemoattractant SDF1. In addition, the phosphorylation levels of T cell receptor (TCR) signaling proteins Lck and Zap70 were significantly reduced, demonstrating an inhibitory effect on the early events downstream to TCR activation. In a lung inflamed mouse model, we observed a reduction in leukocytes including neutrophil migration to the lungs and decreased levels of IL-1β, MCP-1, IL-6 and TNFα, in response to the administration of the high-CBD extract. The results presented in this work offer that certain high-CBD extract has a high potential in the management of pathological conditions, in which the secretion of cytokines is dysregulated, as it is in severe COVID-19 disease or other infectious or inflammatory diseases.
Molecular Determinants Regulating the Plasticity of the MHC Class II Immunopeptidome
Authors: Santambrogio Laura
Published: May 2022

In the last few years, advancement in the analysis of the MHC class II (MHC-II) ligandome in several mouse and human haplotypes has increased our understanding of the molecular components that regulate the range and selection of the MHC-II presented peptides, from MHC class II molecule polymorphisms to the recognition of different conformers, functional differences in endosomal processing along the endocytic tract, and the interplay between the MHC class II chaperones DM and DO. The sum of all these variables contributes, qualitatively and quantitatively, to the composition of the MHC II ligandome, altogether ensuring that the immunopeptidome landscape is highly sensitive to any changes in the composition of the intra- and extracellular proteome for a comprehensive survey of the microenvironment for MHC II presentation to CD4 T cells.
A Novel GMP Protocol to Produce High-Quality Treg Cells From the Pediatric Thymic Tissue to Be Employed as Cellular Therapy
Authors: Bernaldo-de-Quirós Esther , Cózar Beatriz , López-Esteban Rocío , Clemente Maribel , Gil-Jaurena Juan Miguel , Pardo Carlos , Pita Ana , Pérez-Caballero Ramón , Camino Manuela , Gil Nuria , Fernández-Santos María Eugenia , Suarez Susana , Pion Marjorie , Martínez-Bonet Marta , Correa-Rocha Rafael
Published: May 2022

Due to their suppressive capacity, the adoptive transfer of regulatory T cells (Treg) has acquired a growing interest in controlling exacerbated inflammatory responses. Limited Treg recovery and reduced quality remain the main obstacles in most current protocols where differentiated Treg are obtained from adult peripheral blood. An alternate Treg source is umbilical cord blood, a promising source of Treg cells due to the higher frequency of naïve Treg and lower frequency of memory T cells present in the fetus’ blood. However, the Treg number isolated from cord blood remains limiting. Human thymuses routinely discarded during pediatric cardiac surgeries to access the retrosternal operative field has been recently proposed as a novel source of Treg for cellular therapy. This strategy overcomes the main limitations of current Treg sources, allowing the obtention of very high numbers of undifferentiated Treg. We have developed a novel good manufacturing practice (GMP) protocol to obtain large Treg amounts, with very high purity and suppressive capacity, from the pediatric thymus (named hereafter thyTreg). The total amount of thyTreg obtained at the end of the procedure, after a short-term culture of 7 days, reach an average of 1,757 x106 (range 50 x 106 – 13,649 x 106) cells from a single thymus. The thyTreg product obtained with our protocol shows very high viability (mean 93.25%; range 83.35% – 97.97%), very high purity (mean 92.89%; range 70.10% – 98.41% of CD25+FOXP3+ cells), stability under proinflammatory conditions and a very high suppressive capacity (inhibiting in more than 75% the proliferation of activated CD4+ and CD8+ T cells in vitro at a thyTreg:responder cells ratio of 1:1). Our thyTreg product has been approved by the Spanish Drug Agency (AEMPS) to be administered as cell therapy. We are recruiting patients in the first-in-human phase I/II clinical trial worldwide that evaluates the safety, feasibility, and efficacy of autologous thyTreg administration in children undergoing heart transplantation (NCT04924491). The high quality and amount of thyTreg and the differential features of the final product obtained with our protocol allow preparing hundreds of doses from a single thymus with improved therapeutic properties, which can be cryopreserved and could open the possibility of an “off-the-shelf” allogeneic use in another individual.
A TIL-Type Serine Protease Inhibitor Involved in Humoral Immune Response of Asian Corn Borer Ostrinia furnaculis
Authors: Guan Ruobing , Hu Shaoru , Li Xiang , An Shiheng , Miao Xuexia , Li Haichao
Published: May 2022

To elucidate the application value of insect endogenous protease and its inhibitor genes in pest control, we analyzed in detail the transcriptome sequence of the Asian corn borer, Ostrinia furnacalis. We obtained 12 protease genes and 11 protease inhibitor genes, and comprehensively analyzed of their spatiotemporal expression by qRT-PCR. In which, a previous unstudied serine protease inhibitor gene attracted our attention. It belongs to the canonical serine proteinase inhibitor family, a trypsin inhibitor-like cysteine-rich domain (TIL)-type protease inhibitor, but its TIL domain lacks two cysteine residues, and it was named as ACB-TIL. Its expression level is relatively very low in the absence of pathogen stimulation, and can be up-regulated expression induced by Gram-negative bacteria (Escherichia coli), virus (BmNPV), and dsRNA (dsEGFP), but cannot be induced by fungus spores (Metarrhizium anisopliae). Prokaryotic expressed ACB-TIL protein can significantly inhibit the melanization in vitro. Injecting this protein into insect body can inhibit the production of antimicrobial peptides of attacin, lebocin and gloverin. Inhibition of ACB-TIL by RNAi can cause the responses of other immune-, protease- and inhibitor-related genes. ACB-TIL is primarily involved in Asian corn borer humoral immunity in responses to Gram-negative bacteria and viruses. This gene can be a potential target for pest control since this will mainly affect insect immune response.
Transcriptomic Responses of Adult Versus Juvenile Atlantids to Ocean Acidification
Authors: Ramos-Silva Paula , Odendaal Mari-Lee , Wall-Palmer Deborah , Mekkes Lisette , Peijnenburg Katja T. C. A.
Published: May 2022

Shelled holoplanktonic gastropods are among the most vulnerable calcifiers to ocean acidification. They inhabit the pelagic environment and build thin and transparent shells of aragonite, a metastable form of calcium carbonate. While shelled pteropods have received considerable attention and are widely regarded as bioindicators of ocean acidification, atlantids have been much less studied. In the open ocean, atlantids are uniquely positioned to address the effects of ocean acidification at distinct trophic levels. From juvenile to adult, they undergo dramatic metamorphosis. As adults they are predatory, feeding primarily on shelled pteropods, copepods and other zooplankton, while as juveniles they feed on algae. Here we investigated the transcriptome and the impact of a three-day CO2 exposure on the gene expression of adults of the atlantid Atlanta ariejansseni and compared these to results previously obtained from juveniles. Individuals were sampled in the Southern Subtropical Convergence Zone (Atlantic Ocean) and exposed to ocean chemistry simulating past (~mid-1960s), present (ambient) and future (2050) conditions. In adults we found that the changes in seawater chemistry had significantly affected the expression of genes involved in biomineralization and the immune response, although there were no significant differences in shell growth between the three conditions. In contrast, juveniles experienced substantial changes in shell growth and a broader transcriptomic response. In adults, 1170 genes had the same direction of expression in the past and future treatments when compared to the ambient. Overall, this type of response was more common in adults (8.6% of all the genes) than in juveniles (3.9%), whereas a linear response with decreasing pH was more common in juveniles (7.7%) than in adults (4.5%). Taken together, these results suggest that juveniles are more sensitive to increased acidification than adults. However, experimental limitations including short incubation times, one carboy used for each treatment and two replicates for transcriptome analysis, require us to be cautious about these conclusions. We show that distinct transcriptome profiles characterize the two life stages, with less than 50% of shared transcripts. This study provides an initial framework to understand how ocean acidification may affect the molecular and calcification responses of adult and juvenile atlantids.
Cracking and Photo-Oxidation of Polyoxymethylene Degraded in Terrestrial and Simulated Marine Environments
Authors: Tang Chih-Cheng , Chen Ying-Ting , Zhang Yi-Ming , Chen Huey-Ing , Brimblecombe Peter , Lee Chon-Lin
Published: May 2022

Marine plastic debris is an environmental problem, and its degradation into microplastics (1-5000 μm) introduces them into the food chain. In this study, small polyoxymethylene (global production ~3000 Tg per year) pellets were exposed in terrestrial and simulated marine environments to heat and light, resulting in cracking during decay with increasing IR absorption (OH-bonds). Furthermore, sunlight over three years reduced pellet mass and diameter (~10% and ~40%), initially yielding 100-300 μm fragments. Changes under UV irradiation were smaller as it could not penetrate into particle interiors. Characteristic spacing of surface striations (100-300 µm) initiated radial cracks to pellet interiors, and breakdown ultimately meant 95% of particles were <300 µm, which are potentially incorporated in marine turbidites.
Laboratory Investigation on Key Technological Parameters of Brick Concrete Recycled Coarse Aggregate Strengthened by Negative Pressure
Authors: Liu Hongzhe , Zhao Zhizhong , Yang Zhenyu , Wang Risheng , Xu Meng
Published: May 2022

The strengthening application of brick concrete recycled coarse aggregate (BCRCA) has become a “troublesome issue.” In this sense, an in-depth study on the strengthening method of BCRCA is needed. In order to improve the strengthening effect of BCRCA and perform the large-scale application of brick concrete waste, the strengthening method of BCRCA was investigated. Briefly, the performance of BCRCA was initially analyzed. Then, the pore characteristics of BCRCA were tested by CT scanning technology. The evaluation index of filling saturation was proposed. Finally, the BCRCA was strengthened by the negative pressure, and the influences of key parameters such as negative pressure, negative pressure time, negative pressure temperature, and stirring times on the strengthening effect were investigated. The test results showed that the best performance can be obtained by using the following parameters: negative pressure from −55 kPa to −80 kPa, the negative pressure time from 6 to 14 min, the negative pressure temperature from 40 to 80°C, and the stirring times from 1 to 4 times. Combined with the influence of negative pressure strengthening process parameters on filling saturation, it can be determined that a negative pressure of −75 kPa, a negative pressure time of 12 min, and a negative pressure temperature of 70°C with two times of stirring were the best negative pressure strengthening parameters. The unconfined compressive strength and indirect tensile strength reached 4.9 and 0.55 MPa, respectively, when the reinforced BCRCA was used for the cement-stabilized macadam. Therefore, the negative pressure strengthening process parameters determined in this study can achieve a good strengthening effect.